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1.
Br J Surg ; 108(10): 1225-1235, 2021 10 23.
Article in English | MEDLINE | ID: mdl-34498666

ABSTRACT

BACKGROUND: The incidence of gastric poorly cohesive carcinoma (PCC) is increasing. The prognosis for patients with peritoneal metastases remains poor and the role of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is controversial. The aim was to clarify the impact of gastric PCC with peritoneal metastases treated by CRS with or without HIPEC. METHODS: All patients with peritoneal metastases from gastric cancer treated with CRS with or without HIPEC, in 19 French centres, between 1989 and 2014, were identified from institutional databases. Clinicopathological characteristics and outcomes were compared between PCC and non-PCC subtypes, and the possible benefit of HIPEC was assessed. RESULTS: In total, 277 patients were included (188 PCC, 89 non-PCC). HIPEC was performed in 180 of 277 patients (65 per cent), including 124 of 188 with PCC (66 per cent). Median overall survival (OS) was 14.7 (95 per cent c.i. 12.7 to 17.3) months in the PCC group versus 21.2 (14.7 to 36.4) months in the non-PCC group (P < 0.001). In multivariable analyses, PCC (hazard ratio (HR) 1.51, 95 per cent c.i. 1.01 to 2.25; P = 0.044) was associated with poorer OS, as were pN3, Peritoneal Cancer Index (PCI), and resection with a completeness of cytoreduction score of 1, whereas HIPEC was associated with improved OS (HR 0.52; P < 0.001). The benefit of CRS-HIPEC over CRS alone was consistent, irrespective of histology, with a median OS of 16.7 versus 11.3 months (HR 0.60, 0.39 to 0.92; P = 0.018) in the PCC group, and 34.5 versus 14.3 months (HR 0.43, 0.25 to 0.75; P = 0.003) in the non-PCC group. Non-PCC and HIPEC were independently associated with improved recurrence-free survival and fewer peritoneal recurrences. In patients who underwent HIPEC, PCI values of below 7 and less than 13 were predictive of OS in PCC and non-PCC populations respectively. CONCLUSION: In selected patients, CRS-HIPEC offers acceptable outcomes among those with gastric PCC and long survival for patients without PCC.


Subject(s)
Cytoreduction Surgical Procedures , Hyperthermic Intraperitoneal Chemotherapy , Stomach Neoplasms/drug therapy , Stomach Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Disease-Free Survival , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Ovarian Neoplasms/secondary , Peritoneal Neoplasms/secondary , Prognosis , Retrospective Studies , Stomach Neoplasms/mortality , Stomach Neoplasms/pathology , Young Adult
2.
Surg Endosc ; 34(6): 2803-2806, 2020 06.
Article in English | MEDLINE | ID: mdl-32166545

ABSTRACT

BACKGROUND: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new intraabdominal technique to approach non-resectable peritoneal carcinomatosis (PC). PIPAC can be performed alone or alternated with systemic chemotherapy to increase tumor regression. We describe our initial experience performed in an expert hyperthermic intraperitoneal chemotherapy (HIPEC) French center to demonstrate the safety and the feasibility of PIPAC. METHODS: Between January 2016 and March 2019, PIPAC was proposed to 43 consecutive patients affected by digestive, ovarian, peritoneal and mammary carcinomatosis. Initially PIPAC was proposed to patients non eligible for cytoreductive surgery for palliative purposes. In five patients we associated PIPAC to systemic chemotherapy to improve tumor regression and enhance the chance of patients to undergo HIPEC. Three PIPAC treatments were supposed to be performed for each patient with an interval of 6 weeks in between each procedure. Peritoneal biopsies were always performed to evaluate microscopic tumor regression. In case of postoperative clinical deterioration or quick tumor progression during the cycles, PIPAC was interrupted. Depending on the primary tumor, chemotherapies used were oxaliplatin or a combination of cisplatin and doxorubicin. RESULTS: Twenty-six (60.4%) patients have already had a surgical resection or intervention of primary cancer removal. In 5 patients abdominal access was impossible. Of the 38 patients operated, seventy-one procedures were performed. In the series, one patient died because of tumor progression. Only one major complication occurred intraoperatively. Two of thirteen patients receiving oxaliplatin had postoperative abdominal pain and needed more drugs assumption and a longer hospitalization. Three patients after a three cycles procedure underwent HIPEC. Nine of the patients who had at least two PIPACs had last biopsies showing a major or complete tumor response. CONCLUSION: PIPAC is a safe and feasible procedure that can be performed in patients with peritoneal carcinomatosis initially not eligible for surgery to reduce tumor invasion or for palliation to reduce symptoms. Contraindications are bowel obstruction and multiple intraabdominal adhesions.


Subject(s)
Antineoplastic Agents/administration & dosage , Carcinoma/drug therapy , Hyperthermic Intraperitoneal Chemotherapy/methods , Peritoneal Neoplasms/drug therapy , Adult , Aerosols/administration & dosage , Carcinoma/surgery , Cisplatin/administration & dosage , Combined Modality Therapy , Cytoreduction Surgical Procedures/methods , Doxorubicin/administration & dosage , Feasibility Studies , Female , France , Humans , Middle Aged , Oxaliplatin/administration & dosage , Peritoneal Neoplasms/surgery , Treatment Outcome
3.
Surg Oncol ; 29: 120-125, 2019 Jun.
Article in English | MEDLINE | ID: mdl-31196475

ABSTRACT

BACKGROUND: Approximately 20% of initially eligible patients in a HIPEC procedure eventually underwent a simple surgical exploration. These procedures are called 'open & close' (O & C) representing up to 48% of surgery. The objective of this study was to predict the resecability of peritoneal carcinomatosis using a machine-learning model for decision-making support, for eligible patients of HIPEC. METHODS: The study was conducted as an intention to treat based on three databases including a prospective, between January 2000 and December 2015. A propensity score allowed us to obtain two groups of comparable and matched patients. Subsequently, several algorithm models of classification were studied (simple classification, conditional tree, support vector machine, random forest) to determine the model having the best performance and accuracy. RESULTS: Two groups of 155 patients were obtained: one group without resection and one group with resection. Nine criteria of non-resecability reflecting the organ involvement have been retained. They were coded according to their importance. Five classification algorithms were tested. The training data included 218 patients and 92 test data. The random forest model exhibited the best performance with an accuracy of close to 98%. Only two errors of predictions were observed. DISCUSSION: The largest number of patients will allow us to improve the precision prediction. Gathering more data such as biologic, radiologic, and even laparoscopic features, should improve the knowledge of the disease and decrease the number of 'O & C' procedures.


Subject(s)
Cytoreduction Surgical Procedures/statistics & numerical data , Decision Support Techniques , Laparoscopy/statistics & numerical data , Machine Learning , Peritoneal Neoplasms/diagnosis , Peritoneal Neoplasms/surgery , Adult , Aged , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prognosis , Prospective Studies , ROC Curve , Young Adult
4.
Eur J Cancer ; 65: 69-79, 2016 09.
Article in English | MEDLINE | ID: mdl-27472649

ABSTRACT

PURPOSE: Diffuse malignant peritoneal mesothelioma (DMPM) is a severe disease with mainly locoregional evolution. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is the reported treatment with the longest survival. The aim of this study was to evaluate the impact of perioperative systemic chemotherapy strategies on survival and postoperative outcomes in patients with DMPM treated with curative intent with CRS-HIPEC, using a multi-institutional database: the French RENAPE network. PATIENTS AND METHODS: From 1991 to 2014, 126 DMPM patients underwent CRS-HIPEC at 20 tertiary centres. The population was divided into four groups according to perioperative treatment: only neoadjuvant chemotherapy (NA), only adjuvant chemotherapy (ADJ), perioperative chemotherapy (PO) and no chemotherapy before or after CRS-HIPEC (NoC). RESULTS: All groups (NA: n = 42; ADJ: n = 16; PO: n = 16; NoC: n = 48) were comparable regarding clinicopathological data and main DMPM prognostic factors. After a median follow-up of 61 months, the 5-year overall survival (OS) was 40%, 67%, 62% and 56% in NA, ADJ, PO and NoC groups, respectively (P = 0.049). Major complications occurred for 41%, 45%, 35% and 41% of patients from NA, ADJ, PO and NoC groups, respectively (P = 0.299). In multivariate analysis, NA was independently associated with worse OS (hazard ratio, 2.30; 95% confidence interval, 1.07-4.94; P = 0.033). CONCLUSION: This retrospective study suggests that adjuvant chemotherapy may delay recurrence and improve survival and that NA may impact negatively the survival for patients with DMPM who underwent CRS-HIPEC with curative intent. Upfront CRS and HIPEC should be considered when achievable, waiting for stronger level of scientific evidence.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cytoreduction Surgical Procedures , Hyperthermia, Induced , Lung Neoplasms/therapy , Mesothelioma/therapy , Peritoneal Neoplasms/therapy , Adolescent , Adult , Aged , Chemotherapy, Adjuvant , Cytoreduction Surgical Procedures/methods , Female , Humans , Injections, Intraperitoneal , Lung Neoplasms/mortality , Male , Mesothelioma/mortality , Mesothelioma, Malignant , Middle Aged , Peritoneal Neoplasms/mortality , Retrospective Studies , Survival Analysis , Young Adult
5.
Gynecol Oncol ; 142(2): 237-42, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27246305

ABSTRACT

PURPOSE: Hyperthermic intraperitoneal chemotherapy (HIPEC) may improve the outcome of patients with initially unresectable ovarian cancer who are eligible for complete cytoreductive surgery (CCRS) after neoadjuvant chemotherapy. The main objective of this multicenter phase-I study was to identify the recommended dose of cisplatin for HIPEC at CCRS after neoadjuvant carboplatin and paclitaxel (CP). METHODS: Patients were treated with 6cycles of CP followed by CCRS and HIPEC using cisplatin heated for one hour at 42°C+/-1°C. Four cisplatin dose-levels were evaluated: 50, 60, 70, 80mg/m(2). Dose-limiting toxicities (DLTs) were defined as a grade≥IIIb adverse event (Dindo classification). The Continual Reassessment Method was used for this dose-finding study, with a target percentage of DLT set at 20%. Twenty-two cycles (15mg/kg/cycle) of maintenance bevacizumab therapy were planned after surgery. RESULTS: Between June-2011 and September-2012, 30 patients were recruited. No DLT occurred at the first three dose-levels (4, 4 and 5 patients at 50, 60 and 70mg/m(2) respectively). At dose-level 4 (80mg/m(2), 17 patients), four DLTs occurred: renal failure (n=2), peritonitis (n=1) and hemorrhage (n=1). Eight weeks after surgery, creatinine clearance was reduced to <30mL/min in 3 patients, all treated at 80mg/m(2), and between 30 and 60mL/min in 6 patients (2, 1, 1 and 2 at the four dose-levels respectively). Twenty patients started maintenance bevacizumab, and 7 received the 22 courses initially planned. CONCLUSIONS: Based on the observed DLTs and prolonged impairment of renal function, we recommend a dose of 70mg/m(2) of cisplatin for HIPEC.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Bevacizumab/administration & dosage , Cisplatin/administration & dosage , Hyperthermia, Induced/methods , Neoplasms, Glandular and Epithelial/therapy , Ovarian Neoplasms/therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carboplatin/administration & dosage , Carcinoma, Ovarian Epithelial , Chemotherapy, Adjuvant , Cisplatin/adverse effects , Dose-Response Relationship, Drug , Female , Humans , Maintenance Chemotherapy , Middle Aged , Neoadjuvant Therapy , Neoplasms, Glandular and Epithelial/drug therapy , Ovarian Neoplasms/drug therapy , Paclitaxel/administration & dosage
6.
Ann Surg Oncol ; 23(6): 1971-9, 2016 06.
Article in English | MEDLINE | ID: mdl-26753751

ABSTRACT

BACKGROUND: Peritoneal carcinomatosis is an increasingly common finding in gastric carcinoma. Previously, patients were treated as terminal, and median survival was poor. The use of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in this context is still highly debatable. OBJECTIVE: The aim of this study was to evaluate the long-term outcomes associated with CRS and HIPEC, and define prognostic factors for cure, if possible. PATIENTS AND METHODS: All patients with gastric carcinomatosis from five French institutions who underwent combined complete CRS and HIPEC and had a minimum follow-up of 5 years were included in this study. Cure was defined as a disease-free interval of more than 5 years from the last treatment until the last follow-up. RESULTS: Of the 81 patients who underwent CRS and HIPEC from 1989 to 2009, 59 had a completeness of cytoreduction score (CCS) of 0 (complete macroscopic resection), and the median Peritoneal Cancer Index (PCI) score was 6. Mitomycin C was the most commonly used drug during HIPEC (88 %). The 5-year overall survival (OS) rate was 18 %, with nine patients still disease-free at 5 years, for a cure rate of 11 %. All 'cured' patients had a PCI score below 7 and a CCS of 0. Factors associated with improved OS on multivariate analysis were synchronous resection (p = 0.02), a lower PCI score (p = 0.12), and the CCS (p = 0.09). CONCLUSION: The cure rate of 11 % for patients with gastric carcinomatosis who are deemed terminal emphasizes that CRS and HIPEC should be considered in highly selected patients (low disease extent and complete CRS).


Subject(s)
Adenocarcinoma/therapy , Carcinoma/therapy , Chemotherapy, Cancer, Regional Perfusion , Cytoreduction Surgical Procedures , Hyperthermia, Induced , Peritoneal Neoplasms/therapy , Stomach Neoplasms/therapy , Adenocarcinoma/pathology , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma/pathology , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Male , Middle Aged , Peritoneal Neoplasms/secondary , Prognosis , Stomach Neoplasms/pathology , Survival Rate , Young Adult
7.
Oncogene ; 35(2): 261-8, 2016 Jan 14.
Article in English | MEDLINE | ID: mdl-25867070

ABSTRACT

The occurrence of peritoneal carcinomatosis is a major cause of treatment failure in colorectal cancer and is considered incurable. However, new therapeutic approaches have been proposed, including cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC). Although HIPEC has been effective in selected patients, it is not known how HIPEC prolongs a patient's lifespan. Here, we have demonstrated that HIPEC-treated tumor cells induce the activation of tumor-specific T cells and lead to vaccination against tumor cells in mice. We have established that this effect results from the HIPEC-mediated exposure of heat shock protein (HSP) 90 at the plasma membrane. Inhibition or blocking of HSP90, but not HSP70, prevented the HIPEC-mediated antitumoral vaccination. Our work raises the possibility that the HIPEC procedure not only kills tumor cells but also induces an efficient anticancer immune response, therefore opening new opportunities for cancer treatment.


Subject(s)
Cancer Vaccines/pharmacology , HSP90 Heat-Shock Proteins/metabolism , Hyperthermia, Induced/methods , Peritoneal Neoplasms/immunology , Peritoneal Neoplasms/therapy , Animals , Cancer Vaccines/immunology , Cell Line, Tumor , Cell Membrane/metabolism , Coculture Techniques , Combined Modality Therapy , Dendritic Cells/immunology , HSP90 Heat-Shock Proteins/genetics , Humans , Mice, Inbred BALB C , Peritoneal Neoplasms/drug therapy , Xenograft Model Antitumor Assays
8.
Eur J Surg Oncol ; 41(10): 1361-7, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26263848

ABSTRACT

BACKGROUND: Over the last two decades, many surgical teams have developed programs to treat peritoneal carcinomatosis with extensive cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). Currently, there are no specific recommendations for HIPEC procedures concerning environmental contamination risk management, personal protective equipment (PPE), or occupational health supervision. METHODS: A survey of the institutional practices among all French teams currently performing HIPEC procedures was carried out via the French network for the treatment of rare peritoneal malignancies (RENAPE). RESULTS: Thirty three surgical teams responded, 14 (42.4%) which reported more than 10 years of HIPEC experience. Some practices were widespread, such as using HIPEC machine approved by the European Community (100%), individualized or centralized smoke evacuation (81.8%), "open" abdominal coverage during perfusion (75.8%), and maintaining the same surgeon throughout the procedure (69.7%). Others were more heterogeneous, including laminar flow air circulation (54.5%) and the provision of safety protocols in the event of perfusate spills (51.5%). The use of specialized personal protective equipment is ubiquitous (93.9%) but widely variable between programs. CONCLUSION: Protocols regarding cytoreductive surgery/HIPEC and the associated professional risks in France lack standardization and should be established.


Subject(s)
Air Conditioning/methods , Antineoplastic Agents/therapeutic use , Carcinoma/therapy , Cytoreduction Surgical Procedures/methods , Hyperthermia, Induced/methods , Infusions, Parenteral/methods , Peritoneal Neoplasms/therapy , Personal Protective Equipment/statistics & numerical data , Practice Patterns, Physicians' , France , Humans , Occupational Health , Risk Management , Smoke , Surveys and Questionnaires
9.
Gynecol Obstet Fertil ; 42(9): 622-5, 2014 Sep.
Article in French | MEDLINE | ID: mdl-25153435

ABSTRACT

Secondary localization to vagina had a severe prognosis, suggesting a disseminated metatastic disease. We report the case of prevalent vaginal metastasis of adenocarcinoma of the transverse colon. A 65 years old patient has consulted for vaginal mass. After delayed diagnosis, she presented with disseminated metastatic disease with peritoneal carcinomatosis. After neoadjuvant chemotherapy, the following treatment consisted of complete cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy and vaginal adjuvant radiotherapy. No recurrence occurred after one year. Vaginal metastasis of colon cancer are rare. The dark prognosis might justify a systematic gynecological examination of women presenting colorectal neoplasy.


Subject(s)
Adenocarcinoma/secondary , Colonic Neoplasms/pathology , Vaginal Neoplasms/secondary , Aged , Antineoplastic Agents/administration & dosage , Colon, Transverse , Combined Modality Therapy , Cytoreduction Surgical Procedures , Female , Humans , Peritoneal Neoplasms/drug therapy , Peritoneal Neoplasms/secondary , Peritoneal Neoplasms/surgery , Radiotherapy, Adjuvant , Vaginal Neoplasms/drug therapy , Vaginal Neoplasms/surgery
10.
J Visc Surg ; 151(1): 61-3, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24462837

ABSTRACT

We report a case of grade III pseudomyxoma peritonei revealed by mucusuria and abdominal mass. These symptoms are unusual; the most frequent clinical presentation is acute appendicitis or progressively increasing abdominal diameter.


Subject(s)
Appendix , Cecal Diseases/etiology , Digestive System Fistula/etiology , Peritoneal Neoplasms/diagnosis , Pseudomyxoma Peritonei/diagnosis , Urinary Bladder Fistula/etiology , Appendix/diagnostic imaging , Appendix/pathology , Cecal Diseases/diagnosis , Digestive System Fistula/diagnosis , Humans , Male , Middle Aged , Peritoneal Neoplasms/complications , Pseudomyxoma Peritonei/complications , Radiography , Urinary Bladder Fistula/diagnosis
11.
Eur J Surg Oncol ; 39(12): 1435-43, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24209430

ABSTRACT

BACKGROUND: Despite a high response rate to front-line therapy, prognosis of epithelial ovarian carcinoma (EOC) remains poor. Approaches that combine Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) have been developed recently. The purpose of this study was to assess early and long-term survival in patients treated with this strategy. PATIENTS AND METHODS: A retrospective cohort multicentric study from French centres was performed. All consecutive patients with advanced and recurrent EOC treated with CRS and HIPEC were included. RESULTS: The study included 566 patients from 13 centres who underwent 607 procedures between 1991 and 2010. There were 92 patients with advanced EOC (first-line treatment), and 474 patients with recurrent EOC. A complete cytoreductive surgery was performed in 74.9% of patients. Mortality and grades 3 to 4 morbidity rates were 0.8% and 31.3%, respectively. The median overall survivals were 35.4 months and 45.7 months for advanced and recurrent EOC, respectively. There was no significant difference in overall survival between patients with chemosensitive and with chemoresistant recurrence. Peritoneal Cancer Index (PCI) that evaluated disease extent was the strongest independent prognostic factor for overall and disease-free survival in all groups. CONCLUSION: For advanced and recurrent EOC, curative therapeutic approach combining optimal CRS and HIPEC should be considered as it may achieve long-term survival in patients with a severe prognosis disease, even in patients with chemoresistant disease. PCI should be used for patient's selection.


Subject(s)
Antineoplastic Agents/administration & dosage , Carcinoma/drug therapy , Carcinoma/surgery , Chemotherapy, Cancer, Regional Perfusion , Ovarian Neoplasms/pathology , Peritoneal Neoplasms/drug therapy , Peritoneal Neoplasms/surgery , Adult , Aged , Antineoplastic Agents/therapeutic use , Carcinoma/secondary , Chemotherapy, Cancer, Regional Perfusion/adverse effects , Digestive System Fistula/etiology , Disease-Free Survival , Female , France , Humans , Hyperthermia, Induced , Kaplan-Meier Estimate , Leukopenia/chemically induced , Middle Aged , Peritoneal Neoplasms/secondary , Postoperative Hemorrhage/etiology , Proportional Hazards Models , Renal Insufficiency/etiology , Retrospective Studies , Survival Rate
12.
Eur J Surg Oncol ; 39(7): 742-7, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23510853

ABSTRACT

AIM: Primary peritoneal serous carcinoma (PPSC) is a rare condition, histologically identical to ovarian serous carcinoma and often diagnosed at late stage. There is not any standardized treatment for PPSC. A retrospective multicentric study was performed in French speaking centers to evaluate cytoreduction surgery and Hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of peritoneal carcinomatosis from different origins. The manuscript's aim was to study the particular population with PPSC. METHODS: Between September 1997 and July 2007, 36 patients with PPSC from 9 institutions underwent 39 procedures. RESULTS: Mortality and morbidity rates were 5.6% and 20.6% respectively. The overall survival at 1, 3 and 5 years are respectively 93.6, 71.5 and 57.4%. The median overall survival was not reached. By univariate analysis, the only factor that had prognostic value was PCI (p = 0.03). CONCLUSIONS: The therapeutic approach combining cytoreductive surgery with HIPEC may achieve long-term survival in patients with PPSC.


Subject(s)
Carcinoma/mortality , Carcinoma/therapy , Chemotherapy, Cancer, Regional Perfusion/methods , Peritoneal Neoplasms/mortality , Peritoneal Neoplasms/therapy , Adult , Aged , Analysis of Variance , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Carcinoma/pathology , Chemotherapy, Adjuvant , Cohort Studies , Combined Modality Therapy , Disease-Free Survival , Female , France , Humans , Hypothermia, Induced/methods , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Staging , Peritoneal Neoplasms/pathology , Prognosis , Retrospective Studies , Risk Assessment , Survival Analysis , Treatment Outcome
13.
Ann Surg Oncol ; 19(13): 4052-8, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22825772

ABSTRACT

BACKGROUND: Epithelial ovarian carcinoma is the main cause of death from gynaecological cancers in the western world. The initial response rate to the frontline therapy is high. However, the prognosis of persistent and recurrent disease remains poor. During the two past decades, a new therapeutic approach to peritoneal carcinomatosis has been developed, combining maximal cytoreductive effort with hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: A retrospective, multicentric study of 246 patients with recurrent or persistent ovarian cancer, treated by cytoreductive surgery and HIPEC in two French centers between 1991 and 2008, was performed. RESULTS: An optimal cytoreductive surgery was possible in 92.2 % of patients. Mortality and morbidity rates were 0.37 % and 11.6 %, respectively. The overall median survival was 48.9 months. There was no significant difference in overall survival in patients with persistent or recurrent disease. In multivariate analysis, performance status was a significant prognostic factor in patients with extensive peritoneal carcinomatosis (peritoneal cancer index >10). CONCLUSIONS: Salvage therapy combining optimal cytoreductive surgery and HIPEC is feasible and may achieve long-term survival in highly selected patients with recurrent ovarian carcinoma, including those with platinum resistant disease, with acceptable morbidity.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hyperthermia, Induced , Neoplasm Recurrence, Local/therapy , Neoplasms, Glandular and Epithelial/therapy , Ovarian Neoplasms/therapy , Peritoneal Neoplasms/therapy , Adult , Aged , Carcinoma, Ovarian Epithelial , Chemotherapy, Adjuvant , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Middle Aged , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/pathology , Neoplasms, Glandular and Epithelial/mortality , Neoplasms, Glandular and Epithelial/pathology , Ovarian Neoplasms/mortality , Ovarian Neoplasms/pathology , Peritoneal Neoplasms/mortality , Peritoneal Neoplasms/secondary , Prognosis , Prospective Studies , Retrospective Studies , Survival Rate
14.
Cell Death Dis ; 2: e199, 2011 Sep 01.
Article in English | MEDLINE | ID: mdl-21881601

ABSTRACT

Metformin is the most widely used antidiabetic drug because of its proven efficacy and limited secondary effects. Interestingly, recent studies have reported that metformin can block the growth of different tumor types. Here, we show that metformin exerts antiproliferative effects on melanoma cells, whereas normal human melanocytes are resistant to these metformin-induced effects. To better understand the basis of this antiproliferative effect of metformin in melanoma, we characterized the sequence of events underlying metformin action. We showed that 24 h metformin treatment induced a cell cycle arrest in G0/G1 phases, while after 72 h, melanoma cells underwent autophagy as demonstrated by electron microscopy, immunochemistry, and by quantification of the autolysosome-associated LC3 and Beclin1 proteins. In addition, 96 h post metformin treatment we observed robust apoptosis of melanoma cells. Interestingly, inhibition of autophagy by knocking down LC3 or ATG5 decreased the extent of apoptosis, and suppressed the antiproliferative effect of metformin on melanoma cells, suggesting that apoptosis is a consequence of autophagy. The relevance of these observations were confirmed in vivo, as we showed that metformin treatment impaired the melanoma tumor growth in mice, and induced autophagy and apoptosis markers. Taken together, our data suggest that metformin has an important impact on melanoma growth, and may therefore be beneficial in patients with melanoma.


Subject(s)
Antineoplastic Agents/pharmacology , Antineoplastic Agents/toxicity , Apoptosis/drug effects , Autophagy/drug effects , Metformin/pharmacology , Metformin/toxicity , Animals , Apoptosis Regulatory Proteins/metabolism , Autophagy-Related Protein 5 , Beclin-1 , Cell Line, Tumor , G1 Phase , Humans , Melanoma/drug therapy , Melanoma/metabolism , Membrane Proteins/metabolism , Mice , Mice, Nude , Microtubule-Associated Proteins/antagonists & inhibitors , Microtubule-Associated Proteins/genetics , Microtubule-Associated Proteins/metabolism , RNA Interference , RNA, Small Interfering/metabolism , Resting Phase, Cell Cycle , Transplantation, Heterologous
15.
Eur J Surg Oncol ; 36(6): 589-93, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20466507

ABSTRACT

INTRODUCTION: The aim of the present study was to prospectively evaluate morbidity of intra-peritoneal hyperthermic chemotherapy (HIPEC) using Oxaliplatin as consolidation therapy for advanced epithelial ovarian carcinoma and, secondly, to study peritoneal recurrence. METHODS: Between 2004 and 2007, 31 patients from 18 to 65 years with FIGO stage IIIC epithelial ovarian carcinoma were treated by surgery and a total of 6 cycles of platinum based chemotherapy. Those patients were eligible for consolidation therapy. We performed a second look laparotomy operation with intra-peritoneal hyperthermic chemotherapy. We used Oxaliplatin 460 mg/m(2) with 2 l/m(2) of dextrose in an open medial laparotomy for a total of 30 min at a temperature of 42-44 degrees C. RESULTS: The grade 3 morbidity rate was 29% (95 CI: 14-45%). Nine patients experienced a total of 13 exploratory laparotomies for intra-abdominal bleeding after HIPEC. Two-year disease free and overall survival were 27% and 67% respectively. As a result of this high level of morbidity the trial was closed. CONCLUSION: Using intra-peritoneal Oxaliplatin associated with hyperthermia as consolidation therapy for advanced ovarian cancer results in a high risk of grade 3 morbidities with only a small benefit on survival.


Subject(s)
Antineoplastic Agents/administration & dosage , Hyperthermia, Induced , Organoplatinum Compounds/administration & dosage , Ovarian Neoplasms/drug therapy , Adolescent , Adult , Aged , Female , Hemorrhage/surgery , Humans , Infusions, Parenteral , Middle Aged , Neoplasm Staging , Ovarian Neoplasms/pathology , Ovarian Neoplasms/surgery , Oxaliplatin , Prospective Studies , Reoperation , Survival Rate , Treatment Outcome
16.
Eur J Surg Oncol ; 36(5): 456-62, 2010 May.
Article in English | MEDLINE | ID: mdl-20227231

ABSTRACT

OBJECTIVE: To analyze a large series of patients with pseudomyxoma peritonei (PMP) treated with cytoreductive surgery associated with perioperative intraperitoneal chemotherapy (PIC) in 18 French-speaking centers. PATIENTS AND METHODS: From March 1993 to December 2007, 301 patients with diffuse PMP were treated by cytoreductive surgery with PIC. Complete cytoreductive surgery was achieved in 219 patients (73%), and hyperthermic intraperitoneal chemotherapy (HIPEC) was performed in 255 (85%), mainly during the latter period of the study. RESULTS: Postoperative mortality and morbidity were 4.4% and 40%, respectively. The mean follow-up was 88 months. The 5-year overall and disease-free survival rates were 73% and 56%, respectively. The multivariate analysis identified 5 prognostic factors: the extent of peritoneal seeding (p=0.004), the center (p=0.0004), the pathologic grade (p=0.03), gender (p=0.02), and the use of HIPEC (p=0.04). When only the 206 patients with complete cytoreductive surgery were considered, the extent of peritoneal seeding was the only significant prognostic factor (p=0.004). CONCLUSION: This large multicentric retrospective study confirms that cytoreductive surgery combined with PIC (with the use of hyperthermia) should be considered as the gold standard treatment of PMP and should be performed in specialized centers. It underlines the prognostic impact of the extent of peritoneal seeding, especially in patients treated by complete cytoreductive surgery. This prognostic impact appears to be greater than that of the pathologic grade.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Peritoneal Neoplasms/drug therapy , Peritoneal Neoplasms/surgery , Pseudomyxoma Peritonei/drug therapy , Pseudomyxoma Peritonei/surgery , Adult , Aged , Female , Fluorouracil/administration & dosage , France , Humans , Hyperthermia, Induced , Infusions, Parenteral , Male , Middle Aged , Mitomycin/administration & dosage , Prognosis , Retrospective Studies , Survival Analysis , Treatment Outcome
18.
Ann Chir ; 130(3): 178-80, 2005 Mar.
Article in French | MEDLINE | ID: mdl-15784222

ABSTRACT

Aneurysms of pancreaticoduodenal arteries represent only 2% of all aneurysms of digestive arteries. Occurrence of these aneurysms are favoured by stenosis or occlusion of the celiac axis. Aneurysm rupture is frequent and carries a mortality rate of 20%. Computed tomography with intravenous contrast and selective coeliomesenteric arteriography can make the diagnosis of this disease which can be treated by either surgery or embolotherapy. We report the case of a patient with a ruptured aneurysm of the pancreaticoduodenal arcades mimicking a perforated duodenal ulcer, and successfully treated by surgical ligation.


Subject(s)
Aneurysm, Ruptured/diagnosis , Aneurysm, Ruptured/surgery , Duodenal Ulcer/diagnosis , Duodenum/blood supply , Ligaments/pathology , Pancreas/blood supply , Aged , Aneurysm, Ruptured/complications , Diagnosis, Differential , Female , Humans , Ligation , Syndrome , Tomography, X-Ray Computed , Treatment Outcome
19.
J Clin Oncol ; 22(16): 3284-92, 2004 Aug 15.
Article in English | MEDLINE | ID: mdl-15310771

ABSTRACT

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.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma/drug therapy , Carcinoma/secondary , Colorectal Neoplasms/pathology , Peritoneal Neoplasms/drug therapy , Peritoneal Neoplasms/secondary , Adolescent , Adult , Aged , Aged, 80 and over , Carcinoma/surgery , Chemotherapy, Adjuvant , Female , Humans , Infusions, Parenteral , Male , Middle Aged , Perioperative Care , Peritoneal Neoplasms/surgery , Prognosis , Retrospective Studies , Survival Analysis , Treatment Outcome
20.
Ann Chir ; 129(6-7): 353-8, 2004.
Article in French | MEDLINE | ID: mdl-15297225

ABSTRACT

UNLABELLED: Self-expanding metallic stents is an alternative treatment to colostomy that is the treatment of choice in acute tumoral left colonic obstruction. AIM OF THE STUDY: To compare morbidity, mortality, length of hospital stay and treatment performed after desobstruction using the two methods. PATIENTS AND METHODS: Thirty-three patients admitted for acute obstruction of the left colon were retrospectively separated in two groups depending on the type of intervention performed to treat the obstruction ("colostomy" group: 17 patients and "self-expanding stent group": 16 patients). We studied complications after desobstruction, hospital courses and surgical strategy performed after the acute phase. RESULTS: Time between desobstruction and colectomy was shorter in the "self-expanding stent group" than in the "colostomy group" (18.5 days versus 73 days). Age superior than 75 years and colostomy were the two main factors predicting the risk of definitive colostomy (P < 0.05). Global mean hospital stay was longer in the colostomy group (32.7 days versus 19.3 days, P = 0.02). Two perforations and one local recurrence occurred in the "self-expanding stent group". CONCLUSIONS: Self-expanding metallic stent can decrease the permanent colostomy rate and the number of interventions. The recurrence rate seems to be theoretically increased with the stenting method. Then, colostomy must be done for patients in curative situation. The self-expanding metallic stent should be used as a palliative care.


Subject(s)
Colon/pathology , Colon/surgery , Colostomy/methods , Intestinal Obstruction/etiology , Intestinal Obstruction/therapy , Stents , Acute Disease , Adult , Aged , Aged, 80 and over , Female , Humans , Length of Stay , Male , Middle Aged , Morbidity , Mortality , Palliative Care , Recurrence , Retrospective Studies
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