A novel germline SMAD4 variant detected in a Japanese family with juvenile polyposis syndrome and hereditary hemorrhagic telangiectasia.

Juvenile polyposis syndrome (JPS) is an autosomal dominant, inherited disorder caused by pathogenic germline variants of mainly SMAD4 or BMPR1A genes. Some patients with JPS, especially with SMAD4 variants, also develop hereditary, hemorrhagic telangiectasia (HHT). HHT is also an autosomal dominant inherited disorder. Herein, we identified a novel germline pathogenic variant of the SMAD4 in a Japanese family with JPS and HHT. A six-base pair deletion in the SMAD4 gene (NM_005359.6:c.1495_1500delTGCATA) was identified in the patients. Two amino acids are deleted from SMAD4 protein (p.Cys499_Ile500del), which are located in MSH2 domain essential for the binding with SMAD3. This is a novel variant that has not been registered in any database surveyed. Amino acid structural analysis predicted significant changes in the secondary and three-dimensional structures in the vicinity of the two amino acids' deletion. The variant is classified as 'Likely Pathogenic' according to the American College of Medical Genetics and Genomics guidelines.

Feeding gastrostomy and duodenostomy using the round ligament of the liver versus conventional feeding jejunostomy after esophagectomy: a meta-analysis.

Esophageal cancer patients require enteral nutritional support after esophagectomy. Conventional feeding enterostomy to the jejunum (FJ) is occasionally associated with small bowel obstruction because the jejunum is fixed to the abdominal wall. Feeding through an enteral feeding tube inserted through the reconstructed gastric tube (FG) or the duodenum (FD) using the round ligament of the liver have been suggested as alternatives. This meta-analysis aimed to compare short-term outcomes between FG/FD and FJ. Studies published prior to May 2022 that compared FG or FD with FJ in cancer patients who underwent esophagectomy were identified via electronic literature search. Meta-analysis was performed using the Mantel-Haenszel random-effects model to calculate Odds Ratios (ORs) with 95% confidence intervals (CIs). Five studies met inclusion criteria to yield a total of 1687 patients. Compared with the FJ group, the odds of small bowel obstruction (OR 0.09; 95% CI, 0.02-0.33), catheter site infection (OR 0.18; 95% CI, 0.06-0.51) and anastomotic leakage (OR 0.53; 95% CI, 0.32-0.89) were lower for the FG/FD group. Odds of pneumonia, recurrent laryngeal nerve palsy, chylothorax and hospital mortality did not significantly differ between the groups. The length of hospital stay was shorter for the FG/FD group (median difference, -10.83; 95% CI, -18.55 to -3.11). FG and FD using the round ligament of the liver were associated with lower odds of small bowel obstruction, catheter site infection and anastomotic leakage than FJ in esophageal cancer patients who underwent esophagectomy.

[A Case of Pathological Complete Response Achieved with Neoadjuvant DCS Therapy in Gastric Cancer].

A 77-year-old man with appetite loss was referred to our hospital. Upper gastrointestinal endoscopy and computed tomography(CT)revealed advanced gastric cancer in the antrum with duodenal and pancreatic invasion. After 6 courses of neoadjuvant docetaxel, cisplatin, and S-1(DCS)therapy, CT revealed marked tumor shrinkage. Distal gastrectomy was performed. Histopathological examination showed no residual tumor cells or lymph node metastasis, and thus, finally, pathological complete response was considered to have been achieved. The patient was doing well and disease-free 3 years later. Thus, neoadjuvant DCS therapy can be a promising treatment option for borderline resectable advanced gastric cancer.

Current Status of Robotic Hepatobiliary and Pancreatic Surgery.

Laparoscopic surgery is performed worldwide and has clear economic and social benefits in terms of patient recovery time. It is used for most gastrointestinal surgical procedures, but laparoscopic surgery for more complex procedures in the esophageal, hepatobiliary, and pancreatic regions remains challenging. Minimally invasive surgery that results in accurate tumor dissection is vital in surgical oncology, and development of surgical systems and instruments plays a key role in assisting surgeons to achieve this. A notable advance in the latter half of the 1990s was the da Vinci Surgical System, which involves master-slave surgical support robots. Featuring high-resolution three-dimensional (3D) imaging with magnification capabilities and forceps with multi-joint function, anti-shake function, and motion scaling, the system compensates for the drawbacks of conventional laparoscopic surgery. It is expected to be particularly useful in the field of hepato-biliary-pancreatic surgery, which requires delicate reconstruction involving complex liver anatomy with diverse vascular and biliary systems and anastomosis of the biliary tract, pancreas, and intestines. The learning curve is said to be short, and it is hoped that robotic surgery will be standardized in the near future. There is also a need for a standardized robotic surgery training system for young surgeons that can later be adapted to a wider range of surgeries. This systematic review describes trends and future prospects for robotic surgery in the hepatobiliary-pancreatic region.

Minimally invasive surgery for esophagogastric junction cancer with Leriche's syndrome-induced ischemic enteritis in the rectum: A case report.

The incidence of esophagogastric junction cancer has been increasing, leading to growing interest in surgical treatment. Leriche syndrome, characterized by occlusion limited to the infrarenal aorta, has not been reported to be associated with ischemic enteritis, and there are no previous reports on the surgical approaches for esophagogastric junction cancer in this disease.We describe the case of a male patient in his fifties with lower abdominal pain and melena who was diagnosed with esophagogastric junction cancer, Leriche syndrome, and ischemic enteritis. Contrast-enhanced computed tomography (CT) showed a hemorrhage from the cancer, occlusion of the abdominal aorta beyond the renal artery branches, and rectal contrast deficiency. Three-dimensional (3D)-CT angiography revealed occlusion from the lumbar artery bifurcation to the distal portions of both common iliac arteries plus numerous collateral pathways, indicating a precarious rectal blood supply. Based on 3D-CT angiography, minimally invasive surgery (MIS) using laparoscopy and thoracoscopy for esophagogastric junction cancer was performed after whole-body control. The patient was discharged without any postoperative complications.Esophagogastric junction cancer with Leriche syndrome can be complicated by ischemic enteritis due to tumor bleeding and fragile collateral pathways. MIS using laparoscopy and thoracoscopy guided by 3D-CT angiography can be safely performed for this disease.

Current Status of Robotic Gastrointestinal Surgery.

Development of surgical support robots began in the 1980s as a navigation and auxiliary device for endoscopic surgery. For remote surgery on the battlefield, a master-slave-type surgical support robot was developed, in which a console surgeon operates the robot at will. The da Vinci surgical system, which currently dominates the global robotic surgery market, received United States Food and Drug Administration and regulatory approval in Japan in 2000 and 2009 respectively. The latest, fourth generation, da Vinci Xi has a good field of view via a three-dimensional monitor, highly operable forceps, a motion scale function, and a tremor-filtered articulated function. Gastroenterological tract robotic surgery is safe and minimally invasive when accessing and operating on the esophagus, stomach, colon, and rectum. The learning curve is said to be short, and robotic surgery will likely be standardized soon. Therefore, robotic surgery training should be systematized for young surgeons so that it can be further standardized and later adapted to a wider range of surgeries. This article reviews current trends and potential developments in robotic surgery.

Protein-losing enteropathy caused by a jejunal ulcer after an internal hernia in Petersen's space: A case report.

BACKGROUND: The incidence of internal hernias has recently increased in concordance with the popularization of laparoscopic surgery. Of particular concern are internal hernias occurring in Petersen's space, a space that is surgically created after treatment for gastric cancer and obesity. These hernias cause devastating sequelae, such as massive intestinal necrosis, fatal Roux limb necrosis, and superior mesenteric vein thrombus. In addition, protein-losing enteropathy (PLE) is a rare syndrome involving gastrointestinal protein loss, although its relationship with internal Petersen's hernias remains unknown. CASE SUMMARY: A 75-year-old man with a history of laparotomy for early gastric cancer developed Petersen's hernia 1 year and 5 mo after surgery. He was successfully treated by reducing the incarcerated small intestine and closure of Petersen's defect without resection of the small intestine. Approximately 3 mo after his surgery for Petersen's hernia, he developed bilateral leg edema and hypoalbuminemia. He was diagnosed with PLE with an alpha-1 antitrypsin clearance of 733 mL/24 h. Double-balloon enteroscopy revealed extensive jejunal ulceration as the etiology, and it facilitated minimum bowel resection. Pathological analysis showed extensive jejunal ulceration and collagen hyperplasia with nonspecific inflammation of all layers without lymphangiectasia, lymphoma, or vascular abnormalities. His postoperative course was unremarkable, and his bilateral leg edema and hypoalbuminemia improved after 1 mo. There was no relapse over the 5-year follow-up period. CONCLUSION: PLE and extensive jejunal ulceration may occur after Petersen's hernia. Double-balloon enteroscopy helps identify and resect these lesions.

Impact of Second-line Chemotherapy on Prognosis: Response of Advanced Gastric Cancer to Taxanes Plus Ramucirumab.

BACKGROUND/AIM: The impact of clinical response to taxanes plus ramucirumab (RAM) on overall survival (OS) has not been clarified for advanced gastric cancer (AGC), although this type of therapy is already in use as second-line chemotherapy (CTx). This study aimed to investigate the prognostic impact of the clinical response to taxanes plus ramucirumab (RAM) for AGC patients. PATIENTS AND METHODS: This study included AGC patients treated with paclitaxel (PTX) or nab-paclitaxel (nab-PTX) and RAM. A retrospective analysis of response and survival rates in consecutive medical records of patients was performed. RESULTS: Forty-two patients were enrolled. Median progression-free survival and OS were 5.4 months [95% confidence interval (CI)=4.440-6.361] and 11.8 months (95% CI=8.648-15.019), respectively. In Cox-hazard multivariate analysis, peritoneal metastasis [hazard ratio (HR)=2.830; 95% CI=1.320-6.067; p=0.008], and disease control rate (HR=0.310; 95% CI=0.129-0.741; p=0.008) were independent factors. CONCLUSION: The response to taxanes plus RAM CTx had an impact on the survival of patients with AGC.

A case of vascular Ehlers-Danlos syndrome with a ruptured hepatic artery after surgical treatment of peritonitis caused by the perforation of the colon.

BACKGROUND: Ehlers-Danlos syndrome (EDS) is an inherited disorder that causes connective tissue fragility. The vascular type of EDS (vEDS) caused by defective collagen type III production accounts for 5%-10% of all EDS cases. Patients can develop gastrointestinal or arterial ruptures, which cause poor prognosis. We report a case of a patient who experienced colonic rupture, which was immediately followed by arterial rupture. CASE PRESENTATION: A 40-year-old man who had been genetically diagnosed with vEDS 6 years previously was admitted to our hospital with ischemic colitis. After 3 days of conservative treatment, his abdominal pain worsened, and computed tomography (CT) revealed free air in the abdominal cavity. Pan-peritonitis due to perforation of the sigmoid colon was diagnosed. Intraperitoneal lavage and drainage and Hartmann's operation were urgently performed. Because the patient had confirmed vEDS, we performed the surgery in a protective manner. The postoperative course was initially good, and he was transferred to the general ward 3 days after surgery. However, 5 days after surgery, massive intra-abdominal hemorrhage suddenly occurred, and contrast-enhanced CT showed an aneurysm in the common hepatic artery that had ruptured; this aneurysm was not present before surgery and was far from the surgical field. Although we considered an emergency operation, the patient suddenly experienced cardiac arrest and was unresponsive to resuscitation. CONCLUSIONS: In cases of vEDS, vascular rupture can occur immediately after surgery for intestinal rupture. We recommend paying special attention to vascular complications in patients in their forties, as such complications are the most common causes of death.

Methylation status and long-fragment cell-free DNA are prognostic biomarkers for gastric cancer.

BACKGROUND: Circulating tumor DNA (ctDNA) detected before surgery disappears after complete surgical resection of the cancer. Residual ctDNA indicates minimal residual disease (MRD), which is a cause of recurrence. The presence of long-fragment circulating cell-free DNA (cfDNA) or methylated cfDNA also implies the presence of cancer. In this study, we evaluated the prognostic value of cfDNA methylation and long-fragment cfDNA concentration in gastric cancer patients undergoing curative surgery METHODS: Ninety-nine gastric cancer patients were included. Peripheral blood samples were collected before and 1 month after surgery. In patients administered chemotherapy, samples were collected before starting chemotherapy. qPCR was performed to detect long- and short-fragment LINE-1. A plasma HELP (HpaII tiny fragment Enrichment by Ligation-mediated PCR) assay to determine the concentration of HpaII small fragments was performed using ligation-mediated PCR and HpaII was quantified as the HpaII:MspI ratio to detect methylation levels of cfDNA. RESULTS: Overall survival (OS) of patients with low methylation levels before starting treatment was significantly worse than that of patients with high methylation levels (P = 0.006). In the 90 patients who underwent curative surgery, recurrence-free survival (RFS) and OS of patients with low methylation levels before surgery were worse than those with high methylation levels (P=0.08 and P = 0.11, respectively). RFS and OS of patients with high concentrations of long-fragment LINE-1 after surgery were significantly worse than those with low concentrations of long-fragment LINE-1 (P = 0.009, P = 0.04). CONCLUSIONS: Pre-surgical low methylation levels of LINE-1 are a negative prognostic factor. Post-surgical high concentrations of long-fragment LINE-1 indicate MRD and a high risk of recurrence.

Ligation and Fibrin Glue Spraying for Intractable Chylous Ascites after Radical Gastrectomy for Gastric Cancer: Case Report and Literature Review.

Chylous ascites associated with radical resection of gastric cancer is a serious clinical condition. Lymph node dissection is indispensable during gastrectomy for gastric cancer. However, postoperative chylous ascites prolongs the hospital stay and re-operation. There are few reports on this subject. Most cases of chylous ascites resolve without treatment, but the condition can result in substantial morbidity. The definition of chylous ascites is ambiguous and varies in the English literature. In this report, we discuss a case of chylous ascites in a 68-year-old man who underwent distal gastrectomy for early gastric cancer at our hospital. He was admitted 8 months after surgery with a main complaint of abdominal swelling. Abdominal puncture helped to diagnose chylous ascites with marked elevation of triglyceride level. The patient received a hypercaloric infusion through a central line, and octreotide acetate, but did not improve. After assessment of lymph outflow by lymph scintigraphy, surgical ligation of the lymph vessels was performed through laparotomy. The volume of milky-white ascites in the abdominal cavity was 3,000 mL. Macroscopically, the fluid was confirmed as flowing from behind the common hepatic artery. Thus, ligation was performed. Chylous ascites has not recurred at 12 months after the re-operation. In summary, a case of chylous ascites after radical gastrectomy for gastric cancer was successfully treated by surgery. We review and discuss the relevant literature.

Treatment of Gastric Cancer in Japan.

Although the incidence of gastric cancer has decreased because of the lower rate of Helicobacter pylori infection, it still accounts for a large number of deaths in Japan. Gastric cancer is mainly treated by resection, and the rate of radical resection is high in Japan because approximately 50% of cases are diagnosed at an early stage. Treatment advances have increased the number of endoscopic submucosal dissections, and development of laparoscopic surgery and robot-assisted surgery as minimally invasive approaches has yielded results similar to those of conventional surgeries, at least in the short term. Cases for which resection is contraindicated are treated with chemotherapy if performance status can be maintained. Although anticancer drugs are continuously under development, treatment outcomes remain unsatisfactory. As Japan becomes a super-aging society, the number of refractory cases is projected to increase. Therefore, evidence of any benefit for minimally invasive surgery and function-preserving surgery needs to be reported quickly. In this paper, we discuss gastric cancer treatment modalities recommended in the fifth edition of the gastric cancer treatment guidelines and describe recent research findings.

Preoperatively diagnosed gastric collision tumor with mixed adenocarcinoma and gastrointestinal stromal tumor: a case report and literature review.

Reports of gastric collision tumors, comprising adenocarcinoma and gastrointestinal stromal tumor, are extremely rare. Here, we report the case of a 68-year-old male who was diagnosed with a lower-body, moderately differentiated, tubular-type adenocarcinoma and submucosal tumor and underwent an elective D2 distal gastrectomy. The tumor cells of the gastrointestinal stromal tumor were positive for H-caldesmon and CD117, weakly positive for smooth muscle actin and DOG-1, and negative for desmin, S-100 protein, CD31, and AE1/AE3. The tumor had grown into a mixed form of adenocarcinoma and gastrointestinal stromal tumor. Thus, we report the first case of a preoperatively diagnosed collision tumor in the stomach consisting of adenocarcinoma and gastrointestinal stromal tumor.

An advanced case of gastric histiocytic sarcoma treated with chemotherapy and gastrectomy: a case report and review of literature.

Histiocytic sarcoma is a relatively new disease category and the gastrointestinal origin is sporadic. We report a case of a 74-year-old woman who underwent chemotherapy and proximal gastrectomy for extremely rare, advanced gastric histiocytic sarcoma. The resected specimen was subjected to numerous immunostainings to meet the diagnostic criteria of histiocytic sarcoma and was positive for the histiocyte markers' cluster of differentiation 68 and lysozyme. The markers of Langerhans cells, follicular dendritic cells, and myelocyte were all negative. Six reports of surgical resection of histiocytic sarcoma originating in the stomach exist, including our case. We reviewed the clinical course and the histological and immunohistochemical diagnostic features of surgically resected gastric histiocytic sarcoma.

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.

Skeletal Muscle Mass Depletion After Gastrectomy Negatively Affects the Prognosis of Patients With Gastric Cancer.

BACKGROUND/AIM: Skeletal muscle mass (SMM) is often depleted in patients with gastric cancer undergoing gastrectomy. Using a novel method, we evaluated the effect of SMM depletion after gastrectomy on disease prognosis. PATIENTS AND METHODS: The maximum cross-sectional area of the psoas-muscle (MCA-PM) was measured before surgery and at 1 year after in 233 patients with gastric cancer who underwent radical gastrectomy to determine the ratio (MCA-PMR) as an indicator of SMM depletion. RESULTS: The MCA-PMR cutoff value was set at 90%, and patients were divided into the groups with <90% and ≥90%. MCA-PMR <90% was an independent prognostic factor for all patients. In 88 patients who received adjuvant chemotherapy including S-1, the 5-year cancer-specific survival rate was significantly better for those with MCA-PMR ≥90% than for those with MCA-PMR <90% (84.1% vs. 59.1%; p=0.010; hazard ratio=2.974; 95% confidence interval=1.241-7.124). CONCLUSION: SMM depletion after gastrectomy can be measured using the MCA-PMR. This novel measurement can be easily implemented in the clinical setting.

Silicon drain with channels along the sides for internal biliary stenting of hepaticojejunostomy in hepatic hilar malignancies.

BACKGROUND: We compared two types of stents in patients who underwent surgery for hepatic hilar malignancies. METHODS: Twenty-one patients with hepatic hilar malignancies who underwent hepatectomy were randomly assigned to one of two groups. A 5-Fr silicon drain with an internal lumen and side holes was used for the hepaticojejunostomy in one group (intraluminal stent group), and a 10-Fr silicon drain with channels along the sides was used in the other (channel stent group). RESULTS: Leakage developed in four patients (36.4%) in the intraluminal stent group versus two (20.0%) in the channel stent group. Cholangitis developed in three patients with leakage (27.3%) in the intraluminal stent group versus no patient in the channel stent group. After operation, the times required for the serum alkaline phosphatase and total bilirubin levels to return to the normal range were significantly shorter in the channel stent group (5.3 +/- 2.9, 3.8 +/- 2.2 days) than in the intraluminal stent group (17.0 +/- 5.8, 9.4 +/- 5.7 days) (P < 0.0001, P = 0.0093). CONCLUSION: A 10-Fr silicon drain with channels is superior to a 5-Fr silicon drain with an internal lumen for internal biliary stenting of hepaticojejunostomy in patients with hepatic hilar malignancies.

Simultaneous evaluation of portal hemodynamics and liver function by scintiphotosplenoportography in pediatric recipients of living-donor liver transplants.

BACKGROUND/AIMS: The aim of this study was to simultaneously evaluate portal hemodynamics and liver function by scintiphotosplenoportography (SSP) using technetium-99m-diethylenetriaminepentaacetic asid-galactosyl-human serum albumin (99mTc-GSA) in recipients of living-donor liver transplants (LDLT). METHODOLOGY: Three LDLT recipients with biliary atresia who underwent SSP using 99mTc-GSA were studied. The clearance index of 99mTc-GSA (HH15) was calculated by dividing the radioactivity of the heart region of interest (ROI) 15 minutes after injection (H15) by that of the heart ROI 3 minutes after injection (H3), (HH15=H15/H3). The hepatic uptake ratio of 99mTc-GSA (LHL15) was calculated by dividing the radioactivity of the liver ROI at 15 minutes (L15) by H15 plus L15, (LHL15=L15/(H15+L15)). H/L15 (HH15/LHL15). RESULTS: Patient 1: On SSP before transplantation, digital images showed hepatofugal flow, but not the portal vein in early phase (HH15: 0.647, LHL15: 0.861, H/L15: 0.751). On SSP after transplantation, digital images showed the portal vein clearly, and the hepatofugal flow had disappeared (HH15: 0.633, LHL15: 0.971, H/L15: 0.652). Patient 2: On SSP before transplantation, digital images showed hepatofugal flow, and the liver was slightly visible in early phase (HH15: 0.673, LHL15: 0.869, H/L15: 0.774). Patient 3: On SSP before transplantation, digital images showed splenorenal shunt, but not the liver in early phase (HH15: 0.697, LHL15: 0.838, H/L15: 0.832). CONCLUSIONS: SSP using 99mTc-GSA is useful for the simultaneous evaluation of portal hemodynamics and liver function in pediatric recipients of LDLT.

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.

Quantitative analysis of fluorouracil-related genes in chronic viral hepatitis using microdissection.

BACKGROUND/AIMS: Dihydropyrimidine dehydrogenase is the initial and rate-limiting enzyme in the catabolism of 5-fluorouracil. The aim of this study was to determine the levels of messenger RNA for 5-fluorouracil-related metabolic enzymes in cirrhotic liver and to assess the correlation between these mRNA levels and clinicopathological features. METHODOLOGY: The study material consisted of 33 liver samples. The levels of mRNA for the 5- fluorouracil-related metabolic enzymes were quantified by real-time reverse transcription polymerase chain reaction combined with laser-captured microdissection. RESULTS: The Dihydropyrimidine dehydrogenase mRNA level in patients with grade B liver damage was significantly lower than that in patients with grade A liver damage (p=0.009). The Dihydropyrimidine dehydrogenase and orotate phosphoribosyl transferase mRNA level in al samples was higher than that in a2 and a3 samples (p= 0.01 and 0.013, respectively). Statistically significant correlations were found between the hyaluronic acid and the thymidylate phosphorylase mRNA level (p= 0.0001), and the T-BIL and the dihydropyrimidine dehydrogenase mRNA level (p=0.01). CONCLUSIONS: The level of Dihydropyrimidine dehydrogenase mRNA may be affected by the clinicopathological status of patients with cirrhosis.