Cholecystocolonic fistula with a giant colonic gallstone: the mainstay of treatment in an acute setting.

A cholecystoenteric fistula (CEF) is a rare complication of cholelithiasis with cholecystitis. Cholecystocolonic fistulas (CCFs) account for 8-26.5% of all CEFs. CCFs can cause colonic bleeding, obstruction or perforation, with such complications being mainly reported in the narrower sigmoid colon. Colonic biliary ileus, or obstruction due to the colonic gallstone impaction, is extremely rare in the proximal colon and its best management is yet to be elucidated. We present the case of a 73-year-old male patient with multiple comorbidities and previous abdominal surgeries who presented with hematochezia and intestinal obstructive symptoms. Imaging revealed a giant 5 × 7 cm2 gallstone in the proximal transverse colon. Laparotomy and stone extraction via colotomy were performed. Complicated proximal colonic gallstones are exceedingly rare with several operative and non-operative treatments already described. A time-saving surgery in a patient with serious comorbidities is reasonable when compared to a more extensive procedure including enterolithotomy, cholecystecomy and fistula closure.

Validation of the PMD100 and its NOL Index to detect nociception at different infusion regimen of remifentanil in patients under general anesthesia.

BACKGROUND: The NOL index is based on multiparametric analysis of heart rate (HR), skin conductance, wave plethysmography, and their time derivative. The aim of this study was to evaluate the NOL to detect standardized nociceptive stimuli with various remifentanil dosages under general anesthesia. METHODS: A prospective, observational study at a single center (NCT02602379) included 40 ASA I to III patients undergoing laparotomy under remifentanil-desflurane anesthesia with epidural analgesia. A tetanic stimulation was applied (forearm) at remifentanil intravenous (IV) infusion of 0.005, 0.05, 0.1, and 0.15 µg/kg/min. NOL and its variations were compared with other parameters namely heart rate, mean arterial pressure, Bispectral Index, and Analgesia Nociception Index (ANI). Receiver operating characteristic (ROC) curves were plotted to assess the response to both intubation and standardized stimulus under remifentanil infusion of 0.005 µg/kg/min. RESULTS: The post-stimulation NOL values at remifentanil doses of 0.005, 0.05, 0.1 and 0.15 µg/kg/min (39 [23-55], 15 [7-30], 8 [4-14] and 8.5 [4-15]) were significantly higher than pre-stimulation counterparts (P<0.0001). For all other parameters, there was also significant difference between pre- and post-stimulation values at all remifentanil dosages (P<0.0001). Area under the ROC curve (AUC) for the NOL during standardized stimulation was larger than for all other parameters at the exception of ANI (P=0.94). The AUC of NOL for nociception during tracheal intubation was greater (0.93 vs. 0.84 and 0.64 for ANI and HR, respectively). CONCLUSIONS: NOL monitoring is a promising index to assess the level of nociception in patients under general anesthesia.

A cathepsin L isoform that is devoid of a signal peptide localizes to the nucleus in S phase and processes the CDP/Cux transcription factor.

The subclass of cysteine proteases termed lysosomal cathepsins has long been thought to be primarily involved in end-stage protein breakdown within lysosomal compartments. Furthermore, few specific protein substrates for these proteases have been identified. We show here that cathepsin L functions in the regulation of cell cycle progression through proteolytic processing of the CDP/Cux transcription factor. CDP/Cux processing in situ was increased following ectopic expression of cathepsin L but was reduced in Cat L(-/-) cells. Furthermore, catalytically active cathepsin L was localized to the nucleus during the G1-S transition as detected by immunofluorescence imaging and labeling using activity-based probes. Trafficking of cathepsin L to the nucleus is accomplished through a mechanism involving translation initiation at downstream AUG sites and the synthesis of proteases that are devoid of a signal peptide. Overall, these results uncover an as yet unsuspected role for cysteine proteases in the control of cell cycle progression.

Characterization of a tissue-specific CDP/Cux isoform, p75, activated in breast tumor cells.

Two isoforms of the CCAAT-displacement protein/cut homeobox (CDP/Cux) transcription factor have been characterized thus far. The full length protein, p200, which contains four DNA binding domains, transiently binds to DNA and carries the CCAAT-displacement activity. The p110 isoform is generated by proteolytic processing at the G1-S transition and is capable of stable interaction with DNA. Here we demonstrate the existence of a shorter CDP/Cux isoform, p75, which contains only two DNA binding domains, Cut repeat 3 and the Cut homeodomain, and binds more stably to DNA. CDP/Cux p75 was able to repress a reporter carrying the promoter for the cyclin-dependent kinase inhibitor p21 gene and to activate a DNA polymerase alpha gene reporter. Expression of CDP/Cux p75 involved a novel mechanism: transcription initiation within intron 20. The intron 20-initiated mRNA (I20-mRNA) was expressed at higher level in the thymus and in CD4+/CD8+ and CD4+ T cells. I20-mRNA was expressed only weakly or not at all in normal human mammary epithelial cells and normal breast tissues but was detected in many breast tumor cells lines and breast tumors. In invasive tumors a significant association was established between higher I20-mRNA expression and a diffuse infiltrative growth pattern (n = 41, P = 0.0137). In agreement with these findings, T47D breast cancer cells stably expressing p75 could not form tubule structures in collagen but rather developed as solid undifferentiated aggregates of cells. Taken together, these results suggest that aberrant expression of the CDP/Cux p75 isoform in mammary epithelial cells may be associated with the process of tumorigenesis in breast cancer.