New diagnostic criteria of acute pancreatitis

Practical guidelines for the diagnosis of acute pancreatitis are presented so that a rapid and adequate diagnosis can be made. When acute pancreatitis is suspected in patients with acute onset of abdominal pain and tenderness mainly in the upper abdomen, the diagnosis of acute pancreatitis is made on the basis of elevated levels of pancreatic enzymes in the blood and/or urine. Furthermore, other acute abdominal diseases are ruled out if local findings associated with pancreatitis are confirmed by diagnostic imaging. According to the diagnostic criteria established in Japan, patients who present with two of the following three manifestations are diagnosed as having acute pancreatitis: characteristic upper abdominal pain, elevated levels of pancreatic enzymes, and findings of ultrasonography (US), CT or MRI suggesting acute pancreatitis. Detection of elevated levels of blood pancreatic enzymes is crucial in the diagnosis of acute pancreatitis. Measurement of blood lipase is recommended, because it is reported to be superior to all other pancreatic enzymes in terms of sensitivity and specificity. For measurements of the blood amylase level widely used in Japan, it should be cautioned that, because of its low specificity, abnormal high values are also often obtained in diseases other than pancreatitis. The cut-off level of blood pancreatic enzymes for the diagnosis of acute pancreatitis is not able to be set because of lack of sufficient evidence and consensus to date. CT study is the most appropriate procedure to confirm image findings of acute pancreatitis. Elucidation of the etiology of acute pancreatitis should be continued after a diagnosis of acute pancreatitis. In the process of the etiologic elucidation of acute pancreatitis, judgment whether it is gallstone-induced or not is most urgent and crucial for deciding treatment policy including the assessment of whether endoscopic papillary treatment should be conducted or not. The diagnosis of gallstone-induced acute pancreatitis can be made by combining detection of elevated levels of bilirubin, transamylase (ALT, AST) and ALP detected by hematological examination and the visualization of gallstones by US.     

Post-ERCP pancreatitis

Pancreatitis remains the most common severe complication of endoscopic retrograde cholangiopancreatography (ERCP). Detailed information about the findings of previous studies concerning post-ERCP pancreatitis has not been utilized sufficiently. The purpose of the present article was to present guidelines for the diagnostic criteria of post-ERCP pancreatitis, and its incidence, risk factors, and prophylactic procedures that are supported by evidence. To achieve this purpose, a critical examination was made of the articles on post-ERCP pancreatitis, based on the data obtained by research studies published up to 2009. At present, there are no standardized diagnostic criteria for post-ERCP pancreatitis. It is appropriate that post-ERCP pancreatitis is defined as acute pancreatitis that has developed following ERCP, and its diagnosis and severity assessment should be made according to the diagnostic criteria and severity assessment of the Japanese Ministry of Health, Labour and Welfare. The incidence of acute pancreatitis associated with diagnostic and therapeutic ERCP is 0.4–1.5 and 1.6–5.4%, respectively. Endoscopic papillary balloon dilation is associated with a high risk of acute pancreatitis compared with endoscopic sphincterotomy. It was made clear that important risk factors include dysfunction of the Oddi sphincter, being of the female sex, past history of post-ERCP pancreatitis, and performance of pancreaticography. Temporary prophylactic placement of pancreatic stents in the high-risk group is useful for the prevention of post-ERCP pancreatitis [odds ratio (OR) 3.2, 95% confidence interval (CI) 1.6–6.4, number needed to treat (NNT) 10]. Use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with a reduction in the development of post-ERCP pancreatitis (OR 0.46, 95% CI 0.32–0.65). Single rectal administration of NSAIDs is useful for the prevention of post-ERCP pancreatitis [relative risk (RR) 0.36, 95% CI 0.22–0.60, NNT 15] and decreases the development of pancreatitis in both the low-risk group (RR 0.29, 95% CI 0.12–0.71) and the high-risk group (RR 0.40, 95% CI 0.23–0.72) of post-ERCP pancreatitis. As for somatostatin, a bolus injection may be most useful compared with short- or long-term infusion (OR 0.271, 95% CI 0.138–0.536, risk difference 8.2%, 95% CI 4.4–12.0%). The usefulness of gabexate mesilate was not apparent in any of the following conditions: acute pancreatitis (control 5.7 vs. 4.8% for gabexate mesilate), hyperamylasemia (40.6 vs. 36.9%), and abdominal pain (1.7 vs. 8.9%). Formulation of diagnostic criteria for post-ERCP pancreatitis is needed. Temporary prophylactic placement of pancreatic stents in the high-risk group offers the most promise as a means of preventing post-ERCP pancreatitis. As for pharmacological attempts, there are high expectations concerning NSAIDs because they are excellent in terms of cost-effectiveness, ease of use, and safety. There was no evidence of effective prophylaxis with the use of protease inhibitors, especially gabexate mesilate.     

Laparoscopic Resection for Colorectal Cancer in Japan

The first laparoscopic surgery for colorectal cancer in Japan was reported in 1992. In the early phase, many cases were indicated for early cancer. The number of operations has been increasing year by year, and now even some advanced cases undergo laparoscopic surgery. According to questionnaires administered in 2003 by the Japan Society for Endoscopic Surgery, more than half of 3,892 cases were indicated for advanced cancer. In 2004, the 60th biannual meeting of the Japanese Society for Cancer of the Colon and Rectum took up "the current status of laparoscopic resection for colorectal cancer" as one of the main topics of the meeting, and conducted a questionnaire survey of the member’s opinions to laparoscopic resection for colorectal cancer prior to the meeting. It was revealed that at least ninety institutes had already performed a laparoscopic resection for colorectal cancer. In order to evaluate the feasibility of laparoscopic resection for colorectal cancer, a randomized control study comparing laparoscopic and open resection of colorectal cancer was started in 2004. This study is scheduled to collect 818 cases. The characteristic of this study was to enroll only advanced cancer cases. The primary endpoint is the survival, while the secondary end points are disease-free survival, early postoperative course, adverse events and conversion to open surgery. As more surgeons perform laparoscopic colorectal surgery, the importance for education and credentialing has been discussed. The Japan Society for Endoscopic Surgery started a system to qualify the surgeon’s technique for endoscopic and laparoscopic surgery in 2004. One hundred and three surgeons took the examination for laparoscopic colorectal surgery in 2004, and 43 passed. Reprints are not available.     

Total splenic vein thrombosis after laparoscopic splenectomy: a possible candidate for treatment

BACKGROUND: Portal or splenic vein thrombosis (PSVT) is a common disorder after laparoscopic splenectomy (LS). Splenomegaly is a well-known risk factor for PSVT. However, no treatment strategy for PSVT has been established. METHODS: Thirty-three consecutive patients who had undergone LS and postoperative imaging surveillance were examined. PSVT was classified according to the site of thrombosis. We evaluated patient background, operative factors, and clinical symptoms. RESULTS: Spleen weight of patients with PSVT (n = 17, median 218 g) was greater than that of patients without PSVT (n = 16, median 101 g). Seven patients developed thrombosis involving the entire splenic vein (total splenic vein thrombosis), and 4 of them had clinical symptoms (fever >38 degrees C and/or abdominal pain). The incidence of clinical symptoms was significantly more frequent in patients with than without total SVT. Operation time, blood loss, and spleen weight were also significantly greater in patients with total SVT. Multiple logistic regression analysis demonstrated spleen weight was the strongest predictor of PSVT and total SVT. CONCLUSION: Patients with total SVT have greater risk factors for PSVT and frequently have clinical symptoms. They are candidates for anticoagulation therapy.     

C4.4A is associated with tumor budding and epithelial-mesenchymal transition of colorectal cancer

C4.4A is a glycolipid-anchored membrane protein expressed in several human malignancies. The aim of this study was to explore the association between C4.4A expression at the invasion front of colorectal cancer (CRC) and tumor budding, a putative hallmark of cell invasion of CRC. Advanced CRCs (T2-4, n = 126) had a budding count of 3.66 ± 5.66, which was significantly higher than that of T1 early CRCs (1.75 ± 2.78, n = 87). C4.4A-positive CRC specimens showed a larger budding cell number than C4.4A-negative CRC specimens in T1 CRCs, and especially advanced CRCs (9.45 ± 5.83 vs 1.60 ± 3.93). Furthermore, we found a correlation between the percentage of C4.4A-positive cases and budding count in advanced CRC. Multivariate analysis for patients' survival showed that C4.4A was superior to tumor budding as a prognostic factor. With siRNA treatment, C4.4A levels were associated with cell invasion, but not with proliferation, in HCT116 and DLD1 cell lines. An immunohistochemical study in a subset of CRCs showed no relationship between C4.4A and Ki-67 proliferation marker. In vitro assays using HCT116 indicated that C4.4A levels correlated well with epithelial-mesenchymal transition (EMT) with regard to cell morphology and alterations of EMT markers including E-cadherin, vimentin, and partially N-cadherin. We also found that C4.4A expression was significantly associated with loss of E-cadherin and gain of β-catenin in clinical CRC tissue samples. These findings suggest that a tight association between C4.4A and tumor budding may, in part, be due to C4.4A promoting EMT at the invasive front of CRC.     

Fanconi anemia--genotoxic stress and senescence of hematopoietic stem cells

Fanconi anemia (FA) is a genetically heterogeneous inherited disorder characterized by progressive bone marrow failure, development of hematopoietic and solid malignancies and genomic instability. 13 FA proteins, identified to date, closely cooperate with familial breast cancer susceptibility proteins such as BRCA2 and PALB2, thereby forming 'the FA/BRCA molecular network'. Here I summarize our recent understanding of the molecular network and its significance in the pathogenesis of FA. I emphasize that FA provides an excellent genetic model for studying senescence and malignant transformation of human hematopoietic stem cells.     

Reduced frontal asymmetry of delta waves during all-night sleep in schizophrenia

Delta wave deficits during sleep have been observed in patients with schizophrenia. Decreased slow-wave sleep is reported to be associated with negative symptoms. Frontal lobe dysfunction is also believed to underlie negative symptoms of schizophrenia. This study was designed to identify functional abnormalities in schizophrenia manifested on patients' electroencephalograms. Polysomnograph examinations were performed in 12 healthy male volunteers and 11 male outpatients with schizophrenia. We investigated the laterality of frontal cortical delta waves in patients with schizophrenia and in healthy control subjects. Laterality of frontal cortex delta wave counts during all-night sleep was investigated by computer analysis. Total delta wave counts were lower in patients with schizophrenia than in control subjects. Control subjects showed significantly higher delta wave counts in the right frontal cortex than in the left. This asymmetry was not observed in patients with schizophrenia. These findings suggest that reduced right frontal delta wave dominance is involved in the pathophysiology of schizophrenia.     

The gene expression profile represents the molecular nature of liver metastasis in colorectal cancer

The major cause of death in colorectal cancer is related to liver metastasis. Although the metastatic process has been well studied, many aspects of the molecular genetic basis of metastasis remain unclear. Elucidation of the molecular nature of liver metastasis is urgent to improve the outcome of colorectal cancer. We analyzed the chronological gene expression profiles of 104 colorectal samples corresponding to oncogenic development including normal mucosa, localized and metastasized primary tumors, and liver metastatic lesions as fundamental samples using a custom cDNA microarray. The gene expression patterns in 104 samples were classified into four groups closely associated with their metastatic status, and the genes of each group appropriately reflected the metastatic process. To investigate the existence of metastatic potential in primary tumors using metastasis-related genes detected by chronological analysis, we performed a hierarchical cluster and supervised classification analysis of 28 independent primary tumors. Hierarchical cluster analysis segregated the tumors according to their final metastatic status, rather than their clinical stages, and the profile of metastasized primary tumors resembled one of a metastatic lesion apart from a primary lesion rather than one of a non-metastasized primary tumor. Using the supervised classification approach, the expression profile of these genes allowed the classification of tumors diagnosed as localized cancer into two classes, the localized and the metastasized class, according to their final metastatic status. The disease-free survival and overall survival were significantly longer in the localized class than the metastasized class. Chronological analysis of the gene expression profile provides a better understanding of the metastatic process. Our results suggest that the metastatic potential is already encoded in the primary tumor and is detectable by a gene expression profile, which allows the prediction of liver metastasis in patients diagnosed with localized tumors and also the design of new strategies for the treatment and diagnosis of colorectal cancer.