Establishment of a trastuzumab-resistant extramammary Paget disease model: loss of PTEN as a potential mechanism.

BACKGROUND/OBJECTIVES: Extramammary Paget disease (EMPD) is a rare, cutaneous intraepithelial adenocarcinoma typically treated with wide local excision. Unfortunately, a number of patients with metastases show poor responses to chemotherapy. While some studies have explored trastuzumab's effectiveness against EMPD positive for human epidermal growth factor receptor 2 (HER2), trastuzumab resistance (TR) may emerge after anti-HER2 therapy. METHODS/SUBJECTS: In this study, we established TR EMPD patient-derived xenografts (PDX) that replicated the histological and HER2 expression traits of naive EMPD tumours. RESULTS: Cancer gene analyses revealed a loss of the PTEN gene in TR tumours, which was further confirmed by immunohistochemical staining and immunoblotting to test for protein expression levels. Reduced PTEN levels correlated with increased protein kinase B (Akt) phosphorylation and p27 downregulation, suggesting a potential mechanism for trastuzumab resistance in EMPD cells. In the trastuzumab-sensitive EMPD-PDX mouse model, PTEN inhibitors partially restored trastuzumab-mediated tumour regression. The TR EMPD-PDX responded favourably to targeted therapy (lapatinib, abemaciclib, palbociclib) and chemotherapy (eribulin, docetaxel, trastuzumab deruxtecan). CONCLUSIONS: This study demonstrates an innovative TR EMPD-PDX model and introduces promising antineoplastic effects with various treatments for TR EMPD tumours.

Bile lakes in patients with biliary atresia who presented with jaundice-free native liver survival indicating the risk of subsequent liver transplantation due to various factors.

PURPOSE: The prognostic factors of subsequent liver transplantation (LT) in patients with biliary atresia (BA) who presented with jaundice-free native liver survival were investigated. METHODS: This study retrospectively reviewed patients who underwent portoenterostomy (PE) for BA. Patients with jaundice-free native liver survival at 1 year postoperatively were divided into the autologous liver survivor and liver transplant recipient groups. Peri- and postoperative data were compared between the two groups. RESULTS: Among 97 patients with BA, 29 who received LT within 1 year after PE were excluded from the analysis. Further, 48 patients currently living with native liver and 20 who received LT after 1 year postoperatively were compared. Bile lake (BL) was the strongest risk factor of LT. The risk score was 2.38 ∗ B L s c o r e + 0.00466 ∗ T B A , and the area under the receiver operating characteristic curve was 0.83. Patients with BL and those without significantly differed in terms of the native liver survival rate. Patients with BL who presented with not only cholangitis but also gastrointestinal hemorrhage and hepatopulmonary syndrome received LT. CONCLUSION: BL can cause different pathologies. Moreover, it is an evident risk factor of subsequent LT in patients with BA who are living with native liver at 1 year after PE.

A fatal case of peritonitis caused by Dysgonomonas capnocytophagoides harboring the novel metallo-beta-lactamase gene blaDYB-1.

Dysgonomonas capnocytophagoides shows multidrug resistance to antibiotics and causes opportunistic infections in immunocompromised hosts. The drug resistance mechanisms of D. capnocytophagoides have not yet been identified. In this work, we analyzed D. capnocytophagoides isolated from a fatal case of peritonitis to clarify its drug resistance mechanisms. Whole genome sequencing revealed that our isolate harbored a chromosomally encoded metallo-beta-lactamase (designated blaDYB-1) and a chromosomally encoded ermFS gene. Phylogenetic analysis, primary sequence comparison, and structural modeling analysis of DYB-1 showed it was highly similar to CfiA in Bacteroides fragilis and belonged to the B1 MBL family. Transformation analysis into Escherichia coli TOP10 showed that a recombinant plasmid containing blaDYB-1 increased the minimum inhibitory concentration of beta-lactams, including carbapenem. We identified a novel chromosomally encoded class B1 metallo-beta-lactamase gene designated blaDYB-1 and an ermFS gene that contributed to multidrug resistance. This study indicates the importance of further surveillance for D. capnocytophagoides harboring blaDYB-1.

Ruptured Occipital Artery Aneurysm Following Craniotomy in a Patient with Neurofibromatosis Type 1: Case Report.

Objective: Neurofibromatosis type 1 (NF1) is associated with vascular fragility, which results in aneurysms, arteriovenous fistulas, and dissections. Here, we describe a case of endovascular treatment of a ruptured occipital artery aneurysm that occurred after a craniotomy in a patient with NF1. Case Presentation: A 46-year-old man with a history of NF1 underwent a right lateral suboccipital craniotomy to remove a cavernous hemangioma in the right middle cerebellar peduncle. Severe bleeding occurred in the occipital artery during the craniotomy. Due to vessel fragility, coagulation and ligation were not possible, and pressure hemostasis was achieved using cellulose oxide and fibrin glue. On postoperative day 12, the patient developed a sudden swelling on the right side of the neck as well as tracheal compression. Contrast-enhanced CT revealed a ruptured aneurysm in the right occipital artery. Transarterial embolization was performed under general anesthesia the same day. Right external carotid angiography showed an 18-mm-diameter fusiform aneurysm in the occipital artery. The aneurysm ruptured inferiorly to form a large pseudoaneurysm with significant jet flow. An arteriovenous fistula was also observed in a nearby vein. A microcatheter was inserted into the fusiform aneurysm under proximal blood flow control, and embolization was performed using coils and N-butyl-2-cyanoacrylate. Conclusion: Compared to surgical repair of ruptured occipital artery aneurysms, endovascular treatment appears to be safe, effective, minimally invasive, and rapid. Ruptured occipital artery aneurysms in NF1 patients can cause neck swelling and airway compression and should be recognized as a potentially lethal condition.

Thoracoscopic primary repair is useful for esophageal atresia with tracheoesophageal fistula in neonates with low body weight.

PURPOSE: The surgical indication of thoracoscopic primary repair for esophageal atresia with tracheoesophageal fistula is under debate. The current study aimed to investigate the outcome of thoracoscopic primary repair for esophageal atresia with tracheoesophageal fistula in patients weighing < 2000 g and those who underwent emergency surgery at the age of 0 day. METHODS: The surgical outcomes were compared between patients weighing < 2000 g and those weighing > 2000 g at surgery and between patients who underwent surgery at the age of 0 day and those who underwent surgery at age ≥ 1 day. RESULTS: In total, 43 patients underwent thoracoscopic primary repair for esophageal atresia with tracheoesophageal fistula. The surgical outcomes according to body weight were similar. Patients who underwent surgery at the age of 0 day were more likely to develop anastomotic leakage than those who underwent surgery at the age of ≥ 1 day (2 vs. 0 case, p = 0.02). Anastomotic leakage was treated with conservative therapy. CONCLUSION: Thoracoscopic primary repair is safe and useful for esophageal atresia with tracheoesophageal fistula even in newborns weighing < 2000 g. However, emergency surgery at the age of 0 day should be cautiously performed due to the risk of anastomotic leakage.

Duodenal duplication cyst at the second part of the duodenum with congenital duodenal position anomaly completely resected by laparoscopic partial duodenectomy: a case report.

BACKGROUND: Duodenal duplication cysts (DDC) are rare duplications of the alimentary tract. Their treatment depends on their size and location. A radical treatment is total resection, if possible. However, partial excision, puncture, and marsupialization can be selected to prevent surgical injury to the pancreaticobiliary tract despite the risk of recurrence. There are some reports of pancreaticoduodenectomy for DDC because of the risk of recurrent symptoms and malignancy. However, this is considered excessively invasive for DDC, particularly in pediatric cases, because of its extremely low rate of malignancy and high morbidity and mortality rates. We encountered a case of DDC with a congenital duodenal position anomaly occurring in the second part of the duodenum. Taking advantage of the congenital duodenal position anomaly, the DDC was completely resected without injuring the pancreaticobiliary duct. CASE PRESENTATION: A 6-year-old boy was diagnosed with a duodenal duplication cyst with obstruction. There was a congenital duodenal position anomaly. The distal second part of the duodenum was the dorsal side of the proximal second part of the duodenum and ascended upward from the proximal second part of the duodenum. The third and fourth parts of the duodenum ran downward to the left and posterior parts of the portal vein, forming the ligament of Treitz. Complete laparoscopic resection of the duodenal duplication cyst and the second to fourth parts of the duodenum, and duodenojejunostomy with retrocolic reconstruction was performed because the duodenum was easily mobilized to the ligament of Treitz owing to the duodenal position anomaly. The duodenojejunostomy with retrocolic reconstruction achieved a more physiologically normal appearance compared to what would have been achieved with a Roux-en-Y reconstruction. The patient was discharged on postoperative day 12 without any complications. CONCLUSIONS: The procedure used in this case might not be easily applied in all laparoscopy cases. However, it could be an option for duodenal duplication cysts with congenital duodenal position anomalies.

Renal ultrasonography predicts worsening renal function in patients with heart failure under tolvaptan administration.

AIMS: Renal dysfunction in patients with chronic heart failure predicts a poor prognosis. Tolvaptan has a diuretic effect in patients with chronic kidney disease and heart failure without adverse effects on renal function. We aimed to determine the effects of tolvaptan and predictors of worsening renal function in patients with heart failure. METHODS AND RESULTS: This post hoc analysis was a sub-analysis of a single-centre prospectively randomized trial on the early and short-term tolvaptan administration. We enrolled 201 participants with decompensated heart failure between January 2014 and March 2019 (early group, n = 104; age: 79.0 ± 12.8 years; late group, n = 97; age: 80.3 ± 10.8 years). Renal ultrasonography was performed before and after the administration of tolvaptan. Urine output and oral water intake significantly increased during tolvaptan administration. The difference between water intake and urine volume increased during tolvaptan administration. Changes in body weight, blood pressure, heart rate, and estimated glomerular filtration rate (eGFR) in both groups were comparable. The changes in peak-systolic velocity (PSV), acceleration time (AT) of the renal arteries, and resistance index were comparable. The changes in PSV and end-diastolic velocity (EDV) of the interlobar arteries increased following tolvaptan administration (Δmax PSV: 0.0 ± 14.8 cm/s before tolvaptan vs. 5.6 ± 15.7 cm/s after tolvaptan, P = 0.002; Δmean PSV: 0.4 ± 12.3 vs. 4.9 ± 12.7 cm/s, P = 0.002; Δmax EDV: -0.2 ± 3.5 vs. 1.4 ± 4.0 cm/s, P = 0.001; Δmean EDV: -0.0 ± 3.1 vs. 1.1 ± 3.4 cm/s, P = 0.003). The renal artery AT was negatively correlated with the eGFR (Δmax AT: beta = -0.2354, P = 0.044; Δmean AT: beta = -0.2477, P = 0.035). CONCLUSIONS: Tolvaptan increased the PSV and EDV of the interlobar artery, which may mean tolvaptan increased renal blood flow. The renal artery AT may be a surrogate for worsening renal function.

A systematic review of Sandifer syndrome in children with severe gastroesophageal reflux.

PURPOSE: Sandifer syndrome (SS), which combines gastroesophageal reflux (GER) and a neurological or psychiatric disorder, is an uncommon condition that often takes a long time to diagnosis. We aimed to systematically review available papers regarding SS. METHODS: After presenting our two cases of SS, we systematically reviewed articles published in MEDILINE/PubMed, Cochrane Library, and Web of Science. RESULTS: The meta-analysis included 54 reported cases and 2 of our own cases. Our results showed that all cases achieved symptom improvement with appropriate treatment for GER. Notably, 19 of the 56 cases exhibited anatomical anomalies, such as hiatal hernia and malrotation. Significantly more patients with than without anatomical anomalies required surgery (p < 0.001). However, 23 of the 29 patients without anatomical anomalies (79%) achieved symptom improvement without surgery. Patients who did not undergo surgery had a median (interquartile range) duration to symptom resolution of 1 (1-1) month. CONCLUSION: The primary care providers should keep SS in the differential diagnosis of patients presenting with abnormal posturing and no apparent neuromuscular disorders. Fundoplication may be effective especially for patients with anatomical anomalies or those whose symptoms do not improve after more than 1 month with nonsurgical treatment.

Laparoscopic Fundoplication in Patients with Ventriculoperitoneal Shunts: A Systematic Review and Our Experience.

Background: Data on the outcomes of laparoscopic fundoplication (LF) in patients with ventriculoperitoneal (VP) shunts are limited. Materials and Methods: We retrospectively evaluated the demographic characteristics and outcomes of patients who underwent LF at our institutions between 2014 and 2022. Then, we systematically reviewed articles in MEDILINE/PubMed, Cochrane Library, and Web of Science. Results: There was no significant difference in terms of the outcomes between patients with VP shunt (n = 10) and those without (n = 96) at our institutions. None of the patients presented with shunt trouble after LF. The meta-analysis included four retrospective studies and our institutional data. In total, 605 patients (55 with VP shunt) underwent LF. Furthermore, 2 (3.6%) of 55 patients (1 with infection and 1 with occlusion) had shunt troubles. The conversion and complication rates, operative time, and length of hospital stay did not significantly differ between patients with VP shunt and those without. Conclusions: LF can be safely performed on children with VP shunts and is associated with a low risk of shunt troubles. The Clinical Trial Registration number is 2022-387.

Eribulin for patients with metastatic extramammary Paget disease: Study protocol for a single-arm phase II trial.

Extramammary Paget disease (EMPD) is a rare cutaneous malignancy that predominantly affects the anogenital areas of the elderly. Although the efficacy of docetaxel and other cytotoxic agents for advanced EMPD has been reported in small retrospective case studies, no treatment has been proven effective in prospective clinical trials. We established the world's first in vivo EMPD experimental model (a patient-derived xenograft model). In our treatment experiment, xenograft tumours showed a remarkable response to eribulin. This study evaluates the efficacy of eribulin for patients with advanced EMPD. In October 2022, we started a single-arm phase II trial to evaluate the efficacy of eribulin as a treatment for adult patients with unresectable EMPD with measurable lesions. Enrolment in this clinical trial is open to patients with any prior treatment for EMPD. The primary endpoint is overall response rate; the secondary endpoints include disease control rate, overall survival, progression-free survival and adverse events. The study protocol was approved by the Ethics Committee of Hokkaido University and the other collaborating institutions. If the primary endpoint is met, it is our hope that eribulin will be regarded as a standard medication for patients with advanced EMPD.

Dermoscopic Features of Heterotopic Salivary Gland Tissue in the Neck: Report of a Case.

Introduction: Heterotopic salivary gland tissue (HSGT) is diagnosed when salivary gland tissue is found in areas other than the major or minor salivary glands. No dermoscopic findings of HSGT have been reported. Case Presentation: This case report gives the dermoscopic findings of a 45-year-old woman with HSGT who presented with a longstanding pale red macule on her neck, characterized by repeated clear fluid discharge. Dermoscopic examination showed a red dot with a pale pink halo and telangiectasia throughout the lesion. An excisional biopsy confirmed the diagnosis of HSGT, revealing the presence of mucous and serous salivary glandular structures within subcutaneous fat tissue. It has been reported that HSGT is associated with periductal lymphocytic infiltration, which was also observed in this case. Conclusion: We think that the "red dot with a pale pink halo" is a unique dermoscopic finding of HSGT, which is rarely observed in branchial anomalies.

Association of affected and non-affected side ability with postoperative outcomes in patients undergoing total hip arthroplasty.

BACKGROUND: Although several reports have examined the association between preoperative function and postoperative outcomes in patients undergoing total hip arthroplasty (THA), it is unclear whether the ability of the affected or non-affected side particularly impacts on outcomes. We aimed to investigate the association between affected and non-affected side ability and walking independence. METHODS: We prospectively enrolled 721 consecutive patients who underwent THA. Preoperatively, quadriceps isometric strength (QIS) and one-leg standing time (OLST) were measured. The endpoints were walking independence within 3, 5, 7, 10, and 14 days postoperatively. The associations between preoperative abilities and outcomes were examined using multivariate Cox hazard model, and the area under the curves (AUCs) for outcomes were compared. RESULTS: We analysed 540 patients after excluding patients who met the exclusion criteria. Both affected and non-affected QIS predicted walking independence within 3 (p = 0.006 and 0.001, respectively), 5, 7, 10, and 14 (both p < 0.001) days postoperatively. For OLST, only the affected side did not predict walking independence within 3 days postoperatively (p = 0.154 and 0.012, respectively), and both sides did at days 5 (p = 0.019 and <0.001, respectively), 7, 10, and 14 (both p < 0.001). The AUCs of the non-affected side ability for walking independence were significantly greater than those of the affected side on postoperative days 3 (0.66 vs. 0.73; p = 0.021) and 5 (0.67 vs. 0.71; p = 0.040), with no significant difference after day 7. CONCLUSIONS: Both sides abilities were associated with walking independence after THA, but non-affected side was found to be particularly crucial for early walking independence.

Association between weight loss and death in patients with malignant melanoma: A retrospective study of 28 cases.

Malignant melanoma (MM) is often associated with a poor prognosis due to metastasis and cancer death. The monitoring of prognostic factors is of vital importance, and among these factors, elevated lactate dehydrogenase (LDH) should be closely observed during the disease course. Important factors for predicting the survival of MM patients include tumor thickness, ulceration, the number of lymph node metastases, metastatic lesions, and the sites of metastasis. Weight loss is not generally included in the prognostic factors of MM, but it is monitored in other cancers, such as lung cancer and gastrointestinal cancer. The objective of this study was to investigate the association between weight loss and MM prognosis. Using data from MM patients who had been treated at our institution, we assessed the prognoses of two groups: weight loss of at least 5% body weight or weight loss not exceeding 5% body weight within a 12-month period. As a result, a higher mortality rate was found for the former group. Furthermore, the loss of at least 5% of body weight within a month was found to almost always adversely affect the patient's prognosis. The present study indicates that there may be an association between MM prognosis and weight loss of at least 5% within a year, and body weight could potentially serve as an informative factor for MM survival.

A new criterion including the aspartate aminotransferase-to-platelet ratio index and liver and spleen stiffness to rule out varices needing treatment in children with biliary atresia: Modification of the Baveno VII criteria.

AIMS: Biliary atresia (BA) is a congestive biliary disease that develops in the neonatal period or early infancy. It may present with portal hypertension and varices needing treatment (VNT) even after successful Kasai portoenterostomy. This study aimed to stratify the risk of VNT in children and adolescents with BA. METHODS: In this prospective cross-sectional study, we measured liver stiffness (LS) and spleen stiffness (SS) by two-dimensional shear wave elastography and checked for VNT endoscopically in 53 patients with BA who attended for follow-up between July 2018 and September 2022. Varices needing treatment were defined as large esophageal varices, esophageal varices of any size with red color signs, and/or gastric varices along the cardia. RESULTS: Twenty-five patients (aged 0-18 years) had VNT. Eighteen patients met the Baveno VI criteria (LS <20 kPa; platelet count >150 000/L) and were deemed to be at low risk of VNT (spared endoscopies) while three had missed VNT (16.7%). Applying the Baveno VII criteria, which combines the SS cut-off value of 40 kPa with the Baveno VI criteria, resulted in five missed VNTs among 22 spared endoscopies (22.7%). A modification of the Baveno VII criteria using the aspartate aminotransferase-to-platelet ratio index (APRI) instead of the platelet count with cut-off values of 25 kPa, 30 kPa, and 1.04 for LS, SS, and APRI, respectively, missed only one VNT (5.0%) among 20 spared endoscopies. CONCLUSIONS: A novel diagnostic criterion that combines LS, SS, and APRI reduced the risk of missing VNT to 5% in children and adolescents with BA.

Surgical Strategies for Neonates with Prenatally Diagnosed Congenital Biliary Dilatation.

BACKGROUND: This study aimed to develop a postnatal treatment strategy for infants with prenatally diagnosed congenital biliary dilatation. METHODS: We performed a retrospective study of patients with prenatal diagnosed congenital biliary dilatation (CBD), aged <1 year who underwent surgery at our hospital between 2013 and 2023. We classified the patients into two groups, the "early group," consisting of patients who could not wait for growth, and required early surgery, and the "scheduled group," consisting of patients who were asymptomatic and could undergo scheduled surgery, and compared them. The parameters for early surgical prediction were AST, ALT, TB, DB, and CRP levels at birth, 1 week, 2 weeks, 1 month, 2 months, and 3 months after birth, and immediately before surgery, as well as the cyst diameter, presence of intrahepatic bile duct dilation, and presence of debris in the common bile duct. RESULTS: During the study period, 15 patients were diagnosed prenatally. The cyst diameter was significantly larger at all points in the early group. Patients with a cyst diameter of >30 mm at birth, intrahepatic bile duct dilatation at birth, and postnatal enlargement of the common bile duct to >30 mm are more likely to develop symptoms early. Blood biochemistry tests showed no significant differences between the two groups. CONCLUSIONS: Patients with a cyst diameter >30 mm in the early postnatal period require careful postnatal management and parents should be counseled regarding the high likelihood of their child needing surgery within the first 3 months of life. LEVEL OF EVIDENCE: Level IV.

Vancomycin-resistant Enterococcus faecium in Japan, 2007-2015: a molecular epidemiology analysis focused on examining strain characteristics over time.

IMPORTANCE: Our study emphasizes the efficacy of whole-genome sequencing (WGS) in addressing outbreaks of vancomycin-resistant enterococci. WGS enables the identification and tracking of resistant bacterial strains, early detection and management of novel infectious disease outbreaks, and the appropriate selection and use of antibiotics. Furthermore, our approach deepens our understanding of how resistant bacteria transfer genes and adapt to their environments or hosts. For modern medicine, these insights have significant implications for controlling infections and effectively managing antibiotic use in the current era, where antibiotic resistance is progressing.

Preoperative management comprising tube irrigation using a trans-anal indwelling tube for infants with hirschsprung disease can allow single-stage radical surgery.

BACKGROUND: Preoperative management of Hirschsprung's disease (HD) is currently being conducted with the goal of performing single-stage radical surgery without ileostomy. METHODS: We retrospectively reviewed HD cases between 2013 and 2022, as well as their outcomes related to preoperative management. RESULTS: Thirty-nine patients with HD were included in this study, including short-segment HD (30 cases), long-segment HD (4 cases), and total colonic aganglionosis (5 cases). Among these 39 patients, 95% (37 of 39 patients) underwent single-stage radical surgery after management with glycerin enema use (n = 13), irrigation with tube insertion each time irrigation was performed (n = 13), and irrigation using a tube placed in the bowel (n = 11). CONCLUSIONS: Preoperative management of patients with HD allowed for single-stage surgery of long-segment HD and total colonic aganglionosis. Cases that could be managed without performing an emergency enterostomy during the neonatal period were managed with irrigation until radical surgery was performed.