Nationwide and long-term molecular epidemiologic studies of mumps viruses that circulated in Japan between 1986 and 2017.

In Japan, major mumps outbreaks still occur every 4-5 years because of low mumps vaccine coverage (30-40%) owing to the voluntary immunization program. Herein, to prepare for a regular immunization program, we aimed to reveal the nationwide and long-term molecular epidemiological trends of the mumps virus (MuV) in Japan. Additionally, we performed whole-genome sequencing (WGS) using next-generation sequencing to assess results from conventional genotyping using MuV sequences of the small-hydrophobic (SH) gene. We analyzed 1,064 SH gene sequences from mumps clinical samples and MuV isolates collected from 25 prefectures from 1986 to 2017. The results showed that six genotypes, namely B (110), F (1), G (900), H (3), J (41), and L (9) were identified, and the dominant genotypes changed every decade in Japan since the 1980s. Genotype G has been exclusively circulating since the early 2000s. Seven clades were identified for genotype G using SH sequence-based classification. To verify the results, we performed WGS on 77 representative isolates of genotype G using NGS and phylogenetically analyzed them. Five clades were identified with high bootstrap values and designated as Japanese clade (JPC)-1, -2, -3, -4, -5. JPC-1 and -3 accounted for over 80% of the total genotype G isolates (68.3 and 13.8%, respectively). Of these, JPC-2 and -5, were newly identified clades in Japan through this study. This is the first report describing the nationwide and long-term molecular epidemiology of MuV in Japan. The results provide information about Japanese domestic genotypes, which is essential for evaluating the mumps elimination progress in Japan after the forthcoming introduction of the mumps vaccine into Japan's regular immunization program. Furthermore, the study shows that WGS analysis using NGS is more accurate than results obtained from conventional SH sequence-based classification and is a powerful tool for accurate molecular epidemiology studies.

[Case of lymphomatoid gastropathy detected during follow-up after chemoradiotherapy for esophageal cancer].

A man in his 70s underwent chemoradiotherapy for squamous cell carcinoma of the esophagus in 2009. A follow-up gastroendoscopy performed 3 years later revealed a reddish depressed lesion in the greater curvature of the middle stomach body. On the basis of histological and immunohistochemical findings and clinical features, including endoscopic findings, a diagnosis of lymphomatoid gastropathy was made. Follow-up studies revealed a decrease in the size of the lesion and the development of chronic gastritis. Although lymphomatoid gastropathy is rare, recognition of this disease is important because misdiagnosis as lymphoma may lead to unnecessary radical therapeutic procedures.

Genetic analysis of attachment glycoprotein (G) gene in new genotype ON1 of human respiratory syncytial virus detected in Japan.

We studied the evolution of the G gene in the new genotype ON1 of RSV detected from patients with acute respiratory infection in Japan. Phylogenetic analyses and the evolutionary timescale were obtained by the Bayesian MCMC method. We also analyzed p-distance and positive selection sites. A new genotype ON1 emerged around 2001. The evolution rate was rapid (3.57 × 10(-3) substitutions/site per year). The p-distance was short and no positive selection site was found in the present strains. These results suggested that a new genotype ON1 of RSV-A emerged approximately10 years ago and spread to some countries with a high evolution rate.

[A case of duodenal epithelioid hemangioma causing gastrointestinal bleeding].

A case of epithelioid hemangioma of the duodenum causing bleeding was encountered. A 32-year-old man was admitted because of anemia. Endoscopic examination revealed a submucosal tumor with central depression in the 2nd portion of the duodenum. It was considered to be the bleeding focus of anemia. A partial resection of the duodenum was performed. The macro- and microscopic examination of the specimen revealed an epithelioid hemangioma. Hemangiomas of the intestinal tract are rare, representing only 0.3% of all tumors of the intestinal tract, and among them, hemangiomas of the duodenum are extremely rare, representing only 3.4% of those of the intestinal tract. Most hemangiomas of the duodenum are cavernous hemangiomas or capillary hemangiomas. We report the first case of epithelioid hemangioma of the duodenum.

[Detection and subgrouping of respiratory syncytial virus RNA by real-time RT-PCR].

The TaqMan-based quantitative real-time RT-PCR assay we developed uses specific probes to identify respiratory syncytial virus (RSV) and to distinguish RSV subgroups A (RSV-A) and B (RSV-B). We selected conserved regions of the F gene as assay targets and designed new primers and TaqMan MGB probes to detect RSV-A and B. RSV-A and B control plasmids confirmed real-time reverse transcription polymerase chain reaction (RT-PCR) reactivity whose efficiency was 2.5 x 10(1) to 2.5 x 10(7) copies/tube. The assay detection limit was 10 to 10(2) times higher than that of the conventional RT-PCR assay and was equal to the nested PCR assay. No cross-reactions occurred against other respiratory viruses, including influenza virus, metapneumovirus, measles virus, coxsackievirus, enterovirus, echovirus, mumps virus, parainfluenza virus, and rhinovirus. Of 154 clinical specimens derived from subjects with acute respiratory infection and tested by using both real-time RT-PCR and nested PCR, 40 were RSV-positive in both assays. Of these, 25 were identified as RSV-A and 15 as RSV-B by both assays. There was 100% concordance in RSV subgroup identification between real-time RT-PCR and nested PCR assays. These results indicate that our real-time RT-PCR assay can be used for rapid detection, quantitative analysis and subgrouping of RSV-A and RSV-B.

Prospective study on the outcome of patients with hepatocellular carcinoma registered for living donor liver transplantation: how long can they wait?

BACKGROUND.: In countries where cadaveric organ donation is limited, living donor liver transplantation (LDLT) has been reserved as a rescue option for the patients with uncontrollable hepatocellular carcinoma (HCC). PATIENTS AND METHODS.: Between March 2002 and June 2006, 56 patients with HCC had been registered as a LDLT candidate after HCC cannot be treated conventionally. We compared the survival rates between the patients who underwent LDLT (living donor liver transplantation group: LT, n=29) and those who did not undergo LDLT (no transplantation group: NLT, n=27). In the NLT group, we examined the periods suitable for resection or ablation (from first diagnosis to registration), suitable for LDLT, and unsuitable for LDLT. RESULTS.: Even among the patients who did not meet Milan criteria (LT: n=10, NLT: n=16), 1- and 3-year survival rates were significantly higher in the LT group than in the NLT group: 90.0% and 60.0% vs. 75.0% and 8.3%, respectively (P=0.046). In the NLT group, the median periods suitable for resection or ablation, suitable for LDLT, and unsuitable for LDLT were 28.9, 12.2, and 3.5 months, respectively. CONCLUSIONS.: LDLT is acceptable for the patients who gave up the conventional treatment. Approximately 12 months remain for the LDLT candidates with HCC to decide to undergo it.

[Astrovirus RNA detection using real-time reverse transcription-polymerase chain reaction].

The TaqMan-based real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) assay we developed is sensitive and detects seven (1-7) human astrovirus (HAstV) serotypes. We chose conserved regions at the 5' end of the open reading frame2 (ORF2) was chosen at the assay targets for designing new primers and the TaqMan MGB probe that detects all HAstV serotypes. Real-time RT-PCR reactivity was confirmed with HAstV serotype 1 through 7 control plasmids and efficiency ranged from 30 to 3.0 x 10(7)copies/tube. The assay developed detected HAstV sequences from clinical HAstV-positive samples. The assay was 10 to 10(3) times more sensitive than Conventional RT-PCR assay and free of crossreactivity against other enteric viruses, including norovirus, sapovirus, rotavirus, and adenovirus. These results indicate that our real-time RT-PCR assay rapidly detects and quantitatively analyzes HAstV serotype 1 through 7.

Early-stage hepatocellular carcinoma: radiofrequency ablation combined with chemoembolization versus hepatectomy.

PURPOSE: To retrospectively evaluate the long-term results of radiofrequency (RF) ablation combined with chemoembolization (combination therapy) as compared with hepatectomy for the treatment of early-stage hepatocellular carcinoma (HCC). MATERIALS AND METHODS: The study was approved by the institutional review board, and informed consent was waived. Patients with early-stage HCC were included if they underwent either combination therapy or hepatectomy and met the following inclusion criteria: no previous treatment for HCC, three or fewer tumors with a maximum diameter of 3 cm or less each or a single tumor with a maximum diameter of 5 cm or less, Child-Pugh class A liver profile, no vascular invasion, and no extrahepatic metastases. The primary endpoint was overall survival, and the secondary endpoint was recurrence-free survival. RESULTS: One hundred four patients (mean age, 66.5 years +/- 8.7 [standard deviation]; 79 men, 25 women) underwent combination therapy, and 62 patients (mean age, 64.5 years +/- 9.6; 51 men, 11 women) underwent hepatectomy. The 1-, 3-, and 5-year overall survival rates following combination therapy (98%, 94%, and 75%, respectively) were similar (P = .87) to those following hepatectomy (97%, 93%, and 81%, respectively). The 1-, 3-, and 5-year recurrence-free survival rates were also comparable (P = .70) for combination therapy (92%, 64%, and 27%, respectively) and hepatectomy (89%, 69%, and 26%, respectively). CONCLUSION: RF ablation combined with chemoembolization in patients with early-stage HCC provides overall and disease-free survival rates similar to those achieved by hepatectomy.

Survival rates according to the Cancer of the Liver Italian Program scores of 345 hepatocellular carcinoma patients after multimodality treatments during a 10-year period in a retrospective study.

BACKGROUND AND AIM: The Cancer of the Liver Italian Program (CLIP) score has been demonstrated to have superior prognostic ability in hepatocellular carcinoma (HCC) patients worldwide, but there has never been sufficient assessment of the efficacy of treatment modalities according to the CLIP score. This retrospective cohort study of HCC patients was conducted to assess the efficacy of treatment modalities according to the CLIP score. METHODS: We compared the efficacy of hepatic resection (HR) (n = 101), radiofrequency ablation with prior transcatheter arterial chemoembolization (RFA + TACE) (n = 115), percutaneous ethanol injection with prior TACE (PEI + TACE) (n = 43), and TACE (n = 86) as a primary treatment in terms of survival among 345 patients treated at Mie University Hospital between 1995 and 2004, according to CLIP score. RESULTS: The overall survival rates in the RFA + TACE group were significantly higher in the patients with CLIP scores of 1, 2, and 3 or more (5-year, 70.9%; 3-year, 73.7%; and 3-year, 100%, respectively), but they were not significantly different from the 5-year survival rates of the HR group with a CLIP score of 0 (83.7%). Among the patients with a CLIP score of 0, a significantly higher disease-free survival rate (5-year: 33.7%) was obtained in the HR subgroup (n = 35) than in the RFA + TACE subgroup (n = 35), both of which were followed since 2000, but morbidity (21.8%) was highest in the HR group. CONCLUSION: RFA + TACE is concluded to be a safe treatment modality with better overall survival (5-year, > 60%) in HCC patients regardless of their CLIP score.

The role of living-donor liver transplantation in surgical treatment for hepatocellular carcinoma.

BACKGROUND/PURPOSE: The role of living-donor liver transplantation (LDLT) in the surgical treatment of patients with hepatocellular carcinoma (HCC) has not been established as yet. METHODS: Preliminary experience gained from 24 patients who underwent LDLT for HCC between March 2002 and November 2004, and the results of the 131 patients who underwent hepatic resection (HR) for HCC between January 1990 and December 2003 were retrospectively analyzed. The exclusion criteria for LDLT for HCC included extrahepatic metastasis and major vascular invasion. RESULTS: (1) LDLT: the median age of the patients was 57 years and the Child-Pugh grades (A/B/C) of the patients were 6, 12, and 6, respectively. The tumor size was 3 cm or less in 15 patients, multinodular tumors were present in 23 patients, and 11 patients (45.8%) met the Milan Criteria. The overall 2-year survival rate was 72.3%, without a significant difference as to whether or not patients met the Milan criteria. (2) HR: on multivariate analysis, the Child-Pugh grade, the presence of cirrhosis, and the number of tumor nodules were considered as independent risk factors for unfavorable survival (P < 0.05). The 84 patients who met the Milan criteria and were Child-Pugh grade A had a 5-year survival rate of 71.3%; this was significantly better than those of the other patients (P < 0.005). Among the 57 patients with intrahepatic recurrence, 18 patients who were Child-Pugh grade A, met the Milan criteria, and were treated by re-resection or ablation therapy achieved a significantly better 5-year survival rate, of 73.1%, as compared to 19.7% in the other 39 patients (P < 0.0045). CONCLUSIONS: HR could be a first-line treatment with a favorable prognosis for patients who have resectable HCC, preserved liver function, and who meet the Milan criteria. Salvage LDLT could be employed in patients with recurrent tumors that cannot be controlled by conventional treatment or in patients in whom liver function has deteriorated to Child-Pugh grade B or C.

Primary liposarcoma of gallbladder diagnosed by preoperative imagings: a case report and review of literature.

A 49-year-old Japanese woman was referred to our department because of high fever and a huge abdominal mass. Computed tomography (CT) and magnetic resonance (MR) imagings revealed a tumor, about 30 cm in diameter,occupied the right hepatic lobe and the peritoneal cavity. Abdominal angiography showed that the tumor was fed mainly by the cystic artery. We preoperatively diagnosed angiosarcoma of the gallbladder and performed tumor resection with cholecystectomy because the tumor was almost capsulated,however the posterior wall of the gallbladder attached to the tumor firmly. Histologically,the tumor was composed of spindle cells including lipoblasts with cellular pleomorphism, which were also detected in the muscular layer of the gallbladder. We finally diagnosed pleomorphic liposarcoma of the gallbladder. At 10 mo and 29 mo after the first operation, she underwent two more operations because of recurrence. Now she has a good quality of life 3 yr and 6 mo after the first operation.

Donor outcome and liver regeneration after right-lobe graft donation.

Sufficiently detailed information on donor safety and the liver regeneration process following right-lobe living donation has been unavailable, so we evaluated donor outcome and liver regeneration in 13 males and 14 females (39.0 +/- 14.8 years old) who provided 27 right-lobe grafts without the middle hepatic vein. Preoperative total liver volume (TLV), graft volume, and postoperative changes in residual liver volume (RLV) were measured by volumetric computed tomography. Histological steatosis of the liver was graded as none, minimal (< or =10%), and mild (11-30%). The median follow-up period was 337 days. Estimated graft volume and actual graft weight were linearly correlated (Y = 177.85 + 0.795X, R(2) = 0.812, P < 0.0001). Graft-to-recipient weight ratio was 1.08 +/- 0.19%. Four donors had postoperative complications, but they resolved in response to conservative treatment. Postoperative hospital stay was 15.2 +/- 5.5 days. Peak liver enzyme values were significantly higher in donors with mild steatosis (n = 7) than without steatosis (n = 16) (P < 0.05). Donor RLV was 40.8 +/- 6.6% of original TLV at surgery, 79.8 +/- 12.0% by 6 months, and 97.2 +/- 10.8% by 12 months. At 3 months the liver of the older donors (> or =50 years) had grown significantly more slowly than in younger donors (70.4 +/- 9.2% vs. 79.3 +/- 9.6%, P = 0.0391). In conclusion, right hepatectomy without middle hepatic vein of living donors is a safe procedure with acceptable morbidity, and the residual liver regenerated to its preoperative size by 1 year. However, meticulous care should be taken in donors with liver steatosis and aged donors.

Outflow block secondary to stenosis of the inferior vena cava following living-donor liver transplantation?

Although it is well known that outflow block is caused by stenosis or occlusion of hepatic vein anastomoses following living donor liver transplantation (LDLT), there have been few reports on inferior vena cava (IVC) stenosis following LDLT. In this paper, we report two cases of IVC stenosis and hepatic vein outflow block following right hepatic LDLT in the absence of stenosis of any of the anastomoses. Both patients presented with liver dysfunction, an ascitic fluid volume of approximately 2000 mL, and congestion in their biopsy specimens, and venocavography demonstrated IVC stenosis with gradients of more than 10 mmHg in patients with a dominant inferior right hepatic vein (IRHV) anastomosis. After a Gianturco expandable metallic stent successfully implanted in the IVC, the patient's liver function recovered and the volume of ascitic fluid decreased. The pathogenesis of hepatic vein outflow block secondary to IVC stenosis following LDLT may involve the anastomosis with the IRHV, which is the dominant draining vein of the graft and larger than the RHV, caudal to the IVC stenosis and a significant IVC pressure gradient that results in increased IRHV pressure. In conclusion, it is important to include hepatic vein outflow block in the differential diagnosis when patients who have undergone right hepatic LDLT in which anastomosis of the large IRHV has been performed develop manifestations of liver dysfunction.

Using a radial artery as an interpositional vascular graft in a living-donor liver transplantation for hepatocellular carcinoma.

With increasing numbers of living-donor liver transplantations (LDLTs) for hepatocellular carcinoma (HCC), cases with some arterial troubles are encountered; because most HCC cases waiting for LDLT have undergone interventional treatments. In these patients, the reconstruction of the graft artery needs to be planned preoperatively. We report a 52-year-old male, with hepatitis C-related liver cirrhosis and advanced HCC, who for 4 years repeatedly underwent continuous intraarterial chemotherapy through an implanted reservoir port. A suitable artery was not available for arterial reconstruction and the patient underwent LDLT using an autologous radial artery conduit based on the infrarenal aorta. Postoperatively, the patient is well with normal liver function and efficient arterial flow. Autologous radial artery can be safely and successfully used as an aortic-based arterial conduit when HCC patients waiting for LDLT have undergone long-term repeated intraarterial chemotherapy.

Approach to fine-needle aspiration cytology-negative cases of breast cancer.

OBJECTIVE: To clarify the clinical usefulness of fine-needle aspiration (FNA) cytology of breast tumours and the management of FNA cytology-negative cases suspected of or equivocal for malignancy. METHODS: FNA cytology was performed in 94 patients between 1995 and 2002. We calculated the sensitivity, specificity and accuracy of FNA cytology for the diagnosis of malignancy. We also compared clinical and radiological findings between false-negative and true-negative cases. RESULTS: The sensitivity of FNA was 91% (72/79), specificity was 93% (14/15), accuracy was 91% (86/94), positive predictive value was 99% (72/73) and negative predictive value was 67% (14/21). There were seven false-negative cases and one false-positive case. Findings that aroused suspicion of malignancy were more frequent in the false-negative cases, especially from mammography and magnetic resonance imaging (MRI). CONCLUSION: FNA cytology was an accurate preoperative diagnostic procedure for the evaluation of breast masses. In FNA cytology-negative cases, repeated FNA, core needle biopsy or excisional biopsy needs to be performed based on MRI findings.

Laparoscopic spleen-preserving pancreatic tail resection for an intrapancreatic accessory spleen mimicking a nonfunctioning endocrine tumor: report of a case.

Laparoscopic surgery is now performed for several pancreatic disorders, such as benign tumors of the pancreatic body or tail, which are a good indication for laparoscopic resection. However, the risk of pancreatic fistula after distal pancreatectomy, performed laparoscopically or by open surgery, is a topic of debate. We report the case of a 61-year-old man in whom a routine follow-up computed tomography (CT) scan showed a solid, well-defined mass, 1.5 cm in diameter, in the pancreatic tail. The mass was homogeneously enhanced from the early phase to the super-delayed phase on enhanced CT. We suspected a nonfunctioning endocrine tumor of the pancreas, and surgery was performed laparoscopically. After dissecting the pancreatic tail away from the splenic hilum and the splenic vessels, it was resected using only a linear stapler. The histological diagnosis was an intrapancreatic accessory spleen. The patient was discharged on postoperative day 14, but was readmitted 6 days later because of a pancreatic fistula, which was treated by CT-guided percutaneous drainage.

Early graft hemodynamics in living related liver transplantation evaluated by Doppler ultrasonography.

The aim of this study was to clarify the perioperative hemodynamics of liver grafts without vascular complications during and early after liver transplantation from living donors. This study was carried out in 4 child recipients (lateral segment left lobe grafts) and 6 adult recipients (right lobe grafts) of liver transplantation from living donors. The hemodynamics of the hepatic artery, portal vein, and hepatic vein of the grafts during and until 7 days after surgery were studied by Doppler ultrasonography. The maximum flow velocity of the hepatic artery, mean portal blood flow velocity, and pulsatility index (PI) of the hepatic artery increased in all 10 grafts with no vascular complication after vascular anastomosis. After surgery, the mean portal blood flow velocity showed a peak 3 days after surgery and reached a nadir 7 days after surgery in both the lateral segment left lobe grafts in children and the right lobe grafts in adults, but it was significantly higher in the right lobe grafts in adults (mean +/- SD 31.0 +/- 6.3 vs. 22.4 +/- 0.9 cm/sec). Also, as the hepatic artery blood flow velocity increased the portal blood flow velocity decreased, the hepatic blood flow during liver regeneration was suggested to be controlled by both the artery and portal vein. The range of PI of the hepatic artery was 0.60-1.86. The mean hepatic venous blood flow was stable throughout the observation period (30.4 +/- 8.8 cm/sec). Although the hepatic venous flow waves changed widely from pulsed waves to a flat flow, its changes did not suggest a vascular complication. Evaluation of changes by Doppler ultrasonography in the hemodynamics of the liver grafts without vascular complications during and early after liver transplantation from living donors is considered to be useful for accurate monitoring of the hemodynamics during liver regeneration and early detection of abnormalities.