Use of early postoperative intraperitoneal 5-fluorouracil with index cytoreduction improves survival with secondary cytoreductive surgery.

BACKGROUND: In patients with appendiceal mucinous neoplasm with peritoneal dissemination, a cytoreductive surgery (CRS) with perioperative chemotherapy may result in long-term survival. Disease progression may require secondary cytoreductive surgery (SCRS) and other treatments in selected patients to improve survival and preserve an optimal quality of life. METHODS: The clinical- and treatment-related variables associated with the index CRS and SCRS were statistically assessed for impact on survival after SCRS. RESULTS: A total of 186 of 687 complete CRS patients (27.1%) had SCRS. Median follow-up was 10 years and median survival was 12 years. In 95 males (51%) the median age was 45.0 years. Survival benefit with SCRS was observed if early postoperative intraperitoneal chemotherapy (EPIC) with 5-fluorouracil (EPIC 5-FU) or hyperthermic intraperitoneal chemotherapy (HIPEC) plus EPIC 5-FU was used with the index CRS (hazard ratio [HR]: 0.6, p = 0.0360; HR: 0.4, p = 0.0004, respectively). By propensity matching of 51 pairs of patients, EPIC 5-FU used with index CRS caused a survival advantage compared to HIPEC alone (p = 0.0100) with index CRS (p = 0.0100). CONCLUSIONS: Use of EPIC 5-FU at a complete index CRS was a prognostic variable that improved survival in patients requiring SCRS. Further investigations into the benefits of antiadhesion treatments with CRS and HIPEC are warranted.

Critical reappraisal of prognostic indicators for 949 mucinous appendiceal neoplasm patients.

BACKGROUND AND OBJECTIVES: The standard of care for treatment of an appendiceal mucinous neoplasm with peritoneal dissemination is cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC). These two treatments are combined in the operating room. A crucial requirement for benefit long-term is proper patient selection. Clinical and histopathologic prognostic indicators are used, along with the patient's fitness for surgery, to select patients to receive CRS and HIPEC. METHODS: This study seeks to identify the reliable prognostic indicators for four different groups of patients. They are (1) the low-grade appendiceal mucinous neoplasms (LAMN) with a complete CRS, (2) the mucinous appendiceal adenocarcinomas (MACA) with complete CRS, (3) MACA with lymph node metastases (MACA-LN) with complete CRS, and (4) all histologic subtypes with incomplete cytoreduction. The prognostic indicators were evaluated for their impact on overall survival in these four groups of patients. RESULTS: The completeness of cytoreduction (CC) score statistically significantly showed survival differences in all three histologic subtypes. The peritoneal cancer index (PCI) showed significance with LAMN and MACA-LN but not with MACA and not with incomplete CRS. The prior surgical score (PSS) was a prognostic indicator that predicted the outcome with LAMN, MACA-LN, and incomplete CRS patients but not with the MACA group. Patients who were symptomatic or who had extensive systemic chemotherapy before CRS had a significantly reduced survival. CONCLUSION: The utility of prognostic indicators varied greatly within our four different groups of appendiceal mucinous neoplasms. CC score was always a reliable prognosticator. Surprisingly, PCI was not.

Critical appraisal of total gastrectomy plus total colectomy with hyperthermic intraperitoneal chemotherapy as a treatment for advanced pseudomyxoma peritonei.

BACKGROUND: The absolute requirement for a long-term favorable result with cytoreductive surgery for pseudomyxoma peritonei is a complete resection of all visible disease. A combination of parietal peritonectomy procedures and visceral resections is required for this to occur. The cytoreductive surgery is supplemented by hyperthermic intraperitoneal chemotherapy. METHODS: We searched our database and secured files for patients who required a total gastrectomy and a total colectomy to achieve a complete cytoreductive surgery. Survival of low-grade mucinous neoplasm (LAMN) and mucinous appendiceal adenocarcinoma (MACA) histologies were determined. Clinical and histologic variables were assessed for their impact on survival. RESULTS: Thirteen of 450 patients (2.9%) with LAMN histology and 14 of 186 patients (7.5%) with MACA histology had these visceral resections. Median survival of these 27 patients was 10 years. LAMN and MACA patients showed the same survival. For LAMN histology, this requirement for extensive visceral resection markedly reduced survival (p < 0.0001). For MACA, there was no adverse impact on survival (p = 0.4359). Class 4 adverse events caused reduced survival (p = 0.0014). CONCLUSIONS: A 10-year median survival accompanies total gastrectomy plus total colectomy for advanced pseudomyxoma peritonei. Systemic chemotherapy and class 4 adverse events reduced survival.

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

BACKGROUND: Limited success in the management of mucinous appendiceal adenocarcinoma (MACA) has been reported. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Clinical and Histopathologic Features of 35 Patients Treated for Colorectal Peritoneal Metastases Who Survived 5 Years.

BACKGROUND: Currently, patients with a limited extent of peritoneal metastases from colon and rectal cancer are treated by cytoreductive surgery combined with perioperative chemotherapy performed at experienced centers. OBJECTIVE: To statistically evaluate features that may impact survival of ≥5 years. These data are used in the risk/benefit analyses performed by the multidisciplinary team. DESIGN: This was a retrospective review of a prospective database. SETTINGS: This single-institution study was conducted at an academic center. PATIENTS: All patients who had biopsy-proven colon or rectal peritoneal metastases treated by systemic chemotherapy, complete cytoreductive surgery, and perioperative surgery were included. MAIN OUTCOME MEASURES: The primary outcomes measured were the clinical-, histologic-, and treatment-related features that had an impact on 5-year survival. RESULTS: From 131 patients who had complete cytoreduction, 35 patients (26.7%) were identified as 5-year survivors. The median survival time was 27 months. The median age was 50.5 (range, 25-80) years. By univariant analysis, an absence of lymph node involvement at the time of primary colorectal cancer resection (HR 1.899 [95% CI, 1.064-3.388]; p = 0.03), complete or near-complete response to neoadjuvant chemotherapy (HR 0.251 [95% CI, 0.092-0.684]; p = 0.007), peritoneal cancer index ≤17 (HR 0.509 [95% CI, 0.329-0.788]; p = 0.002), complete visible resection of disease indicated by the completeness of cytoreduction score of 0 (HR 0.412 [95% CI, 0.224-0.756]; p = 0.004), and well-differentiated tumor (HR 0.34 [95% CI, 0.157-0.737]; p = 0.006) were significantly associated with ≥5 years survival. LIMITATIONS: Limitations include its retrospective nature, unmeasured confounders, and data from a single institution. CONCLUSIONS: The tumor biology as revealed by lymph node status and tumor differentiation plus extent of disease as measured by the response to neoadjuvant chemotherapy, peritoneal cancer index, and no visible residual disease indicated a favorable outcome. See Video Abstract at http://links.lww.com/DCR/C62 . CARACTERSTICAS CLNICAS E HISTOPATOLGICAS EN PACIENTES TRATADOS POR METASTASIS PERITONEALES DE ORGEN COLORECTAL Y QUE SOBREVIVIERON AOS: ANTECEDENTES:Actualmente, los pacientes con extensión limitada de metástasis peritoneales de orígen colorectal son tratados mediante cirugía citorreductora asociada con una quimioterapia peri-peratoria realizadas en centros experimentados.OBJETIVO:Estúdio y evaluación estadística de las características que puedan impactar en la sobrevida de los pacientes a 5 años o más. Se utilizaron estos datos en el análisis de riesgo /beneficio realizados por un equipo multidisciplinario.DISEÑO:Revisión retrospectiva de una base de datos prospectiva.AJUSTES:Estudio realizado en una sola institución académica.PACIENTES:Todos aquellos que presentaban metástasis peritoneales de orígen colorectal, comprobadas por biopsia y tratadas con quimioterapia sistémica, cirugía peri-operatoria y citorreductora completas.MEDIDAS DE RESULTADO PRINCIPALES:Las medidads de resultados primarios fueron las características clínicas, histológicas y relacionadas con el tratamiento que tuvieron un impacto en la sobrevida a 5 años.RESULTADOS:De 131 pacientes que tuvieron una cirugía de citorreducción completa, 35 pacientes (26, 7%) fueron identificados como sobrevivientes a 5 años. La mediana de sobrevida fué de 27 meses. Se identificarion 16 varones. La mediana de edad fue de 50, 5 años con un rango de 25 a 80 años. Según análisis univariante, la ausencia de compromiso de los ganglios linfáticos en el momento de la resección del cáncer colorrectal primario (HR 1,899 (1,064, 3,388) p = 0,03), la respuesta completa o casi completa al tratamiento neoadyuvante con quimioterapia (HR 0,251 (0,092, 0,684) p = 0,007), el índice de cáncer peritoneal ≤17 (HR 0,509 (0,329, 0,788) p = 0,002), la resección completa y visible de la enfermedad indicada por la puntuación de citorreducción de 0 (HR 0,412 (0,224), 0,756) p = 0,004) y los tumores bien diferenciados (HR 0,34 (0,157, 0,737) p = 0,006) se asociaron significativamente con 5 o más años de sobrevida.LIMITACIONES:El estudio se encontró limitado por su naturaleza retrospectiva, por la no medida de factores de confusión y por los datos provenientes de una sola institución.CONCLUSIONES:La biología tumoral demostrada según el estado de los ganglios linfáticos y la diferenciación tumoral, agregada a la extensión de la enfermedad medida por la respuesta a la quimioterapia neoadyuvante, el índice de cáncer peritoneal y la ausencia visible de enfermedad residual, demostraron un resultado favorable. Consulte Video Resumen en http://links.lww.com/DCR/C62(Traducción-Dr. Xavier Delgadillo ).

Secondary cytoreductive surgery for 86 patients with mucinous appendiceal adenocarcinoma.

BACKGROUND: After patients have a surgical procedure for a gastrointestinal cancer, follow-up is indicated. If cancer progression is documented in patients with mucinous appendiceal adenocarcinoma (MACA), a secondary cytoreductive surgery (SCRS) may be considered. METHODS: In patients who had a prior complete cytoreductive surgery (CRS), variables associated with the index CRS and SCRS were extracted. These variables were statistically assessed for their impact on survival. RESULTS: Of 198 MACA patients, 86 (43.4%) had SCRS. The median follow-up was 5.0 years and the median survival was 7 years. Significant prognostic variables associated with the index CRS by univariant analysis was histopathologic grade of MACA-Intermediate (MACA-Int) as compared to other MACA histologic subtypes (p = 0.0164). Significant prognostic variables associated with the SCRS were bowel obstruction (p = 0.0149), interval of CRS to SCRS (p = 0.0059), and completeness of cytoreduction (p = 0.0014). CONCLUSIONS: In the analysis of variables from SCRS, the interval from CRS to SCRS ≤24 months indicates an aggressive biology of the disease. The CC score of complete versus incomplete decreased median survival from 11 to 4 years. A composite of these two variables allowed prediction of survival of 50% when patients showed these two favorable variables and only 9.1% when these variables were unfavorable.

Palliation of mucinous appendiceal neoplasms with peritoneal metastases with total abdominal colectomy.

BACKGROUND: Incomplete cytoreduction for mucinous appendiceal neoplasms is often required to temporarily alleviate symptoms. The surgical technology for this intervention may be complex and result in extensive morbidity and even mortality. Knowledgeable patient selection for this surgery is mandatory. METHODS: A database was used to identify patients who had palliative surgery that included total abdominal colectomy (TAC). Clinical- and treatment-related variables were assessed for their impact on overall survival. RESULTS: Seventy-eight patients had an incomplete cytoreductive surgery (CRS) that included a TAC. The median survival was 2.5 years and the median follow-up was 2 years. Patients with symptoms of abdominal distention and ascites showed a reduced prognosis (p = 0.0254). The low-grade appendiceal mucinous neoplasms (LAMN) and mucinous appendiceal adenocarcinoma intermediate type (MACA-Int) grouped together showed a prolonged survival (p = 0.0003). MACA with positive lymph nodes showed a reduced survival (p = 0.0009) when compared to MACA patients without positive lymph nodes. A peritoneal cancer index of 1-30 versus >30 and completeness of cytoreduction score of 2 versus 3 were not significant. CONCLUSION: TAC with end ileostomy was used as a treatment option to provide palliation of patients having an incomplete CRS for appendiceal mucinous neoplasms. With LAMN or MACA-Int, median survival was 5.0 years. The surgery can be performed with a morbidity of 9.0% and mortality of 2.6%. Although not considered a palliative option in the past, these data suggest TAC may be used with acceptable results in this group of patients.

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

BACKGROUND: 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). METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Prognostic indicators for colorectal peritoneal metastases are different for patients with complete versus incomplete cytoreductive surgery.

BACKGROUND: In the management of peritoneal metastases in patients with colorectal cancer, the completeness of cytoreduction has consistently been the most prominent prognostic indicator. Other clinical and histologic features have been described that may also have an impact on survival. METHODS: The colorectal peritoneal metastases patients treated by cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy were divided into two groups. One group had complete CRS and the second group had an incomplete CRS. The prognostic variables in these two groups of patients were statistically analyzed for their impact on survival. RESULTS: In the complete CRS group of 124 patients lymph node positivity, poorly differentiated histopathology, asymptomatic status following treatment with systemic chemotherapy, incomplete response to systemic chemotherapy, and moderate to high peritoneal cancer index showed a significantly reduced survival. All five of these prognostic variables ceased to show statistical significance in the group of 82 patients with incomplete cytoreduction. CONCLUSION: The cause for significance of five prognostic indicators identified in patients with complete cytoreduction versus loss of significance of these indicators in patients with incomplete cytoreduction has not been determined. An absence of residual disease in complete CRS patients and a widely variable extent of residual disease in incomplete CRS patients may be important. Prognostic indicators in patients with colorectal peritoneal metastases find their greatest usefulness in patients who have had a complete cytoreduction.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Secondary cytoreductive surgery for low-grade appendiceal mucinous neoplasms.

BACKGROUND: In patients with low-grade appendiceal mucinous neoplasms (LAMN), a secondary cytoreductive surgery (SCRS) is often performed if recurrent disease is detected. METHODS: In patients with a complete cytoreductive surgery (CRS), the clinical- and treatment-related variables associated with the index CRS and the SCRS were statistically assessed for their impact on overall survival after SCRS. RESULTS: Eighty-eight patients of 450 patients (19.6%) had SCRS. The mean survival was 15.3 years for patients requiring SCRS as compared to 24.5 years for the group as a whole. Variables associated with improved survival as a result of the index CRS by multivariant modeling were absence of total gastrectomy (p = 0.0038), moderate peritoneal cancer index of 15-30 (p = 0.0020) and time interval of greater than 36 months from CRS to SCRS (p = 0.0013). Multivariant modeling associated with SCRS were complete CRS (p = 0.0104) and disease progression limited to the abdominal wall (p = 0.0106). Early postoperative intraperitoneal chemotherapy (EPIC) 5-fluorouracil used with CRS improved the outcome with SCRS (p = 0.0095). CONCLUSIONS: A requirement for SCRS in 88 patients decreased median survival to 15.3 years as compared to 24.5 years in all 450 LAMN patients (p < 0.0001). Prognostic indicators from both the index CRS and the SCRS had an impact on the outcome of SCRS.

Incomplete cytoreduction with peritoneal metastases from appendiceal mucinous neoplasms.

BACKGROUND: Complete cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy is the standard of care for mucinous appendiceal neoplasms with peritoneal metastases. Despite many publications regarding selection factors favoring a complete CRS, incomplete CRS does occur. Patients with an incomplete CRS are the focus of this manuscript. METHODS: A retrospective analysis of prospective, histologic, and perioperative data was performed. Overall survival was the endpoint for the numerous assessments. Judgments regarding when to and when not to proceed with an incomplete CRS were sought. RESULTS: From a database of 949 patients who underwent an index CRS for appendiceal mucinous neoplasm, 264 patients (27.8%) had an incomplete CRS. The median overall survival was 1.8 years. Low-grade histopathology and absence of tense ascites or bowel obstruction were significantly associated with increased overall survival. More extensive surgery suggested a more favorable outcome. CONCLUSIONS: When a surgeon is confronted by a procedure that will inevitably end with an incomplete CRS, a current trend is to close quickly and always avoid complications. Patients with low-grade neoplasms who present in the absence of tense ascites or bowel obstruction may gain years of survival by surgical reduction of tumor burden.

Optimizing regional chemotherapy for epithelial ovarian cancer.

AIM: The response with intravenous chemotherapy using cisplatin and paclitaxel in patients with advanced ovarian cancer is often substantial. However, this regression of the malignancy is not durable, and a majority of patients succumb to this disease process. It is possible that alternative types of chemotherapy and alternative routes of chemotherapy administration can improve the results of treatment and perhaps, reduce the morbidity and mortality that patients experience. METHODS: Regional chemotherapy treatments previously presented in the ovarian cancer literature were reviewed and critically analyzed. New methods for chemotherapy delivery for both advanced primary and recurrent ovarian cancer were reviewed. This included hyperthermic intraperitoneal chemotherapy (HIPEC), early postoperative intraperitoneal chemotherapy (EPIC), and normothermic intraperitoneal chemotherapy (NIPEC) long-term. RESULTS: An important addition to perioperative chemotherapy delivery is the simultaneous use of heat with intraperitoneal drug delivery after a complete cytoreductive surgery. Drugs to be considered for HIPEC are cisplatin, gemcitabine, and melphalan. For EPIC, chemotherapy agents to consider include paclitaxel, pemetrexed, gemcitabine, and liposomal doxorubicin. For NIPEC, paclitaxel is the drug of choice usually combined with a systemic agent as bidirectional chemotherapy. Also, pemetrexed, gemcitabine, and liposomal doxorubicin are drugs to be considered for NIPEC in phase I/II trials. CONCLUSIONS: Innovative regimens of regional chemotherapy may improve the outcome of patients with advanced ovarian cancer. These chemotherapy treatments must be integrated with complete cytoreductive surgery and the availability of peritoneal access for repeated delivery of chemotherapy solutions.

Cytoreductive Surgery Plus HIPEC With and Without NIPEC for Malignant Peritoneal Mesothelioma: A Propensity-Matched Analysis.

BACKGROUND: Malignant peritoneal mesothelioma is a rare and often fatal disease. Dissemination is confined to the abdominal and pelvic peritoneal spaces in a great majority of patients. METHODS: Standardized cytoreductive surgery and perioperative chemotherapy was used in all patients. Long-term normothermic intraperitoneal chemotherapy (NIPEC) was added to the treatment of our most recent group of patients. Survival with and without NIPEC was compared using a propensity-matched analysis. RESULTS: In a uniform group of 74 patients, the clinical- and treatment-related features that had an impact on survival were age (hazard ratio [HR] 1.99, 95% confidence interval [CI] 0.929-4.238, p = 0.0766), completeness of cytoreduction (HR 2.356, 95% CI 1.113-4.989, p = 0.0251), and treatments administered (HR 3.497, 95% CI 1.199-10.20, p = 0.0219). In the Cox proportional hazards multivariant model, sex and age were borderline significant. Treatments administered were significant (HR 3.549, 95% CI 1.157-10.888, p = 0.0268). Using five features to match 29 patients in the control group (no NIPEC) to 29 patients in the experimental group (with NIPEC), the propensity-matched survival was significantly different (p = 0.0263). CONCLUSIONS: The addition of NIPEC was associated with long-term survival in this cohort of patients. A multi-institutional randomized trial may be the next step.

Decision-Making Analysis for Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer: A Survey by the Executive Committee of the Peritoneal Surface Oncology Group International (PSOGI).

OBJECTIVES: To assess the individual treatment strategies among international experts in peritoneal carcinosis, specifically their decision-making in the process of patient selection for hyperthermic intraperitoneal chemotherapy (HIPEC) in women suffering from ovarian cancer, to identify relevant decision-making criteria, and to quantify the level of consensus for or against HIPEC. METHODS: The members of the executive committee of the Peritoneal Surface Oncology Group International (PSOGI) were asked to describe the clinical conditions under which they would recommend HIPEC in patients with ovarian cancer and to describe any disease or patient characteristics relevant to their decision. All answers were then merged and converted into decision trees. The decision trees were then analyzed by applying the objective consensus methodology. RESULTS: Nine experts in surgical oncology provided information on their multidisciplinary treatment strategy including HIPEC for patients with advanced ovarian cancer. Three of the total of 12 experts did not perform HIPEC. Five criteria relevant to the decision on whether HIPEC is performed were applied. In patients with resectable disease, a peritoneal cancer index (PCI) <21, and epithelial ovarian cancer without distant metastasis, consent was received by 75% to perform HIPEC for women suffering from recurrent disease. Furthermore, in the primary disease setting, consent was received by 67% to perform HIPEC according to the same criteria. DISCUSSION AND CONCLUSION: Among surgical oncology experts in peritoneal surface malignancy and HIPEC, HIPEC plays an important role in primary and recurrent ovarian cancer, and the PCI is the most important criterion in this decision.

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

BACKGROUND: Pseudomyxoma peritonei is a disease caused by the widespread distribution of mucinous tumor into the peritoneal space from a perforated appendiceal neoplasm. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Peritoneal cytology as an indicator of peritoneal metastases in colorectal cancer.

BACKGROUND: In the management of peritoneal metastases from colon and rectal cancer, the most favorable results are reported with an aggressive combined treatment on patients who have a small extent of the disease. A test to detect occult peritoneal metastases would greatly facilitate the management of this component of colorectal dissemination. METHODS: Currently, the standard test by which to confirm the diagnosis of the peritoneal spread of colorectal cancer is peritoneal cytology. To study the utility of this test, we gathered information from patients with biopsy-proven peritoneal metastases. The clinical, histologic, and treatment-related features of these patients at the time of a cytoreductive surgery were statistically correlated with the results of the peritoneal cytology test. RESULTS: Forty-nine patients with colorectal cancer peritoneal metastases and a peritoneal cytology determination at the time of a cytoreductive surgery were available for analysis. Twenty-eight patients (55.1%) had a positive test. Patients with a high peritoneal cancer index and mucinous histology were most likely to have positive peritoneal cytology. CONCLUSION: Peritoneal cytology identified patients with mucinous histology and a large extent of disease but was consistently negative in patients who had a small extent of disease compatible with a favorable response to treatment.

Management of recurrent granulosa cell tumor of the ovary: Contemporary literature review and a proposal of hyperthermic intraperitoneal chemotherapy as novel therapeutic option.

Granulosa cell tumors of the ovary (GCT) are the most common type of sex cord stromal tumors. Although most of patients are diagnosed at early stage and has favorable 5-year overall survival rate, 16-23% of GCT ultimately develop recurrent disease. Recurrences are characterized by disseminated peritoneal metastasis. The treatment options include systemic chemotherapy, secondary CRS or palliative localized radiation therapy have not yet standardized due to the rarity of disease. Aggressive CRS followed up by hyperthermic intraperitoneal chemotherapy (HIPEC) has been shown to provide benefit in other peritoneal disease but limited data available for recurrent GCT. We have a case of recurrent Adult-type GCT (AGCT) who was treated with CRS followed by HIPEC with mitomycin C and doxorubicin. The patient has no evidence of recurrence for approximately 11 years. An electronic search of the PubMed database with the following search terms: GCT, HIPEC showed that there were total 21 patients with recurrent GCT treated in seven different studies and 13 of 21 (61.9%) patients had no evidence of disease during follow-up ranging from 6 to 100 months. Three patients (14.2%) died of the disease. Six studies used cisplatin for HIPEC. At least 76.2% (16 of 21, data not available for five patients) had complete cytoreduction with total 16 cases of perioperative complications but no perioperative mortality was observed. Although further investigation is needed, we propose that CRS and HIPEC can be an effective therapeutic option for recurrent GCT at experienced institutions.

Body surface area-based vs concentration-based perioperative intraperitoneal chemotherapy after optimal cytoreductive surgery in colorectal peritoneal surface malignancy treatment: COBOX trial.

BACKGROUND AND OBJECTIVES: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal perioperative chemotherapy (HIPEC) are the standard of care for patients diagnosed with colorectal peritoneal surface malignancy (PSM). Despite a clearly defined standardization of CRS, a large variety of HIPEC modalities are still used in clinical practice. METHODS: Body surface area (BSA)- and concentration-based HIPEC protocols were clinically and pharmacologically evaluated in a randomized phase III clinical pilot trial. Oxaliplatin dose was 460 mg/m 2 (BSA-based) in 2 L/m 2 carrier solution (concentration-based). Platinum quantification was performed using a validated inductively coupled plasma mass spectrometry method. Three-month morbidity, mortality, and health-related quality of life (HRQOL) were assessed. RESULTS: Thirty-one patients were randomized to either BSA- or concentration-based HIPEC. Toxicity and efficacy were higher (P < 0.001) in patients receiving concentration-based HIPEC. There was no difference in pharmacologic advantage between the two groups. A higher drug concentration in the tumor nodule at the end of HIPEC was found in the HIPEC-concentration group. There was no difference in major morbidity and mortality between the treatment groups. HRQOL was decreased 3 months postoperatively in the HIPEC-concentration group. CONCLUSION: Concentration-based chemotherapy delivers the drug in the most standardized way to the tumor nodule, resulting in increasing drug concentrations in the tumor nodule without increasing major morbidity.

Iterative cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastases: A multi-institutional experience.

BACKGROUND AND OBJECTIVES: The aims of this multi-institutional study were to assess the feasibility of iterative cytoreductive surgery (iCRS)/hyperthermic intraperitoneal chemotherapy, iCRS in colorectal peritoneal carcinomatosis (CRPC), evaluate survival, recurrence, morbidity and mortality outcomes, and identify prognostic factors for overall survival. METHODS: Patients with CRPC that underwent an iCRS, with or without intraperitoneal chemotherapy, from June 1993 to July 2016 at 13 institutions were retrospectively analyzed from prospectively maintained databases. RESULTS: The study comprised of 231 patients, including 126 females (54.5%) with a mean age at iCRS of 51.3 years. The iterative high-grade (3/4) morbidity and mortality rates were 23.4% and 1.7%, respectively. The median recurrence-free survival was 15.0 and 10.1 months after initial and iCRS, respectively. The median and 5-year survivals were 49.1 months and 43% and 26.4 months and 26% from the initial and iCRS, respectively. Independent negative predictors of survival from the initial CRS included peritoneal carcinomatosis index (PCI) > 20 ( P = 0.02) and lymph node positivity ( P = 0.04), and from iCRS, PCI > 10 ( P = 0.03 for PCI 11-20; P < 0.001 for PCI > 20), high-grade complications ( P = 0.012), and incomplete cytoreduction ( P < 0.001). CONCLUSION: iCRS can provide long-term survival benefits to highly selected colorectal peritoneal carcinomatosis patients with comparable mortality and morbidity rates to the initial CRS procedure. Careful patient selection is necessary to improve overall outcomes.