[A rare case of intraductal tumor of the pancreas in which an intraductal tubulopapillary neoplasm was mixed with a widely spreading gastric-type intraductal papillary-mucinous neoplasm].

A 70-year-old man receiving treatment for diabetes mellitus presented with a cystic mass in the border area of the pancreatic body and tail on plain computed tomography (CT) due to impaired glucose intolerance. Contrast-enhanced CT showed a faint hyperattenuated nodular mass extending from the dilated main pancreatic duct (MPD) to the branch duct. Endoscopic retrograde cholangiopancreatography revealed a mildly dilated orifice of the papilla of Vater and MPD stenosis with entire upstream and immediate downstream dilatations. The patient underwent distal pancreatectomy due to the suspicion of mixed-type intraductal papillary-mucinous carcinoma. A pathological examination showed an intraductal solid-nodular mass measuring 25mm in length, consisting of two types of neoplasms. One showed tubulopapillary growth with entirely high-grade (HG) atypical cuboidal epithelium, in which immunohistochemical examinations were positive for MUC6 but negative for human gastric mucin (HGM), MUC1, MUC2, and MUC5AC, fitting the concept of intraductal tubulopapillary neoplasm (ITPN). The other showed the same growth of low-grade (LG) atypical columnar cells positive for HGM and MUC5AC and negative for MUC1 and MUC2, which corresponded to gastric-type intraductal papillary-mucinous neoplasm (IPMN) -LG. The tumor had not invaded the duct walls, and no metastatic lymph nodes were observed. The ITPN was adjacent to the IPMN mainly composed of tubular glands mimicking pyloric glands with LG dysplasia that corresponded to the so-called IPMN-pyloric gland variant. Moreover, the proliferation of low-papillary gastric-type IPMN spread around the intraductal tumors. Consequently, the patient was diagnosed with an intraductal tubular neoplasm comprising a noninvasive ITPN and gastric-type IPMN-LG. ITPN is a recently identified intraductal neoplasm of the pancreas proposed by Yamaguchi et al. and is distinguished by intraductal tubulopapillary growth with HG cellular atypia without overt mucin production, in contrast to IPMN. To date, no cases of intraductal nodular tumors comprising ITPN and IPMN have been reported. We report this original case with imaging and pathological observations and discuss potential processes via which ITPN and IPMN may arise adjacent to each other in the same pancreatic duct.

[Carcinoma in situ arising in adenomyomatous hyperplasia of the ampulla of Vater: the first case report].

A man in his 70s was admitted to our hospital due to jaundice and upper abdominal pain. Laboratory findings indicated elevated serum hepatobiliary enzyme and amylase levels. Contrast-enhanced computed tomography revealed smooth wall thickening of the terminal bile duct (tBD) with a faintly enhanced inner line. ERCP revealed stenosis from the tBD to the ampulla of Vater (AV) with upstream dilatation. Intraductal ultrasound (IDUS) circumferentially revealed a thickened wall preserving a three-layered structure throughout the same region. Furthermore, a thick innermost hyperechoic layer was identified in the bile duct portion of the AV (Ab). Findings suggestive of adenocarcinoma were obtained from the tissue samples from the biliary stricture using biopsy forceps. Thus, pancreatoduodenectomy was performed. A pathological examination revealed a thickened AV wall spreading over the tBD with hyperplasia of the glands and smooth muscle fibers. In addition, low-grade biliary intraepithelial neoplasia (BilIN) was scattered throughout the lesion, and high-grade BilIN was partly observed in the peribiliary glands of the Ab. Based on these results, a diagnosis of carcinoma in situ arising in adenomyomatous hyperplasia (ADMH) of the AV was made. To date, there are no reports on ADMH-associated carcinoma of the BD or AV. We here report this original case with the IDUS findings, which are presumed to reflect the histologic features of ADMH showing ductal proliferation surrounded by smooth muscle fibers. Also, we discuss the process through which carcinoma arises from ADMH in AV.

Acute liver failure due to severe Herpes simplex viral hepatitis in an elderly woman: A case of initial infection.

The high mortality rate due to severe Herpes simplex viral (HSV) hepatitis is associated with the difficulty of its diagnosis. We describe the extremely rapid disease course of a patient who died of severe HSV hepatitis. A 73-year-old woman was admitted for a bronchial asthma attack. Her symptoms improved with steroid treatment, but she developed a sore throat and painful swallowing. On day 12 after admission, she suddenly went into shock. Blood test results showed a significant increase in the liver enzyme levels, with remarkable disseminated intravascular coagulation. She died the same day. The autopsy revealed extensive coagulative necrosis of the liver. Viral inclusion of type A Cowdry bodies was found in the residual hepatocytes in the hepatic lobule. Immunostaining revealed HSV type 1 positivity. We diagnosed the cause of death as severe HSV hepatitis. On examination of a stored serum sample, the patient tested positive for the HSV immunoglobulin (Ig)-M antibody, and the HSV RNA level was very high (1 × 109 copies/mL). Remarkably, the HSV IgG test result was negative, and we diagnosed her as having had an initial HSV infection. Hepatitis due to HSV is very rare in healthy adults; however, there are many reports of immune-deficient cases. The presence of HSV IgG is decreasing in the elderly population because of the change in living environments/lifestyles. The increasing use of immunosuppressive drugs, such as steroids, for treating diseases in elderly patients could be linked to the increased prevalence of initial HSV infections, resulting in liver injury.

[Rupture of a pancreaticoduodenal artery aneurysm into the common bile duct secondary to chronic pancreatitis: a case report].

A 57-year-old man with a history of excessive drinking presented to our emergency department complaining of chest discomfort. He had been attending a clinic for diabetes mellitus and hypertension, at which he had been informed that he had anemia that was worsening. Computed tomography (CT) of the abdomen revealed hemobilia and chronic pancreatitis. Due to complicated cholangitis, endoscopic nasobiliary drainage was performed, and a contrast-enhanced abdominal CT scan showed a pancreaticoduodenal aneurysm close to the common bile duct. We diagnosed a ruptured pancreaticoduodenal artery aneurysm causing hemobilia, and performed selective transcatheter arterial embolization with intravascular microcoils. Complete occlusion of the aneurysm was confirmed on follow-up CT.

[Multiple gastrointestinal stromal tumors during nilotinib treatment for chronic myelogenous leukemia in a patient with neurofibromatosis type 1].

A 60-year-old woman with neurofibromatosis type 1 presented to our hospital with melena. She reported a 1-year history of treatment with nilotinib hydrochloride hydrate for chronic myelogenous leukemia. Contrast-enhanced abdominal computed tomography revealed multiple intestinal tumors that were subsequently diagnosed as gastrointestinal stromal tumors (GIST) using single-balloon enteroscopy. Although the tumors showed no significant change over 1 year, partial jejunal resection was performed to confirm the diagnosis. Immunohistochemically, the tumors were GIST.

Prognostic impact of clinical outcome after endoscopic gastroduodenal stent placement for malignant gastric outlet obstruction: a multicenter retrospective cohort study using a time-dependent analysis.

Background: Endoscopic gastroduodenal stent (GDS) placement is widely used as a safe and effective method to rapidly improve gastrointestinal symptoms of malignant gastric outlet obstruction (MGOO). While previous studies reported the utility of chemotherapy after GDS placement for prognosis improvement, they did not fully address the issue of immortal time bias. Objectives: To examine the association between prognosis and clinical course following endoscopic GDS placement, using a time-dependent analysis. Design: Multicenter retrospective cohort study. Methods: This study included 216 MGOO patients who underwent GDS placement between April 2010 and August 2020. Data of patient baseline characteristics, including age, gender, cancer type, performance status (PS), GDS type and length, GDS placement location, gastric outlet obstruction scoring system (GOOSS) score, and history of chemotherapy before GDS were collected. The clinical course following GDS placement was evaluated by GOOSS score, stent dysfunction, cholangitis, and chemotherapy. A Cox proportional hazards model was used to identify prognostic factors after GDS placement. Stent dysfunction, post-stent cholangitis, and post-stent chemotherapy were analyzed as time-dependent covariates. Results: Mean GOOSS scores before and after GDS were 0.7 and 2.4, respectively, with significant improvement after GDS placement (p < 0.001). The median survival time after GDS placement was 79 [95% confidence interval (CI): 68-103] days. In multivariate Cox proportional hazards model with time-dependent covariates, PS 0-1 [hazard ratio (HR): 0.55, 95% CI: 0.40-0.75; p < 0.001], ascites (HR: 1.45, 95% CI: 1.04-2.01; p = 0.028), metastasis (HR: 1.84, 95% CI: 1.31-2.58; p < 0.001), post-stent cholangitis (HR: 2.38, 95% CI: 1.37-4.15; p = 0.002), and post-stent chemotherapy (HR: 0.01, 95% CI: 0.002-0.10; p < 0.001) significantly affected prognosis after GDS placement. Conclusion: Post-stent cholangitis and tolerability to receive chemotherapy after GDS placement influenced prognosis in MGOO patients.

Mucosal color changes on narrow-band imaging in esophageal eosinophilic infiltration.

This study aimed to examine the range of beige colored mucosa (BCM) in patients with esophageal eosinophilic infiltration (EEI) using narrow-band imaging (NBI). In this retrospective study, EEI was confirmed histologically in 12 consecutive patients from January 2014 to December 2017. The BCM tone on NBI without magnifying endoscopy was evaluated, and red, green, and blue (RGB) values of BCM and normal mucosa were measured. BCM was macroscopically classified into 2 groups (bright and dark) using cluster analysis. Histopathological analysis was performed in 1 patient who underwent biopsy for both normal mucosa and BCM. All 12 patients presented with BCM. Endoscopy revealed fixed rings, longitudinal furrows, mucosal edema, and exudate in 3, 12, 10, and 8 patients, respectively. Strictures were absent. Five patients had findings suggestive of gastroesophageal reflux disease. In the cluster analysis, 5 and 7 patients had bright and dark BCM, respectively. Consistent results were noted when we categorized patients according to their macroscopic characteristics. RGB values of the BCM and normal mucosa were measured-normal mucosa: R: 99.8 ± 16.5, G: 121.7 ± 23.1, and B: 93.4 ± 19.2; BCM: R: 152.0 ± 31.3, G: 123.9 ± 35.0, and B: 97.5 ± 29.5. BCM had significantly higher R values than normal mucosa (P = .0001). All parameters were significantly lower in the dark BCM group than in the bright BCM group (P < .001). Histopathological analysis revealed expansion of the epithelial intercellular space, eosinophilic infiltration, and basal cell hyperplasia at the BCM sites. BCM was observed in all cases of EEI. RGB values differed between bright and dark BCM. Assessing BCM tone using NBI is a potentially novel diagnostic method for EEI.

Solitary extrahepatic hepatocellular carcinoma in vertebrae without a primary lesion in the liver might originate from bone marrow: a case report and new hypothesis based on a review of the literature and the latest findings.

Solitary extrahepatic hepatocellular carcinoma without a primary lesion in the liver is rare and unique. In such patients, in addition to hepatocellular carcinoma, hepatoid adenocarcinoma, hepatoid teratoma, and hepatoid yolk sac tumor must be considered as differential diagnoses, and patients must be investigated in detail by histopathological studies with immunohistochemistry, especially using epithelial markers for which tumor cells are generally negative in hepatocellular carcinoma. A case with a solitary neoplasm of the vertebrae, which was diagnosed histopathologically as hepatocellular carcinoma, without a primary lesion is presented. The primary lesion was not identified even on autopsy, and the liver was pathologically almost normal. Given the review of the literature and circumstantial evidence, we would like to propose a bold new hypothesis that hepatocellular carcinoma might primarily originate from bone marrow.

Image quality of abdominal ultrasonography after esophagogastroduodenoscopy is preserved by using carbon dioxide insufflation: A non-inferiority test in the same subject.

Because bowel gas deteriorates the image quality of abdominal ultrasonography (AUS), it is common to perform AUS prior to esophagogastroduodenoscopy (EGD). This one-way order limits the availability of examination appointments. To evaluate whether EGD using insufflation of carbon dioxide (CO2), which is rapidly absorbed by the gastrointestinal mucosa, preserves the image quality of AUS performed subsequently, we designed a non-inferiority test in which each subject underwent AUS, EGD with CO2 insufflation, and a second AUS, in that order. All saved AUS moving images were randomized and imaging quality was evaluated at 16 organs using a four-point Likert-like scale that divides the depiction rate by 25%. Sample size was calculated to be 26 using the following: non-inferiority margin of -0.40 corresponding to depiction rate of -10%, difference of means of 0.40, common standard deviation of 1.25, power of 90%, and 1-sided α-level of 0.025. We enrolled 30 subjects. The mean and 95% confidence interval (CI) of the image quality score of all 16 organs at pre- and post-EGD AUS in the 30 subjects were 3.54 [3.48-3.60] and 3.46 [3.39-3.52], respectively. The difference in the means was 0.08 of the scores, corresponding to a 2% depiction rate. The effect size was 0.172. The image quality of post-EGD AUS was not inferior, as demonstrated by the 97.5% CI of the difference, which did not cross the non-inferiority margin of -0.40. In conclusion, the use of CO2 for insufflation in EGD does not cause much deterioration in the image quality of AUS performed subsequently. Therefore, it is permissible to perform EGD prior to AUS, which is expected to improve the efficiency of examination setup.

Comprehensive gene expression analysis of 5'-end of mRNA identified novel intronic transcripts associated with hepatocellular carcinoma.

To elucidate the molecular feature of human hepatocellular carcinoma (HCC), we performed 5'-end serial analysis of gene expression (5'SAGE), which allows genome-wide identification of transcription start sites in addition to quantification of mRNA transcripts. Three 5'SAGE libraries were generated from normal human liver (NL), non-B, non-C HCC tumor (T), and background non-tumor tissues (NT). We obtained 226,834 tags from these libraries and mapped them to the genomic sequences of a total of 8,410 genes using RefSeq database. We identified several novel transcripts specifically expressed in HCC including those mapped to the intronic regions. Among them, we confirmed the transcripts initiated from the introns of a gene encoding acyl-coenzyme A oxidase 2 (ACOX2). The expression of these transcript variants were up-regulated in HCC and showed a different pattern compared with that of ordinary ACOX2 mRNA. The present results indicate that the transcription initiation of a subset of genes may be distinctively altered in HCC, which may suggest the utility of intronic RNAs as surrogate tumor markers.

Long-term outcomes after endoscopic retrograde pancreatic drainage for symptomatic pancreaticojejunal anastomotic stenosis.

There is limited evidence supporting the usefulness of endoscopic retrograde pancreatic drainage (ERPD) for symptomatic pancreaticojejunal anastomotic stenosis (sPJS). We examined the usefulness of ERPD for sPJS. We conducted a retrospective analysis of 10 benign sPJS patients. A forward-viewing endoscope was used in all sessions. Following items were evaluated: technical success, adverse events, and clinical outcome of ERPD. The technical success rate was 100% (10/10) in initial ERPD; 9 patients had a pancreatic stent (no-internal-flap: n = 4, internal-flap: n = 5). The median follow-up was 920 days. Four patients developed recurrence. Among them, 3 had a stent with no-internal-flap in initial ERPD, the stent migrated in 3 at recurrence, and a stent was not placed in 1 patient in initial ERPD. Four follow-up interventions were performed. No recurrence was observed in 6 patients. None of the stents migrated (no-internal-flap: n = 1, internal-flap: n = 5) and no stents were replaced due to stent failure. Stenting with no-internal-flap was associated with recurrence (p = 0.042). Mild adverse events developed in 14.3% (2/14). In conclusions, ERPD was performed safely with high technical success. Recurrence was common after stenting with no-internal-flap. Long-term stenting did not result in stent failure.Clinical trial register and their clinical registration number: Nos. 58-115 and R2-9.

More than half of hypoxemia cases occurred during the recovery period after completion of esophagogastroduodenoscopy with planned moderate sedation.

Guidelines advise precautionary measures for possible adverse events that may occur due to sedation during endoscopic procedures. To avoid complications, intraprocedural and postprocedural monitoring during recovery is considered important. However, since not many studies have reported on hypoxemia during the recovery period, findings for specific monitoring methods are insufficient. The aim of this retrospective study was to determine the incidence of hypoxemia during the recovery period using continuous central-monitoring by pulse oximetry and to characterize the hypoxemia cases. Among the 4065 consecutive esophagogastroduodenoscopy (EGD) procedures under planned moderate sedation, 84 (2.1%) procedures developed unexpected hypoxemia (SpO2 ≤ 90%). Hypoxemia was observed during the procedure, at the end of the procedure, and during the recovery period in 21, 17, and 46 (1.1%) procedures, respectively. More than half of the hypoxemia cases occurred during the recovery period. Many hypoxemia cases were characterized by neither serious co-morbid illness nor low body mass index which have been reported as risk factors of hypoxemia. The lack of risk factors is no guarantee that hypoxemia will not occur. Therefore, continuous monitoring by pulse oximetry is more important during the recovery period and is recommended in all EGD procedures under planned moderate sedation.

Tumor lysis syndrome in a patient with metastatic melanoma treated with nivolumab.

A 79-year-old man with metastatic melanoma of the right maxillary sinus and multiple liver metastases received a single dose of nivolumab. Eight days later, he experienced impaired consciousness, accompanied by abnormal laboratory and electrocardiographic findings. He was therefore diagnosed with tumor lysis syndrome (TLS). Laboratory and electrocardiographic findings improved immediately after continuous hemodiafiltration; however, he died 22 days after receiving nivolumab. Autopsy revealed massive tumor necrosis in the liver. There are few case reports of TLS associated with immune checkpoint inhibitors, indicating that we should be prepared to manage especially in a patient with liver involvement of high tumor burden.

Association of interleukin-28B genotype and hepatocellular carcinoma recurrence in patients with chronic hepatitis C.

PURPOSE: Several single-nucleotide polymorphisms (SNP) in the interleukin-28B (IL-28B) locus have recently been shown to be associated with antiviral treatment efficacy for chronic hepatitis C (CHC). However, such an association with hepatocellular carcinoma (HCC) is unkno3 we investigated the association between the IL-28B genotype and the biology and clinical outcome of patients with HCC receiving curative treatment. EXPERIMENTAL DESIGN: Genotyping of 183 patients with HCC with CHC who were treated with hepatic resection or radiofrequency ablation (RFA) was carried out, and the results were analyzed to determine the association between the IL-28B genotype (rs8099917) and clinical outcome. Gene expression profiles of 20 patients with HCC and another series of 91 patients with CHC were analyzed using microarray analysis and gene set enrichment analysis. Histologic and immunohistochemical analyses were also conducted. RESULTS: The TT, TG, and GG proportions of the rs8099917 genotype were 67.8% (124 of 183), 30.6% (56 of 183), and 1.6% (3 of 183), respectively. Multivariate Cox proportional hazard analysis showed that the IL-28B TT genotype was significantly associated with HCC recurrence (P = 0.007; HR, 2.674; 95% confidence interval, 1.16-2.63). Microarray analysis showed high expression levels of IFN-stimulated genes in background liver samples and immune-related genes in tumor tissues of the IL-28B TG/GG genotype. Histologic findings showed that more lymphocytes infiltrated into tumor tissues in the TG/GG genotype. CONCLUSIONS: The IL-28B genotype is associated with HCC recurrence, gene expression, and histologic findings in patients with CHC.