AIM: To verify the utility of fluorescent cholangiography for more rigorous identification of the extrahepatic biliary system. METHODS: MEDLINE and PubMed searches were performed using the key words “fluorescent cholangiography”, “fluorescent angiography”, “intraoperative fluorescent imaging”, and “laparoscopic cholecystectomy” in order to identify relevant articles published in English, French, German, and Italian during the years of 2009 to 2014. Reference lists from the articles were reviewed to identify additional pertinent articles. For studies published in languages other than those mentioned above, all available information was collected from their English abstracts. Retrieved manuscripts (case reports, reviews, and abstracts) concerning the application of fluorescent cholangiography were reviewed by the authors, and the data were extracted using a standardized collection tool. Data were subsequently analyzed with descriptive statistics. In contrast to classic meta-analyses, statistical analysis was performed where the outcome was calculated as the percentages of an event (without comparison) in pseudo-cohorts of observed patients. RESULTS: A total of 16 studies were found that involved fluorescent cholangiography during standard laparoscopic cholecystectomies (n = 11), single-incision robotic cholecystectomies (n = 3), multiport robotic cholecystectomy (n = 1), and single-incision laparoscopic cholecystectomy (n = 1). Overall, these preliminary studies indicated that this novel technique was highly sensitive for the detection of important biliary anatomy and could facilitate the prevention of bile duct injuries. The structures effectively identified before dissection of Calot’s triangle included the cystic duct (CD), the common hepatic duct (CHD), the common bile duct (CBD), and the CD-CHD junction. A review of the literature revealed that the frequencies of detection of the extrahepatic biliary system ranged from 71.4% to 100% for the CD, 33.3% to 100% for the CHD, 50% to 100% for the CBD, and 25% to 100% for the CD-CHD junction. However, the frequency of visualization of the CD and the CBD were reduced in patients with a body mass index > 35 kg/m² relative to those with a body mass index < 35 kg/m² (91.0% and 64.0% vs 92.3% and 71.8%, respectively). CONCLUSION: Fluorescent cholangiography is a safe procedure enabling real-time visualization of bile duct anatomy and may become standard practice to prevent bile duct injury during laparoscopic cholecystectomy.

To evaluate the impact of incidental gallbladder cancer on surgical experience. Between 1998 and 2008 all cases of cholecystectomy at two divisions of general surgery, one university based and one at a public hospital, were retrospectively reviewed. Gallbladder pathology was diagnosed by history, physical examination, and laboratory and imaging studies [ultrasonography and computed tomography (CT)]. Patients with gallbladder cancer (GBC) were further analyzed for demographic data, and type of operation, surgical morbidity and mortality, histopathological classification, and survival. Incidental GBC was compared with suspected or preoperatively diagnosed GBC. The primary endpoint was disease-free survival (DFS). The secondary endpoint was the difference in DFS between patients previously treated with laparoscopic cholecystectomy and those who had oncological resection as first intervention. Nineteen patients (11 women and eight men) were found to have GBC. The male to female ratio was 1:1.4 and the mean age was 68 years (range: 45-82 years). Preoperative diagnosis was made in 10 cases, and eight were diagnosed postoperatively. One was suspected intraoperatively and confirmed by frozen sections. The ratio between incidental and nonincidental cases was 9/19. The tumor node metastasis stage was: pTis (1), pT1a (2), pT1b (4), pT2 (6), pT3 (4), pT4 (2); five cases with stage Ia (T1 a-b); two with stage Ib (T2 N0); one with stage IIa (T3 N0); six with stage IIb (T1-T3 N1); two with stage III (T4 Nx Nx); and one with stage IV (Tx Nx Mx). Eighty-eight percent of the incidental cases were discovered at an early stage (≤ II). Preoperative diagnosis of the 19 patients with GBC was: GBC with liver invasion diagnosed by preoperative CT (nine cases), gallbladder abscess perforated into hepatic parenchyma and involving the transversal mesocolon and hepatic hilum (one case), porcelain gallbladder (one case), gallbladder adenoma (one case), and chronic cholelithiasis (eight cases). Every case, except one, with a T1b or more advanced invasion underwent IVb + V wedge liver resection and pericholedochic/hepatoduodenal lymphadenectomy. One patient with stage T1b GBC refused further surgery. Cases with Tis and T1a involvement were treated with cholecystectomy alone. One incidental case was diagnosed by intraoperative frozen section and treated with cholecystectomy alone. Six of the nine patients with incidental diagnosis reached 5-year DFS. One patient reached 38 mo survival despite a port-site recurrence 2 years after original surgery. Cases with non incidental diagnosis were more locally advanced and only two patients experienced 5-year DFS. Laparoscopic cholecystectomy does not affect survival if implemented properly. Reoperation should have two objectives: R0 resection and clearance of the lymph nodes.

Gallbladder cancer (GBC) is the fifth most common neoplasm of the gastrointestinal tract and the most common cancer of the biliary tract. GBC is suspected preoperatively in only 30-40% of patients. The other 60-70% are discovered incidentally (IGBC) by the pathologist on a gallbladder specimen following cholecystectomy for benign diseases such as polyps, gallstones, and cholecystitis. Between 1995 and 2011, 30 cases of GBC, who underwent resection with curative intent in our institutions, were retrospectively reviewed. They were analyzed for demographic data, and type of operation, surgical morbidity and mortality, histopathological classification, and survival. Incidental GBC was compared with suspected or preoperatively diagnosed GBC. Overall survival, disease-free survival (DFS) and the difference in DFS between patients previously treated with laparoscopic cholecystectomy and those who had oncological resection as first intervention were analyzed. The authors also present a systematic review to evaluate the role of extended surgery in the treatment of the incidental GBC. GBC was diagnosed in 30 patients, 16 women and 14 men. The M/F ratio was 1:1.14 and the mean age was 69.4 years (range 45-83 years). A preoperative diagnosis was possible only in 14 cases; fourteen of the incidental cases were diagnosed postoperatively after the pathological examination; two were suspected intraoperatively at the opening of the surgical specimen and then confirmed by frozen sections. The ratio between incidental and nonincidental cases was 1, 14/1, with twelve cases discovered after laparoscopic cholecystectomy. Eighty-one per cent of the incidental cases were discovered at an early stage (≤II). The preoperative diagnosis of the 30 patients with GBC was: GBC with liver invasion diagnosed by preoperative CT (nine cases); gallbladder abscess perforated into hepatic parenchyma and involving the transversal mesocolon and hepatic hilum (one case); porcelain gallbladder (three cases); gallbladder adenoma (four cases); and chronic cholecystolithiasis (thirteen cases). Every case, except one, with a T1b or more advanced invasion underwent IVb + V wedge liver resection and pericholedochic/hepatoduodenal lymphoadenectomy. One patient refused further surgery. Cases with Tis and T1a involvement were treated with cholecystectomy alone. Nine of the sixteen patients with incidental diagnosis reached 5-year DFS (56.25%) and eight of them are recurrence free. Surprisingly, one patient reached 38 mo survival despite a port-site recurrence (the only one in our experience) 2 years after the original surgery requiring further resection. Cases with non incidental diagnosis were more locally advanced and only two patients experienced 5 years DFS (Tables 2 and 3). Laparoscopic cholecystectomy does not affect survival if implemented properly. Reoperation should have two objectives: R0 resection and clearance of the lymph nodes.

This study reviewed all single experience of splenic injuries after colonoscopy in the last 40 years to define the possible risk factors and the management of this complication. A MEDLINE and a PubMed search was undertaken to identify articles in English, French, Spanish, and Italian from 1974 to 2012 using the key words: "splenic injury," "splenic rupture," and "colonoscopy." Data were analyzed using descriptive statistic. A total of 103 cases have been described in 75 reports. The majority of the patients were women (71.56%) and 6.85% underwent previous pelvic surgery. The mean age was 63 years (range, 29 to 90 y). About 61 of the 103 studies (59.2%) reported the presence or the absence of previous abdominal surgery and within these, only 31 of 61 patients (50.82%) underwent previous abdominal surgery. In this review, over half of the patients with splenic injury underwent colonoscopy for routine surveillance (62.75%), and only one third of the splenic injures were associated with biopsy or polypectomy. The majority of patients (78.57%) developed symptoms within the first 24 hours after colonoscopy and in a minority of cases (21.43%), there was a delayed presentation 24 hours after colonoscopy. Computed tomography was used as the primary modality to make the diagnosis in 69 of 98 cases (70.41%) and as a confirmatory test in many additional cases. Twenty-six of 102 patients (25.49%) were treated by conservative methods, whereas the majority of patients (69.61%) underwent splenectomy as a definitive treatment. Because of possible medicolegal implications, the endoscopists should consider mentioning splenic injury on the consent form of colonoscopy after bowel perforation and bleeding, particularly in higher risk patients.

The major histocompatibility complex-class I chain related proteins A and B (MICA/B) is upregulated because of cellular stress and MICA/B shedding by cancer cells causes escape from NKG2D recognition favoring the emergence of cancers. Cholangiocarcinoma (CCA) is a relatively rare, though increasingly prevalent, primary liver cancer characterized by a late clinical presentation and a dismal prognosis. We explored the NKG2D-MICA/B axis in NK cells from 41 patients with intrahepatic cholangiocarcinoma (iCCA). The MICA/B-specific 7C6 mAb was used for ex vivo antibody-dependent cytotoxicity (ADCC) experiments using circulating, non tumor liver- and tumor-infiltrating NK cells against the HuCCT-1 cell line and patient-derived primary iCCA cells as targets. MICA/B were more expressed in iCCA than in non-tumoral tissue, MICA transcription being higher in moderately-differentiated compared with poorly-differentiated cancer. Serum MICA was elevated in iCCA patients in line with higher expression of ADAM10 and ADAM17 that are responsible for proteolytic release of MICA/B from tumor. Addition of 7C6 significantly boosted peripheral, liver- and tumor-infiltrating-NK cell degranulation and IFNγ production toward MICA/B-expressing established cell lines and autologous iCCA patient target cells. Our data show that anti-MICA/B drives NK cell anti-tumor activity, and provide preclinical evidence in support of 7C6 as a potential immunotherapeutic tool for iCCA.

Multiple factors have been described among the causes of non-hereditary colorectal cancer. In Western countries, the most common risk factors include upper- middle socioeconomic status and dietary regimens rich in proteins and animal fats. High consumption of red meats, smoked foods, cold cuts, or canned foods is believed to contribute to carcinogenesis as they directly affect epithlial turnover and cause metabolism of biliary acids. Dietary fibers have protective effects in that they capture the fats and biliary acids, thereby inhibiting their activity. Tobacco smoking acts both locally and systemically on the colorectal mucosa through the production of carcinogenic agents. Finally, the action of alcohol, in association with nicotine addiction, also increases the risk of developing colorectal tumors. Knowledge of dietary and environmental factors is of paramount importance in implementing preventive strategies for colorectal cancer.