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Short- and Long-Term Outcomes of Patients Requiring Gastrectomy During Cytoreductive Surgery and Intraperitoneal Chemotherapy for Lower-Gastrointestinal Malignancies: A Propensity Score-Matched Analysis
Abstract
Objectives
This study was designed to assess the short- and long-term outcomes of gastric resection in cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC) for lower gastrointestinal (GI) malignancies.
Methods
Patients with adenocarcinoma and appendiceal mucinous neoplasms were included. Redo and incomplete cytoreductions were excluded. A total of 756 patients were identified. Of these, 65 underwent gastric resection, 11 underwent wedge, 43 distal, and 11 subtotal and total gastrectomy. Preoperative differences were assessed for and addressed with matching. Perioperative outcomes, overall survival (OS), and risk-free survival (RFS) were assessed in two analyses: first all gastric resections were included and the second excluded wedge resections. Subgroup analysis according to diagnosis subtype was conducted.
Results
Demographic analysis revealed that markers of tumor aggression and poor nutrition were prevalent in the gastrectomy group. The matched analysis for gastric resections revealed higher rates of reoperation (38% vs. 22%, p = 0.028). After excluding wedge resections, increased rates of reoperation (40% vs. 22%, 0.019), grade 3/4 morbidity (76% vs. 59%, p = 0.036), and hospital stay (34 vs. 27 days, p = 0.012) were observed. For the unmatched cohort, OS (103 vs. 69 months, p = 0.501) and RFS (17 vs. 18 months, p = 0.181) for patients with CC = 0 were insignificantly different. In comparison for CC > 0, OS (31 vs. 83 months, p < 0.001) and RFS (9 vs. 20 months, p < 0.001) were significantly reduced in gastric resection. For the matched cohort, after excluding wedges, gastrectomy did not significantly decrease OS. However, RFS was decreased (11 vs. 20 months, p = 0.016).
Conclusions
Despite high postoperative morbidity, when complete cytoreduction is achieved, the need for gastric resection is not associated with inferior long-term outcomes.
... Patients who have undergone gastrointestinal resection are at risk of short and long term outcomes. Notably, short term outcomes include anastomotic leakage, infections, and reoperations [6]. In addition, long term outcomes include diarrhea, appetite loss, bowel dysfunctions and eating restrictions, significantly affecting quality of life [7]. ...
Background and Aim: Gastrointestinal (GI) resection is a common surgical intervention performed for malignancy, chronic inflammatory bowel disorders, and obstructions. While surgical techniques have improved to enhance survival, there continues to be concern regarding the effects of malabsorption and malnutrition on wound healing. This study aims to review current evidence linking malabsorption syndromes to impaired chronic wound healing following GI resection, examining underlying mechanisms, clinical implications, and potential therapeutic interventions. Methods: A literature review was conducted using PubMed, Scopus, Web of Science, and Cochrane Library. Studies focusing on malabsorption, postoperative nutritional status, wound healing outcomes, and nutritional interventions from the past 30 years were included. Randomized controlled trials, systematic reviews, and meta analyses were prioritized, while non-English studies and non-peer-reviewed articles and publications, opinion pieces, case reports, conference abstracts, and animal studies were excluded. Results: Malabsorption following GI resection is linked to deficiencies in amino acids, vitamin A, vitamin C, vitamin B12, iron, and zinc. These deficiencies result in impaired wound healing as they directly affect collagen synthesis, angiogenesis, and immune function. Nutritional screening tools, as well as laboratory biomarkers such as albumin, prealbumin, and transferrin, can help evaluate malnutrition, although they are best paired with medical history and physical examination. Screening is recommended at least ten days before surgery to allow for appropriate interventions. Nutritional supplementation with arginine, glutamine, vitamin C, and zinc has shown improved wound healing, reduced complications, and shortened hospital stays. Conclusion: Malabsorption following GI resection greatly compromises wound healing due to nutritional deficiencies that disrupt essential cellular processes, leading to delayed healing and increased complications. Early evaluation and intervention are critical to optimizing wound healing outcomes. Future research should focus on refining assessment techniques and evaluating the long-term effects of various interventions on wound healing and patient outcomes.
... As all our patients received complete CRS, the involvement of critical organs in the context of a CC-0/1 resection may have limited oncological impact. However, it is known that gastrectomy as part of the CRS and HIPEC procedure in lower gastrointestinal malignancies has been associated with increased rates of re-operation and prolonged hospitalisation stay [27][28][29]. Similar findings was seen in our patient cohort as well, elucidating to the fact that involvement of 'crucial' organs are more likely to impact morbidity outcomes rather than survival. ...
Objectives
Peritoneal cancer index (PCI) score is a common prognostication tool in peritoneal metastases (PM). We hypothesize that the distribution of PCI score and involvement of specific regions affects survival and morbidity outcomes.
Methods
Data was collected from a prospective database of patients who underwent CRS and HIPEC for PM at the National Cancer Centre Singapore. We evaluate the relationship between PCI, PCI distribution, and survival and morbidity outcomes.
Results
One hundred and fifty-two patients underwent CRS and HIPEC with a median PCI score of nine (range 0–31). Median overall survival (OS) and progression free survival (PFS) were 43 and 17 months, respectively. Region six (pelvis) was most commonly involved and had the highest frequency of heavy disease burden. Presence of PM in the lower abdomen, flanks, and small bowel were associated with poorer OS (p=0.01, 0.03, <0.001) and PFS (p=0.04, 0.02, <0.001). Involvement of porta hepatitis predicted poorer OS but not PFS (p=0.03). Involvement of the gastric antrum resulted in higher rates of postoperative complications.
Conclusions
The pattern of PCI distribution may be associated with varying survival and morbidity outcomes.
Background
This study aimed to clarify the prognostic significance of tumour markers on long-term survival in colorectal peritoneal carcinomatosis (CRPC) following cytoreductive surgery and intraperitoneal chemotherapy.
Patients and Methods
Preoperative serum tumour markers of 164 patients with CRPC were analyzed. Peritoneal cancer index (PCI) was measured and relationship to survival calculated.
Results
Carcinoembryonic antigen (CEA) >6.5 mg/l and cancer antigen 125 (CA125) >16 U/ml remained independent predictors of survival after adjusting for PCI [adjusted hazard ratio (aHR)=2.46, 95% confidence interval (CI)=1.3-4.5, p<0.01 and aHR=2.23, 95% CI=1.21-4.09, p<0.01, respectively]. Patients with high CEA and low CA125 or vice versa had an approximately triple risk of death (HR=3.34, 95% CI=1.21 9.25, p=0.02 and HR=2.76, 95% CI=1.01 7.77, p=0.04, respectively). High CEA with high CA125 produced an additive effect, reflecting a six-fold increase in death (HR=6.57, 95% CI=2.62 13.69, p<0.001, median survival: not reached vs. 22 months).
Conclusion
Serum CEA and CA125 in patients with CRPC treated with cytoreductive surgery and intraperitoneal chemotherapy convey a negative prognostic effect independently of PCI.
Pseudomyxoma peritonei (PMP) originating from an appendiceal mucinous neoplasm remains a biologically heterogeneous disease. The purpose of our study was to evaluate outcome and long-term survival after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) consolidated through an international registry study.
A retrospective multi-institutional registry was established through collaborative efforts of participating units affiliated with the Peritoneal Surface Oncology Group International.
Two thousand two hundred ninety-eight patients from 16 specialized units underwent CRS for PMP. Treatment-related mortality was 2% and major operative complications occurred in 24% of patients. The median survival rate was 196 months (16.3 years) and the median progression-free survival rate was 98 months (8.2 years), with 10- and 15-year survival rates of 63% and 59%, respectively. Multivariate analysis identified prior chemotherapy treatment (P < .001), peritoneal mucinous carcinomatosis (PMCA) histopathologic subtype (P < .001), major postoperative complications (P = .008), high peritoneal cancer index (P = .013), debulking surgery (completeness of cytoreduction [CCR], 2 or 3; P < .001), and not using HIPEC (P = .030) as independent predictors for a poorer progression-free survival. Older age (P = .006), major postoperative complications (P < .001), debulking surgery (CCR 2 or 3; P < .001), prior chemotherapy treatment (P = .001), and PMCA histopathologic subtype (P < .001) were independent predictors of a poorer overall survival.
The combined modality strategy for PMP may be performed safely with acceptable morbidity and mortality in a specialized unit setting with 63% of patients surviving beyond 10 years. Minimizing nondefinitive operative and systemic chemotherapy treatments before definitive cytoreduction may facilitate the feasibility and improve the outcome of this therapy to achieve long-term survival. Optimal cytoreduction achieves the best outcomes.
Cytoreductive surgery (CRS) combined with perioperative intraperitoneal chemotherapy (PIC) has demonstrated improved survival in selected patients with pseudomyxoma peritonei (PMP). However, this aggressive treatment modality has been consistently associated with variable rates of perioperative mortality between 0% and 18% and morbidity between 30% and 70%. This study evaluates the clinical and treatment-related risk factors for perioperative morbidity and mortality in PMP patients who underwent CRS and PIC.
A total of 145 consecutive CRS and PIC procedures for PMP performed between January 1996 and March 2009 were evaluated. The association of 12 clinical and 20 treatment-related risk factors with grades III and IV/V morbidity were assessed by univariable and multivariable analysis.
The mortality (grade V) rate was 3%. The morbidity rates of grades III and IV were 23% and 22%, respectively. Eight factors were associated with grade IV/V morbidity on univariable analysis: peritoneal cancer index >or=21 (P = .034), ASA score >or=3 (P = .003), operation duration >or=10 h (P < .001), left upper quadrant peritonectomy procedure (P = .037), colonic resection (P = .012), ostomy (P = .005), ileostomy (P = .012), and transfusion >or=6 units (p = 0.011). Multivariable analysis showed 2 significant risk factors for grade IV/V morbidity: ASA >or= 3 (P = .006) and an operation length >or=10 h (P < .001).
CRS and PIC has an acceptable rate of perioperative mortality and morbidity in selected patients with PMP. Patients with bulky disease who undergo a long operation are at a particularly high risk of a severe adverse event.
This multi-institutional registry study evaluated cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for diffuse malignant peritoneal mesothelioma (DMPM).
A multi-institutional data registry that included 405 patients with DMPM treated by a uniform approach that used CRS and HIPEC was established. The primary end point was overall survival. The secondary end point was evaluation of prognostic variables for overall survival.
Follow-up was complete in 401 patients (99%). The median follow-up period for the patients who were alive was 33 months (range, 1 to 235 months). The mean age was 50 years (standard deviation [SD], 14 years). Three hundred eighteen patients (79%) had epithelial tumors. Twenty-five patients (6%) had positive lymph nodes. The mean peritoneal cancer index was 20. One hundred eighty-seven patients (46%) had complete or near-complete cytoreduction. Three hundred seventy-two patients (92%) received HIPEC. One hundred twenty-seven patients (31%) had grades 3 to 4 complications. Nine patients (2%) died perioperatively. The mean length of hospital stay was 22 days (SD, 15 days). The overall median survival was 53 months (1 to 235 months), and 3- and 5-year survival rates were 60% and 47%, respectively. Four prognostic factors were independently associated with improved survival in the multivariate analysis: epithelial subtype (P < .001), absence of lymph node metastasis (P < .001), completeness of cytoreduction scores of CC-0 or CC-1 (P < .001), and HIPEC (P = .002).
The data suggest that CRS combined with HIPEC achieved prolonged survival in selected patients with DMPM.
Background:
Formal gastrectomy is occasionally required to achieve complete cytoreduction for patients with peritoneal surface malignancies. In addition, the role of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with gastric cancer is increasingly being explored. Nevertheless, data on the safety of gastrectomy at the time of CRS-HIPEC are limited.
Methods:
The American College of Surgeons-National Surgical Quality Improvement Program databases from 2005 to 2016 were used to identify patients who underwent CRS-HIPEC. Demographic, clinical, and perioperative outcomes were compared between patients who underwent CRS-HIPEC with and without gastrectomy.
Results:
Among 1168 patients who underwent CRS-HIPEC, 43 (4%) underwent partial (n = 20) or total (n = 23) gastrectomy. Patients who underwent gastrectomy at the time of CRS-HIPEC had a longer operative time (529.3 versus 457.6 min, P = 0.004), were more likely to need an intraoperative transfusion (32.6% versus 14.3%, P = 0.001), experienced a longer length of stay (19.0 versus 11.3 d, P < 0.001), and had a significantly greater complication rate (60.5% versus 27.9%, P < 0.001), whereas postoperative mortality was not statistically significantly different (4.7% versus 1.4%, P = 0.09). On multivariate logistic regression, gastrectomy (odds ratio [OR] 3.52, P < 0.001) was the strongest predictor of postoperative morbidity, in addition to American Society of Anesthesiologists class 4 (OR 2.82, P = 0.001), malnutrition (OR 1.63, P = 0.01), liver resection (OR 1.88, P = 0.01), and colectomy (OR 2.04, P < 0.001).
Conclusions:
Patients undergoing gastrectomy at the time of CRS-HIPEC experience a substantial postoperative complication rate (60%) and extended length of stay (mean 19 d). These findings highlight the need for cautious patient selection and preoperative counseling before performing concomitant gastrectomy and CRS-HIPEC.
Background and objectives:
Serum tumor markers are prognostic in patients with colorectal cancer peritoneal carcinomatosis (CRPC) undergoing cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC). Assessment of the ratio of tumor marker to volume, as depicted by peritoneal carcinomatosis index (PCI), and how this may affect overall (OS) and recurrence free survival (RFS) has not been reported.
Methods:
Survival effect of this ratio was analyzed in patients with CRPC managed from 1996 to 2016 with CRS and IPC.
Results:
Of 260 patients included, those with low CEA/PCI ratio (<2.3) had longer median OS (56 vs 24 months, P = 0.001) and RFS (13 vs 9 months, P = 0.02). The prognostic impact of CEA/PCI ratio was most pronounced in patients with PCI ≤ 10 (OS of 72 vs 30 months, P < 0.001; RFS of 21 vs 10 months, P = 0.002). In multivariable analysis, elevated CEA/PCI ratio was independently associated with poorer OS (adjusted HR 1.85, 95%CI 1.11-3.10, P = 0.02) and RFS (adjusted HR 1.58, 95%CI 1.04-2.41, P = 0.03).
Conclusion:
CEA/PCI ratio is an independent prognostic factor for OS and RFS in CRPC. This novel approach allows both tumor activity and volume to be accounted for in one index, thus potentially providing a more accurate indication of tumor biological behavior.
Background:
Serum tumour levels have been shown to be prognostic in patients with epithelial appendiceal mucinous neoplasms with peritoneal dissemination (pseudomyxoma peritonei (PMP)). A singular index which incorporates both tumour activity (as depicted by serum tumour marker levels) and tumour volume (as depicted by peritoneal carcinomatosis index (PCI)), may give a more precise surrogate of tumour biological behaviour. The prognostic implication of this index has not yet been reported.
Methods:
A retrospective cohort study of all patients with PMP managed from 1996 to 2016 with cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC) was performed by analysing the survival effect of the ratio of preoperative serum CEA, CA19.9 and CA125 to PCI.
Results:
Three hundred and eighty-six patients were included. In patients with low-grade PMP, elevated CA19-9/PCI ratio resulted in poorer median overall survival times (104 months vs NR, 95%CI 83 - NR, log-rank p < 0.001) and was an independent predictor of reduced overall survival on multivariable analysis (adjusted HR 5.60, 95%CI 1.60-19.68, p = 0.007). In patients with high-grade PMP, no statistically significant difference in survival was recognised.
Conclusion:
CA19-9/PCI ratio is an independent prognostic factor for overall survival in patients with low-grade PMP undergoing CRS and IPC. By accounting for both tumour activity and tumour volume simultaneously, this novel index behaves as a surrogate of tumour biology and provides a useful adjunct for decisions regarding treatment allocation in this patient group.
Aim: The aim of this study was to assess the outcomes of patients operated on for peritoneal metastases from unusual cancer sites of origin, meaning apart from PM from colorectal, gastric and epithelial ovarian carcinomas, pseudomyxoma peritonei and mesothelioma.
Patients and Methods: A questionnaire concerning patients treated with CRS plus HIPEC for PM arising from unusual cancer sites of origin was sent to all centers that routinely performed HIPEC, through the Peritoneal Surface Oncology Group International and the RENAPE network.
Results: Between Sept 1990 and June 2016, 850 procedures for unusual cases were performed in 781 patients, in 53 centers worldwide. Nearly two-thirds of the procedures were performed for three indications: rare ovarian carcinoma (n = 224), sarcoma (n = 189) and neuroendocrine tumors (n = 127). The median PCI was 12 [0-39]. Grade III-IV postoperative complications occurred in 272 patients (41%). Nineteen patients (2.9%) died postoperatively.
After a median follow-up of 46 months, median overall survival (OS) was 39 months [33.18-44.05]. 5-year OS rates were respectively 38.7%, For the 3 main indications, 5-year OS was significantly greater in patients with PM from rare ovarian carcinoma (57.7%), than that of patients with PM from neuroendocrine tumors (39.9%), and from sarcoma (29.3%) (p < 0.0001).
Conclusion: CRS and HIPEC appear to be safe and effective in patients with peritoneal metastases from unusual cancer sites of origin especially from rare ovarian carcinomas, PM from neuroendocrine tumors. The respective roles of CRS and HIPEC remain unclear and should be evaluated.
Background
Optimal outcomes in pseudomyxoma peritonei (PMP) require complete macroscopic tumor removal by cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC). Partial or complete gastrectomy may be required with ongoing debate as to the risks and benefits of gastrectomy in what is often a low-grade malignancy.
Methods
Retrospective single-center analysis of 1014 patients undergoing CRS and HIPEC for PMP of appendiceal origin. Complications and survival were compared in patients who had gastrectomy versus the nongastrectomy cohort.
Results
Of 1014 patients, 747 (74 %) had CRS and HIPEC with complete cytoreduction. Overall, 86 (12 %) of 747 had partial (n = 80) or total (n = 6) gastrectomy. Median age was 55 years for gastrectomy patients and 56 for nongastrectomy patients (p = 0.591). Preoperative tumor markers [carcinoembryonic antigen, carbohydrate antigen (CA) 125 and CA19-9] were elevated more frequently in the gastrectomy group compared to the nongastrectomy group [81, 61 and 81 % compared to 41 % (p = 0.001), 20 % (p = 0.001) and 39 % (p = 0.001), respectively]. The proportion of high-grade histology was similar in the two groups (gastrectomy 19 % vs. nongastrectomy 18 %, p = 0.882). Postoperative complications (Clavien–Dindo III–IV) were 31 % for the gastrectomy group and 13 % for the nongastrectomy group (p = 0.001). The 30-day postoperative mortality was 3 (0.5 %) of 661 for the nongastrectomy group and 1 (1.2 %) of 86 for the gastrectomy group (p = 0.387). Three- and 5-year overall survival were 96 and 88 % in the nongastrectomy group and 87 and 77 % in the gastrectomy group (p = 0.018). Three- and 5-year disease-free survival were 89 and 77 % in the nongastrectomy group versus 66 and 48 % in the gastrectomy group (p = 0.001).
Conclusions
Gastrectomy is an essential component of complete cytoreduction in advanced PMP and was required in 12 % of patients with good long-term survival.
Whether you are evaluating the effectiveness of a drug, a medical device, a behavioral intervention, a community mobilization, or even a new law, this is the book for you. Written in plain language, it simplifies the process of designing interventions, analyzing the data, and publishing the results. Because the choice of research design depends on the nature of the intervention, the book covers randomized and nonrandomized designs, prospective and retrospective studies, planned clinical trials and observational studies. In addition to reviewing standard statistical analysis, the book has easy-to-follow explanations of cutting edge techniques for evaluating interventions, including propensity score analysis, instrumental variable analysis, interrupted time series analysis and sensitivity analysis. All techniques are illustrated with up-to-date examples from medical and public health literature. This will be essential reading for a wide range of healthcare professionals involved in research as well as those more specifically interested in public health issues and epidemiology.
Cytoreductive surgery (CRS) combined with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) is the optimal treatment for Pseudomyxoma Peritonei (PMP). Despite treatment, disease often recurs and may not be amenable to further CRS. Clinical experience suggests a spectrum of disease which may correlate with tumour marker levels. The aim of this study was to analyse the influence of markers on recurrence and survival.
The details of all patients undergoing surgery for PMP of appendiceal origin at a national centre for peritoneal malignancy were recorded in a dedicated prospective database. The data on all patients who had CRS and HIPEC between March 1994 and January 2012 was analysed and recurrence and survival correlated with pre-operative levels of CEA, CA-125 and CA19-9.
Overall, 519 (69%) of 752 consecutive patients, underwent complete CRS and HIPEC. The median (range) age was 56 (20-82) years with 342/519 (66%) females. The mean overall (OS) and disease free survival (DFS) in the 131/519 patients who had normal preoperative tumour markers was 168 (128-207) and 125 (114-136) months respectively, significantly higher when compared with the 109/519 (21%) who had all three tumour markers elevated (OS of 65 (42-88) and DFS of 55 (41-70) months respectively) (P = 0.002).
Elevated tumour markers predict an increased risk of recurrence and reduced survival after complete CRS. This may reflect cell biology in low grade tumours and is an independent prognostic feature. Further analysis may help to select patients for post-operative chemotherapy, second look procedures or stratification of follow up.
Background:
Perioperative intraperitoneal chemotherapy (PIC) is delivered by intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) and early postoperative intraperitoneal chemotherapy (EPIC). The relative survival benefits of each or both regimens are explored in this large series of patients undergoing cytoreduction at a single institution.
Methods:
Patients with a complete (CCR0) or optimal (CCR1) cytoreduction who received intraperitoneal chemotherapy for appendiceal and colorectal peritoneal carcinomatosis were included for analysis. PIC regimens were delivered according to the treatment protocol. Standardized statistical analyses were performed.
Results:
Of 262 patients, 98 patients (37%) had colorectal peritoneal carcinomatosis, 108 patients (41%) had low-grade pseudomyxoma peritonei and 56 patients (21%) had appendiceal peritoneal carcinomatosis. For pseudomyxoma peritonei, recurrence-free survival (RFS) did not vary with PIC regimen, 5-year survival was 86% in the HIPEC and EPIC group and 64% in the HIPEC or EPIC group (P = 0.070). For appendiceal peritoneal carcinomatosis, RFS and overall survival (OS) did not vary with PIC regimen. For colorectal peritoneal carcinomatosis, the median RFS was 33 months in the HIPEC and EPIC group, 19 months in the HIPEC alone group and 20 months in the EPIC alone group (P = 0.046). OS did not vary with PIC regimen.
Conclusion:
From our experience, without compromising the perioperative morbidity and mortality, PIC consisting of HIPEC and EPIC appears to be associated with potential survival benefits of improved OS in pseudomyxoma peritonei and RFS in colorectal peritoneal carcinomatosis.
Cytoreductive surgery (CRS) combined with perioperative intraperitoneal chemotherapy (PIC) is a treatment option for peritoneal surface malignancy. Despite the survival benefits, this treatment was previously associated with a high morbidity and mortality rates and the perception of the poor perioperative outcomes associated with this regimen remains. The aim of this study was to report the perioperative outcomes of CRS and PIC from a single institution to review factors that are associated with a poor perioperative outcome.
The clinical- and treatment-related data of 243 consecutive procedures performed were prospectively collected and retrospectively reviewed. Adverse events were rated according to the National Cancer Institute's Common Toxicity Criteria (grade I-V). Univariate and multivariate analyses were performed to identify significant clinical and treatment-related factors for a poor perioperative outcome (grades III/IV/V morbidity).
The perioperative mortality rate was 3%. The rate of severe morbidity was 43%. Multivariate analysis demonstrated that left upper quadrant peritonectomy (P < 0.001) and small bowel resection (P < 0.01) were factors that predicted for a poor perioperative outcome.
The morbidity and mortality rates of CRS and PIC are within an acceptable range for a major gastrointestinal surgery which is performed with a curative intent. Patient selection is important in ensuring that suitable patients receive this treatment. A new perspective of this treatment needs to be sought.
Cytoreductive surgery (CRS) including gastric resection combined with hyperthermic intraperitoneal chemotherapy (HIPEC) can improve the prognosis of selected patients with peritoneal surface malignancies. Perioperative morbidity of this aggressive treatment strategy is high; however, overall mortality can be low in specialized centers. The aim of this study was to assess the safety of gastric resections with anastomosis during CRS and HIPEC.
Between 2005 and 2008, 204 patients underwent CRS and HIPEC at our tertiary referral centre. Of these, 37 procedures (male/female 24/13, median age 55 years) included gastric resections. The clinical data of all patients were introduced into a database and analyzed with respect to the morbidity associated with the gastric resections.
Of all patients included, 16 had pseudomyxoma peritonei, 11 gastric carcinoma, 4 ovarian carcinoma, 3 malignant peritoneal mesothelioma, and 3 colon carcinoma. Twenty-seven patients had previous surgery (n = 22) and/or systemic chemotherapy (n = 18). Fifteen total gastrectomies, 3 subtotal gastrectomies, 12 distal gastrectomies, and 7 gastric wedge resections were performed during CRS. The overall postoperative morbidity was 45%; main surgical complications were pancreatitis (n = 6), abdominal abscess (n = 4), bile leakage (n = 2), and digestive fistula (leakage of ileorectostomy and small bowel perforation) (n = 2). However, no complications occurred at the site of the esophageal anastomosis (n = 15), gastric anastomosis (n = 15) or gastric suture (n = 7). No patient died postoperatively during the hospitalization period.
CRS in combination with HIPEC is associated with high postoperative morbidity; however, anastomosis following total or subtotal gastrectomy is safe in experienced centers. No leakages related to gastric resections occurred in this high-risk patient group.
Gastrointestinal and ovarian malignancies frequently recur with metastatic disease limited to the abdominal cavity. Due to full thickness penetration of tumor through bowel wall, spillage of tumor from lymphatic channels by surgical trauma or perforation of the tumor through the ovarian capsule, tumor cells are disseminated throughout the peritoneal surfaces either prior to or at the time of surgical removal of the primary tumor. In the past, diagnosis of recurrent cancer was difficult because no sensitive diagnostic test was available by which to image a small tumor volume present on peritoneal surfaces. Computerized tomography with intraperitoneal infusion of contrast can demonstrate tumor nodules not otherwise detectable. Intraperitoneal installation of I-131 labeled monoclonal antibody has allowed visualization of mucinous tumor on peritoneal surfaces not seen by any other radiologic test. Intraperitoneal chemotherapy has been shown to provide palliation in patients with small volume disease confined to peritoneal surfaces. Because of limited penetration of chemotherapy into large tumor nodules this treatment strategy has not been effective for bulky intraabdominal recurrent cancer. Cytoreductive surgery utilizing high voltage electrocautery and CO2 laser evaporation of tumor can make patients relatively disease free. These surgical technologies combined with postoperative intraperitoneal chemotherapy have been shown to be of benefit for selected patients with recurrent intraabdominal cancer. The wider application of these intraperitoneal chemotherapy treatments for patients in an adjuvant setting may be of value in preventing the occurrence of peritoneal carcinosis and in improving survival.
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.
Cytoreductive surgery supplemented by perioperative intraperitoneal chemotherapy is a therapeutic option for selected patients with pseudomyxoma peritonei syndrome. In some patients, the stomach and/or its vascular supply are so covered by mucinous tumour that total gastrectomy is required for complete resection.
Forty-five patients underwent total gastrectomy with a temporary diverting jejunostomy as part of the surgical treatment of pseudomyxoma peritonei syndrome of appendiceal origin. Heated intraoperative intraperitoneal chemotherapy with mitomycin was used in all patients, and 36 had early postoperative intraperitoneal 5-fluorouracil. To date, 39 patients have had second-look surgery and stoma closure; 37 had additional perioperative intraperitoneal chemotherapy. A prospective database was maintained on all patients.
The median age was 47 (range 33-66) years. Median interval from diagnosis of pseudomyxoma peritonei to definitive cytoreductive surgery was 23 (range 0-140) months. Six patients presented with intestinal obstruction. The need for gastrectomy was predicted before operation by abdominal computed tomography. Mean operative time was 13 (range 9-17) h. Mean intraoperative requirement for packed red blood cells was 3.0 units, and that for fresh frozen plasma was 9.9 units. Six peritonectomy procedures, including total gastrectomy, were required for complete cytoreduction. All except seven patients were maintained on parenteral nutrition before second-look surgery for jejunostomy closure. All but two patients have resumed oral nutrition with discontinuation of parenteral feeding. There was one postoperative death and one late death. Thirty-seven patients are alive and disease-free, 0-56 months after initiation of treatment.
Total gastrectomy with a temporary diverting jejunostomy may be used to facilitate complete cytoreduction in patients with advanced pseudomyxoma peritonei syndrome.
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.
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.
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.
Venous thromboembolic events (VTE) are potentially preventable causes of morbidity and mortality after injury. We hypothesized that the current clinical incidence of VTE is relatively low and that VTE risk factors could be identified.
We queried the ACS National Trauma Data Bank for episodes of deep venous thrombosis (DVT) and/or pulmonary embolism (PE). We examined demographic data, VTE risk factors, outcomes, and VTE prophylaxis measures in patients admitted to the 131 contributing trauma centers.
From a total of 450,375 patients, 1602 (0.36%) had a VTE (998 DVT, 522 PE, 82 both), for an incidence of 0.36%. Ninety percent of patients with VTE had 1 of the 9 risk factors commonly associated with VTE. Six risk factors found to be independently significant in multivariate logistic regression for VTE were age > or = 40 years (odds ratio [OR] 2.01; 95% confidence interval [CI] 1.74 to 2.32), lower extremity fracture with AIS > or = 3 (OR 1.92; 95% CI 1.64 to 2.26), head injury with AIS > or = 3 (OR 1.24; 95% CI 1.05 to 1.46), ventilator days >3 (OR 8.08; 95% CI 6.86 to 9.52), venous injury (OR 3.56; 95% CI 2.22 to 5.72), and a major operative procedure (OR 1.53; 95% CI 1.30 to 1.80). Vena cava filters were placed in 3,883 patients, 86% as PE prophylaxis, including in 410 patients without an identifiable risk factor for VTE.
Patients who need VTE prophylaxis after trauma can be identified based on risk factors. The use of prophylactic vena cava filters should be re-examined.
Because women with advanced ovarian cancer have poor outcomes, it is imperative to continue exploring for novel therapies. The opportunity for intraperitoneal treatment, especially in the subgroup of patients with minimal residual disease, in which the intraperitoneal approach may have a biologic rationale for benefit over and above the standard intravenous route, needs to be explored to the fullest extent. The MEDLINE, EMBASE, and Cochrane Library databases were searched up to January 2006 for randomized trials that compared first-line intraperitoneal-containing chemotherapy with first-line intravenous chemotherapy in the treatment of women with stage III epithelial ovarian cancer. Seven randomized, controlled trials were identified, including 3 large Phase III trials and 4 smaller randomized trials. The 3 large Phase III trials detected statistically significant overall survival benefits with intraperitoneal cisplatin-containing chemotherapy compared with intravenous chemotherapy alone. The improvements in survival were 8 months, 11 months, and 16 months, respectively. Pooled analysis from 6 of the 7 randomized trials confirmed the survival effect with intraperitoneal chemotherapy compared with intravenous chemotherapy alone (relative risk, 0.88; 95% confidence interval, 0.81-0.95). Severe adverse events and catheter-related complications with intraperitoneal chemotherapy were significantly more common and often were dose-limiting. The results from this review indicated that cisplatin-containing intraperitoneal chemotherapy should be offered to patients on the basis of significant improvements in overall survival. The appropriate clinical and institutional multidisciplinary facilities are needed for the safe delivery of this treatment in optimally debulked patients. Further research is needed concerning specific aspects of the treatment, such as optimal agent, dose, and scheduling.
There is controversy about the effect of the influence of hyperthermia and chemotherapeutic agents on the healing of intestinal anastomosis. The effects of hyperthermic intraperitoneal chemoperfusion (HIPEC) of wound healing after colonic anastomosis were investigated in a rat model.
Thirty-six Wag/Rija rats were randomized into three groups of 12 animals each: group I: control (only colonic anastomosis was performed) (n = 12); group II: HIPEC (mitomycin C in a concentration of 20 mg/m(2) (n = 12) colonic anastomosis was performed before HIPEC; group III: HIPEC (mitomycin C in a concentration of 20 mg/m(2) (n = 12) colonic anastomosis was performed after HIPEC. Bursting pressure and bursting sites were recorded 4 and 10 days after intervention. Collagen deposits, inflammation and foreign body reactions were evaluated.
Lower bursting pressure and lost of collagen were found in both HIPEC groups and compared with the control group. There was almost no difference between both HIPEC groups. They were noted overwhelmingly at the anastomosis in the HIPEC group. The degree of collagen accumulation was well-correlated with bursting pressure.
These results have shown that hyperthermic intraperitoneal chemoperfusion (HIPEC) impairs wound healing in colonic anastomosis in rats.
Morbidity and mortality outcome s of cytoreductive surgery and perioperative intraperitoneal chemotherapy at a single tertiary institution: towards a new perspective of this treatment
- T C Chua
- A Saxena
- J F Schellekens
- TC Chua
Intraperitoneal chemotherapy in the first-line treatment of women with stage III epithelial ovarian cancer: a systematic review with meta-analyses
- L Elit
- TK Oliver
- A Covens
Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey
- D Dindo
- N Demartines
- PA Clavein
CEA to peritoneal carcinomatosis index (PCI) ratio is prognostic in patients with colorectal cancer peritoneal carcinomatosis undergoing cytoreduction surgery and intraperitoneal chemotherapy: a retrospective cohort study
- M A Kozman
- O M Fisher
- B J Rebolledo
- MA Kozman
Comparative analysis of perioperative intraperitoneal chemotherapy regimen in appendiceal and colorectal peritoneal carcinomatosis
- T C Chua
- W Liauw
- J Zhao
- TC Chua
Prognostic value of carcinoembryonic antigen (CEA), AFP, CA19-9 and CA125 for patients with colorectal cancer with peritoneal carcinomatosis treated by cytoreductive surgery and intraperitoneal chemotherapy
- Y R Huo
- Y Huang
- W Liauw
- YR Huo
Clinical research methodologies in diagnosis and staging of patients with peritoneal carcinomatosis
- P Sugarbaker