Predictors of recurrence of peritoneal carcinomatosis among patients with colorectal cancer following cytoreductive surgery alone versus cytoreductive surgery plus HIPEC

Background: Peritoneal carcinomatosis (PC) is a lethal regional progression in patients with colorectal cancer (CRC). Treatment with complete cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) achieves better local control than systemic palliative chemotherapy. Objectives: To assess the efficacy on the prognosis of CRS and HIPEC compared with CRS only and to identify possible clinicopathological factors associated with the recurrence of PC. Methods: The present retrospective study included all colorectal carcinoma cases with PC subjected to CRS with or without HIPC from January 2009 to June 2018 at the National Cancer Institute (NCI), Cairo University, Cairo, Egypt. The outcome is evaluated in terms of recurrence-free survival (RFS) and its predictors. Results: Out of the 61 patients, 45 patients (73.8%) underwent CRS plus HIPEC, and 16 (26.2%) underwent CRS alone. The 1-year RFS was 55.7%, with a median of 12 months. The risk factors for recurrence identified in the univariate analysis were T4 primary tumor, high-grade, positive lymphovascular invasion (LVI), positive extracapsular nodal spread, and patients treated with CRS only, without HIPEC. In the multivariate analysis, the independent risk factors for recurrence were high grade and patients treated with CRS only. Conclusion: T4 primary tumor, high grade, positive LVI, and positive extracapsular nodal spread seemed to be important predictors of recurrence following the treatment of PC. Our study also demonstrated that the addition of HIPEC to CRS improved the RFS. (AU)

Efficacy and safety in the use of intraperitoneal hyperthermia chemotherapy and peritoneal cytoreductive surgery for pseudomyxoma peritonei from appendiceal neoplasm: A systematic review

Abstract The objective of this systematic review is to provide efficacy and safety data in the application of Intra-Abdominal Hyperthermia Chemotherapy (HIPEC) and Cytoreductive Surgery (CRS) in patients with Peritoneal Pseudomyxoma (PMP) of origin in the cecal appendix. The databases Medline and Central Cochrane were consulted. Patients with PMP of origin in the cecal appendix, classified as low grade, high or indeterminate, submitted to HIPEC and CRS. The results were meta-analyzed using the Comprehensive Metanalysis software. Twenty-six studies were selected to support this review. For low-grade PMP outcome, 60-month risk of mortality, Disease-Free Survival (DFS), and adverse events was 28.8% (95% CI 25.9 to 32), 43% (95% CI 36.4 and 49.8), and 46.7% (95% CI 40.7 to 52.8); for high-grade PMP, 60-month risk of mortality, Disease-Free Survival (DFS) and adverse events was 55.9% (95% CI 51.9 to 59.6), 20.1% (95% CI 15.5 to 25.7) and 30% (95% CI 25.2 to 35.3); PMP indeterminate degree, 60-month risk of mortality, Disease-Free Survival (DFS) and adverse events was 32.6% (95% CI 30.5 to 34.7), 61.8% (95% CI 58.8 to 64.7) and 32.9% (95% CI 30.5 to 35.4). The authors conclude that the HIPEC technique and cytoreductive surgery can be applied to selected cases of patients with PMP of peritoneal origin with satisfactory results.

International guidelines for the treatment of peritoneal cancer: clinical pathways of cytoreductive surgery plus intraperitoneal hyperthermic chemotherapy / 中国肿瘤临床

Peritoneal cancer originates from a wide range of tumor sources and is associated with poor prognosis. Standardized therapy is of great significance in the treatment for patients with peritoneal cancer. The Peritoneal Surface Oncology Group International (PSOGI) instituted guidelines for peritoneal metastases. This article uses the Chinese version, which is divided into four parts: preoperative evaluation, surgery, chemotherapy, and clinical pathway. The preoperative evaluation consists of preoperative computed tomography, prognostic evaluation model, diagnostic laparoscopic exploration, the peritoneal cancer index, and the cytoreduction score. Peritoneal cancer treatment primarily consists of comprehensive treatment with cytoreductive surgery (CRS) and intraperitoneal hyperthermic chemotherapy. However, complete CRS is the key to the long-term survival of patients. Peritoneal cancer chemotherapy generally includes perioperative chemotherapy and regional chemotherapy. Finally, this guide outlines the clinical pathways. The Chinese version of the guidelines was published under the permission of the Secretary-General of the PSOGI Executive Committee.

Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy for pseudomyxoma peritonei: a single-center experience with 854 patients / 中国肿瘤临床

Pseudomyxoma peritonei (PMP) is a rare clinical syndrome. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is gradually being accepted as the standard treatment for PMP. At Aerospace Hospital, we have been treating patients with PMP since 2008 and performing total peritoneal resection since 2016. This study summarizes the experience at our center and collates past data. Methods: We performed a retrospective analysis of a prospectively maintained database of all patients who had undergone CRS and HIPEC for PMP at our center. Clinical data, such as the surgical approach, completeness of cytoreduction, and surgical complications, were collected. The results from follow-up were analyzed to simultaneously evaluate the clinical value of CRS+HIPEC and peritonectomy procedures. Results: A total of 854 consecutive patients with PMP were included in the study. Their mean age was 50 years. The median modified peritoneal cancer index (PCI) was 29. Of the patients, 25.5% under-

Clinical efficacy of hyperthermic intraperitoneal chemotherapy plus cytoreductive surgery for peritoneal metastasis of gallbladder cancer / 中国肿瘤临床

Objective: To investigate the clinical efficacy of hyperthermic intraperitoneal chemotherapy (HIPEC) for gallbladder cancer with peritoneal metastasis. Methods: Data of 84 patients, who were admitted to Shanghai Eastern Hepatobiliary Surgery Hospital from January 2015 to January 2018, were retrospectively analyzed. Of the total patients, 31 received HIPEC combined with cytoreductive surgery (CRS) plus postoperative systemic chemotherapy one month after surgery as the study group (Group A), and the other 53 underwent CRS plus postoperative systemic chemotherapy one momth after surgery as the control group (Group B). The clinical effects and adverse reactions in the two groups were observed and compared. Results: The median survival time in the Group A was (21.72±2.96) months, significantly longer than that of (14.93±2.09) months in Group B (P0.05). Conclusions: HIPEC has significant clinical efficacy for gallbladder cancer with peritoneal metastasis. HIPEC can prolong the survival time and have less side effects.

Prognostic analysis of intraoperative chemohyperthermic peritoneal perfusion in patients with advanced gastric cancer of different pathological types and Borrmann's classifications / 中国肿瘤临床

Objective: To understand the effect of hyperthermic intraperitoneal chemotherapy (HIPEC) on prognosis of patients with locally advanced gastric cancer, this study retrospectively analyzed the clinical and pathological data of patients undergoing surgery combined with HIPEC and those undergoing surgery alone. Methods: We retrospectively analyzed 80 stage IIIb gastric cancer patients who underwent HIPEC and 90 stage IIIb gastric cancer patients who underwent surgery alone at Tianjin Medical University Cancer Institute and Hospital between January 2009 and January 2014. These patients were divided into the HIPEC group (study group) and the surgery group (control group). The study and control groups included 24 and 26 signet ring cell carcinoma patients and 56 and 64 non-signet ring cell carcinoma patients, respectively. The study and control groups included 12 and 15 Borrmann type I cases, 28 and 30 Borrmann type Ⅱ cases, 23 and 26 Borrmann type III cases, and 17 and 19 Borrmann type cases, respectively. Four weeks after surgery, the two groups were treated with chemotherapy using the S-1 and oxaliplatin (SOX) regimen for 8 courses. This study analyzed and compared the survival of patients with gastric cancer of different pathological types and Borrmann's classifications. The surgical complications of the two groups were retrospectively analyzed. Results: The 5-year survival rates of the study group and the control group were 36.25% and 28.89%, respectively, and the difference was statistically significant (P0.05). The 5-year survival rates between Borrmann type I and typeⅡ patients in the study and control groups were not significantly different (41.67% vs. 40.00%, 35.71% vs. 33.33%, respectively, P>0.05). There was a statistically significant difference in the 5-year survival rates between Borrmann type III and type patients in the study and control groups (39.13% vs. 26.92%, 29.41% vs. 15.79%, respectively, P0.05). Conclusions: Surgery combined with HIPEC is safe and improves the 5-year survival rate of patients with advanced gastric cancer classified as signet ring cell carcinoma, Borrmann type III, and Borrmann type .

Selection strategy for complete cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy among patients with gastric cancer with peritoneal metastasis / 中国肿瘤临床

Objective: To construct a predictive model to assess the completeness of cytoreduction (CC) and help guiding selection for cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CRS+HIPEC) in patients with gastric cancer with peritoneal metastasis (GCPM). Methods: GCPM patients treated with CRS+HIPEC at Beijing Shijitan Hospital were enrolled in this study. The major clinicopathologic and therapeutic characteristics were compared between those with complete CRS (CCRS) and incomplete CRS (ICRS). A nomogram based on a Logistic regression model was constructed for predicting the risk of ICRS. The nomogram was evaluated using area under receiver operating characteristic curve (AUC) and validated using the bootstrap resampling method. The probability of CCRS was predicted using the nomogram. Results: Among the included 125 patients with GCPM, 52 had CC0 cytoreduction and 73 had CC1-3 cytoreduction. The median overall survival (mOS) was 30.0 (95% CI: 16.8-43.3) months in the CC0 group, which was significantly longer than the mOS of 7.3 (95% CI: 5.8-8.8) months in the CC1-3 group (P<0.001). As there were no significant differences in OS among the CC1, CC2, and CC3 groups, CC0 patients were included in the CCRS group and CC1-3 patients were included in the ICRS group. Multivariate Logistic regression demonstrated that the time of peritoneal metastasis development (OR=14, 95% CI: 2.0-97.9, P= 0.008), preoperative tumor markers (TM) (OR=6.5, 95% CI: 2.1-37.8, P=0.037), and peritoneal cancer index (PCI) (OR=1.5, 95% CI: 1.3-1.8, P<0.001) were independent predictive factors for ICRS. The AUC of the nomogram was 0.985. Internal validation displayed good accuracy and consistency between the predictions and the actual observations. The cutoffs of PCI, with the probability of CCRS set at ≥ 50%, were ≤16, ≤12, ≤10, and ≤5 for synchronous GCPM with normal TM, synchronous GCPM with abnormal TM, metachronous GCPM with normal TM, and metachronous GCPM with abnormal TM, respectively. Conclusions: Complete CRS+HIPEC improves the survival of some patients with GCPM. A selection strategy based on PCI combined with the time of peritoneal metastasis development and TM may be a practical way for selecting patients with GCPM eligible for CCRS.

Progress on chemotherapy for peritoneal carcinomatosis / 中国肿瘤临床

Peritoneal carcinomatosis is obtaining extensive attention because of its late detection and poor prognosis. Lately, cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are widely used for the treatment of this condition and could be effective in some carefully selected patients. Different chemotherapies are combined with CRS or HIPEC, and different drug administration routes are used, such as intraperitoneal or pressurized intraperitoneal aerosol chemotherapy. Furthermore, the results of many clinical trials differed among patients with different types of cancer. Herein, we reviewed recent studies in patients with gastric, colon, and ovarian cancer to evaluate the progress of chemotherapy for peritoneal carcinomatosis.

Advances in treatment of peritoneal metastasis from colorectal cancer / 中国肿瘤临床

Peritoneum is the third common metastatic site of colorectal cancer (CRC) following liver and lung. CRC peritoneal metastasis (PM) has been reckoned as an advanced disease with dismal prognosis. With the development of modern chemotherapeutic modalities, the prognosis of patients with metastatic CRC has been dramatically improved, yet patients with CRC PM achieved few survival benefits. It is the emergence and combination of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy that prolong the survival of PM cases. What's more, novel treatments, pressurized intraperitoneal aerosol chemotherapy, and intraperitoneal MOC31PE immunotoxin treatment, for instance, have been under investigation and preliminary results are promising. We aim to comprehensively review the literature focusing on the clinical treatment of PM.

Diagnosis and treatment of pseudomyxoma peritonei of extra-appendiceal origin:analysis of 34 cases / 中国肿瘤临床

Objective: To investigate the clinicopathological features and treatment strategy of pseudomyxoma peritonei (PMP) of ex-tra-appendiceal origin. Methods: Clinical data of 34 patients diagnosed with PMP of extra-appendiceal origin who were treated by cy-toreduction surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in the Aerospace Center Hospital from September 2011 to February 2019 were retrospectively analyzed. Clinical and imaging features were summarized and the Log-rank test was used for survival analysis. Results: The clinical manifestations of the 34 patients with PMP of extra-appendiceal origin were mainly abdomi-nal distension (58.8%) and abdominal pelvic mass (52.9%), which are very similar to those of appendiceal PMP. The incidence of main complications after CRS and HIPEC was 14.7%. During the follow-up period of a median of 12 months (range 1-46 months), 9 patients died, and the 1-and 3-year overall survival rates were 69.6% and 53.5%, respectively. In the univariate analysis, peritoneal cancer in-dex (PCI)>20, no HIPEC, and non-radical surgery were significant risk factors for poor prognosis, while gender, age, origin, and patho-logical type did not show significant correlations. Conclusions: The clinical features of PMP of extra-appendiceal origin are not differ-ent to those of PMP originating from the appendix. It is difficult to ascertain the primary lesion before the operation; however, regard-less of the origin, CRS combined with HIPEC is always a safe and effective treatment choice.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in gastrointestinal cancers: fad or standard of care?

Peritoneal metastases (PM) are the common endpoint for patients with advanced gastrointestinal cancers. PM from these cancers are often managed in a similar fashion to other sites of systemic metastases, but the following must be taken into consideration. (a) PM do not respond to systemic chemotherapy in the same fashion as liver and lung metastases. (b) PM cause local problems, resulting in disruption of chemotherapy. (c) Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) actually work for PM. (d) PM are not easily detected on imaging modalities. There has been mounting evidence of the effectiveness of CRS-HIPEC at prolonging survival in selected patients with colorectal and gastric PM, but there remains a reluctance to explore this treatment modality. This is likely because of the perceived morbidity and mortality. An effective management strategy employing CRS-HIPEC for selected patients with gastrointestinal PM can only be achieved if a concerted effort is made to understand this disease and address the concerns regarding this treatment.

Carcinomatose peritoneal em câncer gástrico: diagnóstico, manejo e conduta / Peritoneal carcinomatosis in gastric cancer: diagnosis, management and conduct

Introdução: O câncer gástrico (CG) é a segunda principal causa de morte relacionada a câncer no mundo. A incidência global e os tipos histológicos estão mudando. A incidência dos tumores da transição esofagogástrica e o adenocarcinoma da cárdia estão aumentando, embora tenha havido uma redução da incidência de CG distal desde a década de 1970. Grande parte dos pacientes apresenta-se com doença localmente avançada ou metastática. A carcinomatose peritoneal (CP) de origem gástrica tem um prognóstico desfavorável e uma sobrevida curta devido à ausência de modalidades terapêuticas efetivas. Métodos: Foi realizada uma revisão da literatura nas bases de busca PubMed, Scielo e Embase, sendo selecionados os artigos mais relevantes a fim de organizar uma revisão concisa e atualizada do assunto. Resultados: O prognóstico do CG depende de estágio e localização. A disseminação metastática pode ser hematogênica ou por disseminação para a cavidade peritoneal. Estudos recentes mostram que a disseminação peritoneal é mais frequente do que metástases hematogênicas. Apesar de ser a causa de 60% das mortes no câncer gástrico, a metástase peritoneal pode ser considerada uma doença local, e uma abordagem multimodal pode melhorar o prognóstico, mesmo se tratando de uma doença avançada. Na falta de tratamento curativo, a quimioterapia sistêmica pode ser considerada uma opção, ainda que seja de valor limitado para pacientes com CG e CP. Atualmente, a quimioterapia intraperitoneal hipertérmica (HIPEC) está sendo muito estudada e debatida no tratamento das doenças da superfície peritoneal. Conclusão: Dado o mau prognóstico, o custo-benefício dos regimes quimioterápicos atuais permanece questionável. Pesquisas adicionais devem ser realizadas para otimizar terapia.

Introduction: Gastric cancer (GC) is the second leading cause of cancer-related death in the world. The overall incidence and histological subtypes is changing. The incidence of esophagogastric transitional tumor and cardia adenocarcinoma is increasing, although there has been a reduction in the incidence of distal GC since the 1970s. Majority of patients present with locally advanced or metastatic disease. Peritoneal carcinomatosis (PC) of gastric origin has an unfavorable prognosis and short survival due to the lack of effective therapeutic modalities. Methods: A review of the literature was carried out in PubMed, Scielo and Embase, and the most relevant articles were selected in order to organize a concise and updated review of the subject. Results: The prognosis of GC depends on stage and location. Metastatic dissemination may be hematogenic or disseminated into the peritoneal cavity. Recent studies show that peritoneal dissemination is more frequent than hematogenous metastases. Although it is the cause of 60% of deaths in gastric cancer, peritoneal metastasis can be considered a local disease, and a multimodal approach may improve the prognosis, even if it is a terminal disease. In the absence of curative treatment, systemic chemotherapy may be considered an option, although it is of limited value for patients with GC and PC. Currently, hyperthermic intraperitoneal chemotherapy (HIPEC) is the most widely accepted treatment for peritoneal diseases. Conclusion: Given the poor prognosis, the cost-effectiveness of current chemotherapy regimens remains questionable. Additional research should be done to optimize therapy.

Citorreduccion con quimioterapia / Citorreduction with chemotherapy

Hasta no hace mucho tiempo el cancer en la superficio peritoneal estaba asociado con un pesimo pronostico. Esta forma extrema de presentacion de algunos tumores de origen peritoneal, digestivo o ginecologico, que se diseminan por vía transcelomica, tenía terapias solamente paliativas. En la actualidad algunos pacientes con diseminacion peritoneal del cancer pueden beneficiarse de un tratamiento que asocia cirugia de citorreduccion y quimoterapia intraperitoneal para brindar una alternativa terapeutica que puede mejorar el tiempo de supervivencia y la calidad de vida de las personas. En este trabajo intento demostrar el desarrollo y propositos de una cirugía desafiante en lo que respecta a nuestro rol como instrumentadores, la citorreducción. La misma consiste en la reseccion de toda enfermedad macroscopica, la que es visible al ojo humano sin ayuda de microscopio y luego la deliminación de la enfermedad microscopica mediante la utilización intraperitoneal de farmacos quimioterapicos a alta temperatura. En la actualidad el Sanatorio Allende es el unico centro de salud de la provincia de Cordoba y unos pocos en el pais, que tiene un programa de estas caracteristicas.

Progression of peritoneal adenomucinosis to the scrotum: a rare occurrence treated with cytoreductive surgery and hyperthermic chemoperfusion of the scrotum in two patients / Progresión de adenomucinosis peritoneal en el escroto de dos pacientes y tratamiento con cirugía citorreductora y quimioperfusión hipertérmica

Introduction: Disseminated Peritoneal Adenomucinosis (DPAM) is an infrequent presentation of appendiceal cancer. Infrequently, umbilical or inguinal hernias could be the first clinical manifestation of this condition; DPAM extension to the scrotum may be anatomically viable. Treatment with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is the standard of treatment for DPAM. We hypothesize that these same treatment principles, consisting of CRS with hyperthermic chemoperfusion of the scrotum (HCS), could be applied to the scrotal dissemination of DPAM. Methods: We reviewed our Institution's prospective cancer database and identified two cases of DPAM with extension to the scrotum. Their medical records were examined, and close follow-up was performed. Tumor histopathology and cytoreduction scores were evaluated. Tumor progression was monitored on follow-up by physical examination, tumor markers (CEA, CA 125, CA 19.9) and abdomino-pelvic CT scan. Results: Two patients who previously had CRS/ HIPEC for DPAM were successfully treated with HSC. Both patients are alive and free of disease at 88 and 57 months following initial CRS/HIPEC, and 50 and 32 months following CRS/HCS, respectively. Conclusion: Increased awareness by surgeons to the coexistence of inguinal hernia with peritoneal neoplasm and the need for a surgical repair is raised. CRS/HCS may be employed to treat patients with DPAM extension to the scrotum. Successful outcome is dependent on complete cytoreduction of metastatic tumor.

Introducción: La Adenomucinosis Peritoneal Diseminada (DPAM, por el término en inglés) es una presentación no frecuente del cáncer de apéndice. Infrecuentemente, las hernias umbilicales o inguinales pueden ser la primera manifestación clínica de esta condición; la extensión al escroto puede ser anatómicamente viable. La cirugía citoreductiva (CRS, por el término en inglés) con quimioterapia hipertérmica intraperitoneal (HIPEC, por el término en inglés) es el tratamiento estándar para DPAM. Nuestra hipótesis es que los mismos principios terapéuticos, consistentes en CRS con quimioterapia hipertérmica del escroto (HCS, por el término en inglés), pueden ser aplicados para DPAM con extensión al escroto. Métodos: Revisamos una base de datos prospectiva en nuestra Institución donde se identificaron dos casos de DPAM con extensión al escroto. Se examinaron sus historias clínicas, y se realizaron controles cercanos. La histopatología tumoral y la citoreducción fueron evaluados. La progresión tumoral fue monitorizada en los controles mediante examen físico, marcadores tumorales (CEA, CA 125, CA 19.9) y TAC abdomino-pélvico. Resultados: Dos pacientes a quienes se les practicó previamente CRS/HIPEC por DPAM fueron exitosamente tratados con CRS/HSC. Ambos pacientes se encuentran vivos y sin evidencia de enfermedad 88 y 57 meses después de la CRS/HIPEC inicial y a 50 y 32 meses post CRS/HCS, respectivamente. Conclusión: La precaución de los cirujanos sobre la coexistencia de hernias inguinales con neoplasias peritoneales y la necesidad de reparo quirúrgico debe ser incrementada. La CRS/HCS puede ser empleada en el tratamiento a pacientes con DPAM con extensión al escroto. Los resultados clínicos son dependientes de una citoreducción completa del tumor metastásico.