Article

Impacts of Peritoneal Cancer Index on The Survival Outcomes of Patients With Colorectal Peritoneal Carcinomatosis

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Abstract

Introduction: Peritoneal cancer index (PCI) has been suggested to be the most important prognostic factors for the outcomes in colorectal peritoneal carcinomatosis (CRPC). Methods: This was a retrospective study of prospectively collected data of 168 consecutive patients with CRPC following cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy (PIC). Patients were divided into five groups according to their PCI. Results: Hospital mortality was 0%. Patients in low PCI groups had a significantly lower major morbidity rate, shorter intensive care unit and high dependency unit stay and higher overall survival (p=0.017, 0.001, 0.046, p<0.001 respectively). Conclusion: Combined CRS with PIC can be safely performed to provide encouraging survival benefits for patients with CRPC. Our findings suggest that this approach is particularly beneficial for patients with low volume of disease. Early referral to specialist centre for evaluation is warranted for better survival outcomes.

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... The presence of peritoneal carcinomatosis (PC) due to GI and ovarian tumors has increased in recent years. It represents advanced disease, has a grim prognosis 1,2 , and limited therapeutic options compared to other sites of metastasis 3,4 . PC mainly originates from GI, gynecological, and peritoneal tumors 1,2 . ...
... In 1995, Sugarbaker et al. 5,6 introduced the Peritoneal Carcinomatosis Index (PCI), a scoring system that quantifies PC to compare overall survival (OS) and recurrence-free survival (RFS) across different studies 4,7 . PCI has prognostic relevance regardless of the origin of PC 8 . ...
... PCI has prognostic relevance regardless of the origin of PC 8 . Former studies have demonstrated that patients with higher PCI have lower survival rates and worse outcomes compared to those with PCIs < 15 2,4,9,10 . Various PCI cut-off values have been described, such as < 10 9,11 , < 11 12 , and < 15 4 , and they are related to OS. ...
... La presencia de carcinomatosis peritoneal (CP) secundaria a tumores gastrointestinales y ováricos aumentó su incidencia en los últimos años, representa enfermedad avanzada y tiene peor pronóstico 1,2 , así como opciones terapéuticas limitadas en comparación con otros sitios de metástasis 3,4 . La CP se origina principalmente de tumores del tubo digestivo, ginecológicos y peritoneales 1,2 . ...
... En 1995, Sugarbaker et al. 5,6 describieron el índice de carcinomatosis peritoneal (ICP). Este es un sistema de puntuación que cuantifica la CP para comparar la supervivencia global (SG) y la supervivencia libre de recurrencia (SLR) en diferentes estudios 4,7 . El ICP tiene relevancia pronóstica, independientemente del origen de la CP 8 . ...
... El ICP tiene relevancia pronóstica, independientemente del origen de la CP 8 . En los estudios se ha comprobado que los pacientes con mayor ICP tienen menor supervivencia y peor evolución que aquellos con ICP < 15 puntos 2,4,9,10 . Se han descrito diferentes puntos de corte de ICP, como < 10 puntos 9,11 , < 11 puntos 12 y < 15 puntos 4 , relacionándolos con la SG. ...
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Background: The peritoneal carcinomatosis (PC) secondary to gastrointestinal or gynecological cancer has increased its incidence. It has a worse prognosis compared to other sites of metastasis. The peritoneal carcinomatosis index (PCI) establishes overall survival in patients with gastrointestinal or gynecological tumors and carcinomatosis. Objective: To evaluate the relationship of PCI to overall survival (OS) and recurrence-free survival (RFS) in patients treated with cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC). Method: A descriptive, retrolective study of 80 charts of patients with CP was conducted. We included patients with colon, ovarian, appendicular, pseudomyxoma and gastric tumors with CP treated with CRS plus HIPEC. The OS and RFS were determined according to the type of adenocarcinoma and the degree of differentiation. The OS and RFS were determined in months in patients with PCI > 15 PCI as well as in patients with PCI < 15 considering the tumor of origin. Results: Patients with ovarian tumors and pseudomyxoma with PCI < 15 presented OS > 70 months, compared to patients with gastric tumors (4 months). Conclusions: The PCI and histology are predictors of OS. Patients with ovarian tumors and PCI < 15 have higher OS, similar to pseudomyxomas. RFS was also higher in patients with PCI < 15.
... In this study, 87% patients did not have disease progression during NACT and could undergo IDS. In other reports, the response rates to chemotherapy in FIGO stage III/IV ovarian carcinoma is higher in colorectal carcinoma (73-90 vs 15-62%) 18,[29][30][31][32] . For colorectal cancer, patients with high score of PCI were reported to have poor prognosis 29,[33][34][35][36] because PCI directly affect the rate of no residual disease after surgery, frequency of postoperative complications, and prognosis 29,33-36 . ...
... The selection criteria for performing PDS or IDS varies among institutions. Notably, 42 of 56 patients with a high PCI score (21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39) were included in the NACT/ IDS group; therefore, it is reasonable to conclude that in addition to aggressive surgery, chemotherapy may have affected the prognosis. In this study, 73% of patients with a high PCI score who could not undergo PDS underwent high-complexity surgery following the administration of NACT. ...
Article
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We examined whether the extent of initial peritoneal dissemination affected the prognosis of patients with advanced ovarian, fallopian tube, and peritoneal carcinoma when initially disseminated lesions > 1 cm in diameter were removed, regardless of the timing of aggressive cytoreductive surgery. The extent of peritoneal dissemination was assessed by the peritoneal cancer index (PCI) at initial laparotomy in 186 consecutive patients with stage IIIC/IV. Sixty patients underwent primary debulking surgery and 109 patients underwent neoadjuvant chemotherapy followed by interval debulking surgery. Seventeen patients could not undergo debulking surgery because of disease progression during neoadjuvant chemotherapy. The median initial PCI were 17. Upper abdominal surgery and bowel resection were performed in 149 (80%) and 171 patients (92%), respectively. Residual disease ≤ 1 cm after surgery was achieved in 164 patients (89%). The initial PCI was not significantly associated with progression-free survival (PFS; p = 0.13) and overall survival (OS; p = 0.09). No residual disease and a high-complexity surgery significantly prolonged PFS (p < 0.01 and p = 0.02, respectively) and OS (p < 0.01 and p ≤ 0.01, respectively). The extent of initial peritoneal dissemination did not affect the prognosis when initially disseminated lesions > 1 cm were resected.
... An estimated 66% of PCs arise from gastrointestinal (GI) tumors (colorectal (60%), gastric (20%), and pancreatic (20%) and 33% arise from tumors of other origins, including ovarian tumors in more than 50% of cases [5]. CRS with or without HIPEC has been reported to be beneficial in terms of outcomes in patients treated for PC from various origins including gastric, ovarian, pseudomyxoma peritonei (PMP), and colorectal cancer, with a median survival of 42 months in patients with PC from colorectal origin, versus 15 months for chemotherapyonly patients, and a 5-year survival of 34.5% [6][7][8][9]. ...
... However, CRS alone or combined with HIPEC may be accompanied by postoperative complications in 30% to 60% of cases [8][9][10][11], these being mainly related to the extent of CRS, the general condition of the patient, and the experience of the center [12]. ...
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Background Relatively high morbidity rates are reported after cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). However, early predictors of complications after CRS plus HIPEC have not been identified. The aim of this study was to evaluate the predictive role of early postoperative serum C-reactive protein (CRP) level (Day 2–4) for the detection of post-operative complications. Patients and methods We performed a retrospective study including 94 patients treated with complete CRS (R1) and HIPEC for PC from various primary origins (2011–2016). Post-operative complications were recorded. The values for postoperative inflammatory markers (white blood cells [WBC] and platelet counts, CRP) were compared between the different groups. Results CRP on post-operative days 2–4 was significantly higher in patients with than without complications (124 mg/L vs 46 mg/L; p < 0.0001) and higher in those with more major complications (162 mg/L vs 80 mg/L; p < 0.0012). WBC and platelet counts showed no difference within 5 days postoperatively. Conclusion CRP levels, and kinetics mainly, between post-operative day 2 and 4, are decisive predictive markers of early and late post-operative complications after CRS plus HIPEC. The presence of post-operative complications should be suspected in patients with a high CRP mean, and a plateau level (days 2–4).
... An estimated 66% of PCs arise from gastrointestinal (GI) tumors (colorectal (60%), gastric (20%), and pancreatic (20%) and 33% arise from tumors of other origins, including ovarian tumors in more than 50% of cases [5]. CRS with or without HIPEC has been reported to be bene cial in terms of outcomes in patients treated for PC from various origins including gastric, ovarian, pseudomyxoma peritonei (PMP), and colorectal cancer, with a median survival of 42 months in patients with PC from colorectal origin, versus 15 months for chemotherapy-only patients, and a 5-year survival of 34.5% [6,7,8,9]. However, CRS alone or combined with HIPEC may be accompanied by postoperative complications in 30% to 60% of cases [8,9,10,11], these being mainly related to the extent of CRS, the general condition of the patient, and the experience of the center [12]. ...
... CRS with or without HIPEC has been reported to be bene cial in terms of outcomes in patients treated for PC from various origins including gastric, ovarian, pseudomyxoma peritonei (PMP), and colorectal cancer, with a median survival of 42 months in patients with PC from colorectal origin, versus 15 months for chemotherapy-only patients, and a 5-year survival of 34.5% [6,7,8,9]. However, CRS alone or combined with HIPEC may be accompanied by postoperative complications in 30% to 60% of cases [8,9,10,11], these being mainly related to the extent of CRS, the general condition of the patient, and the experience of the center [12]. ...
Preprint
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Background: Relatively high morbidity rates are reported after cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). However, early predictors of complications after CRS plus HIPEC have not been identified. The aim of this study was to evaluate the predictive role of early postoperative serum C-reactive protein (CRP) level (Day 2-4) for the detection of post-operative complications. Patients and methods: We performed a retrospective study including 94 patients treated with complete CRS (R1) and HIPEC for PC from various primary origins (2011-2016). Post-operative complications were recorded. The values for postoperative inflammatory markers (white blood cells [WBC] and platelet counts, CRP) were compared between the different groups. Results: CRP on post-operative days 2-4 was significantly higher in patients with than without complications (124 mg/L vs 46 mg/L; p<0.0001) and higher in those with more major complications (162 mg/L vs 80 mg/L; p< 0.0012). WBC and platelet counts showed no difference within 5 days postoperatively. Conclusion: CRP levels, and kinetics mainly, between post-operative day 2 and 4, are decisive predictive markers of early and late post-operative complications after CRS plus HIPEC. The presence of post-operative complications should be suspected in patients with a high CRP mean, and a plateau level (days 2-4).
... 33% arise from tumors of other origins, including ovarian tumors in more than 50% of cases [5]. CRS with or without HIPEC has been reported to be beneficial in terms of outcomes in patients treated for PC from various origins including gastric, ovarian, pseudomyxoma peritonei (PMP), and colorectal cancer, with a median survival of 42 months in patients with PC from colorectal origin, versus 15 months for chemotherapy-only patients, and a 5-year survival of 34.5% [6,7,8,9]. However, CRS alone or combined with HIPEC may be accompanied by postoperative complications in 30-60% of cases [8,9,10,11], these being mainly related to the extent of CRS, the general condition of the patient, and the experience of the center [12]. ...
... CRS with or without HIPEC has been reported to be beneficial in terms of outcomes in patients treated for PC from various origins including gastric, ovarian, pseudomyxoma peritonei (PMP), and colorectal cancer, with a median survival of 42 months in patients with PC from colorectal origin, versus 15 months for chemotherapy-only patients, and a 5-year survival of 34.5% [6,7,8,9]. However, CRS alone or combined with HIPEC may be accompanied by postoperative complications in 30-60% of cases [8,9,10,11], these being mainly related to the extent of CRS, the general condition of the patient, and the experience of the center [12]. ...
Preprint
Full-text available
Background Relatively high morbidity rates are reported after cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). However, early predictors of complications after CRS plus HIPEC have not been identified. The aim of this study was to evaluate the predictive role of early postoperative serum C-reactive protein (CRP) level (Day 2-4) for the detection of post-operative complications. Patients and methods We performed a retrospective study including 94 patients treated with complete CRS (R1) and HIPEC for PC from various primary origins (2011-2016). Post-operative complications were recorded. The values for postoperative inflammatory markers (white blood cells [WBC] and platelet counts, CRP) were compared between the different groups. Results CRP on post-operative days 2-4 was significantly higher in patients with than without complications (124 mg/L vs 46 mg/L; p<0.0001) and higher in those with more major complications (162 mg/L vs 80 mg/L; p< 0.0012). WBC and platelet counts showed no difference within 5 days postoperatively. Conclusion CRP levels, and kinetics mainly, between post-operative day 2 and 4, are decisive predictive markers of early and late post-operative complications after CRS plus HIPEC. The presence of post-operative complications should be suspected in patients with a high CRP mean, and a plateau level (days 2-4).
... However, CT has a wide sensitivity range of 24.5%-79% for detecting peritoneal metastases, potentially underestimating the PCI by 24%-33% [4,[8][9][10][11][12]. Although patients with very low PCIs are ideal candidates for CRS þ HIPEC, small peritoneal lesions are difficult to detect by CT [13][14][15]. Furthermore, if tumor loads are found to be excessive at operation, underestimation can lead to unnecessary "open-and-close" procedures and avoidably prolonged recovery times and complications. Accurate patient identification can therefore ensure optimal use of surgical and financial resources. ...
... To date, we could find no studies comparing diagnostic laparoscopy with CT in patient selection for CRS þ HIPEC based on the estimated PCI. Although some studies have been performed comparing the accuracies of CT and laparotomy [4,[10][11][12], these showed that the median PCI score estimated by CT (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26) was significantly lower than that estimated by laparotomy (13-39) (p-value, <0.001 to 0.003) [4,[10][11][12]. One study illustrated that, despite CT scans underestimating the PCI, only 12% of patients would require an open-and-close procedure [4]. ...
Article
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Background Despite its widespread use, computed tomography (CT) is not perfect for evaluating peritoneal metastases of colorectal origin before cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS + HIPEC). We therefore evaluated the value of adding diagnostic laparoscopy to CT when assessing patient eligibility for CRS + HIPEC. Methods This was a retrospective study of a consecutive series of 112 patients evaluated systematically by diagnostic laparoscopy and CT between January 2012 and January 2018. Patient eligibility for CRS + HIPEC was assessed by the peritoneal cancer index (PCI) both at the time of initial diagnostic laparoscopy and during the retrospective review of CT images. Two experienced radiologists who were blinded to the PCI result at laparoscopy then independently estimated the PCI based on CT imaging. The primary outcome was the number of patients eligible for CRS + HIPEC by each method. Results We identified 112 patients, of whom 95 (85%) were eligible for CRS + HIPEC based on diagnostic laparoscopy and 84 underwent CRS + HIPEC. Overall, 14 patients (17%) experienced an “open-and-close” procedure. In contrast to diagnostic laparoscopy, 100 patients (89%) were identified as being eligible for CRS + HIPEC by CT (p = 0.13), which would have resulted in an additional five open-and-close procedures. Conclusions Adding diagnostic laparoscopy to CT produced a clinically relevant, but statistically non-significant, reduction in the number of patients eligible for CRS + HIPEC. We conclude that diagnostic laparoscopy may be of use in preoperative assessments when systematic analysis by CT scores the PCI as greater than ten. Future research should focus on the cost-effectiveness of this approach.
... Peritoneal carcinomatosis (PC) is a challenge. Detection of peritoneal involvement at an early stage may help improving treatment response and final results (4). Present pre-operative diagnostic and staging techniques and imaging modalities have low sensitivity for PC less than 0.5 cm (5). ...
... Detecting the presence of peritoneal metastasis at an early stage with the use of ICG could well improve oncological results, in both therapeutic pathways and possibilities of surgical treatment. 29 Barabino et al 30 prospective study analyzed 88 peritoneal carcinomatosis of colorectal origin after injection of ICG, from which 58 were classified as cancerous among which 42 were correctly classified using an intraoperative NIR camera. Among the 30 non-cancerous lesions, 18 were correctly classified using the intraoperative NIR camera. ...
Article
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Fluorescence imaging in colorectal surgery is considered a novel predominantly intraoperative method of ensuring a greater surgical success. The use of fluorescence is linked to advanced tumor visualization and projection of its lymphatics, both vessels and nodes, which results in a higher chance of achieving a total excision. Additionally, iatrogenic complications prove to be reduced using fluorescence during the surgical excision. The combination of fluorescence and artificial intelligence to better facilitate oncological surgery will soon become an established approach in operating rooms worldwide.
... Patients who are initially deemed unresectable may convert to resectability following tumor regression through chemotherapy [5,6], although evidence of peritoneal response to systemic treatments is limited. Hyperthermic intraperitoneal chemotherapy (HIPEC) together with complete surgical removal of disease, known as peritonectomy, offers the only choice of care for long term survival of CRC with peritoneal dissemination This, however, is only effective in selected patients with a Peritoneal Cancer Index (PCI) ≤ 15 and is a major procedure [7]. Patients with significant disease burden have limited treatment options and similarly, those that recur after curative-intent surgery may not be suitable for repeat surgical procedures. ...
Article
The combinations of Bromelain and Acetylcysteine (BromAc®) with cytotoxics such as Gemcitabine, 5-Fluorouracil or Oxaliplatin have shown a dramatic reduction in IC50 values in a variety of cancers, including colon cancer, suggesting the possibility of effective treatment without undesired side effects. In the current study, we investigated whether a similar effect is present in vivo using the colorectal cell line LS174T. Animals after acclimatization were randomized and allocated equally in the groups for the different studies (safety, dose-escalation, and efficacy). Drugs were delivered by the intraperitoneal route and animals were monitored for wellbeing. Separately, an efficacy study was conducted with intraperitoneal drug delivery after intraperitoneal tumor induction. At the termination of the experiment, tumors and other tissues were collected for evaluation. BromAc® was safe when delivered intraperitoneally in a rat model at the concentrations used. Subsequent investigations of these adjuvants in combination with Gemcitabine, Oxaliplatin, and 5-Fluorouracil in mice were also proven to be safe. Preliminary efficacy studies with Oxaliplatin and 5-Fluorouracil on tumor growth (LS174T) were negative. Gemcitabine was assessed with BromAc® showing an almost 71% tumor inhibition compared to controls. This in vivo study indicates that Gemcitabine at 2 mg/kg in combination with BromAc® 3 mg/300 mg/Kg was effective and safe, supporting its potential for future clinical application.
... Néanmoins, les données d'un essai récent de phase III semblent attribuer le gain de survie à la cytoréduction chirurgicale plutôt qu'à la CHIP[102,103].Plus son extension est importante, plus l'index est élevé, et plus le pronostic est défavorable. En effet, au-delà d'un certain niveau d'envahissement, l'indication de la CHIP ne sera plus retenue, ou fortement discutée car la survie avec la CHIP est comparable à la survie obtenue avec une chimiothérapie systémique seule[105].Le peritoneal surface disease severity score (PSDSS) est un autre score utilisé pour les cancers colorectaux. Il prend en compte le retentissement clinique de la carcinose, l'IPC et l'analyse histologique de la tumeur[109].La sélection des patients est un élément crucial assurant une balance bénéfice/risque favorable de la CHIP. ...
Thesis
La chimiothérapie hyperthermique intrapéritonéale est une technique chirurgicale de première importance pour la prise en charge des patients atteints de carcinoses péritonéales. Cependant, elle expose les professionnels du bloc opératoire à un risque de contamination par les anticancéreux. L’analyse de la contamination de l’environnement et des soignants lors des CHIP n’a fait l’objet que d’une dizaine de publications entre 1980 et 2020. Au cours de cette thèse, nous avons mis au point et validé une méthode UHPLC-MS/MS de dosage plasmatique et érythrocytaire de l’irinotécan et de deux de ses métabolites, le SN-38 et l'APC. Parmi les prélèvements réalisés chez le chirurgien et l’interne de chirurgie lors des CHIP au CLCC de Caen, une contamination par l’irinotécan a été identifiée dans 20 des 21 échantillons sanguins, avec des concentrations maximales de 266 et 257 pg/mL respectivement au niveau plasmatique et érythrocytaire. Parallèlement, la recherche de contamination par l’oxaliplatine dans les mêmes matrices biologiques a permis de détecter des ultra-traces de platine de l’ordre d’une dizaine de pg/mL. Cette étude, unique par le nombre d’échantillons et l’analyse à la fois plasmatique et érythrocytaire de l’irinotécan et de deux principaux métabolites, fournit des données importantes pour la détermination d’indicateurs biologiques d’exposition pour les soignants impliqués en CHIP. Un dosage biologique régulier des anticancéreux devrait ainsi permettre de suivre les pratiques de manipulation des soignants, le respect des recommandations et l’efficacité des EPC et EPI. La stratégie de réduction des risques d’exposition doit également se baser sur un programme de formation par exemple par la simulation numérique, qui doit contribuer à améliorer le respect des pratiques de protection, voire à diminuer les valeurs de contamination biologique des soignants.
... We have identified that PCI score is independently associated with major morbidity. This mirrors the effect of PCI on the morbidity of standard CRS and HIPEC [31] and reinforces the importance of appropriate patient selection. The utility of liver resection in the setting of CRS and HIPEC for isolated metastatic colorectal cancer is well recognised, as seen from results of an international online survey conducted by the Peritoneal Surface Oncology Group International (PSOGI) [9], as well as the consensus statements from the Chicago Consensus Working Group [10] and the Society of Surgical Oncology [8]. ...
Article
Purpose Synchronous liver resection, cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal liver (CRLM) and peritoneal metastases (CRPM) has traditionally been contraindicated. However, latest practice promotes specialist multidisciplinary-led consideration for select patients. This study aimed to evaluate the perioperative and oncological outcomes of synchronous resection in the management of CRLM and CRPM from two tertiary referral centres. Method This bi-institutional retrospective cohort study included patients undergoing simultaneous liver resection, CRS and HIPEC for metastatic colorectal cancer from 2013 to 2020. Patients treated with ablative liver techniques, staged operative approaches and those with extra abdominal disease were excluded. Overall survival (OS) and disease-free survival (DFS) rates were assessed. Univariate and multivariate analyses identified variables associated with survival and major morbidity (Clavien-Dindo grade III/IV). Results Twenty-three patients were included. The median peritoneal carcinomatosis index (PCI) was 9 (range 0–22). There were two major liver resections and 21 minor resections. CC-0 resections were achieved in all patients. Major morbidity occurred in 7 patients. There were no deaths at 90 days. PCI was independently associated with morbidity (p = 0.04). PCI >10 (p = 0.069), major morbidity (p = 0.083) and presence of KRAS mutation (p = 0.052) approached significance for poor OS. Median follow up was 21 months (4–54 months). Median OS was 37 months, 3-year survival 54%, and median DFS 18 months. Conclusion Synchronous liver resection, cytoreductive surgery and HIPEC is feasible in selected patients with low-volume CRPM and CRLM. Increasing PCI is associated with postoperative major morbidity, and should be considered during operative planning.
... Most colorectal cancer patients with synchronous peritoneal metastasis show poor prognosis [5]. However, resection is useful for some lesions limited to a small region like in P 1 or low PCI cases [6][7][8]. The Japanese Classification of Colorectal Cancer, P classification, defines peritoneal metastasis findings using two parameters: distance from the main tumor and number of peritoneal lesions [1]. ...
Article
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Objectives: In Japan, there are three grades of peritoneal metastasis from colorectal cancer. The grade depends on the extent and number of lesions (P classification). The P classification is useful for its simplicity but lacks objectivity. On the other hand, the peritoneal cancer index (PCI) objectively indicates the peritoneal metastasis grade. However, the evaluation process is complicated clinically. In this study, we compared these two methods and investigated how to improve the P classification's objectivity by referring to PCI. Methods: We investigated 150 cases of synchronous peritoneal metastasis from colorectal cancer. We inspected the correlation between the P classification and the PCI and pointed out the problems which prevented objective evaluation when using the P classification. We also estimated new criteria for extent and number in the P classification. Results: We found the ideal definition for the best alignment between the P classification and the PCI was: ・P1 is metastases confined to one peritoneal region, ・P2 is 19 or fewer peritoneal metastases in two or more regions, and ・P3 is 20 or more metastases in two or more regions. This revision improved the P classification's objectivity and correlated with the PCI. Conclusions: Grading using the P classification was both imprecise and subjective. We propose a new standard value of extent and number in the P classification based on the PCI. This improvement would provide an objective, simple method of grading for peritoneal metastasis from colorectal cancer. Fullsize Image
... Peritoneal carcinomatosis represents a challenging localization of abdominal tumors. Detecting the presence of peritoneal involvement at an early stage could improve oncological results [1], both customizing the therapeutic path and enhancing the possibilities of surgical treatment. The results of cytoreductive surgery, possibly associated with hyper-thermic intraperitoneal chemotherapy (HIPE C), are directly dependent on the completeness of the cytoreduction, and this in turn is directly dependent on the size and number of the nodules. ...
Article
Full-text available
Background: To review the available clinical data about the value of Indocyanine Green (ICG) fluorescence imaging for intraoperative detection of peritoneal carcinomatosis. Methods: We conducted a systematic review, according to the PRISMA guidelines, for clinical series investigating the possible role of ICG fluorescence imaging in detecting peritoneal carcinomatosis during surgical treatment of abdominal malignancies. With the aim to analyze actual application in the daily clinical practice, papers including trials with fluorophores other than ICG, in vitro and animals series were excluded. Data on patients and cancer features, timing, dose and modality of ICG administration, sensitivity, specificity and accuracy of fluorescence diagnosis of peritoneal nodules were extracted and analyzed. Results: Out of 192 screened papers, we finally retrieved 7 series reporting ICG-guided detection of peritoneal carcinomatosis. Two papers reported the same cases, thus only 6 series were analyzed, for a total of 71 patients and 353 peritoneal nodules. The investigated tumors were colorectal carcinomas in 28 cases, hepatocellular carcinoma in 16 cases, ovarian cancer in 26 cases and endometrial cancer in 1 case. In all but 4 cases, the clinical setting was an elective intervention in patients known as having peritoneal carcinomatosis. No series reported a laparoscopic procedure. Technical data of ICG management were consistent across the studies. Overall, 353 lesions were harvested and singularly evaluated. Sensitivity varied from 72.4 to 100%, specificity from 54.2 to 100%. Two series reported that planned intervention changed in 25 and 29% of patients, respectively. Conclusion: Indocyanine Green based fluorescence of peritoneal carcinomatosis is a promising intraoperative tool for detection and characterization of peritoneal nodules in patients with colorectal, hepatocellular, ovarian carcinomas. Further prospective studies are needed to fix its actual diagnostic value on these and other abdominal malignancies with frequent spread to peritoneum.
... Peritoneal carcinomatosis represents a challenging localization of abdominal tumors. Detecting the presence of peritoneal involvement at an early stage could improve oncological results [1], both customizing the therapeutic path and enhancing the possibilities of surgical treatment. The results of cytoreductive surgery, possibly associated with hyper-thermic intraperitoneal chemotherapy (HIPEC), are directly dependent on the completeness of the cytoreduction, and this in turn is directly dependent on the size and number of the nodules. ...
Preprint
Full-text available
BACKGROUND. To review the available clinical data about the value of Indocyanine Green (ICG) fluorescence imaging for intraoperative detection of peritoneal carcinomatosis. METHODS. We conducted a systematic review, according to the PRISMA guidelines, for clinical series investigating the possible role of ICG fluorescence imaging in detecting peritoneal carcinomatosis during surgical treatment of abdominal malignancies. With the aim to analyze actual application in the daily clinical practice, papers including trials with fluorophores other than ICG, in vitro and animals series were excluded. Data on patients and cancer features, timing, dose and modality of ICG administration, sensitivity, specificity and accuracy of fluorescence diagnosis of peritoneal nodules were extracted and analyzed. RESULTS. Out of 192 screened papers, we finally retrieved 7 series reporting ICG-guided detection of peritoneal carcinomatosis. Two papers reported the same cases, thus only 6 series were analyzed, for a total of 71 patients and 353 peritoneal nodules. The investigated tumors were colorectal carcinomas in 28 cases, hepatocellular carcinoma in 16 cases, ovarian cancer in 26 cases and endometrial cancer in 1 case. In all but 4 cases, the clinical setting was an elective intervention in patients known as having peritoneal carcinomatosis. No series reported a laparoscopic procedure. Technical data of ICG management were consistent across the studies. Overall, 353 lesions were harvested and singularly evaluated. Sensitivity varied from 72.4% to 100%, specificity from 54.2% to 100%. Two series reported that planned intervention changed in 25% and 29% of patients, respectively. CONCLUSION. Indocyanine Green based fluorescence of peritoneal carcinomatosis is a promising intraoperative tool for detection and characterization of peritoneal nodules in patients with colorectal, hepatocellular, ovarian carcinomas. Further prospective studies are needed to fix its actual diagnostic value on these and other abdominal malignancies with frequent spread to peritoneum.
... Peritoneal carcinomatosis represents a challenging systemic localization of abdominal tumors. In the clinical management of patients suffering from abdominal cancer, detecting the presence of tumor cells on the peritoneum at an early stage could improve oncological results [1]. On the one hand, a better staging would allow to personalize the therapeutic path. ...
Preprint
Full-text available
BACKGROUND. To review the available clinical data about the value of Indocyanine Green (ICG) fluorescence imaging for intraoperative detection of peritoneal carcinomatosis. METHODS. We conducted a systematic review, according to the PRISMA guidelines, for clinical series investigating the possible role of ICG fluorescence imaging in detecting peritoneal carcinomatosis during surgical treatment of abdominal malignancies. Key words for search were “indocyanine green”, “carcinomatosis”, “peritoneum”, “fluorescence”. Papers including trials with fluorophores other than ICG were excluded. Papers including in vitro and experimental animals series were also excluded. We extracted data on patients and cancer features, timing, dose and modality of ICG administration, sensitivity, specificity and accuracy of fluorescence diagnosis of peritoneal nodules. RESULTS. Out of 192 screened papers, we finally retrieved 7 series reporting ICG-guided detection of peritoneal carcinomatosis. Two papers reported the same cases, thus only 6 series were analyzed, for a total of 71 patients. The investigated tumors were colorectal carcinomas in 28 cases, hepatocellular carcinoma in 16 cases, ovarian cancer in 26 cases and endometrial cancer in 1 case. In all but 4 cases, the clinical setting was an elective intervention in patients known as having peritoneal carcinomatosis. No series reported a laparoscopic procedure. Technical data of ICG management were consistent across the studies. Overall, 353 lesions were singularly analyzed and evaluated. Sensitivity varied from 72.4–100%, specificity from 54.2–100%. Two series reported that planned intervention changed in 25% and 29% of patients, respectively. CONCLUSION. Indocyanine Green based fluorescence of peritoneal carcinomatosis is a promising intraoperative tool for detection and characterization of peritoneal nodules in patients with colorectal, hepatocellular, ovarian carcinomas. Further prospective studies are needed, including stanging laparoscopy for pancreato-biliary, gastric cancer and other abdominal malignancies with frequent spread to peritoneum.
... At present, the main method of diagnosis of locally advanced processes in the abdomen is computed tomography with intravenous contrast (CT) [3]. Correct preoperative staging with the help of peritoneal index of carcinomatosis proposed by P. Shugarbaker allows to determine the order of combinated treatment, the expediency of surgical treatment and its probable volume and radicality [4,5]. However, according to the literature, CT does not allow to achieve a significant correlation in the estimation of the extent of abdominal tumour and the possibility of its complete removal. ...
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The aim of the research. Development and implementation of new methods for pre-operative staging of advanced ovarian, gastric and colorectal cancer to improve patient selection for cytoreductive surgery and increase its radicality. Materials and methods. Data from 120 patients with advanced ovarian cancer, 28 with advanced gastric cancer and 119 with advanced colorectal cancer were analyzed. Preoperative detection of the incidence of peritoneal carcinoma and the possibility of surgery in radical or cytoreductive volume performed by CT with intravenous contrast (72 patients with ovarian cancer, 17 patients with gastric cancer, and 69 patients with colorectal cancer), and MR T1 and T2, contrast-enhanced T1, and diffuse-weighted sequences (48 patients with ovarian cancer, 11 patients with gastric cancer, and 50 patients with colorectal cancer). Subsequently, preoperative and intraoperative assessment of the prevalence of the tumour process with peritoneal carcinoma index (PCI) by Sugarbaker was performed. Results. A statistically significant increase in the informativeness of the preoperative assessment of the incidence of tumour process in peritoneum and the presence of distant metastases using DWI / MRI compared with CT with intravenous contrast was determined. Patients from all groups were categorized according to the completeness index of cytoreduction achieved by preoperative staging and patient selection using DWI / MRI and CT. The use of DWI / MRI allowed to significantly reduce the number of suboptimal and non-optimal cytoreductive interventions. Conclusions. DWI / MRI has made it possible to significantly improve the preoperative incidence of advanced ovarian, gastric, and colorectal cancer compared to CT, predict the radicality of future surgery, and detect inoperable cases.
... 21 stated a PCI ≥20 as a predictor of poor prognosis in their study of 180 patients. There are publications that detected a negative correlation between survival and PCI as in these studies, 22,23 and there is also a study of 50 patients reported that PCI is more effective than PSDSS in predicting prognosis. 6 PCI values used to evaluate PSDSS are obtained by examining preoperative abdominal contrast enhanced CT scans. ...
... Twenty-four unique studies 11,18,20,31 -51 reporting on 3128 patients with CPM presented adequate data to be included in the meta-analysis ( Fig. 1). Of the 24 cohort studies, six 18,34,37,40,44,47 were prospective and the remaining 18 11,20,[31][32][33]35,36,38,39,[41][42][43]45,46,[48][49][50][51] were retrospective (Table S1, supporting information). A number of studies presented both an unadjusted and adjusted HR. ...
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Background: Up to 15 per cent of colorectal cancers present with peritoneal metastases (CPM). Cytoreductive surgery and heated intraperitoneal chemotherapy (CRS + HIPEC) aims to achieve macroscopic tumour resection combined with HIPEC to destroy microscopic disease. CRS + HIPEC is a major operation with significant morbidity and effects on quality of life (QoL). Improving patient selection is crucial to maximize patient outcomes while minimizing morbidity and mortality. The aim of this study was to identify prognostic factors for patients with CPM undergoing CRS + HIPEC. Methods: A systematic search of MEDLINE, Embase and Cochrane Library electronic databases was performed using terms for colorectal cancer, peritoneal metastasis and CRS + HIPEC. Included studies focused on the impact of prognostic factors on overall survival following CRS + HIPEC in patients with CPM. Results: Twenty-four studies described 3128 patients. Obstruction or perforation of the primary tumour (hazard ratio (HR) 2·91, 95 per cent c.i. 1·5 to 5·65), extent of peritoneal metastasis as described by the Peritoneal Carcinomatosis Index (PCI) (per increase of 1 PCI point: HR 1·07, 1·02 to 1·12) and the completeness of cytoreduction (CC score above zero: HR 1·75, 1·18 to 2·59) were associated with reduced overall survival after CRS + HIPEC. Conclusion: Primary tumour obstruction or perforation, PCI score and CC score are valuable prognostic factors in the selection of patients with CPM for CRS + HIPEC.
Article
The Peritoneal Cancer Index (PCI), calculated intraoperatively, has previously yielded mixed results when correlated with computed tomography. This study aimed to quantify variation in this scoring method comparing radiologists’ and surgeons’ radiologic PCI (rPCI) assessment. The rPCI of 104 patients treated at a single institution for peritoneal carcinomatosis was calculated by an abdominal radiologist and a surgeon. An additional 36-patient cohort was studied to compare preoperative rPCI with intraoperative gold standard PCI. Agreement was compared using kappa statistics. The rPCI of the 104 patients studied ranged from 2 to 39 (median, 12; interquartile range [IQR], 6–23) by the radiologist’s analysis and 2 to 37 (median, 9; IQR, 6–15) by the surgeon’s analysis. There was good agreement for PCI cutoffs of 15 (77.48%; kappa, 0.40) and 20 (78.63%; kappa, 0.24). The 36-patient cohort undergoing surgical exploration showed a median rPCI of 4 (IQR, 2–5.75) and a median intraoperative PCI of 11 (IQR, 6–12), with a significant difference in score by method (p < 0.001, Wilcoxon signed-rank test). For rPCI cutoffs greater than 15 and 20, the surgeon’s and radiologist’s rPCI showed strong concordance, denoting the interobserver reproducibility of rPCI. Moreover, concordance with intraoperative PCI translated to radiographic assessment. The rPCI consistently underestimated intraoperative PCI, suggesting that rPCI may be a useful conservative tool for assessing peritoneal burden. Although surgical exploration is needed to “rule in” patients as candidates for CRS, the authors suggest that rPCI can be used to “rule out” patients as CRS candidates based on institutional PCI cutoffs.
Article
Background Despite thorough preoperative work-up for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC), so called open-close (OC) procedures as a result of irresectable disease remain common. Currently, diagnostic laparoscopy (DLS) is considered the gold standard, and consequently overrules the results of computed tomography (CT) scans; however, certain regions of the abdomen are difficult to assess and postoperative adhesion formation may further compromise staging during DLS. Purpose To determine whether better clinical assessment could be achieved by combining the results of DLS and preoperative CT scans during a multidisciplinary team (MDT) meeting. Material and Methods All patients who were eligible for CRS-HIPEC after DLS, but eventually underwent an OC procedure between 2010 and 2018 were selected. Radiological reassessment of CT scans was performed and combined with assessment of the DLS during a MDT meeting. The MDT was blinded for the outcome of the procedure (OC vs. CRS-HIPEC). Results The majority of the OC procedures (69%) was correctly predicted by the MDT. In most patients (88%), this conclusion was based on the combination of the radiological and surgical peritoneal cancer index (PCI). CT was particularly accurate for detection of larger tumor deposits in the abdominal regions, as 84%–86% was detected. Assessment of lesions in the small bowel regions is troublesome; 72% of lesions are missed on the preoperative CT scan. Conclusions A combination of radiological and surgical assessment of the PCI may lead to improved preoperative patient selection for CRS-HIPEC.
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Indocyanine green (ICG) fluorescence-guided surgery is a modality of intra-operative navigation that might support the surgeon with enhanced visualization of anatomical structures in real time. Over the last years, it has emerged as one of the most promising and rapidly developing technical innovations in surgery. The most popular current clinical applications include fluorescence cholangiography, bowel anastomotic perfusion assessment, fluorescence-guided lymphography for sentinel lymph-node identification and guided lymphadenectomy and the possible use in oncological surgery for the identification and localization of tumors and the diagnosis and treatment of peritoneal carcinosis. This paper provides an overview of the multiple fields of applications of ICG fluorescence-guided surgery in visceral and oncological surgery, discussing indications summarizing most recent and significative available literature and giving technical notes of use.
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The peritoneum is a unique serosal membrane, which can be the site of primary tumors and, more commonly, secondary pathologic processes. Peritoneal carcinomatosis is the most common malignant process to affect the peritoneal cavity, and the radiologist plays an important role in making the diagnosis and assessing the extent of disease, especially in sites that may hinder surgery. In this review we address the role of the radiologist in the setting of peritoneal pathology, focusing on peritoneal carcinomatosis as this is the predominant malignant process, followed by revising typical imaging findings that can guide the differential diagnosis. We review the most frequent primary and secondary peritoneal tumor and tumor-like lesions, proposing a systemic approach based on clinical history and morphological appearance, namely distinguishing predominantly cystic from solid lesions, both solitary and multiple.
Article
Purpose This study was to understand the perianesthesia care for patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS + HIPEC). Method This is a retrospective study. Design The perioperative electronic medical records of 189 CRS + HIPEC surgical cases at a hospital of Western Pennsylvania from 2012 to 2018 were analyzed to study the characteristics of perianesthesia care for CRS + HIPEC surgery. Findings The patients' median age was 57 (range 21-83) years, and 60% were men. The mean anesthesia time was 10.47 ± 2.54 hours. Most tumors were appendix or colorectal in origin, and the mean peritoneal cancer index score was 16.19 ± 8.76. The mean estimated blood loss was 623 ± 582 mL. The mean total intravenous crystalloid administered was 8,377 ± 4,100 mL. Fifty-two patients received packed red blood cells during surgery. Postoperatively, 100% of the patients were transferred to the intensive care unit. A majority (52%) of patients were extubated in the operating room. Median lengths of hospital and intensive care unit stays were 13 and 2 days, respectively. A majority (73%) of patients had 1 or more postoperative complications and 29% of patients experienced major postoperative complications (Clavien-Dindo grade III or higher) during the hospital stay. Prolonged hospitalization was owing to gastrointestinal dysfunctions and respiratory failure related to atelectasis and pleural effusion. Conclusions CRS + HIPEC is a major surgery with numerous challenges to the perianesthesia care team regarding hemodynamic adjustment, pain control, and postoperative complications, which demand training and future studies from the perianesthesia care team.
Article
Background: Pathological response of colorectal peritoneal metastasis (CRPM) may affect prognosis. We investigated the relationship between oncological outcomes and pathological response to chemotherapy of CRPM following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Methods: We conducted a retrospective analysis of a prospectively maintained Peritoneal Surface Malignancies database between 2015 and 2020. Analysis included patients with CRPM who underwent a CRS/HIPEC procedure (n = 178). The cohort was divided into three groups according to the response ratio (ratio of tumor-positive specimens to the total number of specimens resected): Group A, complete response; Group B, high response ratio, and Group C, low response ratio. Results: The group demographics were similar, but the overall complication rate was higher in Group C (65.2%) compared with Groups A (55%) and B (42.8%) [p = 0.03]. Survival correlated to response ratio; the estimated median disease-free survival of Group C was 9.1 months (5.97-12.23), 14.9 months (4.72-25.08) for Group B, and was not reached in Group A (p = 0.001). The estimated median overall survival in Group C was 35 months (26.69-43.31), and was not reached in Groups A and B (p = 0.001). Conclusions: The pathological response ratio to systemic therapy correlates with survival in patients undergoing CRS/HIPEC. This study supports the utilization of preoperative therapy for better patient selection, with a potential impact on survival.
Article
Background Peritoneal Cancer Index (PCI) and complete cytoreduction are the best outcome predictors following cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). Lesions in critical areas, regardless of PCI, complicate surgery and impact oncological outcomes. We prospectively defined “Critical lesions” (CL) as penetrating the hepatic hilum, diaphragm at hepatic outflow, major blood vessels, pancreas, or urinary tract. Methods Retrospective analysis of a prospective database of 352 CRS + HIPEC patients from 2015 to 2019. Excluded patients with aborted/redo operation (n = 112), or incomplete data (n = 19). Patients categorized by CL status and compared: operative time, estimated blood loss (EBL), PCI, transfusions, hospital stay, post-operative complications and mortality, overall survival (OS) and disease-free survival (DFS). Results Included 221 patients (78 CL; 143 no-CL). No difference in patients' characteristics: age, BMI, gender or co-morbidities noted. Operative time longer (5.3 h vs 4.3 h, p < 0.01), EBL higher (769 ml vs 405 ml, p < 0.01), transfusions higher (1.9 vs 0.7 Units, p < 0.001) and PCI higher (15.5 vs 9.5, p < 0.01) in CL. No difference in major complications. Postoperative complications, CL, OR-time and transfusions were predictive of OS in univariate analysis, while only complications remained on multivariate analysis. Median follow up of 21.4 months, 3-year DFS/OS was 22% vs 30% (p < 0.037) and 73% vs 87% (p < 0.014) in CL and non-CL, respectively. Despite CL complete resection, 17/38 patients (44.7%) that recurred had recurrence at previous CL site. Conclusions Critical lesions complicate surgery and may be associated with poor oncological outcomes with high local recurrence rate, despite no significant difference in complications. Utilizing adjuvant or intra-operative radiation may be beneficial.
Article
Background: This study examines the impact of intraoperative macroscopic tumour consistency on short-term and long-term outcomes after cytoreductive surgery (CRS) with intraperitoneal chemotherapy (IPC) for appendiceal adenocarcinoma with peritoneal metastases. Methods: Macroscopic intraoperative tumour consistency was classified in three groups as soft (jelly-like geltatinous tumours), hard (hard tumour nodules without gelatinous features) and intermediate (both soft and hard features). In-hospital mortality, major morbidity, intensive care unit (ICU), high dependency unit (HDU) and total hospital stay, disease-free survival (DFS) and overall survival (OS) were compared. Results: The three groups had similar perioperative short-term outcomes. Patients with soft, intermediate and hard tumours revealed differences in OS (p < 0.001) and DFS (p = 0.03). Multivariable analysis revealed a shorter OS for patients with hard versus soft tumours (HR for hard tumours = 4.43, 95%CI 2.19-9.00). Conclusions: Intraoperative macroscopic tumour consistency may be used as a prognostic marker for survival in patients with appendiceal adenocarcinoma with peritoneal metastases.
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Die chirurgische Zytoreduktion (CRS) mit hyperthermer intraperitonealer Chemotherapie (HIPEC) kann bei geeigneten Patienten mit peritonealen Metastasen kolorektaler Karzinome das Gesamtüberleben im Vergleich zu reiner systemischer Chemotherapie signifikant verlängern. Entscheidend für ein gutes onkologisches Ergebnis ist einerseits die makroskopisch komplette Zytoreduktion, andererseits aber auch eine möglichst frühe chirurgische Therapie, da eine lineare Korrelation zwischen der peritonealen Tumorlast und dem Gesamtüberleben besteht. Eine synchrone Resektion von Lebermetastasen ist mit guten Ergebnissen möglich und hat keinen Einfluss auf die Morbidität. Für die intraperitoneale Chemotherapie sind die Substanzen Mitomycin C und Oxaliplatin derzeit als gleichwertig zu betrachten. Diskrepante Ergebnisse liegen zur perioperativen systemischen Chemotherapie vor, da einzelne Studien ein schlechteres Gesamtüberleben nach neoadjuvanter Therapie zeigten. Im Hinblick auf die adjuvante Therapie gibt es Hinweise auf einen Überlebensvorteil, sofern mindestens 6 Zyklen verabreicht werden. Die derzeit noch schwierige Früherkennung peritonealer Metastasen wird möglicherweise zukünftig durch den Einsatz von „liquid biopsies“ mit Nachweis freier Tumor-DNA oder -RNA sicherer und einfacher, bis dahin kommt für Risikopatienten eine geplante Second-look-Laparotomie infrage. Ergänzend hierzu wird in mehreren Studien derzeit der Stellenwert einer adjuvanten oder prophylaktischen HIPEC geprüft. Im Falle eines Rezidivs nach HIPEC sollte ein erneutes chirurgisches Vorgehen erwogen werden, wobei zur Indikationsstellung dieselben Kriterien anzuwenden sind wie für den Primäreingriff. Ein rezidivfreies Intervall >2 Jahre ist prognostisch günstig.
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Background Measurement of cell-free DNA (cfDNA) in plasma – the so called liquid biopsy - is a novel method for early detection of cancer. Necrotic cancer cells release various DNA fragments that can be detected in plasma or serum. The aim of our study was to investigate the concentration of circulating ALU115, LINE79 and LINE297 fragments in plasma from venous and arterial blood of colorectal cancer (CRC) patients before, during and 5 days after surgical intervention. Patients and methods Thirty patients (16 female, 14 male, median age 56 years), undergoing surgery for colorectal and appendix cancer, and 17 healthy volunteers were included in this study. Plasma samples were collected from patients and healthy individuals. Qualitative polymerase chain reaction (PCR) and quantitative real-time PCR analyses were conducted using specific primers for ALU115, LINE79 and LINE297. Results The concentration of ALU115 was significantly increased in plasma of CRC patients compared to the control group (p = 0.002). Interestingly, the concentration of LINE297 was significantly higher in healthy individuals than patients (p = 0.031). We did not find any difference regarding LINE79 between the two groups (p = 0.893). The total cfDNA concentration was slightly increased in plasma after the surgery (p < 0.056), however, the difference was not significant. Interestingly, no correlation was detected between the peritoneal carcinosis index (PCI) and conventional tumor markers. Conclusion According to our results, the concentration of ALU115 in cfDNA could be a potential biomarker for diagnosis of CRC. LINE79 or the conventional tumor markers CEA or CA19-9 do not seem useful for the detection of malignant tumors. Whether the amount of LINE297 in cfDNA represents a reliable biomarker for early diagnosis has yet to be confirmed.
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Background. Prolonged survival of patients affected by peritoneal metastasis (PM) of colorectal origin treated with complete cytoreduction followed by intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) has been reported. However, two-thirds of the patients after complete cytoreduction and perioperative chemotherapy (POC) develop recurrence. This study is to analyze the prognostic factors of PM from colorectal cancer following the treatment with cytoreductive surgery (CRS) + POC. Patients and Methods. During the last 8 years, 142 patients with PM of colorectal origin have been treated with CRS and perioperative chemotherapy. The surgical resections consisted of a combination of peritonectomy procedures. Results. Complete cytoreduction (CCR-0) was achieved at a higher rate in patients with peritoneal cancer index (PCI) score less than 10 (94.7%, 71/75) than those of PCI score above 11 (40.2%, 37/67). Regarding the PCI of small bowel (SB-PCI), 89 of 94 (91.5%) patients with ≤2 and 22 of 48 (45.8%) patients with SB-PCI ≥ 3 received CCR-0 resection (P < 0.001). Postoperative Grade 3 and Grade 4 complications occurred in 11 (7.7%) and 14 (9.9%). The overall operative mortality rate was 0.7% (1/142). Cox hazard model showed that CCR-0, SB-PCI ≤ 2, differentiated carcinoma, and PCI ≤ 10 were the independent favorite prognostic factors. Conclusions. Complete cytoreduction, PCI, SB-PCI threshold, and histologic type were the independent prognostic factors.
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Peritoneal carcinomatosis (PC) is one manifestation of metastatic colorectal cancer (CRC). Tumor growth on intestinal surfaces and associated fluid accumulation eventually result in bowel obstruction and incapacitating levels of ascites, which profoundly affect the quality of life for affected patients. PC appears resistant to traditional 5-fluorouracil-based chemotherapy, and surgery was formerly reserved for palliative purposes only. In the absence of effective treatment, the historical prognosis for these patients was extremely poor, with an invariably fatal outcome. These poor outcomes likely explain why PC secondary to CRC has received little attention from oncologic researchers. Thus, data are lacking regarding incidence, clinical disease course, and accurate treatment evaluation for patients with PC. Recently, population-based studies have revealed that PC occurs relatively frequently among patients with CRC. Risk factors for developing PC have been identified: right-sided tumor, advanced T-stage, advanced N-stage, poor differentiation grade, and younger age at diagnosis. During the past decade, both chemotherapeutical and surgical treatments have achieved promising results in these patients. A chance for long-term survival or even cure may now be offered to selected patients by combining radical surgical resection with intraperitoneal instillation of heated chemotherapy. This combined procedure has become known as hyperthermic intraperitoneal chemotherapy. This editorial outlines recent advancements in the medical and surgical treatment of PC and reviews the most recent information on incidence and prognosis of this disease. Given recent progress, treatment should now be considered in every patient presenting with PC.
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The study compared the outcome in patients with advanced colonic cancer at high risk of peritoneal metastases (mucinous or signet-ring cell) without peritoneal or systemic spread, treated with standard colectomy or a more aggressive combined surgical approach. The study included patients with colonic cancer with clinical T3/T4, any N, M0, and mucinous or signet ring cell histology. The 25 patients in the experimental group underwent hemicolectomy, omentectomy, bilateral adnexectomy, hepatic round ligament resection, and appendectomy, followed by HIPEC. The control group comprised 50 patients treated with standard surgical resection during the same period in the same hospital by different surgical teams. Outcome data, morbidity, peritoneal recurrence rate, and overall, and disease-free survival, were compared. Peritoneal recurrence developed in 4% of patients in the experimental group and 22% of controls without increasing morbidity (P < 0.05). Actuarial overall survival curves disclosed no significant differences, whereas actuarial disease-free survival curves showed a significant difference between groups (36.8 versus 21.9 months, P < 0.01). A more aggressive preventive surgical approach combined with HIPEC reduces the incidence of peritoneal recurrence in patients with advanced mucinous colonic cancer and also significantly increases disease-free survival compared with a homogeneous control group treated with a standard surgical approach without increasing morbidity.
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The objective of this study was to investigate the efficacy of first-line chemotherapy containing irinotecan and/or oxaliplatin in patients with advanced mucinous colorectal cancer. Prognostic factors associated with response rate and survival were identified using univariate and multivariate logistic and/or Cox proportional hazards analyses. The population included 255 patients, of whom 49 (19%) had mucinous and 206 (81%) had non-mucinous colorectal cancer. The overall response rates for mucinous and non-mucinous tumours were 18.4 (95% CI, 7.5-29.2%) and 49% (95% CI, 42.2-55.8%), respectively (P=0.0002). After a median follow-up of 45 months, median overall survival for the mucinous patients was 14.0 months compared with 23.4 months for the non-mucinous group (hazard ratio (HR), 1.74; CI 95%, 1.27-3.31; P=0.0034). After adjustment for significant features by multivariate Cox regression analysis, mucinous histology was associated with poor overall survival (HR, 1.593, 95% CI, 1.05-2.40; P=0.0267), together with performance status ECOG 2, number of metastatic sites > or =2, and peritoneal metastases. This retrospective analysis shows that patients with mucinous colorectal cancer have poor responsiveness to oxaliplatin/irinotecan-based first-line combination chemotherapy and an unfavourable prognosis compared with non-mucinous colorectal cancer patients.
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To compare the long-term survival of patients with isolated and resectable peritoneal carcinomatosis (PC) in comparable groups of patients treated with systemic chemotherapy containing oxaliplatin or irinotecan or by cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC). All patients with gross PC from colorectal adenocarcinoma who had undergone cytoreductive surgery plus HIPEC from 1998 to 2003 were evaluated. The standard group was constituted by selecting patients with colorectal PC treated with palliative chemotherapy during the same period, but who had not benefited from HIPEC because the technique was unavailable in the center at that time. Forty-eight patients were retrospectively included in the standard group and were compared with 48 patients who had undergone HIPEC and were evaluated prospectively. All characteristics were comparable except age and tumor differentiation. There was no difference in systemic chemotherapy, with a mean of 2.3 lines per patient. Median follow-up was 95.7 months in the standard group versus 63 months in the HIPEC group. Two-year and 5-year overall survival rates were 81% and 51% for the HIPEC group, respectively, and 65% and 13% for the standard group, respectively. Median survival was 23.9 months in the standard group versus 62.7 months in the HIPEC group (P < .05, log-rank test). Patients with isolated, resectable PC achieve a median survival of 24 months with modern chemotherapies, but only surgical cytoreduction plus HIPEC is able to prolong median survival to roughly 63 months, with a 5-year survival rate of 51%.
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In patients with metastatic colorectal cancer (mCRC), several prognostic factors such as performance status (PS), number of metastatic sites, carcinoembryonic antigen (CEA), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) have been reported. The objective of this study was to clarify the prognostic impact of Baseline Sum of Longest Diameter (BSLD) of target lesions by Response Evaluation Criteria in Solid Tumor (RECIST) in patients with mCRC. The subjects of this study were consecutive 103 patients with mCRC who had been received the first line systemic chemotherapy between September 2002 and March 2005. The chemotherapy regimens included leucovorin-modulated 5-fluorouracil (5-FU) (n = 27) and 5-FU plus irinotecan (n = 76). The median overall survival time was 547 days. The median BSLD was 14.3 cm (range, 1.1-54.7). In univariate analysis, identified prognostic variables on survival were PS (0, 1 versus 2), number of metastatic sites (1 versus >1), peritoneal dissemination (+ versus -), pleural effusion (PE) and/or ascites, white blood cell (> or = versus <10,000/mm(3)), ALP (> or = versus <300 IU), LDH (> or = versus <300 IU), CEA (> or = versus <5 ng/ml), chemotherapy regimen, presence of liver metastasis, and BSLD. In multivariate analysis with covariates of the above significant factors, BSLD (> or = versus <10 cm) (HR 0.431, 95% CI 0.237-0.785, P = 0.0059), PS (HR 0.248, 95% CI 0.107-0.577, P = 0.0012), PE and/or ascites (HR 0.402, 95% CI 0.228-0.708, P = 0.0016) were independent prognostic factors. BSLD of target lesions by RECIST representing tumor volume might be an independent prognostic factor of patients with mCRC after systemic chemotherapy.
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Carcinoma of the colon complicated by obstruction or perforation has been recognized as having a poorer prognosis than tumors without obstruction or perforation. To clarify the natural history, failure patterns, and implications for adjuvant treatment after resection with curative intent, a review of the recent Massachusetts General Hospital (MGH) experience was undertaken. From 1970 to 1977, 77 patients with obstructive colonic carcinoma and 34 patients with localized perforation at the tumor site were identified and compared with a control group of 400 patients without obstruction or perforation undergoing curative resection. All patients were observed for a minimum of five years or until the patient's death. The actuarial five-year survival and disease-free survival rates in patients with obstruction was 31% and 44%, respectively, in contrast to 59% and 75% in control patients. For patients with localized perforation, the five-year actuarial survival and disease-free survival rates were 44% and 35%, re...
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We study spinor Bose-Einstein condensates with dipolar interaction in double well potentials. We consider the two-site Bose Hubbard model and find single atom tunneling occurs for the small tunneling strength. We also investigate the entanglement between the two wells and show that the entanglement is due to both number and spin degrees of freedom. The number entanglement is insensitive to the dipolar interaction, while the spin entanglement is suppressed by dipolar interaction. In addition, we show that the single atom tunneling behavior can be manipulated by adiabatically varying the energy offset between the two wells. Graphical abstract
Article
Introduction: The combination of cytoreductive surgery (CRS) and perioperative chemotherapy (PIC) have been proposed as an innovative technique for peritoneal carcinomatosis and is currently considered as a standard treatment for colorectal peritoneal carcinomatosis (CRPC) in selected patients. Peritoneal cancer index (PCI) has been suggested to be the most important prognostic factors for the outcomes of patients with CRPC. In this paper, we have studied patients with CRPC and a very low PCI of 5 or less and their survival outcomes. Methods: This is a retrospective study of prospectively collected data of 60 consecutive patients with CRPC and PCI ≤5, who underwent CRS and PIC by the same surgical team at St George hospital in Sydney, Australia between January 1996 and April 2015. Clinical outcomes of these patients were analysed. Results: Hospital mortality was 0%. 14 patients (23.4%) had grade III/IV morbidity. The median follow-up was 22.2 months (range=0.1-104.2). The median survival was 80.6 months (95% confidence interval (CI)=35.1-126.1), with an overall 1-year, 3-year, and 5-year survival rate of 96.1%, 72.6% and 54.7% respectively. Among 60 patients, 31 patients experienced the recurrence of the disease (51.7%). The median disease-free survival was 10.8 months (95%CI=7.2-14.4). Conclusion: This innovative approach combining CRS and PIC has shown encouraging outcomes and offers hope for patients with CRPC. Our results suggest that CRS and PIC can be performed safely to provide significant survival benefits for patients with low volume of disease. Early referral to specialist centre for evaluation is warranted for better survival outcomes.
Article
The peritoneal cancer index (PCI) is the main prognostic factor for establishing potentially resectable peritoneal metastases from colorectal cancer. Attempts have been made to set a PCI cutoff on which to base indications of complete cytoreductive surgery (CCRS) with hyperthermic intraperitoneal chemotherapy (HIPEC), but none have reached consensus. The aim of this study was to investigate the relation between the PCI and overall survival (OS). We included all consecutive patients homogeneously treated with CCRS and HIPEC between 2003 and 2012. The PCI was calculated at the end of the surgical procedure. The correlation between the PCI and OS was studied using statistical modeling from the simplest to the most complex methods (including linear, quadratic, cubic, and spline cubic). These models were compared by Akaike's information criteria (AIC). For the 173 treated patients, 5-year OS reached 41 %. The mean PCI was 10.2 (±6.8). The linear model was the most appropriate to relate the PCI to OS as confirmed with the AIC scoring system. In multivariate analysis, the PCI was confirmed as being the most important prognostic factor (hazard ratio = 1.1 for each supplementary point, p < 0.0001). There is a perfect linear correlation between the PCI and OS, which precludes setting a unique PCI cutoff for CCRS + HIPEC. Overall, CCRS + HIPEC is generally indicated for PCI < 12 and contraindicated for PCI > 17. Between 12 and 17, other parameters have to be taken into account, such as the presence of extraperitoneal metastases, general performance status, and chemosensitivity.
Article
Background: Nonresectable colorectal cancer often causes malignant intestinal obstruction due to peritoneal dissemination. However, no previous report has specifically investigated which patients, with peritoneal dissemination from colorectal cancer, would actually benefit from palliative surgery. This study defines the selection criteria for patients who are likely to benefit from palliative surgery. Methods: Twenty-one patients underwent palliative surgery for malignant bowel obstruction due to peritoneal dissemination from colorectal cancer. In all cases, the advanced and nonresectable nature of the tumor was confirmed at laparotomy. Clinical factors such as age, gender, serum level of carcinoembryonic antigen, amount of ascites, location of the primary cancer, surgical procedure, and postoperative chemotherapy were analyzed for prognostic significance in symptom-free and overall survival using the Kaplan–Meier product limit method and the log-rank test. Results: All the postoperative courses were uneventful. Obstruction recurred after a median symptom-free interval of 61 days in the group with less than 100 ml of ascites, whereas it recurred after 9 days in the group with more than 100 ml of ascites. Symptom-free survival rates in patients who manifested ascites were significantly lower than in those without ascites (P = 0.0321, log-rank method). The symptom-free and overall survival rates in patients who underwent postoperative chemotherapy were significantly higher (P = 0.0225 and 0.0003). Conclusions: Palliative surgery can be performed effectively for patients without ascites. For patients who do not meet this criterion, a non-surgical procedure may be preferable.
Article
Background Complete cytoreductive surgery (CCRS) plus hyperthermicintraperitoneal chemotherapy (HIPEC) is on the verge of becoming the gold standard treatment for selected patients presenting peritoneal metastases (PM) of colorectal origin. PM is scored with the peritoneal cancer index (PCI), which is the main prognostic factor. However, small bowel (SB) involvement could exert an independent prognostic impact. Aim To define an adequate cut-off for the PCI and to appraise whether SB involvement exerts an impact on this cut-off. Patients and methods Patients (n=139) treated with CCRS plus HIPEC were prospectively verified and retrospectively analyzed. One hundred presented with SB involvement of different extents and at different locations. Results All the patients with a PCI ≥ 15 exhibited SB involvement. Five-year overall survival was 48% when the PCI was < 15 vs 12% when it was ≥ 15 (p<0.0001. The multivariate analysis retained two prognostic factors: PCI ≥ 15 (p=0.02, HR=1.8), and the involvement of area 12 (lower ileum) (p=0.001, HR=3.1). When area 12 was invaded, it significantly worsened the prognosis: 5-year overall survival of patients with a PCI < 15 and area 12 involved was 15% , close to that of patients with a PCI ≥15 (12%) and far lower than that of patients with a PCI < 15 and no area 12 involvement (70%). Conclusion A PCI greater than 15 appears to be a relative contraindication for treatment of colorectal PM with CCRS+HIPEC. Involvement of the lower ileum is also a negative prognostic factor to be taken into consideration.
Article
To analyze and compare survival in patients operated for colorectal liver metastases (LM) with that in patients optimally resected for peritoneal metastases (PM). This study concerns 287 patients with LM and 119 patients with PM treated with surgery plus chemotherapy between 1993 and 2009, excluding patients presenting both LM and PM. Mortality (respectively, 2.7% and 4.2%), morbidity (respectively, 11% and 17%), and 5-year overall survival (OS) rates (respectively, 38.5% and 36.5%) were not statistically different between the LM group and the PM group. Multivariate analysis showed that the extent of the disease was the main prognostic factor, which led us to divide the population into 5 subgroups. The best 5-year OS rate (72.4%) was obtained in patients with minimal peritoneal disease [peritoneal cancer index (PCI) ≤5]. OS was similar for the patients with less than 10 LM and those with a PCI between 6 and 15 (respectively, 39.4% and 38.7%). Five-year OS was lower in patients with more than 10 LM (18.1%), and dramatically low for patients with a PCI > 15 (11.8%). This study underlines the prognostic impact of the tumor burden in metastatic colorectal disease. In selected patients, similar survival rates can be obtained after optimal treatment of LM and PM. As the role of optimal surgical resection of LM is widely accepted, our results confirm that an optimal attitude should also be adopted to treat PM with a PCI < 16, particularly in patients with very low PCI (<5) where survival could be better than LM.
Article
Background: Although a randomized trial demonstrated a survival benefit of cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC) over systemic chemotherapy alone, the treatment of peritoneal carcinomatosis from colorectal cancer (CRPC) is still a matter of debate. The aims of this study were to evaluate long-term outcome after CRS and IPC and to identify the prognostic factors associated with a cure. Methods: Patients were considered cured if the disease-free survival interval lasted at least 5 years after the treatment of CRPC or its last recurrence. Patients who had died postoperatively, or from non-cancer-related deaths, or patients with a follow-up of less than 5 years since the last curative treatment were excluded from the analysis. Results: From 1995 to 2006, 107 patients (median age, 48 years; range, 19-67 years) underwent complete CRS, followed by IPC. Postoperative complications occurred in 50 patients (53%), including 4 postoperative deaths. After a median follow-up of 77 months (range, 60-144 months), 5-year and 10-year overall survival rates were 35% and 15%, respectively. Seventeen patients (16%) were considered cured after a disease-free interval of at least 5 years, of whom 14 never developed a recurrence. Cured patients had a significantly lower median peritoneal cancer index than noncured patients, respectively 4 (3-16) and 12 (2-36) (P = 0.0002). In multivariate analysis, a peritoneal cancer index of 10 or less was the only independent factor predicting cure. Conclusions: The cure rate (16%) after complete CRS of colorectal peritoneal carcinomatosis, followed by IPC, in selected patients is close to that obtained after resection of colorectal liver metastases.
Article
Background: We assessed the learning curve (LC) of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in treating peritoneal surface malignancies (PSM) in two centers and evaluated in which extent surgical tutoring could abbreviate the learning process. Methods: Six hundred and forty-one cases submitted to CRS using peritonectomy procedures and HIPEC were considered. After having overcome its own LC, the NCI of Milan has provided technical assistance to Bentivoglio's centre for the development of a new PSM program since 2003. The risk-adjusted sequential probability ratio test (RA-SPRT) was employed to assess the LC of the two centers. Outcomes were incomplete cytoreduction, G3-5 morbidity (NCI-CTCAE.v3) and procedure-related mortality (PRM). Results: Rates of incomplete cytoreduction, G3-5 morbidity, and PRM were 8.4%, 30.1%, and 3.9%, respectively, in the entire series. The breaking points of the LC concerning incomplete cytoreduction, G3-5 morbidity, and PRM were achieved at 141, 158, and 144 cases, in the Milan's experience, and at 126, 134, and 60 cases in the Bentivoglio's experience. Conclusions: Surgical tutoring could substantially shorten the steep LC associated with CRS and HIPEC. Our data should be confirmed by further studies on LC focusing oncological outcomes. Other factors that could influence the length of learning process should be identified.
Article
Peritoneal carcinomatosis is a common presentation in patients with metastatic colorectal cancer and the overall survival is poor. In most patients, the disease remains limited to the peritoneal cavity. Therefore, investigators have applied cytoreductive surgery and hyperthermic perioperative chemotherapy as the standard approach for selected patients with peritoneal metastases from colorectal cancer. Overall, very promising long-term survival has been shown in a subset of patients with a limited extent of peritoneal disease before treatment. Whether randomised, controlled trials are needed to definitively show the magnitude of benefit, if any, of this approach is an important question. This Debate outlines the arguments on each side of this issue.
Article
BACKGROUND Peritoneal carcinomatosis (PC) is a common evolution of digestive cancer, associated with a poor prognosis. Yet it is poorly documented in the literature.METHODS Three hundred seventy patients with PC from non-gynecologic malignancies were followed prospectively: the PC was of gastric origin in 125 cases, of colorectal origin in 118 cases, of pancreatic origin in 58 cases, of unknown origin in 43 cases, and of miscellaneous origins in 26 cases. A previously reported PC staging system was used to classify these 370 patients.RESULTSMean and median overall survival periods were 6.0 and 3.1 months, respectively. Survival rates were mainly affected by the initial PC stage (9.8 months for Stage I with malignant peritoneal granulations less than 5 mm in greatest dimension, versus 3.7 months for Stage IV with large, malignant peritoneal masses more than 2 cm in greatest dimension). The presence of ascites was associated with poor survival of patients with gastric or pancreatic carcinoma. Differentiation of the primary tumor did not influence the prognoses of patients with PC.CONCLUSIONSA better knowledge of the natural history of PC is needed, in view of the many Phase I, II, and III trials currently being conducted to evaluate aggressive multimodal therapeutic approaches to treating patients with PC from non-gynecologic malignancies. Cancer 2000;88:358–63. © 2000 American Cancer Society.
Article
Inadvertent perforation of the bowel during curative resection for colorectal cancer has serious consequences. In 174 curative resections with spillage, five-year survival was 29 per cent. In 67 patients where the cancer itself was disrupted during dissection, five-year surival fell to 14 per cent in the colon and to 9.3 per cent in the rectum. Local recurrence developed in 65 per cent of spillage cases. In Dukes' C tumors that were perforated during surgery, local recurrence occurred in 87 per cent. As surgeons, our efforts must be directed toward preventing injury to the bowel during definitive resection of colorectal cancers. The instillation of tumoricidal solutions within the bowel lumen and the application of bowel ligatures prior to dissection may help toward preventing recurrence, should inadvertent perforation and spillage occur.
Article
To analyze the impact of systematic second-look surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC) performed 1 year after resection of the primary tumor in asymptomatic patients at high risk of developing peritoneal carcinomatosis (PC). From 1999 to 2009, 41 patients without any sign of recurrence on imaging studies underwent second-look surgery aimed at treating limited PC earlier and more easily. They were selected based on 3 primary tumor-associated criteria: resected minimal synchronous macroscopic PC (n = 25), synchronous ovarian metastases (n = 8), and perforation (n = 8). PC was found and treated with complete surgery plus HIPEC in 23 of the 41 (56%) patients. The other patients underwent complete abdominal exploration plus systematic HIPEC. Median follow-up was 30 (9-109) months. One patient died postoperatively at day 69. Grade 3-4 morbidity was low (9.7%). The 5-year overall survival rate was 90% and the 5-year disease-free survival rate was 44%. Peritoneal recurrences occurred in 7 patients (17%), 6 of whom had macroscopic PC discovered during the second-look (26%), and one patient had no macroscopic PC (6%). In the univariate analysis, the presence of PC at second-look surgery was a significant risk factor for recurrence (P = 0.006). Selection criteria for high-risk patients appear to be accurate. In these patients, the second-look strategy treated peritoneal carcinomatosis preventively or at an early stage, yielding promising results. This study has allowed us to design a multicentric randomized trial (comparing the second-look + HIPEC approach versus standard follow-up alone), which is beginning.
Article
To evaluate the role of modern systemic therapies and its role as palliative or curative therapy for patients with colorectal peritoneal carcinomatosis with an emphasis on patient selection with the colorectal Peritoneal Surface Disease Severity Score (PSDSS). From three specialized treatment centers, patients with colorectal peritoneal carcinomatosis were identified between December 1988 to December 2009 to receive best supportive care, standard, or modern systemic therapies. Intent was classified as palliative or curative (if treated by cytoreductive surgery combined with perioperative intraperitoneal chemotherapy). Patients were stratified according to the PSDSS. Survival was estimated by the Kaplan-Meier method. Palliative and curative treatment achieved a median survival of 9 (95% confidence interval [95% CI] 5.9-12.8) and 38 (95% CI 30.2-45.2) months, respectively (P < 0.001). The type of chemotherapy in the palliative and curative group influenced outcome (P < 0.001, P = 0.011, respectively). In the palliative group, PSDSS I/II had a median survival of 24 (95% CI 15.6-32.6) and PSDSS III/IV had a median survival of 6 (95% CI 4.9-8.0) months (P < 0.001). In the curative group, PSDSS I/II had a median survival of 49 (95% CI 40.0-58.3) and PSDSS III/IV had a median survival of 31 (95% CI 20.4-40.9) months (P = 0.002). Modern systemic therapies were associated with improved outcome in patients with colorectal peritoneal carcinomatosis treated systemically alone or with cytoreductive surgery combined with perioperative intraperitoneal chemotherapy. Preoperative evaluation with the PSDSS may improve patient selection and optimize outcomes.
Article
The aim of our study was to provide population-based data on incidence and prognosis of synchronous peritoneal carcinomatosis and to evaluate predictors for its development. Diagnosed in 1995-2008, 18,738 cases of primary colorectal cancer were included. Predictors of peritoneal carcinomatosis were analysed by multivariable logistic regression analysis. Median survival in months was calculated by site of metastasis. In the study period, 904 patients were diagnosed with synchronous peritoneal carcinomatosis (4.8% of total, constituting 24% of patients presenting with M1 disease). The risk of peritoneal carcinomatosis was increased in case of advanced T stage [T4 vs. T1,2: odds ratio (OR) 4.7, confidence limits 4.0-5.6), advanced N stage [N0 vs. N1,2: OR 0.2 (0.1-0.2)], poor differentiation grade [OR 2.1 (1.8-2.5)], younger age [<60 years vs. 70-79 years: OR 1.4 (1.1-1.7)], mucinous adenocarcinoma [OR 2.0 (1.6-2.4)] and right-sided localisation of primary tumour [left vs. right: OR 0.6 (0.5-0.7)]. Median survival of patients with peritoneum as single site of metastasis remained dismal [1995-2001: 7 (6-9) months; 2002-2008: 8 (6-11) months], contrasting the improvement among patients with liver metastases [1995-2001: 8 (7-9) months; 2002-2008: 12 (11-14) months]. To conclude, synchronous peritoneal metastases from colorectal cancer are more frequent among younger patients and among patients with advanced T stage, mucinous adenocarcinoma, right-sided tumours and tumours that are poorly differentiated. The prognosis of synchronous peritoneal carcinomatosis remains poor with a median survival of 8 months and even worse if concomitant metastases in other organs are present.
Article
Survival benefit of cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion was demonstrated by a prospective randomized trial for colorectal peritoneal carcinomatosis. Because of a recent substantial improvement in chemotherapy, the authors analyzed treatment options of colorectal carcinomatosis in the current era. Consecutive patients with colorectal carcinomatosis treated by cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion from 2001 to 2007 were included. The control group patients with carcinomatosis received contemporary chemotherapy alone. Overall survival was the primary endpoint. All patients underwent systemic chemotherapy. The cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion group (n=67) was similar to the control group (n=38) in sex, tumor grade, site of tumor origin, T status, and N status. The control group was, however, older (59 vs 51 years; P<.001). Median survival measured from the diagnosis of peritoneal disease was longer with cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion (34.7 months vs 16.8 months; P<.001). Presence of liver metastasis was a significant negative predictor of survival (hazard ratio, 2.13). The authors concluded that 1) contemporary chemotherapy is associated with prolonged survival among patients with carcinomatosis as compared with historical controls, and 2) addition of cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion to modern chemotherapy regimens may significantly prolong survival. Cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion and systemic chemotherapy are not competitive therapies, and they both have a role in a multidisciplinary approach to patients with carcinomatosis.
Article
To analyze a large series of patients with pseudomyxoma peritonei (PMP) treated with cytoreductive surgery associated with perioperative intraperitoneal chemotherapy (PIC) in 18 French-speaking centers. From March 1993 to December 2007, 301 patients with diffuse PMP were treated by cytoreductive surgery with PIC. Complete cytoreductive surgery was achieved in 219 patients (73%), and hyperthermic intraperitoneal chemotherapy (HIPEC) was performed in 255 (85%), mainly during the latter period of the study. Postoperative mortality and morbidity were 4.4% and 40%, respectively. The mean follow-up was 88 months. The 5-year overall and disease-free survival rates were 73% and 56%, respectively. The multivariate analysis identified 5 prognostic factors: the extent of peritoneal seeding (p=0.004), the center (p=0.0004), the pathologic grade (p=0.03), gender (p=0.02), and the use of HIPEC (p=0.04). When only the 206 patients with complete cytoreductive surgery were considered, the extent of peritoneal seeding was the only significant prognostic factor (p=0.004). This large multicentric retrospective study confirms that cytoreductive surgery combined with PIC (with the use of hyperthermia) should be considered as the gold standard treatment of PMP and should be performed in specialized centers. It underlines the prognostic impact of the extent of peritoneal seeding, especially in patients treated by complete cytoreductive surgery. This prognostic impact appears to be greater than that of the pathologic grade.
Article
Purpose Peritoneal carcinomatosis (PC) from colorectal cancer traditionally is considered a terminal condition. Approaches that combine cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy (PIC) have been developed recently. The purpose of this study was to assess early and long-term survival in patients treated with that strategy. Patients and Methods A retrospective-cohort, multicentric study from French-speaking countries was performed. All consecutive patients with PC from colorectal cancer who were treated with CRS and PIC (with or without hyperthermia) were included. Patients with PC of appendiceal origin were excluded. Results The study included 523 patients from 23 centers in four French-speaking countries who underwent operation between 1990 and 2007. The median follow-up was 45 months. Mortality and grades 3 to 4 morbidity at 30 days were 3% and 31%, respectively. Overall median survival was 30.1 months. Five-year overall survival was 27%, and five-year disease-free survival was 10%. Complete CRS was performed in 84% of the patients, and median survival was 33 months. Positive independent prognostic factors identified in the multivariate analysis were complete CRS, PC that was limited in extent, no invaded lymph nodes, and the use of adjuvant chemotherapy. Neither the grade of disease nor the presence of liver metastases had a significant prognostic impact. Conclusion This combined treatment approach against PC achieved low postoperative morbidity and mortality, and it provided good long-term survival in patients with peritoneal scores lower than 20. These results should improve in the future, because the different teams involved will gain experience. This approach, when feasible, is now considered the gold standard in the French guidelines.
Article
Cytoreductive surgery and Hyperthermic Intraperitoneal Chemotherapy have achieved good long-term results in patients with complete surgical eradication of their peritoneal dissemination but at the expense of significant perioperative morbidity and mortality. The high complication rate has been attributed to the steep learning curve associated with this procedure. We report on the current literature regarding the learning curve for this procedure and the key components that determine the success in learning this new skill.
Article
: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has been offered in many institutions worldwide since the 1990s. Despite its existence of more than 10 years, this treatment has received heavy criticism for its morbidity and mortality rates. This consequentially resulted in a lack of randomized trials being conducted and translates into a lack of the most reliable form of scientific evidence in clinical research, hence limiting its general acceptance. : To report the morbidity and mortality outcomes of CRS and HIPEC from all institutions performing this treatment as a prelude toward establishing the safety of this treatment for peritoneal carcinomatosis. : A systematic review of relevant studies before August 2008 was performed. Each study was appraised using a predetermined protocol. The quality of studies was assessed. The morbidity and mortality of the treatment were synthesized through a narrative review with full tabulation of results of all included studies. : The morbidity and mortality outcomes of CRS and HIPEC are similar to a major gastrointestinal surgery, such as a Whipple's procedure. To derive the maximal benefit of this treatment, careful patient selection with an optimal level of postoperative care must be advocated to avoid undesirable complications of this treatment.
Article
The objective of the present meta-analysis was to analyze the survival outcomes of patients with colorectal peritoneal carcinomatosis (CRPC), with particular focus on cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy (PIC). A search was conducted on Medline from 1950 to February 2009 and Pubmed from 1950 to February 2009 for original studies on CRS with PIC. All articles included in this study were assessed with the application of predetermined selection criteria. Results regarding the overall survival in the meta-analysis were expressed as hazard ratios with 95% confidence intervals. Forty-seven manuscripts were selected in the present systematic review, including 4 comparative studies and 43 observational studies of CRS with PIC. From the meta-analysis, it can be seen that a significant improvement in survival was associated with treatment by CRS and hyperthermic intraperitoneal chemotherapy compared with palliative approach (P < 0.0001). The pooled data did not show a significant improvement in overall survival for patients treated by CRS and early postoperative intraperitoneal chemotherapy versus surgery and systemic chemotherapy (P = 0.35). The overall effect of PIC is significantly better than the control group (P = 0.0002). The current literature suggests that patients with liver metastasis amendable to resection should not be excluded from CRS and PIC. However, there is a need for further evaluation of the prognostic significance of lymph node and liver involvement, ideally in large prospective trials. The meta-analysis showed that combined therapy involving CRS and PIC had a statistically significant survival benefit over control groups.
Article
Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has been demonstrated to have an improved survival over systemic chemotherapy for patients with colorectal peritoneal carcinomatosis (CRPC) in a randomized controlled trial. Despite the increasing clinical evidence, controversies still exist regarding the standard treatment for these patients. Between January 1997 and October 2007, 50 patients with isolated CRPC underwent CRS and HIPEC at the St. George Hospital, Sydney. All patients underwent preoperative chest, abdominal and pelvic computed tomography scans, and positron emission tomography. All clinicopathologic and treatment-related data were obtained prospectively and computed in univariate and multivariate analyses to determine their prognostic significance for overall survival. The mean age at the time of CRS was 55 (SD = 14) years. There were 19 (38%) male patients. The overall median survival was 29 months (range 1-102) with a 3-year survival rate of 39%. Three clinicopathologic factors were found to be significant for overall survival: tumor differentiation (P < 0.001), peritoneal cancer index (P = 0.021), and completeness of cytoreduction (P < 0.001). In the multivariate analysis of overall survival, 2 factors were identified to be independently associated with an improved survival: well-differentiated tumor (P = 0.045) and complete cytoreduction (P = 0.023). CRPC patients with low tumor volume, well/moderately differentiated tumors and complete cytoreduction may potentially benefit from the combined treatment. The combined treatment for patients with isolated colorectal peritoneal carcinomatosis should be considered to be the current standard of care.
Article
Carcinoma of the colon complicated by obstruction or perforation has been recognized as having a poorer prognosis than tumors without obstruction or perforation. To clarify the natural history, failure patterns, and implications for adjuvant treatment after resection with curative intent, a review of the recent Massachusetts General Hospital (MGH) experience was undertaken. From 1970 to 1977, 77 patients with obstructive colonic carcinoma and 34 patients with localized perforation at the tumor site were identified and compared with a control group of 400 patients without obstruction or perforation undergoing curative resection. All patients were observed for a minimum of five years or until the patient's death. The actuarial five-year survival and disease-free survival rates in patients with obstruction was 31% and 44%, respectively, in contrast to 59% and 75% in control patients. For patients with localized perforation, the five-year actuarial survival and disease-free survival rates were 44% and 35%, respectively. Of the 77 patients with obstructing tumors, 32 patients (42%) developed local failure--nine with local failure only and 23 patients with local failure and distant metastases. Thirty-four patients (44%) developed distant metastases. Fifteen (44%) patients of 34 with perforative colonic carcinoma had local failure. Distant metastases occurred in 15 patients (44%). The incidence of local failure and distant metastases in the control group was 14% and 21%, respectively. The rate of local failure and distant metastases increased with stage and was generally higher stage for stage than in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)
Article
The following methodologies may be strictly applied to quantitatively evaluate patients with peritoneal carcinomatosis or sarcomatosis in regard to disease progression or regression: (1) Preoperative CT scan and the intraoperative assessment of cancer extent is analyzed region by region (AR-0-12) and an estimation of tumor volume (V0-V3) is evaluated according to the standardized scoring system previously described. At laparotomy, the volume of tumor nodules to adjacent organs, the viscosity (mucinous vs. solid) of tumor mass, and the pattern of distribution is assessed. (2) Radiologic abdominopelvic CT parameters that predict an incomplete cytoreduction are focal obstructions of bowel by CT assessment and tumor involvement of proximal ileum (AR-11). (3) The extent of prior surgical interventions (PS-1 through PS-3) must be recorded because aggressive deep dissections without perioperative chemotherapy severely jeopardize the possibility for complete cytoreduction. (4) Many tumor samples should be sent for histopathologic analysis. A proportion of mucin > 80% confirms a mucinous cancer. The malignant differentiation of cells, stroma morphology, the presence of signet ring cells, and evidence of invasion are used to grade cancers as mucinous tumor grade 0-3 (MTG-0 through MTG-3). (5) Once the cytoreductive procedure is accomplished, the surgeon estimates the residual volume of disease. (6) Objective response criteria from CT scan, tumor marker, and radiolabeled monoclonal antibody studies are necessary in a regular follow-up schedule.
Article
Peritoneal carcinomatosis (PC) is a common evolution of digestive cancer, associated with a poor prognosis. Yet it is poorly documented in the literature. Three hundred seventy patients with PC from non-gynecologic malignancies were followed prospectively: the PC was of gastric origin in 125 cases, of colorectal origin in 118 cases, of pancreatic origin in 58 cases, of unknown origin in 43 cases, and of miscellaneous origins in 26 cases. A previously reported PC staging system was used to classify these 370 patients. Mean and median overall survival periods were 6.0 and 3.1 months, respectively. Survival rates were mainly affected by the initial PC stage (9.8 months for Stage I with malignant peritoneal granulations less than 5 mm in greatest dimension, versus 3.7 months for Stage IV with large, malignant peritoneal masses more than 2 cm in greatest dimension). The presence of ascites was associated with poor survival of patients with gastric or pancreatic carcinoma. Differentiation of the primary tumor did not influence the prognoses of patients with PC. A better knowledge of the natural history of PC is needed, in view of the many Phase I, II, and III trials currently being conducted to evaluate aggressive multimodal therapeutic approaches to treating patients with PC from non-gynecologic malignancies.
Article
To confirm the findings from uncontrolled studies that aggressive cytoreduction in combination with hyperthermic intraperitoneal chemotherapy (HIPEC) is superior to standard treatment in patients with peritoneal carcinomatosis of colorectal cancer origin. Between February 1998 and August 2001, 105 patients were randomly assigned to receive either standard treatment consisting of systemic chemotherapy (fluorouracil-leucovorin) with or without palliative surgery, or experimental therapy consisting of aggressive cytoreduction with HIPEC, followed by the same systemic chemotherapy regime. The primary end point was survival. After a median follow-up period of 21.6 months, the median survival was 12.6 months in the standard therapy arm and 22.3 months in the experimental therapy arm (log-rank test, P =.032). The treatment-related mortality in the aggressive therapy group was 8%. Most complications from HIPEC were related to bowel leakage. Subgroup analysis of the HIPEC group showed that patients with 0 to 5 of the 7 regions of the abdominal cavity involved by tumor at the time of the cytoreduction had a significantly better survival than patients with 6 or 7 affected regions (log-rank test, P <.0001). If the cytoreduction was macroscopically complete (R-1), the median survival was also significantly better than in patients with limited (R-2a), or extensive residual disease (R-2b; log-rank test, P <.0001). Cytoreduction followed by HIPEC improves survival in patients with peritoneal carcinomatosis of colorectal origin. However, patients with involvement of six or more regions of the abdominal cavity, or grossly incomplete cytoreduction, had still a grave prognosis.
Article
Colorectal peritoneal carcinomatosis (PC) is a frequent and very lethal event. However, cure may be possible with maximal cytoreductive surgery associated with early postoperative intraperitoneal chemotherapy (EPIC). Between 1996 and 2000, we conducted a two-center prospective randomized trial comparing EPIC plus systemic chemotherapy with systemic chemotherapy alone, both after complete cytoreductive surgery of colorectal PC. Only 35 patients could be included among the 90 who were theoretically required, mainly because of patient dissatisfaction with the inclusion criteria. For this reason, the trial was stopped prematurely. Analysis of these 35 patients showed that complete resection of PC resulted in a 2-year survival rate of 60%-far above the classic 10% survival rate among patients with colorectal PC treated with systemic chemotherapy and symptomatic surgery. In this small series, EPIC did not demonstrate any advantage for survival. This supports the use of complete cytoreductive surgery in selected patients and calls for a prospective randomized trial comparing adjuvant systemic chemotherapy with intraperitoneal chemohyperthermia after complete resection.
Article
Although quality assessment is gaining increasing attention, there is still no consensus on how to define and grade postoperative complications. This shortcoming hampers comparison of outcome data among different centers and therapies and over time. A classification of complications published by one of the authors in 1992 was critically re-evaluated and modified to increase its accuracy and its acceptability in the surgical community. Modifications mainly focused on the manner of reporting life-threatening and permanently disabling complications. The new grading system still mostly relies on the therapy used to treat the complication. The classification was tested in a cohort of 6336 patients who underwent elective general surgery at our institution. The reproducibility and personal judgment of the classification were evaluated through an international survey with 2 questionnaires sent to 10 surgical centers worldwide. The new ranking system significantly correlated with complexity of surgery (P < 0.0001) as well as with the length of the hospital stay (P < 0.0001). A total of 144 surgeons from 10 different centers around the world and at different levels of training returned the survey. Ninety percent of the case presentations were correctly graded. The classification was considered to be simple (92% of the respondents), reproducible (91%), logical (92%), useful (90%), and comprehensive (89%). The answers of both questionnaires were not dependent on the origin of the reply and the level of training of the surgeons. The new complication classification appears reliable and may represent a compelling tool for quality assessment in surgery in all parts of the world.
Article
The three principal studies dedicated to the natural history of peritoneal carcinomatosis (PC) from colorectal cancer consistently showed median survival ranging between 6 and 8 months. New approaches combining cytoreductive surgery and perioperative intraperitoneal chemotherapy suggest improved survival. A retrospective multicenter study was performed to evaluate the international experience with this combined treatment and to identify the principal prognostic indicators. All patients had cytoreductive surgery and perioperative intraperitoneal chemotherapy (intraperitoneal chemohyperthermia and/or immediate postoperative intraperitoneal chemotherapy). PC from appendiceal origin was excluded. The study included 506 patients from 28 institutions operated between May 1987 and December 2002. Their median age was 51 years. The median follow-up was 53 months. The morbidity and mortality rates were 22.9% and 4%, respectively. The overall median survival was 19.2 months. Patients in whom cytoreductive surgery was complete had a median survival of 32.4 months, compared with 8.4 months for patients in whom complete cytoreductive surgery was not possible (P <.001). Positive independent prognostic indicators by multivariate analysis were complete cytoreduction, treatment by a second procedure, limited extent of PC, age less than 65 years, and use of adjuvant chemotherapy. The use of neoadjuvant chemotherapy, lymph node involvement, presence of liver metastasis, and poor histologic differentiation were negative independent prognostic indicators. The therapeutic approach combining cytoreductive surgery with perioperative intraperitoneal chemotherapy achieved long-term survival in a selected group of patients with PC from colorectal origin with acceptable morbidity and mortality. The complete cytoreductive surgery was the most important prognostic indicator.
Article
To report the results of standard therapy for peritoneal carcinomatosis of colorectal origin, which consists of conventional surgery and systemic chemotherapy. In a prospective study 50 patients with proven peritoneal carcinomatosis of colorectal origin were treated with conventional surgery combined with 5-fluorouracil and leucovorin, or irinotecan in patients treated by 5-fluorouracil within 12 months prior to entry. Survival and progression-free survival were studied and prognostic factors were analysed. The median survival time was 12.6 months. The median time to progression was 7.6 months. Location of primary tumour and result of conventional surgery and systemic chemotherapy were prognostic factors related to survival. The survival time of patients with peritoneal carcinomatosis of colorectal origin seems to be increased in patients treated by conventional surgery and systemic chemotherapy when compared to minimal treatment.
Article
Among 125 patients with peritoneal dissemination (P1-3) of colorectal cancer, including those with other synchronous metastases, the 5-year overall survival (OS) rate was 13.3% for P1 patients (n=30), 12.8% for P2 patients (n=39), and 1.8% for P3 patients (n=56) (P1 vs. P2, p=N.S.; P2 vs. P3, p=0.02; P1 vs. P3, p=0.001), while the median survival time (MST) was 12.0, 14.1, and 3.1 months, respectively. The 5-year OS rates for patients who had peritoneal dissemination without other metastases were 17.6% (n=17), 12.5% (n=19), and 3.4% (n=28) (P1 vs. P2, p=N.S.; P2 vs. P3, p=N.S.; P1 vs. P3, p=0.039), while the MST was 25.1, 15.1, and 12.5 months, respectively. In the P3 short survival group (SSG; n=13), TS expression was high in 7.7% (1/13) and low in 92.3% (12/13) of tumors, while DPD expression was high in 38.5% (5/13) and low in 61.5% (8/13) of tumors. In the P3 long survival group (LSG; n=15), the corresponding values were 80.0% (12/15), 20.0% (3/15), 33.3% (5/15), and 66.7% (10/15). High TS and low DPD expression was found in only 7.7% (1/13) of the SSG tumors vs. 46.7% (7/15) of the LSG tumors (p=0.028). These results suggest that the prognosis of stage IV colorectal cancer with P3 peritoneal dissemination is extremely poor. In addition, patients fitting the SSG criteria are unlikely to respond to treatment with 5-FU+LV, and may need combination chemotherapy using CPT-11 and/or L-OHP.
Article
The efficacy of cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for patients with peritoneal carcinomatosis from colorectal carcinoma remains to be established. A systematic review of relevant studies before March 2006 was performed. Two reviewers independently appraised each study using a predetermined protocol. The quality of studies was assessed. Clinical effectiveness was synthesized through a narrative review with full tabulation of results of all included studies. Two randomized controlled trials, one comparative study, one multi-institutional registry study, and 10 most recent case-series studies were evaluated. The level of evidence was low in 13 of the 14 eligible studies. The median survival varied from 13 to 29 months, and 5-year survival rates ranged from 11% to 19%. Patients who received complete cytoreduction benefited most, with median survival varying from 28 to 60 months and 5-year survival ranging from 22% to 49%. The overall morbidity rate varied from 23% to 44%, and the mortality rate ranged from 0% to 12%. The current evidence suggests that cytoreductive surgery combined with perioperative intraperitoneal chemotherapy is associated with an improved survival, as compared with systemic chemotherapy for peritoneal carcinomatosis from colorectal carcinoma.
Article
Although lymph node and liver metastases are recognized as indications for resection of metastatic disease from colorectal cancer, carcinomatosis has not traditionally been regarded as having surgical treatment options. Reports have suggested that complete surgical removal of carcinomatosis combined with thorough irrigation of the peritoneal cavity with chemotherapy could result in longterm survival in selected patients. Proper selection factors are important because palliative surgery in these patients has not proved beneficial. From a database of 156 patients with carcinomatosis from colorectal cancer, a retrospective analysis of data prospectively recorded in 70 patients with complete cytoreduction was performed. Eleven clinical and treatment factors were studied in univariate and multivariable analyses using survival as an end point. By univariate analysis, patients with peritoneal cancer index (PCI) of<20 had a median survival of 41 months compared with 16 months for patients with PCI>20 (p=0.004). The difference in negative versus positive lymph nodes was also significant; differences in survival that were improved but not significant were present for age greater than 30 years, mucinous histology, location within the colon versus rectum, and absence of an adverse factor such as cancer perforation or obstruction present at the time of primary cancer resection. Only PCI<20 versus PCI>20 and lymph node status were significant in the multivariable analysis. Favorable longterm results of complete cytoreduction in patients treated for carcinomatosis are associated with a limited volume of carcinomatosis observed at the time of cytoreduction and in patients with negative lymph nodes at the time of primary operation.
Article
Cytoreductive surgery with intraperitoneal chemotherapy has emerged as a new standard approach for peritoneal surface disease. This study investigated the learning curve of this combined modality treatment at a single institute. Variables analysed over three consecutive treatment periods (1996-1998, 1999-2002 and 2003-2006) included number of abdominal regions affected, Simplified Peritoneal Cancer Index (SPCI) score, result of cytoreduction, morbidity, duration of hospital stay and survival. A total of 323 procedures were performed between January 1996 and June 2006, 184 for peritoneal carcinomatosis of colorectal cancer origin and 139 for pseudomyxoma peritonei (PMP), including second procedures in 11 patients with PMP. The mean SPCI score decreased significantly over the study period (P < 0.001), but the number of regions affected did not. The rate of complete cytoreductions increased from 35.6 to 65.1 per cent (P = 0.012). The postoperative morbidity rate decreased from 71.2 to 34.1 per cent (P < 0.001). The median duration of hospital stay decreased from 24 to 17 days. The peak of the learning curve, graded by the percentage of complete cytoreductions, was reached after approximately 130 procedures. The learning curve of combined modality treatment for peritoneal surface disease is long, and reflects patient selection and treatment expertise.
Article
Decisions regarding the treatment of cancer depend on the anatomic location of the malignancy and the biologic aggressiveness of the disease. Some patients may have isolated intraabdominal seeding of malignancy of limited extent or of low biologic grade. In the past these clinical situations have been regarded as lethal. We have used the cytoreductive approach to achieve long-term disease-free survival in some patients with peritoneal carcinomatosis, peritoneal sarcomatosis, or mesothelioma. The cytoreductive approach may require six peritonectomy procedures to resect or strip cancer from all intraabdominal surfaces. These are (1) greater omentectomy-splenectomy, (2) left upper quadrant peritonectomy, (3) right upper quadrant peritonectomy, (4) lesser omentectomy-cholecystectomy with stripping of the omental bursa, (5) pelvic peritonectomy with sleeve resection of the sigmoid colon, and (6) antrectomy. These peritonectomy procedures and preparation of the abdomen for early postoperative intraperitoneal chemotherapy are described.
Article
The aim of this prospective study was to analyze the impact of second-look surgery in an attempt to treat peritoneal carcinomatosis (PC) at an early stage in a series of patients at high risk of developing PC from colorectal cancer. The prognosis of colorectal PC has recently been improved with hyperthermic intraperitoneal chemotherapy (HIPEC) after complete cytoreductive surgery (CCRS), and could be further improved if PC could be treated at an early stage. But, currently, the diagnosis of early PC is not accessible to imaging. From 1999 to 2006, 29 patients without any sign of recurrence on imaging studies underwent second-look surgery 13 months after resection of the primary tumor. Patients were selected according to primary tumor-associated criteria: resected minimal synchronous macroscopic PC (n = 16), synchronous ovarian metastases (n = 4), perforated primary tumor (n = 9). PC was found and treated with CCRS plus HIPEC in 16 of 29 (55%) cases, corresponding to 10 of 16 patients with initial PC, 3 of 4 patients with synchronous ovarian metastases and 3 of 9 patients with a perforated primary tumor. There was no postoperative mortality, and morbidity (grade III/IV) occurred in 14% of cases. After a median follow-up of 27 months (range, 6-96), 8 of 16 patients treated with CCRS and HIPEC are free of disease, 4 relapsed in the peritoneum, and 4 developed isolated visceral metastases. Performing second-look surgery at 1 year in selected patients at high risk of developing PC allowed the early detection and treatment of PC in 55% of cases. Our preliminary results have encouraged us to pursue this strategy and to evaluate it in a prospective multicenter trial.
Should the treatment of peritoneal carcinomatosis by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy still Be regarded as a highly morbid procedure?: a systematic review of morbidity and mortality
  • Chua
Predictors and survival of synchronous peritoneal carcinomatosis of colorectal origin: a population-based study
  • Lemmens
Learning curve of combined modality treatment in peritoneal surface disease
  • Smeenk
Clinical research methodologies in diagnosis and staging of patients with peritoneal carcinomatosis
  • Jacquet