Shigeatsu Fujiki

Risk factors associated with local recurrence of early gastric cancers after endoscopic submucosal dissection

BACKGROUND Although endoscopic submucosal dissection (ESD) is expected to reduce the local recurrence of gastric cancers, we still experience cases of recurrence after an ESD. OBJECTIVE To characterize clinical and pathologic features of cases with local recurrence of early gastric cancer after an ESD. DESIGN A prospective cohort study. SETTING AND PATIENTS A total of 306 patients with gastric cancers removed by ESD at Okayama University Hospital and Tsuyama Central Hospital between March 2001 and December 2005 were enrolled. INTERVENTION ESD. MAIN OUTCOME MEASUREMENT Local recurrence. RESULTS The incidence of a complete en bloc resection was 80.4% when pathologically evaluated. Within a median follow-up period of 26 months (12-64 months), a local recurrence was found in 7 cases, all of which had been declared incomplete resections. One patient underwent a second ESD, and the remaining 6 underwent a surgical resection. All removed lesions were mucosal cancers. No lymph-node metastases were found in patients with a surgical resection. There was a significant correlation between the incidence of an incomplete resection and that of a local recurrence (P < .0001). Among the clinical characteristics, tumor size (>30 mm vs <20 mm; odds ratio [OR] 16 mm [95% CI, 2.0-130 mm]) and tumor location (upper vs middle or lower; OR 7.6 [95% CI, 1.3-45]) were identified as factors that were significantly associated with the incidence of a local recurrence. LIMITATION Short follow-up duration. CONCLUSIONS The incidence of a local recurrence was strongly associated with that of an incomplete resection. The frequency of a local recurrence also showed significant correlations with the tumor size and location within the stomach.

Reactivation of hepatitis B virus during interferon‐free therapy with daclatasvir and asunaprevir in patient with hepatitis B virus/hepatitis C virus co‐infection

Direct‐acting antiviral agents (DAA) for hepatitis C virus (HCV) are not effective for hepatitis B virus (HBV), which may be suggestive of reactivation of anti‐HBe hepatitis during interferon (IFN)‐free DAA therapy in HBV/HCV co‐infected patients with inactive HBV. A 69‐year‐old male patient was diagnosed with chronic hepatitis due to HBV/HCV co‐infection with serum levels of alanine aminotransferase (ALT) of 94 U/L, HCV RNA of 4.2 log IU/mL and HBV DNA of 2.5 log copies/mL. HCV was thought to be responsible for the hepatitis activity because of low level of HBV core‐related antigen (3.1 log U/mL). He was treated with combination therapy of daclatasvir and asunaprevir. Serum ALT gradually increased, and reached 237 U/L on day 43 in spite of undetectable HCV RNA. Serum HBV DNA was increasing to 7.0 log copies/mL at that time. The treatment was stopped due to suspicion of drug‐induced liver injury and/or HBV reactivation. Administration of entecavir reduced HBV DNA levels, followed by improvement in ALT levels. This report proposes that close monitoring of HBV DNA during the anti‐HCV DAA therapy and the commencement of anti‐HBV therapy with nucleoside analogs after the increase of HBV DNA should be considered in patients with HBV/HCV co‐infection.

Endoscopic submucosal dissection for cancers of the remnant stomach after distal gastrectomy

BACKGROUND Endoscopic submucosal dissection (ESD) of early gastric cancer is less invasive than surgical resection, and if technically feasible, it may result in less long-term morbidity than does incisional surgery. However, ESD is technically difficult in patients who have had a previous distal gastrectomy. OBJECTIVE Our purpose was to retrospectively assess the results of ESD of early gastric cancer in the remnant stomach. DESIGN Case series. SETTING AND PATIENTS A total of 31 lesions in 30 patients with early remnant gastric cancer were treated with ESD at Okayama University Hospital, Tsuyama Central Hospital, Hiroshima City Hospital, Kagawa Prefectural Central Hospital, and Mitoyo General Hospital from March 2001 to January 2007. INTERVENTION ESD. MAIN OUTCOME MEASUREMENTS En bloc resection rate, complete resection rate, operation time, and complications. RESULTS En bloc resection and complete resection were achieved in 30 (97%) and in 23 (74%) lesions, respectively. The median operation time required for ESD in the remnant stomach was 113 minutes (range 45-450 minutes). Perforation occurred in 4 (13%). The incidence of delayed bleeding requiring blood transfusion was 0%. LIMITATION Short duration of follow-up. CONCLUSIONS ESD is feasible in the remnant stomach but has a relatively high complication rate and should only be performed by experienced endoscopists.

HLA-DQA1*0103-DQB1*0601 Haplotype and Helicobacter pylori-Positive Gastric Mucosa-Associated Lymphoid Tissue Lymphoma

BACKGROUND & AIMS Immune responses to Helicobacter pylori are important in the pathogenesis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma. In this retrospective case study, we investigated whether certain alleles and haplotypes of major histocompatibility complex genes are associated with gastric MALT lymphoma and the efficacy of H pylori eradication therapy on the lymphoma. METHODS Blood samples were obtained from 18 patients with H pylori-positive gastric MALT lymphoma (5 men and 13 women; age range, 51-80 years), 30 patients with H pylori-positive non-ulcer dyspepsia (17 men and 13 women; age range, 37-77 years), and 30 patients with H pylori-negative non-ulcer dyspepsia (12 men and 18 women; age range, 37-77 years). HLA-DQA1 and DQB1 allele typing was performed by use of a polymerase chain reaction sequence-specific oligonucleotide procedure. All patients with MALT lymphoma were treated with H pylori eradication therapy and followed up by repeated endoscopy and biopsy. RESULTS We found a significant increase in alleles HLA-DQA1*0103 and HLA-DQB1*0601, and a haplotype DQA1*0103-DQB1*0601, in MALT lymphoma patients when compared with non-ulcer dyspepsia patients who were either H pylori-positive or not and with a healthy control population. After H pylori eradication, the lymphomas regressed completely in all 10 patients who possessed the DQA1*0103-DQB1*0601 haplotype but in only 4 of the 8 without this haplotype (P = .023). CONCLUSIONS DQA1*0103-DQB1*0601 haplotype-positive gastric MALT lymphoma is likely to respond to therapy by eradication of H pylori.

Cellular immune response in liver of patients with chronic hepatitis B —Electron microscopic observation of lymphocyte subsets by the immunoperoxidase method using monoclonal antibodies

SummaryThe morphological association between lymphocytes and hepatocytes was studied at the light and electron microscopic levels by the peroxidase-labeled antibody method using mouse monoclonal antibodies against Leu-1, Leu-2a, Leu-3a, Leu-7 and Leu-10 antigens in liver biopsy specimens from patients with chronic hepatitis B. Leu-1 + cells (T cells), especially Leu-2a + cells (cytotoxic/suppressor T cells), infiltrated mostly in periportal areas with piecemeal necrosis and in parenchymal areas with focal necrosis. By double staining techniques, Leu-2a + cells were often seen in contact with hepatocytes containing membranous hepatitis B surface and/or core antigens in patients with chronic active hepatitis. At the ultrastructural level, Leu-2a + cells frequently occupied the sinusoid and also migrated into both the space of Disse and between hepatocytes. Furthermore, they often showed intimate surface-contact with hepatocytes having hepatitis B surface and/or core antigens, and, occasionally, injured hepatocytes were surrounded by several Leu-2a + cells. In contrast, Leu-3a + cells, Leu-7 + cells and Leu-10 + cells sometimes appeared in the sinusoid, but seldom in the space of Disse and between hepatocytes. These findings suggest that cytotoxic T lymphocytes may be associated with the necrosis of hepatocytes in chronic hepatitis B.

Diagnostic role of 18F-fluorodeoxyglucose positron emission tomography for follicular lymphoma with gastrointestinal involvement

AIM To investigate the capacity for 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) to evaluate patients with gastrointestinal lesions of follicular lymphoma. METHODS This retrospective case series consisted of 41 patients with follicular lymphoma and gastrointestinal involvement who underwent 18F-FDG-PET and endoscopic evaluations at ten different institutions between November 1996 and October 2011. Data for endoscopic, radiological, and biological examinations performed were retrospectively reviewed from clinical records. A semi-quantitative analysis of 18F-FDG uptake was performed for each involved area by calculating the maximum standardized uptake value (SUVmax). Based on the positivity of 18F-FDG uptake in the gastrointestinal lesions analyzed, patients were subdivided into two groups. To identify potential predictive factors for 18F-FDG positivity, these two groups were compared with respect to gender, age at diagnosis of lymphoma, histopathological grade, pattern of follicular dendritic cells, mitotic rate, clinical stage, soluble interleukin-2 receptor levels detected by 18F-FDG-PET, lactate dehydrogenase (LDH) levels, hemoglobin levels, bone marrow involvement, detectability of gastrointestinal lesions by computed tomography (CT) scanning, and follicular lymphoma international prognostic index (FLIPI) risk. RESULTS Involvement of follicular lymphoma in the stomach, duodenum, jejunum, ileum, cecum, colon, and rectum was identified in 1, 34, 6, 3, 2, 3, and 6 patients, respectively. No patient had esophageal involvement. In total, 19/41 (46.3%) patients exhibited true-positive 18F-FDG uptake in the lesions present in their gastrointestinal tract. In contrast, false-negative 18F-FDG uptake was detected in 24 patients (58.5%), while false-positive 18F-FDG uptake was detected in 5 patients (12.2%). In the former case, 2/19 patients had both 18F-FDG-positive lesions and 18F-FDG-negative lesions in the gastrointestinal tract. In patients with 18F-FDG avidity, the SUVmax value of the involved gastrointestinal tract ranged from 2.6 to 17.4 (median: 4.7). For the 18F-FDG-negative (n = 22) and -positive (n = 19) groups, there were no differences in the male to female ratios (10/12 vs 4/15, P = 0.186), patient age (63.6 ± 2.4 years vs 60.1 ± 2.6 years, P = 0.323), presence of histopathological grade 1 vs 2 (20/2 and 17/2, P = 1.000), follicular dendritic cell pattern (duodenal/nodal: 13/5 vs 10/3, P = 1.000), mitotic rate (low/partly high, 14/1 vs 10/3, P = 0.311), clinical stage according to the Ann Arbor system (stages IE and IIE/other, 15/7 vs 15/4, P = 0.499), clinical stage according to the Lugano system (stages I and II-1/other, 14/8 vs 14/5, P = 0.489), soluble interleukin-2 receptor levels (495 ± 78 vs 402 ± 83, P = 0.884), LDH levels (188 ± 7 vs 183 ± 8, P = 0.749), hemoglobin levels (13.5 ± 0.3 vs 12.8 ± 0.4, P = 0.197), bone marrow involvement (positive/negative, 1/8 vs 1/10, P = 1.000), detectability by CT scanning (positive/negative, 1/16 vs 4/13, P = 0.335), and FLIPI risk (low risk/other, 16/6 vs 13/6, P = 0.763), respectively in each case. CONCLUSION These findings indicate that it is not feasible to predict 18F-FDG-avidity. Therefore, 18F-FDG-PET scans represent a complementary modality for the detection of gastrointestinal involvements in follicular lymphoma patients, and surveillance of the entire gastrointestinal tract by endoscopic examinations is required.

A Randomized Trial of Monopolar Soft-mode Coagulation Versus Heater Probe Thermocoagulation for Peptic Ulcer Bleeding.

Background and Aim: Endoscopic therapy has been demonstrated to be effective in achieving hemostasis for bleeding peptic ulcers. Thermal coagulation is one of the most commonly used methods, with a high success rate. Recently, endoscopic submucosal dissection for early gastric carcinoma was developed and hemostasis with soft coagulation using hemostatic forceps was introduced. The aim of this study was to compare the hemostatic efficacy of soft coagulation with heater probe thermocoagulation for peptic ulcer bleeding. Methods: Patients who visited our hospital with hematemesis or melena underwent emergency endoscopy. Inclusion criteria were presentation with an actively bleeding ulcer, a nonbleeding visible vessel, or an adherent clot. Patients were excluded if they were unwilling to give written informed consent or had a bleeding gastric malignancy. Patients were randomized to receive endoscopic hemostasis with soft coagulation (Group S) or heater probe thermocoagulation (Group H). The primary endpoint was the primary hemostasis rate and secondary endpoints were rebleeding rate, complications, and the procedure time. Results: Between May 2010 and February 2012, a total of 111 patients (89 gastric ulcers and 22 duodenal ulcers) were enrolled. Primary hemostasis was achieved in 54 patients (96%) in Group S and 37 (67%) in Group H (P<0.0001). Rebleeding occurred in 7 patients in Group H and none in Group S. Of these 7 patients, urgent surgery was performed in 1. Perforation occurred in 2 patients in Group H, which was managed conservatively. Conclusions: For patients with gastroduodenal ulcer bleeding, soft coagulation using monopolar hemostatic forceps is more effective than heater probe thermocoagulation for achieving hemostasis.

Hepatitis type C virus infection in patients with type B chronic liver disease.

SummaryAnti-c100-3 (Ortho) was determined in the sera of 152 patients with HBs antigen-positive chronic liver diseases to assess coinfection of hepatitis B virus (HBV) and hepatitis C virus (HCV). Eleven patients (7.2%) were positive for anti-c100-3. Anti-CP-9 (Okamoto) and HCV-RNA (RT-PCR) were also examined in these 11 patients. Anti-CP-9 was detected in 7 patients and HCV-RNA was detected in all 11 patients. Four of the 11 anti-c100-3-positive patients were positive for HBe antigen (HBeAg) and others were negative. In 8 of the 11 patients, HCV was suspected to be superinfected by blood transfusion. In HBeAgpositive patients, serum glutamic pyruvic transaminase (SGPT) was elevated in relation to active replication of HBV shown by DNA-polymerase activity. The histological findings showed chronic active hepatitis, with or without cirrhosis. On the other hand, in HBeAg-negative patients, SGPT fluctuated without evidence of active replication of HBV. Active inflammation in the liver was observed in 3 of 5 HBeAg-negative patients by liver biopsy. These findings suggest that HBV might play an important role in chronic active inflammation in HBeAg-positive patients coinfected with HCV, and that HCV might be responsible for continuous inflammation in HBeAg-negative patients coinfected with HCV.

Chromoendoscopy of gastric adenoma using an acetic acid indigocarmine mixture.

AIM To investigate the usefulness of chromoendoscopy, using an acetic acid indigocarmine mixture (AIM), for gastric adenoma diagnosed by forceps biopsy. METHODS A total of 54 lesions in 45 patients diagnosed as gastric adenoma by forceps biopsy were prospectively enrolled in this study and treated by endoscopic submucosal dissection (ESD) between January 2011 and January 2012. AIM-chromoendoscopy (AIM-CE) was performed followed by ESD. AIM solution was sprinkled and images were recorded every 30 s for 3 min. Clinical characteristics such as tumor size (< 2 cm, ≥ 2 cm), surface color in white light endoscopy (WLE) (whitish, normochromic or reddish), macroscopic appearance (flat or elevated, depressed), and reddish change in AIM-CE were selected as valuables. RESULTS En bloc resection was achieved in all 54 cases, with curative resection of fifty two lesions (96.3%). Twenty three lesions (42.6%) were diagnosed as well-differentiated adenocarcinoma and the remaining 31 lesions (57.4%) were gastric adenoma. All adenocarcinoma lesions were well-differentiated tubular adenocarcinomas and were restricted within the mucosal layer. The sensitivity of reddish color change in AIM-CE is significantly higher than that in WLE (vs tumor size ≥ 2 cm, P = 0.016, vs normochromic or reddish surface color, P = 0.046, vs depressed macroscopic type, P = 0.0030). On the other hand, no significant differences were found in the specificity and accuracy. In univariate analysis, normochromic or reddish surface color in WLE (OR = 3.7, 95%CI: 1.2-12, P = 0.022) and reddish change in AIM-CE (OR = 14, 95%CI: 3.8-70, P < 0.001) were significantly related to diagnosis of early gastric cancer (EGC). In multivariate analysis, only reddish change in AIM-CE (OR = 11, 95%CI: 2.3-66, P = 0.0022) was a significant factor associated with diagnosis of EGC. CONCLUSION AIM-CE may have potential for screening EGC in patients initially diagnosed as gastric adenoma by forceps biopsy.

Tolerability of magnifying narrow band imaging endoscopy for esophageal cancer screening.

AIM To compare the tolerability of magnifying narrow band imaging endoscopy for esophageal cancer screening with that of lugol chromoendoscopy. METHODS We prospectively enrolled and analyzed 51 patients who were at high risk for esophageal cancer. All patients were divided into two groups: a magnifying narrow band imaging group, and a lugol chromoendoscopy group, for comparison of adverse symptoms. Esophageal cancer screening was performed on withdrawal of the endoscope. The primary endpoint was a score on a visual analogue scale for heartburn after the examination. The secondary endpoints were scale scores for retrosternal pain and dyspnea after the examinations, change in vital signs, total procedure time, and esophageal observation time. RESULTS The scores for heartburn and retrosternal pain in the magnifying narrow band imaging group were significantly better than those in the lugol chromoendoscopy group (P = 0.004, 0.024, respectively, ANOVA for repeated measures). The increase in heart rate after the procedure was significantly greater in the lugol chromoendoscopy group. There was no significant difference between the two groups with respect to other vital sign. The total procedure time and esophageal observation time in the magnifying narrow band imaging group were significantly shorter than those in the lugol chromoendoscopy group (450 ± 116 vs 565 ± 174, P = 0.004, 44 ± 26 vs 151 ± 72, P < 0.001, respectively). CONCLUSION Magnifying narrow band imaging endoscopy reduced the adverse symptoms compared with lugol chromoendoscopy. Narrow band imaging endoscopy is useful and suitable for esophageal cancer screening periodically.