Giant cavernous hepatic hemangioma shrunk by use of sorafenib.

Here we report a case of a 76-year-old man with a giant cavernous hepatic hemangioma of more than 20 cm in diameter. Since the hepatic hemangioma was actually growing and might possibly rupture and he complained of abdominal symptoms, we decided to perform interventional therapy. First we performed transcatheter arterial embolization (TAE) of the hepatic arteries. However, since this was not sufficiently effective, we added sorafenib (600 mg/day). As a result, the tumor shrank with symptomatic improvement. Subsequently, an adverse event occurred, and we suspended the sorafenib therapy. Then, the tumor began to grow, and we resumed administering sorafenib at 400 mg/day. The tumor shrank again, and we continued the sorafenib therapy thereafter. The tumor shrinkage, although possibly induced by the effect of TAE, is considered primarily due to the effect of treatment with sorafenib, because (1) TAE did not sufficiently reduce the blood supply to the inside of the tumor; (2) other tumors shrank in the area not targeted by TAE; and (3) the tumor grew during suspension of sorafenib therapy and shrank again after resuming the treatment.

[A case of anorectal malignant melanoma appearing 1 year after endoscopic mucosal resection of a rectal adenocarcinoma].

We present a case of a 61-year-old woman who underwent endoscopic mucosal resection (EMR) for early-stage colorectal cancer. However, because the condition of the horizontal margin of the resected tumor was unknown, she further underwent local transanal excision. Lower gastrointestinal endoscopy performed 1 year later showed protruding lesions both on the scar tissue and in the vicinity. Biopsy revealed malignant melanoma. She then underwent laparoscopic abdominoperineal resection and colostomy. This was an extremely rare case of adenocarcinoma complicated by malignant melanoma after resection.

Factors predicting incomplete endoscopic hemostasis in bleeding gastroduodenal ulcers.

BACKGROUND/AIMS: To investigate the factors contributing to failure of initial hemostasis in patients undergoing endoscopic hemostasis. METHODOLOGY: A total of 316 patients underwent endoscopic hemostasis for bleeding peptic ulcers in a period of 4 years. RESULTS: For hemostatic procedures, application of hemostatic clips, band ligation, injection of hypertonic saline epinephrine solution, soft coagulation, and argon plasma coagulation were employed either singly or in combination. Patients were divided into the following 2 groups for multivariate analysis: durable hemostasis (n = 268) and failed initial (incomplete) hemostasis (n = 48). Hemodialysis was a risk factor of incomplete hemostasis (Odds Ratio [OR] = 2.306, 95% confidence interval [CI] = 1.033-5.147; p = 0.041). Compared with the duodenal 2nd portion, the following bleeding sites had significantly lower risk of incomplete hemostasis (approximately 5 times less likely): The duodenal bulb (D), OR = 0.215, 95% CI = 0.058-0.797 (p = 0.022); the L region, OR = 0.207, 95% CI = 0.046-0.919 (p = 0.038); the M region, OR = 0.132, 95% CI = 0.036-0.482 (p = 0.002); and the U region, OR = 0.164, 95% CI = 0.041-0.649 (p = 0.01). CONCLUSIONn: Hemodialysis and a bleeding site located in the duodenal second portion were the factors strongly associated with incomplete hemostasis in bleeding gastroduodenal ulcers.

[A case report of internal hernia through an abnormal defect in the broad ligament of the uterus].

We report a rare case of internal hernia through an abnormal defect in the broad ligament of the uterus. A 49-year-old woman, without any previous surgery, was admitted because of vomiting and lower abdominal pain. Three days after admission a small amount of small intestinal gas was pointed out on her plain abdominal X-ray film. An enema examination by ileus tube revealed a pooling of gastrografin on the left side of the pelvic cavity, showing an obstruction of the ileum. Therefore, an emergency operation was performed, whereupon we found an abnormal defect in the left broad ligament of the uterus. This case describes an internal hernia through an abnormal defect in a female ileus patient without a history of surgery.

The clinical meaning of mucin phenotype and Epstein-Barr virus infection in gastric cancer.

BACKGROUND/AIMS: Differentiated type adenocarcinomas producing gastric type mucin are receiving much attention because of their degree of clinical malignancy. Most Epstein-Barr virus (EBV)-associated gastric cancers are undifferentiated type, and correlate with gastric type mucin. We analyzed the clinical meaning of mucin phenotypes and the detection of EBV in gastric cancers. METHODOLOGY: The objects of study were 120 consecutive gastric cancer lesions, resected endoscopically (EMR group, n=54) or surgically (surgery group, n=66). The mucin phenotypes were determined using immunostaining for human gastric mucin (HGM), MUC2, and CD10. Changes in histological type within the lesions were examined. The presence of EBV was determined using in situ hybridization for EBV-encoded small RNA 1 (EBER-1). RESULTS: The incomplete intestinal phenotype accounted for 83% of the EMR group, and the gastric phenotype for only 13%. None of the EMR group lesions had changes in the degree of differentiation, and there was no EBER-1-positive lesion. In the surgery group, the gastric phenotype accounted for 29%, significantly more than in the EMR group (p=0.0363). The incomplete intestinal phenotype accounted for 64% of surgically resected lesions. Changes in the degree of differentiation were significantly more common in the surgery group (16/66) than in the EMR group (0/54) (p=0.0001), tending to be more common in the gastric phenotype lesions. There were 3 EBER-1-positive lesions in the surgery group, accounting for 5%, and all were HGM positive. CONCLUSIONS: There appears to be little need to determine the mucin phenotype or EBV status of endoscopically resected lesions. In cases of gastric cancer where surgical resection is indicated, however, where the preoperative findings indicate a depth of invasion to SM or greater, and/or an undifferentiated lesion, then mucin phenotyping of biopsy specimens may be useful in predicting the predominant histological type of the tumor.

The long-term efficacy of Helicobacter pylori eradication therapy in patients with idiopathic thrombocytopenic purpura.

BACKGROUND AND AIM: A beneficial effect of Helicobacter pylori (H. pylori) eradication in patients with H. pylori-positive idiopathic thrombocytopenic purpura (ITP) has been reported by several investigators; however, it was not clear whether the recovered platelet count after H. pylori eradication was maintained for a long period. METHOD: Thirty-eight ITP patients who were examined for H. pylori infection were assessed. H. pylori-positive patients received a standard antibiotic therapy for H. pylori eradication. We investigated the long-term effect of H. pylori eradication on platelet recovery in patients with H. pylori-positive ITP. RESULTS: Of the 38 ITP patients, 26 (68.4%) were positive for H. pylori. The response rate of platelet recovery was 56.5% (13/23 patients). Twelve patients showed complete response (CR) and one showed partial response (PR). The mean platelet counts 6 months after eradication significantly increased from 31 x 10(9)/L to 129 x 10(9)/L in 23 H. pylori-eradicated patients (P < 0.001). The median platelet counts of responders 1, 2, 3, and 4 years after eradication were 168 x 10(9)/L (n = 10), 193 x 10(9)/L (n = 9), 168 x 10(9)/L (n = 7), and 243 x 10(9)/L (n = 4) after a mean follow-up of 25.8 months. CONCLUSION: Eradication therapy for H. pylori-positive patients with ITP was effective and a favorable effect was maintained for long periods.

Mucin and differentiation in Epstein-Barr virus-associated gastric carcinoma.

BACKGROUND/AIMS: Epstein-Barr virus (EBV) is present in roughly 1 in 10 cases of gastric carcinoma, particularly in undifferentiated adenocarcinomas. To clarify the histological developmental processes in EBV-associated gastric carcinoma, we investigated the presence of EBV infection, changes in the degree of differentiation within lesions, and mucin phenotypes of gastric carcinomas. METHODOLOGY: We had already examined 124 gastric carcinomas using in situ hybridization for EBV-encoded small RNA1 (EBER-1) and 12 lesions were EBER-1-positive. From these lesions we selected 8 carcinomas positive for EBER-1, and then chose 16 EBER-1-negative carcinomas as controls. Hematoxylin and eosin (H&E) stained specimens were examined for changes in histological type within each lesion. Mucin phenotypes of the specimens were determined using human gastric mucin (HGM), MUC2 and CD10 immunostaining. RESULTS: Of the EBER-1-positive lesions, 50% exhibited the gastric type mucin phenotype, whereas only 19% of the EBER-1-negative lesions were of the gastric phenotype. Changes in the histological type were seen within 75% of the EBER-1-positive lesions and within 62.5% of the EBER-1-negative lesions. CONCLUSIONS: The gastric mucin phenotype tended to be more common in the EBV-associated gastric carcinomas. The influence of EBV infection on the change in the histological type within the lesion was considered to be slight.

Endoscopic findings potentially predictive of gastric cancer in borderline lesions diagnosed by forceps biopsy.

BACKGROUND/AIMS: When a benign-malignant borderline lesion is diagnosed by the usual small gastric biopsy, there is sometimes difficulty in making a clinical decision. To clarify potentially useful findings to predict the existence of gastric cancer in borderline lesions diagnosed by forceps biopsy, we retrospectively analyzed endoscopic features. METHODOLOGY: We diagnosed 68 consecutive gastric benign-malignant borderline lesions (57 cases) by forceps biopsy and endoscopically resected them. The final diagnosis for 24 lesions (35.3%) was adenocarcinoma (adenocarcinoma group), and for 40 lesions (58.8%) was adenoma (adenoma group). Comparison with endoscopic findings for the groups was carried out using digitally filed endoscopic photos. RESULTS: We found six endoscopic findings (distal location, reddish surface color, lack of smoothness, lack of glossiness, focal roughness, and focal redness) having statistically significant relationships with adenocarcinoma at the final pathological diagnosis. In multivariate analysis, focal redness (p<0.01) and lack of glossiness (p<0.05) were found to have a significant relationship to gastric cancer. CONCLUSIONS: Endoscopic findings such as focal redness and lack of glossiness were potentially predictive of gastric cancer in borderline lesions diagnosed by forceps biopsy.

Clinical impact of strip biopsy for early gastric cancer.

BACKGROUND: The impact of EMR (strip biopsy method) on the selection of subsequent treatment for early gastric cancer was analyzed retrospectively. METHODS: A total of 163 consecutive patients with gastric epithelial tumors (186 lesions) underwent strip biopsy. On the basis of pretherapeutic findings, the indications for strip biopsy were classified into 4 groups: benign-malignant borderline group (93 lesions), curative indication group (65), diagnostic indication group (22), and palliative indication group (6). The clinical impact of the strip biopsy result on the subsequent treatment strategy was assessed. RESULTS: Of the lesions in the benign-malignant borderline group, 36.6% were intramucosal cancer. In the curative indication group, the results of strip biopsy differed from the pretherapeutic findings for 7.7% of the lesions. Strip biopsy was effective treatment for all lesions in the benign-malignant borderline group and for 92.3% of those in the curative indication group. Strip biopsy avoided unnecessary surgery in 50% of patients in the diagnostic indication group and 16.7% of those in the palliative indication group. After the strip biopsy results were explained, 50% of the patients in the palliative indication group reversed their initial decision and opted for surgery. Strip biopsy results reversed the decision for surgery, which had been based on inaccurate pretherapeutic information, in 20% of cases of early gastric cancer. CONCLUSIONS: Strip biopsy has a major clinical impact, because it provides an accurate diagnosis, aids in the selection of an appropriate treatment strategy, and reduces unnecessary surgery.

Preferential expansion of Vgamma9-JgammaP/Vdelta2-Jdelta3 gammadelta T cells in nasal T-cell lymphoma and chronic active Epstein-Barr virus infection.

We recently established an Epstein-Barr virus (EBV)-positive gammadelta T-cell line from a nasal T/natural killer (NK)-cell lymphoma (Nagata H, Konno A, Kimura N, Zhang Y, Kimura M, Demachi A, Sekine T, Yamamoto K, Shimizu N: Characterization of novel natural killer (NK)-cell and gammadelta T-cell lines established from primary lesions of nasal T/NK-cell lymphomas associated with the Epstein-Barr virus. Blood 2001, 97:708-713). Subsequently, we established two novel EBV-positive gammadelta T-cell lines from the peripheral blood of patients with chronic active EBV infection. Analysis of the terminal repeat of EBV showed that the three cell lines consisted of monoclonal populations, and flow cytometry showed that they had a common phenotype of gammadelta T cells: CD3(+) CD4(-) CD8(-) CD16(-) CD19(-) CD56(+) CD57(-) HLA-DR(+) T-cell receptor (TCR) alphabeta(-) TCR gammadelta(+). Analysis for the expression of TCR by flow cytometry showed that all three cell lines were Vgamma9(+)/Vdelta2(+), but negative for VgammaI, Vdelta1, or Vdelta3 TCR. Southern blot analysis for TCR genes showed that the three cell lines had a common rearrangement of Vgamma9-JgammaP and Jdelta3 genes. Polymerase chain reaction and sequence analysis of the junction between Vdelta and Jdelta genes revealed that the Jdelta3 genes were rearranged with the Vdelta2 genes. In contrast, none of the EBV-negative gammadelta T-cell lines, Molt-14, Peer, or Loucy, which were analyzed for controls, had Vgamma9 or Vdelta2 TCR, or a rearrangement of Jdelta3 genes. These results indicated that Vgamma9-JgammaP/Vdelta2-Jdelta3(+) gammadelta T cells were preferentially affected by EBV and expanded in patients with nasal gammadelta T-cell lymphoma and chronic active EBV infection. Jdelta3(+) gammadelta T cells are known to be a very minor population in gammadelta T cells of peripheral blood, whereas Vgamma9-JgammaP/Vdelta2-Jdelta1(+) cells are the major population. The close association of EBV with this particular gammadelta T-cell population may provide a key to the etiology of EBV-positive lymphoproliferative diseases.

Prognostic value and interobserver agreement of endoscopic ultrasonography for superficial squamous cell carcinoma of the esophagus: a prospective study.

BACKGROUND AND AIMS: Submucosal invasion of superficial esophageal cancer (SEC) is related to the prognosis. We prospectively analyzed outcomes of SEC in patients staged by endoscopic ultrasonography (EUS). PATIENTS AND METHODS: We staged 31 endoscopically diagnosed SEC cases using a 20/15-MHz thin probe. The EUS tumor stage was classified as EUSM (limited within mucosa), EUS-SM (with submucosal invasion), or EUS-MP over (invading the muscularis propria or deeper). Lymph node metastasis and 2-yr survival were analyzed according to the EUS tumor stage in 29 squamous cell carcinoma cases. Interobserver agreement of the EUS stage was tested between the examiner and a blind reviewer. RESULTS: Lymph node metastasis was significantly frequent in the EUS-SM group (8 of 18 cases [44.4%]) compared with the EUS-M group (1 of 10 cases [10%]) (p = 0.03). Patient survival at 2 yr after initial therapy was 72.2% in the EUS-SM group and 90% in the EUS-M group. Death from cancer was noted only in the EUS-SM group (three cases). The accuracy rates of EUS tumor staging were 74.1% by the examiner and 66.7% by the blind reviewer, with moderate interobserver agreement (kappa = 0.46). CONCLUSIONS: Thin-probe EUS can classify SEC into two groups: the EUS-M group with excellent outcome and the EUS-SM group with a significant risk of lymph node metastasis.

Evaluation of epstein-barr virus DNA load in gastric mucosa with chronic atrophic gastritis using a real-time quantitative PCR assay.

PURPOSE: It is hypothesized that Epstein-Barr virus (EBV) has already infected the noncarcinomatous gastric mucosa before carcinogenesis of EBV-associated gastric carcinoma. However, the frequency and distribution of EBV infection in the gastric mucosa of chronic atrophic gastritis (CAG) are still unclear. To clarify these points, we evaluated the EBV DNA load in gastric mucosa with CAG. METHODS: We tested samples from 35 CAG cases. Paired biopsy specimens from five sites of the stomach were obtained according to the Updated Sydney System. One of each pair of specimens was subjected to areal-time quantitative polymerase chain reaction (Q-PCR) assay to detect EBV. Q-PCR was performed using the LightCycler System (Roche, Mannheim, Germany). The other was subjected to hematoxylin and eosin (H&E) and Giemsa staining. The histological degree of CAG was graded according to the Updated Sydney System. To evaluate the surface distribution of gastric mucosal atrophic changes of CAG, we modified the endoscopic classification of Kimura and Takemoto. RESULT: EBV DNA was detected in 65.7% (23 of 35 cases) of the gastric biopsy specimens of the cases examined. EBV DNA was detected most frequently (92.3%; 12 of 13 cases) in the cases with endoscopically moderate CAG (p < 0.01). There was a significant association between EBV detection and the presence of inflammatory cell infiltration and atrophy in the stomach with endoscopically moderate CAG. CONCLUSION: EBV mainly infects the gastric mucosa of patients with moderate CAG.

Epstein-Barr virus association is rare in esophageal squamous cell carcinoma.

BACKGROUND: A critical role of Epstein-Barr virus (EBV) in carcinogenesis of nasopharyngeal squamous cell carcinoma and gastric adenocarcinoma is strongly suspected. We analyzed the possible EBV association for Japanese squamous cell carcinoma (SCC)-dominant esophageal cancer cases. METHODS: We retrospectively screened 36 surgically resected esophageal cancer lesions from 36 patients mainly with SCC using in situ hybridization (ISH) for EBV-encoded small RNA1 (EBER-1). EBV DNA analysis using real-time quantitative polymerase chain reaction (Q-PCR) was performed for three recent cases. RESULTS: We found no EBER-1-positive cancer cell in any tested esophageal cancer lesion. There were many EBER-1-positive tumor-infiltrating lymphocytes in the basaloid SCC lesion and a small number of positive lymphocytes in the other five advanced SCC lesions (14.7% of SCC). One SCC lesion with a highcopy number of EBV DNA had EBER-1-positive lymphocytes. CONCLUSIONS: EBV is rarely associated with esophageal SCC, and may appear through tumorinfiltrating lymphocytes in some advanced lesions.

The pilot experience of immunotherapy-combined photodynamic therapy for advanced gastric cancer in elderly patients.

BACKGROUND: Therapeutic efficacy of endoscopic photodynamic therapy (PDT) for advanced gastric cancer is limited. Recent animal studies have clarified the very important role of host immune cells in PDT. We expected a potential cooperative effect of PDT and immunotherapy, and developed immunotherapycombined PDT (I-PDT) for advanced gastric cancer. METHODS AND MATERIALS: We applied I-PDT for two elderly patients with complicated advanced gastric cancer (92- and 89-yr-old males). Tumor bleeding prevented them from leading an ordinary home life. Initial simple PDT was not effective. Patients received over 109 activated T-lymphocyte-predominant autologous immune cells, mainly intravenously, 5x for one course. PDT was performed endoscopically on the day of the third infusion. RESULTS: Two or three courses of I-PDT safely stopped tumor bleeding, and the initial poor prognoses of a few months of survival seemed to be improved (patient 1, over 32 mo; patient 2, 14 mo). CONCLUSIONS: I-PDT was found to be a safe, feasible treatment that could improve symptoms resulting from advanced gastric cancer.