A Pilot Study Analyzing the Clinical Utility of Comprehensive Genomic Profiling Using Plasma Cell-Free DNA for Solid Tumor Patients in Japan (PROFILE Study).

BACKGROUND: The clinical utility of plasma cell-free DNA in precision cancer medicine has not been established. A pilot study was conducted to investigate the clinical utility of comprehensive genomic profiling by liquid biopsy in a Japanese population. METHODS: In this PROFILE study, 102 patients with advanced solid tumors who showed progression with standard systemic therapy underwent liquid biopsy between August 2017 and February 2020. Liquid biopsy was performed using Guardant360. RESULTS: Of the 102 patients, 56 were women, and the median age was 65 years. Regarding the types of cancer, 31 were hepatobiliary and pancreatic cancer, 17 were gastrointestinal cancer, and 13 were breast cancer. Frequently altered genes were TP53 (53.9%, 46/102), KRAS (25.5%, 26/102), PIK3CA (19.6%, 20/102), and EGFR (17.6%, 18/102). At least one genetic aberration was detected in 92 patients (90.2%). Actionable mutation was discovered in 88 patients (86.3%), and 67 patients (65.7%) were clinical trial candidates. Of the 102 patients, 22 (21.6%) were able to receive biomarker-matched therapy. Their best responses were as follows: 1 complete response, 3 partial responses, 7 stable diseases, and 11 progressive diseases. Additionally, the treated patients were divided on the basis of matching scores (≥ 50% vs. < 50%). The patients were divided into high and low groups. The high group had a higher disease control rate (DCR) of 75% compared with 20% in the low group (P = 0.010). CONCLUSIONS: The results indicate that liquid biopsy is useful for identifying actionable mutations associated with the clinical response of selected patients.

Peak C-reactive protein levels do not predict 30-day mortality for bacteremia: A retrospective cohort study.

INTRODUCTION: Although peak C-reactive protein (CRP) levels are correlated with the prognosis of some diseases, there have been no reports regarding the association between peak CRP levels and mortality in patients with bacteremia. The present study aimed to determine the association between peak CRP levels and prognosis in patients with bacteremia. METHODS: This retrospective cohort study was conducted in a single tertiary hospital and included patients with bacteremia admitted to the emergency department from November 2012 to March 2017. Cox regression analysis was performed to examine the association between peak CRP levels and 30-day mortality. We also performed propensity score adjustment using potential confounding factors. RESULTS: One hundred fifty-nine patients were included in the study. Peak CRP levels were significantly higher in the ß-hemolytic streptococci (P = 0.001) and Streptococcus pneumoniae (P = 0.003) groups. The C-statistic of the multivariate logistic regression model for the propensity score was 0.88. For 30-day mortality, peak CRP levels >20 mg/dL did not show significance in the Cox regression analysis (hazard ratio, 0.866; 95% confidence interval, 0.489-1.537; P = 0.62). Even after propensity score adjustment, no significance was noted (hazard ratio, 0.865; 95% confidence interval, 0.399-1.876; P = 0.71). CONCLUSIONS: Peak CRP levels were not an independent predictor of mortality in patients with bacteremia in the emergency department. Clinicians should consider that patients with extremely high peak CRP levels do not necessarily have high mortality and vice versa.

A pediatric case of Burkitt's lymphoma with bile duct obstruction requiring surgical biliary reconstruction.

BACKGROUND: Biliary obstruction due to compression by a B-cell solid tumor occurs rarely. A few reports have described biliary reconstruction surgery for obstructive jaundice caused by Burkitt's lymphoma. However, there are no detailed reports on pediatric cases. We report a pediatric case of obstructive jaundice due to malignant lymphoma treated with biliary reconstruction surgery. CASE PRESENTATION: A 5-year-old girl presented to our hospital with a massive abdominal tumor that caused biliary stricture. Chemotherapy was initiated after an open tumor biopsy. However, endoscopic biliary stent placement was performed owing to elevated bilirubin levels. We treated the patient with chemotherapy for 9 months while endoscopically replacing the biliary stent every few months. She achieved complete tumor remission. However, sclerotic lymph nodes were persistent on the dorsal side of the cholecystic duct junction, and biliary stricture at the same site had changed to stent-dependent biliary obstruction. Therefore, we performed choledochojejunostomy and retrocolic Roux-en-Y reconstruction 15 months after initial admission. There were no postoperative complications or tumor recurrences, and the bilirubin level remained low. Histopathologically, the resected bile duct wall was fibrotic and thick, and the bile duct lumen narrowed. CONCLUSIONS: Biliary reconstruction is effective to achieve long-term biliary patency in pediatric patients with stent-dependent biliary obstruction due to malignant lymphoma. However, the decision on when to stop biliary stent replacement and proceed to biliary reconstruction surgery is a matter of debate. Further case studies are required to address this issue.

Lithium-induced Nephrogenic Diabetes Insipidus with Efficacy of Desmopressin in Combination with Thiazide Diuretics and Non-steroidal Anti-inflammatory Drugs: A Case Report with a Review of the Literature.

Nephrogenic diabetes insipidus (NDI) is characterized by excessive urination and an inability to concentrate urine. Lithium is the most common cause of acquired NDI. Treatment typically involves thiazide diuretics and nonsteroidal anti-inflammatory drugs (NSAIDs). However, the efficacy of desmopressin in NDI remains unclear. We herein report a case of lithium-induced NDI in a 71-year-old woman with lithium-induced NDI. Thiazide diuretics and NSAIDs reduced the urine output by approximately 40% compared to pretreatment, while the addition of desmopressin reduced it by approximately 70%. This case suggests that desmopressin can be a viable treatment option for lithium-induced NDI.

Successful combined laparoscopic and thoracoscopic surgery for esophago-mediastinal fistulae.

Minimally invasive surgeries have been developed, not only for gastrointestinal cancer, but also for benign or emergency cases. We report the case of a 62-year-old male who underwent laparoscopic and thoracoscopic combined surgery for an esophago-mediastinal fistula caused by a press-through package. In the initial laparoscopic phase, transhiatal dissection of the lower thoracic esophagus and harvesting of the greater omentum were performed. In the thoracoscopic phase, resection of the fistula and esophageal wall closure were performed. Thereafter, the greater omentum was lifted via the esophageal hiatus and wrapped around the repaired part of the esophagus for reinforcement. The total operative time was 371 min, with 163 and 208 min for the laparoscopic and thoracoscopic phases, respectively. In total, 20 ml of blood was lost. No perioperative complications or recurrences were observed. Laparoscopic and thoracoscopic combined omentoplasty was effective for refractory esophago-mediastinal fistula.

Histopathological evaluation of the effectiveness of oral Eppikajutsuto treatment for lymphatic malformation.

BACKGROUND: Lymphatic malformation (LM) is a congenital disease caused by lymphatic vessel malformation. Although standard therapies for LMs are sclerotherapy and/or surgical excision, a new therapy using Japanese herbal medicine Eppikajutsuto (TJ-28) has been recently reported as clinically effective. We aimed to experimentally confirm the therapeutic effectiveness of TJ-28 for LMs. METHODS: LM lesions were generated in the mesentery and peritoneum of mice by intraperitoneal injection of Freund's incomplete adjuvant. Mice with LMs were treated by gavage or dietary administration of TJ-28 for 2 months. Formalin-fixed paraffin-embedded tissue sections of mesentery and peritoneum tissues were histologically and immunohistochemically examined by focusing on lymph nodes and perinodal lymph vessels. RESULTS: Multiple Freund's incomplete adjuvant-associated foreign-body granulomas were formed in the mesentery and peritoneum, resulting in congestion of lymph fluid and dilatation of lymph vessels. The numbers and sizes of lymph nodes were not significantly different between TJ-28-treated and control groups. However, the luminal areas of lymphatic vessels were reduced significantly in the TJ-28 treatment group by both gavage and dietary administrations. CONCLUSION: TJ-28 conspicuously reduced congestion of lymph fluid. This is the first histopathological evaluation of LM model mice to study the effectiveness of oral TJ-28 treatment.

Machine learning analysis to identify the association between risk factors and onset of nosocomial diarrhea: a retrospective cohort study.

BACKGROUND: Although several risk factors for nosocomial diarrhea have been identified, the detail of association between these factors and onset of nosocomial diarrhea, such as degree of importance or temporal pattern of influence, remains unclear. We aimed to determine the association between risk factors and onset of nosocomial diarrhea using machine learning algorithms. METHODS: We retrospectively collected data of patients with acute cerebral infarction. Seven variables, including age, sex, modified Rankin Scale (mRS) score, and number of days of antibiotics, tube feeding, proton pump inhibitors, and histamine 2-receptor antagonist use, were used in the analysis. We split the data into a training dataset and independant test dataset. Based on the training dataset, we developed a random forest, support vector machine (SVM), and radial basis function (RBF) network model. By calculating an area under the curve (AUC) of the receiver operating characteristic curve using 5-fold cross-validation, we performed feature selection and hyperparameter optimization in each model. According to their final performances, we selected the optimal model and also validated it in the independent test dataset. Based on the selected model, we visualized the variable importance and the association between each variable and the outcome using partial dependence plots. RESULTS: Two-hundred and eighteen patients were included. In the cross-validation within the training dataset, the random forest model achieved an AUC of 0.944, which was higher than in the SVM and RBF network models. The random forest model also achieved an AUC of 0.832 in the independent test dataset. Tube feeding use days, mRS score, antibiotic use days, age and sex were strongly associated with the onset of nosocomial diarrhea, in this order. Tube feeding use had an inverse U-shaped association with the outcome. The mRS score and age had a convex downward and increasing association, while antibiotic use had a convex upward association with the outcome. CONCLUSION: We revealed the degree of importance and temporal pattern of the influence of several risk factors for nosocomial diarrhea, which could help clinicians manage nosocomial diarrhea.

MERS associated with bacterial translocation in a pediatric patient with congenital portal vein hypoplasia: A case report.

A case of mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) in a female child who developed bacterial translocation from a congenital portal vein hypoplasia is reported. The patient was diagnosed as having portal hypertension after examinations and laboratory results showing splenomegaly and thrombocytopenia at the age of 1 year. The patient required three endoscopic variceal ligation (EVL) surgeries before the age of 9 due to development of multiple esophageal varices. After the second and third EVL procedures, she developed septicemia, possibly due to bacterial translocation associated with the administration of general anesthesia. The day after the third EVL, the patient presented with high fever and neurological disturbances (altered consciousness). Magnetic resonance imaging detected abnormal intensities in the corpus callosum ampulla and cerebral white matter, which suggested a diagnosis of MERS type 2. Considering this clinical course, the possible association between bacterial translocation and MERS in a patient with congenital portal vein hypoplasia and portal hypertension is discussed.

Waardenburg syndrome with isolated deficiency of myenteric ganglion cells at the sigmoid colon and rectum.

Waardenburg syndrome (WS) has the characteristic clinical features caused by the embryologic abnormality of neural crest cells. WS patients sometimes suffer from functional intestinal obstruction. When it is Hirschsprung disease (HD), the WS is diagnosed as type 4 WS. We report a case of WS which did not have myenteric ganglion cells in the sigmoid colon and rectum. Whether to diagnosis this case as type 1 or 4 WS is controversial. Moreover, this is the third report which has peristalsis failure caused by abnormal myenteric plexus. In all three cases, the eosinophils had aggregated in the myenteric layer of the transition zone. During embryonic life, enteric ganglion cells migrate to the myenteric layer from the proximal to the distal side sequentially and, subsequently, to the submucosal layer through the circular muscle. Therefore, we hypothesize that myenteric ganglion cells that had already migrated were eliminated by an eosinophil-mediated mechanism in these three cases. We believe this report may be helpful to elucidate the pathogenesis of some types of HD.

Asymptomatic Mesenchymal Hamartoma of the Chest Wall in Child With Fluorodeoxyglucose Uptake on PET/CT-Report of a Case.

We had experience with a case of mesenchymal hamartoma of the chest wall (MHCW) with fluorodeoxyglucose (FDG) uptake on positron emission tomography/computed tomography (PET/CT). We reported the first case of asymptomatic MHCW in a child with preoperative PET/CT. Mesenchymal hamartoma of the chest wall is a rare benign tumor that usually presents as a visible chest wall mass or respiratory problems secondary to compression of the lung in early infancy. It is often reported that malignant transformation is extraordinarily rare. Positron emission tomography/CT is useful for diagnosis of malignancy. There is no report of MHCW in a child with preoperative PET/CT before. We examined an asymptomatic 1-year-old girl with an incidental finding on a chest x-ray. Scans of CT and PET/CT were performed before surgical resection. After surgery, the resected tumor was examined histologically. Chest x-ray and CT scan of the chest confirmed a 25- × 20-mm round shaped intrapleural mass containing calcification and destructing the rib, arising from the third rib. Scan of PET/CT demonstrated the mass with light FDG accumulation. Histologically, the mass was homogenous, with thick funicular of hyaline cartilage interdigitating with scattered fiber. There were no malignant cells. No malignant MHCW was demonstrated in the mass, with light FDG accumulation by PET/CT. PET/CT might be a useful tool to distinguish malignant MHCW in children.

Utility of FDG-PET/CT in the evaluation of the response of locally advanced breast cancer to neoadjuvant chemotherapy.

Neoadjuvant chemotherapy (NAC) is effective in down-staging a primary tumor before surgery, and quick differentiation between responders to NAC and nonresponders is needed. We investigated the utility of [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) and computed tomography (CT) in evaluating the therapeutic effectiveness of NAC. We investigated 25 patients who underwent NAC for stage II and III noninflammatory breast cancer. FDG-PET/CT was undertaken before and after NAC to determine the maximum standardized uptake value (SUVmax) reduction rate. Findings were compared with postoperative histopathologic evaluation of therapeutic response. It was not possible to accurately assess tumor response to NAC using CT. However, using the SUVmax reduction rate, we noted a significant difference (P=0.0420) between patients who were responsive and nonresponsive to NAC. The sensitivity and specificity were as high as 83.3% and 78.9%, respectively. This study demonstrated that FDG-PET/CT can differentiate responders from nonresponders. This improves patient management by avoiding unnecessary chemotherapy.