[Show abstract][Hide abstract] ABSTRACT: Background Leiomyosarcoma (LMS) is an aggressive soft tissue sarcoma derived from smooth muscle cells typically of uterine, gastrointestinal or soft tissue origin. The prognosis for this tumor is poor, with survival rates among the lowest of all soft tissue sarcomas. Surgery is the best approach for localized disease. The principal role of chemotherapy is prevalently in the treatment of metastatic disease. Trabectedin, a promising new DNA-damaging agent with a mechanism of action that differs from that of traditional alkylating agents, has been approved in Europe for the treatment of patients with advanced soft tissue sarcoma after failure of anthracyclines and ifosfamide, Case presentation We report the case of a 53-year-old woman with metastatic well differentiated uterine leiomyosarcoma refractory to multiple treatments who underwent 22 cycles of trabectedin over 30 months, obtaining a partial response according to RECIST (Response Evaluation Criteria in Solid Tumors) criteria, with good tolerability, and maintaining the response for 10 months after trebectedin withdrawal. Conclusion This very prolonged response, which persisted after drug discontinuation, suggests that trabectedin exerts an oncostatic effect rather than the cytotoxic one produced by other chemotherapeutic agents. Our experience also raises the question of the best way to evaluate trabectedin efficacy.
[Show abstract][Hide abstract] ABSTRACT: The aim of this study is to demonstrate the hypothesis that the experience of the surgeon is sufficient to partially compensate for the lack of haptic feedback of the robotic system da Vinci Si HD (Intuitive®
). Twenty-five international surgeons belonging to different areas of surgical specialization were divided into two groups of investigation: experts and non-experts in the use of da Vinci Platform. This allocation was made on the basis of the following criteria: the number of performed procedures, the number of robotic working days and the number of true console hours. All participants underwent a specific test to assess their ability to recognize the thickness of custom-made membranes, without the availability of haptic feedback. After the performance of the surgeons, score was given according to an appropriate evaluation system (time, preciseness, force of tension and finding a metallic object). The analysis of the performances of participants provided the following results: an average score of 8.87 for the experts compared to 3.57 of non-experts with significant difference (P < 0.05). Other parameters of interest as the average time to conduct the test showed a result of 28.8 s for experts and 71.3 s of non-experts. After our results, a significant difference between the two groups in terms of performance was found. Our hypothesis that the expertise ability of the experts might partially overcome the lack of haptic feedback was confirmed. Probably visual feedback may play a role.
Full-text · Article · Nov 2015 · Journal of Robotic Surgery
[Show abstract][Hide abstract] ABSTRACT: Colonic diverticular disease is the most common cause of lower gastrointestinal bleeding. In the past, this condition was usually managed with urgent colectomy. Recently, the development of endoscopy and interventional radiology has led to a change in the management of colonic diverticular bleeding. The aim of this systematic review is to define the best treatment for colonic diverticular bleeding. A systematic bibliographic research was performed on the online databases for studies (randomized controlled trials [RCTs], observational trials, case series, and case reports) published between 2005 and 2014, concerning patients admitted with a diagnosis of diverticular bleeding according to the PRISMA methodology. The outcomes of interest were: diagnosis of diverticulosis as source of bleeding; incidence of self-limiting diverticular bleeding; management of non self-limiting bleeding (endoscopy, angiography, surgery); and recurrent diverticular bleeding. Fourteen studies were retrieved for analysis. No RCTs were found. Eleven non-randomized clinical controlled trials (NRCCTs) were included in this systematic review. In all studies, the definitive diagnosis of diverticular bleeding was always made by urgent colonoscopy. The colonic diverticular bleeding stopped spontaneously in over 80% of the patients, but a re-bleeding was not rare. Recently, interventional endoscopy and angiography became the first-line approach, thus relegating emergency colectomy to patients presenting with hemodynamic instability or as a second-line treatment after failure or complications of hemostasis with less invasive treatments. Colonoscopy is effective to diagnose diverticular bleeding. Nowadays, interventional endoscopy and angiographic treatment have gained a leading role and colectomy should only be entertained in case of failure of the former.
[Show abstract][Hide abstract] ABSTRACT: To this day, the treatment of generalized peritonitis secondary to diverticular perforation is still controversial. Recently, in patients with acute sigmoid diverticulitis, laparoscopic lavage and drainage has gained a wide interest as an alternative to resection. Based on this backdrop, we decided to perform a systematic review of the literature to evaluate the safety, feasibility, and efficacy of peritoneal lavage in perforated diverticular disease.
A bibliographic search was performed in PubMed for case series and comparative studies published between January 1992 and February 2014 describing laparoscopic peritoneal lavage in patients with perforated diverticulitis.
A total of 19 articles consisting of 10 cohort studies, 8 case series, and 1 controlled clinical trial met the inclusion criteria and were reviewed. In total these studies analyzed data from 871 patients. The mean follow-up time ranged from 1.5 to 96 months when reported. In 11 studies, the success rate of laparoscopic peritoneal lavage, defined as patients alive without surgical treatment for a recurrent episode of diverticulitis, was 24.3%. In patients with Hinchey stage III diverticulitis, the incidence of laparotomy conversion was 1%, whereas in patients with stage IV it was 45%. The 30-day postoperative mortality rate was 2.9%. The 30-day postoperative reintervention rate was 4.9%, whereas 2% of patients required a percutaneous drainage. Readmission rate after the first hospitalization for recurrent diverticulitis was 6%. Most patients who were readmitted (69%) required redo surgery. A 2-stage laparoscopic intervention was performed in 18.3% of patients.
Laparoscopic peritoneal lavage should be considered an effective and safe option for the treatment of patients with sigmoid diverticulitis with Hinchey stage III peritonitis; it can also be consider as a “bridge” surgical step combined with a delayed and elective laparoscopic sigmoidectomy in order to avoid a Hartmann procedure. This minimally invasive staged approach should be considered for patients without systemic toxicity and in centers experienced in minimally invasive surgery techniques. Further evidence is needed, and the ongoing RCTs will better define the role of the laparoscopic peritoneal lavage/drainage in the treatment of patients with complicated diverticulitis.
[Show abstract][Hide abstract] ABSTRACT: ABSTRACT Gastrointestinal stromal tumors are rare malignancies characterized by c-kit and PDGFR-α mutations targeted by imatinib. Pleural effusion is a very rare side effect of imatinib treatment. A 65-year-old female with metastatic gastrointestinal stromal tumor developed electrolyte imbalance, severe peripheral edema and progressively worsening dyspnea 2 months after starting imatinib. Having excluded cardiovascular and pulmonary disorders, imatinib was discontinued and prednisone 25 mg orally daily was begun. The patient's condition improved substantially over the next 48 h with a progressive decrease in dyspnea and a reduction in pleural effusion and peripheral edema. All side effects had resolved within 1 month. In view of the partial response obtained, the patient re-started imatinib after a 1-week interruption. Prednisone was maintained and there was no further toxicity.
[Show abstract][Hide abstract] ABSTRACT: Many of the treatment strategies for sigmoid diverticulitis are actually focusing on nonoperative and minimally invasive approaches. The aim of this systematic review was to evaluate the actual role of damage control surgery (DCS) in the treatment of generalized peritonitis caused by perforated sigmoid diverticulitis.
A literature search was performed in PubMed and Google Scholar for articles published from 1960 to July 2013. Comparative and noncomparative studies that included patients who underwent DCS for complicated diverticulitis were considered.
Acute Physiology and Chronic Health Evaluation score, duration of open abdomen, intensive care unit length of stay, reoperation, bowel resection performed at first operation, fecal diversion, method, and timing of closure of abdominal wall were the main outcomes of interest.
According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses algorithm for the literature search and review, 10 studies were included in this systematic review. DCS was exclusively performed in diverticulitis patients with septic shock or requiring vasopressors intraoperatively. Two surgical different approaches were highlighted: limited resection of the diseased colonic segment with or without stoma or reconstruction in situ, and laparoscopic washing and drainage without colonic resection.
Despite the heterogeneity of patient groups, clinical settings, and interventions included in this review, DCS appears to be a promising strategy for the treatment of Hinchey III and IV diverticulitis, complicated by septic shock. A tailored approach to each patient seems to be appropriate.
[Show abstract][Hide abstract] ABSTRACT: Background
We present a retrospective analysis of metronomic capecitabine in metastatic gastroenteropancreatic neuroendrocrine tumors (GEP-NETs). A review of the literature is also presented.
From January 2007 to December 2013, ten patients with metastatic GEP-NETs (four pancreatic and six ileal) who progressed after treatment with somatostatin analogs and other cytotoxic agents received oral capecitabine 1,500 mg/day continuously. The median patient age was 68 (range 29–82) years. The median treatment duration was 8 months.
Five (50%) patients achieved a partial radiographic response, four (40%) showed stable disease, and one (10%) progressed. Median overall survival was 56 months. Three of the four pancreatic patients achieved a partial radiographic response that lasted for a median of 15.5 months; overall survival and progression-free survival in this subgroup was 58 and 6 months, respectively.
Data in the literature show that capecitabine has only occasionally been used as a single agent, with increased toxicity. Only one study using single-agent capecitabine reported a progression-free survival of 9.9 months and overall survival of 36.5 months, without an objective response or major toxicity. In our experience, metronomic capecitabine was well tolerated, although minor side effects may have been underestimated due to the retrospective nature of our study. This regimen also seems to be feasible in elderly people. Although high response rates and prolonged response duration indicate the potential efficacy of this treatment, our results should be interpreted cautiously because of the small number of patients involved. Capecitabine was most effective in the pancreatic subgroup, which would seem to be more sensitive to chemotherapy.
Full-text · Article · Oct 2014 · OncoTargets and Therapy
[Show abstract][Hide abstract] ABSTRACT: Background:
Today, we do not have a universally accepted evidence on how to treat peritoneal carcinomatosis (PC) from colorectal cancer (CRC) in international guidelines.
The present study is a review of the literature investigating current strategies to treat CRC PC.
Despite the progresses of systemic chemotherapy, the presence of PC among patients with metastatic CRC reduces the overall survival to 30 %, and only 4 % of patients with PC from CRC treated are alive for 5 years. Many trials evaluate the combined treatment of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for CRC PC, suggesting a survival benefit in highly selected patients. Only one trial is randomized and presents some biases. The two main prognostic factors are Peritoneal Cancer Index (PCI) and completeness of cytoreduction score (CC score). There is no universal agreement on how to approach the synchronous presence of PC and liver metastasis with a curative intent during the same procedure. A growing interest among the scientific community has arisen about systematic second-look surgery and HIPEC treatment in high-risk patients.
Current evidences suggest that CRS and HIPEC might be beneficial in highly selected patients affected with PC from CRC. Anyway, today, there is a shortage of well-designed phase 3 trials.
No preview · Article · Jun 2014 · International Journal of Colorectal Disease
[Show abstract][Hide abstract] ABSTRACT: Background. Angiogenesis is a complex process involved in both growth and progression of several human and animal tumours. Tryptase is a serin protease stored in mast cells granules, which plays a role in tumour angiogenesis. Mast cells (MCs) can release tryptase following c-Kit receptor (c-KitR) activation.
Method. In a series of 25 gastric cancer patients with stage T3N2-3M0 (by AJCC for Gastric Cancer 7th Edition), immunohistochemistry and image analysis methods were employed to evaluate in the tumour tissue the correlation between the number of mast cells positive to tryptase (MCPT), c-KitR expressing cells (c-KitR-EC), and microvascular density (MVD). Results. Data demonstrated a positive correlation between MCPT, c-KitR-EC, and MVD to each other. In tumour tissue the mean number of MCPT was 15, the mean number of c-KitR-EC was 20, and the mean number of MVD was 20. The Pearson test correlating MCPT and MVD, c-KitR-EC and MVD was significantly (r = 0.64, P = 0.001; r = 0.66, P = 0.041, resp.). Conclusion. In this pilot study, we suggest that MCPT and c-KitR-EC play a role in gastric cancer angiogenesis, so we think that several c-KitR or tryptase inhibitors such as gabexate mesilate and nafamostat mesilate might be evaluated in clinical trials as a new antiangiogenetic approach.
Full-text · Article · Nov 2013 · Gastroenterology Research and Practice
[Show abstract][Hide abstract] ABSTRACT: Background:
The stomach is the most common site for gastrointestinal stromal tumors (GIST) development. Surgical treatment consists of excision of the entire neoplastic mass, with sufficient surgical margins within healthy tissue. This can be achieved with different techniques ranging from wedge resections, typical gastric resections, right up to total gastrectomy. There aren't clear guidelines for the use of minimally invasive approach.
Materials and methods:
From January 2011 to April 2012, 5 patients with presumed preoperative diagnosis of GIST were treated by robotic surgery at the Unit of Surgery and Advanced Oncologic Therapies, Forlì Hospital, Forlì, Italy. We report operative techniques, perioperative outcomes and follow-up.
Lesions were localized at anterior wall of gastric antrum (N = 2) and near pyloric area (N = 3). Mean tumor size was 5 cm (range 4-7 cm). Surgical procedures were 5 distal gastrectomy. None intervention was converted to open surgery and there weren't major intraoperative complications. Median operative time was 240 min (range 210-300 min) and mean intraoperative blood loss was 96 ml (80-120 ml). All lesions had microscopically negative resection margins. Median follow-up was 13.5 months (range 12-15 months) with a disease-free survival rate of 100%.
Surgical robotic approach for large GISTs is feasibility and new evidences are needed to clarify the effective role of different surgical strategies.
Full-text · Article · Jan 2013 · International Journal of Surgery (London, England)
[Show abstract][Hide abstract] ABSTRACT: Purpose:
Treating hepatocellular carcinoma involves many different specialists and requires multidisciplinary management. In light of the current discussion on the role of ablative therapy, the aim of this study is to compare patients who undergo hepatic resection to those treated with radiofrequency ablation.
The procedures have been conducted in two institutes following the same methodologies. Ninety-six patients with Child-Pugh class A cirrhosis, single or multinodular hepatocellular carcinoma (HCC) and a diameter less than or equal to 3 cm, have been included in this retrospective study: 52 patients have been treated by surgical resection and 44 by radiofrequency ablation. Patient characteristics, survival and disease-free survival have all been analysed.
Disease-free survival was longer in the resection group in comparison to the radiofrequency group with a median disease-free time of 48 versus 34 months, respectively (P = 0.04, hazard ratio = 1.5, 95 % confidence interval = 0.9-2.5). In the resection group, median survival was 54 months with a survival rate at 1, 3 and 5 years of 100, 98 and 46.2 %. In the radiofrequency group, median survival was 40 months with 1-, 3- and 5-year survival rate of 95.5, 68.2 and 36.4 %.
The current study shows that for small HCC in the presence of compensated cirrhosis, surgical resection gives better results than radiofrequency, both in terms of overall survival, as well as disease-free survival. Further evidence is required to clarify the role of ablative therapy as a curative treatment and whether it can replace surgery.
No preview · Article · Dec 2012 · Langenbeck s Archives of Surgery
[Show abstract][Hide abstract] ABSTRACT: Colorectal cancer (CRC) is the most common malignant tumour and the third leading cause of cancer deaths in USA. For advanced CRC, the liver is the first site of metastatic disease; approximately 50 % of patients with CRC will develop liver metastases either synchronously or metachronously within 2 years after primary diagnosis. Hepatic resection (HR) is the only curative option, but only 15-20% of patients with liver metastases from CRC (CRLMs) are suitable for surgical standard treatment. In patients with unresectable CRLMs downsizing chemotherapy can improve resectability (16%). Modern systemic chemotherapy represents the only significant treatment for unresectable CRLMs. However several loco-regional treatments have been developed: hepatic arterial infusion (HAI), cryosurgical ablation (CSA), radiofrequency ablation (RFA), microwave ablation and selective internal radion treatment (SIRT). During the past decade RFA has superseded other ablative therapies, due to its low morbidity, mortality, safety and patient acceptability.
The objective of this study was to systematically review the role of radiofrequency ablation (RFA) in the treatment of CRLMs.
We performed electronic searches in the following databases:CENTRAL, MEDLINE and EMBASE. Current trials were identified through the Internet using the Clinical-Trials.gov site (to January 2, 2012) and ASCO Proceedings. The reference lists of identified trials were reviewed for additional studies.
Randomized clinical trials (RCTs), quasi-randomised or controlled clinical trials (CCTs) comparing RFA to any other therapy for CRLMs were included. Observational study designs including comparative cohort studies comparing RFA to another intervention, single arm cohort studies or case control studies have been included if they have: prospectively collected data, ten or more patients; and have a mean or median follow-up time of 24 months. Patients with CRLMs who have no contraindications for RFA. Patients with unresectable extra-hepatic disease were also included.Trials have been considered regardless of language of origin.
A total of 1144 records were identified through the above electronic searching. We included 18 studies: 10 observational studies, 7 Clinical Controlled Trials (CCTs) and an additional 1 Randomized Clinical Trial (RCT) (abstract) identified by hand searching in the 2010 ASCO Annual Meeting. The most appropriate way of summarizing time-to-event data is to use methods of survival analysis and express the intervention effect as a hazard ratio. In the included studies these outcome are mostly reported as dichotomous data so we should have asked authors research data for each participant and perform Individual Patient Data (IPD) meta-analysis. Given the study design and low quality of included studies we decided to give up and not to summarize these data.
Seventeen studies were not randomised and this increases the potential for selection bias. In addition, there was imbalance in the baseline characteristics of the participants included in all studies. All studies were classified as having a elevate risk of bias. The assessment of methodological quality of all non-randomized studies included in meta-analysis performed by the STROBE checklist has allowed us to identify several methodological limits in most of the analysed studies. At present, the information from the single RCT included (Ruers 2010) comes from an abstract of 2010 ASCO Annual Meeting where the allocation concealment was not reported; however in original protocol allocation concealment was adequately reported (EORTC 40004 protocol). The heterogeneity regarding interventions, comparisons and outcomes rendered the data not suitable.
This systematic review gathers information from several controlled clinical trials and observational studies which are vulnerable to different types of bias. The imbalance between characteristics of patients in the allocated groups appears to be the main concern. Only one randomised clinical trial (published as an abstract), comparing 60 patients receiving RFA plus CT versus 59 patients receiving CT alone, was identified. This study showed that PFS was significantly higher in the group that received RFA. However, it was not able to provide information on overall survival. In conclusion, evidence from the included studies are insufficient to recommend RFA for a radical oncological treatment of CRLMs.
No preview · Article · Jun 2012 · Cochrane database of systematic reviews (Online)
[Show abstract][Hide abstract] ABSTRACT: Although standard treatment for advanced epithelial ovarian cancer (EOC) consists of surgical debulking and intravenous platinum- and taxane-based chemotherapy, favorable oncological outcomes have been recently reported with the use of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The aim of the study was to analyze feasibility and results of CRS and HIPEC in patients with advanced EOC.
This is an open, prospective phase 2 study including patients with primary or recurrent peritoneal carcinomatosis due to EOC. Thirty-nine patients with a mean (SD) age of 57.3 (9.7) years (range, 34-74 years) were included between September 2005 and December 2009. Thirty patients (77%) had recurrent EOC and 9 (23%) had primary EOC.
For HIPEC, cisplatin and paclitaxel were used for 11 patients (28%), cisplatin and doxorubicin for 26 patients (66%), paclitaxel and doxorubicin for 1 patient (3%), and doxorubicin alone for 1 patient (3%). The median intra-abdominal outflow temperature was 41.5°C. The mean peritoneal cancer index (PCI) was 11.1 (range, 1-28); and according to the intraoperative tumor extent, the tumor volume was classified as low (PCI <15) or high (PCI ≥15) in 27 patients (69%) and 12 patients (31%), respectively. Microscopically complete cytoreduction was achieved for 35 patients (90%), macroscopic cytoreduction was achieved for 3 patients (7%), and a gross tumor debulking was performed for 1 patient (3%). Mean hospital stay was 23.8 days. Postoperative complications occurred in 7 patients (18%), and reoperations in 3 patients (8%). There was one postoperative death. Recurrence was seen in 23 patients (59%) with a mean recurrence time of 14.4 months (range, 1-49 months).
Hyperthermic intraperitoneal chemotherapy after extensive CRS for advanced EOC is feasible with acceptable morbidity and mortality. Complete cytoreduction may improve survival in highly selected patients. Additional follow-up and further studies are needed to determine the effects of HIPEC on survival.
Full-text · Article · May 2012 · International Journal of Gynecological Cancer
[Show abstract][Hide abstract] ABSTRACT: Laparoscopic and open rectal resection for cancer were compared by analysing a total of 26 end points which included intraoperative and postoperative recovery, short-term morbidity and mortality, late morbidity and long-term oncological outcomes.
We searched for published randomized clinical trials, presenting a comparison between laparoscopic and open rectal resection for cancer using the following electronic databases: PubMed, OVID, Medline, Cochrane Database of Systematic Reviews, EBM Reviews, CINAHL and EMBASE.
Nine randomized clinical trials (RCTs) were included in the meta-analysis incorporating a total of 1544 patients, having laparoscopic (N = 841) and open rectal resection (N = 703) for cancer. Laparoscopic surgery for rectal cancer was associated with a statistically significant reduction in intraoperative blood loss and in the number of blood transfusions, earlier resuming solid diet, return of bowel function and a shorter duration of hospital stay. We also found a significant advantage for laparoscopy in the reduction of post-operative abdominal bleeding, late intestinal adhesion obstruction and late morbidity. No differences were found in terms of intra-operative and late oncological outcomes.
The meta-analysis indicates that laparoscopy benefits patients with shorter hospital stay, earlier return of bowel function, reduced blood loss and number of blood transfusions and lower rates of abdominal postoperative bleeding, late intestinal adhesion obstruction and other late morbidities.
Full-text · Article · Feb 2012 · Colorectal Disease
[Show abstract][Hide abstract] ABSTRACT: Laparoscopic adhesiolysis has been demonstrated to be technically feasible in small bowel obstruction and carries advantages in terms of post-surgical course. The increasing dissemination of laparoscopic surgery in the emergency setting and the lack of concrete evidence in the literature have called for a consensus conference to draw recommendations for clinical practice.
A literature search was used to outline the evidence, and a consensus conference was held between experts in the field. A survey of international experts added expertise to the debate. A public jury of surgeons discussed and validated the statements, and the entire process was reviewed by three external experts.
Recommendations concern the diagnostic evaluation, the timing of the operation, the selection of patients, the induction of the pneumoperitoneum, the removal of the cause of obstructions, the criteria for conversion, the use of adhesion-preventing agents, the need for high-technology dissection instruments and behaviour in the case of misdiagnosed hernia or the need for bowel resection.
Evidence of this kind of surgery is scanty because of the absence of randomized controlled trials. Nevertheless laparoscopic skills in emergency are widespread. The recommendations given with the consensus process might be a useful tool in the hands of surgeons.
Full-text · Article · Feb 2012 · Colorectal Disease
[Show abstract][Hide abstract] ABSTRACT: Laparoscopic adhesiolysis has been demonstrated technically feasible in small bowel obstruction, and carries advantages in terms of post-surgical course. The increasing dissemination of laparoscopic surgery in the emergency setting, and the lack of concrete evidence in the literature, have called for a consensus conference to draw recommendations for the clinical practice. Method: A literature research was used to outline the evidence, and a consensus conference was held between experts in the field. A survey between international experts added expertise to the debate. A public jury of surgeons discussed and validated the statements, and the entire process was reviewed by three external experts. Results: Recommendations concern the diagnostic work-up, the timing of the operation, the patients' selection, the induction of the pneumoperitoneum, the removal of the cause of obstruction, the criteria for conversion, the use of adhesion preventing agents, the need for high-technology dissection instruments, the behavior in case of misdiagnosed hernia, or in case of need for bowel resection. Conclusion: Evidence on this kind of surgery is scanty because of the absence of randomized controlled trials. Nevertheless laparoscopic skills in emergency is widespread. The recommendations given with the consensus process might be a useful tool in the hands of surgeons.