Perioperative Intraperitoneal Chemotherapy Research Articles

Perioperative intraperitoneal plus systemic chemotherapy and cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for gastric cancer: Phase Ib/II single-arm prospective study.

In gastric cancer, peritoneal metastasis is the most common form of metastasis and leads to dismal prognosis. We aimed to evaluate the safety and efficacy of combining perioperative intraperitoneal (IP) plus systemic chemotherapy, cytoreductive surgery (CRS), and hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with gastric cancer with limited peritoneal metastasis, or even after reducing peritoneal tumor burden by upfront IP chemotherapy. Phase Ib enrolled patients in a 3+3 dose-escalation of IP paclitaxel plus a fixed dose of IP cisplatin and oral S-1. In Phase II, patients were managed according to the peritoneal cancer index (PCI) by diagnostic laparoscopy. For patients with a PCI of >12, upfront IP and systemic chemotherapy were given. Patients with a PCI of ≤12 or reduced to ≤12 after upfront chemotherapy underwent CRS with HIPEC. The primary endpoints were safety and the recommended Phase II dose (RP2D) confirmation for Phase Ib and the one-year overall survival rate for Phase II. The RP2D was defined as IP 175mg/m2 paclitaxel and 60mg/m2 cisplatin and oral 70mg/m2/day S-1 for 14 days. A total of 22 patients were included. After CRS with HIPEC, there were no grade 3 or higher complications. The median hospital stay was 7 days (range, 6-11). The median overall and progression-free survival were 27.3 months (95% confidence interval [CI], 14.4-not estimable) and 12.6 months (95% CI, 7.7-14.5), respectively. One-year overall and progression-free survival rates were 81.0% (95% CI, 65.8-99.6) and 54.5% (95% CI, 37.2-79.9), respectively. A combination of IP plus systemic chemotherapy, CRS, and HIPEC was safe and resulted in good survival outcomes.

Cytoreductive surgery and perioperative intraperitoneal chemotherapy in recurrent ovarian cancer: 18 years of experience

AimTo identify the clinical and pathological factors associated with relapse in women who had undergone secondary cytoreductive surgery due to locally advanced recurrent ovarian cancer. MethodsWomen with locally advanced recurrent ovarian cancer who had undergone cytoreduction between 2000 and 2018 were included in this study. Demographic, clinical and biochemical intraoperative findings were recorded for each woman. All factors were assessed in order to identify which correlated with the outcomes of interest (i.e. disease relapse, mortality and morbidity). ResultsIn total, 181 women who had undergone secondary cytoreduction were analysed. The hospital mortality rate was 1.7 % (n = 3) and the morbidity rate was 32.1 % (n = 58). Recurrence was recorded in 101 (55.8 %) women. Infiltration of large bowel lymph nodes was a negative prognostic indicator of morbidity (p = 0.029). A prior surgical score of 1 (PSS-1) [odds ratio (OR) 0.465] and complete cytoreduction (OR 0.518) were found to be significant independent predictors for disease relapse. Median overall survival was greater for patients with PSS-1 (151.3 vs 59.4 vs 44.1 months; p = 0.049) and patients with complete cytoreduction (137.6 vs 36.2 vs 10.0 vs 27.4 months; p < 0.001). ConclusionComplete cytoreduction and PSS-1 are associated with reduced disease relapse and increased overall survival. Infiltration of large bowel lymph nodes is associated with increased morbidity.

Total abdominal colectomy to facilitate complete cytoreduction in 56 patients with mucinous appendiceal neoplasms with peritoneal metastases.

Cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy are currently the standard of care for management of appendiceal mucinous neoplasms with peritoneal metastases. The goal of the CRS is complete removal of all visible disease through the use of peritonectomy procedures and visceral resections. One of the major resections that may be required is total abdominal colectomy (TAC). From a database and secured files of patients having a complete CRS, all patients who had TAC were identified. The clinical and histologic variables associated with these patients were identified and assessed for their impact on overall survival. The 450 complete CRS with low-grade appendiceal mucinous neoplasms had 26 TAC (5.8%) with a 16.0-year median survival. The mucinous adenocarcinoma (MACA)-Intermediate (MACA-Int) group consisted of 37 patients with 8 patients (21.6%) having TAC that resulted in a median survival of 11.5 years. The 159 complete CRS with MACA had 22 TAC (13.8%) with a median survival of 7.5 years. There was a single mortality with a class 4 adverse event in 5 patients (10.7%). With a class 4 adverse event, survival decreased significantly (p = 0.0006, hazard ratio: 6.2). Complete CRS required TAC in 56 of 646 patients (8.7%) with appendiceal mucinous neoplasms. With TAC, median survival was 12.0 years. A class 4 adverse event markedly reduced survival.

Similar Survival Among All Subtypes of Mucinous Appendiceal Adenocarcinoma Except the Intermediate Subtype, Which Shows an Improved Survival.

Limited success in the management of mucinous appendiceal adenocarcinoma (MACA) has been reported. Cytoreductive surgery with perioperative intraperitoneal chemotherapy was used to treat a cohort of patients with peritoneal dissemination of MACA. The clinical and histopathologic variables were assessed for their impact on overall survival. The study analyzed 196 patients during a median follow-up period of 8 years. The patients had a median age was 46 years, a median survival of 12 years, and a mean survival of 12.4 years. Preoperative systemic chemotherapy and a high prior surgical score had a negative impact on prognosis. Survival was better for 37 patients (18.9%) with mucinous appendiceal adenocarcinoma-Intermediate (MACA-Int) histology than for 159 patients (81.1%) with MACA grade 1, 2, or 3, or signet ring cells (S) (p = 0.0004). Although MACA-1 and MACA-2 versus MACA-3 and MACA-S had a difference in survival of 63.9 versus 43.2 years at 5 years, with long-term follow-up evaluation, the differences in survival became insignificant (p = 0.5841). The histologic subtype of MACA-Int had a 10-year survival of 81.1%, which was markedly superior to that of MACA-1, -2, -3, or -S (32.7%). With long-term follow-up evaluation, MACA-1, -2, -3, and -S did not differ significantly in survival.

Gelatinous peritoneal disease secondary to appendiceal mucinous adenocarcinoma: a case study and review of the literature

Pseudomyxoma peritonei also referred to as gelatinous ascites, is a rare disorder, described for the first time by R. Wyerth in 1884. It is characterized by the presence of mucous disseminated throughout the peritoneal cavity generally arising from the rupture of an appendicular mucocele. Pseudomyxoma peritonei can be asymptomatic, discovered during a laparotomy. The most common symptom is abdominal distension associated with diffuse abdominal pain. An abdominal CT scan is the most specific diagnostic tool. It shows pathognomonic signs of gelatinous ascites. Mucinous neoplasms of the appendix are the most frequent cause of pseudomyxoma peritonei accounting for 90% of cases. Pseudomyxoma peritonei needs to be considered as a borderline malignant disease because of its inevitable persistence and progression without an adapted therapeutic approach: cytoreductive surgery combined with perioperative intraperitoneal chemotherapy in specialized centers. The principal prognostic factors are the prior surgical history, the completeness of cytoreduction and especially the histopathologic grade. We report the case of pseudomyxoma peritonei secondary to appendiceal mucinous adenocarcinoma.

Extent of Disease on Visceral Peritoneal Surfaces of Mucinous Appendiceal Neoplasms Controls Survival.

To determine causes of treatment failure of low-grade appendiceal mucinous neoplasms (LAMN). For 3 decades, LAMN have been treated by cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy. This combined treatment has resulted in a large change in the survival of these patients. A retrospective review of a prospectively maintained database was performed. A restricted cohort of patients with only LAMN histology and complete CRS were included in the statistical analysis. Four hundred and fifty patients were available with a median follow-up of 15.3 years (range 10-35 years). The median age was 49.7 and there were 196 males (43.6%). The mean survival was 24.5 years. Extent of parietal peritonectomy, resection of uterus, ovaries and apex of vagina had no impact on survival. Variables that indicated an increased extent of disease on visceral peritoneal surfaces had a significant impact on survival. Early postoperative intraperitoneal chemotherapy with 5-fluorouracil did not augment hyperthermic intraperitoneal chemotherapy (HIPEC). Patients who required reoperation for recurrence or patients with class 4 adverse events had a reduced prognosis. The mean survival of LAMN treated by complete CRS and perioperative chemotherapy was 24.5 years. Extent of disease quantitated on visceral peritoneal surfaces by the extent of visceral resections was the variable associated with treatment failure. Peritonectomy plus HIPEC was able to control disease on parietal peritoneal surfaces. Not only a larger extent of disease but also its location on visceral peritoneal surfaces controlled survival.

Outcomes and prognostic factors of cytoreductive surgery and perioperative intraperitoneal chemotherapy in high-volume peritoneal carcinomatosis

Background and objectives The management of patients with extensive appendiceal mucinous neoplasms and mesothelioma is controversial. Our aims were to analyze overall survival (OS), disease-free survival (DFS) and independent prognostic factors associated with high peritoneal cancer index (PCI) status in patients who underwent cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy (PIC). Methods A prospectively-maintained database for patients with appendiceal neoplasms and mesothelioma undergoing CRS/PIC from year 1996 to 2018 was retrospectively analyzed. Patients who achieved complete cytoreduction were stratified into limited (PCI < 30) and extensive (PCI ≥ 30) disease groups. Results 260 female and 235 male patients were identified. The 5-year survival for low-grade appendiceal mucinous neoplasms (LAMN) was significantly higher in the low PCI group (96.2% vs. 63.5%, p < 0.001). There was no difference in the OS across both groups in high-grade appendiceal mucinous neoplasms (HAMN) (63 vs. 69 months; p = 0.942) and mesothelioma (72 vs. 42 months; p = 0.058). Overall mortality was 2%. Grade III/IV complications were significantly higher in extensive disease (68% vs. 36.6%, p < 0.001). On multivariate analysis, use of EPIC and blood transfusion (>8 units) were independent positive and negative prognostic factors, respectively, associated with OS. Meanwhile, use of EPIC conferred benefit in DFS while increased blood transfusion (>8 units) and elevated preoperative CA125 were predictive of a poor DFS. Conclusion Long-term survivals following CRS/PIC are achievable with acceptable mortality and higher morbidity rates in extensive appendiceal mucinous neoplasms and mesothelioma. High PCI status does not preclude treatment with CRS/PIC.

Incomplete Cytoreduction of Colorectal Cancer Peritoneal Metastases: Survival Outcomes by a Cytoreduction Score

Background: The surgical management of peritoneal metastases from colorectal cancer has been a topic of controversial discussion for many decades. Peritonectomy and perioperative intraperitoneal chemotherapy added options for surgical treatment of this condition beyond palliative surgery. The most favorable outcomes are recorded when peritoneal metastases from colorectal cancer can be resected to no visible evidence of disease. Methods: To determine if any benefit from surgical treatment of patients with colorectal peritoneal metastases can occur from incomplete resection of peritoneal metastases, we studied patients by the completeness of cytoreduction (CC) score. The CC-3 indicated a palliative resection, CC-2 gross residual disease, and CC-1 almost complete cytoreduction but visible residual disease. The impact of clinical-, pathologic-, and treatment-related variables on the survival of the three groups was compared. Results: Eighty-five patients with long-term follow-up were available for study. The median age was 53 years (range 18–82). There were 60 males (70.6%). Symptomatic patients, those with bowel obstruction, and patients with positive retroperitoneal lymph nodes had significantly reduced survival. The median survival of the CC-3, CC-2, and CC-1 groups were significantly different (p = 0.0027). The 2-year or greater survivals of the three groups were 4.8%, 15.1%, and 38.7%, respectively. Conclusions: If a near complete cytoreduction combined with hyperthermic intraperitoneal chemotherapy can be performed, short-term survival benefit could be observed.

Pseudomyxoma Peritonei: A Case Report

Pseudomyxoma peritonei (PMP) is a rare condition, consisting of mucinous ascites and multifocal mucinous epithelial implants. This disease mainly affects women. It may remain asymptomatic, discovered during laparotomy. The most frequent symptom is abdominal distension associated with diffuse abdominal pain. Mucinous tumours of the appendix are the most frequent cause of pseudomyxoma peritoneum, accounting for 90% of cases, and ovarian origin remains very rare. There are essentially two types of treatment for PMP: firstly multiple surgical debulking and secondly cytoreduction surgery with peri-operative intraperitoneal chemotherapy consisting of hyperthermic intraperitoneal chemotherapy with or without immediate post-operative intraperitoneal chemotherapy. We report a case of peritoneal pseudomyxoma secondary to a mucinous tumour of the right ovary.

44 Hipec Therapy-A New Development to Fight Cancer; Report Of 3 Cases

Abstract Introduction HIPEC is highly concentrated, heated chemotherapy treatment that is delivered directly to the abdomen during surgery. HIPEC delivers chemotherapy directly to cancer cells in abdomen. Cytoreductive surgery(CRS) combined with perioperative intraperitoneal chemotherapy is currently a valid treatment option for peritoneal dissemination of gastrointestinal, gynaecological cancers or primary peritoneal neoplasms. Method 3 patients with peritoneal surface malignancy were selected. PET scan was done for all the patients to assess metastasis and peritoneal carcinomatosis index(PCI) calculated was&amp;lt;20 for all 3 patients They were then treated with CRS+HIPEC therapy with disease-specific chemotherapeutic agents like Cisplatin, Mitomycin and Doxorubicin and Oxaliplatin . Aim was Results All the 3 patients had a good post-operative recovery with no recurrence in the follow-up period Conclusions HIPEC and CRS plays synergistic role. A complete CRS followed by HIPEC with the disease-specific chemotherapeutic agent at 41-43ºC constitutes optimal treatment for certain malignancies. High regional concentration with low systemic concentration of chemotherapy, increased tissue penetration and thermal enhancement of cytotoxicity are some of the advantages with HIPEC therapy

Treatment of advanced pseudomyxoma peritonei using cytoreductive surgery including total gastrectomy and perioperative chemotherapy.

Pseudomyxoma peritonei is a disease caused by the widespread distribution of mucinous tumor into the peritoneal space from a perforated appendiceal neoplasm. All patients in this study had cytoreductive surgery with total gastrectomy plus perioperative intraperitoneal chemotherapy. A high diverting jejunostomy was used on all patients. Patient characteristics, adverse events, and survival were accumulated prospectively. Fifty-eight patients were available for long-term follow-up. In the univariate analysis, features associated with a less favorable outcome included female gender (p = 0.0127), intestinal obstruction before treatment (p = 0.00791), and prior surgical score (PSS) (p = 0.0054). In the multivariate analysis, the two significant variables were grade (p = 0.0458) and PSS (p = 0.0041). Median survival was 12 years with a 5-, 10-, and 20-year survival of 76%, 58%, and 37%, respectively. There were two postoperative deaths (3.4%) and Grades 3 and 4 adverse events in 20 (34.5%) patients. A 10-year survival after cytoreductive surgery, total gastrectomy with temporary high diverting jejunostomy, and perioperative chemotherapy occurred in 58% of these patients with advanced pseudomyxoma peritonei. High-grade disease and extensive prior surgery with a high PSS were associated with reduced benefit.

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.

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.

Low Preoperative Serum Albumin Levels Are Associated With Impaired Outcome After Cytoreductive Surgery and Perioperative Intraperitoneal Chemotherapy for Peritoneal Surface Malignancies.

Preoperative hypoalbuminemia is known to be associated with postoperative morbidity and mortality, as well as with poor survival after gastrointestinal cancer surgery. However, limited data exist regarding the prognostic significance of hypoalbuminemia in patients with peritoneal metastases undergoing cytoreductive surgery, combined with perioperative intraperitoneal chemotherapy. We performed a systematic literature review of the previously published studies addressing the potential association between preoperative albumin levels and overall surgical outcomes after the performance of cytoreductive surgery and perioperative intraperitoneal chemotherapy for peritoneal surface malignancies. Our research yielded a total of nine retrospective studies which met our inclusion criteria, and despite their heterogeneity; and we can conclude that preoperatively low albumin levels are associated with greater likelihood of overall and major morbidity, as well as less favorable oncological outcome after the performance of cytoreductive surgery and perioperative intraperitoneal chemotherapy.

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.

Early recurrence in peritoneal metastasis of appendiceal neoplasm: Survival and prognostic factors

IntroductionEarly recurrence (ER) is defined as development of loco-regional peritoneal disease within 12-month of the initial CRS/PIC. Our aims were to identify overall survival (OS), recurrence-free survival (RFS) and independent prognostic factors associated with ER in PM of appendiceal neoplasm. Materials and methodsA prospectively-maintained database for patients with appendiceal neoplasm undergoing cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy (PIC) from year 1996–2018 was retrospectively analysed. Results208 female and 185 male patients were identified. With a median follow-up of 40-month, 40.2% of the patients developed ER. The median OS for ER was 24 months compared to late (LR) at 64 months. Median OS was not reached in non-recurrence (NR). 5-year survival for ER was less favourable compared to LR and NR (19.3%vs54.6%vs94%). No patients in ER group survived beyond 10-year. Independent negative predictors associated with ER on multivariate analysis were male patient (p = 0.013), blood transfusion of >8 units (p = 0.013), elevated preoperative CEA levels (>5 ng/ml; p = 0.002) and hard intraoperative tumour consistency (p < 0.001). Protective factor was a combination of CC1, hard tumour consistency and use of EPIC (p = 0.039). Independent prognostic factors that predicted recurrence of appendiceal PM were PCI >20 (p = 0.049), non-use of EPIC (p = 0.012), hard tumour consistency (p = 0.004) and use of previous chemotherapy (p = 0.023). ConclusionER following CRS and PIC of appendiceal PM is associated with reduced survival outcomes. Our data alludes to the importance of optimising the risk factors in order to delay loco-regional recurrence and improve long-term survival of these patients.

Body surface area-based versus concentration-based intraperitoneal perioperative chemotherapy in a rat model of colorectal peritoneal surface malignancy: pharmacologic guidance towards standardization.

Worldwide, cytoreductive surgery (CRS) and hyperthermic intraperitoneal perioperative chemotherapy (HIPEC) are used in current clinical practice for colorectal peritoneal surface malignancy (PSM) treatment. Although, there is an acknowledged standardization regarding the CRS, we are still lacking a much-needed standardization amongst the various intraperitoneal (IP) chemotherapy protocols, including the HIPEC dosing regimen. We should rely on pharmacologic evidence building towards such a standardization. The current IP chemotherapy dosing regimens can be divided into body surface area (BSA)-based and concentration-based protocols. A preclinical animal study was designed to evaluate pharmacologic advantage (PA), efficacy and survival. WAG/Rij rats were IP injected with the rat colonic carcinoma cell line CC-531. Animals were randomized into three groups: CRS alone or CRS combined with oxaliplatin-based HIPEC (either BSA- or concentration-based). There was no difference in PA between the two groups (p=0.283). Platinum concentration in the tumor nodule was significantly higher in the concentration-based group (p<0.001). Median survival did not differ between the treatment groups (p<0.250). This preclinical study, in contrast to previous thinking, clearly demonstrates that the PA does not provide any information about the true efficacy of the drug and emphasizes the importance of the tumor nodule as pharmacologic endpoint.

Who Undergoes Cytoreductive Surgery and Perioperative Intraperitoneal Chemotherapy for Appendiceal Cancer? An Analysis of the National Cancer Database

BackgroundWe sought to identify patterns of care for patients with appendiceal cancer and identify clinical factors associated with patient selection for multimodality treatment, including cytoreductive surgery and perioperative intraperitoneal chemotherapy (CRS/PIC). Materials and methodsNational Cancer Database (NCDB) data from 2004 to 2014 of all diagnoses of appendiceal cancers were examined. We examined treatment modalities, as well as demographic, tumor-specific, and survival data. A multivariate logistic regression analysis was performed to determine the patient cohort most likely to receive CRS/PIC. Kaplan–Meier was used to estimate survival for all treatment groups. Significance was evaluated at P ≤ 0.05. ResultsWe analyzed data on 18,055 patients. Nine thousand nine hundred ninety-two (55.3%) were treated with surgery only, 5848 (32.4%) received surgery and systemic chemotherapy, 1393 (7.71%) received CRS/PIC, 520 (2.88%) received chemotherapy alone, and 302 (1.67%) received neither surgery nor chemotherapy. Significant predictors of receiving CRS/PIC included male sex (OR 1.33, 95% CI: 1.11-1.59), white race (OR 2.00, 95% CI 1.40-2.86), non-Hispanic ethnicity (OR 1.92, 95% CI 1.21-3.05), private insurance (OR 1.52, 95% CI 1.26-1.84), and well-differentiated tumors (OR 4.25, CI: 3.39-5.32) (P < 0.05). Treatment with CRS/PIC was associated with a higher 5-year survival for mucinous malignancies, when compared to surgery alone (65.6% versus 62.4%, P < 0.01). Treatment with CRS/PIC was also associated with higher 5-year survival for well-differentiated malignancies, when compared to all other treatment modalities (74.9% versus 65.4%, P < 0.01). ConclusionsPatients were more likely to undergo CRS/PIC if they were male, white, privately insured, and with well-differentiated tumors. CRS/PIC was associated with improved survival in patients with mucinous and low-grade tumors.

Severe hematologic toxicity following cytoreductive surgery combined with perioperative intraperitoneal chemotherapy

Severe hematologic toxicity following cytoreductive surgery combined with perioperative intraperitoneal chemotherapy