GNAS but Not Extended RAS Mutations Spectrum are Associated with a Better Prognosis in Intraductal Pancreatic Mucinous Neoplasms.

BACKGROUND: The management of intraductal papillary mucinous neoplasms (IPMNs) is mainly based on imaging features and clinical symptoms, and remains challenging. OBJECTIVE: The aim of this study was to assess GNAS, RAS family (KRAS, NRAS and HRAS), BRAF, and PIK3CA mutation status in resected IPMNs and correlate it with clinicopathological characteristics and patient survival. METHODS: Overall, 149 consecutive unselected patients who underwent pancreatectomy for IPMNs were included. After dissection from formalin-fixed and paraffin-embedded tumors, GNAS mutational screening was assessed by allelic discrimination using Taqman® probes and confirmed by SNaPshot analysis. RAS family, BRAF, and PIK3CA mutational screening was assessed by high resolution melt and Sanger sequencing. RESULTS: Gastric- and intestinal-type IPMNs were the most frequent lesions (52% and 41%, respectively). Intestinal-type IPMNs were more frequently associated high-grade dysplasia (49%) and were the only IPMNs associated with colloid-type carcinoma. All pancreatobiliary IPMNs were invasive lesions, located in the main pancreatic duct. GNAS-activating mutations were strongly associated with the intestinal phenotype (p < 10-4), while RAS pathway mutations were not associated with any particular phenotype. Mutations within other members of the epidermal growth factor receptor (EGFR) pathway were very rare (2%). GNAS-mutated IPMNs were rarely invasive (11%) and almost exclusively (83%) of the colloid type. For invasive lesions, multivariate analyses determined that only node negativity was associated with improved cancer-specific survival, but, in univariate analysis, GNAS mutation was associated with prolonged survival. CONCLUSION: In patients selected for surgery, GNAS mutation analysis and tumor phenotype can help to better predict patient prognosis. In the near future, a more precise mutational analysis of IPMNs might help to better tailor their management.

Liver angulometry: a simple method to estimate liver volume and ratios.

OBJECTIVES: Volumetry is standard method for evaluating the volumes of the right liver (RL), left liver (LL), left lateral segments (LLS), total liver (TL) and future liver remnant (FLR). The aim of this study was to report a simple technique based on measurements of liver angles (angulometry) that can be used to predict liver ratios. METHODS: Fifty computed tomography (CT) scans obtained in subjects with normal liver were studied. Four CT scan levels were preselected: level 1 passed by the upper part of the hepatic veins; level 2 passed by the left portal vein branch division; level 3 passed by the right portal vein branch division, and level 4 passed by the gallbladder bed. Left and right tangent lines passing the liver edges were drawn and joined to the centre of the vertebra defining the TL angle. Two lines through, respectively, the plane of the middle hepatic vein and the left portal branches determined the angles of the RL, LL and LLS. Volumetric and angulometric data obtained on levels 2 and 3 in 50 different subjects were compared. RESULTS: Level 2 CT scans represented the most accurate way of obtaining angulometric measurements. The mean ± standard deviation (SD) angles of the TL and LL were 134 ± 12 ° and 55 ± 12 °, respectively. The mean ± SD percentages of the TL represented by the LL in angulometry and volumetry were 38 ± 7% and 36 ± 6%, respectively (non-significant difference). The mean ± SD percentages of the TL represented by the LLS in angulometry and volumetry were 25 ± 4% and 20 ± 3%, respectively (P < 0.05). The mean ± SD overestimation of the percentage of the TL represented by the LLS in angulometry was 2.7 ± 7.0%. CONCLUSIONS: Angulometry is a simple and accurate technique that can be used to estimate the ratio of the FLR to TL volume on one or two CT (or magnetic resonance imaging) slices. It can be helpful for clinicians, especially before right or extended right hepatectomy and after right portal vein occlusion techniques.

Complicated Meckel's diverticulum: Presentation modes in adults.

Complicated Meckel's diverticulum represents a common etiology of acute abdomen in children. However, this condition is less frequent in adults. We reviewed the records of adult patients who underwent the surgical removal of complicated Meckel's diverticulum between 2001 and 2017 at 2 tertiary French medical centers. We then analyzed the clinical characteristics, mode of presentation, and management for all patients.The Meckel's diverticulum was resected in 37 patients (24 males and 13 females). The mean patient age was 46.1 ±â€Š21.4 years. The most common clinical presentations of complicated Meckel's diverticulum were diverticulitis (35.1%, n = 13), small-bowel obstruction (35.1%, n = 13), and gastrointestinal bleeding (29.8%, n = 11) (anemia, n = 1; hematochezia, n = 10). Age distribution was significantly different (P = .02) according to the 3 Meckel's diverticulum complications: patients with diverticulitis (P = .02) were statistically more frequently over 40 (P = .05), significantly older than patients with gastrointestinal bleeding who were more frequently <40 (P = .05). There was a preoperative diagnosis available for 15 of the 37 patients (40%). An exploratory laparoscopy was necessary to determine the cause of disease for the other 22 patients (60%). An intestinal resection was performed in 33 patients (89%) and diverticulectomy was performed in 4 patients (11%). There was heterotopic tissue found in only 6 patients (16%). Postoperative complications were as follows: 1 death by cardiac failure in a 92-year-old patient and 2 patients with postoperative wound infections. The follow-up time was 3 to 12 months.The correct diagnosis of complicated Meckel's diverticulum in adults is difficult due to the lack of specific clinical presentation. As a result, exploratory laparoscopy appears to play a central role in cases of acute abdomen with uncertain diagnosis.

Lessons from McCune-Albright syndrome-associated intraductal papillary mucinous neoplasms: : GNAS-activating mutations in pancreatic carcinogenesis.

GNAS-activating mutations are reported in intraductal papillary mucinous neoplasms (IPMNs) and in McCune-Albright syndrome, characterized by fibrous dysplasia, precocious puberty, and café au lait spots. Recently, IPMNs have been described as a McCune-Albright syndrome-associated tumor, present in about 15% of patients. The aim of the present work was to assess the prevalence of polyostotic fibrous dysplasia and McCune-Albright syndrome among patients operated on for presumptive sporadic IPMNs. All patients operated on for IPMNs between January 1, 2007, and December 31, 2012, with available imaging were retrospectively screened for polyostotic fibrous dysplasia based on their preoperative abdominal or thoracoabdominal spiral computed tomography images. Systematic screening of 272 patients operated on for IPMNs revealed 1 patient with axial and peripheral polyostotic fibrous dysplasia and café au lait spots on clinical examination suggestive of McCune-Albright syndrome. This patient had been operated on for an unusually large invasive colloid adenocarcinoma (pT3N0M0 R0) derived from an intestinal subtype GNAS-mutated IPMN. The patient underwent adjuvant chemotherapy with gemcitabine for 6 months and was alive without recurrence 6 years later. Besides providing additional evidence of a syndromic IPMN as a feature of McCune-Albright syndrome, this observation is further evidence of the functional oncogenic consequences of GNAS mutations in the pancreas.