Current prognostic factors of advanced gastric cancer patients treated with chemotherapy: real world data from a Japanese 12 institutions.

BACKGROUND: Understanding the prognostic factors of advanced gastric cancer before starting chemotherapy is important to determine personalized treatment strategies. However, the details of chemotherapy and the prognosis of advanced gastric cancer patients have changed with the time and environment. The aim of this study was to understand the current reality of chemotherapy and to estimate the prognostic factors of advanced gastric cancer patients before starting chemotherapy at multiple centers. This includes specialized cancer hospitals and community hospitals, with the latest data under the Japanese insurance system. METHODS: We evaluated the clinical parameters and treatment details of 1025 patients who received systemic chemotherapy for unresectable advanced gastric cancer from 2012 to 2018 at 12 institutions in Japan. Prognostic factors were analyzed using the Cox proportional hazards regression model. RESULTS: As of April 2021, 953 (93%) patients had died, while 72 (7%) patients survived. The median overall survival and progression-free survival of first-line chemotherapy was 11.8 months (95% confidence interval, 10.8-12.3 months) and 6.3 months (95% confidence interval, 5.9-6.9 months), respectively. Multivariate analysis revealed eight prognostic factors: age < 40 years, performance status ≥2, no gastrectomy, diffuse histological type, albumin <3.6, alkaline phosphatase ≥300, creatinine ≥1.0 and neutrophil-to-lymphocyte ratio > 3.0. Patients using trastuzumab showed better survival than patients without (16.1 months vs. 11.1 months; P = 0.0005). CONCLUSIONS: We identified eight prognostic factors for patients with advanced gastric cancer undergoing Japanese standard chemotherapy. Our results will help clinicians develop treatment strategies for every patient.

Endoscopic features of oxyntic gland adenoma and gastric adenocarcinoma of the fundic gland type differ between patients with and without Helicobacter pylori infection: a retrospective observational study.

BACKGROUND: The endoscopic features of oxyntic gland adenoma and gastric adenocarcinoma of the fundic gland type have not been fully investigated in relation to Helicobacter pylori infection status. We compared the morphology, color, and location of these lesions between patients with and without H. pylori infection. METHODS: We retrospectively enrolled 165 patients (180 lesions) from 10 institutions. We divided the patients into the (i) Hp group (patients with current H. pylori infection [active gastritis, n = 13] and those with past infection [inactive gastritis, n = 76]) and (ii) uninfected group (H. pylori-uninfected patients, n = 52). We compared the clinical and endoscopic features of the two groups. We also performed an analysis between (i) lesions with atrophy of the surrounding gastric mucosa (atrophy group) and (ii) lesions without atrophy of the surrounding gastric mucosa (non-atrophy group). RESULTS: The average age was older in the Hp group than in the uninfected group (68.1 ± 8.1 vs. 63.4 ± 8.7 years, p < 0.01). Although the difference was not statistically significant (p = 0.09), multiple lesions were observed in 9 of 89 patients (10.1%) in the Hp group and in only 1 of 52 patients (1.9%) in the uninfected group. Meanwhile, significant differences were observed in the prevalence of lesions located in the gastric fornix or cardia (uninfected group: 67.3% vs. Hp group: 38.0%, p < 0.01), with an elevated morphology (80.0% vs. 56.0%, p < 0.01), with a subepithelial-like appearance (78.2% vs. 42.0%, p < 0.01), and with a color similar to that of the peripheral mucosa (43.6% vs. 25.0%, p = 0.02). The male-to-female ratio, lesion size, and presence or absence of vascular dilatation or black pigmentation on the surface were not different between the two groups. In the analysis comparing lesions with and without mucosal atrophy, the prevalence of multiple lesions was significantly higher (p = 0.02) in the atrophy group (5/25 patients, 20.0%) than in the non-atrophy group (7/141 patients, 5.0%). CONCLUSIONS: The endoscopic features of oxyntic gland adenoma and gastric adenocarcinoma of the fundic gland type differ between patients with and without H. pylori infection.

A prospective multicenter study of the magnifying endoscopic evaluation of the invasion depth of superficial esophageal cancers.

BACKGROUND: Treatment strategies for superficial esophageal squamous cell carcinoma (SESCC) are determined mainly on the basis of the invasion depth. The Japan Esophageal Society (JES) developed a simplified magnifying endoscopic classification for estimating the invasion depth of SESCC. We aimed to evaluate its accuracy. METHODS: We prospectively applied the JES classification for estimating the invasion depth of SESCC to 204 consecutive lesions from 6 hospitals in Japan between April 2016 and October 2018. We analyzed the accuracy of the endoscopic diagnosis by adding the following two categories to the JES classification: ≥ 7 mm lesion in B2 vessels (defined as B2 ≥ 7 mm) and B2 vessels with inflammation (defined as B2i). RESULTS: After applying the exclusion criteria, 201 lesions remained in the analysis. The diagnostic value of type B1, B2, B3 vessels were as follows: sensitivity, 93.9%, 68.0%, 25.0%; specificity, 81.1%, 89.2%, 99.4%; positive predictive value (PPV), 95.6%, 47.2%, 75.0%; negative predictive value (NPV), 75.0%, 95.1%, 95.4%; and accuracy, 91.5%, 86.5%, 95.0%, respectively. A retrospective analysis showed that the diagnostic accuracy was higher in type B2 vessels (86.5% to 92.0%). An avascular area (AVA) was found in 55 (27%) of the 201 lesions, which tended to be associated with a deeper pathological diagnosis of each Type B vessel. In an additional analysis, B2 ≥ 7 mm and B2i improved the diagnostic accuracy of type B2 vessels from 86.5% to 92.0%. CONCLUSIONS: The JES classification is useful for estimating the invasion depth of SESCC. The diagnostic accuracy for type B2 vessels was low, which may be improved by using B2 ≥ 7 mm and B2i.

[Use of a somatostatin analog to improve a patient's condition and the subsequent diagnosis of pancreatic VIPoma:a case report].

A 68-year-old woman with an 11-day history of sudden abdominal pain and severe watery diarrhea was transferred to our hospital due to an exacerbation of renal function despite hydration. After treatment for dehydration and acidemia was provided in our intensive care unit, patient's renal function improved. Contrast-enhanced abdominal computed tomography was finally performed, revealing a hypervascular pancreatic mass with multiple hepatic masses. This imaging finding along with her clinical symptoms indicated watery diarrhea hypokalemia achlorhydria (WDHA) syndrome caused by a pancreatic VIPoma. Somatostatin analog was administered immediately leading to the improvement of her diarrhea and her general condition. As a result, endoscopic ultrasonography-guided fine-needle aspiration could be performed. Consequently, she was diagnosed with a pancreatic neuroendocrine tumor. She then underwent surgical resection of the pancreatic tumor and liver metastasis. As revealed in the immunohistochemical analysis of the excised tumor tissue, VIP was highly expressed, resulting in the final diagnosis of pancreatic VIPoma. Therefore, the immediate use of a somatostatin analog is crucial for improving the patient's general condition and achieving a definitive diagnosis pathologically when a patient is suspected of having a pancreatic VIPoma.

Oxidative stress controlling agents are effective for small intestinal injuries induced by non-steroidal anti-inflammatory drugs.

BACKGROUND AND AIM: Video-capsule endoscopy (VCE) has shown that intestinal ulcers are common in non-steroidal anti-inflammatory drugs (NSAIDs) users, although the mechanisms and management have not been clearly defined. To explore the contribution of oxidative stress and potential of anti-oxidants for NSAIDs-induced intestinal ulcers, we assessed human serum oxidative stress balance and the effect of anti-oxidants using a mouse model. METHODS: A total of 30 NSAIDs users (17 aspirin and 13 non-aspirin users) received VCE. Serum reactive oxygen metabolite (d-ROM) and antioxidative OXY-adsorbent test (OXY) were measured. The indomethacin (IND)-induced mouse intestinal ulcer model was used to assess the effect of anti-oxidants. Eight-week-old mice were divided into four groups; control diet and diet including IND (N group), IND and L-carnitine (NC group), and IND and vitamin E (NE group). RESULTS: Serum OXY levels among non-aspirin users were lower in the mucosal injuries positive group than the negative group (P < 0.05). In the mouse models, the degree of mucosal injuries was lower in NC and NE than N (P < 0.01). Serum d-ROM levels were lower in NC and NE than N (P < 0.01), and OXY levels were higher in NC than N and NE (P < 0.01). The degeneration of intestinal mitochondria was mild in NC and NE. The serum KC/CXCL-1 level and hepatic expression of the anti-oxidant molecule Gpx4 were lower in NC than N. CONCLUSIONS: Non-aspirin NSAID-induced intestinal ulcers are related to decreased anti-oxidative stress function. Anti-oxidants, especially L-carnitine, are good candidates for intestinal ulcers.

[A case of Hamman's syndrome associated with acute-onset type 1 diabetes mellitus presenting with abdominal pain].

A 21-year-old female presented at an emergency department with abdominal pain and nausea. Computed tomography (CT) of the chest and abdomen revealed a small amount of mediastinal emphysema in the precardiac area, but the underlying cause could not be identified. On admission, her plasma glucose was 371 mg/dl, glycated hemoglobin (HbA1c) was 14.0%, and blood pH was 6.91. These findings supported a diagnosis of Hamman's syndrome associated with diabetic ketoacidosis. Her diabetic ketoacidosis was managed with insulin and fluid therapy, and the mediastinal emphysema disappeared spontaneously by the time of discharge. Presence of free air of the chest and abdominal cavity must warrant a differential diagnosis of gastrointestinal perforation; however, when the free air is accompanied by diabetic ketoacidosis, it is not necessary to perform urgent endoscopy.

Endoscopic submucosal dissection of esophageal cancer using the Mucosectom2 device: a feasibility study.

BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) is being increasingly used for superficial esophageal cancers. However, esophageal ESD is technically difficult, time consuming, and less safe compared with endoscopic mucosal resection (EMR). To perform ESD safely and more efficiently, various types of knives have been developed. This study compared the efficacy of our newly developed device, Mucosectom2, with that of conventional devices for esophageal ESD. PATIENTS AND METHODS: Between May 2007 and February 2011, ESD was performed for 172 esophageal lesions. Of these, 120 lesions were treated by conventional devices only, whereas 52 lesions were treated by conventional devices and the Mucosectom2. Procedure time, en bloc and R0 resection rates, and adverse events were retrospectively compared between the conventional and Mucosectom2 groups. RESULTS: The median procedure time was 48.0 minutes in the conventional group and 21.5 minutes in the Mucosectom2 group; the procedure time was significantly shorter in the Mucosectom2 group than in the conventional group (P < 0.0001). The en bloc and R0 resection rates were lower in the conventional group than those in the Mucosectom2 group, although these differences were not significant. The rate of exposure of the muscle layer in the Mucosectom2 group was significantly lower than in the conventional group (P = 0.04). The rates of perforation and postoperative bleeding were not significantly different between the two groups. CONCLUSIONS: This feasibility study suggests that, compared with conventional ESD devices, the Mucosectom2 may decrease the time required for esophageal ESD. Although our groups appeared comparable, they were studied at different times. Endoscopic expertise and endoscope quality may have differed during these periods, thereby affecting the results of our study. A prospective trial is therefore required to confirm our results.

Serum oxidative-anti-oxidative stress balance is dysregulated in patients with hepatitis C virus-related hepatocellular carcinoma.

AIM: Oxidative stress is associated with progression of chronic liver disease (CLD). This association is best established in chronic hepatitis C. However, the anti-oxidative state is not well characterized. The objective of the present study was to investigate the balance of oxidative and anti-oxidative stress in CLD patients. METHODS: We recruited a study population of 208 patients, including healthy volunteers (HV; n = 15), patients with hepatitis B virus (HBV)-related CLD without or with hepatocellular carcinoma (HBV-non-HCC, n = 25, and HBV-HCC, n = 50, respectively), and patients with hepatitis C virus (HCV)-related CLD without or with HCC (HCV-non-HCC, n = 49, and HCV-HCC, n = 69, respectively). Serum levels of reactive oxygen metabolites (ROM) and anti-oxidative markers (OXY-adsorbent test; OXY) were determined, and the balance of these values was used as the oxidative index. Correlations among ROM, OXY, oxidative index and clinical characteristics were investigated. RESULTS: Patients with CLD exhibited elevated ROM and oxidative index compared to HV. Among patients with CLD, HCV positive status correlated with increased ROM. In CLD, HCV-HCC patients exhibited the highest ROM levels. Among HCV-related CLD patients, lower OXY correlated with HCC positive status, but was recovered by eradication of HCC. In HCV-HCC, lower OXY correlated with high PT-INR. CONCLUSION: HCV positive CLD patients displayed higher oxidative stress and HCV-HCC patients displayed lower anti-oxidative state. Anti-oxidative state depression was associated with liver reservoir-related data in HCV-HCC and could be reversed with HCC eradication.

Evaluation of the effect of sorafenib using serum NX-des-γ-carboxyprothrombin in patients with hepatocellular carcinoma.

AIM: Des-γ-carboxyprothrombin (DCP) is known to be increased by the use of sorafenib for the treatment of hepatocellular carcinoma (HCC), despite its therapeutic efficacy. In addition to the tumor progression, hypoxia that impairs vitamin K uptake is known to induce DCP and this mechanism may explain DCP elevation by sorafenib. In this study, we tried to evaluate the effect of sorafenib treatment using a new marker, NX-DCP, which is specific to vitamin K absence. METHODS: Serum DCP and NX-DCP were measured in 50 consecutive HCC patients before and 1 week after starting sorafenib, and compared with the treatment effect using the modified Response Evaluation Criteria in Solid Tumors guidelines. RESULTS: DCP and NX-DCP increased 1.58- (median, range 0.21-28.7) and 1.20-fold (median, range 0.41-14.2) after the administration of sorafenib, respectively. The increases of both markers were less than twofold in approximately half of the patients (low-elevation group). However, 12 patients showed over twofold increase of both DCP and NX-DCP (double-elevation group), and eight patients showed over twofold increase of DCP alone (DCP-elevation group). The disease control rate (DCR) of the DCP-elevation group (12.5%) was significantly lower than those of the double-elevation group (75.0%, P = 0.020) and the low-elevation group (60.0%, P = 0.042). Progression-free survival (PFS) was significantly shorter in the DCP-elevation group than in the double-elevation group (P = 0.006) and the low-elevation group (P = 0.001). CONCLUSION: NX-DCP in combination with DCP could be a useful biomarker of sorafenib treatment for advanced HCC.

Prognotic impact of serum follistatin in patients with hepatocellular carcinoma.

BACKGROUND AND AIM: Follistatin (FST) is a glycoprotein expressed in most organs, which interacts with activins or other members of the transforming growth factor beta family. Recently, several reports have shown that FST regulates a variety of processes during tumor progression. Here, serum FST in patients with liver diseases was measured, and its clinical utility as a biomarker was assessed. METHODS: Serum was collected from 162 patients (91 hepatocellular carcinoma [HCC], 43 liver cirrhosis, and 28 chronic hepatitis) as well as from 16 healthy volunteers. FST was quantified by enzyme-linked immunosorbent assays, and levels were compared with clinical parameters including survival of the HCC patients. RESULTS: Median serum FST levels in HCC, liver cirrhosis, chronic hepatitis, and healthy volunteers were 1168, 1606, 1324, and 1661 pg/mL, respectively, not significantly different. In HCC patients, higher serum FST was associated with greater age, hepatitis C virus antibody-negativity, large tumor size, g-glutamyl transpeptidase, des-gamma carboxyprothrombin and presence of portal vein tumor thrombus. Survival of HCC patients with high FST levels was significantly shorter than for those with low levels (P = 0.004). Multivariate analysis revealed that in addition to large tumor size and presence of portal vein thrombus, high FST levels were independently correlated with poor prognosis (hazard ratio = 2.41, 95% confidence interval = 1.16-5.00, P = 0.02). CONCLUSIONS: Serum FST levels are significantly associated with HCC prognosis and could represent a predictive biomarker in this disease.

Lesion size, elevated morphology, and non or closed-type atrophy are predictive factors for gastric adenocarcinoma of the fundic gland type rather than oxyntic gland adenoma.

Background: An oxyntic gland neoplasm confined to the mucosal layer (T1a) is classified as an oxyntic gland adenoma, whereas that with submucosal invasion (T1b) is defined as gastric adenocarcinoma of the fundic gland type (GA-FG). Methods: To reveal the differences in clinical features between them, we retrospectively investigated 136 patients with 150 oxyntic gland adenoma and GA-FG lesions. Results: The univariate analysis revealed that the mean size (GA-FG vs. oxyntic gland adenoma, 7.7±5.4 vs. 5.5±3.1 mm), the prevalence of elevated morphology (79.1% vs. 51.8%), black pigmentation within the lesion (23.9% vs. 9.6%), and non or closed-type atrophy (81.2% vs. 65.1%) were different between the two groups. A multivariate logistic regression analysis revealed that ≥5 mm lesion size (odds ratio, 2.96; 95% confidence interval: 1.21-7.23), elevated morphology (odds ratio, 2.40; 95% confidence interval: 1.06-5.45), and no or closed-type atrophy (odds ratio, 2.49; 95% confidence interval: 1.07-5.80) were factors in distinguishing GA-FG from oxyntic gland adenoma. When oxyntic gland neoplasms with no or one feature were judged as oxyntic gland adenomas and those with two or three features were judged as GA-FG, the sensitivity and specificity were 85.1% and 43.4% for GA-FG, respectively. Conclusions: We identified three possible distinctive features of GA-FG compared to oxyntic gland adenoma: lesion size ≥5 mm, elevated morphology, and no or closed-type atrophy.

Long-term outcomes of patients with primary intestinal follicular lymphoma managed with watch-and-wait strategy.

Patients with primary intestinal follicular lymphoma are often followed-up without a specific treatment, and this approach is called the "watch-and-wait approach." However, the long-term outcomes of this patient group have not been sufficiently investigated. We enrolled patients with primary intestinal follicular lymphoma who were diagnosed before 2016 and managed with the watch-and-wait approach in 20 institutions. We retrospectively investigated the overall, disease-specific, and event-free survival rates as well as the rate of spontaneous regression. Among the 248 patients with follicular lymphoma with gastrointestinal involvement, 124 had localized disease (stage I or II1). We analyzed the data of 73 patients who were managed using the watch-and-wait approach. During the mean follow-up period of 8.3 years, the follicular lymphoma had spontaneously resolved in 16.4% of the patients. The 5-year and 10-year overall survival rates were 92.9% and 87.1%, respectively. With disease progression (n = 7), initiation of therapy (n = 7), and histologic transformation to aggressive lymphoma (n = 0) defined as events, the 5-year and 10-year event-free survival rates were 91.1% and 86.9%, respectively. No patient died of progressive lymphoma. Thus, both 5-year and 10-year disease-specific survival rates were 100%. In conclusion, an indolent long-term clinical course was confirmed in the patients with primary intestinal follicular lymphoma. The watch-and-wait strategy is a reasonable approach for the initial management of these patients.

Genetic risk of hepatocellular carcinoma in patients with hepatitis C virus: a case control study.

BACKGROUND AND AIM: Chronic hepatitis C virus (HCV) infection is a well known risk factor for hepatocellular carcinoma (HCC). The aim of this study is to elucidate the genetic risk of development and recurrence of HCC in patients with HCV. METHODS: A total of 468 patients with HCV, including 265 with HCC were enrolled. We genotyped 88 single nucleotide polymorphisms (SNPs) in 81 genes expected to influence hepatocarcinogenesis using the iPLEX assay. Risk of HCC was clarified by stratifying patients into risk groups based on the multiplied odds ratio (MOR) for SNPs associated with HCC, and the cumulative effects on the development and recurrence of HCC were analyzed. RESULTS: Six SNPs associated with risk of HCC were identified (OR range: 0.29-1.76). These included novel SNPs for hepatocarcinogenesis with HCV CCND2 rs1049606, RAD23B rs1805329, CEP164 rs573455, and GRP78rs430397 in addition to the known SNPs MDM2 rs2279744 and ALDH2 rs671. MOR analysis revealed that the highest risk group exerted about a 19-fold higher relative OR compared with the lowest risk group (P = 1.08 × 10(-5)). Predicted 10-year HCC risk ranged from 1.7% to 96% depending on the risk group and the extent of fibrosis. Recurrence-free survival of radiofrequency ablation-treated HCC in the high risk group (n = 53) was lower than that of low risk group (n = 58, P = 0.038). CONCLUSION: Single nucleotide polymorphisms of CCND2, RAD23B, GRP78, CEP164, MDM2, and ALDH2 genes were significantly associated with development and recurrence of HCC in Japanese patients with HCV.

[Classification of the bleeding pattern in colonic diverticulum is useful to predict the risk of bleeding or re-bleeding after endoscopic treatment].

We examined the re-bleeding rate after endoscopic hemostasis according to the bleeding pattern in patients with an acute lower gastrointestinal hemorrhage from colonic diverticula in 34 patients with active bleeding (Type 1) and 49 patients with exposed vessels and/or erosions in the base of diverticulum and no active bleeding (Type 2). Endoscopic hemostasis was performed by clipping the exposed vessel or erosions (direct method) or the entire diverticular orifice (reefing method). The incidence of re-bleeding was significantly higher in the Type 1 group than in the Type 2 group (p=0.002). All Type 1 cases were treated by the reefing method. In contrast, 14 of the 49 Type 2 cases were treated by the direct method, and no re-bleeding was observed in these cases. Of the other 35 Type 2 cases treated by reafing, rebleeding was seen in 5 cases. More effective endoscopic treatment is needed to prevent early re-bleeding, especially for Type 1 patients. The direct method may therefore reduce the rate of re-bleeding in Type 2 patients.

Pancreatic Exocrine Insufficiency in Intraductal Papillary Mucinous Carcinoma Presenting with Leg Edema Treated with Pancreatic Exocrine Replacement Therapy.

An 89-year-old woman underwent examinations for leg edema. Blood tests indicated low nutrition and low pancreatic enzymes, and a stool examination indicated fatty stool. Computed tomography showed pleural effusion, ascites, and cystic lesions in the pancreatic head and mural nodules within the cysts. Pancreatic juice cytology revealed adenocarcinoma. The diagnosis was pancreatic exocrine insufficiency caused by intraductal papillary mucinous carcinoma. The patient did not wish to undergo surgery. Therefore, diuretics, component nutrients, and pancreatic exocrine replacement therapy using pancrelipase were initiated. After starting treatment, her leg edema, pleural effusion, and ascites disappeared, and her activities of daily living improved markedly.

Mediastinal Lymph Node Metastasis of Esophageal Cancer with Esophageal Stenosis Diagnosed via Transesophageal Endoscopic Ultrasound with Bronchoscope-guided Fine-needle Aspiration.

An 80-year-old man underwent follow-up examinations after endoscopic submucosal dissection (ESD) for esophageal cancer. Computed tomography showed enlarged lymph nodes of the right recurrent nerve. The patient had esophageal stenosis due to repeated ESD for multiple esophageal tumors. The stenosis made the passage of an endoscopic ultrasound (EUS) scope through the esophagus difficult. Thus, an endobronchial ultrasound bronchoscope, which had a thinner diameter than that of the EUS scope, was used for transesophageal endoscopic ultrasound with bronchoscope-guided fine-needle aspiration. This technique led to the diagnosis of mediastinal lymph node metastasis of esophageal cancer.

Clinicopathological Characteristics of Superficial Barrett's Adenocarcinoma in a Japanese Population: A Retrospective, Multicenter Study.

Objective Although Barrett's adenocarcinoma (BA) remains a minor disease in Japan, its incidence has been gradually increasing. We analyzed the characteristics of BA in Japanese populations. Methods We retrospectively reviewed medical records and analyzed the clinicopathological differences between short-segment Barrett's esophagus (SSBE) and long-segment Barrett's esophagus (LSBE), as well as metastasis. Local recurrence and metachronous lesions were analyzed only in patients who underwent endoscopic resection (ER). Patients Consecutive patients who had pathological T1 BAs resected by ER or surgery from January 2003 to December 2017. Results A total of 168 patients were analyzed, including 139 with SSBE and 29 with LSBE. In total, 67% of the SSBE lesions and 32% of the LSBE lesions were located between 0 and 3 o'clock (p=0.0014). No patients who achieved pathological margin-free resection (pR0) and 17% of patients who did not achieve pR0 experienced local recurrence (p=0.0131). None of the patients without lymphovascular involvement, a poorly differentiated component, lesion size of >30 mm, and submucosal invasion of >500 µm experienced metastasis. The 5-year cumulative incidence rate of metachronous BA after ER was 0% in patients with SSBE and 40% in patients with LSBE (p=0.0005). Conclusion Superficial BA was likely to be detected at the right anterior wall of SSBE in the Japanese population. The risk for metachronous BA after ER was high in Japanese patients with LSBE, as in Western patients.

Prognostic importance of fucosylated alpha-fetoprotein in hepatocellular carcinoma patients with low alpha-fetoprotein.

BACKGROUND AND AIM: Fucosylated alpha-fetoprotein (AFP-L3) is known to be a marker of poor prognosis in patients with hepatocellular carcinoma (HCC). However, it has been difficult to measure AFP-L3 under low AFP (≤ 20 ng/mL). The aim of this study was to elucidate the role of AFP-L3 in HCC patients with low AFP conditions. METHODS: One hundred and ninety six consecutive newly developed HCC patients with low AFP (≤ 20 ng/mL) were examined for serum AFP-L3 expression by a newly-developed micro-total analysis system that could stably measure AFP-L3 in low AFP circumstances, and its clinical importance was analyzed. RESULTS: Positivity of AFP-L3 in HCC patients was 13.3% at a cut-off level of 10%. Five-year survivals of HCC patients with AFP-L3 (< 10%) and AFP-L3 (≥ 10%) were 69.4% and 41.1%, respectively (P = 0.001). Among 18 clinical parameters, low alanine aminotransferase, large tumor size, presence of portal vein tumor thrombus, high AFP and high des-gamma carboxy prothrombin were observed in the high AFP-L3 (≥ 10%) group. Multivariate analysis revealed that high aspartate aminotransferase (AST) (risk ratio [RR]= 3.24, 95% confidence interval [CI] = 1.27-8.26), the presence of ascites (RR = 3.44, 95% CI = 1.22-9.34), multiple tumor number (RR= 3.06, 95% CI = 1.33-7.17), and high AFP-L3 (RR = 8.36, 95% CI= 2.79-25.5) were risk factors for survival. High AFP-L3 was also a risk factor for survival in HCC patients who received radiofrequency ablation (P = 0.048). CONCLUSIONS: AFP-L3 is a strong prognostic factor for survival even in HCC patients with low AFP (≤ 20 ng/mL).

Predicting the treatment effect of sorafenib using serum angiogenesis markers in patients with hepatocellular carcinoma.

BACKGROUND AND AIM: Sorafenib, the first agent demonstrated to have efficacy to improve the survival of patients with advanced hepatocellular carcinoma (HCC), is an active multikinase inhibitor affecting angiogenesis and tumor proliferation. We analyzed cytokines related to angiogenesis or cell proliferation, and tried to determine their utility as biomarkers of sorafenib treatment effect for HCC. METHODS: Nine serum cytokines (angiopoietin-2 [Ang-2], follistatin, granulocyte colony-stimulating factor [G-CSF], hepatocyte growth factor [HGF], interleukin-8 [IL-8], leptin, platelet-derived growth factor-BB, platelet endothelial cell adhesion molecule-1, and vascular endothelial growth factor) were measured in 30 HCC patients treated with sorafenib, and the effects of treatment were compared using modified Response Evaluation Criteria in Solid Tumors. RESULTS: All but IL-8 were significantly higher at baseline in patients with progressive disease. Progression-free survival was significantly shorter in patients with high levels of Ang-2, G-CSF, HGF, and leptin, and the hazard ratios were 2.51, 6.89, 2.55, and 4.14, respectively. As the number of cytokines at a high level increased, the treatment response deteriorated. Disease progression was seen in three of 12 (25.0%) patients with zero to two high biomarkers, two of six (33.3%) patients with 3-5 high biomarkers, and 10 of 12 (83.3%) patients with six to eight high biomarkers (P=0.008). The prognosis of all patients with eight high biomarkers was progressive disease. CONCLUSION: High levels of serum cytokines at baseline were correlated with poor effects of sorafenib treatment in patients with HCC.

[Dynamic computed tomography is useful for the diagnosis and colonoscopic treatment of colonic diverticular bleeding].

We investigated whether emergency dynamic computed tomography (CT) is helpful to identify bleeding colonic diverticulum treatable by colonoscopy. We enrolled 95 consecutive patients given diagnoses of colonic diverticular bleeding at Hiroshima City Hospital in the present study, of whom 60 underwent CT before colonoscopy (CT group), and 35 underwent colonoscopy alone (CS group). In the CT group, bleeding diverticula were identified and treated by colonoscopy in 31 of 32 (96.9%) patients in whom extravasation was detected by CT. The interval between bleeding being recognized and CT (median 1.0 hours) in patients in whom extravasation was detected by CT was shorter than that in whom extravasation was not detected (median 5.0 hours). To identify and treat bleeding diverticula by colonoscopy, the use of emergency dynamic CT prior to colonoscopy is recommended.