A prospective study of surgeons' workloads and associated factors in real-world practice.

New technologies such as laparoscopic and robotic surgery are spreading, and there is a demand for physicians to keep up with novel methods. In contrast to the recent focus on healthcare professional burnout, the mental and physical costs during surgery are not well-understood. We aimed to quantify surgeons' workloads in daily urological surgical practice and clarify potential background factors associated with such workloads. Urologists in Hokkaido, Japan, were invited to this study. Between December 2020 and December 2021, participants repeatedly reported workloads, which were assessed using the National Aeronautics and Space Administration-Task Load Index (NASA-TLX), after each surgery in conjunction with participants' names, patients' backgrounds, their roles (independent operator, operator under supervision, instructor, and 1st or 2nd assistant), and surgical outcomes, via SurveyMonkey®. Because of the heterogeneity among individuals, a linear mixed-effects model was utilized to analyze factors associated with NASA-TLX, calculating the parameter estimates (PE) of regression coefficients for each factor and their 95% confidence interval (CI). Sixty-five urologists (5 women) joined the study, and 2169 data were collected within 7 days after surgeries. A linear mixed-effects model revealed that female surgeons (PE + 15.56, 95% CI 2.36-28.77), urgent/emergency surgery (PE + 6.65, 95% CI 4.59-8.70), intraoperative complications (PE + 9.26, 95% CI 6.76-11.76), and near-miss incidents (PE + 3.81, 95% CI 2.27-5.36) were associated with higher workloads. Regarding the surgeons' role, operator under supervision (PE + 12.46, 95% CI 9.86-15.06) showed the highest workloads. Surgeons' workloads decreased as the number of previous cases of the same procedure increased. Surgeons' workloads were associated with various factors. Given that the highest workloads were for operators under supervision, instructors should be aware of trainees' high workloads and devise appropriate instructional interventions.

Gap analysis between trainees' subjective competencies and the competencies expected by instructors in urology: A need assessment survey in Japan.

OBJECTIVE: According to the rapid progress in surgical techniques, a growing number of procedures should be learned during postgraduate training periods. This study aimed to clarify the current situation regarding urological surgical training and identify the perception gap between trainees' competency and the competency expected by instructors in Japan. METHODS: Regarding the 40 urological surgical procedures selected via the Delphi method, we collected data on previous caseloads, current subjective autonomy, and confidence for future skill acquisition from trainees (<15 post-graduate years [PGY]), and the competencies when trainees became attending doctors expected by instructors (>15 PGY), according to a 5-point Likert scale. In total, 174 urologists in Hokkaido Prefecture, Japan were enrolled in this study. RESULTS: The response rate was 96% (165/174). In a large proportion of the procedures, caseloads grew with accumulation of years of clinical practice. However, trainees had limited caseloads of robotic and reconstructive surgeries even after 15 PGY. Trainees showed low subjective competencies at present and low confidence for future skill acquisition in several procedures, such as open cystectomy, ureteroureterostomy, and ureterocystostomy, while instructors expected trainees to be able to perform these procedures independently when they became attending doctors. CONCLUSION: Trainees showed low subjective competencies and low confidence for future skill acquisition in several open and reconstructive procedures, while instructors considered that these procedures should be independently performable by attending doctors. We believe that knowledge of these perception gaps is helpful to develop a practical training program.

Use of Mixed Lymphocyte Reaction Assay to Evaluate Immune Tolerance before Kidney Transplantation with an Immunosuppression-Free Protocol following Hematopoietic Stem Cell Transplantation from the Same Donor.

Several cases of kidney transplantation after hematopoietic stem cell transplantation (HSCT) from the same donor for end-stage renal disease have been reported. In those cases, immunosuppressive drugs were discontinued since immune tolerance was supposed to be induced. Theoretically, the recipient's immune system recognizes the kidney allograft as its own tissue with the same human leukocyte antigen (HLA) profile, and the kidney allograft will not be rejected, even without the use of immunosuppressive agents. However, almost all recipients receive immunosuppressants in the early stages after kidney transplantation owing to concerns of acute rejection. Here, we report a successful case of post-HSCT kidney transplantation without the use of immunosuppressive drugs, in which a mixed lymphocyte reaction (MLR) assay was used to evaluate immune tolerance before kidney transplantation. The patient was a 25-year-old woman. Five years prior, she developed acute myeloid leukemia and underwent HLA-half-matched peripheral blood stem cell transplantation. Thereafter, she was in remission of the acute myeloid leukemia, but 1 year later, she developed renal graft-versus-host disease. Subsequently, the patient's renal function gradually deteriorated to end-stage renal failure, and she underwent kidney transplantation with the previous stem cell donor: her mother. HLA typing of donor and recipient showed a complete chimerism in the peripheral blood. The pretransplantation complement-dependent cytotoxic crossmatch and flow cytometric T-cell crossmatch results were both negative, and HLA antibody measurements were all negative. The MLR assay revealed no T-lymphocyte reaction to the donor; therefore, immunosuppressants were not used. Two years after transplantation, the patient's serum creatinine concentration was around 0.8 mg/dL (down from 4 mg/dL before transplantation). No abnormalities were observed in a renal biopsy performed after 3 months. Our study, along with others, indicates that immune tolerance to a donor develops in post-HSCT kidney transplantation from the same donor.

Factors Contributing to the Prognosis after Second-line Therapy with Ramucirumab in Advanced Hepatocellular Carcinoma.

Objective Multiple therapeutic agents exist for advanced hepatocellular carcinoma (HCC), but prognostic factors in second-line and subsequent therapies are unclear. Ramucirumab is a molecular-targeted agent effective against hepatocytes with alpha-fetoprotein (AFP) >400 ng/mL after sorafenib failure. We examined the prognostic factors and efficacy of ramucirumab with prior therapy other than sorafenib. Methods In our retrospective multicenter study, 33 patients were treated with ramucirumab for HCC with prior therapy other than sorafenib, including 1 patient who received 2 lines of ramucirumab. We analyzed background factors, liver reserve, the prognosis, and treatment duration and efficacy. Results The median albumin-bilirubin (ALBI) value showed little change during ramucirumab treatment. The ALBI value improved in 32% of patients, and their prognoses were better than in those who did not improve. Response and efficacy rates were not as high as those in the REACH-2 study but were similar when limited to patients with 2,500 ng/mL AFP. Thirteen patients received further treatment after ramucirumab failure and they had a significantly better prognosis from ramucirumab administration and also had a significantly better prognosis from the start of the first tyrosine kinase inhibitor than who did not received further treatment. In univariate and multivariate analyses of prognostic factors, the continuation of treatment with another drug after ramucirumab failure and a good ALBI value at initiation were significant. The presence of a ramucirumab response and treatment duration were not associated with the prognosis. A good ALBI value at initiation and ALBI value improvement during treatment were also identified as independent factors associated with eligibility for further treatment after ramucirumab failure. The treatment line did not correlate with the availability of treatment with another drug after treatment failure. Conclusions ALBI value improvement with ramucirumab treatment allows for subsequent treatment after failure and an improved overall prognosis.

Atezolizumab plus bevacizumab treatment for unresectable hepatocellular carcinoma progressing after molecular targeted therapy: A multicenter prospective observational study.

To evaluate the efficacy of atezolizumab plus bevacizumab treatment in patients with hepatocellular carcinoma (HCC) previously treated with molecular targeted agents (MTAs). Thirty-one patients treated with atezolizumab plus bevacizumab for unresectable HCC and previously treated with MTAs were enrolled in this study. The treatment lines ranged from second to sixth lines. The treatment effect on HCC differed from that during first-line treatment. The treatment effect was determined using the Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST. The treatment response was different for each MTA immediately prior to atezolizumab + bevacizumab treatment. Tumors treated with lenvatinib followed by atezolizumab + bevacizumab showed rapid growth for a short period of time followed by shrinkage. However, patients who received ramucirumab, sorafenib, and regorafenib did not show such changes. This was likely because of differences in the mechanism of action of the MTA administered immediately beforehand. The side-effect profile differed from that observed in the IMbrave150 phase 3 study of atezolizumab plus bevacizumab, which showed more adverse events related to hepatic reserve. Patients treated with the combination of atezolizumab and bevacizumab after lenvatinib therapy may experience rapid tumor growth and subsequent shrinkage.

Successful immunomodulation in kidney transplant recipients with cytokine release syndrome after coronavirus disease.

Introduction: Patients with coronavirus disease, especially solid organ transplant recipients, are more susceptible to developing cytokine release syndrome than those with other viral infections. However, currently, treatment methods for such patients have not been established. Here, we describe two cases of successful immunomodulation in Japanese kidney transplant recipients with cytokine release syndrome following coronavirus disease. Case presentation: Two patients who had been receiving long-term immunosuppressant therapy developed coronavirus disease-associated pneumonia caused by cytokine release syndrome, following immunosuppressant dosage reduction. However, they recovered immediately after administration of tocilizumab with or without dexamethasone. Conclusion: The immunosuppressant dosage should be reduced to restore host immunity; however, immunomodulation should be considered in cases of suspected cytokine release syndrome.

Effects of Switching from Fenofibrate to Pemafibrate for Asymptomatic Primary Biliary Cholangitis.

Background/Aims: The addition of a fibrate to ursodeoxycholic acid (UDCA) is the standard treatment for asymptomatic primary biliary cholangitis (aPBC) with an incomplete response to UDCA. Among the fibrates, bezafibrate and fenofibrate increase the serum creatinine level and reduce the estimated glomerular filtration rate (eGFR). Pemafibrate is an selective peroxisome proliferator-activated receptor alpha modulator (SPPARM-α) mainly metabolized by the liver that was recently approved to treat dyslipidemia. This study confirmed the changes in the biochemical markers after switching from fenofibrate to pemafibrate in aPBC patients. Methods: This study examined the effects of switching treatment from fenofibrate to pemafibrate in 16 aPBC patients. The biological parameters of these patients were examined at the initiation of fenofibrate and after switching to pemafibrate, then at 24 and 48 weeks later, respectively. Results: Among patients with aPBC treated with UDCA and fenofibrate, the ALP, GGT, and serum IgM levels decreased significantly (p<0.0001) over 48 weeks. On the other hand, serum creatinine levels increased significantly, and eGFR decreased significantly (p<0.0001). After switching to pemafibrate plus UDCA, patients with aPBC exhibited significantly lower serum creatinine levels (p=0.007) and significantly higher eGFR levels (p=0.014). Conclusions: Pemafibrate has therapeutic efficacy for aPBC patients with an inadequate response to UDCA. Pemafibrate might be another option for aPBC patients given its beneficial effects on renal function, but larger, multicenter studies with a longer follow-up are needed.

Deteriorated portal flow may cause liver failure in patients with hepatocellular carcinoma being treated with sorafenib.

We encountered two patients with hepatocellular carcinoma (HCC) who showed rapid progression of liver failure during sorafenib treatment. One had portal vein tumor thrombus (PVTT) and the other developed portal vein thrombosis (PVT) during the treatment, and both of them experienced the elevation of serum lactate dehydrogenase (LDH) concentration during the administration of sorafenib. Their clinical courses indicate that the liver failure might have been caused by sorafenib-induced liver hypoxia, being amplified in the circumstances with reduced portal flow. To our best knowledge, all the reported patients who achieved complete remission (CR) during sorafenib monotherapy had a condition that could decrease portal blood flow. We hypothesized that pathogenesis of disease may be similar in HCC patients who achieve CR and those who experience liver failure while on sorafenib. Sorafenib treatment of patients with HCC and deteriorated portal flow may be a double-edged sword.

Regorafenib could cause sinusoidal obstruction syndrome.

A 74-year-old man with advanced colon cancer was admitted to our hospital with jaundice and ascites. Four weeks before admission, he had started treatment with regorafenib because other chemotherapies had failed. Blood tests showed a characteristic increase in his serum lactate dehydrogenase level, which indicated intrahepatic hypoxia. The liver was not cirrhotic, but Doppler ultrasonography (US) showed that the portal flow was markedly decreased. These findings suggested that his liver failure could be caused by sinusoidal obstruction syndrome (SOS). We therefore started treatment with anticoagulants that included antithrombin III and recombinant thrombomodulin. His portal flow gradually increased, and his hepatic function improved in parallel with the increased flow. Although regorafenib could cause fatal liver failure, the mechanism remains unclear. SOS might be a route by which regorafenib induces liver failure. Additionally, lactate dehydrogenase could be a marker for identifying the adverse effects at an early stage of regorafenib-induced liver failure.

Low-grade elevation of fibrinogen-degradation products is an important parameter to identify acute presentation of autoimmune hepatitis.

OBJECTIVE: Diagnosing early-stage acute autoimmune hepatitis (AIH) without pathological findings is difficult. Recent reports indicated that macrophages are not activated during disease development, unlike in other acute liver injuries. We suggest that hepatitis without macrophage activation should lack sinusoidal fibrin deposition, which might help diagnose the acute presentation of AIH. MATERIAL AND METHODS: To test this hypothesis, 295 consecutive patients with acute liver injury enrolled into this study. Their clinical data on admission were analyzed to verify the differences between acute presentation of AIH and other liver injuries. RESULTS: The distribution of plasma fibrinogen degradation products (FDP) showed two clusters: patients without elevated FDP and those with measurable FDP levels of various degrees. Most AIH patients are included in the former. Multivariate logistic analysis of patients' laboratory data was performed for useful parameters to identify the acute presentation of AIH. FDP, alanine transaminase, zinc sulfate turbidity test and HBsAg levels were significant. Based on the odds ratio obtained from the analysis, we assigned each result individual points and constructed a convenient scoring system, which showed high sensitivity and specificity to identify AIH. Additionally, the area under the receiver operating characteristic curve was 0.928. CONCLUSIONS: Our results indicated that the process of macrophage activation and subsequent sinusoidal fibrin deposition was not involved in the development of the acute presentation of AIH. Our new scoring system including FDP levels could contribute to rapid diagnosis of the acute presentation of AIH without liver biopsy.

[Axillo-axillary bypass for coronary-subclavian steal syndrome].

We describe a case of coronary-subclavian steal syndrome in a 77-year-old man who presented with progressive coronary ischemia 8 years after coronary artery bypass grafting with an in-situ left internal thoracic artery graft. Coronary and left subclavian artery angiogram revealed completely patent internal thoracic artery graft and 90% stenosis in the proximal left subclavian artery. We performed axilloaxillary artery bypass using expanded polytetrafluoroethylene (ePTFE)[8 mm] graft. No coronary ischemia was noted postoperatively. Axillo-axillary artery bypass grafting was effective for coronary subclavian steal syndrome.

A cervical myelopathy due to invaginated laminae of the axis into the spinal canal.

STUDY DESIGN: A case report and review of previous literature are presented. OBJECTIVE: The objective of this manuscript was to report a case of cervical myelopathy due to anomalous laminae of the axis in a patient with spina bifida. SUMMARY OF BACKGROUND DATA: In previous studies, few cases of invaginated anomalous laminae of the axis have been reported. Treatment was surgical removal of the invaginated laminae. METHODS: The patient's history, clinical examination, imaging findings, and treatment were reported. RESULTS: Characteristic findings were revealed from imaging studies, a multiplane reconstruction of the CT images, and a stereolithographic model of the cervical spine. The patient was treated with a posterior decompressive operation. The outcome was satisfactory, with an improvement in the patient's neurology. CONCLUSIONS: This is a report of a rare characteristic anomaly of the laminae of the axis. A multiplane reconstruction of the CT images and a stereolithographic model were useful for treatment of this case. Possible causes of this anomaly may be the failure of ossification or fusion of the embryological term.

[A case of synchronous esophageal and gastric cancer successfully treated by combination TS-1/CDDP therapy with irradiation].

We report a case of synchronous esophageal and gastric cancer in a patient with severe liver dysfunction who was treated successfully using TS-1/CDDP therapy combined with irradiation therapy. A 56-year-old man with a chief complaint of dysphagia was diagnosed with thoracic esophageal cancer by endoscopy, and was referred to our hospital. Synchronous esophageal and gastric cancer were diagnosed by endoscopy and barium swallow. The preoperative diagnosis was T3N0M0, Stage II esophageal cancer and T1N0M0, Stage I A gastric cancer, both of which were diagnosed to be resectable. However, surgery was contraindicated because of severe liver dysfunction, due to an ICG15 of 35%. TS-1 (80 mg/day) and CDDP (3 mg/day) therapy was combined with irradiation, 60 Gy given in a T-pattern to the mediastinum. The patient did not suffer any side-effects, and endoscopy performed 44 days after the start of treatment showed that the esophageal lesion was now only a scar. Only a slight elevation of the esophagus was seen by endoscopy 219 days after the start of the therapy. The patient is currently undergoing only TS-1 treatment as an outpatient and is under observation. No metastasis to the liver or any other organ has been detected. TS-1 and CDDP therapy combined with radiotherapy appears to be effective in treating thoracic esophageal cancer.