Clinicopathological Study of Intracholecystic Papillary-Tubular Neoplasms (ICPNs) of the Gallbladder

Intracholecystic papillary-tubular neoplasm (ICPN) has recently been proposed as a new disease concept in the classification of gallbladder tumors. ICPN is defined as a papillary or polypoid glandular neoplasm forming a localized, non-invasive mass (≥ 1cm) in the gallbladder. We analyzed the clinicopathological characteristics of ICPN. Resected gallbladder cancer specimens from 57 patients were classified as ICPN or non-ICPN and clinicopathological characteristics were compared. ICPN cell characteristics were also analyzed using immunostaining and genetic analysis. Twenty-three cases were classified as ICPN and 34 as non-ICPN. In the ICPN and non-ICPN groups, mean ages were 69 and 74 years, male:female ratios were 14:9 and 15:19, mean tumor diameters were 2.8 and 2.6cm, invasion depths were Tis+T1/T2+T3 in 14/9 cases and 13/21 cases, lymph node metastases were present in 6% and 43%, distant metastases in 0% and 6% and 3-year survival rates were 91% and 52%, respectively. Significant intergroup differences were seen in lymph node metastases and the 3-year survival rate. ICPN cell lineage was biliary-type in 13 cases, gastric-type in 8 and intestinal-type in 2. This proportion differs from that of pancreatic intraductal papillary mucinous neoplasm (IPMN), in which gastric- and intestinal-type are more common. KRAS gene mutations were only seen in 1 of 13 ICPN cases. ICPN is frequently seen in gallbladder cancer, showing similar pathology to pancreatic IPMN, which is considered to have a relatively good prognosis among pancreatic cancers. However, ICPN cell characteristics are not necessarily identical to those of pancreatic IPMN

Congenital multiple colonic atresias in the sigmoid colon and upper rectum

Introduction: Congenital colonic atresia develops in 1 in 20,000 to 66,000 births, accounting for 1.8–15% of all intestinal atresias. Approximately 8.9% of patients with colonic atresia have multiple colonic atresias. Case presentation: A female infant with abdominal distention and bilious vomiting did not have a bowel movement until day 3 of life. Plain radiography showed significant dilation of the intestinal tract and no gas in the pelvic cavity. A contrast enema at the age of 3 days showed microcolon and obstruction at the level of the upper rectum. Operative findings included 3 membranous atresias (Type Ⅲ). For the 2 proximal membranous atresias, membranectomy and colostomy in the sigmoid colon were performed. Preoperative contrast enema at 10 months showed a gap between the distal side of the stoma and the blind end of the rectum. The sigmoid colon and rectum were completely resected 6 cm distal to the stoma. Colostomy closure was performed. A total of 4 membranous atresias were present in the sigmoid colon and the upper rectum. Conclusions: In a patient with multiple atresias in the sigmoid colon and upper rectum, multiple-stage surgery could be safe after searching for complicating malformations and evaluating the intestinal tract preoperatively

Cyclic GMP and protein kinase-G in myocardial ischaemia-reperfusion: opportunities and obstacles for survival signaling

It is clear that multiple signalling pathways regulate the critical balance between cell death and survival in myocardial ischaemia–reperfusion. Recent attention has focused on the activation of survival or salvage kinases, particularly during reperfusion, as a common mechanism of many cardioprotective interventions. The phosphatidyl inositol 3′-hydroxy kinase/Akt complex (PI3K/Akt) and p42/p44 mitogen-activated protein kinase cascades have been widely promoted in this respect but the cyclic guanosine 3′,5′-monophosphate/cGMP-dependent protein kinase (cGMP/PKG) signal transduction cassette has been less systematically investigated as a survival cascade. We propose that activation of the cGMP/PKG signalling pathway, following activation of soluble or particulate guanylate cyclases, may play a pivotal role in survival signalling in ischaemia–reperfusion, especially in the classical preconditioning, delayed preconditioning and postconditioning paradigms. The resurgence of interest in reperfusion injury, largely as a result of postconditioning-related research, has confirmed that the cGMP/PKG pathway is a pivotal salvage mechanism in reperfusion. Numerous studies suggest that the infarct-limiting effects of preconditioning and postconditioning, exogenously donated nitric oxide (NO), natriuretic peptides, phosphodiesterase inhibitors, and other diverse drugs and mediators such as HMG co-A reductase inhibitors (statins), Rho-kinase inhibitors and adrenomedullin, whether given before and during ischaemia, or specifically at the onset of reperfusion, may be mediated by activation or enhancement of the cGMP pathway, either directly or indirectly via endogenous NO generation downstream of PI3K/Akt. Putative mechanisms of protection include PKG regulation of Ca2+ homeostasis through the modification of sarcoplasmic reticulum Ca2+ uptake mechanisms, and PKG-induced opening of ATP-sensitive K+ channels during ischaemia and/or reperfusion. At present, significant technical obstacles in defining the precise roles played by cGMP/PKG signalling include the heavy reliance on pharmacological PKG inhibitors of uncertain selectivity, difficulties in determining PKG activity in intact tissue, and the growing recognition that intracellular compartmentalisation of the cGMP pool may contribute markedly to the nucleotide's biological actions and biochemical determination. Overall, the body of experimental evidence suggests that cGMP/PKG survival signalling ameliorates irreversible injury associated with ischaemia–reperfusion and may be a tractable therapeutic target