Search

Background: A rare appendiceal malignancy is characterized by both glandular and neuroendocrine histology. It often presents with dissemination of the perforated tumor to peritoneal surfaces. Current treatments involve systemic chemotherapy, cytoreductive surgery and perioperative intraperitoneal chemotherapy., Methods: The impact of clinical, histological and treatment-related characteristics on survival were evaluated and subjected to univariate statistical analyses. All patients had stage IV disease and were treated by a uniform treatment strategy. Survival was determined from onset of disease until death or most recent follow-up., Results: There were 47 patients available for study of whom 17 were male. Median age was 48 with a range of 27-65. None or a single symptom vs. 2 or more symptoms had a significant effect on survival. Median survival of the entire cohort was 45 months and 34.88% and 8.72% of patients survived 5 and 10 years, respectively. The use of neoadjuvant chemotherapy showed no impact on survival. Patients with a peritoneal cancer index (PCI) of 0-20 as compared to PCI > 20 survived longer (p = 0.012). The survival of patients able to have a complete resection as compared to an incomplete resection of disease was significant (p = 0.0087). The type of perioperative chemotherapy did not alter survival., Conclusions: These data show that patients with a lesser extent of disease with a complete cytoreduction had an improved prognosis. No benefit from systemic or perioperative regional chemotherapy was apparent. With long-term follow-up, patients with the combined glandular and neuroendocrine histology exhibiting peritoneal metastases have a guarded prognosis., Competing Interests: Declaration of competing interest For our manuscript entitled, “Appendiceal Tumors with Glandular and Neuroendocrine Features Exhibiting Peritoneal Metastases - Critical Evaluation of Outcome Following Cytoreductive Surgery with Perioperative Chemotherapy”, we do not have any disclosures to declare., (Copyright © 2021 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Importance: Studies on the prognostic role of hyperthermic intraperitoneal chemotherapy (HIPEC) in pseudomyxoma peritonei (PMP) are currently not available., Objectives: To evaluate outcomes after cytoreductive surgery (CRS) and HIPEC compared with CRS alone in patients with PMP., Design, Setting, and Participants: This cohort study analyzed data from the Peritoneal Surface Oncology Group International (PSOGI) registry, including 1924 patients with histologically confirmed PMP due to an appendiceal mucinous neoplasm. Eligible patients were treated with CRS with or without HIPEC from February 1, 1993, to December 31, 2017, and had complete information on the main prognostic factors and intraperitoneal treatments. Inverse probability treatment weights based on the propensity score for HIPEC treatment containing the main prognostic factors were applied to all models to balance comparisons between the CRS-HIPEC vs CRS-alone groups in the entire series and in the following subsets: optimal cytoreduction, suboptimal cytoreduction, high- and low-grade histologic findings, and different HIPEC drug regimens. Data were analyzed from March 1 to June 1, 2018., Interventions: HIPEC including oxaliplatin plus combined fluorouracil-leucovorin, cisplatin plus mitomycin, mitomycin, and other oxaliplatin-based regimens., Main Outcomes and Measures: Overall survival, severe morbidity (determined using the National Cancer Institute Common Terminology for Adverse Events, version 3.0), return to operating room, and 30- and 90-day mortality. Differences in overall survival were compared using weighted Kaplan-Meier curves, log-rank tests, and Cox proportional hazards multivariable models. A sensitivity analysis was based on the E-value from the results of the main Cox proportional hazards model. Differences in surgical outcomes were compared using weighted multivariable logistic models., Results: Of the 1924 patients included in the analysis (997 [51.8%] men; median age, 56 [interquartile range extremes (IQRE), 45-65] years), 376 were in the CRS-alone group and 1548 in the CRS-HIPEC group. Patients with CRS alone were older (median age, 60 [IQRE, 48-70] vs 54 [IQRE, 44-63] years), had less lymph node involvement (14 [3.7%] vs 119 [7.7%]), received more preoperative systemic chemotherapy (198 [52.7%] vs 529 [34.2%]), and had higher proportions of high-grade disease (179 [47.6%] vs 492 [31.8%]) and suboptimal cytoreduction residual disease (grade 3, 175 [46.5%] vs 117 [7.6%]). HIPEC was not associated with a higher risk of worse surgical outcomes except with mitomycin, with higher odds of morbidity (1.99; 95% CI, 1.25-3.19; P = .004). HIPEC was associated with a significantly better overall survival in all subsets (adjusted hazard ratios [HRs], 0.60-0.68, with 95% CIs not crossing 1.00). The weighted 5-year overall survival was 57.8% (95% CI, 50.8%-65.7%) vs 46.2% (95% CI, 40.3%-52.8%) for CRS-HIPEC and CRS alone, respectively (weighted HR, 0.65; 95% CI, 0.50-0.83; P < .001; E-value, 2.03). Such prognostic advantage was associated with oxaliplatin plus fluorouracil-leucovorin (HR, 0.42; 95% CI, 0.19-0.93; P = .03) and cisplatin plus mitomycin (HR, 0.57; 95% CI, 0.42-0.78; P = .001) schedules., Conclusions and Relevance: In this cohort study, HIPEC was associated with better overall survival when performed after CRS in PMP, generally without adverse effects on surgical outcomes.

Background: A unique time in which to effectively treat an intraabdominal malignancy is the time at which the surgeon attempts complete removal of the malignant process. Although surgery is effective for visible disease, micrometastases or multiple small cancer nodules are not amenable to resection. Alternative interventions to deal with residual disease disseminated on peritoneal surfaces are needed., Materials and Methods: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) can be combined with early postoperative intraperitoneal chemotherapy (EPIC) in order to maximally treat gross disease within the abdomen and pelvis and also the minimal residual disease that exists in many patients after resection. The third component of this treatment for ovarian malignancy was EPIC paclitaxel in this study. The clinical features, pharmacologic assessments, and survival were determined in ovarian cancer patients in whom EPIC was added to the perioperative treatment plan., Results: Patients with high grade serous ovarian cancer underwent CRS, HIPEC with cisplatin/doxorubicin, and EPIC paclitaxel. These treatments combined as a single intervention were studied in 10 patients. The median number of peritonectomy procedures was 1, the median number of visceral resections was 5, and the median time required in the operating room was 8 h. Two patients had a class 3 adverse event. The median survival of patients was 50 months. Pharmacokinetic analysis of the intraperitoneal paclitaxel showed 252 ± 153 times exposure of peritoneal surfaces as compared to intravenous exposure when the drug was instilled into the peritoneal space., Conclusions: EPIC paclitaxel was successfully combined with CRS and HIPEC in 10 patients with ovarian cancer. The treatment was tolerated approximately the same as other major cytoreductive surgical procedures for ovarian cancer or other malignancies. Survival of these ovarian cancer patients seemed unusually prolonged as compared to other patients with stage 3b or recurrent disease. In this pilot study CRS, HIPEC and EPIC were safe and effective., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: The multi-institutional registry in this study evaluated the outcome after cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with peritoneal metastases (PM) from small bowel adenocarcinoma (SBA)., Methods: A multi-institutional data registry including 152 patients with PM from SBA was established. The primary end point was overall survival (OS) after CRS plus HIPEC., Results: Between 1989 and 2016, 152 patients from 21 institutions received a treatment of CRS plus HIPEC. The median follow-up period was 20 months (range 1-100 months). Of the 152 patients, 70 (46.1%) were women with a median age of 54 years. The median peritoneal cancer index (PCI) was 10 (mean 12; range 1-33). Completeness of cytoreduction (CCR) 0 or 1 was achieved for 134 patients (88.2%). After CRS and HIPEC, the median OS was 32 months (range 1-100 months), with survival rates of 83.2% at 1 year, 46.4% at 3 years, and 30.8% at 5 years. The median disease-free survival after CCR 0/1 was 14 months (range 1-100 months). The treatment-related mortality rate was 2%, and 29 patients (19.1%) experienced grades 3 or 4 operative complications. The period between detection of PM and CRS plus HIPEC was 6 months or less (P = 0.008), and multivariate analysis identified absence of lymph node metastasis (P = 0.037), well-differentiated tumor (P = 0.028), and PCI of 15 or lower (P = 0.003) as independently associated with improved OS., Conclusion: The combined treatment strategy of CRS plus HIPEC achieved prolonged survival for selected patients who had PM from SBA with acceptable morbidity and mortality.

Purpose: Peritoneal carcinomatosis or pseudomyxoma peritonei from urachus is a rare form of presentation, often diagnosed at an advanced state of tumor burden. Because of its rarity, little is known about its natural history, prognosis, or optimal treatment. We searched a large international multicenter database of peritoneal surface disease to identify cases of peritoneal carcinomatosis of urachus that were treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) at expert centers. The aim is to improve knowledge and understanding of the disease and standardize its treatment., Methods: A prospective multicenter international database was retrospectively searched to identify all patients with urachus tumor and peritoneal metastases who underwent CRS and HIPEC through the Peritoneal Surface Oncology Group International (PSOGI). Postoperative complications, long-term results, and principal prognostic factors were analyzed., Results: The analysis included 36 patients. After median follow-up of 48 months, median overall survival (OS) was 58.5 months. Three- and 5-year OS was 55.4 and 46.2%, respectively. Patients who underwent complete macroscopic CRS had significantly better survival than those treated with incomplete CRS, with median OS not achieved and of 20.1 months, respectively [95% confidence interval (CI) 4.4-30.5, p < 0.001]. There were no postoperative deaths, and 37.9% of patients had major complications., Conclusion: CRS and HIPEC may increase long-term survival in selected patients with peritoneal metastases of urachus origin, especially when complete CRS is achieved.

Purpose: Malignant peritoneal mesothelioma (MPM) is a rare disease with about 300 new cases per year in the USA. Its natural history is described as local progression within the peritoneal space in the absence of liver metastases or systemic disease., Methods: Cytoreductive surgery (CRS) is a series of peritonectomy procedures and visceral resections with a goal of complete removal of all visible disease from the abdomen and pelvis. Over 20 years, three protocols investigating increasing efficacy of additional chemotherapy treatments added to CRS have been initiated. Initially, hyperthermic perioperative chemotherapy (HIPEC) with doxorubicin and cisplatin was used in the operating room. Then, early postoperative intraperitoneal chemotherapy (EPIC) with paclitaxel was added for the first 5 days after CRS. The third protocol employed HIPEC, then EPIC, and then long-term intraperitoneal (IP) paclitaxel or IP pemetrexed plus intravenous (IV) cisplatin as a adjuvant normothermic intraperitoneal chemotherapy (NIPEC)., Result: The 5-year survival of 42 patients treated with CRS and HIPEC was 44%, for 58 patients treated with EPIC and HIPEC was 52% and 29 patients who received HIPEC, EPIC, and NIPEC was 75% (p = 0.0374). Prognostic variables of age, gender, treatment administered, peritoneal cancer index (PCI) and completeness of cytoreduction were significant by univariate analysis and treatments administered and completeness of cytoreduction significant by multivariate analysis., Conclusions: Long-term regional chemotherapy was associated with improved survival in patients with MPM. In this rare disease, additional phase 2 investigations are suggested., (Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: Pseudomyxoma peritonei is a disease that results from a perforated mucinous neoplasm of the appendix so that mucinous ascites and mucin-producing tumor cells are widely disseminated in a characteristic pattern throughout the abdomen and pelvis. The intraabdominal mucus can accumulate in the inguinal canal and by physical examination be indistinguishable from the usual inguinal hernia., Methods: A database of patients with pseudomyxoma peritonei was used to identify patients who had an inguinal hernia prior to or at the time of cytoreductive surgery (CRS) and perioperative hyperthermic chemotherapy (HIPEC). At the time of CRS, care was taken in all patients to remove the peritoneal lining of the inguinal canal. Patients who had the inguinal hernia repaired prior to definitive treatment with CRS and HIPEC had all tissue and mesh associated with prior herniorrhaphy resected., Results: In 178 pseudomyxoma peritonei patients, 17 had a new onset or previously repaired inguinal hernia that required extraction of mucus and mucinous tumor from the hernia site. No repair of the open inguinal canal was attempted at the time of CRS. No recurrent inguinal hernias were recorded and no patients required an inguinal incision at a later time to resect progressive disease within the inguinal canal., Conclusions: Inguinal hernias caused by mucinous ascites and tumor were definitively treated by cytoreductive surgery plus HIPEC. Extraction of tumor and peritoneum from the inguinal canal facilitates fibrous closure of the hernia defect so that hernia recurrence was not observed., (Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: Peritoneal metastasis of colonic origin is associated with a poor prognosis. This study aimed to analyze the clinicopathologic characteristics and prognostic predictors of survival in a cohort of patients treated with cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy (POIC) during two decades., Methods: A retrospective study analyzed a prospectively maintained database for all patients treated for peritoneal metastasis of a colonic origin (PCC) from January 1990 to April 2015., Results: The 318 patients in our study comprised 171 men (53.8%) and 147 women (46.2%). The mean age of the patients at presentation was 50.6 years, (range 18-86 years). Overall survival was 42.5%, median survival and follow-up time was 21.5 and 15.0 months respectively. The 3 and 5 years survival rates were respectively 35 and 25%. The median survival time was 20.6 months for the men and 23.1 months for the women (p = 0.14). The mean intraoperative peritoneal carcinomatosis index (PCI) was 15.2. The patients who had a completeness of cytoreduction (CC) score of 0 or 1 (no residual disease <0.25 mm) had a median survival time of 36.6 months compared with 18.3 months for the patients with a CC-2 score and 7.6 months for the patients with a CC-3 score (p < 0.000). The significant independent predictors of survival in the multivariate analysis were the CC score and elevated tumor makers CA153 and CA125., Conclusion: For patients with a limited extent of peritoneal metastases, CC is the most important prognostic variable for improved survival of colon cancer patients with peritoneal metastases.

Recently, Peritoneal Surface Oncology Group International (PSOGI) developed a novel comprehensive treatment consisting of cytoreductive surgery (CRS) and perioperative chemotherapy (POC) for the treatment of peritoneal metastases (PM) from gastric cancer with curative intent. This article reviews the results of this treatment and verifies its indication. In this strategy, peritoneal cancer index (PCI) is determined by laparoscopy, and a peritoneal port is placed. Neoadjuvant bidirectional intraperitoneal/systemic chemotherapy (NIPS) is performed for 3 cycles, and then laparotomy is performed. Cytoreductive surgery with peritonectomy procedures and hyperthermic intraperitoneal chemoperfusion (HIPEC) are performed. Multivariate analyses showed that completeness of cytoreduction, pathologic response to NIPS and PCI level and cytologic status after NIPS, as independent prognostic factors. PCI less than cut-off level after NIPS, negative cytology after NIPS, and positive response to NIPS were identified as the indications for comprehensive treatment. Patients who hold these criteria should be considered as the candidates for CRS and HIPEC., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Despite advances in surgical oncology, most patients with primary ovarian cancer develop a recurrence that is associated with a poor prognosis. The aim of this review was to establish the impact of Heated IntraPEritoneal Chemotherapy (HIPEC) in the overall survival of patients with recurrent ovarian cancer., Methods: A search of PubMed/MEDLINE databases was performed in February 2015 using the terms "recurrent ovarian cancer," "cytoreductive surgery/cytoreduction," and "heated/hyperthermic intraperitoneal chemotherapy." Only English articles with available abstracts assessing the impact of HIPEC in patients with recurrent ovarian cancer were examined. The primary outcome measure was overall survival, whereas secondary outcomes included disease-free survival and HIPEC-related morbidity., Results: Sixteen studies with 1168 patients were analyzed. Most studies were Level IV, with 4 studies graded as Level III and 1 Level II. Cisplatin was the main chemotherapeutic agent used, but variations were observed in the actual technique, temperature of perfusate, and duration of treatment. In patients undergoing cytoreductive surgery and HIPEC, the overall survival ranged between 26.7 and 35 months, with disease-free survival varying between 8.5 and 48 months. Heated IntraPEritoneal Chemotherapy seems to confer survival benefits to patients with recurrent disease, with a randomized controlled study reporting that the overall survival is doubled when cytoreductive surgery is compared with cytoreductive surgery and chemotherapy (13. 4 vs 26.7 months). Heated IntraPEritoneal Chemotherapy-related morbidity ranged between 13.6% and 100%, but it was mainly minor and not significantly different from that experienced by patients who only underwent cytoreduction., Conclusions: Cytoreductive surgery and HIPEC seem to be associated with promising results in patients with recurrent ovarian cancer. Large international prospective studies are required to further quantify the true efficacy of HIPEC and identify the optimal treatment protocol for a maximum survival benefit.

Background: Tumors that show a signet ring or adenocarcinoid histomorphology have been associated with a poor prognosis. This study aimed to analyze the clinicopathologic and prognostic features in patients with peritoneal metastasis from mucinous adenocarcinoma (PMCA), adenocarcinoma with signet ring cell (PMCA-S), or adenocarcinoid (PMCA-A) of the appendix treated with cytoreductive surgery and perioperative intraperitoneal chemotherapy., Methods: Retrospective analysis of a prospectively maintained database for all patients treated for appendiceal adenocarcinoma from 1989 to 2012 was performed., Results: The study cohort consisted of 494 patients including 361 patients with PMCA (73.1 %), 80 patients with PMCA-S (16.2 %), and 53 patients with PMCA-A (10.7 %). The patients comprised 273 men (55.3 %) and 221 women (44.7 %) with a mean age at presentation of 50.7 years for the PMCA-S patients, 47.3 years for the PMCA patients, and 47.5 years for the PMCA-A patients (p < 0.03). The 3- and 5-year survival rates were respectively 51 and 38 % for PMCA compared with 30 and 22 % for PMCA-S and 26 and 15 % for PMCA-A. The median survival time was 45.4 months for PMCA compared with 18.9 months for PMCA-S and 26.8 months for PMCA-A (p < 0.000). The groups did not differ significantly in the completeness of cytoreduction achieved, with 53.5 % of the PMCA patients having a CC0/1 compared with 46.2 % of the PMCA-S patients and 41.6 % of the PMCA-A patients (p < 0.20). In the multivariate analysis, the independent predictors of a reduced survival were incompleteness of cytoreduction, histomorphology of PMCA-S or PMCA-A, and distant metastasis., Conclusion: The findings showed that PMCA-S or PMCA-A histomorphology contributes to the poor prognosis associated with peritoneal metastasis from appendiceal adenocarcinoma. The independent predictors for a poor overall survival included incompleteness of cytoreduction, PMCA-S and PMCA-A histomorphology, and distant metastasis.

Background: Pseudomyxoma peritonei (PMP) is a rare locoregional disease characterized by disseminated intraperitoneal mucinous tumors. However, little is known about PMP from urachal neoplasm as a result of its rarity., Methods: A total of 9 patients with PMP of urachal origin were treated by cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) in our institution. All specimens of surgeries were submitted for pathologic examination. Representative slides of tumors and normal urachus were submitted for immunohistochemical staining., Results: Four patients were men; the median age was 48 years (range 27-65 years). Initial radiologic examination of all patients showed a cystic tumor located between posterior aspect of umbilicus and the dome of urinary bladder, with or without leaking mucin. Complete CRS and HIPEC were performed in all patients. Until the latest follow-up, local recurrence occurred in 1 patient. Other 8 patients had a median disease-free survival of 27.5 months. Primary urachal tumors of 9 cases were all mucinous adenocarcinoma. Six patients had low-grade mucinous carcinoma peritonei, and 3 patients had high-grade mucinous carcinoma peritonei. Signet ring cells were noted in 4 patients. All tumor specimens of 9 patients were diffuse positive for CK-20, CDX-2, MUC-2, and MUC-5AC, and were variant positive for CK-7., Conclusions: PMP arising from urachus comes from neoplastic cells with development of intestinal-type mucinous neoplasm. It shares a similar pathophysiology as PMP from appendix. CRS including total urethrectomy, partial cystectomy, and peritonectomy plus HIPEC can be considered as a new option of treatment for PMP originating from urachus.

Background: Diffuse malignant peritoneal mesothelioma (DMPM) is an aggressive disease for which cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been used with remarkable survival benefits. Our aim was to analyze the clinicopathologic characteristics and prognosis of recurrent DMPM managed with iterative CRS and HIPEC., Methods: A retrospective analysis of a prospectively maintained database for all patients treated for DMPM from 1989 to 2012., Results: Of 205 consecutive CRS and HIPEC procedures, 44 (21.5 %) patients underwent an iterative procedure-22 (50.0 %) males versus 22 (50.0 %) females. Mean age at recurrence was 51.5 years. There was no 30-day mortality following an iterative procedure, and the grade III-V morbidity was 2.3 %. The median overall survival of patients undergoing an iterative CRS and HIPEC was 54 months versus 77 months following an initial CRS and HIPEC (p = 0.96). Patients undergoing an iterative surgery had a 3- and 5-year survival of 61 and 46 %, respectively, versus 60 and 52 % following an initial CRS and HIPEC. Amongst the iterative group, the achieved complete cytoreduction (CC) score was 15.9, 18.2, 22.7, and 43.2 % for CC0, CC1, CC2 and CC3, respectively, versus 3.1, 43.5, 28.6 and 24.8 %, respectively, following initial CRS (p = 0.000). Significant predictors of an improved survival in multivariate analysis were an epithelioid subtype, female sex, complete or near CC (CC0 or CC1), HIPEC regimen utilized, absence of postoperative complication, and age at diagnosis., Conclusion: Iterative CRS and HIPEC can be performed safely and appear to have benefits with this group of patients showing an improved median survival.

Background: The learning curves for cytoreductive surgery with intraperitoneal chemotherapy for treatment of pseudomyxoma peritonei (PMP) were explored between international centres/surgeons to identify institutional or other factors that might affect performance., Methods: Data from patients with PMP treated with the combined procedure across 33 international centres between 1993 and 2012 were analysed retrospectively. A risk-adjusted sequential probability ratio test was conducted after defining the target outcome as early oncological failure (disease progression within 2 years of treatment), an acceptable risk for the target outcome (odds ratio) of 2, and type I/II error rates of 5 per cent. The risk prediction model was elaborated and patients were evaluated sequentially for each centre/surgeon. The learning curve was considered to be overcome and proficiency achieved when the odds ratio for early oncological failure became smaller than 2., Results: Rates of optimal cytoreduction, severe postoperative morbidity and early oncological failure were 84·4, 25·7 and 29·0 per cent respectively. The median annual centre volume was 17 (range 6-66) peritoneal malignancies. Only eight of the 33 centres and six of 47 surgeons achieved proficiency after a median of 100 (range 78-284) and 96 (86-284) procedures respectively. The most important institutional factor affecting surgical performance was centre volume., Conclusion: The learning curve is extremely long, so centralization and/or networking of centres is necessary to assure quality of services. One centre for every 10-15 million inhabitants would be ideal., (© 2014 BJS Society Ltd. Published by John Wiley & Sons Ltd.)

The prevention of a disease process has always been superior to the treatment of the same disease throughout the history of medicine and surgery. Local recurrence and peritoneal metastases occur in approximately 8% of colon cancer patients and 25% of rectal cancer patients and should be prevented. Strategies to prevent colon or rectal cancer local recurrence and peritoneal metastases include cytoreductive surgery and hyperthermic perioperative chemotherapy (HIPEC). These strategies can be used at the time of primary colon or rectal cancer resection if the HIPEC is available. At institutions where HIPEC is not available with the treatment of primary malignancy, a proactive second-look surgery is recommended. Several phase II studies strongly support the proactive approach. If peritoneal metastases were treated along with the primary colon resection, 5-year survival was seen and these results were superior to the results of treatment after peritoneal metastases had developed as recurrence. Also, prophylactic HIPEC improved survival with T3/T4 mucinous or signet ring colon cancers. A second-look has been shown to be effective in two published manuscripts. Unpublished data from MedStar Washington Cancer Institute also produced favorable date. Rectal cancer with peritoneal metastases may not be so effectively treated. There are both credits and debits of this proactive approach. Selection factors should be reviewed by the multidisciplinary team for individualized management of patients with or at high risk for peritoneal metastases.

Peritoneal carcinomatosis is a common presentation in patients with metastatic colorectal cancer and the overall survival is poor. In most patients, the disease remains limited to the peritoneal cavity. Therefore, investigators have applied cytoreductive surgery and hyperthermic perioperative chemotherapy as the standard approach for selected patients with peritoneal metastases from colorectal cancer. Overall, very promising long-term survival has been shown in a subset of patients with a limited extent of peritoneal disease before treatment. Whether randomised, controlled trials are needed to definitively show the magnitude of benefit, if any, of this approach is an important question. This Debate outlines the arguments on each side of this issue., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Purpose: Pseudomyxoma peritonei (PMP) originating from an appendiceal mucinous neoplasm remains a biologically heterogeneous disease. The purpose of our study was to evaluate outcome and long-term survival after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) consolidated through an international registry study., Patients and Methods: A retrospective multi-institutional registry was established through collaborative efforts of participating units affiliated with the Peritoneal Surface Oncology Group International., Results: Two thousand two hundred ninety-eight patients from 16 specialized units underwent CRS for PMP. Treatment-related mortality was 2% and major operative complications occurred in 24% of patients. The median survival rate was 196 months (16.3 years) and the median progression-free survival rate was 98 months (8.2 years), with 10- and 15-year survival rates of 63% and 59%, respectively. Multivariate analysis identified prior chemotherapy treatment (P < .001), peritoneal mucinous carcinomatosis (PMCA) histopathologic subtype (P < .001), major postoperative complications (P = .008), high peritoneal cancer index (P = .013), debulking surgery (completeness of cytoreduction [CCR], 2 or 3; P < .001), and not using HIPEC (P = .030) as independent predictors for a poorer progression-free survival. Older age (P = .006), major postoperative complications (P < .001), debulking surgery (CCR 2 or 3; P < .001), prior chemotherapy treatment (P = .001), and PMCA histopathologic subtype (P < .001) were independent predictors of a poorer overall survival., Conclusion: The combined modality strategy for PMP may be performed safely with acceptable morbidity and mortality in a specialized unit setting with 63% of patients surviving beyond 10 years. Minimizing nondefinitive operative and systemic chemotherapy treatments before definitive cytoreduction may facilitate the feasibility and improve the outcome of this therapy to achieve long-term survival. Optimal cytoreduction achieves the best outcomes.

Background: Cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) can improve survival in selected patients with primary or secondary peritoneal malignancies. With the opportunity for long-term survival, questions about the impact of those procedures in fertility in women of childbearing age can be raised., Materials and Methods: An international survey was performed among all teams participating in the International Peritoneal Surface Malignancy Group in order to collect data about pregnancies and their outcome in women having undergone previous CRS with adjuvant HIPEC., Results: There were 7 pregnancies reported after CRS and HIPEC in women treated for peritoneal malignancies. All these women conceived spontaneously, most of them within 2 years after the procedure. They delivered most often by vaginal way after an uneventful pregnancy. Their newborns were healthy, except 1 case of congenital diaphragmatic hernia requiring emergent surgery. There were 2 additional uneventful pregnancies reported after the diagnosis of pseudomyxoma peritonei and before CRS and HIPEC, with the support of the medical team. Another woman having undergone oocytes retrieval and embryo cryopreservation prior to the surgery was mother of twins after the procedure via a surrogate mother., Conclusion: Childbearing after cytoreductive surgery and heated intraperitoneal chemotherapy is possible in women conserving their genital organs after the procedure. The question of fertility should be considered and discussed in women in reproductive age prior to cytoreductive surgery and heated intraperitoneal chemotherapy. Different options could be offered in this setting. Multidisciplinary decision making involving surgical oncologists and fertility specialists is important.

Background: This study was undertaken to measure survival of patients with multicystic peritoneal mesothelioma treated by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy through a multi-institutional collaboration., Methods: A multi-institutional data registry, established by the Peritoneal Surface Oncology Group, was used to identify patients with peritoneal mesothelioma and the subgroup with multicystic tumours, treated by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Outcomes for this subgroup are reported. The primary endpoint was overall survival. A secondary endpoint was the incidence of treatment-related complications., Results: Of 405 patients with peritoneal mesothelioma, 26 (6·4 per cent) had multicystic tumours. There were 20 women and six men with a mean(s.d.) age of 42(12) years. The median peritoneal carcinomatosis index (PCI) was 14 (range 6-39). There was no perioperative mortality. Six patients developed grade III or IV complications. After a median follow-up of 54 (range 5-129) months, all 26 patients were still alive., Conclusion: Multicystic peritoneal mesothelioma appears to be a distinct subtype of peritoneal mesothelioma, where long-term survival may be achieved through cytoreductive surgery and hyperthermic intraperitoneal chemotherapy., (Copyright © 2010 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

Background: A treatment option for patients with peritoneal mucinous carcinomatosis (PMCA) from an appendiceal neoplasm is cytoreductive surgery and perioperative intraperitoneal chemotherapy. Also, these patients are recommended for systemic chemotherapy using an oxaliplatin and 5-fluorouracil (FOLFOX) regimen. A major question concerns the proper timing (neoadjuvant vs. adjuvant) of the systemic chemotherapy., Methods: In January of 2005 a prospective study was initiated to routinely treat patients with peritoneal dissemination of a mucinous adenocarcinoma of the appendix with neoadjuvant chemotherapy using FOLFOX. All patients had a clinical, CT, intraoperative, and histopathological assessment of chemotherapy effects. The study was closed in July of 2009., Results: Thirty-four consecutive patients were available for evaluation. In the clinical evaluation and CT evaluation, 24 (71%) and 22 (65%), respectively, had stable disease on chemotherapy. By intraoperative examination 17 (50%) patients were observed to have progressed. By histopathology seven had a partial response and three patients a complete response (29%)., Conclusions: In these carcinomatosis patients clinical and CT assessment of response to neoadjuvant chemotherapy seldom provided useful data over this short time period. Intraoperative findings indicated progression in 50% of patients. By histopathology, 29% of patients had a response.

Introduction: An analysis of experience of surgical and gynecologic oncologists in the United States with the use of hyperthermic intraperitoneal chemotherapy for women with invasive epithelial ovarian cancer (EOC)., Methods: An Internet-based registry (HYPER-O) collected data from collaborating institutions. Eligibility included women with EOC treated with hyperthermic intraperitoneal chemotherapy. Borderline and nonepithelial cancers were excluded., Results: As of July 1, 2008, 141 women were eligible for analysis treated at the following time points: frontline (n = 26), interval debulking (n = 19), consolidation (n = 12), and recurrence (n = 83). The mean perfusion temperatures were 38.5 to 43.6 degrees C (median, 41.9 degrees C) for inflow and 36.9 to 42.9 degrees C (median, 41 degrees C) for outflow for 30 to 120 minutes. Treatment was with a platinum agent (n = 72), mitomycin (n = 53), or a combination (n = 14). Median follow-up was 18 months (range, 0.3-140.5 months) and median overall survival 30.3 months (95% confidence interval, 23.0-37.6) with 2-, 5-, and 10-year overall survival probabilities of 49.1%, 25.4%, and 14.3%, respectively. Of the 141 patients, 110 (78%) experienced recurrence of ovarian cancer and 87 died, 3 (0.5%) dying within 30 days of surgery. In the multivariable analysis, the factors significant for increased survival were sensitivity to platinum response (P = 0.048), completeness of cytoreduction scores of 1 or 0 (P = 0.025), carboplatin alone or a combination of 2 or more chemotherapy agents used (P = 0.011), and duration of hospital stays of 10 days or less (P = 0.021)., Conclusions: Hyperthermic intraperitoneal chemotherapy is a viable additional treatment option for patients with invasive EOC and may extend life in selected groups. It warrants further study in randomized controlled trials.

Background: Mucinous neoplasms within the abdomen may disseminate by direct extension through the diaphragm to involve the pleural space. Treatment of this condition is by parietal and visceral pleurectomy followed by hyperthermic intrapleural chemotherapy., Case Presentation: In this case report a patient developed persistent right upper lobe interstitial pneumonitis and progressive parenchymal fibrosis following intrapleural chemotherapy treatment with mitomycin C and doxrubicin. The condition persisted until death 28 months later. Death was from progressive intraabdominal disease with intestinal obstruction and sepsis associated with progressive pulmonary parenchymal disease. The right pleural space disease did not recur., Conclusion: This manuscript is the first case report describing interstitial pneumonitis and lung fibrosis following intrapleural chemotherapy. Since pulmonary toxicity from chemotherapy is a dose-dependent phenomenon, dose reduction of intrapleural as compared to intraperitoneal hyperthermic chemotherapy may be necessary.

Background: A successful new treatment for a particular disease may change the natural history of that disease as patients go on to longer survival. The goal of this study was to investigate the porta hepatis as a site of recurrence of appendiceal mucinous neoplasms., Methods: A prospective database on patients with peritoneal dissemination of mucinous appendiceal neoplasms has been maintained for 21 years. In patients with complete cytoreduction, disease progression/recurrence in and around the porta hepatis has been noted as a new manifestation of this disease., Results: In 710 patients treated for mucinous appendiceal cancer with a complete cytoreduction, 140 developed recurrent disease. Seven patients (5%) had disease recurrence in and around the porta hepatis. Four of the seven had biliary obstruction and three had masses within the liver hilum not causing bile duct obstruction. Four of the seven patients were successfully palliated by surgical procedures within the liver and biliary tree. Two patients were successfully palliated using a biliary stent and one patient was not treated., Conclusions: Progression of mucinous neoplasms within the porta hepatis may be related to imperfect cytoreduction technique. Reoperative surgical treatment and biliary stents were beneficial in some of these patients.

Background: The purpose of this systematic review and meta-analysis was to determine the effectiveness and safety of adjuvant intraperitoneal chemotherapy for patients with locally advanced resectable gastric cancer., Methods: Studies eligible for this systematic review included those in which patients with gastric cancer were randomly assigned to receive surgery combined with intraperitoneal chemotherapy versus surgery without intraperitoneal chemotherapy. There were no language restrictions. After independent quality assessment and data extraction, data were pooled for meta-analysis., Results: Thirteen reports of randomized controlled trials (RCTs) were included for quality appraisal and data extraction. Ten reports were judged to be of fair quality and subjected to meta-analysis. A significant improvement in survival was associated with hyperthermic intraoperative intraperitoneal chemotherapy (HIIC) alone (hazard ratio [HR] = 0.60; 95% CI = 0.43 to 0.83; p = 0.002) or HIIC combined with early postoperative intraperitoneal chemotherapy (EPIC) (HR = 0.45; 95% CI = 0.29 to 0.68; p = 0.0002). There was a trend towards survival improvement with normothermic intraoperative intraperitoneal chemotherapy (p = 0.06), but this was not significant with either EPIC alone or delayed postoperative intraperitoneal chemotherapy. Intraperitoneal chemotherapy was also found to be associated with higher risks of intra-abdominal abscess (RR = 2.37; 95% CI = 1.32 to 4.26; p = 0.003) and neutropenia (RR = 4.33; 95% CI = 1.49 to 12.61; p = 0.007)., Conclusions: The present meta-analysis indicates that HIIC with or without EPIC after resection of advanced gastric primary cancer is associated with improved overall survival. However, increased risk of intra-abdominal abscess and neutropenia are also demonstrated.

Background: Although many reports regarding morbidity and mortality of cytoreductive surgery plus perioperative intraperitoneal chemotherapy are available, there are no prospective data on morbidity and mortality limited to patients with diffuse malignant peritoneal mesothelioma (DMPM)., Methods: This prospective morbidity and mortality assessment was performed on 70 consecutive cytoreductive procedures with perioperative intraperitoneal chemotherapy for DMPM. Forty-seven adverse events by eight categories were rated from grades I to IV with increasing severity. Grade I morbidity was self-limiting; grade II required medical treatments; grade III required an invasive intervention; grade IV required returning to the operating room or intensive care management. Risk factors for grades III and IV morbidity were determined., Results: The perioperative mortality rate was 3%. The grades III and IV morbidity rates were 27 and 14%, respectively. Primary colonic anastomosis (P = 0.028), more than four peritonectomy procedures (P = 0.015), duration of the operation of more than 7 h (P = 0.027) were the risk factors for grade IV morbidity. Survival analysis of these 70 patients was provided., Conclusions: The morbidity and mortality results for cytoreductive surgery and perioperative intraperitoneal chemotherapy for patients with DMPM were within the acceptable range for major gastrointestinal surgery. Grade IV morbidity was associated with more extensive cytoreduction.

Background: This study evaluates clinical, radiological and histopathological prognostic indicators for survival of patients undergoing cytoreductive surgery and perioperative intraperitoneal chemotherapy for diffuse malignant peritoneal mesothelioma (DMPM)., Methods: Sixty-two consecutive patients with DMPM underwent cytoreduction and perioperative intraperitoneal chemotherapy at the Washington Cancer Institute. Twenty-six clinical, radiological and histopathological parameters were analyzed in univariate and multivariate analyses using overall survival as an endpoint., Results: The overall survival was 79 months (range 1-143 months), with 1-, 3- and 5-year survival rates of 84%, 58% and 50%, respectively. The following 14 prognostic variables were significant for survival in the univariate analysis: gender (P = .045), peritoneal cancer index (P = .038), completeness of cytoreduction score (P = .010), interpretive CT findings of the small bowel and mesentery (P = .001), mesothelioma cell type (P < .001), mesothelioma nuclear size (P < .001), nuclear/cytoplasmic ratio (P < .001), mitotic count (P < .001), atypical mitosis (P < .001), chromatin pattern (P < .001), cellular necrosis (P < .001), perineural invasion (P = .037), stroma pattern (P < .001) and depth of invasion (P = .014). In the multivariate analysis, the only factor that was independently associated with an improved survival after cytoreduction and perioperative intraperitoneal chemotherapy was mesothelioma nuclear size., Conclusions: Mesothelioma nuclear size was the dominant factor determining overall survival in patients with DMPM. A histopathological staging system based on measurement of the nuclear size was proposed.

Background: Although lymph node and liver metastases are recognized as indications for resection of metastatic disease from colorectal cancer, carcinomatosis has not traditionally been regarded as having surgical treatment options. Reports have suggested that complete surgical removal of carcinomatosis combined with thorough irrigation of the peritoneal cavity with chemotherapy could result in longterm survival in selected patients. Proper selection factors are important because palliative surgery in these patients has not proved beneficial., Study Design: From a database of 156 patients with carcinomatosis from colorectal cancer, a retrospective analysis of data prospectively recorded in 70 patients with complete cytoreduction was performed. Eleven clinical and treatment factors were studied in univariate and multivariable analyses using survival as an end point., Results: By univariate analysis, patients with peritoneal cancer index (PCI) of<20 had a median survival of 41 months compared with 16 months for patients with PCI>20 (p=0.004). The difference in negative versus positive lymph nodes was also significant; differences in survival that were improved but not significant were present for age greater than 30 years, mucinous histology, location within the colon versus rectum, and absence of an adverse factor such as cancer perforation or obstruction present at the time of primary cancer resection. Only PCI<20 versus PCI>20 and lymph node status were significant in the multivariable analysis., Conclusions: Favorable longterm results of complete cytoreduction in patients treated for carcinomatosis are associated with a limited volume of carcinomatosis observed at the time of cytoreduction and in patients with negative lymph nodes at the time of primary operation.

Purpose: The efficacy of cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for patients with peritoneal carcinomatosis from colorectal carcinoma remains to be established., Methods: A systematic review of relevant studies before March 2006 was performed. Two reviewers independently appraised each study using a predetermined protocol. The quality of studies was assessed. Clinical effectiveness was synthesized through a narrative review with full tabulation of results of all included studies., Results: Two randomized controlled trials, one comparative study, one multi-institutional registry study, and 10 most recent case-series studies were evaluated. The level of evidence was low in 13 of the 14 eligible studies. The median survival varied from 13 to 29 months, and 5-year survival rates ranged from 11% to 19%. Patients who received complete cytoreduction benefited most, with median survival varying from 28 to 60 months and 5-year survival ranging from 22% to 49%. The overall morbidity rate varied from 23% to 44%, and the mortality rate ranged from 0% to 12%., Conclusion: The current evidence suggests that cytoreductive surgery combined with perioperative intraperitoneal chemotherapy is associated with an improved survival, as compared with systemic chemotherapy for peritoneal carcinomatosis from colorectal carcinoma.

Aims: To report our experience of neoadjuvant intraperitoneal and systemic chemotherapy (NIPS) for patients having a complete resection of the primary gastric cancer and peritoneal carcinomatosis (PC)., Patients and Methods: Patients with advanced peritoneal dissemination of primary gastric cancer had the placement of a peritoneal port system. For intraperitoneal chemotherapy, 40 mg of docetaxel and 150 mg of carboplatin were introduced in 1000 ml of saline on a weekly basis. Simultaneously, 100 mg/m2 of methotrexate and 600 mg/m2 of 5-fluorouracil were infused via a peripheral vein. A minimum of two cycles and up to six cycles of NIPS were used prior to cancer resection. At surgery a complete removal of the primary gastric cancer and the peritoneal implants by peritonectomy was attempted., Results: Sixty-one patients were enrolled in the study. Thirty-nine had positive intraperitoneal cytology which reverted to negative cytology after treatment in 22. Thirty-eight showed a partial response. Thirty patients came to resection and 14 patients could be made disease-free. Median survival time of all patients was 14.4 months. Patients who received a complete resection had a median survival time of 20.4 months. Grade III/IV toxicities were not found after two courses of NIPS, but did develop in seven patients after more than three courses of NIPS., Conclusion: NIPS can downstage large volume peritoneal dissemination of gastric cancer. When combined with gastrectomy including peritonectomy a complete surgical resection was possible in one-quarter of the patients and resulted in a prolonged survival. This combined intraperitoneal and systemic chemotherapy for PC from gastric cancer is worthy of consideration for phase III clinical investigations.

Aims: In the past, diffuse malignant peritoneal mesothelioma (DMPM) has been regarded as a terminal condition. The length of the survival was dependent upon the aggressive versus indolent biology of the neoplasm, nevertheless cure was not considered as a reasonable expectation and the overall median survival was approximately one year., Methods: A comprehensive literature review and a collection of pertinent data published on DMPM from the Washington Cancer Institute were used to construct this report., Results: Recent publications from Bethesda MD, New York, Milan Italy, Lyon France and Washington DC have shown a remarkable prolongation in the median survival of this group of patients with approximately half the patients alive at 5 years. These prolonged survivors were treated with an intensive local-regional treatment strategy that included cytoreductive surgery (CRS) with peritonectomy and hyperthermic intraoperative intraperitoneal chemotherapy (HIIC) and some patients with early postoperative intraperitoneal chemotherapy (EPIC). As larger numbers of patients have been treated, clinical features by which to select patients most likely to benefit from this approach have been identified. Also, as the experience in the management of patients receiving these treatments has increased, the morbidity and mortality associated with their management is being reduced., Conclusions: A new standard of care involves surgical removal of large disease deposits combined with perioperative intraperitoneal chemotherapy. Knowledgeable management uses selection criteria and incurs low morbidity and mortality.

Aim: To report the use of laparoscopic Intraperitoneal Hyperthermic Chemotherapy (LIPHC) in the treatment of malignant ascites., Methods: From September 2001 to December 2003, 14 patients between the age of 56 and 78years were treated. Ascites was from gastric cancer (5 cases), colorectal cancer (3 cases), ovarian cancer (3 cases), breast cancer (2 cases) and peritoneal mesothelioma (1 case). The LIPHC was carried out at 42 degrees C for 90 min with 1.5% dextrose solution as a carrier. Chemotherapy was cisplatin and doxorubicin or mitomycin depending on the type of primary tumor. The drains were left in situ after surgery and removed when perfuse drainage ceased., Results: Ascites was controlled in all the treated cases. A CT scan performed in follow-up showed a small, clinically undetectable, fluid accumulation in the pelvis of one patient., Conclusions: This method resulted in benefit for those peritoneal carcinomatosis patients with debilitating malignant ascites who were excluded from cytoreductive surgery. Proficiency in laparoscopic staging procedures and experience in the management of carcinomatosis and intraperitoneal hyperthermic chemotherapy (IPHC) are required for the success of the procedure.

Background: Appendiceal mucinous neoplasms present, in most patients, with peritoneal dissemination at the time of initial diagnosis. Patients may have a borderline tumor showing disseminated peritoneal adenomucinosis or an aggressive malignancy identified as peritoneal mucinous adenocarcinoma. Patients with these diagnoses were treated by cytoreductive surgery and perioperative intraperitoneal chemotherapy., Methods: A database was established in 1998 that prospectively evaluated the morbidity and mortality of this group of patients. By using common toxicity grading criteria, 8 categories were scored on a grade of I to V. Grade IV indicated that the adverse event required urgent and definitive intervention: often a return to the operating room or to the surgical intensive care unit. Grade V indicated that the adverse events resulted in the patient's death. Adverse events were tabulated for each cytoreduction performed in these appendiceal malignancy patients., Results: There were 356 procedures in patients taken to the operating room who received cytoreductive surgery with peritonectomy procedures plus heated intraoperative intraperitoneal chemotherapy. Only patients who had this combined treatment at our institution were included in the analysis. The total 30-day or in-hospital mortality was 2.0%. Nineteen percent of procedures were accompanied by at least one grade IV adverse event, and 11.1% of patients returned to the operating room. The most common category of grade IV complications was hematological (28%), followed by gastrointestinal (26%)., Conclusions: The mortality of 2.0% and the overall grade IV morbidity of 19% in these patients may be acceptable in light of modern standards for the management of gastrointestinal cancer.

Background: Peritoneal dissemination of appendiceal malignancy combined with regional lymph node metastasis is an unusual combination of patterns of cancer dissemination., Methods: A database of 501 appendiceal malignancy patients, all with documented peritoneal seeding, was used to identify 25 patients with involvement of the regional lymph nodes. All patients were uniformly treated with cytoreductive surgery plus perioperative intraperitoneal chemotherapy with mitomycin C and 5-fluorouracil. The clinical and pathologic features of the lymph node-positive patients were compared with those of the lymph node-negative patients. The effect of regional lymph node involvement on survival was determined. Within the group of lymph node-positive patients, clinical and pathologic features were tested for their effect on survival., Results: When compared with patients with no apparent lymph node positivity, patients with positive lymph nodes were more likely to have an acute abdomen as the initial presentation (P < .001). The intestinal (nonmucinous) histological type was more common (P < .001), and the disseminated peritoneal adenomucinosis histology was less common (P < .001). Survival with the aggressive treatment strategy used in these patients was not different for lymph node-positive as compared with lymph node-negative patients (P = .15 by univariate and P = .38 by multivariate analysis)., Conclusions: Appendiceal malignancy with dissemination to the lymph nodes has a more acute onset and a more frequent nonmucinous histology. With aggressive treatment strategies, lymph node-positive patients did not show a statistically significantly diminished survival.

Background: Peritoneal surface malignancy can result from full thickness invasion of gastrointestinal cancer through the bowel wall or from dissemination of cancer cells from the trauma of cancer surgery. In the past, this clinical situation was treated only with palliative intent., Methods: An aggressive approach to peritoneal surface malignancy involves peritonectomy procedures, perioperative intraperitoneal chemotherapy and knowledgeable patient selection. The clinical assessments necessary for valid clinical judgements include the cancer histopathology (invasive vs. expansive progression), the preoperative abdominal and pelvic CT, the peritoneal cancer index and the completeness of cytoreduction score. Proper patient selection is mandatory for optimizing the results of treatment., Results: In a series of phase II studies, appendiceal tumors with peritoneal seeding became the paradigm for success with an 85% long-term survival in selected patients. Carcinomatosis from colon cancer had an overall 5-year survival of 50% with selected patients. In all malignancies, early aggressive treatment of minimal peritoneal surface dissemination showed the greatest benefit., Conclusions: Oncologists must accept responsibility for knowledgeable management of peritoneal surface dissemination of cancer because a curative approach has been demonstrated in both phase II studies and phase III studies. All historical controls show 0% long-term survival. Surgical interventions combined with perioperative intraperitoneal chemotherapy in diseases where peritoneal surface spread occurs must be considered a treatment option.

Purpose: The three principal studies dedicated to the natural history of peritoneal carcinomatosis (PC) from colorectal cancer consistently showed median survival ranging between 6 and 8 months. New approaches combining cytoreductive surgery and perioperative intraperitoneal chemotherapy suggest improved survival., Patients and Methods: A retrospective multicenter study was performed to evaluate the international experience with this combined treatment and to identify the principal prognostic indicators. All patients had cytoreductive surgery and perioperative intraperitoneal chemotherapy (intraperitoneal chemohyperthermia and/or immediate postoperative intraperitoneal chemotherapy). PC from appendiceal origin was excluded., Results: The study included 506 patients from 28 institutions operated between May 1987 and December 2002. Their median age was 51 years. The median follow-up was 53 months. The morbidity and mortality rates were 22.9% and 4%, respectively. The overall median survival was 19.2 months. Patients in whom cytoreductive surgery was complete had a median survival of 32.4 months, compared with 8.4 months for patients in whom complete cytoreductive surgery was not possible (P <.001). Positive independent prognostic indicators by multivariate analysis were complete cytoreduction, treatment by a second procedure, limited extent of PC, age less than 65 years, and use of adjuvant chemotherapy. The use of neoadjuvant chemotherapy, lymph node involvement, presence of liver metastasis, and poor histologic differentiation were negative independent prognostic indicators., Conclusion: The therapeutic approach combining cytoreductive surgery with perioperative intraperitoneal chemotherapy achieved long-term survival in a selected group of patients with PC from colorectal origin with acceptable morbidity and mortality. The complete cytoreductive surgery was the most important prognostic indicator.

Rare diseases are often associated with uninformed medical decisions and poorly executed treatments because of inexperience of the physicians. Desmoplastic small round-cell tumor is a rare disease that is a form of peritoneal surface malignancy usually affecting young males, with a mean survival of 29 months. In order to begin to build a more knowledgeable clinical pathway all 7 patients treated at the Washington Hospital Center were studied and compared to patients described in the medical literature. Clinical and pathological data, tumor distribution, cytoreductive surgery, completeness of cytoreduction and survival were recorded and analyzed. The first most common symptoms were pain, increased abdominal girth and palpable abdominal mass in our patients and in the literature review. The overall survival did not improve with cytoreductive surgery plus intraperitoneal chemotherapy (mean survival 32 months); however, 2 long-term survivors who responded to systemic chemotherapy of 55 and 101 months were recorded. The latter may be the longest survivor reported in the literature. No consistent response to chemotherapy was observed in our patients or in any literature review. Complete surgical removal of this malignancy did not correlate with survival in our patients. The absence of improved survival of our aggressively treated patients as compared to the literature was thought to be a consequence of an advanced stage of the disease. A new comprehensive approach that uses complete clearing of cancer by surgery and perioperative systemic and perioperative intraperitoneal chemotherapy as early as is possible in the natural history of the disease emerged as goals for future management.

This article reviews a single institution's experience with 68 patients (21 females, 47 males) prospectively treated over the last 2 decades with an aggressive local-regional approach, combining maximal cytoreductive surgery with heated intraoperative intraperitoneal chemotherapy and early postoperative intraperitoneal chemotherapy. This multimodality treatment has resulted in a median survival of 67 months. Female patients had a significantly better prognosis than males. The other significant predictive factors of survival were: age, diagnosis by incidental findings, tumor extent, pathology, and completeness of cytoreduction.

Gastric cancer disseminates by hematogenous, lymphatic, and transcoelomic routes. For maximal containment of the malignant process, perioperative intraperitoneal chemotherapy is necessary in two groups of patients in whom the primary cancer can be resected. Those patients who have been resected for cure and have a high likelihood of microscopic residual disease require intraperitoneal chemotherapy. This includes all T3 and T4 patients, and patients with N2 nodes present. A series of randomized and nonrandomized clinical studies have established the benefits of perioperative intraperitoneal chemotherapy in this group of patients. Patients with stage IV disease who are able to undergo a palliative resection require these treatments if peritoneal seeding is observed. Systemic chemotherapy is largely ineffective for peritoneal seeding, while intraperitoneal chemotherapy is most likely to produce a response with small volume, surgically debulked carcinomatosis. In addition, intraperitoneal chemotherapy can eliminate the future development of debilitating ascites. Sufficient data are available from the gastric cancer literature to support the use of these combined treatments on a routine basis if the primary cancer is resectable and gastrointestinal function can be reestablished., (Copyright 2003 Wiley-Liss, Inc.)

Despite new developments in multi-modality treatments, complete resection remains as an absolute requirement for cure of gastrointestinal cancer. We have reported benefits from combined treatment with complete cytoreduction and intraperitoneal chemotherapy. This has been achieved with low morbidity and mortality. Success in the surgical management of peritoneal surface malignancy depends on the surgeon's ability to complete complex cytoreductive procedures so that only microscopic residual disease remains. This paper describes the current strategy that the surgical oncologist should pursue in the treatment of patients with peritoneal carcinomatosis, sarcomatosis and mesothelioma. Technical details required for this surgery include patient position, incision and exposure, complete lysis of adhesion, electroevaporative dissection with irrigation and suction to preserve the translucent quality of tissues, peritonectomy procedures, proper positioning of tubes and drains for intraperitoneal chemotherapy, and reconstructive surgery. Understanding the treatment and mastery of surgical skills to manage the peritoneal surface spread of cancer has led to long-term survival of selected patients. Combination of this treatment strategy with proper patient selection has reduced the mortality and morbidity. The success of cytoreductive surgery and perioperative intraperitoneal chemotherapy depends on a long-term dedication to achieve the full potential of a curative outcome. Our unit has continued to achieve good results over two decades as improved results of treatment have evolved., (Copyright Harcourt Publishers Limited.)

Peritoneal carcinomatosis, regardless of primary tumour type, has always been a lethal condition. Recently special treatments using cytoreductive surgery with peritonectomy procedures combined with peri-operative intraperitoneal chemotherapy have resulted in long-term survival. Pseudomyxoma peritonei may be especially appropriate for these aggressive local regional treatments. All patients treated prior to 1999 are presented; patients left with gross residual disease after surgery were not given intraperitoneal chemotherapy, but were later treated with intravenous chemotherapy after cytoreduction. The intraperitoneal chemotherapy was given in the peri-operative period, starting with mitomycin C. For patients whose pathology showed adenomucinosis, intraperitoneal chemotherapy was limited to treatment in the operating theatre with heated mitomycin C. Patients with mucinous adenocarcinoma or pseudomyxoma/adenocarcinoma hybrid had, in addition to mitomycin C, 5 consecutive days of intraperitoneal 5-fluorouracil. A complete cytoreduction was defined as tumour nodules <2.5 mm in diameter remaining after surgery. The histopathology categorized the patients as adenomucinosis, intermediate type, or mucinous carcinomatosis. A prior surgical score was used to estimate the extent of previous surgical procedures. The morbidity of treated patients was 27% and the mortality was 2.7%. In a multivariate analysis, prognostic factors for survival included the completeness of cytoreduction (P<0.0001), the histopathological character of the appendix malignancy (P<0.001) and the extent of previous surgical interventions (P=0.001). Patients with a complete cytoreduction and adenomucinosis by pathology had a 5-year survival of 86%; while hybrid pathology survival at 5 years was 50%. Incomplete cytoreduction had a 5-year survival of 20% and 0% at 10 years. Cytoreductive surgery and peri-operative intraperitoneal chemotherapy is the current standard treatment for selected patients with peritoneal surface spread of appendiceal primary tumours. Similar strategies for other patients with peritoneal surface malignancy such as peritoneal carcinomatosis from colon or gastric cancer, peritoneal sarcomatosis, or peritoneal mesothelioma should be pursued., (Copyright Harcourt Publishers Limited.)

Purpose: The initial dissemination of colon cancer occurs through three routes: the lymphatics, the portal blood, and the peritoneal surfaces. Although lymphatic and hematogenous metastases indicate an aggressive disease process, it is possible that dissemination to peritoneal surfaces may be only superficial contamination of the parietal and visceral peritoneum that may be treatable for cure. Unfortunately, surgery may have an adverse impact on peritoneal surface dissemination. Surgical interventions may convert a superficial process into an invasive condition with a greatly reduced prognosis. This study was conducted to test this hypothesis by the use of data prospectively recorded from patients treated for peritoneal carcinomatosis concomitant with resection of the primary colon cancer or treated for carcinomatosis after disease recurrence prompted referral., Methods: Our first group of patients had definitive treatment of carcinomatosis simultaneous with resection of the primary colon cancer. They had cytoreductive surgery including peritonectomy procedures followed by heated intraoperative intraperitoneal chemotherapy with mitomycin C plus early postoperative intraperitoneal 5-fluorouracil. The comparison group was treated with a colon resection at an outside hospital and then later referred to us with progressive disease for treatment. The major difference between the groups is the timing of the definitive treatment of carcinomatosis. These patients were also studied by use of the completeness of the cytoreduction score and the peritoneal cancer index as prognostic indicators. Survival was the end point for all the analysis., Results: Of 104 patients with peritoneal carcinomatosis from colon or rectal adenocarcinoma, five patients (4.8 percent) had definitive treatment of the peritoneal surface spread of the cancer concomitant with resection of the primary lesion. Median survival for these patients has not been reached and their five-year survival rate is 100 percent. The remainder of the patients (n = 99) were referred for local and regional recurrence after their primary cancer had been removed and there was progression of carcinomatosis. Forty-four patients (42.3 percent) had a complete cytoreduction resulting in a 24-month median survival and a 30 percent five-year survival (P < 0.0001). The other 55 patients (52.9 percent) had an incomplete cytoreduction resulting in a 12-month median survival and a 0 percent five-year survival (P < 0.0001). Patients with a peritoneal cancer index of 10 or less had a 48-month median survival and a 50 percent five-year survival rate. Patients with a peritoneal cancer index between 11 and 20 had a 24-month median survival and a 20 percent five-year survival rate (P < 0.0001). Patients with a peritoneal cancer index of more than 20 had a 12-month median survival and a 0 percent five-year survival (P < 0.0001)., Conclusions: In patients with peritoneal seeding occurring at the time of resection of the primary malignancy, peritonectomy procedures and perioperative intraperitoneal chemotherapy should be performed concomitantly. By use of a quantitative scoring system, the mass of cancer present in the abdomen and pelvis at the time of treatment of carcinomatosis correlated directly with survival. Aggressive treatment of patients with peritoneal carcinomatosis requires consideration in the management of colorectal cancer.

Peritoneal seeding from primary gastric cancer occurs in 10-20% of patients. The diagnosis of this advanced disease is usually not provided by clinical studies prior to abdominal exploration. From the data available in the literature, the surgeon is forced to make an intraoperative judgement concerning the risks and benefits of an aggressive management plan versus supportive care. A strategy has evolved that utilizes peritonectomy and extended gastrectomy to maximally cytoreduce tumor combined with perioperative intraperitoneal chemotherapy. In the current state of the art, the perioperative intraperitoneal chemotherapy is heated and manually distributed to provide uniform treatment to all peritoneal surfaces and the resection site. The pharmacologic parameters have been established and the results of phase II studies are reported. Five-year survival of patients in whom a complete cytoreduction was possible is approximately 10% with a median survival of 12 months. Gastrectomy with peritonectomy to eliminate all visible implants combined with perioperative intraperitoneal chemotherapy should be used in selected patients with primary gastric cancer and carcinomatosis., (Copyright 2000 S. Karger AG, Basel)

Introduction: The purpose of this retrospective report was to evaluate clinical features associated with profound neutropenia in patients with peritoneal carcinomatosis who were treated with heated intraoperative intraperitoneal chemotherapy (HIIC) followed by early postoperative intraperitoneal chemotherapy (EPIC). Common clinical denominators for significant neutropenia were analyzed., Materials and Methods: A retrospective study of all available clinical data of six patients with postoperative neutropenia out of a total of 242 was undertaken. All patients underwent cytoreductive surgery, HIIC with mitomycin C (n = 4) or cisplatin (n = 1) and EPIC with 5-fluorouracil (5-FU) for 4 (n = 1) or 5 (n = 5) days., Results: All six patients presented with hematologic toxicity of WHO criteria grade 4; four of them died postoperatively. Two of the patients who died, and one who did not die, developed bowel perforations. Five patients had prior chemotherapy with 5-FU; three of them had toxic side effects. All patients were overweight, and three patients were anemic preoperatively. The neutropenia presented with fever, leukopenia and thrombocytopenia on postoperative days 10-15. The leukocyte count courses showed a pattern suggesting the 5-FU as the cause of leukopenia. There was no consistent warning signal for predicting severe neutropenia., Discussion: Neutropenia following cytoreductive surgery combined with HIIC and EPIC has a high mortality (66%). Patients who are at special risk and should have a dose reduction include patients who had toxicities from prior chemotherapy, who present with obesity and anemia. The groups have an increased risk of developing postoperative profound neutropenia. This condition can result in a prohibitively high mortality and morbidity rate. Therefore, reduced doses of chemotherapy in selected patients are necessary to prevent this condition from developing.

Intraperitoneal chemotherapy (IC) is emerging as a valuable adjuvant therapeutic modality in patients with gastric cancer. The purpose of this study was to assess morbidity and mortality of early postoperative IC (EPIC) in gastric cancer patients. Two hundred forty-eight gastric cancer patients thought to have resectable cancer were randomized intraoperatively to receive EPIC with mitomycin C on postoperative day 1 and 5-fluorouracil on postoperative days 2 to 5 versus surgery only. Sixty-four patients who were stage IV at histopathologic examination remain in the analysis. Morbidity and mortality were compared using Fisher's exact test. All patients completed the therapy. In the study group, overall morbidity was higher than in the control group (28.8% versus 20.3%, respectively), although the difference was not significant (P = 0.121). Intra-abdominal sepsis without anastomotic leak (P = 0.008) and bleeding (P = 0.002) occurred significantly more often in the study group. Also, 37.6 per cent of patients who received EPIC experienced a variety of minor complications attributable to EPIC. Postoperative mortality was higher in the study group (5.6%) than in controls (0.8%), but not significantly (P = 0.299). Patients treated with EPIC stayed in the hospital an average of 4 days longer (P = 0.002); in patients with morbidity, however, there was no difference with the control group. A period analysis of the morbidity demonstrated that it followed the pattern of a learning curve. Surgery with EPIC tended to increase the postoperative morbidity and mortality. The therapy-associated risk must be justified by a significant improvement in survival of treated patients with stage III disease. Selective application of perioperative IC may be indicated.