Single-facility study of the effectiveness of rehabilitation therapy using wearable hybrid assistive limb for patients with bleeding disorders: study protocol for a randomised controlled trial.

INTRODUCTION: Haemophilic arthropathy, a serious complication of haemophilia, results from recurrent joint bleeding, causing progressive joint damage and severely impacting patient quality of life. Rehabilitation therapy (RT) effectively addresses declining physical function due to joint degradation, but pain during RT can hinder its success. Therefore, an effective pain-alleviating treatment method is required. The single-joint hybrid assistive limb (HAL-SJ), a powered exoskeleton, measures bioelectric potential during muscle contraction and provides motorised support, potentially alleviating pain. OBJECTIVE: This study outlines our protocol for a randomised, prospective, single-blind (evaluator) trial aimed to investigate the effects of HAL-SJ on pain reduction during RT, kinesiophobia and other physical functions in patients with haemophilia. METHODS AND ANALYSIS: This two-group comparison intervention study will include 24 male patients aged 12-85 years diagnosed with a bleeding disorder necessitating RT for pain and physical function improvement. The primary outcome measures pain changes during the first and second RT session in patients receiving HAL-SJ-assisted RT compared with traditional RT without HAL-SJ. The secondary outcomes include kinesiophobia (Japanese version of the Tampa Scale for Kinesiophobia), standing position gait (zebris FDM-T treadmill), range of motion (manual goniometer) and body surface temperature (infrared thermography camera) during the study period of up to 3 months or until the end of 10 RTs. RT intensity remains below that required to move the affected joint against gravity, given HAL-SJ's muscular support. The follow-up period extends to 1 month after the last RT. Intergroup study variables are compared by an unpaired t-test or Mann-Whitney test. Intragroup comparisons of secondary outcomes are analysed by a paired t-test or Wilcoxon signed-rank test. ETHICS AND DISSEMINATION: This study was approved by the accreditation committee of Nara Medical University Hospital. The study results will disseminate through publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: jRCTs052220076.

Efficacy and safety of tazobactam/ceftolozane in combination with metronidazole for intraabdominal infection in a hepato-biliary-pancreatic field in clinical practice.

INTRODUCTION: This single-center study evaluated the efficacy and safety of tazobactam/ceftolozane (TAZ/CTLZ) in combination with metronidazole for intraabdominal infection in a hepato-biliary-pancreatic field in clinical practice. METHODS: This study included 50 patients, including 35 with intraabdominal abscess or peritonitis, 5 with liver abscess, 4 with cholecystitis, and 6 with cholangitis with sepsis. Of the 50 patients, 29 received TAZ/CTLZ and metronidazole after a prior antibacterial therapy failure, including tazobactam/piperacillin, cefmetazole, and levofloxacin. Source control was performed in 36 patients. RESULTS: The clinical response could be evaluated in 49 patients. The clinical cure rate at end-of-therapy was 91.8% (45 of 49 patients) and that at test-of-cure was 89.6% (43 of 48 patients). Of 5 patients in whom clinical response at test-of-cure was a failure, 1 developed infectious disease during chemoradiotherapy for recurrent cancer and 4 after liver resection or pancreatoduodenectomy. Three of the 4 patients were associated with pancreatic juice leakage. Isolated pathogens were eradicated or presumably eradicated in 27 of 31 (87.1%) patients in whom microbiological response at test-of-cure could be evaluated. The response rate for AmpC-producing Enterobacteriaceae was 87.5%. Nausea was observed in two patients. Aspartate and alanine aminotransferase activities were increased in 3 of the 50 (6.0%) patients. The activities improved after the antibiotic discontinuation. CONCLUSIONS: This observational study demonstrated that TAZ/CTLZ in combination with metronidazole has a favorable effect without major drug-related adverse events for intraabdominal infection in the hepato-biliary-pancreatic field in clinical practice although the efficacy of TAZ/CTLZ may decrease in compromised patients.

[Early Experience with MRI-Ultrasound Fusion-Guided Prostate Biopsy in Our Institution].

A total of 100 patients were retrospectively analyzed with magnetic resonance imaging-ultrasonography (MRI-US) fusion biopsy(KOELIS, TRINITY®) at our institution between October 2019 and May 2020. The median patient age was 71 years, median prostate specific antigen (PSA) level was 7.4 ng/ml, and median PSA-density was 0.183 mg/ml. Sixty-one of the patients were positive for cancer ; 14 of them were positive by targeted biopsy only, 9 were positive by systematic biopsy only, and 38 were positive by both. Clinically significant prostate cancer (CPSC ; Gleason Score ≥3＋4 and % core ≥50%) was detected by target biopsies in 46 patients and by systematic biopsies in 33 patients. The positive core detection rate for CSPC was 32.5% for targeted biopsies and 7.0% for systematic biopsies(P＜0.0001), with a significantly higher rate for targeted biopsies. These results indicate that in MRI-US fusion biopsy, targeted biopsy has a higher detection rate for cancer and a significantly higher detection rate for clinically significant prostate cancer compared with systematic biopsy.

Laparoscopic liver resection reduces postoperative infection in patients with hepatocellular carcinoma: a propensity score-based analysis.

BACKGROUND: This study is aimed to compare the occurrence of postoperative infections between patients with hepatocellular carcinoma (HCC) undergoing laparoscopic liver resection (LLR) and those undergoing open liver resection (OLR). METHODS: This study included 446 patients who underwent initial curative liver resection for HCC 5 cm or less in size without macroscopic vascular invasion. To adjust for confounding factors between the LLR and OLR groups, propensity score matching and inverse probability weighting (IPW) analysis were performed. The incidence rates of postoperative infection, including incisional surgical site infection (SSI), organ/space SSI, and remote infection (RI), were compared between the two groups. RESULTS: An imbalance in several confounding variables, including period of surgery, extent of liver resection, difficult location, proximity to a major vessel, tumor size ≥ 3 cm, and multiple tumors, was observed between the two groups in the original cohort. After matching and weighting, the imbalance between the two groups significantly decreased. Compared with OLR, LLR was associated with a lower volume of intraoperative blood loss (140 vs. 350 mL, P < 0.001 in the matched cohort; 120 vs. 320 mL, P < 0.001 in the weighted cohort) and reduced risk of postoperative infection (2.0% vs. 12%, P = 0.015 in the matched cohort; 2.9% vs. 14%, P = 0.005 in the weighted cohort). Of the types of postoperative infections, organ/space SSI and RI were less frequently observed in the LLR group than in the OLR group in the matched cohort (1.0% vs. 6.0%, P = 0.091 for organ/space SSI; 0% vs. 6.0%, P < 0.001 for RI) and in the weighted cohort (1.2% vs. 7.8%, P < 0.001 for organ/space SSI; 0.3% vs. 5.1%, P = 0.009 for RI). CONCLUSIONS: Compared with OLR, LLR for HCC might reduce postoperative infections, including organ/space SSI and RI.

Improvement in lower extremity hemiplegia in a post-operative brain tumor patient by applying an integrated volitional control electrical stimulator.

[Purpose] This study aimed to evaluate the improvement in lower extremity hemiplegia following brain tumor operation with an integrated volitional control electrical stimulator (IVES). [Participant and Methods] A 40 year-old male with anaplasic oligodendroglioma in the right frontal lobe underwent IVES in the rectus femoris and tibialis anterior muscles using the power-assist and sensor-trigger modes. Lower extremity motor function was assessed before and after the therapy sessions. An assessment was conducted using various techniques, including static posturography and surface electromyography. [Results] Static posturography showed an improvement in the center of pressure and sway area after IVES gait training. Based on a time-series statistical parametric mapping analysis, the activation pattern of each muscle after the treatment was different. Muscle synergy analysis revealed decreased total variance accounted for by a single synergy in the affected and normal sides after the treatment. [Conclusion] Patients with chronic hemiplegic lower extremity impairment responded well to IVES gait training. Electromyography-triggered functional electrical stimulation may enhance sensory-motor integration. Proprioceptive feedback plays a crucial role in improving motor control.

Prognostic Factors and Lymph Node Metastasis Patterns of Primary Duodenal Cancer.

BACKGROUND: The effectiveness and extent of regional lymph node dissection in primary duodenal cancer (DC) remains unclear. This study aimed to analyze the prognostic factors and lymph node metastasis (LNM) patterns in DC. METHODS: Fifty-three patients who underwent surgical resection for DC between January 1998 and December 2018 at two institutions were retrospectively analyzed. Univariate and multivariate analyses were performed on the prognostic factors of resected DC. Moreover, the relationships between depth of tumor invasion and incidence of LNM and between tumor location and LNM stations were analyzed. RESULTS: The five-year survival rate of the study population was 68.9%. Multivariate survival analysis demonstrated that histologic grade G2-G4, presence of LNM, pT3-4, and elevated preoperative CA19-9 were the independent poor prognostic factors. No patient with pTis-T2 had LNM. On the other hand, LNM was found in 70% of patients with pT3-4. Among 36 patients who underwent pancreaticoduodenectomy (PD), LNM around the pancreatic head was observed, regardless of the duodenal cancer site, including the duodenal bulb and the third to the fourth portion. CONCLUSIONS: Histologic grade G2-G4, presence of LNM, pT3-T4, and elevated preoperative CA19-9 were the independent poor prognostic factors in patients with resected DC. Our results suggested that lymph node dissection could be omitted for DC Tis-T1a. Moreover, based on the high frequency of LNM in T3-4 cases, PD with lymph node dissection in the pancreatic head region was considered necessary for T3-4 DC at any site.

Impact of alcohol abstinence on survival after hepatic resection for hepatocellular carcinoma in patients with alcohol-related liver disease.

BACKGROUND: This study aimed to evaluate the prognostic impact of alcohol abstinence on survival after hepatic resection for hepatocellular carcinoma (HCC) in patients with alcohol-related liver disease (ALD). PATIENTS AND METHODS: In total, 92 patients with ALD-HCC who underwent initial and curative hepatic resection were identified, including 56 and 36 patients with and without alcohol abstinence, respectively. RESULTS: The 3-, 5-, and 7-year recurrence-free survival (RFS) were 46%, 43%, and 37% in the abstinence group, and 61%, 36%, and 36% in the non-abstinence group, respectively (p = 0.71). The 3-, 5-, and 7-year overall survival (OS) were 91%, 76%, and 66% in the abstinence group, and 87%, 57%, and 44% in the non-abstinence group, respectively (p = 0.023). Multivariate analysis revealed that non-abstinence was an independent prognostic factor for OS (P = 0.026). The incidence rate of liver-related death including HCC-specific death, liver failure, and renal failure in cirrhosis (hepatorenal syndrome) between the non-abstinence and abstinence groups were 41.7% vs. 19.6% (p = 0.032). Worsening of the Child-Pugh grade at intrahepatic recurrence was more frequently observed in the non-abstinence (33.3%) than that in the abstinence group (6.5%) (p = 0.039). CONCLUSIONS: Alcohol abstinence might improve the long-term survival of patients with ALD-HCC undergoing hepatic resection.

Durable response after discontinuation of pembrolizumab therapy for intrahepatic cholangiocarcinoma: a case report.

Although it has recently been reported that immune checkpoint inhibitors (ICIs) constitute effective treatment for solid tumors, the success rate in patients with intrahepatic cholangiocarcinoma is limited. We administered pembrolizumab to a patient as treatment for liver and lymph node metastases of intrahepatic cholangiocarcinoma. The patient had abundant infiltration of programmed death ligand 1-positive macrophages, cytotoxic T cells (CD8-positive lymphocytes), and programmed death 1-positive lymphocytes as well as a high combined positive score of 33.1, high-frequency microsatellite instability, and mismatch repair deficiency. These characteristics are predictive biomarkers of the efficacy of ICIs. After pembrolizumab was administered four times (triweekly administration), the carbohydrate antigen 19-9 serum level fell within the normal range, and computed tomography revealed that the size of the metastatic liver tumors and enlarged hilar lymph node had markedly decreased. However, the patient developed pruritus and exanthema on the trunk and limbs after 14 administrations and was diagnosed with bullous pemphigoid. We discontinued pembrolizumab therapy and started treatment for bullous pemphigoid. Nine months after discontinuation of pembrolizumab therapy, the patient remains alive without tumor relapse. This patient had durable response even after discontinuation of pembrolizumab therapy for multiple metastases of intrahepatic cholangiocarcinoma.

Precancerous Lesions and Liver Atrophy as Risk Factors for Hepatolithiasis-Related Death after Liver Resection for Hepatolithiasis.

BACKGROUND: Cholangiocarcinoma and secondary biliary cirrhosis can develop after liver resection for hepatolithiasis and are causes of hepatolithiasis-related death. We determined potential risk factors for hepatolithiasis-related death and subsequent cholangiocarcinoma, including precancerous lesions such as biliary intraepithelial neoplasia (BilIN) and intraductal papillary neoplasm of the bile duct, in patients undergoing liver resection for hepatolithiasis. METHODS: The study cohort included 62 patients who underwent liver resection for hepatolithiasis without concomitant cholangiocarcinoma and had surgical specimens available for pathological examination. Univariate and multivariate analyses were conducted to examine risk factors associated with subsequent cholangiocarcinoma after hepatolithiasis and hepatolithiasis-related death. In 28 patients with BilIN lesions, the specimens were immunohistochemically stained for γ-H2AX and S100P. RESULTS: In the study cohort, the causes of death were subsequent cholangiocarcinoma, biliary cirrhosis, and other diseases in 5, 3, and 7 patients, respectively. Liver atrophy, precancerous lesions, postoperative repeated cholangitis, and jaundice for ≥1 week during the follow-up period were risk factors for hepatolithiasis-related death. Multivariate analysis showed that liver atrophy and precancerous lesions were independent risk factors for hepatolithiasis-related death. Liver atrophy or precancerous lesions were also risk factors for subsequent cholangiocarcinoma by univariate analysis. The positive expression of γ-H2AX and S100P was observed in 18 and 14 of the 28 BilIN lesions, respectively. CONCLUSIONS: Liver atrophy and precancerous lesions with malignant transformation were risk factors not only for subsequent cholangiocarcinoma but also hepatolithiasis-related death after liver resection for hepatolithiasis, indicating that long-term follow-up is necessary even after liver resection in patients harboring these risk factors.
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[A Case of Advanced Hepatocellular Carcinoma Successfully Treated with Liver Resection after Administration of Sorafenib].

CASE: A 76-year-old man was referred to our hospital for advanced hepatocellular carcinoma(HCC)with chronic hepatitis type B. Although he underwent right anterior sectionectomy and S3 segmentectomy, multiple recurrences were found in the hepatic remnant after 2 months. Transcatheter arterial chemoembolization(TACE)and transcatheter arterial infusion (TAI)were performed separately. One and a half month after the last TAI, AFP and PIVKA-Ⅱ levels markedly elevated, and multiple early enhancing nodules with portal vein tumor thrombosis were detected on CT. A half dose of sorafenib(400mg/ day)was administered to the patient who was refractory to TACE. Sorafenib was discontinued after 4 weeks because the patient developed general fatigue and anorexia(Grade 3). Furthermore, these adverse events became worse, and ascites appeared. He was hospitalized in the palliative care unit for best supportive care for 3 weeks and also received outpatient treatment for more than 14 months. Fifteen months after discontinuing sorafenib administration, his condition improved dramatically, and CT revealed that the multiple HCC had reduced in size. Moreover, the portal vein tumor thrombosis disappeared. As his performance status and liver function were well preserved, he underwent partial hepatectomy for residual HCC. The patient remains alive without recurrence at 18 months, despite no administration of sorafenib. CONCLUSION: This case demonstrates that sorafenib administration combined with surgical treatment could possibly cure advanced HCC refractory to TACE.