Characteristics of gastric cancer detected within 1 year after successful eradication of Helicobacter pylori.

Gastric cancers are sometimes diagnosed in patients who have successfully undergone Helicobacter pylori (H. pylori) eradication. We analyzed the clinicopathological features of gastric cancers detected after eradication to clarify their characteristics. We reviewed 31 patients with 34 cases of gastric cancer detected after successful H. pylori eradication. Clinicopathological characteristics analyzed included interval since eradication, interval since last endoscopy, tumor size, and depth of invasion. Patients were classified into two groups: early detection (<1 year since eradication) and delayed detection (≥1 year since eradication). The interval since last endoscopy was significantly shorter in the early detection group than in the delayed detection group. However, gastric cancers were significantly larger and more invasive in the early detection group than in the delayed detection group. In conclusion, diligent endoscopy is necessary during the first year after successful H. pylori eradication. (The University Hospital Medical Information Network clinical trial registration number is UMIN000018541.).

Impact of serum levels of interleukin-6 and adiponectin on all-cause, liver-related, and liver-unrelated mortality in chronic hepatitis C patients.

BACKGROUND AND AIM: Various inflammatory cytokines and adipokines have been implicated in hepatitis C virus (HCV)-mediated liver disease, and interleukin-6 (IL-6) and adiponectin may play key roles. In addition, these factors may be associated with chronic hepatitis C (CHC)-induced extrahepatic manifestations. However, little data are available on the role of these factors on future outcomes of CHC patients. This study aims to evaluate the impact of serum levels of IL-6 and adiponectin on all-cause mortality, liver-related mortality, and liver-unrelated mortality. METHODS: A long-term follow-up study was conducted, consisting of 325 CHC patients, for which we previously reported positive associations between these factors (Serum levels of IL-6 and adiponectin) and hepatocellular carcinoma (HCC) development. RESULTS: During the follow-up period (mean, 13.0 year), there were 92 events consisting of 91 deaths (liver related, 72; liver unrelated, 19) and 1 liver transplantation due to liver failure. High IL-6 and adiponectin levels, defined as being higher than each median value at baseline, were associated with significantly higher incidences of not only HCC development but also all-cause mortality. Interestingly, high IL-6 was strongly associated with only liver-related mortality, whereas high-serum adiponectin was associated with not only liver-related, but also liver-unrelated mortality. Multivariate analysis identified high IL-6 as an independent risk factor for liver-related mortality and high adiponectin as an independent risk factor for liver-unrelated mortality. CONCLUSION: High serum levels of IL-6 and adiponectin were associated with higher all-cause and liver-related mortality in CHC patients. In addition, high adiponectin was associated with liver-unrelated mortality. The measurement of these factors may provide information useful for predicting future outcomes in CHC patients.

CT with hepatic arterioportography as a pretreatment examination for hepatocellular carcinoma patients: a randomized controlled trial.

OBJECTIVES: The combination of computed tomography with hepatic arteriography and arterial portography (CTHA/CTAP) can detect additional hepatocellular carcinoma (HCC) nodules undetected by conventional dynamic CT. METHODS: In this single-center, randomized, open-label, controlled trial, we randomly assigned 280 patients who were diagnosed as having HCC by conventional dynamic CT, and eligible for radiofrequency ablation (RFA), to undergo CTHA/CTAP before treatment, or to the control group. Newly detected HCC nodules by CTHA/CTAP were intended to be ablated completely. The primary end point was recurrence-free survival and the key secondary end point was overall survival. The analysis was conducted on an intention-to-treat basis. Those with nonablated nodules were treated as for recurrence. RESULTS: A total of 75 nodules were newly diagnosed as HCC by CTHA/CTAP in 45 patients. Three patients (one in the CTHA/CTAP group and two in the control group) who refused treatment were excluded from all analyses. The cumulative recurrence-free survival rates at 1, 2, and 3 years were 60.1, 29.0, and 18.9% in the CTHA/CTAP group and 52.2, 29.7, and 23.1% in the control group, respectively (P=0.66 by log-rank test; hazard ratio, 0.94 for CTHA/CTAP vs. control; 95% confidence interval (CI), 0.73-1.22). The cumulative overall survival rates at 3 and 5 years were 79.7 and 56.4% in the CTHA/CTAP group and 86.8 and 60.1% in the control group, respectively (P=0.50; hazard ratio, 1.15, 95% CI, 0.77-1.71). CONCLUSIONS: CTHA/CTAP may detect recurrent lesions earlier. However, CTHA/CTAP before RFA did not improve cumulative recurrence-free survival or overall survival.

Radiofrequency ablation for hepatocellular carcinoma: 10-year outcome and prognostic factors.

OBJECTIVES: Radiofrequency ablation (RFA) is widely performed for hepatocellular carcinoma (HCC). However, there has been no report on 10-year outcome of RFA. The objective of this study was to report a 10-year consecutive case series at a tertiary referral center. METHODS: We performed 2,982 RFA treatments on 1,170 primary HCC patients and analyzed a collected database. RESULTS: Final computed tomography images showed complete tumor ablation in 2,964 (99.4%) of 2,982 treatments performed for the 1,170 primary HCC patients. With a median follow-up of 38.2 months, 5- and 10-year survival rates were 60.2% (95% confidence interval (CI): 56.7-63.9%) and 27.3% (95% CI: 21.5-34.7%), respectively. Multivariate analysis demonstrated that age, antibody to hepatitis C virus (anti-HCV), Child-Pugh class, tumor size, tumor number, serum des-γ-carboxy-prothrombin (DCP) level, and serum lectin-reactive α-fetoprotein level (AFP-L3) were significantly related to survival. Five- and 10-year local tumor progression rates were both 3.2% (95% CI: 2.1-4.3%). Serum DCP level alone was significantly related to local tumor progression. Five- and 10-year distant recurrence rates were 74.8% (95% CI: 71.8-77.8%) and 80.8% (95% CI: 77.4-84.3%), respectively. Anti-HCV, Child-Pugh class, platelet count, tumor size, tumor number, serum AFP level, and serum DCP level were significantly related to distant recurrence. There were 67 complications (2.2%) and 1 death (0.03%). CONCLUSIONS: RFA could be locally curative for HCC, resulting in survival for as long as 10 years, and was a safe procedure. RFA might be a first-line treatment for selected patients with early-stage HCC.

Brown slits for colorectal adenoma crypts on conventional magnifying endoscopy with narrow band imaging using the X1 system.

BACKGROUND: Accurate diagnosis of colorectal premalignant polyps, including adenomas, is vital in clinical practice. AIM: To investigate the diagnostic yields of novel findings of brown slits for adenomas. METHODS: Patients who underwent colonoscopy at the Toyoshima Endoscopy Clinic were enrolled. Polyps sized ≥ 5 mm suspected of adenomas or clinically significant serrated polyps were included in the study. We defined the surface structures of colorectal polyps, which were brown curves inside and along the tubular glands identified using a combination of a new X1 system (Olympus Corporation) and a conventional magnifying colonoscope with non-staining narrow band imaging (NBI), as brown slits. The brown slits corresponded to slit-like lumens on endocytoscopy and histological crypt openings of an adenoma. We evaluated the diagnostic performance of brown slits for adenoma. RESULTS: A total of 108 Lesions from 62 patients were eligible. The average age was 60.4 years and 41.9% were male. The mean polyp size was 7.45 ± 2.83 mm. Fifty-seven lesions were positive for brown slits. Histopathological diagnosis comprised 59 low-grade tubular adenomas, 16 sessile serrated lesions, and 33 hyperplastic polyps. Among 59 adenomas, 56 (94.9%) were positive for brown slits. Among 16 sessile serrated lesions, 0 (0%) was positive for brown slits. Among 33 hyperplastic polyps, 1 (3.0%) was positive for brown slits. The sensitivity, specificity, and accuracy of brown slits for adenoma were 94.9%, 98.0%, and 96.3%, respectively. The positive predictive value and negative predictive value of brown slits for adenoma were also excellent for 98.2%, and 94.1%, respectively. CONCLUSION: Brown slits on conventional magnifying endoscopy with non-staining NBI using the X1 system were useful for diagnosing colorectal adenoma. The new endoscopy system could be examined using new standards.

Impact of looping on premalignant polyp detection during colonoscopy.

BACKGROUND: The presence of premalignant polyps on colonoscopy is an indicator of metachronous colorectal cancer. Looping during colonoscopy is associated with old age, female sex, and colonoscopy insertion time. However, the clinical significance of looping is not fully understood. We aimed to clarify the effect of looping on colorectal premalignant polyp detection. AIM: To assess the effects of looping on premalignant polyp detection using logistic regression analyses. METHODS: We retrospectively investigated patients who underwent colonoscopy at Toyoshima Endoscopy Clinic between May, 2017 and October, 2020. From the clinic's endoscopy database, we extracted data on patient age, sex, endoscopist-assessed looping, colonoscopy duration, endoscopist experience, detection rate, and number of premalignant polyps. RESULTS: We assessed 12259 patients (mean age, 53.6 years; men, 50.7%). Looping occurred in 54.3% of the patients. Mild and severe looping were noted in 4399 and 2253 patients, respectively. The detection rates of adenomas, advanced adenomas, high-risk adenomas, clinically significant serrated polyps (CSSPs), and sessile serrated lesions (SSLs) were 44.7%, 2.0%, 9.9%, 8.9% and 3.5%, respectively. The mean numbers of adenomas and SSLs were 0.82 and 0.04, respectively. The detection rates of adenomas, high-risk adenomas, and CSSPs increased with looping severity (all P < 0.001). The number of adenomas increased with looping severity (P < 0.001). Multivariate analyses found that detection of adenomas, high-risk adenomas, and CSSPs was associated with severe looping (P < 0.001, P < 0.001, and P = 0.007, respectively) regardless of age, sex, time required for colonoscope insertion and withdrawal, and endoscopist experience. CONCLUSION: Looping severity was independently associated with high detection rates of premalignant polyps. Therefore, looping may predict the risk of metachronous colorectal cancer. Endoscopists should carefully examine the colorectum of patients with looping.

Serum level of adiponectin and the risk of liver cancer development in chronic hepatitis C patients.

Obesity and metabolic syndrome are recognized risk factors for development of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C (CHC). Dysregulation of adipokines, particularly the decreased secretion of adiponectin, appears to play a key role. To investigate the association between adiponectin and hepatocarcinogenesis, we conducted a large-scale retrospective cohort study. We enrolled 325 patients with CHC (146 men, 179 women; mean age 58.0 ± 10.3 years) whose serum samples were collected between January 1994 and December 2002. Subjects were divided into two groups according to their serum adiponectin levels. We evaluated the association between adiponectin level and the risk of subsequent HCC development using univariate and multivariate Cox proportional hazard regression. Because average serum adiponectin level was higher in females than males, each gender was analyzed separately. Patients with CHC had significantly higher adiponectin levels than healthy controls. During the follow-up period (mean: 9.0 years), HCC developed in 122 subjects. Unexpectedly, subjects with higher serum adiponectin levels had a higher incidence of HCC (males: p = 0.032; females: p = 0.01; log-rank test). Multivariate analysis revealed that a high serum adiponectin level was independently associated with HCC development (hazard ratio [HR] = 2.07; p = 0.031 in females and HR = 1.82; p = 0.05 in males). Isoform analysis revealed that middle- and low-molecular-weight isoforms contributed to the risk of HCC. In conclusion, Patients who had CHC with high serum adiponectin levels had a higher risk of liver cancer development. Adiponectin may thus be tumorigenic or indicate a liver disease state independently of other clinical parameters.

Intrahepatic bile duct dilatation after percutaneous radiofrequency ablation for hepatocellular carcinoma: impact on patient's prognosis.

BACKGROUND: Percutaneous radiofrequency ablation (RFA) has been widely accepted as an alternative to surgery for small hepatocellular carcinoma (HCC). In RFA, a portion of liver tissue surrounding tumour is also ablated to achieve a safety margin. The intrahepatic bile duct may be injured and result in chronic bile duct dilatation upstream of the injured site. However, the impact of such an injury on the overall prognosis has been unclear. METHODS: Patients who showed bile duct dilatation following RFA were identified by a retrospective review of imaging studies. Each dilatation was classified as mild (limited to one hepatic subsegment) or severe (affecting two or more subsegments). The relation between the incidence of intrahepatic bile duct dilatation and HCC recurrence or survival was analysed using proportional hazard models. RESULTS: Among 589 consecutive HCC patients treated with RFA, 70 (11.9%) and 21 (3.6%) patients showed mild and severe bile duct dilatation respectively. Patients with severe dilatation, but not those with mild dilatation, had lower survival and higher HCC recurrence than patients without dilatation. Severe dilatation, but not mild dilatation, was significantly associated with death [hazard ratio (HR) 2.17, P=0.035] and recurrence (HR 2.89, P<0.001). CONCLUSION: Whereas mild bile duct dilatation after RFA is clinically negligible, bile duct dilatation affecting two or more subsegments should be regarded as a complication that may affect the prognosis and should be observed carefully.

Simple feedback of colonoscopy performance improved the number of adenomas per colonoscopy and serrated polyp detection rate.

Background and study aims High-quality endoscopy requires improvement of not only the adenoma detection rate (ADR) but also the serrated polyp (SP) detection rate and the mean number of adenomas per positive procedure (MAP +). We evaluated whether a simple feedback of colonoscopy performance improves those quality indicators using propensity-score matching. Patients and methods Eleven endoscopists were evaluated regarding colonoscopy performance including ADRs, SP detection rates, mean numbers of adenomas per procedure (MAPs), and MAPs + with their ranking in the clinic. Endoscopic performance was compared before and after the feedback. Results Colonoscopies were performed for 874 patients before the feedback and 1,272 patients after the feedback. Using propensity-score matching, 803 patients before the feedback and 803 patients after the feedback were matched. ADR after the feedback was significantly higher than that before the feedback (50.8 % and 40.8 %, respectively). MAP after feedback was significantly larger than that before the feedback (0.92 and 0.69, respectively), as well as MAP + (1.96 and 1.69, respectively). Clinically significant SP detection rate was also improved from 10.0 % to 14.9 %. Conclusions Feedback including ADR, MAP, MAP +, and clinically significant SR detection rate could improve on those quality indicators. Further studies are needed to effectively prevent colorectal cancer in colonoscopy practice.

Risk Factors for Prolonged Hospital Stay after Endoscopy.

BACKGROUND/AIMS: The recovery room used after endoscopy has limited capacity, and an efficient flow of the endoscopy unit is desired. We investigated the duration of hospital stay after endoscopy and the risk factors for prolonged hospital stay among outpatients. METHODS: We retrospectively studied consecutive patients who underwent esophagogastroduodenoscopy or colonoscopy at the Toyoshima Endoscopy Clinic. We collected data on age, sex, body weight, midazolam and pethidine dosage, respiratory depression during endoscopy, and duration of hospital stay after endoscopy (scope out to check out). Risk factors for prolonged hospital stay (>100 minutes) were identified using multiple logistic regression analysis. RESULTS: We enrolled 3,898 patients, including 3,517 (90.2%) patients tested under sedation and 381 (9.8%) patients tested without sedation. Overall, 442 (11.3%) patients had prolonged stay (>100 min). The mean time difference between sedation group and non-sedation group was 44.2 minutes for esophagogastroduodenoscopy and 39.1 minutes for colonoscopy. Age (odds ratio [OR], 1.025; 95% confidence interval [CI], 1.014-1.036), female sex (OR, 1.657; 95% CI, 1.220-2.249), and midazolam dose (OR, 1.019; 95% CI, 1.013-1.026) were independently associated with prolonged hospital stay after esophagogastroduodenoscopy, with similar results for colonoscopy. CONCLUSION: Old age, female sex, and midazolam dose were independent risk factors for prolonged hospital stay after endoscopy.

Successful local treatment for repeated hepatic recurrences of cholangiolocellular carcinoma: a report on a long-term survivor.

BACKGROUND: Cholangiolocellular carcinoma (CoCC) is a rare liver tumor arising from the canals of Hering found between the cholangioles and interlobular bile ducts. Although morphologically CoCC mimics intrahepatic cholangiocarcinoma (ICC), CoCC exhibits a unique intermediate biologic behavior between hepatocellular carcinoma (HCC) and ICC. Curative resection is required for prolonged survival in patients with CoCC. However, effective therapy for postoperative hepatic recurrence has not yet been standardized. CASE PRESENTATION: A 40-year-old man had an asymptomatic liver mass found during a regular medical examination. Contrast-enhanced computed tomography revealed a well-enhanced mass, 15 cm in diameter, in the right liver. He underwent right hemihepatectomy at a local hospital under the preoperative diagnosis of hepatocellular carcinoma. Pathologic examination confirmed a moderately differentiated tubular adenocarcinoma, leading to a diagnosis of ordinary ICC. Twelve months after surgery, he was referred to our hospital due to three hepatic recurrences in the left medial segment. He underwent partial hepatectomy for the recurrence, followed by adjuvant chemotherapy using gemcitabine alone. After the second hepatectomy, hepatic recurrences developed an additional seven times. The numbers and sizes of the recurrent tumors were very limited at each recurrence, satisfying the standard criteria for percutaneous radiofrequency ablation (RFA) for the treatment of HCC. All lesions were treated by percutaneous RFA, although this was an exceptional approach for ICC. He is now alive without evidence of disease 9.2 years after the first hepatectomy. Because his clinical outcome was satisfactory and not compatible with the typical negative outcomes of ordinary ICC, we re-reviewed the histological findings of his tumor. The tumor was composed of small gland-forming cells proliferating in an anastomosing pattern; the cell membrane was strongly immunoreactive for epithelial membrane antigen. These findings were in accordance with the typical features of CoCC, revising his final diagnosis from ICC to CoCC. CONCLUSIONS: This case report demonstrates a satisfactory outcome using repeated local treatments, such as hepatectomy and RFA, for hepatic recurrences of CoCC, suggesting that a localized treatment approach can be considered to be a therapeutic option. We should be careful in making a definitive diagnosis of ICC and ruling out CoCC because the diagnosis potentially dictates the treatment strategy for recurrences.

Adiponectin in chronic hepatitis C.

White adipose tissue has been increasingly recognized as an important endocrine organ that secretes a number of biologically active adipokines. Adiponectin, one of the major adipokines, possesses anti-inflammatory and insulin-sensitizing properties, and its serum levels typically decline with increasing body weight. Hypoadiponectinemia has been implicated in the development of obesity-related morbidities such as dyslipidemia and cerebrovascular disease. In addition, hypoadiponectinemia has been reported to enhance hepatic steatosis, inflammation, fibrosis, and hepatocarcinogenesis in animal models or clinical liver diseases. Chronic hepatitis C (CHC) has some features which allow it to be recognized not only as a viral disease but also as a metabolic liver disease that encompasses insulin resistance, inflammation, steatosis and fibrosis. CHC is another disease in which adipokines may represent a link between viral infection and steatosis, or metabolic disturbance. In this report, data indicating a possible role of adiponectin in CHC are summarized.

A case of chemical peritonitis and pleuritis caused by spontaneous rupture of a benign cystic ovarian teratoma that improved without surgical intervention.

Rupture of a benign cystic ovarian teratoma may result in severe chemical granulomatous peritonitis, a condition mimicking peritonitis carcinomatosa, with patients complaining of common abdominal symptoms. As the precipitating cause of rupture is often indeterminate and the rupture itself is hard to recognize, it is difficult to differentiate from peritonitis of other etiologies, such as gastrointestinal malignancy. We report the case of a 72-year-old female who presented with recurrent pyrexia and abdominal distension. Laboratory data showed signs of inflammation and a high level of carbohydrate antigen 125. Imaging examinations showed left-side-dominant pleural effusion, ascites with peritoneal adhesions, and a left cystic ovarian teratoma. Repeat paracentesis of both the pleural effusion and ascites demonstrated exudative characteristics, but there was no indication of malignancy or signs of infection, including those of tuberculosis. Although exploratory laparotomy was then recommended for conclusive diagnosis and ruling out such gynecological malignancy, the patient declined. Fortunately, laboratory data, radiological images, and other clinical findings gradually improved over the following 12 months. Moreover, a retrospective review of the computed tomography images revealed lipid particles in the ascites, indicative of teratoma rupture. The final diagnosis was chemical peritonitis and pleuritis caused by spontaneous rupture of the benign cystic teratoma. The present case was extremely rare with regard to its diagnosis and clinical progression. Our experience suggests that chemical peritonitis should be included in the differential diagnosis of peritonitis.

Systemic combination therapy of intravenous continuous 5-fluorouracil and subcutaneous pegylated interferon alfa-2a for advanced hepatocellular carcinoma.

BACKGROUND: In Japan, sorafenib is now the first-line therapy for individuals with advanced hepatocellular carcinoma (HCC), but no other treatment is available for such patients. The aim of this study was to assess the efficacy and safety of combination therapy with systemic continuous intravenous infusion of 5-fluorouracil (5-FU) and subcutaneous peginterferon alfa-2a, which was used before sorafenib was introduced to Japan. METHODS: Two hundred and twenty-three HCC patients, who were not amenable to curative surgery, percutaneous ablation, or transarterial chemoembolization (TACE), and for whom intraarterial chemotherapy was not indicated because of the presence of extrahepatic metastasis or stenosis of the common hepatic artery, received peginterferon alfa-2a (90 µg subcutaneously on days 1, 8, 15, and 22) and 5-FU (500 mg/day intravenously given continuously on days 1-5 and 8-12). We assessed their response to treatment and survival, and treatment safety. RESULTS: The response rate was 9.4 % (including six patients with complete response) and the disease-control rate was 32.7 %. The median time to progression was 2.0 months. The overall median survival time was 6.5 months (Child-Pugh class A: 9.2 months vs. Child-Pugh class B: 2.8 months). In a multivariate analysis, Eastern Cooperative Oncology Group (ECOG) performance status >0, Child-Pugh class B, and the presence of macroscopic vascular invasion were independent predictors of poor prognosis. The major grade 3-4 adverse events were leucopenia (13.9 %) and thrombocytopenia (5.8 %). No treatment-related deaths occurred. CONCLUSIONS: This combination therapy was well tolerated and showed promising efficacy. Further studies are needed to establish the usefulness of this treatment.

Assessment of disease progression in patients with transfusion-associated chronic hepatitis C using transient elastography.

AIM: To evaluate the relationship between liver stiffness and duration of infection in blood transfusion-associated hepatitis C virus (HCV) patients with or without hepatocellular carcinoma (HCC). METHODS: Between December 2006 and June 2008, a total of 524 transfusion-associated HCV-RNA positive patients with or without HCC were enrolled. Liver stiffness was obtained noninvasively by using Fibroscan (Echosens, Paris, France). The date of blood transfusion was obtained by interview. Duration of infection was derived from the interval between the date of blood transfusion and the date of liver stiffness measurement (LSM). Patients were stratified into four groups based on the duration of infection (17-29 years; 30-39 years; 40-49 years; and 50-70 years). The difference in liver stiffness between patients with and without HCC was assessed in each group. Multiple linear regression analysis was used to determine the factors associated with liver stiffness. RESULTS: A total of 524 patients underwent LSM. Eight patients were excluded because of unsuccessful measurements. Thus 516 patients were included in the current analysis (225 with HCC and 291 without). The patients were 244 men and 272 women, with a mean age of 67.8 ± 9.5 years. The median liver stiffness was 14.3 kPa (25.8 in HCC group and 7.6 in non-HCC group). The patients who developed HCC in short duration of infection were male dominant, having lower platelet count, with a history of heavier alcohol consumption, showing higher liver stiffness, and receiving blood transfusion at an old age. Liver stiffness was positively correlated with duration of infection in patients without HCC (r = 0.132, P = 0.024) but not in patients with HCC (r = -0.103, P = 0.123). Liver stiffness was significantly higher in patients with HCC than in those without in each duration group (P < 0.0001). The factors significantly associated with high liver stiffness in multiple regression were age at blood transfusion (P < 0.0001), duration of infection (P = 0.0015), and heavy alcohol consumption (P = 0.043). CONCLUSION: Although liver stiffness gradually increases over time, HCC develops in patients with high stiffness value regardless of the duration of infection.