BRAF mutation is not associated with an increased risk of recurrence in patients undergoing resection of colorectal liver metastases.

BACKGROUND: BRAF mutation is associated with a poor prognosis in patients with metastatic colorectal cancer. For patients with resectable colorectal liver metastases (CRLMs), the prognostic impact of BRAF mutation is unknown and the benefit of surgery debated. This nationwide intergroup (ACHBT, FRENCH, AGEO) study aimed to evaluate the oncological outcome of patients undergoing liver resection for BRAF-mutated CRLMs. METHODS: The study included patients who underwent resection for BRAF-mutated CRLMs in 24 centres between 2012 and 2016. A case-matched comparison was made with 183 patients who underwent resection of CRLMs with wild-type BRAF during the same interval. RESULTS: Sixty-six patients who underwent resection for BRAF-mutated CRLMs in 24 centres were compared with 183 patients with wild-type BRAF. The 1- and 3-year disease-free survival (DFS) rates were 46 and 19 per cent for the BRAF-mutated group, and 55·4 and 27·8 per cent for the group with wild-type BRAF (P = 0·430). In multivariable analysis, BRAF mutation was not associated with worse DFS (hazard ratio 1·16, 95 per cent c.i. 0·72 to 1·85; P = 0·547). The 1- and 3-year overall survival rates after surgery were 94 and 54 per cent respectively among patients with BRAF mutation, and 95·8 and 82·9 per cent in those with wild-type BRAF (P = 0·004). Median survival after disease progression was 23·0 (95 per cent c.i. 11·0 to 35·0) months among patients with mutated BRAF and 44·3 (35·9 to 52·6) months in those with wild-type BRAF (P = 0·050). Multisite disease progression was more common in the BRAF-mutated group (48 versus 29·8 per cent; P = 0·034). CONCLUSION: These results support surgical treatment for resectable BRAF-mutated CRLM, as BRAF mutation by itself does not increase the risk of relapse after resection. BRAF mutation is associated with worse survival in patients whose disease relapses after resection of CRLM, as for non-metastatic colorectal cancer.

[Digestive neuroendocrine tumors]. / Tumeurs neuroendocrines digestives.

Digestive neuroendocrine tumors (NETs) are a group of rare tumors with increasing incidence. Pathological analysis is critical to establish the diagnosis and evaluate tumor grade that relies on differentiation and proliferation index. NETs are mostly diagnosed at an advanced stage because of late occurrence of nonspecific symptoms, and can be associated with hormone hypersecretion. Chromogranin A is the main biochemical marker of NETs. Extension workup relies on conventional imaging (CT-scan, MRI) and isotopic imaging including somatostatin-receptor scintigraphy, which should be soon replaced by positron-emitting scintigraphy. The main prognostic factors include tumor stage, metastatic volume, histological differentiation and grade. Hormonal syndromes and poorly differentiated tumors are the two therapeutic emergencies. The treatment of localized well-differentiated tumors relies on endoscopic or surgical resection depending on the location and aggressiveness. Surgical removal is the only potentially curative treatment of metastatic NETs but is rarely feasible and is associated with almost constant relapse. Other antitumor therapies include somatostatin analogs, systemic chemotherapy, liver trans-arterial chemo-embolization, targeted therapies and peptide-receptor radionuclide therapy. Management strategy relies on primary tumor location, tumor aggressiveness, metastatic volume and the presence of extra-hepatic metastases. It must take into account the risk of cumulated toxicity in patients whose survival is often prolonged.

Digestive diseases mimicking primary gynecological diseases or with secondary gynecological manifestations.

A wide range of gastrointestinal diseases may spread to and involve genital organs by different pathways. These pathways result in extension of the pathological process into the extraperitoneal spaces and between the extra- and intraperitoneal spaces. These communications occur either via mesenteries and ligaments or via the posterior parietal peritoneum. Thus, infectious, inflammatory or tumoral digestive diseases can extend into the pelvic organs and present with a misleading clinical picture and/or radiological features, showing the complexity of pelvic diseases in women. This article reviews, illustrates and discusses these different presentations and provides certain clues to help reach a definite diagnosis.

Is primary tumor resection associated with a longer survival in colon cancer and unresectable synchronous metastases? A 4-year multicentre experience.

AIM: To explore the survival impact of primary tumor resection (PTR) in patients with metastatic colon cancer (mCC) and unresectable metastases. METHODS: We retrospectively studied a multicenter cohort of consecutive mCC patients with unresectable metastases receiving first-line chemotherapy. A weighted Cox proportional regression model was used to balance for clinical variables associated with the probability of undergoing PTR, using inverse probability of treatment weighting (IPTW) based on a propensity score. RESULTS: Ninety-six patients were included. PTR was performed in 69 (72%). The rates of secondary resection of metastases (p = 0.02) and bevacizumab administration (p = 0.02) were higher in the PTR group. Raw median overall survival (OS) was 23.1 months (95%CI[14.6-27.8]) in the PTR group and 22.1 months (95%CI[12.3-23.7]) in the non-PTR group (p = 0.11). After adjustment on IPTW, OS was 23.1 months (95%CI[17.0-28.7]) in the PTR group and 17.2 months (95%CI[13.5-22.2]) in the non-PTR group (HR 0.68; 95%CI[0.50-0.93]; p = 0.016). This result remained significant on multivariate analysis (HR 0.71; 95%CI[0.50-1.00]; p = 0.05). CONCLUSION: In mCC patients with unresectable metastases receiving chemotherapy, up-front PTR was independently associated with prolonged OS. Patients eligible for secondary metastases resection and/or bevacizumab may benefit the most from PTR. Randomized controlled trials are mandatory.