[A case of severe colitis caused by immune checkpoint inhibitor].

A 74-year-old male with lung squamous cell carcinoma who was treated with the anti PD-1 antibody nivolumab developed frequent diarrhea four months after initiating treatment. However, his condition did not improve despite prednisolone at 20mg. Endoscopic examination revealed loss of vascular pattern, erosions, and mucosal friability, resembling ulcerative colitis. Colonoscopy revealed punch-out ulcers in the affected mucosa. Therefore, he was definitively diagnosed with severe colitis caused by immune checkpoint inhibitor treatment and cytomegalovirus colitis. Nivolumab was discontinued, and he was treated with 60mg prednisolone and ganciclovir. Although his colitis improved, he developed pneumonia and died thereafter. This case highlights adverse events that are associated with immune checkpoint inhibitors which should be treated properly.

[A case of renal salt-wasting syndrome during chemotherapy for advanced gastric cancer].

A 66-year-old woman was admitted to our hospital with heartburn and liver dysfunction. She was diagnosed with advanced gastric cancer. After the initiation of chemotherapy with trastuzumab, capecitabine, and cisplatin, she developed hyponatremia and renal failure with renal salt-wasting syndrome (RSWS). She recovered from these conditions after infusion of hypertonic saline. A diagnosis of RSWS should be considered in patients with hyponatremia who receive cisplatin-based chemotherapy.

Peppermint oil solution is useful as an antispasmodic drug for esophagogastroduodenoscopy, especially for elderly patients.

BACKGROUND: Although hyoscine butyl bromide (HB) and glucagon (GL) are often used as antispasmodic drugs during esophagogastroduodenoscopy (EGD), these agents may cause adverse effects. Recently, it was reported that peppermint oil solution (PO) was very effective and had few side effects. AIM: We clarified the efficacy and usefulness of PO as an antispasmodic during upper endoscopy, especially for elderly patients. METHODS: This study was a non-randomized prospective study. The antispasmodic score (1-5, where 5 represents no spasm) was defined according to the degree of spasms of the antrum and difficulty of biopsy. We compared the antispasmodic scores between non-elderly patients (younger than 70) and elderly patients (70 years old or older) according to the antispasmodic agent. RESULTS: A total of 8,269 (Group PO: HB: GL: NO (no antispasmodic) = 1,893: 6,063: 157: 156) EGD procedures were performed. There was no significant difference in the antispasmodic score between Group PO (mean score ± standard deviation: 4.025 ± 0.925) and Group HB (4.063 ± 0.887). Among the non-elderly patients, those in Group PO (n = 599, 3.923 ± 0.935) had a worse antispasmodic score than those in Group HB (n = 4,583, 4.062 ± 0.876, P < 0.001). However, among the elderly patients, those in Group PO (n = 1,294, 4.073 ± 0.917) had similar scores to those in Group HB (n = 1,480, 4.064 ± 0.921, P = 0.83), and significantly better scores than those in Group GL (n = 69, 3.797 ± 0.933, P < 0.05). CONCLUSION: Peppermint oil was useful as an antispasmodic during EGD, especially for elderly patients.

Effect of low-dose gemcitabine on unresectable pancreatic cancer in elderly patients.

BACKGROUND/AIMS: The efficacy of gemcitabine (GEM) on unresectable pancreatic cancer has been reported. However, in elderly patients, severe toxicities are frequently observed. In this study we aimed to assess the efficacy of low-dose GEM on unresectable pancreatic cancer in elderly patients. METHODS: We reviewed 68 elderly patients (≥65 years) with unresectable pancreatic cancer. Thirty-six patients were treated with low-dose GEM (600-800 mg/m(2); GEM group), and the other 32 received best supportive care (BSC group). RESULTS: Median survival was 7.6 and 2.3 months in the GEM and BSC groups, respectively. In the GEM group, the median survival period was longer in 24 patients showing partial response or stable disease than in 12 patients showing progressive disease (11.4 vs. 5.3 months). Furthermore, the patients showing progressive disease had better 6-month survival than patients in the BSC group. Thirteen patients (36%) developed severe toxicities (grade 3 or 4). Low-dose GEM, stage of disease and performance status were associated with the prognosis. CONCLUSIONS: Low-dose GEM may improve the prognosis of elderly patients with unresectable pancreatic cancer. Furthermore, frequencies of severe toxicity seem lower in patients treated with low-dose GEM compared with previous reports.

Investigation of upper gastrointestinal bleeding after implantation of drug-eluting stents; prospective cohort study.

OBJECTIVE: After implantation of drug-eluting stents (DES), two or more anti-thrombotic agents are required. The risk of upper gastrointestinal bleeding (UGIB) in cases of DES implantation is thought to be significant. However, the incidence of UGIB has not yet been investigated in DES-implanted patients. This study aimed to investigate the incidence of UGIB after DES implantation and the awareness among cardiologists about this complication. MATERIAL AND METHODS: Subjects were 397 consecutive patients implanted with DES from August 2004 to September 2007 at two institutions. Endoscopic examinations were performed on DES-implanted patients who presented with hematemesis and/or tarry stools. The concomitant use of acid-suppressing agents was left to the cardiologists. In addition, 37 cardiologists were administered a questionnaire regarding UGIB after DES implantation. RESULTS: Low-dose aspirin and ticlopidine were prescribed in all patients. Forty-six patients had a past history of peptic ulcer. Acid-suppressing agents were concomitantly prescribed to 224 patients (56%) including 32 patients (70%) with a past history of peptic ulcer. UGIB due to gastric ulcers developed in 5 cases (1.3%). One case had received a half dose of H2-RA. No bleeding occurred in patients who received proton pump inhibitors (PPI). The incidence of UGIB was 4.0 per 1000 patient-years. The cardiologists who were surveyed recognized the risk of UGIB after DES implantation and the necessity for its prevention. However, they indicated that adequate management for preventing this complication has not been established. CONCLUSIONS: This study reassuringly demonstrated a low incidence of UGIB after DES implantation. Further study regarding the prophylaxis for UGIB after DES implantation is necessary.

Eradication of Helicobacter pylori infection improved gastric mucosal atrophy and prevented progression of intestinal metaplasia, especially in the elderly population: a long-term prospective cohort study.

BACKGROUND AND AIMS: It still remains controversial whether gastric mucosal atrophy and intestinal metaplasia are reversible after eradication of Helicobacter pylori infection. The aims of this study were to evaluate the histological changes in gastric mucosa after H. pylori eradication during long-term follow-up periods, and to verify the propriety of H. pylori eradication for the elderly population. METHODS: Two hundred and forty-one patients with H. pylori infection and 84 cases more than 60 years old were classified as the elderly group. The mean follow-up period was 101 months. A series of endoscopic examinations with five-point biopsies were performed before and every year after H. pylori eradication. We evaluated the histological grades according to the Updated Sydney System. Statistical analysis was performed using the Wilcoxon signed rank test and the Mann-Whitney U-test, and P < 0.05 was considered to be statistically significant. RESULTS: The atrophic grades improved only at the angle in the 5th year and at all points, except for the antrum, in the 10th year after H. pylori eradication. In the elderly group, the atrophic score improved in both the 5th and 10th year. However, improvement in the younger group was achieved only in the 10th year. The metaplastic score did not change in either the 5th or 10th year after H. pylori eradication in all patients. CONCLUSION: Eradication of H. pylori infection improved gastric atrophy and prevented the progression of intestinal metaplasia in the elderly population during the long-term follow-up periods. H. pylori eradication for the elderly population is effective.

Large waist circumference is a risk factor for reflux esophagitis in Japanese males.

BACKGROUND/AIMS: The prevalence of reflux esophagitis, which might lead to development of Barrett's esophagus and esophageal adenocarcinoma, has been increasing. The aim of this study was to assess risk factors for reflux esophagitis. METHODS: We conducted a cross-sectional study of 1,495 Japanese subjects undergoing health checkups (822 males and 673 females; median age 50 years) at a tertiary care center. RESULTS: One hundred and twenty-seven subjects (8%) had reflux esophagitis and hiatal hernia was observed in 292 subjects (20%). Reflux esophagitis (13 vs. 3%) and hiatal hernia (28 vs. 9%) were more frequent in males than females. Significant differences in clinical backgrounds were observed between females and males. Multivariate logistic regression analyses revealed that hiatal hernia (OR 6.63, 95% CI 2.47-17.8; p = 0.0002) was associated with reflux esophagitis in females. In males, age (per 1-year increment: OR 0.96, 95% CI 0.94-0.99; p = 0.007), hiatal hernia (OR 3.16, 95% CI 2.05-4.87; p < 0.0001) and waist circumference (per 1-cm increase: OR 1.09, 95% CI 1.02-1.15; p = 0.006) were associated with reflux esophagitis. CONCLUSIONS: Abdominal obesity may be an important risk factor for reflux esophagitis in males compared with females.

[Case of primary malignant lymphoma of the liver treated by R-CHOP therapy].

A 75-year-old man was admitted to our hospital because of right hypochondralgia. Computed tomography (CT) revealed a large tumor in the right lobe of the liver. Ultrasonography (US) showed vessels in the tumor. Needle biopsy specimens showed malignant lymphoma (Diffuse large B cell lymphoma). Ga scintigraphy and FDG-PET did not demonstrate other lesions and the definitive diagnosis was primary malignant lymphoma of the liver. CHOP with Rituximab therapy (R-CHOP therapy) was performed. After 8 courses of therapy the FDG-PET results were negative and we considered complete remission. We describe a case of primary malignant lymphoma of the liver treated successfully by R-CHOP therapy.

Partial splenic embolization prior to combination therapy of interferon and ribavirin in chronic hepatitis C patients with thrombocytopenia.

AIM: A low platelet count leads to dose reduction of interferon (IFN) and is associated with failure to achieve a sustained virological response (SVR) in chronic hepatitis C patients. However, partial splenic embolization (PSE) is effective for treating thrombocytopenia resulting from hypersplenism. METHODS: We compared the clinical features of 10 patients receiving PSE prior to the combination therapy of IFN and ribavirin (RBV) (PSE group) with those of 10 non-receiving PSE patients (non-PSE group). RESULTS: In all 10 patients, PSE was successfully performed without serious adverse events. After PSE, leukocyte, neutrophil, and platelet counts significantly increased. The period from PSE to the initiation of the combination therapy was 15 (7-21) days. In the PSE group, two of six patients (33%) infected with genotype 1, and all four patients infected with genotype 2, achieved SVR. In the non-PSE group, only three patients infected with genotype 2 achieved SVR. Two patients in the PSE group and one in the non-PSE group discontinued the combination therapy. Three patients of the PSE group and five of the non-PSE group reduced the dose of pegylated IFN-alpha-2b because of thrombocytopenia. In the PSE group, platelet counts during the combination therapy fell to baseline levels; however, they did not fall to lower levels than baseline levels. In the non-PSE group, platelet counts 1 month after the initiation of the therapy were lower than baseline levels. CONCLUSION: The increase of platelet counts after PSE may allow the safe use of IFN and RBV and improve the SVR rate in chronic hepatitis C patients with thrombocytopenia.

[Case report of asymptomatic arteriovenous malformation (AVM) of the pancreas; diagnostic advantage of three-dimensional computed tomography].

A 72-year-old man with diabetes mellitus and hypertension was admitted for further examination and therapy of diabetes. In order to evaluate his pancreas, abdominal computed tomography (CT) was performed, showing a space-occupying lesion (SOL) in the pancreatic uncus. He did not show any symptoms related to the pancreas or gastro intestinal tract. Three-dimensional CT (3D-CT) indicated that the SOL was not a solid tumor but a vessel fistula, fed by the superior mesenteric artery and the gastro duodenal artery, drained by the superior mesenteric vein. Abdominal angiography also showed its peculiar vessel structure, confirming arterio-venous (A-V) malformation in the pancreas. Pancreatic A-V malformation is a rare condition but should not be forgotten in the differential diagnosis of pancreatic SOL. Our case showed the advantages of 3D-CT with its low invasiveness and convenience for the diagnosis of A-V malformation in the pancreas.

Sex differences in attachment to spouses among older Japanese couples.

AIM: Attachment among older adults can partially explain sex differences in bereavement outcomes, but there is currently little evidence regarding this. The aim was to quantify sex differences in the proportion of spouses as attachment figures among older couples. METHODS: We carried out a secondary analysis of cross-sectional questionnaire survey data. The dataset included information about 5137 respondents aged 65 years or older in Kanonji and Mitoyo, two rural cities in Kagawa prefecture, Japan; those who were never married or were widowed or divorced were excluded. The questionnaire asked participants whom they most want to be close by when they die (this person was defined as an "attachment figure"), and compared the proportion of older people of each sex who named their spouse. We used multiple logistic regression analyses to examine the independent association of sex with the proportion of spouses as attachment figures. RESULTS: Of the 2513 male respondents, 1494 (59.5%) answered "spouse." Of the 2624 female respondents, 904 (34.5%) answered "spouse." Multiple logistic regression analyses adjusted for age, live-in children, annual income, participation in community activities, presence of a long-term primary care doctor, anxiety about death and preferences for place of death showed that men had a higher probability of attachment to spouses than women (odds ratio 2.83, 95% confidence interval 2.43-3.31). CONCLUSIONS: Spouses are more likely to be attachment figures for men than for women. The present study supports the theory that sex differences in attachment might partially explain the differences in the bereavement effect between sexes among older people. Geriatr Gerontol Int 2017; 17: 834-838.

A target-controlled infusion system with bispectral index monitoring of propofol sedation during endoscopic submucosal dissection.

BACKGROUND AND STUDY AIMS: Propofol administration via a target-controlled infusion system with bispectral index monitoring (BIS/TCI system) is expected to prevent complications from sedation during complex and long endoscopic procedures. We evaluated the feasibility of setting the BIS/TCI system for non-anesthesiologist administration of propofol (NAAP) during endoscopic submucosal dissection (ESD). PATIENTS AND METHODS: From May 2009 to February 2013, 250 patients with esophagogastric neoplasms were treated with ESD using the BIS/TCI system with NAAP. In the TCI system, the initial target blood concentration of propofol was set at 1.2 µg/mL. The titration speed of propofol was adjusted according to the BIS score and the movement of the patient. The BIS target level ranged from moderate to deep sedation, at which a stable BIS score between 60 and 80 was obtained. RESULTS: In 80.4 % of patients, it was possible to maintain stable sedation with a blood concentration of propofol of less than 1.6 µg/mL using TCI throughout the ESD procedure. The default setting for ideal blood concentration of propofol was 1.2 µg/mL, because the medians of the lower and upper bounds of blood concentration were 1.2 µg/mL (range 0.6 - 1.8 µg/mL) and 1.4 µg/mL (range 1.0 - 3.8 µg/mL), respectively. Although hypotension occurred in 27 patients (10.8 %), oxygen desaturation occurred in only nine patients (3.6 %), and severe desaturation in only two patients (0.8 %). CONCLUSIONS: Using our settings, it is possible for a non-anesthesiologist to maintain stable sedation during a lengthy endoscopic procedure through propofol sedation with a BIS/TCI system.

Usefulness of early-phase peritoneal lavage for treating severe acute pancreatitis.

OBJECTIVE: To improve the prognosis of severe acute pancreatitis, preventing infectious complications, particularly infected pancreatic necrosis, is important. The present study evaluated the efficacy of peritoneal lavage for improving the prognosis of patients with severe acute pancreatitis. PATIENTS: We retrospectively reviewed the cases of 23 consecutive patients with severe acute pancreatitis who were treated with peritoneal lavage. RESULTS: Peritoneal lavage was started within 72 hours after the initial onset of symptoms in 20 patients (87%). The duration of peritoneal lavage, which was significantly correlated with the number of prognostic factors according to the revised Japanese criteria, Ranson score and serum C-reactive protein level at the start of peritoneal lavage, was a median of seven (3-22) days. There were no adverse events associated with the peritoneal lavage. Eight patients (35%) concurrently underwent continuous regional arterial infusion. Five days after starting peritoneal lavage, the patients' clinical conditions significantly improved. Overall, the survival rate was 96%. One patient (4%) died due to rupture of a pseudoaneurysm of the splenic artery. Complications occurred in seven patients (30%). Infectious complications were observed in three patients (13%) (one patient developed infected pancreatic necrosis and bacteremia, and two patients developed bacteremia). Pseudocysts and pancreatic fistulas developed in five and one patient, respectively. The incidence of complications was lower in the patients receiving peritoneal lavage within 72 hours from the initial onset of symptoms than in the remaining patients (20% vs. 100%; p=0.005). CONCLUSION: We speculate that peritoneal lavage reduces the mortality and incidence of complications in patients with severe acute pancreatitis.

Long-term combined therapy with very-low-dose peginterferon and ursodeoxycholic acid decreased the spleen size in a patient with hepatitis C virus-related cirrhosis.

A 42-year-old woman with hepatitis C virus-related cirrhosis underwent peginterferon alpha-2b therapy combined with ribavirin but could not achieve a sustained viral response. Following discontinuation of this combined therapy, the patient's serum transaminase levels suddenly became elevated. Therefore, the administration of very-low-dose peginterferon alpha-2a with ursodeoxycholic acid was introduced. Thereafter, the patient's serum transaminase levels gradually improved. Four years later, enhanced computed tomography showed shrinkage of the spleen and enlargement of the liver. Long-term combined therapy with very-low-dose peginterferon and ursodeoxycholic acid may be effective not only in preventing disease progression, but also in improving portal hypertension in patients hepatitis C virus-related cirrhosis.

Partial splenic embolization facilitates the adherence to peginterferon in chronic hepatitis C with thrombocytopenia.

OBJECTIVE: Platelet counts before starting the treatment affect the discontinuation and dose reduction of peginterferon in chronic hepatitis C. Thrombocytopenia leads to failure to achieve sustained virological response. This study was undertaken to evaluate the efficacy of partial splenic embolization (PSE) prior to starting peginterferon therapy combined with ribavirin in chronic hepatitis C patients showing thrombocytopenia. PATIENTS AND METHODS: We compared the clinical features of 11 patients receiving PSE (PSE group) prior to starting the combined therapy with those of 13 patients not receiving PSE (non-PSE group). All of the patients showed platelet counts ≤12×10(4)/mm(3) and serum hepatitis C virus-RNA levels ≥100 KIU/mL at baseline. The end-point of PSE was a volume of splenic infarction over 75%. Peginterferon alpha-2b at a dose of 1.2 µg/kg was administered by subcutaneous injection once a week. The dose of ribavirin was weight adjusted. RESULTS: PSE was successfully performed without serious adverse events. The period from PSE to starting the combined therapy was 14 (6-27) days. After PSE, platelet counts were significantly increased. In PSE group, platelet counts during the combined therapy were maintained above those at baseline. In non-PSE group, platelet counts at the 2nd week after the start of the combined therapy significantly decreased to less than those at baseline. Overall, 80% adherence to expected peginterferon dose was not achieved in 5 patients (45%) of PSE group and in 11 (85%) of non-PSE group (p=0.043). CONCLUSION: Increased platelet counts after PSE facilitates the adherence to peginterferon therapy in chronic hepatitis C patients with thrombocytopenia.

A case of hepatic angiomyolipoma difficult to distinguish from hepatocellular carcinoma.

We report a case of hepatic angiomyolipoma with uncommon clinical features. A 56-year-old man presented with a hepatic tumor in the caudate lobe. The tumor was hypoechoic on ultrasonography, showed early-phase hyperattenuation on enhanced computed tomography and did not absorb iron on superparamagnetic iron oxide-enhanced magnetic resonance imaging. Hepatocellular carcinoma was highly suspected, and the patient underwent hepatic resection. Histologically, the tumor was mainly composed of smooth muscle cells and contained small amounts of adipose cells and blood vessels. On immunohistochemical staining, the smooth muscle cells were positive for a melanocytic cell-specific monoclonal antibody. In cases with uncommon features of angiomyolipoma, it is quite difficult to distinguish angiomyolipoma from hepatocellular carcinoma.

A combination treatment of entecavir and early-phase corticosteroid in severe exacerbation of chronic hepatitis B.

Of patients with severe exacerbation of chronic hepatitis B accompanied by jaundice and coagulopathy, 20%-30% have a fatal outcome. In this report, we describe 2 cases of severe exacerbation of chronic hepatitis B with jaundice and coagulopathy who were successfully treated with a combination of entecavir and corticosteroid. In both cases, rapid reductions in serum hepatitis B virus (HBV)-DNA levels were observed, and corticosteroid was stopped after serum HBV-DNA levels became undetectable. Entecavir treatment was continued. Generally, entecavir treatment reduced serum HBV-DNA levels rapidly, although the improvement in liver function was delayed by a few weeks. During this time lag, liver cell injury continued and the disease progressed. Corticosteroid suppressed the excessive host immune response and was useful for stopping progressive deterioration. A combination of entecavir and early-phase corticosteroid may be a useful treatment in severe exacerbation of chronic hepatitis B.