Assessment for the timing of comprehensive genomic profiling tests in patients with advanced solid cancers.

Comprehensive genomic profiling (CGP) tests have been covered by public insurance in Japan for patients with advanced solid tumors who have completed or are completing standard treatments or do not have them. Therefore, genotype-matched drug candidates are often unapproved or off-label, and improving clinical trial access is critical, involving the appropriate timing of CGP tests. To address this issue, we analyzed the previous treatment data for 441 patients from an observational study on CGP tests discussed by the expert panel at Hokkaido University Hospital between August 2019 and May 2021. The median number of previous treatment lines was two; three or more lines accounted for 49%. Information on genotype-matched therapies was provided to 277 (63%). Genotype-matched clinical trials were ineligible because of an excess number of previous treatment lines or use of specific agents were found in 66 (15%) patients, with the highest proportion in breast and prostate cancers. Many patients met the exclusion criteria of one to two or more treatment lines across cancer types. In addition, previous use of specific agents was a frequent exclusion criterion for breast, prostate, colorectal, and ovarian cancers. The patients with tumor types with a low median number (two or fewer) of previous treatment lines, including most rare cancers, primary unknown cancers, and pancreatic cancers, had significantly fewer ineligible clinical trials. The earlier timing of CGP tests may improve access to genotype-matched clinical trials, with their proportion varying by cancer type. Each relevant society needs to advocate the desirable timing of CGP testing nationwide.

Chronological improvement in precision oncology implementation in Japan.

In Japan, comprehensive genomic profiling (CGP) tests for refractory cancer patients have been approved since June 2019, under the requirement that all cases undergoing CGP tests are annotated by the molecular tumor board (MTB) at each government-designated hospital. To investigate improvement in precision oncology, we evaluated and compared the proportion of cases receiving matched treatments according to CGP results and those recommended to receive genetic counseling at all core hospitals between the first period (11 hospitals, June 2019 to January 2020) and second period (12 hospitals, February 2020 to January 2021). A total of 754 and 2294 cases underwent CGP tests at core hospitals in the first and second periods, respectively; 28 (3.7%) and 176 (7.7%) patients received matched treatments (p < 0.001). Additionally, 25 (3.3%) and 237 (10.3%) cases were recommended to receive genetic counseling in the first and second periods, respectively (p < 0.001). The proportion was associated with the type of CGP test: tumor-only (N = 2391) vs. tumor-normal paired (N = 657) analysis (10.0% vs. 3.5%). These results suggest that recommendations regarding available clinical trials in networked MTBs might contribute to increasing the numbers of matched treatments, and that tumor-normal paired rather than tumor-only tests can increase the efficiency of patient referrals for genetic counseling.

Expert panel consensus recommendations on the use of circulating tumor DNA assays for patients with advanced solid tumors.

Comprehensive genomic profiling is increasingly used to facilitate precision oncology based on molecular stratification. In addition to conventional tissue comprehensive genomic profiling, comprehensive genomic profiling of circulating tumor DNA has become widely utilized in cancer care owing on its advantages, including less invasiveness, rapid turnaround time, and capturing heterogeneity. However, circulating tumor DNA comprehensive genomic profiling has some limitations, mainly false negatives due to low levels of plasma circulating tumor deoxyribonucleic acid and false positives caused by clonal hematopoiesis. Nevertheless, no guidelines and recommendations fully address these issues. Here, an expert panel committee involving representatives from 12 Designated Core Hospitals for Cancer Genomic Medicine in Japan was organized to develop expert consensus recommendations for the use of circulating tumor deoxyribonucleic acid-based comprehensive genomic profiling. The aim was to generate guidelines for clinicians and allied healthcare professionals on the optimal use of the circulating tumor DNA assays in advanced solid tumors and to aid the design of future clinical trials that utilize and develop circulating tumor DNA assays to refine precision oncology. Fourteen clinical questions regarding circulating tumor deoxyribonucleic acid comprehensive genomic profiling including the timing of testing and considerations for interpreting results were established by searching and curating associated literatures, and corresponding recommendations were prepared based on the literature for each clinical question. Final consensus recommendations were developed by voting to determine the level of each recommendation by the Committee members.

Stratification of Postoperative Prognosis by Invasive Tumor Thickness in Perihilar Cholangiocarcinoma.

BACKGROUND: The pathological tumor classification of distal cholangiocarcinoma in the American Joint Committee on Cancer (AJCC) Cancer Staging Manual 8th edition is based on invasive depth, whereas that of perihilar cholangiocarcinoma (PHCC) continues to be layer-based. We aimed to clarify whether invasive depth measurement based on invasive tumor thickness (ITT) could help determine postoperative prognosis in patients with PHCC. METHODS: We enrolled 184 patients with PHCC who underwent hepatectomy plus extrahepatic bile duct resection or hepatopancreatoduodenectomy with curative intent. ITT was measured using simple definitions according to the sectioning direction or gross tumor pattern. RESULTS: The median ITT was 5.8 mm (range 0.7-15.5). Using the recursive partitioning technique, ITT was classified into grades A (ITT < 2 mm, n = 9), B (2 mm ≤ ITT < 5 mm, n = 68), C (5 mm ≤ ITT < 11 mm, n = 81), and D (11 mm < ITT, n = 26). The median survival times (MSTs) in patients with grade B, C, or D were 90.8, 44.6, and 21.1 months, respectively (patients with grade A did not reach the MST). There were significant differences in postoperative prognosis between ITT grades (A vs. B, p = 0.027; B vs. C, p < 0.001; C vs. D, p = 0.004). Through multivariate analysis, regional node metastasis, invasive carcinoma at the resected margin, and ITT grade were determined as independent prognostic factors. CONCLUSION: ITT could be measured using simple methods and may be used to stratify postoperative prognosis in patients with PHCC.

Clinical significance of comprehensive genomic profiling tests covered by public insurance in patients with advanced solid cancers in Hokkaido, Japan.

BACKGROUND: Comprehensive cancer genomic profiling has been used recently for patients with advanced solid cancers. Two cancer genomic profiling tests for patients with no standard treatment are covered by Japanese public health insurance since June 2019. METHODS: We prospectively analyzed data of 189 patients with solid cancers who underwent either of the two-cancer genomic profiling tests at Hokkaido University Hospital and its liaison hospitals and whose results were discussed in molecular tumor board at Hokkaido University Hospital between August 2019 and July 2020. RESULTS: All 189 patients had appropriate results. Actionable gene alterations were identified in 93 patients (49%). Frequent mutations included PIK3CA (12%) mutation, BRCA1/2 alteration (7%), ERBB2 amplification (6%) and tumor mutation burden-High (4%). The median turnaround time from sample shipping to acquisition by the expert panel was 26 days. Although 115 patients (61%) were provided with information for genotype-matched therapies, only 21 (11%) received them. Notably, four of eight patients below the age of 20 years were provided information for genotype-matched therapies, and three received them. Their response rates and disease control rates were 29% and 67%, respectively. Most patients who did not undergo the genotype-matched therapies were provided information for only investigational drugs in phases I and II at distant clinical trial sites in central Japan. Twenty-six patients were informed of suspected germline findings, while 11 patients (42%) received genetic counseling. CONCLUSIONS: The publicly reimbursed cancer genomic profilings may lead to the modest but favorable therapeutic efficacy of genotype-matched therapy for solid cancer patients with no standard therapy. However, poor access to genotype-matched therapy needs to be resolved.

Risk Factors for Delayed Bleeding after Therapeutic Gastrointestinal Endoscopy in Patients Receiving Oral Anticoagulants: A Multicenter Retrospective Study.

BACKGROUND/AIMS: Delayed bleeding is among the adverse events associated with therapeutic gastrointestinal endoscopy. The aim of this study was to evaluate risk factors for delayed bleeding after gastrointestinal endoscopic resection in patients receiving oral anticoagulants as well as to compare the rates of occurrence of delayed bleeding between the oral anticoagulants used. METHODS: We retrospectively analyzed a total of 772 patients receiving anticoagulants. Of these, 389 and 383 patients were receiving direct oral anticoagulants (DOACs) and warfarin, respectively. Therapeutic endoscopic procedures performed included endoscopic submucosal dissection (ESD), endoscopic mucosal resection, polypectomy, and cold polypectomy. RESULTS: Delayed bleeding occurred in 90 patients (11.7%) with no significant difference between the DOAC and warfarin groups (9.5 and 13.8%, respectively). Delayed bleeding occurred significantly more frequently with apixaban than with rivaroxaban (13.5 vs. 6.4%; p < 0.05). A multivariate analysis identified continued anticoagulant therapy (OR 2.29), anticoagulant withdrawal with heparin bridging therapy (HBT; OR 2.18), anticoagulant therapy combined with 1 antiplatelet drug (OR 1.72), and ESD (OR 3.87) as risk factors for delayed bleeding. CONCLUSION: This study identified continued anticoagulant therapy, anticoagulant withdrawal with HBT, anticoagulant therapy combined with 1 antiplatelet drug, and ESD as risk factors for delayed bleeding after therapeutic endoscopy in patients receiving oral anticoagulants. Delayed bleeding rates were not significantly different between those receiving DOACs and warfarin. It was also suggested that the occurrence of delayed bleeding may vary between different DOACs and that oral anticoagulant withdrawal should be minimized during therapeutic gastrointestinal endoscopy, given the thromboembolic risk involved.

The initial assessment of expert panel performance in core hospitals for cancer genomic medicine in Japan.

BACKGROUND: Since June 2019, cancer genomic profiling (CGP) tests have been reimbursed by the National Health Insurance system in Japan, with restrictions for government-designated hospitals with a molecular tumor board composed of multidisciplinary specialists, known as an expert panel (EP). The standardization of EPs is a critical challenge for implementing precision oncology in the clinical setting. METHODS: Data on consecutive cases who underwent the CGP tests at 11 core hospitals between June 2019 and January 2020 were collected. We evaluated the proportions of cases that received genomically matched treatments, including investigational new drugs (INDs) based on CGP results, and/or for which genetic counseling was recommended. Two simulated cases were annotated by each EP. The annotated reports were then centrally assessed. RESULTS: Each EP mainly discussed the applicability to genomically matched treatments and the necessity of performing genetic counseling. A pre-review of the report by key members in each EP reportedly made the EP conference more interactive and efficient, and thereby saved time. A total of 747 cases underwent CGP tests, 28 cases (3.7%) received genomically matched treatment, and 17 cases (2.3%) were referred for genetic counseling. Annotated reports for the simulated cases varied across the EPs, particularly the number of recommended IND trials, which seemed to be associated with the actual number of participants in IND trials. CONCLUSIONS: This investigation provides reference data for the application of precision oncology in a clinical setting. Further investigations on the standardization of clinical annotations are warranted.

Phase II trial of combination treatment with S-1/cetuximab in patients with platinum-ineligible recurrent and/or metastatic squamous cell carcinoma of the head and neck.

BACKGROUND: The standard of care for first-line treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) in patients who cannot tolerate platinum-based regimens has not been clarified. We aimed to develop a new treatment regimen for patients with R/M SCCHN who are ineligible for platinum-based therapy, by evaluating the effects and safety of tegafur/gimeracil/oteracil (S-1) and cetuximab. METHODS: Platinum-ineligibility was defined as: elderly (aged ≥ 75 years), poor PS, comorbidity, platinum resistance and refusal to undergo platinum-based therapy. Patients received S-1 (80 mg/m2/day for 14 days followed by a seven-day break) and cetuximab (initial dose, 400 mg/m2, followed by 250 mg/m2 weekly) until disease progression or unacceptable toxicity. The primary endpoint was overall response rate (ORR). RESULTS: Between September 2014 and September 2018, we enrolled 23 patients. Among the 21 patients who were evaluable, 20 were male [median age, 69 years (range 49-82)]. The ORR was 9 (43%) of 21 patients [95% confidence interval (CI) 22-66]. One and eight patients achieved complete response (CR) and partial response (PR), respectively. The median overall survival (OS) was 13.7 months (95% CI 9.0-18.3) and progression-free survival (PFS) was 5.7 months (95% CI 3.1-8.2). Grade 3/4 adverse events included acneiform rash and skin reactions (33%), hypomagnesemia (19%), hand-foot syndrome (14%), fatigue (14%), mucositis (10%), and anorexia (10%). CONCLUSIONS: Combination treatment with S-1 and cetuximab was effective and tolerated well by patients with platinum-ineligible R/M SCCHN. Registered clinical trial number: UMIN000015123.

Clinical practice guidance for next-generation sequencing in cancer diagnosis and treatment (edition 2.1).

BACKGROUND: To promote precision oncology in clinical practice, the Japanese Society of Medical Oncology, the Japanese Society of Clinical Oncology, and the Japanese Cancer Association, jointly published "Clinical practice guidance for next-generation sequencing in cancer diagnosis and treatment" in 2017. Since new information on cancer genomic medicine has emerged since the 1st edition of the guidance was released, including reimbursement for NGS-based multiplex gene panel tests in 2019, the guidance revision was made. METHODS: A working group was organized with 33 researchers from cancer genomic medicine designated core hospitals and other academic institutions. For an impartial evaluation of the draft version, eight committee members from each society conducted an external evaluation. Public comments were also made on the draft. The finalized Japanese version was published on the websites of the three societies in March 2020. RESULTS: The revised edition consists of two parts: an explanation of the cancer genomic profiling test (General Discussion) and clinical questions (CQs) that are of concern in clinical practice. Particularly, patient selection should be based on the expectation that the patient's post-test general condition and organ function will be able to tolerate drug therapy, and the optimal timing of test should be considered in consideration of subsequent treatment plans, not limited to treatment lines. CONCLUSION: We expect that the revised version will be used by healthcare professionals and will also need to be continually reviewed in line with future developments in cancer genome medicine.

[Development of a System for Providing Cancer Genomic Medicine in Hokkaido-From the Standpoint of a Designated Core Hospital for Cancer Genomic Medicine].

Hokkaido University Hospital has been designated as a Core Hospital for Cancer Genomic Medicine and developed a system to provide cancer genomic medicine in Hokkaido with its liaison hospitals. Since being reimbursed in June 2019, comprehensive cancer genome profiling (CGP) testing showed certain therapeutic efficacy in patients with no standard treatment options, but it also revealed some problems such as the small number of patients who can receive therapeutic drugs matched with gene abnormalities. Since candidate drugs are often unapproved or off-label, it is necessary to smoothly introduce clinical trials, advanced medical treatment system, and patient-proposed health care service. At our hospital, we are focusing on sharing information on clinical trials being conducted in Hokkaido, launching investigator-initiated clinical trials, promoting patient-proposed health care service, promoting a registry study of genetic profiling and targeted therapies in patients with rare cancers and accompanying clinical trials, and incorporating pediatric cancer patients. This paper describes Hokkaido's cancer genomic medicine provision system, including its exit strategy, and the human resource development that serve as its foundation.

Clinical impact of a cancer genomic profiling test using an in-house comprehensive targeted sequencing system.

Precision medicine is a promising strategy for cancer treatment. In this study, we developed an in-house clinical sequencing system to perform a comprehensive cancer genomic profiling test as a clinical examination and analyzed the utility of this system. Genomic DNA was extracted from tumor tissues and peripheral blood cells collected from 161 patients with different stages and types of cancer. A comprehensive targeted amplicon exome sequencing for 160 cancer-related genes was performed using next-generation sequencing (NGS). The sequencing data were analyzed using an original bioinformatics pipeline, and multiple cancer-specific gene alterations were identified. The success rate of our test was 99% (160/161), while re-biopsy was required for 24% (39/161) of the cases. Potentially actionable and actionable gene alterations were detected in 91% (145/160) and 46% (73/160) of the patients, respectively. The actionable gene alterations were frequently detected in PIK3CA (9%), ERBB2 (8%), and EGFR (4%). High tumor mutation burden (TMB) (≥10 mut/Mb) was observed in 12% (19/160) of the patients. The secondary findings in germline variants considered to be associated with hereditary tumors were detected in 9% (15/160) of the patients. Seventeen patients (11%, 17/160) were treated with genotype-matched therapeutic agents, and the response rate was 47% (8/17). The median turnaround time for physicians was 20 days, and the median survival time after the initial visit was 8.7 months. The results of the present study prove the feasibility of implementing in-house clinical sequencing as a promising laboratory examination technique for precision cancer medicine.

Time to Recurrence After Surgical Resection and Survival After Recurrence Among Patients with Perihilar and Distal Cholangiocarcinomas.

BACKGROUND: The differences between perihilar cholangiocarcinoma (PHCC) and distal cholangiocarcinoma (DCC) regarding recurrence and the factors that affect recurrence after surgery are unclear. This study aims to investigate the differences in recurrence patterns between patients with PHCC and those with DCC after surgical resection with curative intent. It also investigates the risk factors associated with recurrence and survival thereafter. PATIENTS AND METHODS: The postoperative courses of 366 patients with extrahepatic cholangiocarcinomas (EHCCs), including 236 with PHCC and 130 with DCC, who underwent surgical resections were investigated retrospectively. RESULTS: During follow-up, tumors recurred in 143 (60.6%) patients with PHCC and in 72 (55.4%) patients with DCC. Overall survival (OS) after surgery, recurrence-free survival (RFS), and OS after recurrence were similar for the patients with PHCC and those with DCC. The cumulative probability of recurrence declined 3 years after surgery in the patients with PHCC and those with DCC. A multivariable analysis determined that, among the patients with PHCC and those with DCC, regional lymph node metastasis was a significant risk factor associated with RFS. Ten patients with PHCC and eight patients with DCC with two or fewer sites of recurrence in a single organ underwent resections. A multivariable analysis determined that recurrent tumor resection was an independent prognostic factor associated with OS after recurrence in the patients with PHCC and those with DCC. CONCLUSIONS: Postoperative survival did not differ between the patients with PHCC and those with DCC. Frequent surveillances for recurrence are needed for 3 years after surgical resection of EHCCs. In selected patients, surgery for recurrent EHCCs might be associated with improved outcomes.

Impact of tumour budding grade in 310 patients who underwent surgical resection for extrahepatic cholangiocarcinoma.

AIMS: Tumour budding is a risk factor for poor prognosis in various cancers. Tumour buds may present an epithelial-mesenchymal transition (EMT) morphological phenotype. This study aimed to elucidate the prognostic impact of tumour budding grade and its association with clinicopathological and EMT-related features in perihilar cholangiocarcinoma (PHCC) or distal cholangiocarcinoma (DCC). METHODS AND RESULTS: Subjects included 195 PHCC and 115 DCC patients. The numbers of tumour buds in different patients were stratified for postoperative survival using the recursive partitioning technique. Consequently, the numbers of tumour buds in PHCC patients were classified into three grades; namely, low (0-4 buds); intermediate (5-11 buds); and high (≥12 buds); those of DCC patients were classified into two grades; namely, low (0-4 buds) and high (≥5 buds). In both PHCC and DCC patients, high tumour budding grade was associated with poor histological differentiation, higher pT factor, presence of lymphatic, venous, perineural invasion and regional lymph node metastasis. In PHCC patients, residual invasive tumour in the resected margin was also associated with high tumour budding grade. For both PHCC and DCC patients, high tumour budding grade was an independent adverse prognostic factor in multivariate analysis (P < 0001 and P = 0.046, respectively). Immunohistochemical examination revealed that the number of tumour buds increased in patients with tumours showing a mesenchymal profile (negative for E-cadherin and positive for vimentin). CONCLUSIONS: Higher tumour budding grade is associated with invasive clinicopathological features, adverse postoperative prognosis and EMT status in extrahepatic cholangiocarcinoma.

Genomic testing for pancreatic cancer in clinical practice as real-world evidence.

BACKGROUND: Precision medicine guided by comprehensive genome sequencing represents a potential treatment strategy for pancreatic cancer. However, clinical sequencing for pancreatic cancer entails several practical difficulties. We have launched an in-house clinical sequencing system and started genomic testing for patients with cancer in clinical practice. We have analyzed the clinical utility of this system in pancreatic cancer. METHODS: We retrospectively reviewed 20 patients with pancreatic cancer who visited our division. Genomic DNA was extracted from both tumor tissue and peripheral blood mononuclear cells obtained from the patients. We performed a comprehensive genomic testing using targeted amplicon sequencing for 160 cancer-related genes. The primary endpoints were the detection rates of potential actionable and druggable gene alterations. The secondary endpoints were the detection rate of secondary germline findings, the rate of re-biopsy required for genome sequencing, survival time after the initial visit (post-sequencing survival time), and turnaround time. RESULTS: Although re-biopsy was required for 25% (5/20) of all patients, genomic testing was performed in all patients. Actionable and druggable gene alterations were detected in 100% (20/20) and 35% (7/20) of patients, respectively, whereas secondary germline findings were detected in 5% (1/20) of patients. The median turnaround times for physicians and patients were 20 and 26 days, respectively. The median post-sequencing survival time was 10.3 months. Only 10% (2/20) of all patients were treated with therapeutic agents based on the outcomes of genomic testing. CONCLUSIONS: The clinical application of comprehensive genomic testing for pancreatic cancer was feasible and promising in clinical practice.

A phase II study of carboplatin, pemetrexed, and bevacizumab followed by erlotinib and bevacizumab maintenance for non-squamous non-small cell lung cancer with wild-type EGFR (HOT1101).

BACKGROUND: This study evaluated the efficacy and safety of switch maintenance erlotinib and bevacizumab after induction therapy with carboplatin/pemetrexed/bevacizumab for non-squamous non-small cell lung cancer (NSCLC) with wild-type EGFR. METHODS: Enrolled patients had treatment-naïve, advanced non-squamous NSCLC with wild-type EGFR. Carboplatin [area under the curve (AUC) 5.0], pemetrexed (500 mg/m2) and bevacizumab (15 mg/kg) were administered on day 1 every 3 weeks for 4-6 cycles. Maintenance therapy with erlotinib (150 mg/body) on day 1 through 21 plus bevacizumab on day 1 every 3 weeks was continued until disease progression or unacceptable toxicity. The primary endpoint was 6-month progression-free survival (PFS); secondary endpoints included overall survival (OS), overall response rate (ORR), toxicity, and quality of life (QOL). RESULTS: Fifty-one patients were enrolled between September 2011 and June 2014. The median number of cycles for induction and maintenance therapy was 4 (range 1-6) and 4 (range 1-20). Twenty-nine patients (58%) received maintenance therapy. The 6-month PFS rate was 59.5% [95% confidence interval (CI) 45.0-72.6%]. The ORR was 48.0% (95% CI 34.8-61.5%), and disease control rate was 86.0% (95% CI 73.8-93.0%). The median PFS and OS were 6.5 months (95% CI 5.8-7.2 months) and 21.4 months (95% CI 15.9-26.9 months), respectively. Although grades ≥ 3 adverse events were observed in 33 patients (66.0%), most were hematologic; there was no febrile neutropenia. QOL was maintained throughout treatment. CONCLUSIONS: Carboplatin/pemetrexed/bevacizumab followed by erlotinib and bevacizumab maintenance showed modest efficacy and was well tolerated in non-squamous NSCLC patients with wild-type EGFR. TRIAL REGISTRATION: UMIN000005872.

Liver elasticity measurement before and after biliary drainage in patients with obstructive jaundice: a prospective cohort studya prospective cohort study.

BACKGROUND: Obstructive jaundice has been reported to influence liver elasticity, independent of liver fibrosis. The aim of our prospective study was to evaluate the changes in liver elasticity, before and after biliary drainage, in patients with obstructive jaundice, and to evaluate the correlation between elasticity measures and serum markers of liver fibrosis. METHODS: This is a prospective cohort study of 20 patients with obstructive jaundice. Liver elasticity was assessed by Transient Elastography (TE) and Virtual Touch™ Quantification (VTQ). Serum total bilirubin (T-Bil) level was measured before biliary drainage (Day 0), with measures repeated at 2 days (Day 2) and 7 days (Day 7) after biliary drainage. Serum levels of the following markers of liver fibrosis were also obtained on Day 0 and Day 7: hyaluronic acid (HA), procollagen-III-peptide (P-III-P). RESULTS: T-Bil, TE, and VTQ for the left (VTQ-L) and right (VTQ-R) lobes of the liver were all elevated before biliary drainage, with respective levels, measured at Day 0, of 11.9 ± 1.5 mg/dl, 12.1 ± 0.9 kPa, 2.23 ± 0.10 m/s, and 1.85 ± 0.10 m/s. All values decreased on Day 7 after drainage: T-Bil, 4.7 ± 1.0 mg/dl (P < 0.001); TE, 7.6 ± 0.6 kPa (P < 0.001); VTQ-L, 1.53 ± 0.08 m/s (P < 0.001); and VTQ-R, 1.30 ± 0.05 m/s (P < 0.001). Similar changes were observed in serum markers of liver fibrosis. Liver elasticity measures correlated with serum levels of T-Bil, P-III-P, and HA (r = 0.35-0.67, P < 0.001). CONCLUSIONS: This study confirmed decreases in liver elasticity, measured by TE and VTQ, after biliary drainage. Measures of liver elasticity correlated to levels of T-Bil and serum markers of liver fibrosis. (UMIN ID: UMIN00001284313). REGISTRATION NUMBER: University Hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN ID: UMIN00001284313 ); Registration date: 2014-01-14.

Value of Virtual Touch Quantification Elastography for Assessing Liver Congestion in Patients With Heart Failure.

BACKGROUND: Heart failure (HF) causes organ congestion, which is thought to increase organ stiffness. The virtual touch quantification (VTQ) method can be used to assess liver stiffness in patients with chronic liver diseases. This study aimed to measure liver and kidney stiffness using VTQ and to determine its value for assessing organ congestion in patients with HF. METHODS AND RESULTS: This study included 10 normal subjects and 38 HF patients (age 52.3±16.7 years, left ventricular ejection fraction 27.0±9.4%, plasma B-type natriuretic peptide [BNP] 1,297.3±1,155.1 pg/ml). We investigated the relationships between clinical characteristics and hemodynamics and liver and kidney stiffness, and assessed the effects of medical treatment on these measurements. Liver stiffness was significantly higher in HF patients (1.17±0.13 m/s vs. 2.03±0.91 m/s, P=0.004) compared with normal subjects, but kidney stiffness was similar in both groups. Central venous pressure (CVP) (P=0.021) and BNP (P=0.025) were independent predictive factors for increased liver stiffness in HF patients. Liver stiffness decreased significantly from 2.37±1.09 to 1.27±0.33 m/s (P<0.001) after treatment. Changes in liver stiffness in HF patients significantly correlated with changes in CVP (R=0.636, P=0.014) and cardiac index (R=-0.557, P=0.039) according to univariate analysis, and with changes in CVP in multivariate analysis. CONCLUSIONS: Liver stiffness measured by noninvasive VTQ methods can be used to assess liver congestion and therapeutic effects in patients with HF. (Circ J 2016; 80: 1187-1195).

Predictive factors of long head of the biceps tendon disorders-the bicipital groove morphology and subscapularis tendon tear.

BACKGROUND: Disorders of the long head of the biceps (LHB) tendon contribute to anterior shoulder pain. Although LHB tendon disorders are associated with rotator cuff disease, distinguishing between biceps and rotator cuff pathology is difficult. The objective was to identify the predictors of LHB tendon disorders associated with a supraspinatus tear. METHODS: In 55 patients (average age, 65 years) undergoing arthroscopic rotator cuff repair, bicipital groove morphology were assessed using computed tomography, and subscapularis tear and bicipital groove effusion were assessed using magnetic resonance imaging, retrospectively. The LHB tendon was evaluated arthroscopically according to the Lafosse classification. Univariate and multivariate ordinal logistic regression analyses were conducted for injury grade with all covariates. RESULTS: The arthroscopic evaluation of the LHB tendon showed that there were 23 shoulders classified as grade 0, 15 as grade 1, and 17 as grade 2. Univariate logistic regression analysis showed that the width and depth, a medial spur of the bicipital groove, and a subscapularis tear were significantly associated with LHB tendon disorders. Multivariate ordinal logistic regression analysis identified a medial spur and subscapularis tear as significant predictors of LHB tendon disorders. CONCLUSIONS: The preoperative computed tomography and magnetic resonance images, notably the presence of a spur on the bicipital groove or a subscapularis tear, were useful for identifying LHB tendon disorders. When these are found in preoperative images, the clinician should evaluate the patient for the presence of an LHB tendon disorder as a pain generator.

Risk factors for a high Comprehensive Complication Index score after major hepatectomy for biliary cancer: a study of 229 patients at a single institution.

BACKGROUND: The Comprehensive Complication Index (CCI) is a new tool to evaluate the postoperative condition by calculating the sum of all complications weighted by their severity. The aim of this study was to identify independent risk factors for a high CCI score (≥40) in 229 patients after major hepatectomies with biliary reconstruction for biliary cancers. METHODS: The CCI was calculated online via www.assessurgery.com. Independent risk factors were identified by multivariable analysis. RESULTS: 57 (25%) patients were classified as having CCI ≥ 40. On multivariable analysis, volume of intraoperative blood loss (≥2.5 L) (p = 0.004) and combined pancreatoduodenectomy (PD) (p = 0.006) were independent risk factors for CCI ≥ 40. A high level of maximum serum total bilirubin was identified as independent risk factors for a high volume of intraoperative blood loss. Liver failure (p = 0.046) was more frequent in patients with combined PD than in those without. DISCUSSION: Patients who undergo preoperative external biliary drainage for severe jaundice might have impaired production of coagulation factors. When blood loss during liver transection becomes difficult to control, surgeons should consider various strategies, such as second-stage biliary or pancreatic reconstruction. In patients planned to undergo major hepatectomy with combined PD, preoperative portal vein embolization is mandatory to prevent postoperative liver failure.