Decision making for anti-VEGF inhibitor continuation: dip stick? or urine protein/creatinine ratio? (VERSiON UP study).

BACKGROUND: Monitoring proteinuria is important for the management of patients with cancer treated with anti-vascular endothelial growth factor (VEGF) or anti-VEGF receptor (VEGFR) inhibitors (VEGF/Ri). Here we investigated the difference between the urine protein/creatinine ratio (UPCR) and a qualitative value test (QV) on the decision making of treatment continuation and the usefulness of UPCR testing in patients with gastrointestinal cancer treated with anti-VEGF/Ri. METHODS: From January 2017 to December 2018, a survey was conducted based on the medical records of patients with gastrointestinal cancer with a QV of ≥2+ during the use of anti-VEGF/Ri at seven Japanese institutions participating in the Onco-nephrology Consortium. The primary endpoint was the ratio of the worst UPCR < 2.0 (low UPCR) in cases with a QV2+ at the point of the first proteinuria onset. The secondary endpoints were a comparison of low UPCR and worst UPCR ≥2.0 (high UPCR), the concordance rate between UPCR and QV in the Common Terminology Criteria for Adverse Events (CTCAE) grading, and the differences in the decision making for anti-VEGF/Ri continuation. RESULTS: Among the 71 patients enrolled, the proportion of low UPCR in onset QV2+ (n = 53) was 66% (n = 35). In a comparison between low (n = 36) and high UPCR cases (n = 24), body weight (P = 0.036), onset QV status (P = 0.0134), and worst QV status (P < 0.0001) were significantly associated with UPCR levels. The concordance rate for CTCAE Grade 2 of both the QV and UPCR was 83%. Regarding the judgment of anti-VEGF/Ri continuation, treatment was continued in 42.4% of cases when the QV became 3+, whereas only 25% continued treatment when the UPCR value became high. CONCLUSION: Urine dipstick test results may overestimate proteinuria, and the UPCR result tended to be more critical than the QV when deciding the treatment policy. TRIAL REGISTRATION: This study is a multiple institutional retrospectively registered observational trial. CLINICAL TRIAL NUMBER: University Hospital Medical Information Network (UMIN) Clinical Trials Registry (protocol ID UMIN000042545 ).

Effectiveness of introducing a 20-gauge core biopsy needle with a core trap in EUS-FNA/B for diagnosing pancreatic cancer.

BACKGROUND: Endoscopic ultrasound-guided fine-needle aspiration/biopsy (EUS-FNA/B) is a standard method for pathological diagnosis of pancreatic solid lesions. The EchoTip ProCore 20G® (PC20), a 20-gauge biopsy needle with a forward-bevel core trap, has been available in Japan since 2015. METHODS: We compared the efficacy of the PC20 with that of the EchoTip ProCore 22G® (PC22) and Acquire 22G® (AC22) in EUS-FNA/B for diagnosing pancreatic cancer. This retrospective study included 191 patients with pancreatic cancer who underwent EUS-FNA/B using the PC20, PC22, or AC22 at our facility from April 2013 to October 2019. We investigated the patients' clinical characteristics and the diagnostic accuracy and safety of each needle. RESULTS: A sufficient stroke length of puncture was secured in all patients. The maximum length under EUS was shorter with the AC22 (22.1 ± 2.2 mm) than PC20 (30.6 ± 0.7 mm, p < 0.01) and PC22 (30.3 ± 0.8 mm, p < 0.01). The histological accuracy was 96.4% with the PC20 but only 58.8% with the PC22 (adjusted p (p-adj) < 0.0001) and 75.0% with the AC22 (p-adj = 0.06). The diagnostic accuracy of the combination of histology and cytology was 96.4% with the PC20, while it was 72.1% with the PC22 (p-adj < 0.0001) and 91.7% with the AC22 (p-adj > 0.99). One patient (0.9%) in the PC20 group developed mild pancreatitis, but no adverse events occurred with the other needles. CONCLUSIONS: The PC20 showed better diagnostic capability than the PC22. The diagnostic efficacy was similar between the PC20 and AC22. The high histological accuracy of the PC20 could be advantageous for lesions in which histological assessment is critical.

Pharmacokinetic-pharmacodynamic comparison of ceftriaxone regimens in acute cholangitis.

The most important factors determining the prognosis of patients with acute cholangitis (AC) are prompt biliary drainage and appropriate choice of antibiotics. This study was performed to evaluate whether dividing the number of doses based on the PK-PD theory contributes to better clinical outcome in the management of acute cholangitis. We measured ceftriaxone levels in blood and bile in 21 cases diagnosed with moderate-to-severe AC. Eleven cases were administered 2 g of ceftriaxone once-daily (group A) and 10 cases were given 1 g of ceftriaxone twice-daily (group B). The theoretical effect of ceftriaxone was evaluated by pharmacokinetic-pharmacodynamic (PK-PD) parameters. Clinical efficacy was evaluated by body temperature, white blood cell count and serum levels of C-reactive protein. Minimum level of ceftriaxone in serum (in mg/L) in groups A and B at 24 h after the first dose was 9.1 and 9.2, whereas that in bile was 2.9 and 2.5, respectively. The minimum inhibitory concentration (MIC) of ceftriaxone for all isolated bacteria was below the minimum serum and biliary concentration of ceftriaxone 24 h after the first administration (except for Enterococcus species). The MIC for isolated bacterial strains was <16 mg/L, which is the PK-PD breakpoint for ceftriaxone at 2 g/day. Both regimens showed clinical efficacy and did not contradict the effect predicted based on PK-PD.

Up-to-seven criteria as a useful predictor for tumor downstaging to within Milan criteria and Child-Pugh grade deterioration after initial conventional transarterial chemoembolization.

AIM: Intermediate-stage hepatocellular carcinoma varies widely in tumor burden and liver function. This study aimed to clarify the importance of subclassification by the up-to-seven criteria in both clinical course and liver function deterioration in such patients. METHODS: We retrospectively analyzed 224 patients with Child-Pugh grade A who underwent initial transarterial chemoembolization (TACE) for hepatocellular carcinoma. Tumor downstaging to within the Milan criteria within 1 year and liver function worsening as Child-Pugh grade deterioration from A to B were analyzed. RESULTS: The median survival time was 35.8 months. Forty-five patients had no recurrence within 1 year after initial TACE. Of the 179 patients with at least one recurrence within a year, 44 (25%) achieved tumor downstaging to within the Milan criteria and showed significantly longer survival than non-downstaged ones (P = 0.02). Logistic regression univariate analysis revealed that up-to-seven criteria fulfillment was associated with tumor downstaging to within the Milan criteria (odds ratio 2.6; P = 0.007). The median deterioration time was 26.7 months. Multivariate analysis revealed that beyond the up-to-seven criteria (hazard ratio [HR] 1.9; P = 0.005) was an independent factor associated with Child-Pugh grade deterioration, along with serum albumin (HR 1.54; P = 0.01), serum bilirubin (HR 1.49; P = 0.02), and prothrombin time (HR 1.54; P = 0.04). CONCLUSIONS: The up-to-seven criteria had prognostic value and could predict non-critical recurrence and maintenance of Child-Pugh grade in patients who underwent initial conventional TACE.

TERT promoter mutations and chromosome 8p loss are characteristic of nonalcoholic fatty liver disease-related hepatocellular carcinoma.

The number of patients with nonalcoholic fatty liver disease (NAFLD)-related hepatocellular carcinoma (HCC) is increasing. To understand the molecular features of the tumor phenotype, we aimed to clarify the overall landscape of genetic aberrations accumulated in NAFLD-related HCC. Of 247 HCC patients who underwent hepatectomy during 2010 to 2014 at a single center in Japan, 10 were diagnosed with NAFLD-HCC based on strict clinical and pathologic criteria. We analyzed the genetic aberrations of 11 NAFLD-HCC tumor samples from these 10 patients by whole-exome sequencing, targeted sequencing of the selected genes, and copy number variation studies. Whole-exome sequencing revealed a mean somatic mutation rate of 1.86 per megabase, and 12 genes were recurrently mutated in NAFLD-HCCs. Targeted sequencing of the 26 selected genes (12 recurrently mutated genes in whole-exome sequencing and 14 representative HCC-associated genes) revealed that TERT promoter mutations occurred in 9 of 11 HCCs (82%), followed by CTNNB1 (45%) and TP53 (36%) mutations. Array-based copy number variation studies identified recurrent gains at 1q and 8q, and recurrent losses at 1p, 4q, 6q, 8p, 13q, 16p, 17p, and 18q. Notably, chromosome 8p loss occurred in all of the NAFLD-HCC samples. The current study provided the characteristics of genetic aberrations in NAFLD-HCC and suggested that TERT promoter mutations and chromosome 8p loss mainly contribute to NAFLD-related liver carcinogenesis.

Recent Advances From Basic and Clinical Studies of Esophageal Squamous Cell Carcinoma.

Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive squamous cell carcinomas and is highly prevalent in Asia. Alcohol and its metabolite, acetaldehyde, are considered definite carcinogens for the esophagus. Polymorphisms in the aldehyde dehydrogenase 2 gene, which encodes an enzyme that eliminates acetaldehyde, have been associated with esophageal carcinogenesis. Studies of the mutagenic and carcinogenic effects of acetaldehyde support this observation. Several recent large-scale comprehensive analyses of the genomic alterations in ESCC have shown a high frequency of mutations in genes such as TP53 and others that regulate the cell cycle or cell differentiation. Moreover, whole genome and whole exome sequencing studies have frequently detected somatic mutations, such as G:C→A:T transitions or G:C→C:G transversions, in ESCC tissues. Genomic instability, caused by abnormalities in the Fanconi anemia DNA repair pathway, is also considered a pathogenic mechanism of ESCC. Advances in diagnostic techniques such as magnifying endoscopy with narrow band imaging or positron emission tomography have increased the accuracy of diagnosis of ESCC. Updated guidelines from the National Comprehensive Cancer Network standardize the practice for the diagnosis and treatment of esophageal cancer. Patients with ESCC are treated endoscopically or with surgery, chemotherapy, or radiotherapy, based on tumor stage. Minimally invasive treatments help improve the quality of life of patients who undergo such treatments. We review recent developments in the diagnosis and treatment of ESCC and advances gained from basic and clinical research.

Two-stage hybrid repair of Kommerell diverticulum with supra-aortic debranching.

OBJECTIVES: The surgical treatment of Kommerell diverticula is associated with high mortality and morbidity rates. In the mid-2000s, hybrid aortic arch repair was developed, and the procedure has since been used to repair Kommerell diverticula. In the present study, we focused on the postoperative outcomes of two-stage hybrid repair of Kommerell diverticula that required supra-aortic debranching (type I hybrid arch repair). METHODS: From August 2010 to July 2013, a total of four patients (aged 73.5 ± 9.5 years) underwent two-stage hybrid repair (type I hybrid arch repair) for Kommerell diverticula, and their cases were retrospectively studied. All four patients had right aortic arches and aberrant left subclavian arteries. The repair procedure consisted of two stages: (1) debranching of the supra-aortic vessels via a median sternotomy; (2) exclusion of the Kommerell diverticulum by performing thoracic endovascular repair via a femoral approach and coil embolization of the orifice of the aberrant subclavian artery. RESULTS: There were no in-hospital deaths. One patient developed an acute kidney injury and required hemodialysis on postoperative day 2, although his renal function recovered within 48 hours. No strokes, paraplegia, or early aortic events were observed in our series. The mean follow-up period was 19.5 months (range, 5-47 months). All patients remained free from aortic events and endoleaks during the follow-up period. CONCLUSION: The early and mid-term outcomes of hybrid repair for Kommerell diverticula that require supra-aortic debranching, which are less invasive and do not involve hypothermic circulatory arrest, are acceptable. However, this procedure requires the insertion of an endograft into the ascending aorta, and careful and long-term follow-up is required to confirm its efficacy.

Weaning from Tube Feeding Post Stroke by Eating, Swallowing, and Nutritional Support In-Home: A Case Report.

In many cases, enteral tube feeding is begun after stroke without adequate assessment of feeding ability, swallowing function, and nutritional status. A 72-year-old man was recovering at home after a stroke and consulted us because he wanted to resume taking food by mouth. He had tube feeding for 13 months after the stroke. We offered him feeding and swallowing training and proper nutrition guidance by visiting dental staff and managerial dietitians at home and concluded the patient was sufficiently able to take oral food. After 4 months, the patient was completely weaned from tube feeding.

Prognostic factors in hepatitis C patients with a single small hepatocellular carcinoma after radiofrequency ablation.

BACKGROUND/AIMS: Hepatitis C is a major cause of hepatocellular carcinoma (HCC). Radiofrequency ablation (RFA) has been widely performed as a curative treatment for small HCC. The knowledge of prognostic factors in hepatitis C patients with small HCC after RFA is therefore important. METHODOLOGY: One hundred consecutive hepatitis C patients with a single HCC3cm or less treated with RFA were enrolled. The cumulative recurrence and survival rates were calculated using Kaplan-Meier analysis. Prognostic factors were investigated using the Cox proportional hazard mod-el. RESULTS: Five-year local and distant intra hepatic recurrence rates were 10.4% and 70.9%, respectively. Five-year overall survival and recurrence-free survival rates were 60.3% and 15.9%, respectively. Multivarlate analysis revealed that an age of 75 years or more[relative hazard (RH) 1.61, p=0.019] and a serum al-bumin level less than 3.5g/dL (RH 1.61, p=0.016)were significant factors for decreased overall survival. Furthermore, a serum albumin level less than 3.5g/dL (RH 1.50, p=0.003) was the only significant factor for decreased recurrence-free survival. CONCLUSIONS: This study suggests that host-related factors (age and serum albumin level) are important in predicting survival in hepatitis C patients with a single small HCC af-ter RFA.

Efficacy of pazopanib in FGFR1-amplified uterine carcinosarcoma: A case report.

•We reported the use of pazopanib in the treatment of recurrent uterine carcinosarcoma with FGFR1 amplification.•The expert tumor board recommended pazopanib for off-label use based on genetic mutations found in cancer gene panels.•Pazopanib, a multi-tyrosine kinase inhibitor, was effective against recurrent uterine sarcoma with FGFR1 amplification.•Pazopanib maintained the patient's quality of life for a certain period.

Estimating the Haemodynamic Streamline Vena Contracta as the Effective Orifice Area Measured from Reconstructed Multislice Phase-contrast MR Images for Patients with Moderately Accelerated Aortic Stenosis.

PURPOSE: In aortic stenosis (AS), the discrepancy between moderately accelerated flow and effective orifice area (EOA) continues to pose a challenge. We developed a method of measuring the vena contracta area as hemodynamic EOA using cardiac MRI focusing on AS patients with a moderately accelerated flow to solve the problem that AS severity can currently be determined only by echocardiography. METHODS: We investigated 40 patients with a peak transvalvular velocity > 3.0 m/s on transthoracic echocardiography (TTE). The patients were divided into highly accelerated and moderately accelerated AS groups according to whether or not the peak transvalvular velocity was ≥ 4.0 m/s. From the multislice 2D cine phase-contrast MRI data, the cross-sectional area of the vena contracta of the reconstructed streamline in the Valsalva sinus was defined as MRI-EOAs. Patient symptoms and echocardiography data, including EOA (defined as TTE-EOA), were derived from the continuity equation using TTE. RESULTS: All participants in the highly accelerated AS group (n = 19) showed a peak velocity ≥ 4.0 m/s in MRI. Eleven patients in the moderately accelerated AS group (n = 21) had a TTE-EOA < 1.00 cm2. In the moderately accelerated AS group, MRI-EOAs demonstrated a strong correlation with TTE-EOAs (r = 0.76, P < 0.01). Meanwhile, in the highly accelerated AS group, MRI-EOAs demonstrated positivity but a moderate correlation with TTE-EOAs (r = 0.63, P = 0.004). MRI-EOAs were overestimated compared to TTE-EOAs. In terms of the moderately accelerated AS group, the best cut-off value for MRI-EOAs was < 1.23 cm2, compatible with TTE-EOAs < 1.00 cm2, with an excellent prediction of the New York Heart Association classification ≥ III (sensitivity 87.5%, specificity 76.9%). CONCLUSION: MRI-EOAs may be an alternative to conventional echocardiography for patients with moderately accelerated AS, especially those with discordant echocardiographic parameters.

A life-saving case of cardiopulmonary arrest with cardiac tamponade caused by erosion 6 years after percutaneous atrial septal defect closure: a case report.

BACKGROUND: Cardiac erosion after percutaneous atrial septal defect (ASD) closure is a rare complication that requires immediate life-saving emergency surgery. In this report, we present our successful life-saving strategy for cardiac arrest due to cardiac tamponade caused by erosion 6 years after the percutaneous closure of an ASD. CASE PRESENTATION: The patient was a 50-year-old man who received treatment using an Amplatzer septal occluder (St. Jude Medical, St. Paul, MN, USA) treatment for ostium secundum atrial septal defect (size: 29.5 × 27.0 mm) at another institution when he was 44 years old. CONCLUSIONS: This case report presents a bailout surgical strategy for patients who are hemodynamically unstable with risks of coagulopathy and multiple organ failure. This case shows that cardiac surgeons need to be aware of percutaneous ASD-closure complications and should consider a bailout surgical strategy for patients at risk of multiple organ failure.

Patient satisfaction with oral health check-ups at a community pharmacy and their effect on oral self-care habits and dental consultation behavior.

Maintaining good oral health is important because oral diseases are related to systemic diseases, and community pharmacies play a key role in maintaining the health of local residents. This study aimed to examine the effects of oral health check-ups and information provision at community pharmacies on oral health-associated behaviors as well as patient satisfaction. We conducted oral health check-ups and provided information about oral health self-care to 84 patients at a community pharmacy, and then asked them to complete a questionnaire survey. One month later, we sent them a follow-up questionnaire and received responses from 66.7% (56/84) of the participants. The large majority were satisfied with the salivary test (95.2%) and the information (96.4%) we provided. Most of the participants (89.3%) indicated that they wanted to use the oral health check-up service again in the future. Compared with baseline, the ratio of participants restricting their intake of sugar-rich foods and drinks significantly increased 1 month later (p = 0.021). About 60% of those who had not undergone a regular dental examination at baseline reported newly visiting or planning to visit a dental clinic. The results revealed high satisfaction with the oral health check-up and information about oral self-care they received at the community pharmacy. The results suggested that oral health check-ups had the potential to change both oral self-care habits and dental consultation behavior. Our findings indicate that community pharmacies can contribute to the maintenance and promotion of oral health by providing oral health check-ups to local residents.

Pegfilgrastim-induced fatigue and leukocytosis improved following dose reduction in a young patient with breast cancer: A case report.

Dose-dense (DD) chemotherapy is a treatment option for patients with high-risk premenopausal breast cancer. Pegfilgrastim may be administered as prophylaxis against the development of febrile neutropenia and enables the continuation of the DD schedule; however, it is associated with adverse effects, including bone and muscle pain and fatigue. We herein describe our experience with pegfilgrastim administration alongside DD chemotherapy in a patient with breast cancer. A 29-year-old female patient was diagnosed with locally advanced breast cancer during lactation. The patient was diagnosed with cT2N1M0, stage IIB triple-negative breast cancer and underwent four cycles of DD chemotherapy with epirubicin plus cyclophosphamide, followed by four cycles of docetaxel (DTX) every 2 weeks preoperatively, with 3.6 mg pegfilgrastim administered subcutaneously on day 3 of each cycle. The absolute neutrophil count (ANC) was 2,700, 8,400, 11,100, 13,300 and 15,000/mm3 on day 1 of each cycle. The patient experienced fatigue after each pegfilgrastim injection and was considered to be a high responder to pegfilgrastim. Therefore, 1.8 mg pegfilgrastim on day 3 of the first DD-DTX cycle was recommended. On day 1 of the second cycle, the ANC was 13,090/mm3. The patient experienced less fatigue after the administration of 1.8 mg pegfilgrastim, but there was a significant decline in her performance status. As there is currently no evidence of pegfilgrastim dose reduction to below 1.8 mg, pegfilgrastim was omitted on day 3. On day 14, the patient developed viral enteritis, fever (38°C), and an ANC of 297/mm3. Therefore, the third cycle was postponed. After 1 week, the patient's ANC recovered to 2,480/mm3 and she was administered the third cycle with 3.6 mg pegfilgrastim on day 3. Between January 2015 and March 2018, a total of 55 patients with breast cancer received chemotherapy with pegfilgrastim at the Shiga General Hospital. No patients other than the one presented herein experienced leukocytosis during chemotherapy. Although this was a rare complication, a dose of 1.8 mg pegfilgrastim was effective in palliating the patient's symptoms and preventing DD chemotherapy discontinuation.

Total arch replacement of late aneurysm after bypass grafting for coarctation of the aorta.

We present the case of a 53-year-old man who underwent a total arch replacement for descending thoracic aortic aneurysm of distal anastomosis site after bypass grafting for coarctation of the aorta at 26 years of age.

Mitral valve repair and cryo-Maze procedure in Ehlers-Danlos syndrome.

A 48-year-old man presented with typical features of Ehlers-Danlos syndrome, such as soft and hyperextensible skin, subcutaneous nodules, clubbed feet, and a mild degree of pigeon chest. In addition, his past history revealed congenital dislocation of the hip joint, retinal detachment, and repeated episodes of congestive heart failure due to severe mitral regurgitation and atrial fibrillation. We subjected the patient to surgical repair of the mitral valve combined with the maze procedure, which proved successful.

Successful treatment of a patient with sepsis and liver abscess caused by Edwardsiella tarda.

Edwardsiella tarda is a bacterium that is associated with both an asymptomatic oral carrier state and self-limiting diarrhoeal illness in humans. We herein report a case of sepsis and liver abscess caused by E. tarda and review the patients with E. tarda sepsis who presented at our hospital. An 85-year-old woman developed enterocolitis and sepsis caused by E. tarda. She was administered intensive care and thus was able to soon show a good recovery, however, she subsequently developed a liver abscess. During a complicated course, she continued to be treated with antibiotics and after a successful course was discharged on the 44th day after admission.