Fabio Caniglia

Laparoscopic robot-assisted major hepatectomy

We herein present a systematic review of English literature on robot‐assisted major hepatectomy (MH).

The odd case of a small and mucinous-like acinar cell cystoadenocarcinoma of the pancreas

Improvement of imaging has made the incidental diagnosis of pancreatic cysts very common. Interpretation of diagnostic information, however, is not always straightforward. We report on one of such patients, initially thought to have a mucinous cystic tumor of the pancreas, and eventually diagnosed with a higher grade acinar cell cystoadenocarcinoma (ACC). In April 2009, a 63-year old woman underwent total gastrectomy because of gastric cancer (undetermined tumor type, T2bN0M0–G1; 48 examined lymph nodes). During preoperative work-up contrast enhanced computed tomography (CT) showed a uniloculated cystic lesion in the head of the pancreas. During gastrectomy the cyst was aspirated. Cytology revealed protein rich fluid without evidence of epithelial cells. The patient underwent a 4 month course of multi-agent adjuvant chemotherapy, based on FOLFIRI (irinotecan, 5-fluoracil, and folinic acid), platinum and taxotere. During the follow-up CT showed progressive increase of the size of the cyst up to 30 mm, and the patient was referred to our center. Magnetic resonance cholangiopancreatography and CT (Fig. 1) demonstrated no communication between the cyst and the main pancreatic duct (MPD). Although the more likely preoperative diagnosis was mucinous cystadenoma, we preferred to proceed with pancreaticoduodenectomy mostly because of the growth of the cystic lesion, despite the patient was receiving multi-agent chemotherapy. We also considered that the digestive changes associated with total gastrectomy could have blurred the interpretation of developing complaints. Finally, concerns on pursuing major surgery in a patient recently operated because of gastric cancer were, at least in part, addressed by favorable tumor staging. Frozen section histology suggested side branch intraductal papillary mucinous neoplasm with normal MPD. On gross examination, the cyst measured 3 2 cm, communicated with the MPD, and was filled with milky content. Final pathology disclosed ACC (Fig. 2). Resection margins were negative and no metastasis was discovered in 30 regional lymph nodes. Post-operative course was uneventful and the patient was discharged on post-operative day 9. She received gemcitabine-based adjuvant chemotherapy for 5 months. One year after pancreaticoduodenectomy the patient is alive and disease-free. Acinar cell carcinoma of the pancreas is a rare solid epithelial exocrine tumor (1–2% of all exocrine pancreatic tumors) [1–5]. It is defined as a carcinoma exhibiting exocrine differentiation and lacking significant (<25%) ductal or endocrine differentiation [2,3].

Left Hepatectomy: Robot-Assisted Approach

Laparoscopy is now the standard approach for left lateral segmentectomy and is the preferred method for resection of liver tumors measuring <5 cm located in anterior segments [1, 2]. In properly selected patients managed at high- volume centers, laparoscopic liver surgery (LLS) is associated with reduced blood loss, diminished need for blood transfusions, low rate of microscopically positive margins, and improved outcome in cirrhotic patients [3]. Despite the fact that gifted hepatic surgeons facile with complex laparoscopic maneuvers have successfully performed posterior segmentectomies and major hepatectomies [1–3], the inherent limitations of the laparoscopic technique have significantly limited its acceptance for challenging hepatic resections [1,2].

The New Automated Algorithm to Evaluate Ki67 in pNET. The Five “W” law: Who, When, Where, What, and Why

Context Ki67 index (Ki67-I), is the percentage Ki67 immunoreactive cells, expressing tumor proliferation, with important clinical relevance in pancreatic neuroendocrine tumors (pNET) and to standardize its evaluation is extremely important. The pNET guideline indicate to evaluate at list 2 mm 2 of tissue or 2,000 tumor cells. However, this type of evaluation is currently done by subjective opinion of pathologist concerning the area of interest (AI). Objective We elaborated a new algorithm of analysis able to catch all tumor cells present in the selected area according to the pathologist’s criteria. Methods The program (D-Sight, 2.0, Menarini, Florence, Italy) catch all color intensity on the tissue surface, to understand whether which type of sensitivity to immunohistochemistry could match with the Ki67-I. The system returns automatically the number of both total and stained cells. Results The first attempts made on the samples previously evaluated (15 cases with the oldest algorithm) showed an improvement of two important parameters: 1) a better evaluation of total tumor cells present in AI; and 2) a good evaluation of nuclei aggregation. These two data showed a better Ki67-I in pNET, very close to the pathologist’s interpretation. Conclusion The possibility to standardize a fully automated methodology to evaluate Ki67 value can improve both pathological evaluation (i.e., grading of the tumor) and clinical management of pancreatic neuroendocrine patients. This application could open also the new analytical evaluations of other protein markers involved in clinical outcome of oncologic patients.

PTEN and MIR-21 Expression in IPMN and PDAC

Context The prognosis of invasive IPMN is better than for PDAC and many authors believe that IPMNs have distinct genetic and biological characteristics underlying this different clinical behavior. Objective Since previous studies correlated miR-21 expression with PTEN levels and worse prognosis in PDAC, we compared PTEN and miR-21 expression in invasive IPMNs and PDACs. Methods Ten invasive IPMN and 16 PDAC were evaluated for both PTEN expressions, with a validated immunohistochemistry method: 4 degrees of score (0 absent, 1 weak, 2 moderate, 3 strong). The miR-21 expression, as assessed by PCR in mRNA isolated from laser-microdissected samples. According to the miR21 quantification, all samples were identified as follow: (IPMN-L, IPMN-H, PDAC-L and PDAC-H). Statistical analysis was performed using ANOVA tests. Results IPMNs with high mi-R21 expression presented a negative/weak PTEN cytoplasmatic staining, with only few scattered positive cells, while IPMNs characterized by low mi-R21, had a moderate or strong cytoplasmic PTEN expression. This inverse correlation of miR-21 and PTEN expression was also observed in PDAC. However, we observed a significant difference comparing PTEN IPMN-L vs . PDAC-L (P=0.021), IPMN-L vs . IPMN-H (P=0.041) and all groups (P=0.037). Conclusion PTEN expression correlated with miR-21 in both invasive IPMNs and PDACs. Moreover, PDAC had significantly higher levels of miR-21 and lower levels of PTEN than IPMNs, suggesting that these biological characteristics might underline the better clinical outcome of IPMN compared to PDAC.