Extent Of Peritoneal Carcinomatosis Research Articles

HIPEC as Up-Front Treatment in Locally Advanced Ovarian Cancer

Purpose: The main objective of the study is to evaluate the effect of hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of naïve ovarian cancer women undergoing complete or near-complete cytoreduction by assessing the overall survival, the disease-specific survival, and the disease-free survival. The secondary objective is the identification of prognostic indicators of survival and recurrence of these patients. Patients—Methods: Retrospective study of treatment in naïve women with locally advanced ovarian cancer treated with cytoreductive surgery (CRS) and HIPEC and compared with those who were treated with cytoreduction alone. Clinicopathologic variables were correlated to overall survival, disease-specific survival, and disease-free survival using Kaplan–Meier method, and the multivariate Cox proportional hazards regression models. Results: 5- and 10-year overall survival, disease-specific survival, and disease-free survival rates were significantly higher in patients treated with CRS and HIPEC. These patients were 67% less likely to die from any cause (adjusted hazard ratio, aHR = 0.33, p = 0.001), 75% less likely to die from cancer (aHR = 0.25, p = 0.003), and 46% less likely to develop recurrence (aHR = 0.54, p = 0.041) compared to patients treated with CRS alone. Moreover, the poor performance status (aHR = 2.96, p < 0.001), the serous carcinomas (aHR = 0.14, p = 0.007), and the morbidity (aHR = 6.87, p < 0.001) were identified as independent indicators of poor overall survival. The degree of differentiation (aHR = 8.64, p = 0.003) was identified as the independent indicator of disease-specific survival (aHR = 4.13, p = 0.002), while the extent of peritoneal carcinomatosis (aHR = 2.32, p < 0.001) as the independent indicator of disease-free survival. Conclusions: Treatment in naïve patients with locally advanced ovarian cancer undergoing CRS plus HIPEC appears to have improved overall, disease-specific, and disease-free survival.

Peritoneal carcinomatosis of gastric cancer : Treatment options for peritoneal carcinomatosis of gastric cancer

Gastric cancer is one of the most aggressive malignant diseases of the gastrointestinal tract with a high rate of metastasis. Peritoneal metastasis occurs in up to 60% of all patients and synchronously in up to 30% in locally advanced gastric cancer. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been an established treatment option in selected patients for several years, as the HIPEC serves as an alternative administration route. This article presents aschematic display of the various treatment options depending on the extent of peritoneal carcinomatosis in a gastric cancer. A literature search and analysis of the current literature on the treatment of gastric cancer with peritoneal metastases were carried out. A differentiation was made between limited and extensive peritoneal carcinomatosis together with the appropriate treatment strategy. Principally, individual systemic chemotherapy is the backbone of treatment of gastric cancer with peritoneal metastases. In selected patients and in cases of limited peritoneal carcinomatosis, CRS and HIPEC can be conducted and survival is improved; however, CRS is still contraindicated in cases of extensive peritoneal carcinomatosis and in exceptional cases pressurized intraperitoneal aerosol chemotherapy (PIPAC) can be carried out. In selected patients CRS and HIPEC can lead to an improvement with respect to overall and disease-free survival. In cases of extensive peritoneal carcinomatosis, individualized chemotherapy remains the major treatment option.

Incidence, Prognosis, and Treatment Options for Patients With Synchronous Peritoneal Carcinomatosis and Liver Metastases from Colorectal Origin

Peritoneal carcinomatosis and liver metastases are common metastatic sites in patients who have colorectal cancer. Quite frequently, patients present with both synchronous liver and peritoneal metastases, which may result in a dilemma regarding the optimal treatment. In the absence of reliable data, the aim of the current study was to provide population-based data on such patients and to review the literature for possible treatment options. This study is a retrospective analysis of a prospective database and a review. All patients diagnosed between 1995 and 2010 with synchronous peritoneal carcinomatosis and liver metastases were identified from the Eindhoven Cancer Registry. Incidence and survival were analyzed. Next, the literature was reviewed for articles reporting on the results of treatment with curative intent. In total, 27,632 patients were diagnosed with colorectal cancer, of whom 5638 patients (20%) presented with metastasized disease. Synchronous liver metastasis and peritoneal carcinomatosis were present in 440 patients, being 11% of patients with liver metastases, 34% of patients with peritoneal carcinomatosis, 8% of patients with metastasized disease, and 2% of all patients diagnosed with colorectal cancer. Median survival for patients with liver metastasis and peritoneal carcinomatosis was 5 months, in comparison with 95 months for patients with nonmetastasized disease. No improvement in survival was noted over time. None of the patients underwent treatment with curative intent during this period. No data on the extent of peritoneal carcinomatosis and liver metastases were available in the population-based study. This complicates comparison with treated patients from the literature review, which probably reflects a highly selected patient population. Both liver metastasis and peritoneal carcinomatosis were present in 8% of patients presenting with metastasized colorectal cancer. Population-based survival was only 5 months, with none of the patients undergoing treatment with curative intent. Median survival rates of up to 36 months after treatment with curative intent as published in the literature may be regarded as promising for selected patients.

Preoperative assessment of peritoneal carcinomatosis: intraindividual comparison of 18F-FDG PET/CT and MRI

Exact determination of localization and extent of peritoneal carcinomatosis (PC) before peritonectomy and hyperthermic intraperitoneal chemotherapy (HIPEC) is crucial for the clinical outcome. Our study compares dynamic contrast enhanced 3D MRI (T1wDCE) and 18F-FDG PET/CT regarding diagnostic accuracy in correlation with surgical exploration (SE) and histological (HI) results. 15 patients with PC were examined on a 1.5T MRI and 16 slice PET/CT. MRI: coronal T1wDCE covering the complete abdomen (0.15 mmol Gd-chelate/kg BW, 2000 mL mannitol solution p.o., 40 mg buscopan i.v.). PET-CT: contrast enhanced 16slice CT (120 mL ultravist 370 i.v., 1000 mL mannitol solution p.o., 40 mg buscopan i.v.), PET: 350 MBq 18-FDG i.v., 3 min acquisition time/bed, 60 min after tracer injektion). Assessment by two independent, experienced observers in correlation with results of SE and HI for each abdominal segment based on the peritoneal cancer index (PCI) proposed by Sugarbaker and co-authors. MRI and PET/CT provided reliable detection of PC. One patient had to be excluded from statistical analysis. In summary, 182 segments were assessed (13/patient, 14 patients, one patient excluded from statistical analysis). PC was found in 118 by MRI, 124 by PET/CT. 4 segments were classified false positive for MRI, 2 for PET/CT. False negative segments (MRI: 17, PET/CT: 9) did not result in irresectability. Positive predictive value for PC/segment was 97/98%, negative predictive value 73/84%, sensitivity 87/93%, specificity 92/96%, and diagnostic accuracy 88/94% (MRI/PET/CT). With high diagnostic accuracy for PC of both, MRI and PET/CT, PET/CT provides better diagnostic accuracy and especially better NPV.

Peritoneal Colorectal Carcinomatosis Treated with Cytoreductive Surgery and Perioperative Intraperitoneal Chemotherapy

Background-Aims: Peritoneal colorectal carcinomatosis is a potentially curative disease. The purpose of the study is the retrospective analysis of survival of the patients with peritoneal colorectal carcinomatosis that underwent cytoreductive surgery and perioperative intraperitoneal chemotherapy and the identification of prognostic variables of the disease. Patients-Methods: Patients with primary or recurrent colorectal cancer and peritoneal carcinomatosis were included in the study. Clinical variables were correlated to survival, recurrence, hospital mortality, and morbidity. Results: From 2000-2010, 28 patients underwent 33 cytoreductive operations. The hospital mortality and morbidity rate was 9.1% and 45.5% respectively. The overall 5-year and median survival time was 29.2% and 19 months respectively. The extent of peritoneal carcinomatosis (p = 0.0003) and the completeness of cytoreduction (p = 0.0002) were related to survival. The completeness of cytoreduction (p = 0.003) was the single prognostic variable of survival. The recurrence rate was 42.4% and the use of systemic chemotherapy was identified as the single prognostic variable of recurrence (p = 0.047). Conclusions: Patients with limited extent of peritoneal colorectal carcinomatosis who undergo complete cytoreduction may be offered long-term survival.

Lymph Nodes Ratio Is Associated with the Survival of Colorectal Cancer Patients with Peritoneal Carcinomatosis

The purpose of this study was to clarify the prognostic factors in patients with peritoneal carcinomatosis from colorectal origin, especially focusing on lymph node status. Between 1998 and 2007, 126 patients who underwent surgical treatment for primary colorectal cancer with peritoneal carcinomatosis were retrospectively assessed concerning prognostic factors. To estimate survival, we formulated a scoring system by numbers of independent poor prognostic factors. According to a multivariate analysis, extent of peritoneal carcinomatosis (hazard ratio, 1.93; 95% confidence interval, 1.19-3.13; P = 0.008) and lymph node ratio (hazard ratio, 1.87; 95% confidence interval, 1.05-3.33; P = 0.034) were found to be independent poor prognostic factors for survival. Furthermore, we demonstrated that score formulated by the number of these criteria was highly predictive of survival (P < 0.001). The 5-year survival rate for patients with score 0 (having no criteria), score 1 (having one criterion), and score 2 (having two criteria) were 25.1 per cent, 6.2 per cent, and 0 per cent, respectively. Lymph node ratio is an important prognostic factor in addition to the extent of peritoneal carcinomatosis after resection of primary colorectal carcinoma. Patients without these criteria have a favorable outcome, and therefore should be considered for further aggressive surgery and intraperitoneal chemotherapy.

Peritoneal metastases in colorectal cancer

Peritoneal carcinomatosis (PC) is a common evolution of cancer of the gastrointestinal tract, and has been traditionally regarded as a terminal disease with short median survival. During the last 20 years, due to its favourable oncologic results, a new loco-regional therapeutic approach, combining cytoreductive surgery with intra-operative intraperitoneal chemotherapy has achieved an important development. After liver metastatic disease, peritoneal carcinomatosis is the second most frequent cause of death in colorectal cancer patient is defined as a stage IV tumour which prognosis is the worst. The extent of peritoneal carcinomatosis is, however, difficult for assessment preoperatively, and precise evaluation is most often performed during surgical exploration. Cytoreductive surgery associated with chemotherapy for the treatment of peritoneal carcinomatosis should be performed in young patients with limited and resectable carcinomatosis, in specialized institutions involved in the management of peritoneal surface malignancies.

Selection of patients and staging of peritoneal surface malignancies

Peritoneal carcinomatosis (PC) is a common evolution of cancer of the gastrointestinal tract, and has been traditionally regarded as a terminal disease with short median survival. During the last 20 years, thanks to its favourable oncologic results, a new loco-regional therapeutic approach, combining cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC), has an important development. Due to its significant, but acceptable, morbidity and mortality, and high cost, this comprehensive management plan requires knowledgeable patient selection. Quantitative prognostic indicators are required to assess a patient's eligibility. Large multicenter studies have identified several prognostic factors, which can be used for a better selection of patients who would benefit from the combination of cytoreductive surgery with HIPEC. Indications for treatment of PC with cytoreduction and HIPEC are now validated for several diseases: peritoneal mesothelioma, pseudomyxoma peritonei, PC from the appendix, and colorectal cancer. Indications are still under discussion for gastric and ovarian carcinomatosis. Computed tomography is the best radiological for staging the disease. The extent of peritoneal carcinomatosis is, however, difficult to evaluate preoperatively, and precise evaluation is most often performed during surgical exploration. Cytoreductive surgery associated with HIPEC for the treatment of peritoneal carcinomatosis should be performed for young patients with limited and resectable carcinomatosis, in specialized institutions involved in the management of peritoneal surface malignancies.

Potentially curative strategies in peritoneal metastases

PURPOSE: Synopsis about the curative possibilities of an aggressive multimodal therapeutic approach for peritoneal metastases using positive prognostic selection criteria. PATIENTS AND METHODS: Published data concerning cytoreductive surgery in combination with intraoperative intraperitoneal hyperthermic chemotherapy and/or early postoperative intraperitoneal chemotherapy ± systemic chemotherapy in patients suffering from peritoneal carcinomatosis were analyzed with regard to subgroups with long-term survivors. RESULTS: Extent of peritoneal carcinomatosis and completeness of cytoreductive surgery are the most important prognostic factors predicting long-term survival. Histological differentiation, lymph node status, performance status, extent of prior therapy and age are further independent factors influencing the outcome. CONCLUSION: Strictly selecting patients with multiple positive prognostic factors might result in 5-year survival rates of 50% and more.

Intraperitoneal chemotherapy with hydroxycamptothecin reduces peritoneal carcinomatosis: results of an experimental study

We studied the efficacy and safety of intraperitoneal chemotherapy with hydroxycamptothecin (HCPT) for the treatment of peritoneal carcinomatosis in animal model. Highly metastatic human hepatocellular carcinoma (HCC) cell line HCCLM3 was injected into the peritoneal cavity of 30 nude mice to construct a model of intraperitoneal carcinomatosis, which were randomized into a treatment group and a control group of 15 mice in each group. The former received intraperitoneal injections of HCPT at the dose of 2 mg/kg body weight for 7 days every other week, on weeks 2, 4 and 6; and the latter received the same dose schedule treatment of 0.9% sodium chloride solution. The mice were observed for 8 weeks. Body weight changes, intraperitoneal carcinomatosis, hematological and biochemical parameters were evaluated. On day 56, 14 mice in the treatment group were still alive, compared against 5 in the control group, and the mean survival time was 55 +/- 1 days [95% confidence interval (CI) 54-57 days] versus 43 +/- 4 days (95% CI 34-51 days) (P = 0.002). The tumor weight in the treatment group (0.8 +/- 0.8 g) was significantly smaller than the control group (2.0 +/- 0.8 g) (P = 0.00028). No bloody ascites or diffuse peritoneal carcinomatosis were observed in the treatment group, as compared with 4 mice (26.7%) that developed bloody ascites and 6 mice (40%) which developed diffuse peritoneal carcinomatosis in the control group (P < 0.001). The treatment group had a significantly lower peripheral white blood cell count [(3.18 +/- 1.72) x 10(9) l(-1)] than the control group [(5.08 +/- 2.03) x 10(9 )l(-1)] (P < 0.05), significantly lower serum alpha fetoprotein level (101.22 +/- 20.12 microg/l) than the control group (244.87 +/- 30.24 microg/l) (P < 0.05), and significantly lower serum gamma glutamyl transpeptidase level (12.45 +/- 2.26 U/l) than the control group (20.75 +/- 3.87 U/l) (P < 0.05). No obvious treatment related toxicities were observed. Intraperitoneal injection of HCPT could inhibit tumor progression, reduce the extent of peritoneal carcinomatosis and improve survival of tumor bearing mice.

Long-term survival in advanced ovarian carcinoma following cytoreductive surgery with standard peritonectomy procedures

The impact of cytoreductive surgery with standard peritonectomy procedures has not been extensively assessed in the treatment of advanced ovarian cancer. The aims of the study are to report the long-term results of patients with advanced ovarian cancer undergoing cytoreductive surgery with standard peritonectomy procedures and to identify the prognostic indicators that may affect outcome. The records of 74 women with advanced ovarian cancer were retrospectively reviewed. Clinical indicators were correlated to survival. The hospital mortality and morbidity rates were 13.5% and 28.4%, respectively. Complete or near-complete cytoreduction was possible in 78.4% of the patients. Overall 10-year survival rate was 52.5%. Complete cytoreductive surgery, small-volume tumor, low-grade tumor, the absence of distant metastases, the use of systemic adjuvant chemotherapy, performance status >70%, and limited extent of peritoneal carcinomatosis were favorable indicators of survival. Complete cytoreduction (P= 0.000) and treatment with systemic chemotherapy (P= 0.001) independently influenced survival. Recurrence was recorded in 37.8% of the patients and was independently influenced by the tumor grade (P= 0.037). Cytoreductive surgery with standard peritonectomy procedures followed by adjuvant chemotherapy offers long-term survival in women with advanced ovarian cancer who have limited peritoneal carcinomatosis and no distant and irresectable metastases.

Peritoneal carcinomatosis from colorectal cancer.

Aggressive therapeutic regimens have been advocated for the treatment of peritoneal carcinomatosis from colorectal cancer. It is essential to understand the clinical and histological features that govern the natural history of this condition if the efficacies of novel therapeutic approaches are to be assessed adequately. A database of 3019 colorectal cancers was used to identify patients with synchronous peritoneal carcinomatosis, patients who developed metachronous peritoneal carcinomatosis, and those without carcinomatosis. Clinical, histological and survival data for the groups were collated and subjected to statistical analysis. Some 349 patients (13 per cent) with peritoneal carcinomatosis were identified; 214 had synchronous disease and 135 had metachronous carcinomatosis. Some 125 patients (58 per cent) in the synchronous group were free of systemic metastases; 80 of these patients had localized disease. Liver metastases, tumour (T) stage, nodal stage, and venous and perineural invasion were independent predictors of metachronous carcinomatosis. The median survival of patients with synchronous disease was 7 months; survival was adversely affected by the extent of peritoneal carcinomatosis and the T stage of the primary cancer. Peritoneal carcinomatosis is a common mode of disease progression in patients with colorectal cancer. For the majority of patients the prognosis is poor, but a small number with localized disease may be suitable for further aggressive therapy.

Octreotide (SMS 201–995) inhibits the growth of colon peritoneal carcinomatosis in BDIX rats

In order to assess the effect of octreotide, a somatostatin analogue, on the growth of colon peritoneal carcinomatosis, 20 BDIX rats were injected i.p. with 1·10 6 colon cancer cells (DHD/K12 tumor cell line) and received octreotide, 65 μg/kg s.c. every 12 h ( n=10) or saline ( n=10) for 42 days, starting 3 days after tumor cell injection. Animals were killed at the end of the treatment. The mean volume of ascites was lower in the octreotide group ( 33.7±7.6 ml ), than in the control group ( 67.5±16.3 ml ; P<0.05). The extent of peritoneal carcinomatosis (in five classes according to a previously published classification) was lower in the octreotide group ( P<0.05). Cell proliferation, using the BrdU technique, was markedly inhibited by octreotide (labeling index of tumor cells: 17.0±0.6% vs. 26.3±2.2% in controls, P<0.001). No significant decrease in labeling index was observed in normal colonic mucosa. Two subtypes of somatostatin receptors were found in all tumors, using the 30F3 monoclonal antireceptor antibody. K D and B max values were not significantly different in the octreotide and control groups: high affinity, low capacity receptors ( K D =1.4·10 −10 M and 0.7·10 −10 M , respectively; B max =3.8 and 2.9 pmol/mg protein, respectively); low affinity, high capacity receptors ( K D =1±0.2·10 −9 M , respectively; B max =27.8±0.1 and 22.8±0.05 pmol/mg protein, respectively). Octreotide inhibits the growth of colon peritoneal carcinomatosis in vivo in BDIX rats through an inhibition of DNA synthesis; this effect is at least partly mediated by somatostatin receptors present on tumor cells.