Vincenzo Neri

TRAP1, a novel mitochondrial chaperone responsible for multi-drug resistance and protection from apoptotis in human colorectal carcinoma cells

TRAP1 is a component of a pro-survival mitochondrial pathway up-regulated in tumor cells. The evaluation of TRAP1 expression in 26 human colorectal carcinomas showed up-regulation in 17/26 tumors. Accordingly, TRAP1 levels were increased in HT-29 colorectal carcinoma cells resistant to 5-fluorouracil, oxaliplatin and irinotecan. Thus, we investigated the role of TRAP1 in multi-drug resistance in human colorectal cancer. Interestingly, TRAP1 overexpression leads to 5-fluorouracil-, oxaliplatin- and irinotecan-resistant phenotypes in different neoplastic cells. Conversely, the inhibition of TRAP1 activity by TRAP1 ATPase antagonist, shepherdin, increased the sensitivity to oxaliplatin and irinotecan in colorectal carcinoma cells resistant to the single agents. These results suggest that the increased expression of TRAP1 could be part of a pro-survival pathway responsible for multi-drug resistance.

Sorcin Induces a Drug-Resistant Phenotype in Human Colorectal Cancer by Modulating Ca2+ Homeostasis

The Ca(2+)-binding protein sorcin regulates intracellular calcium homeostasis and plays a role in the induction of drug resistance in human cancers. Recently, an 18 kDa mitochondrial isoform of sorcin was reported to participate in antiapoptosis in human colorectal cancer (CRC), but information remains lacking about the functional role of the more abundant 22 kDa isoform of sorcin expressed in CRC. We found the 22 kDa isoform to be widely expressed in human CRC cells, whether or not they were drug resistant. Its upregulation in drug-sensitive cells induced resistance to 5-fluorouracil, oxaliplatin, and irinotecan, whereas its downregulation sensitized CRC cells to these chemotherapeutic agents. Sorcin enhances the accumulation of Ca(2+) in the endoplasmic reticulum (ER), preventing ER stress, and, in support of this function, we found that the 22 kDa isoform of sorcin was upregulated under conditions of ER stress. In contrast, RNAi-mediated silencing of sorcin activated caspase-3, caspase-12, and GRP78/BiP, triggering apoptosis through the mitochondrial pathway. Our findings establish that CRC cells overexpress sorcin as an adaptive mechanism to prevent ER stress and escape apoptosis triggered by chemotherapeutic agents, prompting its further investigation as a novel molecular target to overcome MDR.

Laparoscopic treatment of biliary hepatic cysts: short- and medium-term results

BACKGROUND The aim of this study was to evaluate the postoperative morbidity and, in the medium-term results, the incidence of relapses in the laparoscopic treatment of non-parasitic hepatic cysts (NPHC) and polycystic liver disease (PCLD). PATIENTS AND METHODS From 1999 to 2003, 12 patients with NPHC and 3 patients with PCLD with few large cysts in the anterior hepatic segments underwent laparoscopic fenestration and deroofing. RESULTS There were no conversions and no mortality; the mean operative time was 55 min for NPHC and 120 min for PCLD. Postoperative morbidity comprised two patients with bronchopneumonic infiltrations and in one patient with PCLD ascites resolved spontaneously. All the patients experienced resolution of the symptomatology. Follow-up was carried out from 3 to 38 months (mean 18 months). There was no relapse of the disease. DISCUSSION The preoperative selection of patients is fundamental to program the surgical treatment. Laparoscopy can be considered a safe and efficacious treatment for NPHC and PCLD.

A recurrent epidermoid cyst of the spleen: report of a case and literature review

BackgroundSplenic cysts are rare disease. Epidermoid cysts of the spleen belong to the primary nonparasitic splenic cysts group. They are an unusual event in surgical practice. Usually, epidermoid cysts occur in children and young female. Most often, they are asymptomatic, but they may present with abdominal discomfort.Case presentationWe are reporting a rare case of a 23-year-old female came to our attention with history of intermittent pain and previously undergone two times to laparoscopic decapsulation of the cyst in others institutions. During hospitalization, serum and intracystic levels of tumor marker CA19-9 increased. Enhanced CT of the abdomen showed recurrent large cyst in the upper pole of the spleen with satellite nodules. Laparotomic total splenectomy was performed. Histopathological and immunoreactive examinations were executed, and they revealed stratified squamous epithelium on the inner surface of cystic wall, which was positive for EMA, CEA, and CA19-9. The diagnosis of epidermoid cyst was confirmed.ConclusionsRecently, the surgical approach is changing towards conservative treatments in order to save the spleen in young patients for immunological reasons. Sometimes, this target is not achievable. In such circumstances, like recurrent large cyst, anomalous anatomical relationship to the surrounding tissues, total splenectomy is safe and necessary.

Multiple Skeletal Muscle Metastases from Colon Carcinoma Preceded by Paraneoplastic Dermatomyositis

Skeletal muscle metastases are very rare events in colorectal carcinoma. By contrast, dermatomyositis is an idiopathic inflammatory myopathy with characteristic cutaneous manifestations and a well-recognized association with several human malignancies and, among others, colorectal cancer. Here, we report the case of a 71-year-old woman with paraneoplastic dermatomyositis followed by the development of a metastatic colon cancer. Interestingly, this patient developed multiple skeletal metastases which were preceded by the worsening of systemic symptoms of dermatomyositis. This observation suggests that, while muscle tissue is usually resistant to the development of tumor metastases, the inflammatory and immune response which characterizes and boosts paraneoplastic myopathy may represent a favorable soil for tumor cell invasion and metastasization to skeletal muscles.

Voluminous Omental Inflammatory Myofibroblastic Tumor in an Elderly Man: A Case Report and Literature Review

Inflammatory myofibroblastic tumor (IMT) is a rare neoplasm of intermediate biologic potential, with uncertain etiology. This tumor occurs primarily in the lung, but the tumor may affect any organ system. A 75-year-old male was evaluated for voluminous palpable high abdominal mass with continuous and moderately abdominal pain, associated with abdominal distension for the last two months. Abdominal computed tomography showed a large (32 × 29 × 15 cm) heterogeneously enhanced mass with well-defined margins. At surgery, the mass originated from the greater omentum was completely excised. Histologically the tumor was a mesenchymal neoplasm in smooth muscle differentiation and was characterized by spindle-cell proliferation with lymphocytes, plasma cells, and rare eosinophils. Immunohistochemically, the tumor cells were positive for vimentin and smooth muscle actin and negative for anaplastic lymphoma kinase. Complete surgical resection of IMTs remains the mainstay of treatment associated with a low rate of recurrence. Final diagnosis should be based on histopathological and immunohistochemical findings. Appropriate awareness should be exercised by surgeons to abdominal IMTs in combination with constitutional symptoms, abnormal hematologic findings, and radiological definition, to avoid misdiagnosed.

Cholecystoduodenocolic Fistula by Gallbladder Carcinoma that Presenting as Bouveret's Syndrome: Case Report and Review of the Literature

We describe the first case in the literature of Bouveret’s syndrome as the result of a cholecystoduodenocolic fistula secondary to gallbladder carcinoma. A 67-years-old woman was admitted to our department presenting with complaints of severe cramping abdominal pain, localized predominantly in the right hypochondrium and epigastrium, with infrequent alimentary and biliary vomiting for about three months. Based on the radiological and endoscopic findings, the provisional diagnosis of Bouveret’s syndrome in a patient with cholecystoduodenal fistula and history of cholelithiasis was made. The laparotomy showed the presence of the stone in the duodenal bulb, already seen at endoscopy, and adhesions between gallbladder, superior duodenal flexure and hepatic flexure of the colon, and this inflammatory gangue strethed up to the hepatic hilum. During dissection in addition to the communication between the gallbladder and the duodenum, another fistula was found that led from the gallbladder to the colon. The suspicion of malignancy of this multiple biliary enteric fistula was confirmed by intraoperative frozen sections that revealed the precence of a poorly differentiated carcinoma of biliary-pancreatic origin, but the ultimate diagnosis of gallbladder carcinoma was made exclusively after the definitive histopathological examination. For these reasons the surgical procedure involved cholecystectomy with resection of the regional lymph nodes, gastrotomy with extraction of gallstone, trans-mesocolic Roux-en-Y gastro-jejunal mechanical anastomosis, resection of the hepatic flexure of the colon with termino-lateral colo-colic mechanical anastomosis. It’s important to remember that rarely the Bouveret’s syndrome can hide multiple biliary enteric fistulas or even a malignancy. We believe, in the light of our experience, that the surgical approach represents the first choice in the treatment of this serious disease.

Defining a therapeutic program for recurrent acute pancreatitis patients with unknown etiology.

Aim To define a therapeutic program for mild-moderate acute pancreatitis (AP), often recurrent, which at the end of the diagnostic process remains of undefined etiology. Material and Methods In the period 2011-2012, we observed 64 cases of AP: 52 mild-moderate, 12 severe; biliary 39, biliary in alcoholic chronic pancreatitis 5, unexplained recurrent 20. The clinical and instrumental evaluation of the 20 cases of unexplained AP showed 6 patients with biliary sludge, 4 microlithiasis, 4 sphincter of Oddi dysfunction, and 6 cases that remained undefined. Results Among 20 patients with recurrent, unexplained AP at initial etiological assessment, we performed 10 video laparo cholecystectomies (VLCs), 2 open cholecystectomies and 4 endoscopic retrograde cholangiopancreatography/endoscopic sphincterotomies (ERCP/ES) in patients who had undergone previous cholecystectomy; 4 patients refused surgery. Among these 20 patients, 6 had AP that remained unexplained after second-level imaging investigations. For these patients, 4 VLCs and 2 ERCP/ES were performed. Follow-up after six months was negative for further recurrence. Conclusion The recurrence of unexplained acute pancreatitis could be treated with empirical cholecystectomy and/or ERCP/ES in cases of previous cholecystectomy.

Haemostasis in Thyroid Surgery: Collagen-Fibrinogen-Thrombin Patch versus Cellulose Gauze—Our Experience

Purpose. Postoperative hemorrhage is fortunately uncommon but potentially life-threatening complication of thyroid surgery that increases the postoperative morbidity and the hospital stay. In this study we compare the efficacy of collagen patch coated with human fibrinogen and human thrombin (CFTP) (group C) and oxidized regenerated cellulose gauze (group B) versus traditional hemostatic procedures (group A) in thyroid surgery. Methods. From January 2011 to December 2013, 226 were eligible for our prospective, nonrandomized, comparative study. Patients requiring a video-assisted thyroidectomy without drain, “near total,” or hemithyroidectomy were excluded. Other exclusion criteria were a diagnosis of malignancy, substernal goiter, disorders of hemostasis or coagulation, and Graves or hyperfunctioning thyroid diseases. Outcomes included duration of operation, drainage volume, and postoperative complications. Results. Our results show a significant reduction in drainage volume in group C in comparison with the other two groups. In group C there was no bleeding but the limited numbers do not make this result significant. There were no differences in terms of other complications, except for the incidence of seroma in group B. Conclusion. The use of CFTP reduces the drainage volume, potentially the bleeding complications, and the hospital stay. These findings confirm the efficacy of CFTP, encouraging its use in thyroid surgery.

Laparoscopic antegrade cholecystectomy: a standard procedure?

Abstract Retrograde approach (“fundus first”) is often used in open surgery, while in laparoscopic cholecystectomy (LC) is less frequent. LC, with antegrade access, is done by putting in traction the infundibulum and going up to the fundus before to clip the cystic. Our study analyzes a number of surgical procedures performed by experienced surgeons in laparoscopy. From 2002 to 2015, 1740 laparoscopic cholecystectomies were performed at our Institution. The operative procedure performed since 2002 consists of the incision of the visceral peritoneum from the infundibulum away from Calot’s triangle along the gallbladder bed up to the fundus. Then it continues from the fundus up to the infundibulum. Results: There were no bile duct injuries. Average operative time was 40 min. 22 conversions to an open procedure (1.3%) occurred, in cases of acute cholecystitis and cirrhotic patient. Postoperative stay was mean 2 days with no delayed sequelae on follow up. Conclusions: gallbladder antegrade dissection for laparoscopic cholecystectomy can reduce the time of surgery and is an easier technique to perform. Therefore, it can be proposed as the standard procedure and not only be used for difficult cholecystectomies.