Comparison of the specimen quality of endobronchial ultrasound-guided intranodal forceps biopsy using standard-sized forceps versus mini forceps for lung cancer: A prospective study.

BACKGROUND AND OBJECTIVE: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a diagnostic procedure with adequate performance; however, its ability to provide specimens of sufficient quality and quantity for treatment decision-making in advanced-stage lung cancer may be limited, primarily due to blood contamination. The use of a 0.96-mm miniforceps biopsy (MFB) permits true histological sampling, but the resulting small specimens are unsuitable for the intended applications. Therefore, we introduced a 1.9-mm standard-sized forceps biopsy (SFB) and compared its utility to that of MFB. METHODS: We prospectively enrolled patients from three institutions who presented with hilar/mediastinal lymphadenopathy and suspected advanced-stage lung cancer, or those who were already diagnosed but required additional tissue specimens for biomarker analysis. Each patient underwent MFB followed by SFB three or four times through the tract created by TBNA using a 22-gauge needle on the same lymph node (LN). Two pathologists assessed the quality and size of each specimen using a virtual slide system, and diagnostic performance was compared between the MFB and SFB groups. RESULTS: Among the 60 enrolled patients, 70.0% were diagnosed with adenocarcinoma. The most frequently targeted sites were the lower paratracheal LNs, followed by the interlobar LNs. The diagnostic yields of TBNA, MFB and SFB were 91.7%, 93.3% and 96.7%, respectively. The sampling rate of high-quality specimens was significantly higher in the SFB group. Moreover, the mean specimen size for SFB was three times larger than for MFB. CONCLUSION: SFB is useful for obtaining sufficient qualitative and quantitative specimens.

Impact of long-term optimizing atrioventricular delay using device-based algorithms on cardiac resynchronization therapy.

Sub-optimal atrioventricular delay (AVD) is one of the main causes of non-responder for cardiac resynchronization therapy (CRT). Recently, device-based algorithms (DBAs) that provide optimal AVD based on intracardiac electrograms, have been developed. However, their long-term effectiveness is still unknown. This study aims to investigate the effect of optimizing AVD using DBAs over a long period, on the prognosis of patients undergoing CRT. A total of 118 patients who underwent CRT at our hospital between April 2008 and March 2018, were retrospectively reviewed; 61 of them with optimizing AVD using DBAs were classified into the treated group (group 1), and the remaining 57 were classified into the control group (group 2). The median follow-up period was 46.0 months. The responder and survival rate in group 1 were significantly better than those in group 2 (group 1 vs. group 2: responder rate = 64% vs. 46%, p = 0.046; survival rate: 85.2% vs. 64.9%, p = 0.02). Moreover, investigating only the non-responder population showed that group 1 had an improved survival rate compared to group 2 (group 1 vs. group 2 = 72.7% vs. 45.1%, p = 0.02). Optimizing AVD using DBAs was a significant contributor to the improved survival rate in CRT non-responders in multivariate analysis (HR 3.6, p = 0.01). In conclusion, the long-term optimizing AVD using DBAs improved the survival rate in CRT and the prognosis of CRT non-responders, as well.

Sinusoidal obstruction syndrome associated with disseminated toxoplasmosis involving the liver after allogeneic hematopoietic stem cell transplantation: A case report.

Sinusoidal obstruction syndrome (SOS) is a fatal complication after hematopoietic stem cell transplantation (HSCT). Only a few complications after HSCT have been reported as risk factors for SOS, including sepsis. Here, we report the case of a 35-year-old male diagnosed with Philadelphia chromosome-positive acute lymphoblastic leukemia who underwent peripheral blood HSCT from a human leukocyte antigen-matched unrelated female donor in remission. Graft-versus-host disease prophylaxis contained tacrolimus, methotrexate, and low-dose anti-thymoglobulin. The patient was treated with methylprednisolone for engraftment syndrome from day 22. On day 53, he presented worsening fatigue, breathlessness, and abdominal pain in the right upper quadrant that had persisted for 4 days. Laboratory tests showed severe inflammation, liver dysfunction, and positive for Toxoplasma gondii PCR. He died on day 55. An autopsy showed SOS and disseminated toxoplasmosis. Hepatic infection with T. gondii was identified in zone 3 of the liver, which overlapped with the pathological features of SOS. In addition, the timing of the exacerbation of hepatic dysfunction coincided with the onset of systemic inflammatory symptoms and T. gondii reactivation. This rare case of toxoplasmosis is the first to suggest that hepatic infection with T. gondii is strongly associated with SOS after HSCT.

Transvenous lead performance of implantable cardioverter-defibrillators and pacemakers.

BACKGROUND: After the reports of recalled leads, several technological improvements have been introduced and the durability of implantable cardioverter defibrillator (ICD) leads has improved. The incidence of lead failures is now less than in the previous studies. However, there are few reports that have shown the long-term durability of ICD leads as compared to pacemaker (PM) leads. This study analyzed the medium to long-term performance of transvenous ICD leads as compared to PM leads. METHODS: We retrospectively studied 1227 cases from April 2007 to December 2017 who underwent an initial transvenous ICD or PM implantation. The number of lead failures and patient background characteristics were analyzed. RESULTS: During a median 3-3.5 years follow up period, 1 (0.3%) ICD lead and 18 (2.4%) PM leads failed. The incidence of lead failures was significantly higher in the PM group than ICD group (p = .019). Males were associated with a higher incidence of lead failures in the PM group. CONCLUSION: Since the era of recalled ICD leads, the durability of ICD leads has remarkably improved and the incidence of lead failures with non-recalled ICD leads has been less than that for PM leads.

Diploid genome differentiation conferred by RNA sequencing-based survey of genome-wide polymorphisms throughout homoeologous loci in Triticum and Aegilops.

BACKGROUND: Triticum and Aegilops diploid species have morphological and genetic diversity and are crucial genetic resources for wheat breeding. According to the chromosomal pairing-affinity of these species, their genome nomenclatures have been defined. However, evaluations of genome differentiation based on genome-wide nucleotide variations are still limited, especially in the three genomes of the genus Aegilops: Ae. caudata L. (CC genome), Ae. comosa Sibth. et Sm. (MM genome), and Ae. uniaristata Vis. (NN genome). To reveal the genome differentiation of these diploid species, we first performed RNA-seq-based polymorphic analyses for C, M, and N genomes, and then expanded the analysis to include the 12 diploid species of Triticum and Aegilops. RESULTS: Genetic divergence of the exon regions throughout the entire chromosomes in the M and N genomes was larger than that between A- and Am-genomes. Ae. caudata had the second highest genetic diversity following Ae. speltoides, the putative B genome donor of common wheat. In the phylogenetic trees derived from the nuclear and chloroplast genome-wide polymorphism data, the C, D, M, N, U, and S genome species were connected with short internal branches, suggesting that these diploid species emerged during a relatively short period in the evolutionary process. The highly consistent nuclear and chloroplast phylogenetic topologies indicated that nuclear and chloroplast genomes of the diploid Triticum and Aegilops species coevolved after their diversification into each genome, accounting for most of the genome differentiation among the diploid species. CONCLUSIONS: RNA-sequencing-based analyses successfully evaluated genome differentiation among the diploid Triticum and Aegilops species and supported the chromosome-pairing-based genome nomenclature system, except for the position of Ae. speltoides. Phylogenomic and epigenetic analyses of intergenic and centromeric regions could be essential for clarifying the mechanisms behind this inconsistency.

Novel mutation identified in Leber congenital amaurosis - a case report.

BACKGROUND: Leber congenital amaurosis (LCA) is the earliest onset and the most severe form of all inherited retinal degenerative disorders, characterized by blindness, or severe visual impairment from birth, and typically exhibits clinical and genetic heterogeneity. Recently, 14 causative genes of LCA were reported. We performed whole-exome sequencing (WES) for Japanese siblings, and identified a novel homozygous nonsense mutation in the RPGR-interacting protein 1 (RPGRIP1) gene. We also report their follow-up data over 27 years. CASE PRESENTATION: Patient 1 is a 37-year-old male. In 1992, his eye position indicated orthophoria, however, horizontal nystagmus was evident, and he complained of photophobia. His best corrected decimal visual acuity (BCVA) was 0.2 (S + 6.5/C-3.5/170°) OD and 0.1 (S + 6.0/C-2.5/10°) OS. Fundus examination revealed bisymmetrical inferior focal retinal pigment epithelium (RPE) mottling. Bright-flash electroretinogram (ERG) revealed a subnormal pattern, while 30 Hz flicker ERG was non-recordable in both eyes. At his final visit in 2019, his BCVA was 0.09 (S + 3.5/C-3.5/180°) OD and 0.09 (S + 3.0/C-4.0/10°) OS. Patient 2, a 34-year-old female, is the sibling of patient 1. In 1992, her BCVA was 0.05 (S + 6.0) OD and 0.06 (S + 5.0) OS. She was in a chin-up position during visual acuity testing. Horizontal nystagmus was evident, and she also complained of photophobia. Bright-flash ERG was severely attenuated, and 30 Hz flicker ERG was non-recordable in both eyes. At her final visit in 2019, her BCVA was 0.02 (uncorrectable) OD and 0.03 (uncorrectable) OS. There were no other patients with LCA in their family and their parents were non-consanguineous. WES revealed a homozygous, consecutive, two-nucleotide variation in the RPGRIP1 gene (NM_020366: exon15:c.G2294A and c.C2295A, p.C765X), resulting in a premature stop codon. We interpreted this variation as a novel pathogenic mutation of RPGRIP1 that contributes to LCA6 development. CONCLUSIONS: Herein, we report a novel nonsense mutation of RPGRIP1 in two patients with LCA6 and present their long-term follow-up data. These clinical data linked to genotypes provide important information for the development of new treatments, such as gene therapy, as well as for genetic counseling.

Myopotential Oversensing Is a Major Cause of Inappropriate Shock in Subcutaneous Implantable Defibrillator in Japan.

Previous study has identified marked differences in patient characteristics and causes of inappropriate shock (IAS) between Japan and the Western societies in terms of subcutaneous implantable cardioverter-defibrillator (S-ICD). However, evidence of IAS in Asian populations including Japan has been limited to one observational study.Thus, we conducted a single-center registry study that tracks the postoperative course of 61 consecutive patients who received S-ICD from February 2016 to January 2020. Our findings showed that IAS occurred in 9.8% of the study population (6/61), which is comparable to the previously reported incidence. Remarkably, T-wave oversensing did not result in an IAS (0/6). Instead, myopotential oversensing was determined to have caused the most IAS events (4/6), while atrial fibrillation ranked second (2/6). A provocation maneuver (e.g., abdominal clench, push-ups, lifting a heavy item) reproduced myopotential noise disguised as R-waves, which should potentially trigger an IAS if uninterrupted. R-wave amplitude of the IAS group appeared relatively low compared to that of the non-IAS group although this finding was not tested significant. Furthermore, no temporal changes were noted in R-wave amplitude between the time of implantation and IAS events, suggesting that it is neither constantly low nor acutely dropped R-wave amplitude but a relatively high noise level that drives IAS. All the myopotential-IAS patients were found to be male. Right-sided lead implantation was associated with a higher incidence of IAS.This study highlights the fact that IAS continues to occur due to myopotential noise oversensing instead of T-wave oversensing. To minimize the risk of IAS, it is desirable to search and secure high R-wave voltage.

Percutaneous Simple Lead Traction Is a Feasible and Effective Method for Right Ventricular Lead Perforations.

Right ventricular (RV) lead perforations are relatively rare but a potentially life-threatening complication of surgical implantations of cardiac implantable electronic devices (CIEDs). The result of percutaneous simple lead traction after lead perforations in the Japanese population has not been well clarified.We retrospectively studied 1359 patients (pacemakers [PMs], 973 patients; implantable cardioverter defibrillators [ICD], 386 patients) from April 2007 to December 2018 who underwent initial CIED implantation. Fifteen patients (1.1%) were diagnosed with RV lead perforations. The clinical data were evaluated in those patients, and the baseline characteristics and echocardiographic data were compared between the lead perforation group and the non-perforation group. The success and complication rates of the simple traction and repositioning of the RV lead were also assessed.The number of perforated RV leads was seven ICD leads (1.8%) and eight PM leads (0.82%). They were diagnosed on a median seven days (5.5-36.0) after the CIED implantation. Twelve patients were asymptomatic but were detected by an increased capture threshold. Three patients had pericarditis and stimulation of the diaphragm. Only one patient in the ICD lead group who took anticoagulants had a cardiac tamponade and needed an urgent pericardiocentesis (0.07%). No one required a thoracotomy or other devices related to complications after repositioning the RV lead. There was no significant difference in the baseline characteristics and echocardiographic parameters between the groups.RV lead perforations were relatively rare complications of CIED implantations. Percutaneous simple lead traction and repositioning the perforated lead was feasible and effective if the patients did not receive anticoagulants.

[Pulmonary infiltration of acute monoblastic leukemia diagnosed by transbronchial lung biopsy].

A 65-year-old woman was urgently admitted to our hospital for antibiotic-resistant fever, hypoxemia, and hyperleukocytosis and was diagnosed with acute monoblastic leukemia. Chest computed tomography revealed interlobular septal thickening, central ground-glass opacity, and a nodular shadow in the left lower lobe. Although several treatments for infectious disease and acute heart failure were administered, they were less effective. Transbronchial lung biopsy was performed on day 7 of hospitalization, and subsequently, pulmonary leukemic infiltration was confirmed. Based on the diagnosis, we decided to start intensive chemotherapy. Consequently, the abnormal lung shadow on computed tomography vanished, and complete hematological remission was achieved. Although acute myeloid leukemia is frequently associated with lung infiltration during onset, it is often difficult to distinguish it from other pulmonary complications. In clinical practice, intensive chemotherapy is often initiated based on the clinical evaluation without pathological confirmation of the lung disease. Our patient was accurately diagnosed based on the pulmonary leukemic infiltration observed pathologically and recovered well. Here we report our case along with a discussion of the relevant literature.

Analysis of the heart rate variability during cryoballoon ablation of atrial fibrillation.

Aims: Vagal responses such as marked bradycardia or a rapid blood pressure decrease are often observed during pulmonary vein (PV) isolation of atrial fibrillation (AF) using a cryoballoon (CB). However, the relationship between the marked vagal response and change in the heart rate variability (HRV) as a marker of the autonomic tone is not well understood. Methods and results: Fifty-four paroxysmal AF patients underwent CB ablation. The CB ablation was started from the right sided PVs in 25 patients (R group) and left sided PVs in 29 (L group). The HRV and haemodynamic status during the procedure were analysed. A vagal response was observed in 16 L group patients (61.5%) during the ablation of the different PVs (RSPV:1, RIPV:5, LSPV:15, LIPV:5), while it was observed in only 2 R group patients (9.5%) (RSPV:0, RIPV:0, LSPV:1, LIPV:1) (P = 0.0002). The HRV in the L group was significantly higher than that in the R group just after the CB ablation especially for the left sided PVs (L group vs. R group, total power of the HRV, median; RSPV, 11184.7 vs. 4360.0, P = 0.21; RIPV, 9044.3 vs. 2115.1, P = 0.01; LSPV, 21186.0 vs. 1314.2, P = 0.0002; LIPV 10265.9 vs. 1236.2, P = 0.0007). Conclusion: A marked increase in the HRV parameters was observed just after the CB ablation. An initial CB ablation of the right PVs decreased the change in the autonomic tone during the right PV ablation and subsequent left PV ablation. It prevented an excessive vagal response during the CB ablation and might be a safe procedure.

Regulation of endothelial Fas expression as a mechanism of promotion of vascular integrity by mural cells in tumors.

Angiogenesis is a multi-step process that culminates in vascular maturation whereby nascent vessels stabilize to become functional, and mural cells play an essential role in this process. Recent studies have shown that mural cells in tumors also promote and maintain vascular integrity, with wide-reaching clinical implications including the regulation of tumor growth, metastases, and drug delivery. Various regulatory signaling pathways have been hitherto implicated, but whether regulation of Fas-dependent apoptotic mechanisms is involved has not yet been fully investigated. We first compared endothelial FAS staining in human pancreatic ductal adenocarcinomas and colon carcinomas and show that the latter, characterized by lower mural cell coverage of tumor vasculature, demonstrated higher expression of FAS than the former. Next, in an in vitro coculture system of MS-1 and 10T1/2 cells as endothelial and mural cells respectively, we show that mural cells decreased endothelial Fas expression. Then, in an in vivo model in which C26 colon carcinoma cells were inoculated together with MS-1 cells alone or with the further addition of 10T1/2 cells, we demonstrate that mural cells prevented hemorrhage. Finally, knockdown of endothelial Fas sufficiently recapitulated the protection against hemorrhage seen with the addition of mural cells. These results together suggest that regulation of endothelial Fas signaling is involved in the promotion of vascular integrity by mural cells in tumors.

Schwannoma-like tumor in the anterior cranial fossa immunonegative for Leu7 but immunopositive for Schwann/2E.

Schwannoma arising from the olfactory system, often called olfactory groove schwannoma (OGS), is rare, as the olfactory bulb and tract, belonging to the central nervous system, should lack Schwann cells. Another rare entity called olfactory ensheathing cell tumor (OECT) has been reported, which mimics clinical and radiological characteristics of OGS. Here, we report two rare cases of schwannoma-like tumor in the anterior cranial fossa that showed negative staining for Leu7, but positive staining for Schwann/2E, and discuss their origin. Two cases of mass lesions in the anterior cranial fossa in a 26-year-old man and a 24-year-old woman were successfully removed. Morphological examination of these tumors was compatible with a diagnosis of schwannoma. Immunohistochemically, both cases were negative for Leu7, yielding a diagnosis of OECT, but were positive for the schwannoma-specific marker, Schwann/2E. Immunohistochemical staining results in our two cases question the current assumption that OGS and OECT can be distinguished only by Leu7 staining pattern. In conclusion, the origins of OGS and OECT remain to be determined, and further studies in larger numbers of cases are needed to characterize these rare tumors in the anterior cranial fossa.

The association between non-alcoholic steatohepatitis and intrahepatic cholangiocarcinoma: A hospital based case-control study.

BACKGROUND: This study aimed to investigate the association between non-alcoholic steatohepatitis (NASH) and intrahepatic cholangiocarcinoma (ICC). METHODS: This was a case control study of patients who underwent surgical resection either for ICC or for a metastatic liver tumor (the control group). We assessed their clinical characteristics, pathological findings, and the prevalence of known ICC risk factors. For patients without known risk factors, we compared other factors including the prevalence of NASH. RESULTS: In the patients without known risk factors, 15 of 34 patients in the ICC group and 13 of 69 patients in the control group were diagnosed with NASH. Univariate analysis showed significantly higher values in the ICC group for age (P = 0.0478), prevalence of obesity (P = 0.0365) and NASH (P = 0.0078), and serum levels of albumin (P = 0.0051), and gamma-glutamyl transpeptidase (γ-GTP) (P = 0.0006) compared with the control group. Multivariate analysis showed that age and serum levels of γ-GTP and NASH were independent risk factors for ICC. In patients with NASH, the proportion of patients with hepatic fibrosis was significantly higher in the ICC group than in the control group (P = 0.0014). CONCLUSION: NASH is a possible risk factor for ICC development. J. Surg. Oncol. 2016;113:779-783. © 2016 Wiley Periodicals, Inc.

Systemically Injectable Enzyme-Loaded Polyion Complex Vesicles as In Vivo Nanoreactors Functioning in Tumors.

The design and construction of nanoreactors are important for biomedical applications of enzymes, but lipid- and polymeric-vesicle-based nanoreactors have some practical limitations. We have succeeded in preparing enzyme-loaded polyion complex vesicles (PICsomes) through a facile protein-loading method. The preservation of enzyme activity was confirmed even after cross-linking of the PICsomes. The cross-linked ß-galactosidase-loaded PICsomes (ß-gal@PICsomes) selectively accumulated in the tumor tissue of mice. Moreover, a model prodrug, HMDER-ßGal, was successfully converted into a highly fluorescent product, HMDER, at the tumor site, even 4 days after administration of the ß-gal@PICsomes. Intravital confocal microscopy showed continuous production of HMDER and its distribution throughout the tumor tissues. Thus, enzyme-loaded PICsomes are useful for prodrug activation at the tumor site and could be a versatile platform for enzyme delivery in enzyme prodrug therapy.

Two-surgeon technique for liver transection using precoagulation by a soft-coagulation system and ultrasonic dissection.

BACKGROUND/AIMS: A soft-coagulation system (SCS) was introduced as an effective device to reduce blood loss in hepatectomy. Here we evaluated the efficacy of a two-surgeon technique using precoagulation by an SCS and the Cavitron Ultrasonic Surgical Aspirator (CUSA) for liver transection. METHODOLOGY: The 163 patients with liver tumors were divided into two groups (conventional group and two-surgeon group). Liver transection was conducted using saline-coupled bipolar electrocautery and CUSA in 102 patients (conventional group). In 61 patients (the two-surgeon group), a two-surgeon technique using precoagulation by an SCS and CUSA for liver resection was performed. RESULTS: The median blood loss was significantly less in the two-surgeon group compared to the conventional group (354.8 mL vs. 557.8 mL, respec tively: p = 0.0011). The postoperative hospital stay was significantly shorter in the two-surgeon group compared to the conventional group (12.7 days vs. 15.5 days, p = 0.0035). CONCLUSIONS: The two-surgeon technique using precoagulation by an SCS and CUSA was significantly reduced blood loss during liver transection, and associated with low morbidity and mortality. This technique may be useful for many hepatobiliary surgeons.

Clinical impact of the extent of lymph node micrometastasis in undifferentiated-type early gastric cancer.

OBJECTIVE: Lymph node (LN) metastasis is one of the most important prognostic factors for undifferentiated-type early gastric cancer (EGC). The aim of this study was to examine expansion of micrometastasis in regional LNs to clarify the importance of lymphadenectomy for undifferentiated-type EGC. METHODS: Clinicopathological features of 307 patients with undifferentiated-type EGC who underwent gastrectomy with lymphadenectomy between 1997 and 2010 at the Department of Surgical Oncology, Osaka City University, were retrospectively reviewed. Micrometastasis in LNs was detected by immunohistochemistry using anticytokeratin antibody. RESULTS: The incidence of LN metastasis was 1.8% in patients with mucosal (pT1a) tumors and 17.3% in those with submucosal (pT1b) tumors. Multivariate analysis revealed that lymphatic invasion and tumor depth were independently related to LN metastasis. Micrometastasis was found in 41 (13.3%) patients. Twenty-two patients with pN0 had micrometastasis in the perigastric region. Micrometastasis had spread to the area along the left gastric or common hepatic artery in 12 patients. Patients with an upgraded stage by micrometastasis had significantly worse disease-free survival. CONCLUSIONS: LN micrometastasis was observed beyond the perigastric LNs and correlated with poor outcomes in patients with undifferentiated-type EGC. These data underscore the importance of adequate lymphadenectomy for patients with undifferentiated-type EGC. © 2014 S. Karger AG, Basel.

Cholangiocarcinoma in a middle-aged patient working at a printing plant.

A 39-year-old male with elevated serum transferases consulted our hospital in September 2010. Since 1999, he had worked at a printing company using organic solvents. Cholangiography revealed stenosis of the left hepatic duct with peripheral dilation, stricture of the right hepatic duct, and irregularity of the extrahepatic bile duct. As a preoperative diagnosis of sclerosing cholangitis and cholangiocarcinoma was made, extended left hepatectomy with resection of the extrahepatic bile duct and anastomosis of the anterior and posterior branches of the bile duct and the jejunum (Roux-en Y reconstruction) were performed. A histological examination showed papillary carcinoma of the medial hepatic bile duct with intraductal growth, and biliary intraepithelial neoplasia-2/3 lesions from the medial hepatic bile duct to the right hepatic and the common bile ducts. Chronic cholangitis was shown around the tumors. Postoperatively, the patient was treated with adjuvant chemo-radiation, and he is doing well 30 months after the operation, without recurrence. Unknown causes, including exposure to organic solvents, might have induced chronic bile duct injury and contributed to the development of cholangiocarcinoma.

Two Japanese Families with Pigmented Paravenous Retinochoroidal Atrophy and HK1 Mutation: A Case Report.

Hexokinase 1 (HK1) gene is the cause of autosomal dominant retinitis pigmentosa (RP) 79. To date, only E874K mutation has been reported as the causative mutation in patients with nonsyndromic RP. As a Caucasian RP case with a pathological variant of HK1 exhibiting pigmented paravenous retinochoroidal atrophy (PPRCA) phenotype was recently reported, we reviewed RP79 cases in our Japanese RP cohort. Consequently, 2 Japanese patients, who were diagnosed with RP79 by genetic tests in our RP cohort, were included in this study. Patient 1 was a 60-year-old woman. Fundus examination revealed symmetrical donut-shaped retinal degeneration, with pigment deposition avoiding the macula. Moreover, degeneration extended in a peripheral direction along the vessels like a starfish, and degeneration was observed around the veins and arteries. Patient 2 was a 75-year-old man. Fundus examination revealed symmetric macula-avoiding donut-shaped retinal degeneration, with paravenous protruding degeneration along the blood vessels like in case 1. Both Japanese cases, which belonged to two separate families, had the same HK1 pathogenic mutation, with a phenotype of PPRCA. Furthermore, atrophy along retinal arteries was noted. Reviewing previous nonsyndromic RP79 cases revealed symptoms that are believed to be those of PPRCA. Ultra-widefield fundus imaging, especially ultra-widefield fundus autofluorescence, has been useful in detecting PPRCA. If these devices become widely available, more cases may be discovered in the future because PPRCA can be used as a clue to suspect RP79, and Sanger sequencing may be used to identify pathogenic mutations in HK1 at a lower cost and more easily than using whole-exome sequencing.

MUC1 and HER2 might be associated with invasive phenotype of intraductal papillary mucinous neoplasm.

BACKGROUND/AIMS: The purpose of this study was to clarify the biomarkers which distinguish invasive Intraductal papillary mucinous neoplasms (IPMNs) from noninvasive IPMNs. METHODOLOGY: In tumor specimens from sixty patients with IPMNs (42 noninvasive IPMNs and 18 invasive IPMNs) who underwent surgical resection at our institute, we analyzed the correlation between the immunohistochemical expression level of MUC1, MUC2, MUC4, MUC5AC, p53, VEGFR2, HER2, and HER3. RESULTS: The 5-year survival rate was 100% in noninvasive IPMNs, while that of invasive IPMNs was only 36.5%. MUC1, MUC4, HER2 and HER3 were significantly associated with invasive IPMNs in univariate analysis. Multivariate analysis revealed that MUC1 and HER2 were significantly associated with invasive IPMNs. The 5-year survival of IPMN patients with either MUC1-positive and/or HER2-positive (54.5%) is significantly poorer than that of IPMN patients with MUC1 negative and HER2 negative (100%). CONCLUSIONS: MUC1 and HER2 might be closely associated with invasive phenotype of IPMNs.