Laparoscopic cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: Long term oncologic outcomes from the international PSOGI registry.

The laparoscopic approach for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (L-CRS + HIPEC) in highly selected patients was previously reported from the PSOGI registry with a demonstrable reduction in length of stay and post-operative morbidity. This study aims to update this international PSOGI registry with a larger cohort of patients and a longer follow-up period. METHODS: An international registry was designed through a networking database (REDCAP®). All centers performing L-CRS + HIPEC were invited through PSOGI to submit data on their cases. Variables such as demographics, clinical outcomes, and survival were analyzed. RESULTS: A total of 315 L-CRS + HIPEC cases were provided by 14 worldwide centers. A total of 215 patients were included in the L-CRS + HIPEC group. The median peritoneal cancer index (PCI) was 3 (3-5). The median length of stay was 7 days (5-10) and the major morbidity (Clavien-Dindo ≥3) was 6.1% after 30 days. The 5-year disease-free survival (DFS) per tumor origin was: 94% for PMP-LG, 85% for PMP-HG, 100% for benign multicyst peritoneal mesothelioma (MPM), 37.4% for colonic origin, and 54%(at 3 years) for ovarian origin. The 5 years overall survival (OS) per tumor origin was: 100% for PMP-LG, PMP-HG and MPM; 61% for colonic origin, and 74% (at 3 years) for ovarian origin. In addition, a total of 85 patients were analyzed in the laparoscopic risk-reducing HIPEC (L-RR + HIPEC). The median length of stay was 5 days (4-6) and the major morbidity was 6% after 30 days. The 5-year DFS per tumor origin was: 96% for perforated low grade appendiceal mucinous neoplasm (LAMN II) and 68.1% for colon origin. The 5 years OS per tumor origin was: 98% for LAMN II and 83.5% for colonic origin. CONCLUSIONS: Minimally invasive CRS + HIPEC is a safe procedure for selected patients with peritoneal carcinomatosis in specialized centers. It improves perioperative results while providing satisfactory oncologic outcomes. L-RR + HIPEC represents a promising strategy that could be evaluated in patients with high risk of developing peritoneal carcinomatosis into prospective randomized trials.

Appendiceal Goblet Cell Carcinoma: Role of Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC).

Goblet cell carcinoma (GCC) encompasses a separate entity in appendiceal neoplasms with mixed glandular and neuro-endocrine pathological features. GCC mostly presents as an acute appendicitis duo to luminal obstruction or as an incidental finding on the surgical appendectomy specimen. In case of tumour perforation or presence of other risk factors, guidelines suggest additional treatment with a completing right hemicolectomy or cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). We report the case of a 77-year-old male with symptoms of appendicitis for which an appendectomy was performed. The appendix was ruptured during the procedure. There was an incidental finding of GCC on the pathological specimen. Because of possible tumour soiling, the patient received a prophylactic CRS-HIPEC. A literature review was performed to investigate the potential role for CRS-HIPEC as a curative treatment in patients with GCC. GCC of the appendix is an aggressive type of tumour with a high risk of peritoneal and systemic dissemination. CRS and HIPEC is a treatment option: both in a prophylactic setting and in patients with established peritoneal metastases.

The Delphi and GRADE methodology used in the PSOGI 2018 consensus statement on Pseudomyxoma Peritonei and Peritoneal Mesothelioma.

Pseudomyxoma Peritonei (PMP) and Peritoneal Mesothelioma (PM) are both rare peritoneal malignancies. Currently, affected patients may be treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy offering long-term survival or even cure in selected patients. However, many issues regarding the optimal treatment strategy are currently under debate. To aid physicians involved in the treatment of these patients in clinical decision making, the PSOGI executive committee proposed to create a consensus statement on PMP and PM. This manuscript describes the methodology of the consensus process. The Delphi technique is a reliable method for attaining consensus on a topic that lacks scientific evidence through multiple voting rounds which feeds back responses to the participants in between rounds. The GRADE system provides a structured framework for presenting and grading the available evidence. Separate questionnaires were created for PMP and PM and sent during two voting rounds to 80 and 38 experts, respectively. A consensus threshold of 51.0% was chosen. After the second round, consensus was reached on 92.9%-100.0% of the questions. The results were presented and discussed in the plenary session at the PSOGI 2018 international meeting in Paris. A third round for the remaining issues is currently in progress. In conclusion, using the Delphi technique and GRADE methodology, consensus was reached in many issues regarding the treatment of PM and PMP amongst an international panel of experts. The main results will be published in the near future.

Appendiceal tumours and pseudomyxoma peritonei: Literature review with PSOGI/EURACAN clinical practice guidelines for diagnosis and treatment.

Pseudomyxoma Peritonei (PMP) is a rare peritoneal malignancy, most commonly originating from a perforated epithelial tumour of the appendix. Given its rarity, randomized controlled trials on treatment strategies are lacking, nor likely to be performed in the foreseeable future. However, many questions regarding the management of appendiceal tumours, especially when accompanied by PMP, remain unanswered. This consensus statement was initiated by members of the Peritoneal Surface Oncology Group International (PSOGI) Executive Committee as part of a global advisory role in the management of uncommon peritoneal malignancies. The manuscript concerns an overview and analysis of the literature on mucinous appendiceal tumours with, or without, PMP. Recommendations are provided based on three Delphi voting rounds with GRADE-based questions amongst a panel of 80 worldwide PMP experts.

Laparoscopic cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for limited peritoneal metastasis. The PSOGI international collaborative registry.

INTRODUCTION: A laparoscopic approach for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (L-CRS+HIPEC) in highly selected patients has been reported in small cohorts with a demonstrable reduction in length of stay and post-operative morbidity. This study aims to analyse individual patient data from these international centres collected through the Peritoneal Surface Oncology Group International (PSOGI) L-CRS+HIPEC registry. METHODS: An international registry was designed through a networking database (REDCAP®). All centres performing L-CRS+HIPEC were invited through PSOGI to submit data on their cases. Patient's characteristics, postoperative outcomes and survival were analysed. RESULTS: Ten international centres contributed a total of 143 L-CRS+HIPEC patients during the study period. The most frequent indication was low grade pseudomyxoma peritonei in 79/143 (55%). Other indications were benign multicyst mesothelioma in 21/143(14%) and peritoneal metastasis from colon carcinoma in 18/143 (12,5%) and ovarian carcinoma in 13/143 (9%). The median PCI was 3 (2-5). The median length of stay was 6 (5-10) days, with 30-day major morbidity rate of 8.3% and 30-day mortality rate of 0.7%. At a median follow-up of 37 (16-64) months 126/143 patients (88.2%) were free of disease. CONCLUSIONS: Analysis of these data demonstrates that L-CRS+HIPEC is a safe and feasible procedure in highly selected patients with limited peritoneal disease when performed at experienced centres. While short to midterm outcomes are encouraging in patients with less invasive histology, longer follow up is required before recommending it for patients with more aggressive cancers with peritoneal dissemination.

A minimally invasive approach for peritonectomy procedures and hyperthermic intraperitoneal chemotherapy (HIPEC) in limited peritoneal carcinomatosis: The American Society of Peritoneal Surface Malignancies (ASPSM) multi-institution analysis.

BACKGROUND: Minimally invasive surgery is playing an increasing role in the treatment of patients with gastrointestinal and gynaecological malignancies as the data show reduced morbidity, faster recovery and similar oncological outcome when compared to open procedures. MATERIALS AND METHODS: The American Society of Peritoneal Surface Malignancies (ASPSM) conducted a retrospective study to analyse peritonectomy procedures and HIPEC done via the laparoscopic route. A database with standard clinical and pathological parameters was set up and distributed amongst ASPSM members. Rate of relapse, morbidity and mortality were the primary endpoints of the study. RESULTS: A total of 90 patients from 7 centres around the world were identified. Sixty percent were female. Mean age was 50 years. Peritoneal carcinomatosis from appendiceal origin was the most common diagnosis in a 64.9% of patients and colon origin was diagnosed in 16.5% of patients. Mean peritoneal cancer index (PCI) was 4.1 (0-10). Forty-one percent of patients had a bowel resection. Mean operative time was 4.7 h (2.5-8). All patients had a complete cytoreduction and HIPEC. Grade 3 and 4 morbidity was 3.0 and 6.5%, respectively. The most common reason for re-operation was an internal hernia in 2 out of 5 cases. Operative mortality and re-admission rates were 0 and 5%, respectively. Mean hospital stay was 7.4 days (1-18). At a mean follow-up of 31.6 months, 15/90 patients have a disease relapse but loco-regional relapse was identified in only five patients. CONCLUSIONS: Analysis of these data suggests that minimally invasive approach for peritonectomy procedures and HIPEC is feasible, safe and should be considered as part of the armamentarium for highly selected patients with peritoneal surface malignancies with limited tumour burden, defined as PCI of 10 or less and borderline tumours as low-grade pseudomyxoma and benign multicystic mesothelioma.

The Delphi and GRADE methodology used in the PSOGI 2018 consensus statement on Pseudomyxoma Peritonei and Peritoneal Mesothelioma

Pseudomyxoma Peritonei (PMP) and Peritoneal Mesothelioma (PM) are both rare peritoneal malignancies. Currently, affected patients may be treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy offering long-term survival or even cure in selected patients. However, many issues regarding the optimal treatment strategy are currently under debate. To aid physicians involved in the treatment of these patients in clinical decision making, the PSOGI executive committee proposed to create a consensus statement on PMP and PM. This manuscript describes the methodology of the consensus process. The Delphi technique is a reliable method for attaining consensus on a topic that lacks scientific evidence through multiple voting rounds which feeds back responses to the participants in between rounds. The GRADE system provides a structured framework for presenting and grading the available evidence. Separate questionnaires were created for PMP and PM and sent during two voting rounds to 80 and 38 experts, respectively. A consensus threshold of 51.0% was chosen. After the second round, consensus was reached on 92.9%-100.0% of the questions. The results were presented and discussed in the plenary session at the PSOGI 2018 international meeting in Paris. A third round for the remaining issues is currently in progress. In conclusion, using the Delphi technique and GRADE methodology, consensus was reached in many issues regarding the treatment of PM and PMP amongst an international panel of experts. The main results will be published in the near future.

COMPRES: a prospective postmarketing evaluation of the compression anastomosis ring CAR 27(™) /ColonRing(™).

AIM: Preclinical studies have suggested that nitinol-based compression anastomosis might be a viable solution to anastomotic leak following low anterior resection. A prospective multicentre open label study was therefore designed to evaluate the performance of the ColonRing(™) in (low) colorectal anastomosis. METHOD: The primary outcome measure was anastomotic leakage. Patients were recruited at 13 different colorectal surgical units in Europe, the United States and Israel. Institutional review board approval was obtained. RESULTS: Between 21 March 2010 and 3 August 2011, 266 patients completed the study protocol. The overall anastomotic leakage rate was 5.3% for all anastomoses, including a rate of 3.1% for low anastomoses. Septic anastomotic complications occurred in 8.3% of all anastomoses and 8.2% of low anastomoses. CONCLUSION: Nitinol compression anastomosis is safe, effective and easy to use and may offer an advantage for low colorectal anastomosis. A prospective randomized trial comparing ColonRing(™) with conventional stapling is needed.

Handlebar hernia: an uncommon cause of intra-abdominal lesions.

A traumatic abdominal wall hernia (TAWH) is an uncommon complication of abdominal trauma. Handlebar hernia is an even rarer type of traumatic abdominal wall hernia, with only 33 previously reported cases in literature. It is caused by a local trauma with a handlebar-like object which is not sharp enough to penetrate the elastic skin, but has sufficient focused force to breach the muscle and fascia of the abdominal wall. A high index of clinical suspicion for associated intra-abdominal lesions in patients with traumatic abdominal wall hernia is warranted. This may not only influence the immediate treatment of the abdominal hernia but also the type and timing of mesh repair to be performed. Early repair is mandatory to avoid complications. The choice for primary repair versus mesh repair will be discussed according to the size of the hernia and the amount of tissue destruction by the trauma. The type of mesh used for the repair will be determined by presence or absence of contamination in the abdomen.

Pharmacokinetics of the perioperative use of cancer chemotherapy in peritoneal surface malignancy patients.

Background. The peritoneal surface is an acknowledged locoregional failure site of abdominal malignancies. Previous treatment attempts with medical therapy alone did not result in long-term survival. During the last two decades, new treatment protocols combining cytoreductive surgery with perioperative intraperitoneal and intravenous cancer chemotherapy have demonstrated very encouraging clinical results. This paper aims to clarify the pharmacologic base underlying these treatment regimens. Materials and Methods. A review of the current pharmacologic data regarding these perioperative chemotherapy protocols was undertaken. Conclusions. There is a clear pharmacokinetic and pharmacodynamic rationale for perioperative intraperitoneal and intravenous cancer chemotherapy in peritoneal surface malignancy patients.

Impact of surgical and clinical factors on the pharmacology of intraperitoneal doxorubicin in 145 patients with peritoneal carcinomatosis.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are a combined treatment modality considered for selected patients with peritoneal carcinomatosis from colorectal and appendiceal cancer. Doxorubicin is a drug consistently used by our group in this clinical setting. The surgical and clinical factors that modify the pharmacokinetics of HIPEC may be important for the design of future perioperative chemotherapy regimens. MATERIALS AND METHODS: The patients included were 145 who had colorectal or appendiceal carcinomatosis resected using CRS prior to treatment with HIPEC with doxorubicin as part of a multidrug regimen. The effect of clinical and surgical factors on drug distribution after a single intraperitoneal bolus administration with doxorubicin was determined. RESULTS: The pharmacokinetics of 145 patients treated with intraperitoneal doxorubicin showed a 78 times greater exposure to peritoneal surfaces as compared to plasma. At 90 min 12% of the drug remained in the chemotherapy solution and 88% was retained in the body. The extent of visceral resection and peritonectomy increased the clearance of doxorubicin from the peritoneal space. A major resection of visceral peritoneal surface, a contracted peritoneal space, and an incomplete cytoreduction reduced drug clearance. CONCLUSIONS: Surgical and clinical factors may require modifications of chemotherapy administration. A large visceral resection and a contracted peritoneal space caused a reduced doxorubicin clearance. Total diffusion surface is an important determinant of doxorubicin pharmacokinetics.

Laparoscopic hyperthermic intraperitoneal peroperative chemotherapy (HIPEC) in the management of refractory malignant ascites: A multi-institutional retrospective analysis in 52 patients.

Malignant ascites is a debilitating condition affecting cancer patients in their terminal stage of disease. Recently, laparoscopic hyperthermic intraperitoneal peroperative chemotherapy (HIPEC) was introduced as a new approach. From September 2001 to August 2008, 52 patients were treated with this new modality. No treatment-related mortality was observed. Median survival was 98 days. One patient developed a clinical recurrence. Laparoscopic HIPEC is a safe and effective method for palliating malignant ascites.