Importance of gender in diffuse malignant peritoneal mesothelioma.

BACKGROUND: Combined therapy involving cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy has been shown to improve survival outcomes for patients with diffuse malignant peritoneal mesothelioma (DMPM). The present study aims to investigate gender as a potential prognostic factor on overall survival. PATIENTS AND METHODS: Over a period of two decades, 294 patients who underwent CRS and perioperative intraperitoneal chemotherapy were selected from a large multi-institutional registry to assess the prognostic significance of gender on overall survival. RESULTS: Female patients were shown to have a significantly improved survival outcome than male patients (P < 0.001). Staging according to a recently proposed tumor-node-metastasis categorization system was significant in both genders. Older female patients had significantly worse survival than younger female patients (P = 0.019), a finding that was absent in male patients. Female patients with low-stage disease were found to have a very favorable long-term outcome after combined treatment. CONCLUSIONS: Gender has demonstrated a significant impact on overall survival for patients with DMPM after CRS and perioperative intraperitoneal chemotherapy. An improved understanding of the role of estrogen in the pathogenesis of DMPM may improve the prognostication of patients and determine the role of adjuvant hormonal treatment in the future.

Multi-institutional experience of diffuse intra-abdominal multicystic peritoneal mesothelioma.

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.

Radioembolization with yttrium microspheres for neuroendocrine tumour liver metastases.

BACKGROUND: (90)Y microsphere radioembolization is performed by injecting the microspheres through a hepatic artery catheter placed percutaneously via the femoral or brachial artery. This study assessed the efficacy of (90)Y microsphere therapy for patients with unresectable neuroendocrine tumour liver metastases (NETLMs). Potential prognostic factors were analysed for their impact on overall survival. METHODS: A prospectively collected database for patients with NETLMs treated by (90)Y microspheres in two centres from 2003 to 2008 was examined retrospectively. Serial radiographic evidence was collected during follow-up to assess response. RESULTS: Fifty-eight patients were included, 51 of whom had evaluable disease at most recent follow-up. Six patients achieved a complete response, 14 a partial response, 14 had stable disease and 17 had disease progression. Overall survival rates at 1, 2 and 3 years were 86, 58 and 47 per cent respectively; median survival was 36 (range 1-61) months. Extent of tumour involvement, radiographic response to treatment, extrahepatic disease and tumour grade were significant prognostic factors for overall survival. CONCLUSION: (90)Y microsphere radioembolization achieved a radiographic response in a significant proportion of patients with NETLMs.

Critical assessment of preoperative and operative risk factors for complications after iterative peritonectomy procedures.

AIMS: This study is the first to evaluate the clinical and treatment-related risk factors for perioperative toxicity and mortality in patients with peritoneal recurrence that underwent iterative cytoreductive surgery (CRS) with or without perioperative intraperitoneal chemotherapy (PIC). The aim is to improve patient selection. METHODS: Fifty-seven consecutive iterative CRS procedures were performed in 40 patients between June 2000 and September 2008. Forty-seven patients were administered PIC. Adverse events were rated from grades I to V with increasing severity. Grade I toxicity was self limiting; grade II required medical intervention; grade III required an invasive intervention; grade IV required returning to intensive care unit or operating theatre; and grade V resulted in patient death during hospital stay. Risk factors for grades III and IV/V toxicity were determined. RESULTS: The mortality rate was 2%. The grades III and IV/V toxicity rate was 18% and 19%, respectively. A peritoneal cancer index >or=16 (p=0.020), operation length >or=9h (p=0.045), number of peritonectomy procedures >or=2 (p=0.045) and a suboptimal cytoreduction (p=0.031) were the risk factors for grade IV/V toxicity. CONCLUSIONS: Iterative CRS and PIC procedures have an acceptable rate of perioperative toxicity in carefully selected patients. Patients with high tumour burden requiring extensive surgical dissection are at highest risk of a severe adverse event. Thorough preoperative evaluation of patients is necessary to improve both perioperative and postoperative outcomes.

Peritoneal carcinomatosis and liver metastases from colorectal cancer treated with cytoreductive surgery perioperative intraperitoneal chemotherapy and liver resection.

BACKGROUND: An aggressive therapy comprising of cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy (PIC) and liver resection/ablation is generally not offered to patients with both colorectal peritoneal carcinomatosis (CRPC) and liver metastases (LM) as it no longer represents a loco-regional disease. We review the outcomes of patients who underwent an aggressive treatment with a curative intent for both CRPC and LM as a prelude towards determining the suitability of this treatment. METHODS: Patients with CRPC were treated with cytoreductive surgery and perioperative intraperitoneal chemotherapy in our institution. Patients with LM underwent additional treatment of liver resection/ablation. The characteristics and survival of patients with isolated CRPC and those with both CRPC and LM were compared. RESULTS: Fifty-five patients underwent complete cytoreductive surgery for treatment of CRPC, amongst which 16 patients had LM. The overall median survival was 36 months. Fourteen of the 16 patients treated for CRPC and LM underwent synchronous treatment. When patients with CRPC alone or CRPC with LM were compared, patients with CRPC and LM had a lower PCI (p=0.03), received less HIPEC infusion (p<0.001), received less of both HIPEC and EPIC infusion (p=0.007), had a shorter procedural duration (p=0.001) and required less blood transfusion (p=0.02). There was no difference in survival between patients who had CRPC alone or CRPC with LM who underwent aggressive treatment (p=0.77). CONCLUSIONS: A curative procedure may be offered to selected patients with CRPC and LM, especially in those with a low peritoneal cancer index.

Adjuvant lipiodol I-131 after curative resection/ablation of hepatocellular carcinoma.

AIM: A total of 329 patients with hepatocellular carcinoma have been treated at our unit since 1990. Following the randomized controlled trial in Hong Kong by Lau et al. in 1999, patients have been offered adjuvant lipiodol I-131. The aim of this study was to determine the effectiveness of adjuvant lipiodol I-131, following potentially curative surgery with resection and/or ablation, on overall and disease-free survival rates. MATERIAL AND METHODS: The prospectively updated hepatocellular carcinoma database was analysed retrospectively. A total of 34 patients were identified to have received adjuvant lipiodol I-131 post-curative treatment with surgical resection and/or ablation. Patient demographics, clinical, surgical, pathology, and survival data were collected and analysed. RESULTS: Three patients received ablation alone, 24 resection, and 7 resection and ablation. Of the 34 patients treated, there were 2 possible cases of treatment-related fatality (pneumonitis and liver failure). Potential prognostic factors studied for effect on survival included age, gender, serum AFP concentration, Child-Pugh score, cirrhosis, tumor size, portal vein tumor thrombus, tumor rupture, and vascular and margin involvement. The median follow-up duration was 23.3 months. The overall median survival was 40.1 months, while the overall survival rates at 1, 2, 3, and 4 years were 87.1%, 71.7%, 60.7%, and 49.6%, respectively. Median duration to recurrence was 22.3 months. CONCLUSION: Administration of adjuvant lipiodol I-131 is associated with good overall survival.

A systematic review on the efficacy of cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for diffuse malignancy peritoneal mesothelioma.

BACKGROUND: In the past, diffuse malignant peritoneal mesothelioma (DMPM) was regarded as a preterminal condition. The length of survival was dependent upon the aggressive versus indolent biologic behavior of the neoplasm. The overall median survival was approximately 1 year after systemic chemotherapy. Cytoreductive surgery (CRS) combined with perioperative intraperitoneal chemotherapy (PIC) has been used as a treatment alternative, but the efficacy of this combined treatment remains to be established. PATIENTS AND METHODS: Searches for relevant studies published in peer-reviewed medical journals on CRS and PIC for DMPM before May 2006 were carried out on six databases. The reference lists of all retrieved articles were reviewed for further identification of potentially relevant studies. Expert academic surgeons in Washington, DC, USA were asked whether they knew about any important unpublished data. Two investigators independently evaluated each study according to predefined criteria. The quality of each study was assessed. Clinical effectiveness was synthesized through a narrative review with full tabulation of results of all included studies. RESULTS: Seven prospective observational studies from six tertiary institutions were available, allowing 240 DMPM patients for assessment. The median survival ranged from 34-92 months. The 1-, 3- and 5-year survival varied from 60% to 88%, 43% to 65% and 29% to 59%, respectively. The perioperative morbidity varied from 25% to 40% and mortality ranged from 0% to 8%. CONCLUSIONS: This systematic review evaluated the current evidence for CRS and PIC for DMPM. Seven observational studies were available for assessment, which demonstrated an improved overall survival, as compared to historical controls, using systemic chemotherapy and palliative surgery.

Sex difference in diffuse malignant peritoneal mesothelioma.

BACKGROUND: Diffuse malignant peritoneal mesothelioma (DMPM) is rare and in the past has proved an invariably fatal disease. Female patients have been reported to have an improved survival outcome for reasons that are not understood. METHODS: The survival of 34 men and 28 women who underwent cytoreduction and perioperative intraperitoneal chemotherapy for DMPM was compared. Twenty-five clinicopathological variables were subjected to univariate analysis. RESULTS: The women had a 5-year survival rate of 63 per cent and median survival was not reached. The men had a 5-year survival rate of 42 per cent, with a median survival of 32 months (P = 0.045). Women had undergone more extensive previous surgery and had less extensive peritoneal involvement at the time of cytoreduction. Tumours in women more frequently showed a small nuclear size (30 microm or less) and the chromatin pattern was more often granular than clear. CONCLUSION: Women with DMPM had better survival. This observation may be related to the favourable clinical and histopathological features associated with women.

Cytoreductive surgery and perioperative intraperitoneal chemotherapy for peritoneal carcinomatosis from colorectal carcinoma: non-mucinous tumour associated with an improved survival.

AIMS: Cytoreductive surgery combined with perioperative intraperitoneal chemotherapy has been reported as a treatment option for patients with peritoneal carcinomatosis from colorectal carcinoma. METHODS: Thirty patients with colorectal peritoneal carcinomatosis underwent cytoreductive surgery and perioperative intraperitoneal chemotherapy. All appendiceal cancers were excluded. All patients were followed until January 2006 or death. Univariate analysis was performed to evaluate significant prognostic factors for overall survival, defined from the time of surgery. RESULTS: There were 13 male patients. The mean age at the time of surgery was 54years. There was no hospital mortality. The mean duration of hospital stay was 27days. The overall median survival was 29months, with 1- and 2-year survival of 72% and 64%, respectively. Twenty-one patients had complete cytoreduction and their 1- and 2-year survival rates were 85% and 71%, respectively. Univariate analysis demonstrated that patients with non-mucinous colorectal adenocarcinoma, Peritoneal Cancer Index (PCI) < or =13, and complete cytoreduction were associated with an improved survival. CONCLUSIONS: This study reported on 30 patients who underwent cytoreductive surgery and perioperative intraperitoneal chemotherapy for colorectal peritoneal carcinomatosis. Patients with mucinous tumour had relatively more extensive intraperitoneal disease. Non-mucinous colorectal adenocarcinoma, PCI < or =13, and complete cytoreduction were associated with an improved survival.

Cytoreductive surgery and perioperative intraperitoneal chemotherapy for pseudomyxoma peritonei from appendiceal mucinous neoplasms.

BACKGROUND: Cytoreductive surgery (CRS) combined with perioperative intraperitoneal chemotherapy (PIC) has been used to treat pseudomyxoma peritonei. The aim of this prospective study was to evaluate survival outcome and treatment-related prognostic markers in patients who underwent CRS and PIC for pseudomyxoma peritonei from appendiceal mucinous neoplasms. METHODS: Survival data and 12 clinicopathological and treatment-related prognostic variables for survival were obtained prospectively in 50 consecutive patients (23 men). Univariate analysis was used to determine their prognostic significance for overall survival, determined from the time of CRS. RESULTS: The mean(s.d.) age was 52(12) years. Eighteen patients had moderate complications, and six patients had severe complications that required operation or intensive care support. Two patients died after surgery. The actuarial 5-year survival rate was 69 per cent. Univariate analysis demonstrated that the extent of previous surgery (P = 0.045) and Ronnett's histopathological classification (P < 0.001) were significantly related to overall survival. CONCLUSION: CRS combined with PIC was associated with improved survival in patients with less extensive previous surgery and diffuse peritoneal adenomucinosis histopathological type.

Significance of lymph node metastasis in patients with diffuse malignant peritoneal mesothelioma.

BACKGROUND: Diffuse malignant peritoneal mesothelioma (DMPM) is a rare and invariably fatal neoplasm. Some studies have shown that cytoreductive surgery (CRS) combined with perioperative intraperitoneal chemotherapy (PIC) achieved an improved survival, as compared to historical controls. However, the significance of lymph node involvement in this disease has never been well defined. METHODS: One hundred patients with DMPM underwent CRS and PIC at the Washington Hospital Center. The inclusion criteria for surgery consisted of histological diagnosis of DMPM, age <80 years and good performance status. All data were collected prospectively. Lymph node status, seven clinical variables and eight treatment-related prognostic factors were analyzed for survival. RESULTS: Seven patients were lymph node positive and they all died of their disease within 2 years after the surgery. The remaining 93 patients had 5- and 7-year survival of 50% and 43%, respectively. Univariate analysis showed that gender (p<0.001), peritoneal cancer index (p=0.009), lymph node status (p<0.001), extra-abdominal invasion (p=0.026), histological type (p<0.001), intraoperative blood loss (p=0.035), completeness of cytoreduction (p<0.001), intraperitoneal chemotherapy regimen (p=0.041), and redo cytoreductive surgery (p=0.022) were significant for survival. Multivariate analysis demonstrated that female gender, lymph node metastasis not detected, epithelial type, and adequate cytoreduction were independently associated with an improved survival. CONCLUSIONS: CRS and PIC showed an improved survival for DMPM, as compared to historical controls. Lymph node status along with three other prognostic variables was significant in the multivariate analysis.

Management of intrahepatic recurrence after curative treatment of colorectal liver metastases.

BACKGROUND: Management of intrahepatic recurrence after complete surgical treatment for colorectal liver metastases is not well defined. The aim of this study was to analyse the survival results of patients who had repeat liver resection for intrahepatic recurrence and to evaluate prognostic indicators for survival. METHODS: Between 1991 and 2005, 55 patients had repeat liver resection for isolated intrahepatic recurrence. The long-term survival results were assessed. Univariable and multivariable analyses were used to identify prognostic indicators for survival after repeat hepatectomy. RESULTS: The median survival was 53 (range 2-97) months and the 5-year survival rate was 49 per cent. In univariable analysis, size of largest initial liver metastasis, margin of initial liver surgery, carcinoembryonic antigen (CEA) level before and after initial liver surgery, liver disease-free survival, margin of repeat liver surgery, operation type of repeat surgery and CEA level before and after repeat surgery were significant prognostic factors. In multivariable analysis, largest initial liver metastasis 4 cm or less and CEA level 5 ng/ml or less after repeat liver surgery were independently associated with improved survival. CONCLUSION: Repeat hepatectomy can achieve an acceptable survival in selected patients with isolated intrahepatic recurrence.

Comprehensive management of diffuse malignant peritoneal mesothelioma.

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.

Lung metastases after liver resection or cryotherapy for hepatic metastasis from colorectal cancer--there is a difference!

BACKGROUND: The most common site of colorectal extra-abdominal metastases is the lung. The relative risk of lung metastases after resection and cryotherapy has not previously been compared. METHODS: All patients underwent an extensive preoperative staging including clinical examination, abdominal computed tomography (CT) and abdominal angio-CT to assess their hepatic disease. Two groups of patients were compared in this study (hepatic resection alone and hepatic cryotherapy with or without resection). A retrospective analysis of prospectively collected data was performed to assess the incidence and disease-free interval of pulmonary metastasis after surgical treatment of colorectal liver metastasis. RESULTS: This paper clearly shows two differences regarding pulmonary metastases between patients treated with resection only and cryotherapy with or without resection. Among the 10 clinical variables, cryotherapy had the greatest correlation with pulmonary metastases (p=0.004). A patient who undergoes hepatic resection only has a probability of 35% for developing pulmonary recurrence, compared with 51% following cryotherapy. Cryotherapy was also independently associated with shorter pulmonary disease-free interval (p=0.036). CONCLUSION: There clearly is a higher risk of pulmonary metastasis after cryotherapy than after resection, whether this is related to selection of patients or a direct deleterious procedural effect requires more study.

Radiologically placed temporary hepatic artery catheter for treatment of liver cancer.

Summary Hepatic artery infusion (HAI) chemotherapy is associated with higher response rates compared to systemic chemotherapy in those patients with unresectable liver malignancies. Operative hepatic artery catheter (HAC) insertion has significant morbidity and mortality, especially in patients with high-volume disease, some of whom may not respond to HAI chemotherapy. We report our experience in 45 patients with high-volume liver disease who were initially treated with HAI chemotherapy via a radiologically placed temporary HAC to try to select the responders who then went on to have an operative HAC. In these 45 patients who had 62 radiologically placed HAC, we found very few major complications, and certainly no complications such as cholecystitis, vascular or malperfusion problems.

Synchronous liver resection and cryotherapy for colorectal metastases: survival analysis.

INTRODUCTION: The value of synchronous liver resection and cryotherapy ablation remains controversial for colorectal metastases where complete resection is not possible by conventional liver surgery alone. OBJECTIVE: To review the long-term survival of patients treated using this approach at our institution. METHODS: A review was undertaken of data held in the prospectively collected liver surgery database of all patients who underwent synchronous liver resection and cryotherapy. Survival analysis was performed and data recorded on the total number of metastases at initial surgery and the number of lesions treated by cryoablation. RESULTS: Ninety-three patients with colorectal metastases underwent synchronous liver resection and cryotherapy. Data were available on 86 patients with a median follow-up of 18 months (range 1-83). The median number of metastases at initial surgery was four (range 2-11) and the number of lesions treated by cryotherapy ablation was two (range 1-8). Eighty-four per cent had a hepatic artery catheter inserted at surgery and at least one cycle of post-operative hepatic artery chemotherapy. One-, three- and five-year survival was 85%, 43% and 19% respectively, with a median survival of 33 months (95% confidence interval 19.9-42.1). Site of recurrence was recorded and presented. CONCLUSIONS: Patients with liver metastases that are not amenable to resection alone can achieve worthwhile median survival with synchronous liver resection and cryotherapy ablation.

Surveillance-detected hepatic metastases from colorectal cancer had a survival advantage in seven-year follow-up.

PURPOSE: Colorectal cancer is a common cause of cancer-related death. The liver is the most common site of distant metastases and the most amenable to potentially curative surgery. The aim of this study was to determine whether hepatic metastases detected by surveillance following colonic resection were associated with higher resectability rates and to determine whether there was any impact on survival rates. METHODS: A retrospective study of 211 patients who presented to the liver unit between February 1990 and July 1996 with hepatic metastases following colonic resection for adenocarcinoma was performed. Patients were divided into two groups: Group A (n = 154), hepatic metastases diagnosed by carcinoembryonic antigen or by radiology; and Group B (n = 57), patients with symptomatic presentation. RESULTS: Potentially curative operations were possible in 51.3 percent (79/154) of Group A patients and 28.1 percent (16/57) of Group B patients (P = 0.0043, chi-squared test). In Groups A and B, 24 percent (37/154) and 43.9 percent (25/57) of patients, respectively, were inoperable. The three-year and five-year survival rates after detection of liver metastases were 26.8 percent (41/153) in Group A and 12.5 percent (7/56) in Group B, and 5.9 percent (9/153) in Group A and 8.9 percent (5/56) in Group B, respectively. Log-rank analysis resulted in P = 0.05, Breslow test in P = 0.01. CONCLUSION: Our study shows that patients with hepatic metastases from colorectal cancer detected by follow-up were significantly more likely to have a potentially curative operation. Our medium-term survival data show a statistically significant survival benefit in patients with surveillance-detected metastases.