Dominique Béchade

Cytoreductive Surgery of Colorectal Peritoneal Metastases: Outcomes after Complete Cytoreductive Surgery and Systemic Chemotherapy Only

Background Cytoreductive peritoneal surgery (CRS) associated with hyperthermic peritoneal chemotherapy (HIPEC) has long been considered the standard treatment for colorectal peritoneal metastases (CPM). However, although efficacy of surgery has been demonstrated, evidence supporting HIPEC’s role is less certain. Method Overall survival (OS), progression-free survival (PFS) and morbidity were analysed retrospectively for fifty consecutively included patients treated for colorectal CPM with complete CRS and systemic chemotherapy only. Results Median peritoneal cancer index (PCI) was 8 (range 1-24). 23 patients had liver or lung metastases (LLM). 22 patients had synchronous CPM. 27 complications occurred (12 Grade 1/2, 14 Grade 3, 1 Grade 4a, 0 Grade 5). Median follow-up was 62.5 months (95 %CI 45.4-81.3), median survival 32.4 months (21.5-41.7). Three- and 5-year OS were 45.5% (0.31-0.59) and 29.64% (0.17-0.44) respectively. Presence of LLMs associated with peritoneal carcinomatosis was significantly associated with poorer prognosis, with survival at 5 years of 13.95% (95 %CI 2.9-33.6) vs. 43.87% (22.2-63.7) when no metastases were present (P= 0.018). Median PFS was 9.5 months (95 %CI 6.2-11.1). Conclusion With an equivalent PCI range and despite one of the highest rates of LLM in the literature, our survival data of CRS + systemic chemotherapy only compare well with results reported after additional HIPEC. Tolerance was better with acceptable morbidity without any mortality. Extra-hepatic metastasis (LLM) is a strong factor of poor prognosis. Awaiting the results of the randomized PRODIGE trial, these results indicate that CRS + systemic chemotherapy only is a robust hypothesis to treat colorectal CPM.

Pancreatic Acinar Cell Carcinoma.

Pancreatic acinar cell carcinoma (ACC) is a rare malignant neoplasm that accounts for 1–2% of all pancreatic neoplasms. Here we report two cases of ACC and describe their clinical features, the therapies used to treat them, and their prognosis. The first patient was a 65-year-old woman who had an abdominal CT scan for a urinary infection. Fortuitously, a rounded and well-delimited corporeal pancreatic tumor was discovered. An endoscopic ultrasound (EUS)-guided fine needle aspiration revealed an ACC. During the puncture, a hypoechoic cavity appeared inside the lesion, corresponding to a probable necrotic area. Treatment consisted of a distal splenopancreatectomy. The second patient was a 75-year-old man who complained of abdominal pain. An abdominal CT scan showed a cephalic pancreatic lesion and two hepatic metastases. An EUS-guided fine needle aspiration showed a pancreatic ACC. The patient received chemotherapy with gemcitabine plus oxaliplatin (GEMOX regimen), which enabled an objective response after 6 cycles.

Place de l'échoendoscopie œsophagienne (EUS) et bronchique (EBUS) dans l'évaluation des adénopathies médiastinales

Mediastinal lymphadenopathy may be detected by CT-scan or positron emission tomography. Malignant (e.g, lung cancer, metastatic cancer, lymphoma), infectious (e.g, tuberculosis, histoplasmosis), and systemic processes (e.g, sarcoidosis) can cause mediastinal adenopathy. In the posterior and inferior mediastinum, endoscopic ultrasound visualizes and directs transesophageal fine needle aspiration of adenopathy. In the anterior mediastinum, endobronchial ultrasound visualizes and directs transbronchial fine needle aspiration of adenopathy. We discuss the role of EUS and EBUS in the evaluation of mediastinal adenopathy according to their anatomical localization.

Stratégies de dépistage de l’adénocarcinome pancréatique chez les patients à haut risque

Screening high-risk individuals with imaging tests, such as endoscopic ultrasound and computed tomography, can lead to the detection and treatment of predominantly asymptomatic premalignant lesions. These pancreatic lesions consist of resectable, mostly branch-type non-invasive intraductal papillary mucinous neoplasms. Endoscopic ultrasound features of chronic pancreatitis are highly prevalent in high-risk individuals and these directly correlate with multifocal lobulocentric parenchymal atrophy due to pancreatic intraepithelial neoplasia. Long-term, multi-prospective studies are needed to determine if screening for early pancreatic adenocarcinoma and timely intervention will result in decreased pancreatic cancer incidence and mortality in high-risk individuals.

Toxicité hépatique des inhibiteurs des tyrosines kinases : mécanismes en cause et conséquences pratiques

Tyrosine kinase inhibitors (TKIs) are used for the targeted treatment of solid cancers. TKIs produce a variable incidence of liver adverse events (5-25%) which can progress to severe liver injury in a minority of patients if treatment is maintained despite ongoing injury. This risk requires careful patient management to maintain treatment benefit without harm. This review highlights the various mechanisms of idiosyncratic hepatotoxicity, the formation of reactive metabolites and how this leads to toxicity. These critical events depend of the drug-specific characteristics of each TKI and the patient risk factors, especially genetic characterization. With improved understanding of the mechanisms leading to hepatotoxicity, several strategies have been adopted to prevent or treat this side effect. Recommendations on liver function liver test monitoring have been proposed according to each TKI.

Parenchymal sparing surgery for colorectal liver metastases: The need for a common definition.

e15013Background: Colorectal cancer metastases (CRLM) are major public health issue. Recently, surgeons have advocated the use of parenchymal sparing surgery (PSS) however, a common definition of t...

Parenchymal sparing surgery for colorectal liver metastases: The need for a common definition

BACKGROUND The definition of parenchymal sparing surgery (PSS) for colorectal liver metastases (CRLM) diverges requiring a clarification of the concept. METHOD A consecutive series of patients were treated by PSS for their CRLMs, either by resection or intra-operative ablation (IOA), whenever possible a one-stage surgery and minimal usage of portal vein embolization. Post-operative complications were the primary endpoint with a special focus on post-operative liver failure. RESULTS Three hundred and eighty-seven patients underwent a PSS out of which 328 patients received a median of 9 pre-operative cycles of chemotherapy. One hundred and twenty-eight patients had a major resection, combined with IOA in 137 patients and IOA alone in 50 cases. The 5yr-overall survival was 50.3%. There was no difference in post-operative complications between minor and major resections, validating our PSS definition based on the Tumor burden/Healthy liver ratio and not just the retrieved volume. CONCLUSIONS PSS is defined as a high ratio of tumoral burden per specimen retrieved while favoring one-stage surgery approach. Our series, using combined resections and IOAs, matches this definition well. Furthermore, complications were correlated neither to chemotherapy nor to liver-induced toxicities, contrary to extended hepatectomies.

Fatal Acute Liver Failure as a Consequence of Regorafenib Treatment in a Metastatic Colon Cancer

Regorafenib is a multikinase inhibitor which showed benefits in pretreated metastatic colorectal cancer patients. Hepatotoxicity has been described as a frequent side effect. We report the case of a 65-year-old patient presenting with jaundice, fever, and hepatocellular insufficiency which led to death of the patient. She had previously been treated with several lines of chemotherapy for sub- and diaphragmatic ganglionic metastases of a colon adenocarcinoma. There were no liver metastases. The fatal liver failure occurred at the beginning of treatment with regorafenib at a dosage of 3 tablets per day. No concomitant treatment was given, and other causes of liver damage were eliminated. The liver biopsy showed hepatocyte necrosis with lymphocyte infiltration. This observation illustrates the risk of severe hepatic involvement typically occurring within the first 2 months of treatment. Monitoring liver biology every 2 weeks is essential during the first 2 months to detect any hepatotoxicity.

An investigation of the role of irinotecan and oxaliplatin in liver toxicity during first-line neoadjuvant chemotherapy.

689 Background: Neoadjuvant chemotherapy (CT) have been associated with an increased risk of surgery for colorectal liver metastases (CRLM). Irinotecan (IRI) is claimed to induce CT-associated steatohepatitis (CASH) and oxaliplatin (OX) to induce sinusoidal obstruction (SOS). Imputability is sometimes difficult to establish and the impact on postoperative complications is unclear. The objective of this study is to investigate the impact of IRI and OX on induced liver toxicity, and to study the effects of toxicity on surgical outcomes. Methods: Patients (Pts) who received only one line of CT before resection of CRLM were retrospectively included. CASH and SOS were described according to Kleiner and Rubbia-Brandt classifications respectively. Associations were sought between CASH or SOS and various patient and treatment factors, and between patient and treatment factors and the occurrence of post-operative complications grade 3 or over. Results: Among 379 pts operated on for CRLM from 2003 to 2013, 223 were...

Place de l'échoendoscopie œsophagienne (EUS) et bronchique (EBUS) dans l'évaluation des adénopathies médiastinalesRole of endoscopic ultrasound (EUS) and endobronchial ultrasound (EBUS) for the evaluation of mediastinal adenopathy

Mediastinal lymphadenopathy may be detected by CT-scan or positron emission tomography. Malignant (e.g, lung cancer, metastatic cancer, lymphoma), infectious (e.g, tuberculosis, histoplasmosis), and systemic processes (e.g, sarcoidosis) can cause mediastinal adenopathy. In the posterior and inferior mediastinum, endoscopic ultrasound visualizes and directs transesophageal fine needle aspiration of adenopathy. In the anterior mediastinum, endobronchial ultrasound visualizes and directs transbronchial fine needle aspiration of adenopathy. We discuss the role of EUS and EBUS in the evaluation of mediastinal adenopathy according to their anatomical localization.