Early Postoperative Intraperitoneal Chemotherapy Research Articles

Revised prognostic indicators for treatment of lymph node positive colorectal peritoneal metastases

Peritoneal metastases from colon and rectal cancer presents a new target for a regional approach to treatment. Proper patient selection requires an understanding of the natural history of the disease progression. Data from colorectal cancer patients treated for peritoneal metastases by cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy and early postoperative intraperitoneal chemotherapy and the records from the primary colon or rectal cancer surgery were analyzed to assess their impact on survival. Data regarding the anatomic sites of colorectal peritoneal metastases was gathered at the time of a complete CRS. A cohort of 73 patients with peritoneal metastases and lymph node metastases but no liver metastases provided the information. All patients had a complete cytoreduction. Left-sided primary cancer and a complete or near complete response to neoadjuvant chemotherapy (NAC) indicated improved survival. Tumor progression within the abdominal incision, carcinoembryonic antigen (CEA) >10, peritoneal cancer index >9 and peritoneal metastases present in the abdominopelvic regions 6 and 11 carried an especially guarded prognosis. Reduced survival occurred with a right-sided or rectal primary cancer, a CEA >10, tumor cell entrapment, and involvement of abdominopelvic regions 6 and 11. Effective NAC showed a favorable outcome.

Role of Early Bedside HIPEC as Adjuvant Treatment in Colorectal Peritoneal Metastasis

Objectives: Peritoneal metastasis (PM) is a poor prognostic factor for all malignancies and remains difficult to treat with systemic chemotherapy because of poor peritoneal vascularization, resulting in limited drug delivery and penetration into tissues. Our study aims to investigate the efficacy and safety of different locoregional treatment protocols with hyperthermic intraperitoneal chemotherapy (HIPEC), Early Peritoneal Chemotherapy (EPIC), Pressurized Intraperitoneal Chemotherapy (PIPAC) in the management of advanced colorectal cancer with metachronous PM. Methods: A total of 42 patients were divided into three groups, as follows. Group A: After neoadjuvant systemic chemotherapy, 15 patients received cytoreductive surgery (CRS) + hyperthermic intraperitoneal chemotherapy (HIPEC) and then adjuvant systemic chemotherapy. Group B: After neoadjuvant systemic chemotherapy, 12 patients received CRS + HIPEC + early postoperative intraperitoneal chemotherapy for 5 postoperative days and then adjuvant systemic chemotherapy. Group C: After neoadjuvant chemotherapy, 15 patients received CRS + HIPEC and then an adjuvant bedside HIPEC on the 10th postoperative day combined with postoperative adjuvant chemotherapy. Results: Patients in group A had a median overall survival (OS) of 33 months; however, log-rank tests showed that survival distributions of the three groups were not statistically significant different for both OS and disease-free survival. Conclusion: In conclusion, CRS plus HIPEC remains an alternative to locoregional treatment in well-selected patients with PM in combination with systemic neoadjuvant and adjuvant chemotherapy. Keywords: Hyperthermic Intraperitoneal Chemotherapy (HIPEC), Cytoreductive Surgery (CRS), Peritoneal Metastasis (PM), Colorectal Cancer (CRC), adjuvant treatment

The 5 Year Outcomes of Early Postoperative Intra-Peritoneal Chemotherapy (EPIC) in High-Grade Appendiceal Cancer – Does regimen length and cancer subtype make a difference?

Background: Early Post-operative Intra-Peritoneal Chemotherapy (EPIC) following Cytoreductive Surgery (CRS) and Hyperthermic Intra-Peritoneal Chemotherapy (HIPEC) in high-grade appendiceal peritoneal cancer remains controversial with unclear survival benefit. The following study evaluates the survival outcomes in highgrade appendiceal cancer patients receiving varying days of EPIC in addition to CRS and HIPEC, and if survival varied between different appendiceal cancer subtypes. Patients and Methods: A monocentric retrospective analysis of patients with high-grade appendiceal cancers managed from 1994 to 2018 was undertaken. An analysis was performed comparing survival between patients who received HIPEC, HIPEC+EPIC, HIPEC+EPIC <3 days and HIPEC+EPIC ≥3days. All patients received CRS. Results: 212 patients were included in the study. The 5years overall survival was 60% and 55% in the HIPEC+EPIC and HIPEC groups respectively. Patients who received ≥3days of EPIC had an 8% reduction in risk of death compared to those who had <3 days (HR 0.92, CI 0.89-0.94), with a 5-year survival of 62% in the ≥3days group compared to 55% in the <3day group. Patients with signet cell carcinoma had the greatest 5year survival advantage when both HIPEC and EPIC were given (HR 01.23, CI 01.21-01.26). Conclusion: EPIC in combination with HIPEC and CRS offers survival benefit at 5years in high-grade appendiceal peritoneal cancer and is most advantageous in signet cell carcinoma. Completing a ≥3day course of EPIC increases chance of survival at 5years compared to a <3 days course.

EP.FRI.999 Case report of a Low Grade appendiceal mucinous neoplasm (LAMN) and review of literature

Abstract A mucocele refers to an appendix that has dilated due to progressive accumulation of mucus within its lumen. Appendiceal mucocele is a rare cause of an acute abdomen. They represent 0.2-0.7% of all appendix specimens. LAMN account for less than 0.3% of appendicectomy specimens. We present a 38 year old man with an acute RIF’s pain who went on to have CT scan which revealed a mucocele of appendix but did not show any features of perforation or pseudomyxoma peritonei. He had a laparoscopic converted to open appendicectomy. The proximal 2 cm of appendix was oedematous but normal calibre. Histology revealed a low grade appendiceal mucinous neoplasm (LAMN) that was completely excised. The mucocele of the appendix was first described by Rokitansky in 1842. Appendix mucocele may come as a consequence of obstructive or inflammatory processes, cystadenomas or cystadenocarcinomas. Appendiceal mucinous neoplasms commonly presents in the sixth decade of life and our patient was much younger in comparison. Several literatures suggest the value of preoperative CT imaging in obtaining diagnosis and also in planning further treatment. Appendicectomy or a right hemicolectomy is treatment of choice based on presence or absence of following factors 1. Perforated mucocele 2. Involvement of the base of the appendix. 3. Positive lymph nodes of mesoappendix and ileocolic. Patients with malignancy or pseudomyxoma peritonei are likely to require cytoreductive surgery, heated intraoperative intraperitoneal chemotherapy, early postoperative intraperitoneal chemotherapy.

Long-term outcomes after cytoreductive surgery and hyperthermic perioperative chemotherapy for morcellated uterine leiomyosarcoma: case series

<h3>Objectives:</h3> Uterine leiomyosarcoma (uLMS) is a rare aggressive malignant mesenchymal tumor with high risk of recurrence and poor prognosis regardless of stage. If the tumor was morcellated, the oncologist will encounter special problems that require aggressive management of peritoneal metastases. Hyperthermic intraperitoneal chemotherapy (HIPEC) is an intraoperative intraperitoneal chemotherapy administration under hyperthermic condition. Early postoperative intraperitoneal chemotherapy (EPIC) is a second perioperative regional chemotherapy with a goal to eradicate peritoneal metastatic disease. These treatments are possible following a complete cytoreduction surgery (CRS). Only few studies have evaluated outcomes in patients with morcellated uLMS who underwent HIPEC and/or EPIC following CRS. The purpose of the study is to evaluate the long-term outcomes in patients with morcellated uLMS who underwent CRS and HIPEC plus EPIC. <h3>Methods:</h3> We previously reported short-term outcomes (median 14.5 months) in six patients who underwent CRS and HIPEC in an attempt to successfully manage the disseminated disease following morcellation. We reviewed patient demographics, tumor characteristics, treatment history, perioperative complications and outcomes. The grade of the malignancy, peritoneal cancer index (PCI), and completeness of cytoreduction score (CC score) were available for all patients. <h3>Results:</h3> Six patients with morcellated uLMS who underwent CRS and HIPEC were identified in our database. HIPEC was used for 90 minutes following the CRS in the operating room. The regimen consisted of cisplatin 50 mg/m² and doxorubicin 15 mg/m² by intraperitoneal instillation that was manually distributed into the abdominal and pelvic space and maintained at 42.5?. Of the six patients, five patients also received EPIC.Mean age at CRS followed by HIPEC was 49 years (range 40-62) and mean interval from the initial surgery was 17 months (range 1 month to 7 years). The mean PCI was 18 and a CC-0 cytoreduction was achieved in all patients. The 3-year overall survival was 50% and 5-year overall survival was 33% with the median follow-up of 30 months (range 5 months to 73 months). A low grade of sarcoma and a low PCI suggested a favorable outcome. <h3>Conclusions:</h3> Our case series suggests that CRS and HIPEC plus EPIC is well-tolerated and may be a therapeutic option for newly diagnosed uterine leiomyosarcoma following morcellation. Therapeutic options for patients with uLMS post-morcellation are limited and further research to eliminate disease dissemination is needed.

Cytoreductive Surgery and Perioperative Intraperitoneal Chemotherapy Experience in Peritoneal Carcinomatosis: Single-Center Analysis of 180 Cases.

Background In peritoneal carcinomatosis (PC), increased life span and disease-free survival times are shown in patients with hyperthermic intraperitoneal chemotherapy (HIPEC) and early postoperative intraperitoneal chemotherapy (EPIC) following cytoreductive surgery (SRC). In this study, our main objective was to present our experience of performing SRC and perioperative intraperitoneal chemotherapy (HIPEC and EPIC) on patients with PC, in light of the literature. Methods Demographic data, follow-up results, peritoneal carcinomatosis index (PCI), completeness of cytoreduction (CCR) score, and morbidity and mortality rates of 180 patients treated with SRC + HIPEC + EPIC for PC at the Department of Surgical Oncology at Sivas Cumhuriyet University between January 2008 and July 2020 were analyzed retrospectively. Results Distribution of 180 PC cases according to primary organs included 53 ovarian, 39 colorectal, 33 stomach, 25 primary peritoneum, 10 uterus, 10 tuba, five soft tissue, and five appendix originated carcinoma. The average PCI of the cases detected preoperatively was 21 (5–30). Completeness of cytoreduction scores of CCR-0 in 102 cases, CCR-1 in 67 cases, CCR-2 in eight cases, and CCR-3 in three cases was obtained. Median operation time was 300 (200–540) minutes. Perioperative morbidity rate was 47.0%, and perioperative mortality rate was 13.5%. Conclusion The peritonectomy procedure is a difficult, long-lasting, troublesome intervention, but it is the most important treatment option with acceptable morbidity and mortality rates in patients selected for PC treatment in experienced centers.

A narrative review of intraperitoneal chemotherapy and cytoreductive surgery (CRS) for peritoneal metastases in gastric cancer.

Peritoneal carcinomatosis of gastric origin is an aggressive tumor entity. Historically it has been considered a terminal disease with no long-term survival, due to limited therapeutic options. However, as a better understanding of tumor biology has evolved in recent years, novel multimodal treatment strategies incorporating intraperitoneal (IP) chemotherapy-hyperthermic intraperitoneal chemotherapy (HIPEC), early postoperative intraperitoneal chemotherapy (EPIC), neoadjuvant intraperitoneal-systemic chemotherapy protocol (NIPS)-and cytoreductive surgery (CRS) have demonstrated promising oncologic outcomes and even long-term survival in selected patients. Most of the studies published to date are retrospective in nature. These studies involve heterogenous patient populations, a wide variety of chemotherapeutic drugs, and show wide variation in outcomes between institutions. Thus, it is difficult to evaluate the results. This review summarizes our current knowledge regarding IP chemotherapy and CRS for peritoneal metastases (PM) in gastric cancer (GC). We describe our institutional treatment regimens. We also provide a brief overview of new, targeted therapies that may show promise in the future.

Intra-operative hyperthermic intraperitoneal chemotherapy for prevention and treatment of peritoneal metastases from gastric cancer: a narrative review.

Peritoneal metastasis (PM) from gastric cancer (GC) has long been regarded as the terminal disease, lacking of effective treatments. In recent 40 years, cytoreductive surgery (CRS) plus perioperative intraperitoneal chemotherapy, including hyperthermic intraperitoneal chemotherapy (HIPEC), neoadjuvant intraperitoneal and systemic chemotherapy (NIPS), and early post-operative intraperitoneal chemotherapy (EPIC), has been recommended as a preferred treatment option for some selected patients with GCPM. Intraperitoneal free cancer cells were recognized as the pathological cause of PM and the primary target for intraperitoneal chemotherapy. There were a lot of evidence demonstrating that HIPEC could effectively eradiate intraperitoneal free cancer cells and prolong overall survival in GCPM. However, there are still no standard HIPEC protocols. This review summarized the current HIPEC regimens used in GCPM from a literature search, trying to conclude the optimal HIPEC in GCPM, and indicate the future direction of HIPEC study. Moreover, the new data on the exploration of HIPEC in GCPM at Shijitan Hospital, Capital Medical University was shared. In conclusion, there was not enough evidence from publications and our own experience to conclude a recommended HIPEC regimen for GCPM. There is urgent need for standardizing HIPEC protocols worldwide. Accordingly, more international collaborations focusing on pharmacology and HIPEC-related parameters to generate high level evidence are essential.

Long-term outcomes after cytoreductive surgery and HIPEC for morcellated uterine leiomyosarcoma; A case series

Uterine leiomyosarcoma (uLMS) is a rare aggressive malignant mesenchymal tumor with high risk of recurrence and poor prognosis regardless of stage. It is often diagnosed postoperatively following myomectomy, hysterectomy or supracervical hysterectomy for presumed benign disease. Primary surgery at the diagnosis of uLMS is considered to affect outcomes. If the tumor was morcellated, the oncologist will encounter special problems that require knowledgeable management of peritoneal metastases. We previously reported that six patients who successfully underwent cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) plus early postoperative intraperitoneal chemotherapy (EPIC) to manage the disease dissemination that must occur following morcellation. This is a study for long-term outcome of these patients. Six patients were treated with an absence of grade IV adverse events and no mortality. The median Peritoneal Cancer Index (PCI) was 18 and complete cytoreduction without peritoneal metastases visualized within the operative field at the completion of the surgical procedure (CC-0) was achieved in all patients. One patient was diagnosed leiomyomatosis peritonealis postoperatively. Among five patients who were confirmed uterine leiomyosarcoma, the 3-year overall survival was 40.0% and 5-year overall survival was 20.0% with the median follow-up of 18 months (range 5–73 months). The patient with PCI 0 at the time of CRS showed no evidence of disease (NED) at 73 months. We believe that prophylactic CRS contributed her favorable outcome. Therapeutic options for patients with uLMS post-morcellation are limited. Currently, CRS and HIPEC plus EPIC followed by adjuvant systemic chemotherapy may be considered an option for treatment. Further studies in a larger number of patients are needed.

Establishment of an Experimental System for Intraperitoneal Chemotherapy in a Rat Model.

To establish an experimental system for comparing different methods of intraperitoneal chemotherapy in a rat model. We used six-week-old Sprague-Dawley rats, and created an early postoperative intraperitoneal chemotherapy (EPIC) system using 18-gauge syringes and evacuators, and a hyperthermic intraperitoneal chemotherapy (HIPEC) system using two peristaltic pumps which controlled the flow rate and temperature. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) was achieved using a nozzle for dispersing aerosols at a flow rate up to 41.5 ml/min. The distribution and intensity of 0.2% trypan blue dye was compared among three methods. The distribution was limited and the intensity was weak after EPIC, and the dye stained moderately in gravity-dependent regions after HIPEC. On the other hand, the distribution was the most comprehensive, and the intensity was the greatest after PIPAC. This experimental system in a rat model may reflect the comparative effect among EPIC, HIPEC and PIPAC in humans.

Outcome of first relapse of Hodgkin lymphoma: single institution experience.

To determine outcome of first relapse of Hodgkin lymphoma with standard dose chemotherapy, and to identify the prognostic factors predicting survival outcome in paediatric patients. The retrospective study was conducted at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan, and comprised data of Hodgkin lymphoma patients who relapsed at least 3 months after the completion of initial treatment from January 2001 to December 2010. Probabilities of overall survival, event-free survival and cumulative incidence were calculated. Data was analysed using SPSS 21. Of the 43 patients, 31(72%) were males and 12(29%) were females. Mean age at relapse was 11±3.3 years (range: 4-17 years). In 31(72%) patients, early post-operative intraperitoneal chemotherapy was employed. Median follow-up of the cohort was 62 months (interquartile range: 4-187 months). Overall survival and event-free survival at 10 years was 23(54%) and 15(35%) respectively. On univariate analysis, initial disease stage (p=0.021), stage at relapse (p=0.003), treatment protocol (p=0.005), treatment responsiveness at initial two cycles of salvage chemotherapy (p=0.002) and at the end of treatment assessment (p=0.0009) were statistically significant factors. Multivariate cox regression analysis revealed disease stage at relapse (p=0.004), chemotherapy regimen (p=0.025) and end-of-treatment disease evaluation (p=0.005) as the significant variables. Improved outcome with early post-operative intraperitoneal chemotherapy regimen was noted for Hodgkin lymphoma patients who had disease-free interval >2 years.

HIPEC plus EPIC paclitaxel for maximal perioperative treatments of advanced epithelial ovarian cancer. Long-term results of a pilot study

BackgroundA unique time in which to effectively treat an intraabdominal malignancy is the time at which the surgeon attempts complete removal of the malignant process. Although surgery is effective for visible disease, micrometastases or multiple small cancer nodules are not amenable to resection. Alternative interventions to deal with residual disease disseminated on peritoneal surfaces are needed. Materials and methodsCytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) can be combined with early postoperative intraperitoneal chemotherapy (EPIC) in order to maximally treat gross disease within the abdomen and pelvis and also the minimal residual disease that exists in many patients after resection. The third component of this treatment for ovarian malignancy was EPIC paclitaxel in this study. The clinical features, pharmacologic assessments, and survival were determined in ovarian cancer patients in whom EPIC was added to the perioperative treatment plan. ResultsPatients with high grade serous ovarian cancer underwent CRS, HIPEC with cisplatin/doxorubicin, and EPIC paclitaxel. These treatments combined as a single intervention were studied in 10 patients. The median number of peritonectomy procedures was 1, the median number of visceral resections was 5, and the median time required in the operating room was 8 h. Two patients had a class 3 adverse event. The median survival of patients was 50 months. Pharmacokinetic analysis of the intraperitoneal paclitaxel showed 252 ± 153 times exposure of peritoneal surfaces as compared to intravenous exposure when the drug was instilled into the peritoneal space. ConclusionsEPIC paclitaxel was successfully combined with CRS and HIPEC in 10 patients with ovarian cancer. The treatment was tolerated approximately the same as other major cytoreductive surgical procedures for ovarian cancer or other malignancies. Survival of these ovarian cancer patients seemed unusually prolonged as compared to other patients with stage 3b or recurrent disease. In this pilot study CRS, HIPEC and EPIC were safe and effective.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy with or without early post-operative intraperitoneal chemotherapy for appendix neoplasms with peritoneal metastases: A propensity score analysis

Introduction– Early post-operative intraperitoneal chemotherapy (EPIC) can be used after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with resectable peritoneal metastases (PM). Whether EPIC adds any benefit is debatable. Methods– We performed a retrospective case-control analysis of patients with PM of appendiceal origin treated by CRS + HIPEC ± EPIC at Uppsala University Hospital between 2004 and 2012. The 206 patients were divided into two groups depending on if they received EPIC or not. The two groups were propensity-matched with a 1:1 ratio. The patients in the EPIC group were mostly operated in the first three years of the unit’s experience. Results– After matching, 76 patients were left in each group. The groups were similar, except for the proportion of histological subtypes (p = 0.021) and chemotherapy agents used for HIPEC (0.017). Survival outcomes were stratified by histology. The patients who received EPIC had a longer hospital and ICU length of stay (15.71 vs 14.28 days, p = 0.049), (1.45 vs 1.05 days, p = 0.002), respectively. Post-operative complications were similar in both groups. Overall Survival (OS) and recurrence-free survival (RFS) did not differ for the patients with low-grade histology. The patients with high-grade tumors who received EPIC had a significantly worse OS (p = 0.0088) while having the same RFS as the patients who did not receive EPIC. ConclusionOur results suggest there is no benefit of EPIC in patients with advanced appendiceal tumors while increasing hospital and ICU length of stays. A suboptimal group matching might influence our results.

Pseudomyxoma peritonei (PMP) and its therapy - 20 years experience of a single surgical department.

Pseudomyxoma peritonei (PMP) is arare malignant disease with various grades of malignancy, producing mucinous and gelatinous masses. The origin of PMP is usually connected with the rupture of appendiceal mucinous tumours, other mucinous tumours of the gastrointestinal tract or of the ovary. The staging of this disease is determined by the PCI score (peritoneal cancer index), and the efficiency of surgical procedure by the CC score. Clinical presentation is very variable and depends on the stage of the disease. Many patients are asymptomatic with aminimal clinical finding, presented only with abdominal discomfort. Atypical finding of the &#8220;jelly belly&#8220; syndrome expands with progression of the disease. The diagnosis consists in preoperative determination of the tumour characteristics and PCI based on imaging methods, especially CT imaging. The Sugarbaker technique of complete tumour removal or the so-called cytoreductive surgery (CRS) was used, including hyperthermic intraperitoneal chemotherapy (HIPEC) or alternatively early postoperative intraperitoneal chemotherapy (EPIC). We performed retrospective evalu-ation of 73 patients with pseudomyxoma peritonei undergoing surgery, 39 males and 34 females, mean age 50.6 and 56.4 years, respectively. Surgical revision was performed in 18 patients, 14 males and 4 females. The mean age of this group was 48.8 for the males and 47 for the females. The surgical procedures were performed between 1999 and 2018. Survival rates, median survival, complications based on Clavien-Dindo classification, lethality rates, and PCI and CC scores were assessed in the patient group. 96 surgeries were performed in 73 patients with pseudomyxoma peritonei at our surgical department between 19992018. The surgery had to be repeated in 18 patients (24.6%). High grade (HG) pseudomyxoma was diagnosed in 29 patients (39.7%), and low grade (LG) pseudomyxoma in 44 patients (60.3%). Overall morbidity was 27.3%, and the mortality rate was 5.4%. The mean overall survival (OS) was 139.5 months in the LG pseudomyxoma group and 71.5 months in the HG pseudomyxoma group. Median survival was 86 months in the entire group and 72 in the HG pseudomyxoma group; the median was not reached in the LG pseudomyxoma group. Results in the literature and our results are comparable, confirming the high efficiency of this method both in the world and in the Czech republic. The results indicate ahighly statistically significant improvement of the OS with acceptable mortality and morbidity. These results confirm this method as agold standard therapy for selected patients.

Key points of perioperative whole-process management for patients with advanced gastric cancer

Perioperative whole-process management (WPM) for patients with advanced gastric cancer (AGC) mainly focuses on some clinical issues which are easily neglected or underappreciated. WPM is helpful in making a scientific and rational therapeutic plan, and avoiding inadequate communication in multi-disciplinary participation, so that the diagnosis, treatment and rehabilitation for AGC patients can be integrated organically. Based on the current clinical practice for AGC patients, eight key issues in WPM should be emphasized.(1) Preoperative clinical staging. An accurate preoperative staging by endoscopy and imaging technique is helpful in setting up a rational therapeutic plan, and is also a prerequisite to start WPM. (2) Indications and value of diagnostic laparoscopy. Laparoscopic exploration is beneficial to find intraperitoneal micro-metastases so as to avoid unnecessary laparotomy. For cases of AGC infiltrating serosal layer or suspected of peritoneal metastasis, preoperative laparoscopic exploration should be routinely performed. (3) Neoadjuvant therapy. Multiple RCT studies have shown that neoadjuvant chemotherapy can benefit a majority of patients with AGC, improving prognosis and prolonging their overall survival. Therefore, neoadjuvant therapy should be considered first for stage III and IVA AGC patients. (4) Prediction of efficacy in neoadjuvant chemotherapy. Endoscopy, MDCT scan, PET-CT and liquid biopsy have certain predictive value individually, which can be used together or separately to improve the accuracy of prediction. (5) Effective prevention of postoperative peritoneal metastasis. Extensive intraoperative peritoneal lavage (EIPL), neoadjuvant intraperitoneal and systemic chemotherapy (NIPS), hyperthermic intraperitoneal chemotherapy (HIPEC), early postoperative intraperitoneal chemotherapy (EPIC), and normothermic intraperitoneal chemotherapy (NIPEC) have been shown to be of various efficacy in preventing peritoneal metastases. (6) Prediction of postoperative prognosis of AGC patients. The key pathological indicators are tumor regression grade (TRG) and ypTNM staging, especially if there is lymph node metastasis. Usually for AGC patients who received neoajuvant chemotherapy with TRG 0 or ypN0, their prognosis was comparable to that of patients with cTNM stage I.(7) Postoperative adjuvant chemotherapy. Postoperative adjuvant therapy is always an important part of the WPM management of AGC patients. Several recent RCT studies have shown that duplet chemotherapy can significantly reduce the risk of death after D2 radical gastrectomy compared to singlet chemotherapy, especially for stage III patients. (8) Perioperative nutritional support. Due to different degrees of malnutrition in AGC patients, enhanced nutritional treatment in the perioperative period can not only reduce surgical complications, but also enable patients to complete necessary course of chemotherapy, and ultimately further improve their survival rate.

The impact of HIPEC vs. EPIC for the treatment of mucinous appendiceal carcinoma: a study from the US HIPEC collaborative

Introduction Mucinous appendiceal carcinoma is a rare malignancy that commonly spreads to the peritoneum leading to peritoneal metastases. Complete cytoreduction with perioperative intraperitoneal chemotherapy (PIC) is the mainstay of treatment, administered as either hyperthermic intra peritoneal chemotherapy (HIPEC) or early post-operative intraperitoneal chemotherapy (EPIC). Our goal was to assess the perioperative and long term survival outcomes associated with these two PIC methods. Materials and methods Patients with mucinous appendiceal carcinoma were identified in the US HIPEC Collaborative database from 12 academic institutions. Patient demographics, clinical characteristics, and survival outcomes were compared among patients who underwent HIPEC vs. EPIC with inverse probability weighting (IPW) used for adjustment. Results Among 921 patients with mucinous appendiceal carcinoma, 9% underwent EPIC while 91% underwent HIPEC. There was no difference in Grade III–V complications between the two groups (18.5% for HIPEC vs. 15.0% for EPIC, p=.43) though patients who underwent HIPEC had higher rates of readmissions (21.2% vs. 8.8%, p<.01). Additionally, PIC method was not an independent predictor for overall survival (OS) or recurrence-free survival (RFS) after adjustment on multivariable analysis. Conclusions Among patients with mucinous appendiceal carcinoma, both EPIC and HIPEC appear to be associated with similar perioperative and long-term outcomes.

Cytoreductive surgery with or without perioperative intraperitoneal chemotherapy for the management of peritoneal carcinomatosis: Our initial experience

Aim: We studied to present our initial experience of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) or early postoperative intraperitoneal chemotherapy (EPIC) in the treatment of peritoneal carcinomatosis. Material and Methods: The results of 20 consecutive patients treated with CRS±HIPEC or EPIC for peritoneal carcinomatosis in our hospital between November 2014 and February 2019 were evaluated retrospectively. Demographic, clinical and histopathological data of the patients were analyzed. The patients were also divided into two groups as PCI score 10 and PCI score ≥ 10 and a comparison was made between the groups.Results: There were 20 patients in our study. Fifteen patients were female and 5 were male. The mean age was 52.2±15.7 years. Primary tumor was ovarian cancer in 8 patients, colorectal cancer in 8 patients, malignant mesothelioma in 3 patients and gastric cancer in 1 patient. In the ovarian cancer group, CRS alone was applied in 4 patients, CRS+HIPEC in 3 patients and CRS+EPIC in 1 patient. All patients with colorectal cancer underwent CRS+HIPEC. Two of the patients with malignant mesothelioma were treated with CRS+HIPEC and one with CRS+EPIC. The patient with gastric cancer received CRS+HIPEC. The mean peritoneal carcinomatosis index (PCI) was 12.35±7.71. The median completeness of cytoreduction (CC) score was 0 (0-1). The mean operating time was 292.5±59.9 minutes. Perioperative morbidity was developed in 11 patients, and HIPEC-induced toxicity occured in 2 patients. Perioperative mortality was seen in 1 patient. The median overall survival was 17.7 (1.1-56) months. In addition, when two groups were compared, there was no statistically significant difference in terms of age, gender, origin of tumor, surgical method, CC score, operative time, Clavien-Dindo score, postoperative hospital stay and survival (p>0.05). Conclusion: Cytoreductive surgery and intraperitoneal chemotherapy provide satisfactory results in the treatment of patients with peritoneal carcinomatosis. Good preoperative evaluation, appropriate patient selection and multidisciplinary approach are essential for the success of the curative approach to peritoneal carcinomatosis.

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Gastric Cancer.

The management of peritoneal metastases from gastric cancer origin has evolved considerably over the last three decades with the establishment of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) as efficacious therapies in carefully selected patients. Other approaches such as the use of prophylactic/adjuvant HIPEC in patients who are considered high-risk and those with positive peritoneal cytology will benefit from additional data before being adopted into routine clinical practice. Lastly, there are new and emerging intraperitoneal chemotherapy techniques such as early post-operative intraperitoneal chemotherapy (EPIC) for residual microscopic disease, and pressurized intraperitoneal aerosolized chemotherapy (PIPAC) for patients with advanced unresectable peritoneal carcinomatosis, which are currently under evaluation in clinical trials. The following review outlines the natural history of gastric cancer, currently available neoadjuvant and adjuvant therapies for resectable disease, and existing evidence supporting various approaches to CRS and intraperitoneal chemotherapy.

Survival benefits of dose-dense early postoperative intraperitoneal chemotherapy in front-line therapy for advanced ovarian cancer: a randomised controlled study

Dose-dense early postoperative intraperitoneal chemotherapy (DD-EPIC) significantly increased non-progression rate in advanced ovarian cancer (OC) patients. We report final overall survival (OS) results to further strengthen the efficacy of DD-EPIC in the front-line therapy. In this phase 2 trial, 218 patients with FIGO IIIC–IV OC were randomly allocated to receive DD-EPIC followed by intravenous (IV) chemotherapy (DD-EPIC group), or IV chemotherapy alone (IV group). The study was prespecified to detect differences in progression-free survival (PFS) and OS. At a median follow-up period of 69.1 months, the median OS was 67.5 and 46.3 months in the DD-EPIC and IV group, respectively. The probability rate of OS at 5 years was 61.0% with DD-EPIC, and 38.2% with IV (hazard ratio [HR] for death from OC, 0.70; 95% confidence interval [CI], 0.49–1.00). DD-EPIC was associated with a prolonged PFS compared with the IV group (the estimated rate of PFS at 5 years, 26.0% vs. 8.5%; HR for disease progression, 0.64; 95% CI, 0.47–0.86). DD-EPIC was associated with a longer OS than IV chemotherapy alone. It may be considered as a valuable option of the front-line therapy for advanced ovarian cancer.Trial registration: ClinicalTrials.gov, NCT01669226 (date of registration: August 20, 2012).

Dose-dense early postoperative intraperitoneal chemotherapy in ovarian cancer: Randomized, phase II trial.

5514 Background: Dose-dense early postoperative intraperitoneal chemo (DD-EPIC) had been carried out in advanced ovarian cancer (OC) pts in China over the past three decades but it was not proved by a prospective study. This trial was designed to confirm the benefit of DD-EPIC in delaying progression and improving survival. Methods: In a multicenter, phase 2 trial, pts with FIGO IIIC-IV OC and optimal debulking surgery (residual disease ≤1cm) were randomly allocated to receive 4 doses of weekly DD-EPIC with cisplatin (50mg/m2) and etoposide (100mg/m2) followed by 6 cycles of intravenous (iv) chemo with carboplatin and taxane every 3 weeks (DD-EPIC group), or standard iv chemo alone (iv group). (ClinicalTrials.gov, NCT01669226). Results: Between 2009 and 2015, 218 pts were randomized, of whom 215 initiated treatment (106 to DD-EPIC and 109 to iv; for efficacy analyses). Totally, 36 pts (16·7%) were received neoadjuvant chemo. With a median of 61·9 mos follow-up, 122 pts died (54 in DD-EPIC and 68 in iv group). Remarkable OS benefit of DD-EPIC was recorded (67·5 mos for DD-EPIC vs. 46·3 mos for iv; HR 0·70, 95% CI 0·49-1·00, P=0·047). Pts in DD-EPIC had a significantly increased median PFS compared with those in iv group (21·7 vs. 16·8 mos; HR 0·64, 95% CI 0·47-0·86, P=0·003). Median TFST was 25·1 vs. 18·0 mos in favor of DD-EPIC (HR 0·62, 95%CI 0·46-0·83, P=0·002). Similar findings were detected in TSST (42·2 vs. 29·3 mos; HR 0·66, 95%CI 0·47-0·94, P=0·019). Grade 3 and 4 Leucopenia (53·8% vs. 35·2%), anemia (23·6% vs. 5·6%) and gastrointestinal events (10·4% vs. 1·9%) were more common in DD-EPIC ( P=0·006, P&lt;0·001 and P=0·010, respectively). Ninety-one pts were detected by gBRCA testing, with 25·3% of cases carrying deleterious BRCAm, but PFS and OS benefit were observed in patients with BRCA-wild type (HR 0·46 and 0·55, 95%CI 0·27-0·81 and 0·27-1·11, respectively). Conclusions: DD-EPIC with a higher completion rate and acceptable treatment burden was associated with longer OS than standard iv alone. Owing to the benefit of relatively long-term OS, DD-EPIC may be considered as a valuable option for OC, particularly in developing countries and BRCA-wild type pts. Clinical trial information: NCT01669226. [Table: see text]