Treatment Of Peritoneal Surface Malignancies Research Articles

Defining the Values and Quality of Life of Cancer Survivors Following Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: An International Survey Study.

Advances in treatment of peritoneal surface malignancies including cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS±HIPEC) have led to long-term survivorship, yet the subsequent quality of life (QOL) and values of these patients are unknown. Survivors were offered surveys via online support groups. Novel items assessed how patients prioritized experience, costs, longevity, and wellbeing. Of the 453 gastrointestinal/hepatobiliary (GI/HPB) surgical patients that responded, 74 underwent CRS±HIPEC and were 54±12 years old, 87% female, and 93% white. Respondents averaged 29 months from diagnosis, with a maximum survival of 20 years. With a moderate level of agreement (W = 39%), rankings of value metrics among respondents were predictable (p < 0.001). Longevity and functional independence were ranked highest; treatment experience and cost of treatment were ranked lowest (p < 0.001). Those who underwent CRS±HIPEC or other GI/HPB surgeries reported the same rank order. QOL in CRS±HIPEC survivors, both mental (M-QOL) (44±13) and physical (P-QOL) (41±11) were lower than in the general population (50±10); p < 0.001. Impairments persisted throughout survivorship, but M-QOL improved over time (p < 0.05). When comparing CRS±HIPEC with other GI/HPB cancer surgery survivors, M-QOL (43±13 versus 43±14, p = 0.85) and P-QOL (40±11 versus 42±12, p = 0.41) were similar. Although CRS±HIPEC survivors experience long-term mental and physical health impairments, they were similar to those experienced by survivors of other GI/HPB cancer surgeries, and their QOL improved significantly throughout survivorship. As CRS±HIPEC survivors prioritize longevity above all other metrics, survival benefit may outweigh a temporary reduction in QOL.

Functional biomaterials for the diagnosis and treatment of peritoneal surface malignancies (3/2023)

Functional biomaterials for the diagnosis and treatment of peritoneal surface malignancies (3/2023)

Functional biomaterials for the diagnosis and treatment of peritoneal surface malignancies

AbstractPeritoneal surface malignancies (PSM) can originate from tumors in many organs and are highly malignant, and difficult to diagnose and cure, posing a serious threat to the survival of patients. Although the diagnosis and treatment of PSM have made significant progress in the past two decades, numerous challenges remain. Recently, functionalized biomaterials have shown promise for PSM diagnosis and treatment. Hence, we review the progress of functionalized biomaterials for the diagnosis and treatment of PSM. We first introduce the classification and pathogenesis of PSM. We then discuss the applications of functionalized biomaterials for the diagnosis and treatment of PSM. In particular, we focus on functionalized biomaterials as drug carriers for the treatment of PSM, including chemotherapy, immunotherapy, targeted therapy, combination therapy, and other therapies. Finally, we summarized the current challenges and provided a perspective on the diagnosis and treatment of PSM.

Treatment of Peritoneal Surface Malignancies by Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Spain: Results of the National Registry of the Spanish Group of Peritoneal Oncologic Surgery (REGECOP).

Treatment of Peritoneal Surface Malignancies (PSM) with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has achieved results never seen before in these patients, which classically have a poor prognosis. The possibility of conducting clinical trials in these diseases is complicated, since some of them are rare, so the analysis of large databases provides very valuable scientific information. The aim of this study is to analyze the global results of the National Registry of the Spanish Group of Peritoneal Oncologic Surgery (REGECOP), whose objective is to register all patients scheduled for HIPEC nationwide. This is a retrospective analysis of the data recorded in the REGECOP from 36 Spanish hospitals from 2001 to 2021. There were 4159 surgical interventions in 3980 patients. 66% are women and 34% are men with a median age of 59 years (range 17-86). 41.5% of the patients were treated for Peritoneal Metastases (PM) of colorectal cancer (CRC); 32.4% were women with ovarian cancer (OC) with PM; 12.8% were treated for pseudomyxoma peritonei (PMP); 6.2% had PM from gastric cancer (GC); 4.9% had PM of non-conventional origin; and, finally, 2.1% of cases were patients diagnosed with peritoneal mesothelioma. The median Peritoneal Cancer Index (PCI) was 9 (0-39), and complete cytoreduction was achieved in 81.7% of the procedures. Severe morbidity (Dindo-Clavien grade III-IV) was observed in 17.7% of surgeries, with 2.1% mortality. Median hospital stay was 11 days (0-259). Median overall survival (OS) was 41 months for CRC patients, 55 months for women with OC, was not reached in PMP patients, was 14 months for GC patients, and 66 months in mesothelioma patients. large databases provide extremely useful data. CRS with HIPEC in referral centers is a safe treatment with encouraging oncologic results in PSM.

The robotic future of minimally invasive cytoreduction and hyperthermic intraperitoneal chemotherapy for peritoneal surface malignancies.

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) has been increasingly utilized for peritoneal surface malignancies. This has been commonly utilized for a variety of neoplasms, but, especially mucinous neoplasms of the appendix, ovarian cancer, gastric cancer, colorectal cancer and mesothelioma. Traditionally, CRS/HIPEC has been performed as an open, extensive operation associated with prolonged hospitalization. However, when the peritoneal carcinomatosis index (PCI) is small (<10), minimally invasive approaches can be considered. Such less invasive approaches may be associated with improved postoperative recovery, less complications while preserving oncologic outcomes. The robotic platform offers distinct advantages over laparoscopy with superior visualization and ergonomics which account for its increased utilization in oncologic surgery. Herein, we review available data on minimally invasive approaches to CRS/HIPEC procedures, focusing on patient selection and comparative studies to open CRS/HIPEC. We summarize the existing initial studies on robotically assisted CRS/HIPEC and provide technical insights about our approach to robotically assisted CRS/HIPEC. Current data suggests that treatment of peritoneal surface malignancies with minimally invasive CRS/HIPEC is feasible in selected cases and is associated with improved postoperative recovery. The robotically assisted platform for CRS/ HIPEC deserves further investigation and may improve outcomes after this procedure in the future for carefully selected patients with low PCI.

Enhanced Recovery after Surgery (ERAS) Program for Patients with Peritoneal Surface Malignancies Undergoing Cytoreductive Surgery with or without HIPEC: A Systematic Review and a Meta-Analysis.

Enhanced recovery after surgery (ERAS) program refers to a multimodal intervention to reduce the length of stay and postoperative complications; it has been effective in different kinds of major surgery including colorectal, gynaecologic and gastric cancer surgery. Its impact in terms of safety and efficacy in the treatment of peritoneal surface malignancies is still unclear. A systematic review and a meta-analysis were conducted to evaluate the effect of ERAS after cytoreductive surgery with or without HIPEC for peritoneal metastases. MEDLINE, PubMed, EMBASE, Google Scholar and Cochrane Database were searched from January 2010 and December 2021. Single and double-cohort studies about ERAS application in the treatment of peritoneal cancer were considered. Outcomes included the postoperative length of stay (LOS), postoperative morbidity and mortality rates and the early readmission rate. Twenty-four studies involving 5131 patients were considered, 7 about ERAS in cytoreductive surgery (CRS) + HIPEC and 17 about cytoreductive alone; the case histories of two Italian referral centers in the management of peritoneal cancer were included. ERAS adoption reduced the LOS (-3.17, 95% CrI -4.68 to -1.69 in CRS + HIPEC and -1.65, 95% CrI -2.32 to -1.06 in CRS alone in the meta-analysis including 6 and 17 studies respectively. Non negligible lower postoperative morbidity was also in the meta-analysis including the case histories of two Italian referral centers. Implementation of an ERAS protocol may reduce LOS, postoperative complications after CRS with or without HIPEC compared to conventional recovery.

Exploring the potential of taurolidine in inducing mobilization and detachment of colon cancer cells: a preliminary in-vitro study

BackgroundRecently, taurolidine has been intensively studied on a variety of in-vitro cancer cell-lines and first data exhibit encouraging antitumoral effects. While the clinical use of taurolidine is considered, some studies with in-vivo experiments contradict this beneficial effect and even indicate advanced cancer growth. The aim of this study is to further investigate this paradox in-vivo effect by taurolidine and closely analyze the interaction of cancer cells with the surrounding environment following taurolidine exposure.MethodsHT-29 (ATCC® HTB-38™) cells were treated with taurolidine at different concentrations and oxaliplatin using an in-vitro model. Morphological changes with respect to increasing taurolidine dosage were visualized and monitored using electron microscopy. Cytotoxicity of the agents as well as extent of cellular detachment by mechanical stress was measured for each substance using a colorimetric MTS assay.ResultsBoth taurolidine and oxaliplatin exhibit cell toxicity on colon cancer cells. Taurolidine reshapes colon cancer cells from round into spheric cells and further induces cluster formation. When exposed to mechanical stress, taurolidine significantly enhances detachment of adherent colon carcinoma cells compared to the control (p < 0.05) and the oxaliplatin group (p < 0.05). This effect is dose dependent.ConclusionsBeside its cytotoxic effects, taurolidine could also change mechanical interactions of cancer cells with their environment. Local cancer cell conglomerates could be mechanically mobilized and may cause metastatic growth further downstream. The significance of changes in cellular morphology caused by taurolidine as well as its interaction with the microenvironment must be further addressed in clinical cancer therapies. Further clinical studies are needed to evaluate both the safety and efficacy of taurolidine for the treatment of peritoneal surface malignancies.

Early postoperative outcomes of staging laparoscopy for peritoneal metastases with or without pressurized intra-peritoneal aerosol chemotherapy (PIPAC)

BackgroundPressurized intraperitoneal aerosol chemotherapy (PIPAC) has been introduced for palliative treatment of peritoneal surface malignancies (PSM) and is currently tested also in the neoadjuvant and prophylactic setting. The aim was therefore to compare safety and tolerance of staging laparoscopy with or without PIPAC.MethodsThis retrospective analysis compared consecutive patients undergoing staging laparoscopy alone for oesogastric cancer with patients having PIPAC for suspected PSM of various origins from January 2015 until January 2020. Safety was assessed by use of the Clavien classification for complications and CTCAE for capturing of adverse events. Pain and nausea were documented by use of a visual analogue scale (VAS: 0–10: maximal intensity).ResultsOverall, 25 PIPAC procedures were compared to 24 staging laparoscopies. PIPAC procedures took a median of 35 min (IQR: 25–67) longer. Four patients experienced at least one complication in either group (p = 0.741). No differences were noted for postoperative nausea (p = 0.961) and pain levels (p = 0.156). Median hospital stay was 2 (IQR: 1–3) for PIPAC and 1 (IQR: 1–2) for the laparoscopy group (p = 0.104).ConclusionsThe addition of PIPAC did not jeopardize safety and postoperative outcomes of staging laparoscopy alone. Further studies need to clarify its oncological benefits.

The Role of Hyperthermia in the Treatment of Peritoneal Surface Malignancies.

Hyperthermia is used to treat peritoneal surface malignancies (PSM), particularly during hyperthermic intraperitoneal chemotherapy (HIPEC). This manuscript provides a focused update of hyperthermia in the treatment of PSM. The heterogeneous response to hyperthermia in PSM can be explained by tumor and treatment conditions. PSM tumors may resist hyperthermia via metabolic and immunologic adaptation. The thermodynamics of HIPEC are complex and require computational fluid dynamics (CFD). The clinical evidence supporting the benefit of hyperthermia is largely observational. Continued research will allow clinicians to characterize and predict the individual response of PSM to hyperthermia. The application of hyperthermia in current HIPEC protocols is mostly empirical. Thus, modeling heat transfer with CFD is a necessary task if we are to achieve consistent and reproducible hyperthermia. Although observational evidence suggests a survival benefit of hyperthermia, no clinical trial has tested the individual role of hyperthermia in PSM.

Current Medical Care Situation of Patients in Germany Undergoing Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC).

Simple SummaryThe treatment of peritoneal surface malignancies has evolved differently from other fields in surgical oncology in the past decades and modern approaches were introduced into daily-routine. Curative as well as palliative surgical treatment options redefined the fate of patients with this aggressive disease. Nowadays, patients with a limited peritoneal tumor spread of colonic origin have comparable survival rates compared with colorectal liver and pulmonary metastases. After the failure of systemic chemotherapy, the application of PIPAC revolutionized the palliative treatment for these patients and recent results show a high histological response rates, an improvement in quality-of-life and, furthermore, a cost-reduction compared to systemic chemotherapy. The application of PIPAC in other disease-settings (neoadjuvant/adjuvant) needs to be defined in further clinical trials.Objective: Tailored approaches in gastrointestinal oncology have been more frequently introduced in past years and for patients with peritoneal metastases. This article attempts to overview the current strategies in surgical gastrointestinal oncology, with a focus on gastrointestinal peritoneal metastases. Methods: In 2019, all patients undergoing PIPAC therapy in Germany were retrospectively analyzed regarding morbidity and in-hospital mortality rates. Furthermore, patients with chemotherapy-refractory peritoneal metastases from gastric cancer undergoing PIPAC-therapy at our institution were analyzed. Results: In 2019, 534 patients received PIPAC treatment in german hospitals. The in-hospital mortality rate was 0%. In total, 36 patients suffered from postoperative complications (8%). From April 2016 to September 2021, a total of 44 patients underwent 93 PIPAC applications at our institution. The non-access-rate was 0%. The median PRGS was two (range, 1–4). Eleven patients (44%) showed histologically stable disease, whereas six patients (24%) showed histological regression. Median survival, calculated from the date of the first PIPAC application, was 181 days (range, 43–636 days). Conclusions: PIPAC is a safe and feasible procedure with a low in-hospital morbidity and mortality. Furthermore, PIPAC in the palliative and chemorefractory setting and is an appealing approach for patient management in the future.

Gold Nanorod Hydrogel Film for Laser‐Induced Hyperthermic Intraperitoneal Chemotherapy to Treat Peritoneal Malignancies

Treatment of peritoneal surface malignancies with cytoreductive surgery and HIPEC (CRS/HIPEC) has a substantial risk of local recurrence and causes off‐target toxicity. HIPEC is reinvented utilizing a gold nanorod (GNR) platform to provide surgically targeted precision delivery of mild hyperthermia (42 °C) to increase chemotherapeutic efficacy and reduce off‐target toxicity. A biocompatible hydrogel film containing GNRs, mitomycin‐C (MMC), and cisplatin (CisPt) is designed to create controlled, mild hyperthermia generated from NIR laser treatment of GNRs. The concentration of GNRs and duration of hyperthermia is determined using dose‐response curves to titrate goal temperature parameters of mild hyperthermia (42 °C) in a controlled fashion. Loading and release of CisPt and MMC at an inhibitory concentration (IC50) dose is determined to be highly efficient. In vitro and in vivo experiments demonstrate cytotoxicity and reduced tumor growth in murine models of peritoneal malignancy with preferential accumulation of GNRs within peritoneal tumors. Preclinical evidence of efficacy utilizing a biocompatible hydrogel GNR/MMC/CisPt film can lead to clinical trials in patients with peritoneal malignancies. If successful, treatment of other cancers can benefit from this GNR chemotherapy hydrogel film as a method to decrease the incidence of local recurrence in any surgical resection bed.

Twelve-Year Single Center Experience Shows Safe Implementation of Developed Peritoneal Surface Malignancy Treatment Protocols for Gastrointestinal and Gynecological Primary Tumors.

Simple SummaryThe treatment of peritoneal surface malignancies (PSM) has dramatically evolved during the past two decades. Indications, treatment protocols, surgical techniques and the application of HIPEC in the prophylactic setting were evaluated in the surgical community. Nevertheless, the current results of the PRODIGE-7 trial disfavored the application of HIPEC for PSM of colorectal cancer and raised uncertainty among surgeons. On the other hand, cytoreductive surgery and HIPEC represent state-of-the-art therapy for peritoneal mesothelioma (except the sarcomatoid-subtype) and pseudomyxoma peritonei. Comparing the literature is cumbersome due to the variety of HIPEC protocols and differences in indication settings. This article aims to provide an insight into the impact of different HIPEC protocols, different indication settings and the implementation of pre-HIPEC laparoscopy on patients’ morbidity rates and outcomes and serves as guidance for surgeons dealing with these patients in order to guarantee high-quality treatment.(1) Background: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy provide survival benefits to selected patients. We aimed to report our experience and the evolution of our peritoneal surface malignancy program. (2) Methods: From June 2005 to June 2017, 399 patients who underwent cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy at the Tübingen University Hospital were analyzed from a prospectively collected database. (3) Results: Peritoneal metastasis from colorectal cancer was the leading indication (group 1: 28%; group 2: 32%). The median PCI was 15.5 (range, 1–39) in group 1 and 11 (range, 1–39) in group 2 (p = 0.002). Regarding the completeness of cytoreduction (CC), a score of 0 was achieved in 63% vs. 69% for group 1 and 2, respectively (p = 0.010). Median overall survival rates for patients in group 1 and 2 for colon cancer, ovarian cancer, gastric cancer and appendix cancer were 34 and 25 months; 45 months and not reached; 30 and 16 months; 39 months and not reached, respectively. The occurrence of grade-III and -IV complications slightly differed between groups (14.5% vs. 15.6%). No 30-day mortality occurred. (4) Conclusions: Specialized centers are able to provide low-morbidity cytoreductive surgery and hyperthermic intraperitoneal chemotherapy without mortality. Strict patient selection during the time period significantly improved CC scores.

Surgery with hyperthermic intraperitoneal chemotherapy after response to induction chemotherapy in patients with peritoneal metastasis of gastric cancer.

Gastric cancer (GC) with peritoneal metastases (PM) has a dismal prognosis and to date only a few management options have been reported. Of those, cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) after induction bidirectional intraperitoneal and systemic chemotherapy (BIPSC) appear as a promising treatment option for these patients. Outcome data including safety and efficacy of CRS with radical Gastrectomy and HIPEC after response to combination of laparoscopic HIPEC (LHIPEC) with BIPSC as an induction therapy in patients with PM of GC was evaluated in this retrospective observational study. Diagnostic Laparoscopy was performed in 53 patients with PM of GC who admitted to the Center for Treatment of Peritoneal Surface Malignancies, Istanbul, between 2013 and 2016. Peritoneal cancer index (PCI), ascites status and cytology were determined. The patients underwent LHIPEC and then, BIPSC induction chemotherapy using intraperitoneal docetaxel (30 mg/m2) and cisplatin (30 mg/m2) and intravenous Docetaxel/Cisplatin/5-Fluorouracil (DCF) for 3 cycles. In selected patients, CRS with radical gastrectomy and HIPEC were performed after the response to induction therapy. BIPSC was continued for 3 more cycles with a dose reduction in an adjuvant setting. All LHIPEC procedures were uneventful with Grade 1-2 side effects (11/53, 20,8%). As a response to induction chemotherapy PCI was reduced from 19.6±8 (range, 6-39) to 13.6±9.8 (range, 1-39) (P<0.001). Ascites was detected in 55% (29 out of 53) and cytology was positive in 51% (27 out of 53) of the patients before induction chemotherapy. Ascites was completely abolished and all cytology became negative. Then, 34 of 53 (64.15%) patients underwent CRS with radical gastrectomy and HIPEC. CC0/1 resection was achieved in 22 (64.70%) of patients (P<0.05). The median survival time was 18.9±13.4 (95% CI: 15.2-22.6 months. Combined surgery and HIPEC related mortality occurred in 1 out of 34 patients (2.9%) due to developed diffuse intravascular coagulation at postoperative day 2. Grade 2 operative complications included biliary fistula in one, and duodenal stump leakage in two patients (8.7%). All of the fistula closed with conservative management. The median survival time was 18.9±13.4 months and the median progression-free survival time was 15.6±12.9 with 1-, 2-, and 5-year survival rates of 82.4%, 59% and 17.6% in patients with PM of GC. Multivariate analysis identified high peritoneal cancer index (P=0.000) and complete resection (P<0.05) as independent predictors for better progression-free and overall survival. The best outcomes can be expected with optimal cytoreduction and limited peritoneal dissemination in response to induction chemotherapy. Knowledgeable selection of patients with PM of GC is essential to perform surgery with HIPEC safely with acceptable mortality and morbidity.

Impact of Perfusate Glucose Concentration on Perioperative Outcomes in Patients Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy

BackgroundCytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is a common treatment for peritoneal surface malignancies but no standard carrier solution currently exists for the procedure. This study compared a standard low-dextrose perfusate to a higher-dextrose dialysate that has previously shown favorable impact on perioperative patient outcomes in trauma settings. Materials and methodsA single-center retrospective study identified patients undergoing CRS/HIPEC from 2008 to 2019 with recorded dextrose concentration of administered perfusate. An institutional shift to a higher-dextrose solution was made in late 2015. Comparisons of preoperative factors, intraoperative and postoperative glucose levels, and postoperative outcomes were made using the chi-square test, Fisher's exact test, Wilcoxon rank sum test, or repeated measures analysis of variance. ResultsThere were 97 patients in the study, 73 (75%) in the low-dextrose group and 24 (25%) in the high-dextrose group. There was no significant difference in peak intraoperative blood glucose levels between the 1.5% (mean 230 mg/dL) and the 2.5% group (mean 199 mg/dL, P = 0.15). Daily postoperative glucose values were also not statistically different (repeated measures analysis of variance, P = 0.18). Median length of stay was slightly lower for the high-dextrose group (10 d, interquartile range 8-15) than that for the low-dextrose group (12 d, interquartile range 9-17), but was not statistically significant (P = 0.29). Return of bowel function and resumption of diet were similar between the groups. The high-dextrose group had a lower rate of overall complications (20.8%) than the low-dextrose group (49.3%, P = 0.0143). Ninety-day mortality was equivalent between the two groups (2.7% low-dextrose, 4.2% high-dextrose, P = 1.0). ConclusionsUse of 2.5% dextrose-containing perfusate appears safe for CRS/HIPEC operations, does not negatively impact intraoperative or postoperative glucose levels, and may be associated with a decreased risk of complications.

Establishing of Peritoneal Surface Malignancy Treatment Program: Background in Ukraine, Patient Selection, Staff Schedule, Perioperative Outcomes of First 28 Patients.

A combination of cytoreductive intervention with the intrahepatic hyperthermic chemotherapy is a well-established treatment of peritoneal carcinomatosis. There are many challenges in establishing a new peritoneal surface malignancy program in a low-income country regarding perioperative safety and resource allocation. We analyzed the retrospective database to determine the immediate surgical outcomes of the first 28 patients with peritoneal carcinomatosis and the impact of the program on allocation of general hospital and human resources. During the preparatory stage, web conferences with international experts established the goals and general requirements of the program, formalized in a written document; and a peritoneal surface malignancy multidisciplinary team was established. The team created the patient selection criteria, perioperative management checklists, and suggested material and staff requirements for surgical and anesthesia services. Twenty-nine cytoreduction were carried out, of which 18 were followed by HIPEC. The average operative time was 6.2h. The median blood loss was 350mL, which did not result in additional blood transfusion requirements for the blood bank. No additional nursing and supportive staff were provided for the ICU and the surgical unit. The average postoperative stay was 8.7days. One patient died with 30-day mortality rate of 3%. Ten patients (34.5%) developed postoperative complications, of which 6 (20.6%) had grade III and higher Clavien-Dindo complications. Establishing a peritoneal surface malignancy program is possible via staged planning, liberal use of international mentors, and thoughtful resource allocation. This new program did not result in a significant redistribution of resources among other service lines of cancer care within the same institution.

History of Peritoneal Surface Malignancy Treatment in Japan.

In this review, Japanese experience of cytoreductive surgery and perioperative chemotherapy is described. The new concept of peritoneal metastasis (PM) type, i.e., trans-mesothelial, trans-lymphatic, and superficial growing metastasis type was proposed in 2012. Surgeons should perform peritonectomy according to the type of PM. Since 1980, Japanese surgical oncologists have been spearheading the use of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemoperfusion (HIPEC) as treatment for PM from gastric cancer. Two RCTs were conducted to verify the effect of HIPEC for the prophylaxis of peritoneal recurrence after curative resection of advanced gastric cancer. These two studies indicated that HIPEC is effective in preventing peritoneal recurrence of gastric cancer with serosal invasion. In 2002, intraperitoneal chemotherapy using taxans was developed for the treatment of PM from gastric cancer and led to the development of neoadjuvant intraperitoneal/systemic chemotherapy (NIPS), which was reported in 2006. In 2009, extensive intra-operative peritoneal lavage (EIPL) was developed, and contributed to the remarkable improvement in survival of patients with positive lavage cytology as demonstrated by prospective randomized clinical trials. In 2017, the Peritoneal Surface Oncology Group International proposed the value of complete cytoreduction and peritoneal cancer index cut-off as independent prognostic factors after CRS for gastric cancer with PM. Founded in 2016, the Japanese/Asian School of Peritoneal Surface Oncology (JASPSO) trains beginners to perform CRS and HIPEC safely. Sixteen students have already graduated from JASPSO and started to perform the treatment in their home countries.

Treatment of Peritoneal Surface Malignancies with Cytoreductive Surgery and Hyperthermic Intra-peritoneal Chemotherapy (HIPEC): Experience in Israel.

The treatment of peritoneal surface malignancies, either primary or secondary (peritoneal metastasis), has evolved over the past two decades. A nihilistic approach of incurable "carcinomatosis" is changing into treatment of peritoneal metastasis with curative intent. The aim of the present study is to review the current practice, past history, and future of peritoneal surface oncology in Israel. A systematic review of all patients treated in institutions performing cytoreductive surgery (CRS) and hyperthermic intra-peritoneal chemotherapy (HIPEC) for the treatment of peritoneal surface malignancies. Each center provided the following data: start year, number of total cases, number of cases performed in 2017, and the method used (open vs. closed technique). Between 1990 and 2018, there were 1462 patients treated by CRS/HIPEC in Israel by eight different surgical groups in six medical centers. Currently, there are seven surgical groups in six medical centers routinely performing CRS/HIPEC. The annual rate of CRS/HIPEC was 171 cases in 2017 with a range of (4-69 cases/center). This is the first step of establishing an Israeli Peritoneal Surface Oncology Group that will have joined database and perform clinical trials in this challenging field of surgical oncology.

Comparison of Outcomes Following Complete and Selective Parietal Peritonectomy During Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Advanced Epithelial Ovarian Cancer: A Study by Indian Society of Peritoneal Surface Malignancies (ISPSM)

Background Peritonectomy is an important component in surgical treatment for peritoneal surface malignancies. Visual inspection and palpation to estimate the extent of tumor involvement are unreliable. Most gynecologic oncologists are skeptical regarding the benefits of complete peritonectomy and do not perform them, worrying about the benefit and associated morbidity. They believe it is the inherent tumor biology that determines the resectability of the tumor, not surgical aggressiveness. The aim of this study was to assess the recurrence pattern, oncological outcomes, morbidity and mortality based on the extent of parietal peritonectomy performed during CRS and HIPEC in stage IIIc epithelial ovarian cancers.

Current practices of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the treatment of peritoneal surface malignancies: an international survey of oncologic surgeons

BackgroundThe goal of the study was to investigate the current clinical practices among oncologic surgeons regarding cytoreductive surgery (CRS) with intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC).MethodsFrom September to October 2016, an online questionnaire surveyed the oncologic surgeons by email. The questionnaire included 20 multiple-choice questions of the following: eligibility for the CRS with HIPEC procedure, perioperative staging and surgery skill, assessment of residual tumors, and method used for intraperitoneal HIPEC.ResultsThe response rate was 16% (34/217). The majority of respondents (68%) worked at a university hospital. All respondents indicated that mesenteric invasion is the most crucial factor affecting treatment decision. Most surgeons (79%) used the Sugarbaker’s staging system to intraoperatively measure the extent of peritoneal invasion. The methods used to measure the extent of miliary pattern of residual tumor spread, and the amount of residual tumor after electrocauterization varied among the surgeons. Most responders (65%) used the closed system of HIPEC.ConclusionsDespite the fact that CRS HIPEC is the standard treatment for PSM, the clinical practices are very different according to each clinical situation. Nevertheless, mesenteric invasion was found to be the most important factor impacting the treatment decision-making by the majority of responders.

Transient Exocrine Pancreatic Insufficiency: First Report of an Unrecognized Complication of Cytoreductive Surgery and HIPEC.

As cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are being increasingly adopted as the standard treatment for peritoneal surface malignancies, familiarity with this procedure's adverse events is also growing. Herein, we describe an unreported adverse event of exocrine pancreatic insufficiency (EPI) following CRS and HIPEC. Patients who underwent CRS and HIPEC between 9/2016 and 9/2017 were prospectively recruited. Fecal elastase-1 (FE1) and Clostridium difficile toxins were tested in all patients in the immediate postoperative period. Patients with diarrhea who had low FE1 were started on oral pancreatic enzyme replacement therapy (PERT) and their symptomatic progression was followed. A total of 26 patients were included. Eleven patients (42.31%) developed postoperative refractory diarrhea, nine of whom had a low FE1 level. These patients were treated with PERT either directly or after completion of antibiotics course if C. difficile toxin was positive. Eight patients demonstrated symptomatic resolution of their diarrhea, and thus the diagnosis of EPI was established (30.77%). Patients with diarrhea had lower FE1 levels, and were more likely to have had a terminal ileum resection and had a longer hospital stay. Regression analysis identified the rapid rise of a patient's core temperature by >1°C within 15 minutes as the sole predictor of EPI occurrence. EPI is a potential adverse event following CRS and HIPEC and might be largely responsible for refractory diarrhea. In our patients with refractory diarrhea and low FE1, PERT provided immediate symptomatic relief. The biological basis of this phenomenon remains unclear and warrants further investigation.