Lana Bijelic

Critical Analysis of Treatment Failure After Complete Cytoreductive Surgery and Perioperative Intraperitoneal Chemotherapy for Peritoneal Dissemination From Appendiceal Mucinous Neoplasms

BackgroundCytoreductive surgery (CRS) combined with perioperative intraperitoneal chemotherapy (PIC) has been suggested as a treatment strategy for peritoneal carcinomatosis. The objective of this data analysis was to study treatment failure after complete cytoreduction for peritoneal dissemination from appendiceal mucinous neoplasms.MethodsBefore June 2006, a total of 402 patients with peritoneal dissemination from appendiceal mucinous neoplasms underwent complete cytoreduction and PIC at the Washington Cancer Institute. Patient characteristics, pathologic features, and treatment-related data were obtained from a prospective database. Survival analyses were performed by the Kaplan-Meier method and the Cox regression model.ResultsAfter a median follow-up of 66 months, the 5- and 10-year progression-free survival rates for these 402 patients were 70% and 67%, respectively. Disease progression was the only independent risk factor for a reduced overall survival. One hundred eleven patients (28%) developed progressive disease. Of these, 98 patients underwent second-time and 26 patients third-time CRS and PIC. Complete cytoreduction after repeat surgery was the only independent prognostic factor for improved survival. The most common sites of treatment failure were on the small bowel and in the pelvis.ConclusionsThe present study reported the patterns of treatment failure after complete cytoreduction and demonstrated that a disease-free state is important for long-term survival in peritoneal dissemination from appendiceal mucinous neoplasms. Repeat complete cytoreduction should be pursued when possible and is associated with improved overall survival in patients with recurrent disease.

Failure Analysis of Recurrent Disease Following Complete Cytoreduction and Perioperative Intraperitoneal Chemotherapy in Patients with Peritoneal Carcinomatosis from Colorectal Cancer

BackgroundThe aim of this study was to analyze the anatomic distribution, timing, and outcomes of recurrent disease after complete cytoreduction and perioperative intraperitoneal chemotherapy (PIC) for peritoneal carcinomatosis of colorectal origin.MethodsData regarding all patients who underwent complete cytoreduction and PIC for carcinomatosis from colorectal cancer were extracted from a prospectively collected database. The information regarding recurrent disease found on diagnostic evaluation and/or abdominal exploration was analyzed.ResultsSeventy patients underwent complete cytoreduction and perioperative intraperitoneal chemotherapy, and 49 of them had documented recurrent disease. The median time to progression for these 49 patients was 9 months while their median survival was 30 months. Eighteen patients had a localized intra-abdominal recurrence, 10 had diffuse intraperitoneal recurrence, 10 had isolated distant metastases, and 11 had a combination of distant metastases and intra-abdominal recurrence. There was a statistically significant difference in survival for patients with different patterns of recurrence (P = .012). Twenty-six patients underwent a second operation. The median survival of these patients was significantly longer than that of patients who did not have a second operation (39 vs 20 months, P = .0003). Four of the 49 patients with recurrences were still alive at the time of last follow-up, and three of them have no evidence of disease 73, 96, and 206 months after the diagnosis of recurrence.ConclusionsRecurrence is a frequent event after optimal cytoreduction and PIC for carcinomatosis from colorectal cancer. Surgical treatment for a selected group of patients with recurrent disease may result in long-term survival.

Neoadjuvant FOLFOX chemotherapy in 34 consecutive patients with mucinous peritoneal carcinomatosis of appendiceal origin

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.

Treatment failure following complete cytoreductive surgery and perioperative intraperitoneal chemotherapy for peritoneal dissemination from colorectal or appendiceal mucinous neoplasms

Peritonectomy combined with perioperative intraperitoneal chemotherapy is a successful treatment option for patients with peritoneal dissemination of appendiceal and colorectal malignancy. Despite its efficacy, recurrences remain a common problem.

Systemic Chemotherapy prior to Cytoreductive Surgery and HIPEC for Carcinomatosis from Appendix Cancer: Impact on Perioperative Outcomes and Short-Term Survival

Background and Objectives. Systemic chemotherapy administered prior to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal mucinous adenocarcinoma of appendiceal origin (PMCA) is associated with a significant rate of histological response. The impact of preoperative systemic chemotherapy (PSC) on intraperitoneal tumor burden, completeness of cytoreduction, and perioperative complications is unknown. Methods. We analyzed prospectively collected data from our HIPEC database. Thirty-four patients with PMCA were prospectively recruited and treated with PSC. Perioperative variables and survival in this group of patients were compared against 24 patients with PMCA who did not receive PSC. Results. Ten of 34 patients (29%) receiving PSC had a complete or near complete histological response. Patients receiving PSC had a lower peritoneal carcinomatosis index, required fewer peritonectomies and visceral resections, and achieved complete cytoreduction more frequently compared to patients with no preoperative chemotherapy. The incidence of perioperative complications and survival were not significantly different between the two groups. However, patients with complete histological response had better overall survival compared to patients without complete response. Conclusions. Preoperative systemic chemotherapy in appendix-originated PMCA is associated with a significant rate of histological response which may reduce the tumor burden, facilitate less aggressive and more complete CRS, and improve short-term survival in patients with a significant histological response.

Intraperitoneal Gemcitabine Chemotherapy Treatment for Patients with Resected Pancreatic Cancer: Rationale and Report of Early Data

Currently, the surgical management of pancreas cancer is recognized around the world as inadequate. Despite a potentially curative R0 resection, long-term survival is rare. There is a strong rationale for the use of chemotherapy in the operating room to reduce local-regional of recurrent/progressive disease. Gemcitabine monotherapy administered by an intraperitoneal route in the operating room with hyperthermia and then for long-term treatment postoperatively has a pharmacologic basis in that the exposure of peritoneal surfaces to intraperitoneal gemcitabine is approximately 200–500 times the exposure that occurs within the plasma. A standardized treatment with intraoperative and long-term chemotherapy that is well tolerated would greatly facilitate further improvements in pancreas cancer treatment and may lead the way to an evolution of more successful treatment strategies of this dread disease. The aim of this paper is to present the early data on a protocol in progress in patients with resected pancreatic cancer.

Hyperthermic Intraperitoneal Chemotherapy with Melphalan: A Summary of Clinical and Pharmacological Data in 34 Patients

Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is a treatment option for peritoneal metastases. The optimal agents for HIPEC have not been established. Melphalan is a drug with broad activity and a favorable profile for intraperitoneal application. The purpose of this study is to review our experience using melphalan for HIPEC. Pharmacologic data was obtained. Thirty four patients who underwent CRS for peritoneal metastases received melphalan for HIPEC between 2003 and 2011. The first 10 patients received 70 mg/m2; subsequent 24 received 60 or 70 mg/m2. The mean PCI was 21 ± 7. Twenty-eight patients (83%) had a CC score of 1 or 2. The mean length of stay was 18 ± 2 days. Nine patients (26%) had a grade 3 and 6 (17%) had grade 4 morbidity. There were no postoperative deaths. The pharmacologic analysis of plasma to peritoneal fluid levels of melphalan showed an AUC ratio of 33 while the tumor nodules to peritoneal ratio was 8. Melphalan is an acceptable agent for use in HIPEC. The morbidity of intraperitoneal melphalan at the dose of 60–70 mg/m2 appears acceptable. Further studies comparing the effectiveness of melphalan and other HIPEC agents are needed.

Adjuvant bidirectional chemotherapy with intraperitoneal pemetrexed combined with intravenous Cisplatin for diffuse malignant peritoneal mesothelioma.

Cytoreductive surgery (CRS) with heated intraoperative intraperitoneal chemotherapy (HIPEC) has emerged as optimal treatment for diffuse malignant peritoneal mesothelioma (DMPM) showing median survivals of 36–92 months. However, recurrences occur frequently even in patients undergoing optimal cytreduction and are often confined to the abdomen. We initiated a Phase II study of adjuvant intraperitoneal pemetrexed combined with intravenous cisplatin for patients undergoing CRS and HIPEC for DMPM. The treatment consisted of pemetrexed 500 mg/m2 intraperitoneally and cisplatin 50 mg/m2 intravenously given simultaneously on day 1 of every 21 day cycle for 6 cycles. The primary endpoint of the study was treatment related toxicity. From July 2007 until July 2009 ten patients were enrolled. Nine of 10 completed all 6 cycles of adjuvant treatment per protocol. The most common toxicities were fatigue, nausea and abdominal pain grade 1 or 2. There was one grade 3 toxicity consisting of a catheter infection. The median survival for all 10 patients was 33.5 months. Pharmacokinetic analysis of intraperitoneal pemetrexed showed a peritoneal to plasma area under the curve ratio of 70. Our study shows that adjuvant intravenous cisplatin and intraperitoneal pemetrexed can be used following CRS and HIPEC for DMPM with low morbidity.

Rationale for an Intraperitoneal Gemcitabine Chemotherapy Treatment for Patients with Resected Pancreatic Cancer

Currently, the surgical management of pancreas cancer is recognized around the world as inadequate. Long-term survival is rare even though there is a potentially curative R0 resection. There is a strong rationale for the use of chemotherapy in the operating room to reduce local-regional and hepatic sites of recurrent/progressive disease. Gemcitabine monotherapy administered by an intraperitoneal route in the operating room with hyperthermia and then for long-term treatment postoperatively has a strong pharmacologic basis. The exposure of peritoneal surfaces to intraperitoneal gemcitabine is approximately 500 times the exposure that occurs within the plasma. By analogy to another lethal disease, ovarian cancer, intraperitoneal gemcitabine chemotherapy used following potentially curative resection is supported. Data that shows a superiority of multiagent chemotherapy to gemcitabine monotherapy has not been reported. A standardized treatment with intraoperative chemotherapy monitoring of gemcitabine would greatly facilitate further improvements in pancreas cancer treatment and lead the way to an evolution of more successful treatment strategies of this dread disease. The aim of this review is to present the recent available medical information and patents applicable to patients with resected pancreatic cancer.

The porta hepatis as a site of recurrence of mucinous appendiceal neoplasms treated by cytoreductive surgery and perioperative intraperitoneal chemotherapy

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.