The skill qualification system for portal hypertension in Japan.

Objectives: The diverse treatments available for portal hypertension require specialized knowledge of hemodynamics and include endoscopic treatments, interventional radiology (IVR), and surgery. The Japan Society for Portal Hypertension has developed the skill qualification system (SQS) for portal hypertension and began examination in 2014. Here, the status and validity of the judgment of the SQS examination were evaluated. Methods: From 2014 to 2020, 79 applicants were evaluated by the SQS for portal hypertension. Each unedited video submitted as a candidate procedure was evaluated by two judges, and a grade of greater than 70% for the scoring items assessed by the judges was required to pass the examination. Inter-rater agreement of success/failure between the two judges was investigated by the AC1 coefficient. Results: The results of two judges differed for 11 of the 79 videos (13.9%), and five applicants (6.3%) ultimately failed the examination. The percentages of total points received by the applicants with endoscopic treatments, IVR, and surgery were 87.3%, 79.4%, and 80.8%, respectively. There were significant differences in the percentages between endoscopic treatments and IVR (P = 0.0015). The AC1 coefficients were 0.84 for the applicants overall, 0.93 for endoscopic treatments, 0.66 for IVR, and 0.72 for surgery. Similarly, there were significant differences in the AC1 coefficient between endoscopic treatments and IVR (P = 0.021). Conclusions: The SQS for portal hypertension of the Japan Society for Portal Hypertension showed high reliability for video assessments by the judges. This system may contribute to the spread and further development of safe and effective treatments for portal hypertension in Japan.

Development of an Outer Tube That Reduces Nasal Pain and Epistaxis during Transnasal Endoscopy.

BACKGROUND: Transnasal endoscopy has recently become common in Japan. Although transnasal endoscopy has many advantages, nasal pain and epistaxis are common complaints. To reduce nasal pain and epistaxis, we developed a new tube sheath system for transnasal endoscopy. This new tube sheath system (outer sheath and inner tube), called the Nasal Slider, is produced by TOP Corporation, Japan. METHODS: A tube sheath longer than the nasal concha is inserted to reduce pain along the nasal turbinate. Because the sheath is left in place, tubes can be passed through the nose multiple times without causing additional pain. A total of 34 consecutive patients (mean age 68.1 years; 22 men and 12 females) who had undergone transnasal endoscopy in the past were selected for transnasal endoscopy with the Nasal Slider. After the transnasal endoscopy was completed, patients who gave consent for use of the Nasal Slider were interviewed by using 3 questionnaires on nasal discomfort, nasal pain, and epistaxis. RESULTS: Because the transnasal endoscope passes inside the sheath, epistaxis can be prevented. Thirty of 34 selected patients underwent transnasal endoscopy using the Nasal Slider. Twenty-seven and 28 patients reported feeling less nasal discomfort and pain, respectively, with the Nasal Slider than during examinations without the Nasal Slider. No epistaxis developed in any patient examined with the Nasal Slider. CONCLUSIONS: The Nasal Slider appears to reduce nasal pain and epistaxis during transnasal endoscopy and is currently used in many hospitals in Japan.

Randomised phase III study of S-1 alone versus S-1 plus lentinan for unresectable or recurrent gastric cancer (JFMC36-0701).

BACKGROUND: Lentinan (LNT) is a purified ß-1, 3-glucan that augments immune responses. The present study was conducted to assess the efficacy of LNT in combination with S-1 as a first-line treatment for unresectable or recurrent gastric cancer. PATIENTS AND METHODS: Eligible patients were randomly assigned to receive S-1 alone or S-1 plus LNT. The primary end-point was overall survival (OS). Secondary end-points were time-to-treatment failure (TTF), overall response rate (ORR), safety, quality of life (QOL), and biomarker. The percentages of LNT-binding monocytes in peripheral blood prior to treatment were analysed for the biomarker assessment. RESULTS: One hundred and fifty-four and 155 patients were randomly assigned to receive S-1 alone or S-1 plus LNT, respectively. The median OS was 13.8 and 9.9 months (P = 0.208), the median TTF was 4.3 and 2.6 months (P < 0.001), the ORR was 22.3% and 18.7% for the S-1 and S-1 plus LNT groups, respectively. The incidences of haematologic and non-haematologic adverse events were similar, and no significant changes in QOL scores were observed during the treatment in both groups. In a subpopulation of patients with LNT-binding monocytes ≥2%, patients who received more than two cycles of chemotherapy showed a longer survival time in the S-1 plus LNT group. CONCLUSIONS: OS did not improve and TTF was significantly worse in the S-1 plus LNT group as compared with the S-1-only group. This study showed no efficacy of LNT when combined with S-1 treatment in patients with unresectable or recurrent gastric cancer. CLINICAL TRIAL REGISTRATION ID NUMBER: UMIN 000000574.

Q-FISH measurement of hepatocyte telomere lengths in donor liver and graft after pediatric living-donor liver transplantation: donor age affects telomere length sustainability.

Along with the increasing need for living-donor liver transplantation (LDLT), the issue of organ shortage has become a serious problem. Therefore, the use of organs from elderly donors has been increasing. While the short-term results of LDLT have greatly improved, problems affecting the long-term outcome of transplant patients remain unsolved. Furthermore, since contradictory data have been reported with regard to the relationship between donor age and LT/LDLT outcome, the question of whether the use of elderly donors influences the long-term outcome of a graft after LT/LDLT remains unsettled. To address whether hepatocyte telomere length reflects the outcome of LDLT, we analyzed the telomere lengths of hepatocytes in informative biopsy samples from 12 paired donors and recipients (grafts) of pediatric LDLT more than 5 years after adult-to-child LDLT because of primary biliary atresia, using quantitative fluorescence in situ hybridization (Q-FISH). The telomere lengths in the paired samples showed a robust relationship between the donor and grafted hepatocytes (r = 0.765, p = 0.0038), demonstrating the feasibility of our Q-FISH method for cell-specific evaluation. While 8 pairs showed no significant difference between the telomere lengths for the donor and the recipient, the other 4 pairs showed significantly shorter telomeres in the recipient than in the donor. Multiple regression analysis revealed that the donors in the latter group were older than those in the former (p = 0.001). Despite the small number of subjects, this pilot study indicates that donor age is a crucial factor affecting telomere length sustainability in hepatocytes after pediatric LDLT, and that the telomeres in grafted livers may be elongated somewhat longer when the grafts are immunologically well controlled.

Safe technique for laparoscopic distal pancreatectomy involving a large cystic tumor.

BACKGROUND: In patients with large tumors, securing sufficient working space to perform laparoscopic resection can be difficult. The purpose of this technical note is to describe a technique for easy performance of laparoscopic distal pancreatectomy involving large cystic pancreatic tumors. SURGICAL TECHNIQUE: Early in surgery, a small incision was made in the abdominal wall directly above the tumor to remove the laparoscopically resected tissues from the abdominal cavity. After the margin of the incision was secured with a wound protector, a double-balloon catheter was used to remove the contents of the tumor under direct observation, without allowing any leakage into the abdominal cavity. The volume of the tumor could, thus, be safely reduced. As a result, laparoscopic distal pancreatectomy was safely performed, even for 17-cm-diameter mucinous cystic neoplasm of the pancreas. CONCLUSION: A wound protector and a double-balloon catheter are helpful for removing the contents of a cystic tumor. A small abdominal incision for removing the resected tissues can be used during the resection procedure to aspirate the tumor contents, and, as a result, laparoscopic distal pancreatectomy can be performed safely, even for large cystic pancreatic tumors.

Real-time PCR-based analysis of the human bile microRNAome identifies miR-9 as a potential diagnostic biomarker for biliary tract cancer.

Biliary tract cancer (BTC) is often difficult to diagnose definitively, even through histological examination. MicroRNAs (miRNAs) regulate a variety of physiological processes. In recent years, it has been suggested that profiles for circulating miRNAs, as well as those for tissue miRNAs, have the potential to be used as diagnostic biomarkers for cancer. The aim of this study was to confirm the existence of miRNAs in human bile and to assess their potential as clinical biomarkers for BTC. We sampled bile from patients who underwent biliary drainage for biliary diseases such as BTC and choledocholithiasis. PCR-based miRNA detection and miRNA cloning were performed to identify bile miRNAs. Using high-throughput real-time PCR-based miRNA microarrays, the expression profiles of 667 miRNAs were compared in patients with malignant disease (n = 9) and age-matched patients with the benign disease choledocholithiasis (n = 9). We subsequently characterized bile miRNAs in terms of stability and localization. Through cloning and using PCR methods, we confirmed that miRNAs exist in bile. Differential analysis of bile miRNAs demonstrated that 10 of the 667 miRNAs were significantly more highly expressed in the malignant group than in the benign group at P<0.0005. Setting the specificity threshold to 100% showed that some miRNAs (miR-9, miR-302c*, miR-199a-3p and miR-222*) had a sensitivity level of 88.9%, and receiver-operating characteristic analysis demonstrated that miR-9 and miR-145* could be useful diagnostic markers for BTC. Moreover, we verified the long-term stability of miRNAs in bile, a characteristic that makes them suitable for diagnostic use in clinical settings. We also confirmed that bile miRNAs are localized to the malignant/benign biliary epithelia. These findings suggest that bile miRNAs could be informative biomarkers for hepatobiliary disease and that some miRNAs, particularly miR-9, may be helpful in the diagnosis and clinical management of BTC.

Ipomoea batatas and Agarics blazei ameliorate diabetic disorders with therapeutic antioxidant potential in streptozotocin-induced diabetic rats.

Ipomoea batatas, Agaricus blazei and Smallanthus sonchifolius are known to favorably influence diabetes mellitus. To clarify their antidiabetic efficacy and hypoglycemic mechanisms, we treated streptozotocin-induced diabetic rats with daily oral feeding of powdered Ipomoea batatas (5 g kg(-1) d(-1)), Agaricus blazei (1 g kg(-1) d(-1)) or Smallanthus sonchifolius (4 g kg(-1) d(-1)) for 2 months. Treatments with Ipomoea batatas or Agaricus blazei, but not Smallanthus sonchifolius, significantly suppressed the increases of fasting plasma glucose and hemoglobin A1c levels, and restored body weight loss during diabetes. Serum insulin levels after oral glucose administration tests increased along the treatments of Ipomoea batatas or Agaricus blazei. Moreover, Ipomoea batatas and Agaricus blazei reduced superoxide production from leukocytes and vascular homogenates, serum 8-oxo-2'-deoxyguanosine, and vascular nitrotyrosine formation of diabetic rats to comparable levels of normal control animals. Stress- and inflammation-related p38 mitogen-activated protein kinase activity and tumor necrosis factor-α production of diabetic rats were significantly depressed by Ipomoea batatas administration. Histological examination also exhibited improvement of pancreatic ß-cells mass after treatments with Ipomoea batatas or Agaricus blazei. These results suggest that hypoglycemic effects of Ipomoea batatas or Agaricus blazei result from their suppression of oxidative stress and proinflammatory cytokine production followed by improvement of pancreatic ß-cells mass.

Sequencing and bioinformatics-based analyses of the microRNA transcriptome in hepatitis B-related hepatocellular carcinoma.

MicroRNAs (miRNAs) participate in crucial biological processes, and it is now evident that miRNA alterations are involved in the progression of human cancers. Recent studies on miRNA profiling performed with cloning suggest that sequencing is useful for the detection of novel miRNAs, modifications, and precise compositions and that miRNA expression levels calculated by clone count are reproducible. Here we focus on sequencing of miRNA to obtain a comprehensive profile and characterization of these transcriptomes as they relate to human liver. Sequencing using 454 sequencing and conventional cloning from 22 pair of HCC and adjacent normal liver (ANL) and 3 HCC cell lines identified reliable reads of more than 314000 miRNAs from HCC and more than 268000 from ANL for registered human miRNAs. Computational bioinformatics identified 7 novel miRNAs with high conservation, 15 novel opposite miRNAs, and 3 novel antisense miRNAs. Moreover sequencing can detect miRNA modifications including adenosine-to-inosine editing in miR-376 families. Expression profiling using clone count analysis was used to identify miRNAs that are expressed aberrantly in liver cancer including miR-122, miR-21, and miR-34a. Furthermore, sequencing-based miRNA clustering, but not individual miRNA, detects high risk patients who have high potentials for early tumor recurrence after liver surgery (P = 0.006), and which is the only significant variable among pathological and clinical and variables (P = 0,022). We believe that the combination of sequencing and bioinformatics will accelerate the discovery of novel miRNAs and biomarkers involved in human liver cancer.

The controlled release of basic fibroblast growth factor promotes a rapid healing of pancreaticojejunal anastomosis with potent angiogenesis and accelerates apoptosis in granulation tissue.

BACKGROUND: Our previous study demonstrated that bFGF-GH promoted healing of the pancreaticojejunostomy (PJ) in an animal model. We examined the healing process in detail to investigate the significance of treatment with basic fibroblast growth factor (bFGF) incorporated in gelatin hydrogel (GH) microspheres for anastomotic healing. MATERIALS AND METHODS: The optimal dose of bFGF was determined by administering bFGF concentrations of 1, 10, and 100 µg in six beagle dogs and assessing the results on d 7. Next, 28 dogs received a jejunal subserosal injection of 10 µg bFGF-GH or GH alone. The healing process was sequentially analyzed on d 4, 7, 21, and 28. The following types of assessment were performed: breaking strength test, pathologic examination, and calculations of collagen content, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) index, and microvessel density (MVD). RESULTS: The administration of a bFGF dose of more than 10 µg induced a significantly higher breaking strength and more abundant granulation tissues. Histologic observations of the bFGF-GH group on d 7 and the GH-alone group on d 21 revealed abundant granulation tissue with migrating fibroblasts, inflammatory cells, and capillaries. Marked neovascularization and dense collagen deposition were detected in both groups on d 28. The collagen content and breaking strength did not significantly differ between both groups on d 28. A significantly higher TUNEL index and a rapid decline in the number of vimentin-positive cells were detected in the bFGF-GH group from d 21 onward. The MVD in the bFGF-GH group was significantly higher from d 7 onward CONCLUSIONS: Basic FGF-GH administration can promote the rapid completion of PJ anastomosis and may help improve the quality of the healing of granulation tissue by conferring potent angiogenesis and accelerating apoptosis.

Prospective randomized controlled study of short-term perioperative oral nutrition with branched chain amino acids in patients undergoing liver surgery.

BACKGROUND/AIMS: Early prospective randomized clinical trials demonstrated that perioperative parenteral nutrition (PN) with branched chain amino acids (BCAA) is beneficial in cirrhotic patients with hepatocellular carcinoma who undergo hepatectomy. However, PN support is expensive and requires a long hospital stay. Moreover, PN support has not been evaluated in patients with a normal liver who undergo hepatectomy. It was studied the benefits of perioperative oral nutrition (ON) with BCAA in patients who underwent hepatectomy, including those with a non-hepatitis liver. METHODOLOGY: In this prospective, randomized, controlled trial, 38 patients were assessed for eligibility. Fourteen patients were excluded because they had received intraoperative blood transfusions or incomplete resections. The 24 eligible patients (20 with malignant liver tumors and 4 with benign liver tumors) were randomly assigned to receive perioperative ON with BCAA (11 patients, BCAA group) or a usual diet (13 patients, control group). The BCAA group received a BCAA supplement twice daily plus a usual diet for 14 days before operation and on days 1 to 7 after operation. The control group received a usual diet alone. The primary end point was the improvement in postoperative biochemical measurements. RESULTS: Two of the 11 patients in the BCAA group developed postoperative complications, as compared with 3 of the 13 patients in the control group (18.2% vs. 23.1%, p = 0.7686). Serum levels of alanine aminotransferase, aspartate aminotransferase, and ammonia did not differ significantly between the BCAA group and control group; however, peak values were lower in the BCAA group. There was no difference between the groups in serum hemoglobin levels after operation. Among patients with hepatitis, serum erythropoietin (EPO) levels on POD 3, 5, and 7 were slightly but not significantly higher in the BCAA group than in the control group. Among patients with non-hepatitis, serum EPO levels on POD 3, 5, and 7 were significantly higher in the BCAA group than in the control group (p = 0.0174, p = 0.0141, and p = 0.0328, respectively). CONCLUSION: Short-term ON support with BCAA was associated with higher serum EPO levels than was a normal diet in patients with non-hepatitis who underwent curative hepatic resection. Higher EPO levels might be beneficial in protecting liver cells from ischemic injury and preventing intraoperative hemorrhage associated with lower perioperative levels of alanine aminotransferase and aspartate aminotransferase in serum. This is the first study to demonstrate an effect of EN support with BCAA in patients with non-hepatitis, as well as those with hepatitis.

Vagotomy suppresses body weight gain in a rat model of gastric banding.

BACKGROUND: The aim of this study was to evaluate the effect of vagotomy on body weight changes after gastric banding. METHODS: Rats were divided into a sham-operated group (n = 10), a vagotomy alone group (n = 10), a gastric banding alone group (n = 10) and a gastric banding + vagotomy group (n = 10). All groups were given a liquid diet for 5 days after surgery and then given free access to chow. Their body weight was measured through postoperative day (POD) 14, and caloric intake and nitrogen balance were measured until POD 7. RESULTS: The increase in body weight in the banding + vagotomy group between POD 0 and POD 14 was not significant (12.5 +/- 16.8 g; p = 0.48), and it was less than in the banding alone group (52.8 +/- 3.8 g; p = 0.031). Cumulative caloric intake from POD 5 to POD 7 was less in the banding + vagotomy group than in the banding alone group (158.6 +/- 26.3 vs. 223.9 +/- 8.3 kcal; p = 0.030). Daily nitrogen balance from POD 5 to POD 7 in the banding + vagotomy group was less than in the banding group (337 +/- 77 vs. 540 +/- 42 mg; p = 0.033). CONCLUSIONS: Vagotomy suppressed body weight gain in the rat model of gastric banding.

Current status of ectopic varices in Japan: Results of a survey by the Japan Society for Portal Hypertension.

AIM: The Clinical Research Committee of the Japan Society for Portal Hypertension has conducted a nationwide questionnaire survey to clarify the current status of ectopic varices in Japan. METHODS: A total of 173 cases of ectopic varices were collected. RESULTS: Duodenal varices were found in 57 cases, and most of them were located in the descending to transverse parts. There were 11 cases of small intestinal varices and 6 cases of colonic varices, whereas 77 patients had rectal varices, accounting for the greatest proportion (44.5%). Other sites of varices were the biliary tract, anastomotic sites, the stoma, and the diaphragm. Liver cirrhosis was the most frequent diseases (80.3%) underlying ectopic varices. It was noted that patients with rectal varices frequently had a history of esophageal varices (94.8%) and received endoscopic treatment (87.0%). The treatments for ectopic varices were as an emergency in 46.5%, elective in 35.4% and prophylactic in 18.2%. In emergency cases, endoscopic therapy was most frequent (67.4%), followed by interventional radiology (IVR; 15.2%), and endoscopy-IVR combination (6.5%). Elective treatment was performed by endoscopy in 34.3%, IVR in 28.6%, combined endoscopy-IVR in 5.7%, and surgical operation in 25.7%. The prophylactic treatment was endoscopic in 50.0%, IVR in 33.3%, combined treatments in 11.1%, and prophylactic surgery in none. The change of ectopic varices after treatment was disappearance in 54.9%, remnant in 35.4% and recurrence in 9.7%. The rate of disappearance was significantly lower in rectal varices (40.8%) than in duodenal varices (73.4%). The patient outcome did not differ among the various sites of the lesion. Conslusions: Current status of ectopic varices in Japan has been clarified by a nationwide questionnaire survey. The authors expect that the pathophysiology of ectopic varices will be further elucidated, and that improved diagnostic modalities and treatment methods are established in the future.

Use of an endoscopic surgical spacer during laparoscopic pancreatic tumor enucleation.

A number of recent reports have highlighted the usefulness of laparoscopic surgery for pancreatic surgery; however, the procedure is not yet standard because of its technical challenges. Using an endoscopic surgical spacer (SECUREA) that we developed, we performed laparoscopic enucleation of a pancreatic tumor in a patient with pancreatic mucinous cystadenoma. The SECUREA is a polyurethane sponge with a radiopaque marker. It is elliptic-cylindrical and measures 6.5 cm on the major axis, 3.5 cm on the minor axis, and 2 cm in height. Herein, we report the intraoperative findings and examine the usefulness of SECUREA for laparoscopic enucleation. The spacer was introduced into the abdominal cavity through a 12-mm trocar, and was grasped with forceps to isolate or extend organs and tissues, thereby ensuring a safe and relatively uncontaminated surgical field. In addition, the high absorptiveness and water-holding capacity of the sponge facilitated removal of exudate, which created a clearer operative field and reduced the technical challenges of drainage manipulation. Indeed, replacement of the sponge was unnecessary because it returned to its original state after the liquid it contained had been aspirated. Our findings suggest that the SECUREA increases safety and reduces the technical difficulties of laparoscopic enucleation.

General rules for recording endoscopic findings of esophagogastric varices (2nd edition).

General rules for recording endoscopic findings of esophageal varices were initially proposed in 1980 and revised in 1991. These rules have widely been used in Japan and other countries. Recently, portal hypertensive gastropathy has been recognized as a distinct histological and functional entity. Endoscopic ultrasonography can clearly depict vascular structures around the esophageal wall in patients with portal hypertension. Owing to progress in medicine, we have updated and slightly modified the former rules. The revised rules are simpler and more straightforward than the former rules and include newly recognized findings of portal hypertensive gastropathy and a new classification for endoscopic ultrasonographic findings.

Identification of obstructive jaundice-related microRNAs in mouse liver.

BACKGROUND/AIMS: Although microRNAs are known to be post-transcriptional regulators in physiological and pathological events in the liver, their role in the obstructive jaundice liver remains unclear. METHODOLOGY: We sequenced the small RNA libraries of the bile duct ligation (BDL) mouse liver to detect the in vivo microRNA expression profiles of obstructive jaundice. We also validated the differential expression of microRNAs in the BDL liver using real-time PCR. Laser microdissection was performed to identify the origin of BDL-related microRNAs. An IL6-treated normal intrahepatic biliary epithelial cell line was used as an in vitro model of obstructive jaundice. RESULTS: We found microRNAs that were upregulated in the BDL liver (let-7a, let-7d, let-7f, let-7g, miR-21, miR-125a-5p, miR-125b-5p, miR-194, miR-199a-3p, miR-199a-5p, miR-214, miR-221, and miR-486). Furthermore, laser-microdissection analysis showed that miR-199a-5p was significantly upregulated in the intrahepatic bile duct of the BDL liver. The in vitro expression of miR-199a-5p was appreciably elevated in accordance with increased proliferation of IL6-treated cells. CONCLUSIONS: We revealed dynamic changes in microRNA expression during obstructive jaundice using the BDL model. MiR-199a-5p was likely associated with the proliferation of intrahepatic bile ducts. Our data will facilitate further study of the pathophysiological role(s) of microRNAs in the obstructive jaundice liver.

Shunting and nonshunting procedures for the treatment of esophageal varices in patients with idiopathic portal hypertension.

BACKGROUND/AIMS: We evaluated the results of shunting and nonshunting procedures for the treatment of esophagogastric varices in patients with idiopathic portal hypertension (IPH). METHODOLOGY: Between 1981 and 2008, surgery was performed in 9 patients with IPH. Three patients were bleeding before operation, and the other 6 were treated prophylactically. Patients were divided into 2 groups, a shunting group (4 underwent distal splenorenal shunt) and a nonshunting group (3 underwent esophageal transection and 2 underwent Hassab's procedure). RESULTS: Esophagogastric varices were completely eradicated in 3 (75.0%) patients in the shunting group and 4 patients (80.0%) in the nonshunting group. Additional endoscopic treatment (one session) was performed in 2 patients with incompletely eradicated varices. There was no recurrence in the shunting group. In the nonshunting group, esophagogastric varices recurred in all 4 patients with completely eradicated varices. All recurrent esophageal varices were completely eradicated. Postoperative platelet counts (x10(4)/microL) were significantly lower in the shunting group (10.0 +/- 2.6) than in the nonshunting group (42.0 +/- 14.0) (p = 0.0029). The increase in the platelet count after operation was significantly lower in the shunting group (1.7 +/- 0.2 times) than in the nonshunting group (5.8 +/- 2.9 times) (p = 0.0267). No patient received anticoagulants postoperatively. Portal venous thrombus did not develop in the shunting group, but appeared in 4 patients (80.0%) in the nonshunting group. No patient had loss of shunt selectivity or portal-systemic encephalopathy. One patient in the nonshunting group died of cerebral hemorrhage; all others are alive. CONCLUSIONS: Shunting procedure, distal splenorenal shunt, was suggested to be useful for the management of esophagogastric varices in patients with IPH.

Interactions between anti-ulcer drugs and non-steroidal anti-inflammatory drugs in cirrhotic patients with bleeding esophagogastric varices.

BACKGROUND/AIMS: Bleeding from esophagogastric varices is a life-threatening complication of chronic liver disease. As compared with esophageal varices (EV), the risk factors for bleeding from gastric varices remain unclear. This study examined interactions between anti-ulcer drugs and non-steroidal anti-inflammatory drugs (NSAIDs) as related to bleeding esophagogastric varices in cirrhotic patients. METHODOLOGY: Eighty-eight cirrhotic patients with an initial episode of bleeding esophagogastric varices who had not received prior treatment studied. The patients were divided 3 groups: 58 with bleeding from EV, 13 with bleeding from cardiac varices (CV), and 17 with bleeding from cardiofundic or fundic varices (FV). The use of "standard" NSAIDs on 4 or more of the last 7 days before the initial episode of bleeding was defined as "regular" use; all other use was considered "occasional". RESULTS: The number of anti-ulcer drug users was 16 (27.6%) in the EV group, 4 (30.8%) in the CV group, and 5 (29.4%) in the FV group. The number of NSAID users was 9 (15.5%) in the EV group, 4 (30.8%) in the CV group, and 11 (64.7%) in the FV group. The proportion of NSAID users was significantly higher in the FV group than in the EV group (p < 0.0001). All 16 users of anti-ulcer drugs who were nonusers of NSAIDs had varices with red color signs. All NSAID users had used NSAIDs orally within a day before the initial episode of bleeding. All "regular" NSAID users were nonusers of anti-ulcer drugs. All anti-ulcer drug users without red color signs were "occasional" NSAID users. CONCLUSIONS: "Occasional" oral NSAID use is an important step leading to variceal hemorrhage, especially in FV, even if the mucosa is protected by anti-ulcer drugs. The ability to use NSAIDs for several days without variceal bleeding in some patients with esophagogastric varices who are concurrently receiving anti-ulcer drugs suggests that such drugs might protect the esophagogastric mucosa.

HPV infection in an HIV-positive patient with primary squamous cell carcinoma of rectum.

Primary squamous cell carcinoma (SCC) of the colorectum is a rare malignancy of unknown etiology and pathogenesis. We report a case of primary SCC of the rectum. A 55-year-old man with a rectal tumor and human immunodeficiency virus (HIV) infection was referred to our hospital. Histopathology of biopsy specimens showed characteristics of SCC. We diagnosed the patient as having primary moderately differentiated SCC of the rectum according to the criteria proposed by Cooper. Human papillomavirus (HPV) DNA was amplified by polymerase chain reaction analysis of unfixed tumor biopsy specimens. In addition, no p53 overexpression or nuclear staining of retinoblastoma protein (Rb) was observed in neoplastic cells by immunohistochemical staining. We suggest from our case that HPV infection following the inactivation of the cellular tumor suppressor Rb and the immune suppression induced by HIV infection play an etiologic role in the pathogenesis of rectal SCC, consistent with the well-established concept of HPV-associated anal carcinogenesis.

A case of a mesenteric cyst in the sigmoid colon of a 3-year-old girl.

Mesenteric cysts are rare. In this paper we present a case of a mesenteric cyst in the sigmoid colon of a 3-year-old girl. On the first visit to our department, a smooth-surfaced soft mass approximately 15 cm in diameter was noticed in the right lower abdomen. Although the patient complained of lower abdominal pain, there was no tenderness or guarding. Laboratory tests indicated no abnormality except a slightly increased level of C-reactive protein (2.3 mg/dL). A plain abdominal X-ray film revealed displacement of colonic gas from the right lower abdomen, and abdominal ultrasonography and computed tomography revealed a smooth cystic mass measuring 9.5 x 8.7 x 4.7 cm that contained many internal septa. Because the patient had several symptoms, we performed a surgical operation under general anesthesia. We found a light-red cystic mass, 8.5 x 8.0 x 3.0 cm in size, in the mesentery of the sigmoid colon and surrounding the sigmoid colon, without adhesion to any other organ. We approached the cystic mass from the sigmoid colon and the mesentery of sigmoid colon and completely resected it without complications. The content of the cystic mass was a pale-yellow serous fluid. A cytological examination revealed mainly lymphocytes with reactive mesothelial cells. The resulting pathological diagnosis was a multi-lobular mesenteric cyst. Immunohistochemical staining with D2-40 antibody was positive value along the wall of the cyst, indicating that the cyst was derived from a lymphatic vessel.

Aggressive undifferentiated colon carcinoma producing granulocyte-colony stimulating factor: report of a case.

We report a rare case of granulocyte-colony stimulating factor (G-CSF)-producing undifferentiated carcinoma of the ascending colon. A 52-year-old Japanese man presented with a rapidly growing, aggressive abdominal tumor, and severe leukocytosis (63 000/mm(3)). The serum level of G-CSF was remarkably elevated to 640 pg/ml (normal, <18.1 pg/ml). The patient underwent palliative cytoreductive surgery for ascending colon carcinoma with lymph node and liver metastases. Histological examination revealed an undifferentiated carcinoma of the ascending colon. The tumor cells were positive for G-CSF on immunohistochemical staining. The leukocyte counts and G-CSF level decreased after surgery. Thus, we diagnosed G-CSF-producing colon carcinoma. His general condition deteriorated rapidly and he died of residual tumor growth on postoperative day 24.