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Introduction This study aimed to evaluate the short- and long-term outcomes of single-incision laparoscopic colectomy (SILC) for right-sided colon cancer (CC) using a craniocaudal approach. Patients and Methods The data of patients who underwent SILC for right-sided CC at our hospital between January 2013 and December 2022 were retrospectively collected. Surgery was performed using a craniocaudal approach. Short- and long-term operative outcomes were analysed. Results In total, 269 patients (127 men, 142 women; median age 74 years) underwent SILC for right-sided CC. The cases included ileocaecal resection (n = 138) and right hemicolectomy (n = 131). The median operative time was 154 min, and the median operative blood loss was 0 ml. Twenty-seven cases (10.0%) required an additional laparoscopic trocar, and 9 (3.3%) were converted to open surgery. The Clavien–Dindo classification Grade III post-operative complications were detected in 7 (2.6%) cases. SILC was performed by 25 surgeons, including inexperienced surgeons, with a median age of 34 years. The 5-year cancer-specific survival (CSS) was 96.1% (95% confidence interval [CI] 91.3%–98.2%), and CSS per pathological disease stage was 100% for Stages 0–I and II and 86.2% (95% CI 71.3%–93.7%) for Stage III. The 5-year recurrence-free survival (RFS) was 90.6% (95% CI 85.7%–93.9%), and RFS per pathological disease stage was 100% for Stage 0–I, 91.7% (95% CI 80.5%–96.6%) for Stage II and 76.1% (95% CI 63.0%–85.1%) for Stage III. Conclusions SILC for right-sided CC can be safely performed with a craniocaudal approach, with reasonable short- and long-term outcomes.

Abstract Background Postoperative pancreatic fistula (POPF) continues to be the most common complication after distal pancreatectomy (DP). Recent advancements in surgical techniques have established minimally invasive distal pancreatectomy (MIDP) as the standard treatment for various conditions, including pancreatic cancer. However, MIDP has not demonstrated a clear advantage over open DP in terms of POPF rates, indicating the need for additional strategies to prevent POPF in MIDP. This trial (WRAP study) aims to evaluate the efficacy of wrapping the pancreatic stump with polyglycolic acid (PGA) mesh and fibrin glue in preventing clinically relevant (CR-) POPF following MIDP. Methods This multicenter, randomized controlled trial will include patients scheduled for laparoscopic or robotic DP for tumors in the pancreatic body and/or tail. Eligible participants will be centrally randomized into either the control group (Group A) or the intervention group (Group B), where the pancreatic stump will be reinforced by PGA mesh and fibrin glue. In both groups, pancreatic transection will be performed using a bioabsorbable reinforcement-attached stapler. A total of 172 patients will be enrolled across 14 high-volume centers in Japan. The primary endpoint is the incidence of CR-POPF (International Study Group of Pancreatic Surgery grade B/C). Discussion The WRAP study will determine whether the reinforcement of the pancreatic stump with PGA mesh and fibrin glue, a technique whose utility has been previously debated, could become the best practice in the era of MIDP, thereby enhancing its safety. Trial registration This trial was registered with the Japan Registry of Clinical Trials on June 15, 2024 (jRCTs032240120).

Abstract Background Hemostatic devices are now frequently used in femoral artery punctures, and the Angio-Seal (Terumo, Tokyo, Japan) is one of the most commonly used devices for closure of the femoral artery because it provides rapid hemostasis. Although device failure rarely occurs, if the collagen falls into the femoral artery, it may lead to severe limb ischemia. Herein, we describe a case of a novel endovascular technique for the treatment of Angio-Seal arterial closure device failure. Case presentation The patient in Case 1 was a 75-year-old man with severe left limb claudication. We used a contralateral antegrade approach and used the Angio-Seal for hemostasis. However, the Angio-Seal collagen and footplate dropped and stopped at the bifurcation of the superficial femoral artery and deep femoral artery. The collagen with the footplate was caught with myocardial biotome forceps (MBF) and pulled into the external iliac artery (EIA). The distal common femoral artery (CFA) was punctured, and we delivered a 10.0- × 80-mm stent (SMART®; Cordis, USA) to the EIA from the ipsilateral sheath. The stent was deployed at the EIA and crushed the collagen. The patient in Case 2 was an 88-year-old man with rest pain in the right limb. The right CFA was punctured using an ipsilateral approach and the Angio-Seal was used for hemostasis. The Angio-Seal collagen with the footplate dropped into the bifurcation of the deep femoral artery. The collagen and footplate were caught with MBF and pulled up to the EIA. The right CFA was punctured and a 10.0- × 60-mm stent (SMART®; Cordis) was delivered from the ipsilateral sheath. The stent was deployed at the EIA and crushed the collagen with the footplate. Conclusions MBF were used to grasp the dislodged collagen with the anchor and cover it with a stent at the iliac artery. This may be a useful bailout technique for Angio-Seal dislodgement.

Abstract Background Surgical resection is standard treatment for invasive intraductal papillary mucinous carcinoma (IPMC); however, impact of multidisciplinary treatment on survival including postoperative adjuvant therapy (AT), neoadjuvant therapy (NAT), and treatment for recurrent lesions is unclear. We investigated the effectiveness of multidisciplinary treatment in prolonging survival of patients with invasive IPMC. Methods This retrospective multi‐institutional study included 1183 patients with invasive IPMC undergoing surgery at 40 academic institutions. We analyzed the effects of AT, NAT, and treatment for recurrence on survival of patients with invasive IPMC. Results Completion of the planned postoperative AT for 6 months improved the overall survival (OS), disease‐specific survival (DSS), and recurrence‐free survival (RFS) of patients with stage IIB and stage III resected invasive IPMC, elevated preoperative carbohydrate antigen 19–9 level, lymphovascular invasion, perineural invasion, serosal invasion, and lymph node metastasis on un‐matched and matched analyses. Of the patients with borderline resectable (BR) invasive IPMC, the OS (p = 0.001), DSS (p = 0.001), and RFS (p = 0.001) of patients undergoing NAT was longer than that of those without on the matched analysis. Of the 484 invasive IPMC patients (40.9%) who developed recurrence after surgery, the OS of 365 patients who received any treatment for recurrence was longer than that of those without treatment (40.6 vs. 22.4 months, p

Abstract Introduction Survival comparisons among patients with liver metastases from pancreatic and rectal neuroendocrine tumors (NETs) were limited, and the efficacy of observation rules in patients undergoing hepatectomy for neuroendocrine liver metastases (NELMs) was unknown. This study aims to distinguish these characteristics and clarify the effects of the observation rules on NELMs. Methods Clinical data were separately collected from patients with pancreatic and rectal NELMs at medical centers in both Japan and China. The Japanese cohort followed the observation rules for the resection of NELMs. A comparative analysis was conducted on clinical characteristics and prognosis features such as overall survival time (OS) and disease-free survival interval (DFS-I). Results Enrollment included 47 and 34 patients from Japan and China, respectively. Of these, 69 and 12 patients had tumors originating from the pancreas and rectum, respectively. The OS time in patients undergoing primary tumor resection was significantly longer; however, the OS time between the patients undergoing and not undergoing radical resection of liver metastasis was the same. In asynchronous NELMs, patients with rectal (R)-NELMs showed a significantly higher proportion of type III NELMs. Additionally, the median DFS-I of asynchronous R-NELMs was longer than the recommended follow-up time, with 71.4% of them classified as G2. In the Japanese cohort, patients who adhered to the observation rules exhibited a longer median DFS after hepatectomy for NELMs compared with their counterparts. Conclusion Although curative surgery is crucial for primary lesions, personalized approaches are required to manage NELMs. Extended overall follow-ups and shortened follow-up intervals are recommended for G2 stage rectal NETs. The observation rules for NELMs require further validation with a larger sample size.

As novel biomarkers for gastroenteropancreatic neuroendocrine tumors (GEPNET) are in demand, we aimed to validate the clinical value of the NETest in Japanese patients. Between 2021 and 2023, blood and clinical data were collected from patients with GEPNET. Among 35 patients (median age: 59 [49–66] years), 27 cases originated from the pancreas and eight from the gastrointestinal tract. Of 69 samples sent to the laboratory, 56 (81.2%) underwent NETest. The diagnostic sensitivity was 97.1%. Among three patients who underwent R0 resection and four treated with peptide receptor radionuclide therapy, the changes in NETest scores closely correlated with disease progression. The NETest demonstrated high diagnostic efficacy and accurate therapeutic monitoring capabilities in a Japanese population.

Abstract Purpose Operations for malignant diseases of the bile duct, pancreas, and esophagus are the most invasive gastroenterological surgeries. The frequency of complications after these surgeries is high, which affects the postoperative course and mortality. In patients who undergo these types of surgeries, continuous monitoring of the perioperative central venous oxygen saturation (ScvO2) is possible via a central venous catheter. We aimed to investigate the relationship between continuously monitored perioperative ScvO2 values and postoperative complications. Methods The medical records of 115 patients who underwent highly invasive gastroenterological surgeries and ScvO2 monitoring from April 2012 to March 2014 were analyzed. Sixty patients met the inclusion criteria, and their ScvO2 levels were continuously monitored perioperatively. The relationship between ScvO2 levels and major postoperative complications, defined as Clavien–Dindo grade ≥ III, was examined using uni‐ and multivariate analysis. Results Thirty patients developed major postoperative complications. The adequate cut‐off value derived from receiver operating curves of the postoperative average ScvO2 levels for predicting major complications was 75%. Multivariate analysis revealed that low average postoperative ScvO2 levels (p = 0.016) and blood loss ≥ 1000 mL (p = 0.039) were significant predictors of major postoperative complications. Conclusions Low perioperative ScvO2 values were associated with an increased risk of major postoperative complications. Continuous ScvO2 monitoring will help prevent postoperative complications.

Abstract Post-ERCP pancreatitis (PEP) is an acute pancreatitis caused by endoscopic-retrograde-cholangiopancreatography (ERCP). About 10% of patients develop PEP after ERCP. Here we show that gamma-glutamyltransferase 1 (GGT1)-SNP rs5751901 is an eQTL in pancreatic cells associated with PEP and a positive regulator of the IL-6 amplifier. More PEP patients had the GGT1 SNP rs5751901 risk allele (C) than that of non-PEP patients at Hokkaido University Hospital. Additionally, GGT1 expression and IL-6 amplifier activation were increased in PEP pancreas samples with the risk allele. A mechanistic analysis showed that IL-6-mediated STAT3 nuclear translocation and STAT3 phosphorylation were suppressed in GGT1-deficient cells. Furthermore, GGT1 directly associated with gp130, the signal-transducer of IL-6. Importantly, GGT1-deficiency suppressed inflammation development in a STAT3/NF-κB-dependent disease model. Thus, the risk allele of GGT1-SNP rs5751901 is involved in the pathogenesis of PEP via IL-6 amplifier activation. Therefore, the GGT1-STAT3 axis in pancreas may be a prognosis marker and therapeutic target for PEP.

Abstract Background Gait disorder remains a major challenge for individuals with stroke, affecting their quality of life and increasing the risk of secondary complications. Robot-assisted gait training (RAGT) has emerged as a promising approach for improving gait independence in individuals with stroke. This study aimed to evaluate the effect of RAGT in individuals with subacute hemiparetic stroke using a one-leg assisted gait robot called Welwalk WW-1000. Methods An assessor-blinded, multicenter randomized controlled trial was conducted in the convalescent rehabilitation wards of eight hospitals in Japan. Participants with first-ever hemiparetic stroke who could not walk at pre-intervention assessment were randomized to either the Welwalk group, which underwent RAGT with conventional physical therapy, or the control group, which underwent conventional physical therapy alone. Both groups received 80 min of physical therapy per day, 7 days per week, while the Welwalk group received 40 min of RAGT per day, 6 days per week, as part of their physical therapy. The primary outcome was gait independence, as assessed using the Functional Independence Measure Walk Score. Results A total of 91 participants were enrolled, 85 of whom completed the intervention. As a result, 91 participants, as a full analysis set, and 85, as a per-protocol set, were analyzed. The primary outcome, the cumulative incidence of gait-independent events, was not significantly different between the groups. Subgroup analysis revealed that the interaction between the intervention group and stroke type did not yield significant differences in either the full analysis or per-protocol set. However, although not statistically significant, a discernible trend toward improvement with Welwalk was observed in cases of cerebral infarction for the full analysis and per-protocol sets (HR 4.167 [95%CI 0.914–18.995], p = 0.065, HR 4.443 [95%CI 0.973–20.279], p = 0.054, respectively). Conclusions The combination of RAGT using Welwalk and conventional physical therapy was not significantly more effective than conventional physical therapy alone in promoting gait independence in individuals with subacute hemiparetic stroke, although a trend toward earlier gait independence was observed in individuals with cerebral infarction. Trial registration This study was registered with the Japan Registry of Clinical Trials ( https://jrct.niph.go.jp ; jRCT 042180078) on March 3, 2019.

Abstract Background Pancreatic ductal carcinoma (PDAC) is an extremely poor prognostic disease. Even though multidisciplinary treatment for PDAC has developed, supportive therapies, such as nutritional therapy or perioperative rehabilitation to sustain and complete aggressive treatment, have not yet been well-established in PDAC. The aim of this study was to elucidate the relationship between the combined index using psoas muscle mass index (PMI) values and controlling nutritional status (CONUT) score and prognosis. Methods We included 101 patients diagnosed with PDAC who underwent radical pancreatectomy with regional lymphadenectomy. The cut-off value was set at the first quartile (male, 6.3 cm2/m2; female 4.4 cm2/m2), and patients were classified into high PMI and low PMI groups. A CONUT score of 0 to 1 was classified as the normal nutritional status group, and 2 or more points as the malnutritional status group. Patients were further divided into three groups: high PMI and normal nutrition (good general condition group), low PMI and low nutrition (poor general condition group), and none of the above (moderate general condition group). We performed a prognostic analysis of overall survival (OS), stratified according to PMI values and CONUT scores. Results In the poor general condition group, the proportion of elderly people over 70 years of age was significantly higher than that in the other groups (p

Objective: To demonstrate the long-term efficacy of repeated botulinum toxin A injections into the same muscles for ameliorating lower limb spasticity and gait function. Design: Single-case study Patient: A 36-year-old woman with right cerebral haemorrhage received her first botulinum toxin A injection 1,296 days after onset. The patient underwent 30 treatments over 12 years after the first injection to improve upper and lower limb spasticity and abnormal gait patterns. The mean duration between injections was 147 days. Methods: The Modified Ashworth Scale, passive range of motion, gait velocity, and degree of abnormal gait patterns during treadmill gait were evaluated pre-injection and at 2, 6, and 12 weeks after every injection. Results: The follow-up period showed no injection-related adverse events. Comfortable overground gait velocity gradually improved over 30 injections. The Modified Ashworth Scale and passive range of motion improved after each injection. Pre-injection values of the degree of pes varus, circumduction, hip hiking, and knee extensor thrust improved gradually. However, the degree of contralateral vaulting, excessive lateral shift of the trunk, and insufficient knee flexion did not improve after 30 injections. Conclusion: Repeated botulinum toxin A injections effectively improve abnormal gait patterns, even when a single injection cannot change these values.

Abstract Background Revascularization with endovascular therapy (EVT) for complex below-the-knee (BTK) chronic total occlusion (CTO) remains a challenging problem. The Japanese-BTK (J-BTK) CTO score is reported as an indicator of the difficulty of BTK CTO, with the guidewire (GW) passage success rate decreasing as the grade increases. We previously reported an effective GW crossing method for the intravascular ultrasound (IVUS)-guided parallel wiring of complex BTK CTO. In this study, we investigated the feasibility of EVT using IVUS-guided wiring for BTK CTO. Materials and methods This single center, retrospective study analyzed 65 consecutive BTK CTO vessels in which IVUS-guided wiring was attempted after the failure of a conventional antegrade wiring approach from November 2020 to November 2022. The primary endpoint was the clinical success of the target CTO vessel. The secondary endpoints were the GW success rate per grade based on the J-BTK CTO score, number of GW used for CTO crossing, fluoroscopy time, and complications. Results Target vessels were the anterior tibial artery (66.2% of cases), peroneal artery (9.2%), and posterior tibial artery (24.6%). Blunt type CTO entry was performed in 55.4% of cases, calcification of entry was observed in 24.6% of cases, the mean occlusion length was 228.2 ± 93.7 mm, mean reference vessel diameter was 2.1 ± 0.71 mm, and outflow was absent in 38.5% of cases. J-BTK CTO scores of 0/1 (grade A), 2/3 (grade B), 4/5 (grade C), and 6 (grade D) were seen in 18.5%, 43.1%, 36.3%, and 1.5% of cases, respectively. The clinical success rate was 95.4%. The GW success rate by J-BTK CTO grade was as follows: grade A (100%), B (100%), C (91.7%), and D (0%). The mean number of GW used was 3.4 ± 1.4, the mean fluoroscopy time was 72.3 ± 32.5 min, and complications occurred in 7.7% of cases. Conclusion This study showed a very high clinical success rate despite the difficulty of BTK CTO. IVUS-guided EVT might be a feasible strategy for complex BTK CTO.

Abstract Background The prognosis of hepatocellular carcinoma (HCC) with vascular invasion is extremely poor, especially in patients with tumor thrombus (TT) of the inferior vena cava (IVC), which is an oncological emergency with a high risk of sudden death due to TT extension or migration. Herein, we describe a case of HCC with TT of the IVC that rapidly extended into the right atrium (RA), in which right hepatectomy was performed under cardiopulmonary bypass. Case presentation A 64-year-old man was diagnosed with HCC with IVC TT, and right hepatic lobectomy was scheduled. While awaiting surgery, he complained of respiratory distress and rushed to the emergency room. The TT had reached the RA, and the patient was in a state of oncologic emergency. We requested the cooperation of the cardiovascular surgery department, and under artificial cardiopulmonary support, the right atrium was incised, and a part of the TT was removed. The IVC was clamped to prevent tumor dispersal, and right hepatic lobectomy was performed. The remaining thrombus was excised along with the right lobe of the liver by incising the IVC. There were no serious postoperative complications, and the patient is alive 1 year and 5 months postoperatively. Conclusion Hepatic resection with cardiopulmonary bypass could be an option for HCC with TT reaching the RA.

Abstract Background Pemetrexed is an efficacious multi-targeted antifolate with acceptable toxicity for non-squamous non-small cell lung cancer (non-Sq NSCLC) and malignant pleural mesothelioma. Vitamin B12 and folic acid as premedication can reduce the frequency of severe toxicities of pemetrexed chemotherapy. However, adverse effects are frequent in clinical settings. In this study, we aimed to identify the clinical factors and single-nucleotide polymorphisms (SNPs) associated with the toxicity and efficacy of pemetrexed chemotherapy. Methods This observational study was conducted from October 2012 to December 2019; we evaluated the toxicities and efficacies of pemetrexed chemotherapy using multivariate logistic or Cox regression analysis. In total, 106 patients received pemetrexed chemotherapy. SNPs were analyzed for four patients with malignant pleural mesothelioma and 67 with non-Sq NSCLC. Results The median progression-free survival (PFS) and overall survival of 63 patients with non-Sq NSCLC, excluding four in the adjuvant setting, were 6.8 and 33.3 months, respectively. Per propensity-score-adjusted multivariate Cox analyses, favorable factors for PFS were folic acid level ≥ 9.3 ng/mL before premedication, platinum combination, bevacizumab combination, vitamin B12 level A), and A/A + A/C of DHFR (680 C > A). Favorable prognostic factors included good performance status, low smoking index, body mass index ≥ 20.66 kg/m2, folic acid level ≥ 5.55 ng/mL before premedication, higher retinol-binding protein before chemotherapy, and A/G of MTRR (66 A > G). Among the 71 patients who were analyzed for SNPs, the frequencies of hematologic toxicities and non-hematologic toxicities in Grades 3–4 were 38% and 36.6%, respectively. Per propensity-score-adjusted multivariate logistic analyses, risk factors for Grades 3–4 hematologic toxicities were vitamin B12 level T). Risk factors for Grades 2–4 non-hematologic toxicities were homocysteine levels ≥ 11.8 nmol/mL before premedication, transthyretin level T), and A/A + G/G of SLC19A1 [IVS2 (4935) G > A]. Conclusion The information on metabolites and SNPs of the folate and methionine cycle will help predict the toxicities and efficacies of pemetrexed. Trial registration This trial was retrospectively registered with the University hospital Medical Information Network (UMIN000009366) on November 20, 2012.

Purpose General surgeons at regional hospitals should have the primary trauma care skills necessary to treat critically ill trauma patients to withstand transfer. This study was conducted to identify a consensus on primary trauma care skills for general surgeons. Methods An initial list of acute care surgical skills was compiled, and revised by six trauma experts (acute care surgeons); 33 skills were nominated for inclusion in the Delphi consensus survey. Participants (councilors of the Japanese Society for Acute Care Surgery) were presented with the list of 33 trauma care skills and were asked (using web-based software) to rate how strongly they agreed or disagreed (using a 5-point Likert scale) with the necessity of each skill for a general surgeon. The reliability of consensus was predefined as Cronbach’s α ≥ 0.8, and trauma care skills were considered as primarily required when rated 4 (agree) or 5 (strongly agree) by ≥ 80% participants. Results There were 117 trauma care specialists contacted to participate in the Delphi consensus survey panel. In the 1st round, 85 specialists participated (response rate: 72.6%). In the 2nd round, 66 specialists participated (response rate: 77.6%). Consensus was achieved after two rounds, reliability using Cronbach’s α was 0.94, and 34 items were identified as primary trauma care skills needed by general surgeons. Conclusion A consensus-based list of trauma care skills required by general surgeons was developed. This list can facilitate the development of a new trauma training course which has been optimized for general surgeons.

Abstract It is important to ensure the redundancy of communication during remote surgery. The purpose of this study is to construct a communication system that does not affect the operation in the event of a communication failure during telesurgery. The hospitals were connected by two commercial lines, a main line and a backup line, with redundant encoder interfaces. The fiber optic network was constructed using both guaranteed and best-effort lines. The surgical robot used was from Riverfield Inc. During the observation, a random shutdown and restoration process of either line was conducted repeatedly. First, the effects of communication interruption were investigated. Next, we performed a surgical task using an artificial organ model. Finally, 12 experienced surgeons performed operations on actual pigs. Most of the surgeons did not feel the effects of the line interruption and restoration on still and moving images, in artificial organ tasks, and in pig surgery. During all 16 surgeries, a total of 175-line switches were performed, and 15 abnormalities were detected by the surgeons. However, there were no abnormalities that coincided with the line switching. It was possible to construct a system in which communication interruptions would not affect the surgery.

Objective: To investigate the prevalence of post-stroke depression in a rehabilitation ward and elucidate its effect on functional improvement and outcomes. Design: Retrospective cohort study. Setting: A convalescent rehabilitation ward at a University Hospital. Participants: A total of 114 patients with stroke (mean [SD] age, 67.2 [13.5] years; men, 76) assessed at 2 weeks after admission using the Mini-International Neuropsychiatric Interview were enrolled. Main Outcome Measure: Functional independence measure (FIM) efficiency during hospitalization in the ward. Results: Eleven patients (9.6%) had depression based on the Mini-International Neuropsychiatric Interview. Total FIM efficiency and FIM efficiency in the subtotal of motor items were significantly higher in the non-depression group than in the depression group (median [interquartile range]: 0.69 [0.39-0.95] vs 0.41 [0.24-0.63], P=.027; and 0.56 [0.38-0.80] vs 0.42 [0.18-0.49], P=.023, respectively). Patients in the non-depression group had higher FIM scores at discharge (median [interquartile range]: 116.0 [104.5-123.0] vs 104.0 [82.5-112.0], P=.013, respectively), and were more likely to be discharged home (80.6% vs 36.4%, P=.003). Furthermore, patients in the depression group also stayed significantly longer in the ward (71.0 [36.1] vs 106.1 [43.3], P=.010). Conclusions: Patients with post-stroke depression showed poorer efficiency of functional recovery than those without depression. A future multicenter study with a larger sample size is needed to verify these findings.

Objective: To investigate the occurrence of incidents and sudden deteriorations during rehabilitation in an acute care setting by disease category based on the International Classification of Diseases and Related Health Problems, 10th Revision. Design: Retrospective cohort study. Setting: University hospital in Japan with 1376 beds. Participants: A total of 49,927 patients who were admitted to the acute care wards and underwent rehabilitation over 8 years, from April 1, 2013, to March 31, 2021. Interventions: Rehabilitation in an acute care setting. Main Outcome Measures: Incidents and sudden deteriorations reported in medical charts. Results: Among 49,927 admissions, 455 incidents and 683 sudden deteriorations occurred during rehabilitation. The incidents and sudden deteriorations occurred at rates of 0.009/person (0.50 case/1000 h) and 0.012/person (0.75 case/1000 h), respectively. The 3 most frequent incidents were “route-related incidents” (178 cases, 39.1%), followed by “bleeding/abrasions” (131 cases, 28.8%) and “falls” (125 cases, 27.5%). Among 12 disease categories with over 500 admissions and 10,000 rehabilitation hours, the highest incident rate occurred in “certain infectious and parasitic diseases” (0.81 case/1000 h), followed by “diseases of the musculoskeletal system and connective tissue” (0.67 case/1000 h) and “diseases of the genitourinary system” (0.66 case/1000 h). The commonest sudden deterioration was “vomiting” (460 cases, 67.3%), followed by “decreased level of consciousness (with reduced blood pressure)” (42 cases, 6.1%) and “seizure” (39 cases, 5.7%). Furthermore, the highest sudden deterioration rate was in the “endocrine, nutritional, and metabolic diseases” (1.19 case/1000 h) category, followed by “neoplasms” (1.04 case/1000 h) and “certain infectious and parasitic diseases” (0.99 case/1000 h). Conclusions: An incident and sudden deterioration occurred every 2000 and 1333 h, respectively, during rehabilitation. Therefore, understanding the actual occurrence of incidents and sudden deteriorations during rehabilitation may provide valuable insights into preventing incidents and emergencies.

Abstract Introduction The occurrence of massive haemorrhages in various emergency situations increases the need for blood transfusions and increases the risk of mortality. Fibrinogen concentrate (FC) use may increase plasma fibrinogen levels more rapidly than fresh-frozen product or cryoprecipitate use. Previous several systematic reviews and meta-analyses have not effectively demonstrated FC efficacy in significantly improving the risk of mortality and reducing transfusion requirements. In this study, we investigated the use of FC for haemorrhages in emergency situations. Methods and analysis In this systematic review and meta-analysis, we included controlled trials, but excluded randomized controlled trials (RCTs) in elective surgeries. The study population consisted of patients with haemorrhages in emergency situations, and the intervention was emergency supplementation of FC. The control group was administered with ordinal transfusion or placebo. The primary and secondary outcomes were in-hospital mortality and the amount of transfusion and thrombotic events, respectively. The electronic databases searched included MEDLINE (PubMed), Web of Science, and the Cochrane Central Register of Controlled Trials. Results Nine RCTs in the qualitative synthesis with a total of 701 patients were included. Results showed a slight increase in in-hospital mortality with FC treatment (RR 1.24, 95% CI 0.64–2.39, p = 0.52) with very low certainty of the evidence. There was no reduction in the use of red blood cells (RBC) transfusion in the first 24 h after admission with FC treatment (mean difference [MD] 0.0 Unit in the FC group, 95% CI − 0.99–0.98, p = 0.99) with very low certainty of the evidence. However, the use of fresh-frozen plasma (FFP) transfusion significantly increased in the first 24 h after admission with FC treatment (MD 2.61 Unit higher in the FC group, 95% CI 0.07–5.16, p = 0.04). The occurrence of thrombotic events did not significantly differ with FC treatment. Conclusions The present study indicates that the use of FC may result in a slight increase in in-hospital mortality. While FC did not appear to reduce the use of RBC transfusion, it likely increased the use of FFP transfusion and may result in a large increase in platelet concentrate transfusion. However, the results should be interpreted cautiously due to the unbalanced severity in the patient population, high heterogeneity, and risk of bias.

Abstract An 80-year-old man presented to our emergency department complaining of a mass on the right side of his chest and pain in the right flank of his back. A chest computed tomography (CT) scan showed a relatively heterogenous oval-shaped tumor measuring 7.5 × 6.0 cm eroded to the 8th rib, with slightly dense fluid accumulation inside and calcification of the tumor wall. A 1-month follow-up CT scan showed spontaneous shrinkage of the tumor. The tumor was completely excised from the thoracic wall and the wall was reconstructed with a polytetrafluoroethylene mesh. Pathological examination showed coagulation necrosis in the chest wall tumor, but immunohistochemical staining revealed murine double minute 2- and Cyclin-dependent kinase 4-positive cells with irregular nuclear size and bizarre morphology. Therefore, dedifferentiated liposarcoma (DDLPS) was the final pathological diagnosis. Remarkable infiltration of CD8+ lymphocytes into the tumor was observed, along with a 90% positive ratio for programmed cell death-ligand 1. The patient has been followed-up for 1 year without any recurrence, despite not receiving any additional treatment. Liposarcoma is one of the most common types of soft tissue sarcomas; however, spontaneous regression of primary DDLPS arising from the chest wall is extremely rare. Herein, we report a case of DDLPS primary to the chest wall with spontaneous regression, probably due to a spontaneously induced T cell response.

Abstract Aim Communication and video transmission delays negatively affect telerobotic surgery. Since latency varies by communication environment and robot, to realize remote surgery, both must perform well. This study aims to examine the feasibility of telerobotic surgery by validating the communication environment and local/remote robot operation, using secure commercial lines and newly developed robots. Methods Hirosaki University and Mutsu General Hospital, 150 km apart, were connected via a Medicaroid surgical robot. Ten surgeons performed a simple task remotely using information encoding and decoding. The required bandwidth, delay time, task completion time, number of errors, and image quality were evaluated. Next, 11 surgeons performed a complex task using gallbladder and intestinal models in local/remote environments; round trip time (RTT), packet loss, time to completion, operator fatigue, operability, and image were observed locally and remotely. Results Image quality was not so degraded as to affect remote robot operation. Median RTT was 4 msec (2‐12), and added delay was 29 msec. There was no significant difference in accuracy or number of errors for cholecystectomy, intestinal suturing, completion time, surgeon fatigue, or image evaluation. Conclusion The fact that remote surgery succeeded equally to local surgery showed that this system has the necessary elemental technology for widespread social implementation.

Abstract Background The transradial approach (TRA) is associated with fewer serious access site-related complications compared with the transfemoral or transbrachial approach. However, TRA has associated problems in complex aortoiliac (AI) lesions, including the procedural difficulty. A bidirectional approach was used combining TRA with a sheathless technique for femoral artery (FA) puncture to treat complex AI lesions, as a minimally-invasive approach. This report describes a representative cases with AI chronic total occlusion in which the combination of TRA and a sheathless technique for FA puncture was useful for guidewire crossing. Case presentation Case 1 was a 71-year-old man with intermittent claudication (IC). Control angiography showed total occlusion of the left common iliac artery (CIA) ostium to the distal external iliac artery (EIA). Guidewire externalization was achieved by combining TRA using a 6Fr guiding sheath and a sheathless technique for the left FA. Two nitinol stents were deployed in the CIA to EIA. Case 2 was a 63-year-old man with IC. Control angiography revealed total occlusion of the right CIA ostium to the common femoral artery (CFA) with severe calcification. The antegrade wire could not pass through the CTO lesion because of the calcified CFA occlusion. A 21-G metal needle was used to penetrate the CFA calcification through the distal true lumen of the CFA, and the wire was inserted into the EIA for wire externalization. Three nitinol stents were deployed in the CIA to EIA, and a drug-coated balloon was dilated in the CFA with hemostasis of the distal puncture site. In both cases, the retrograde puncture site was hemostatic during the procedure and postoperative bed rest was not required. Conclusions TRA combined with a sheathless technique from the FA has the potential to treat AI complex lesions in a less invasive manner.

We report a fatal subdural empyema caused by Campylobacter rectus in a 66-year-old female who developed acute onset of confusion, dysarthria, and paresis in her left extremities. A CT scan showed hypodensity in a crescentic formation with a mild mid-line shift. She had a bruise on her forehead caused by a fall several days before admission, which initially raised subdural hematoma (SDH) diagnosis, and a burr hole procedure was planned. However, her condition deteriorated on the admission night, and she died before dawn. An autopsy revealed that she had subdural empyema (SDE) caused by Campylobacter rectus and Slackia exigua. Both microorganisms are oral microorganisms that rarely cause extra-oral infection. In our case, head trauma caused a skull bone fracture, and sinus infection might have expanded to the subdural space causing SDE. CT/MRI findings were not typical for either SDH or SDE. Early recognition of subdural empyema and prompt initiation of treatment with antibiotics and surgical drainage is essential for cases of SDE. We present our case and a review of four reported cases.

Pseudoaneurysms of the cystic artery are a rare but significant complication of acute cholecystitis. Laparoscopic cholecystectomy may be a safe alternative to open cholecystectomy in such cases. We report the case of a female patient in her seventies, who presented with anaemia, jaundice, and hepatic dysfunction during hospitalisation for right knee pyogenic arthritis. The patient had no pain in the right upper quadrant. Her serum haemoglobin level was 6.5 g/dL, and upper gastrointestinal endoscopy revealed no abnormalities. Six days later, jaundice worsened, and endoscopic retrograde cholangiopancreatography revealed bloody bile. An endoscopic biliary drainage tube was inserted at the discretion of the gastroenterology department. Contrast-enhanced computed tomography revealed a haematoma in the gallbladder and a pseudoaneurysm in the lateral wall of the gallbladder. On the same day, the endoscopic biliary drainage tube was replaced with an endoscopic nasobiliary drainage tube, which indicated the degree of haemorrhage and enabled lavage of the lumen in cases of obstruction. The next day, angiography revealed a pseudoaneurysm of the deep branch of the cystic artery and coil embolisation was performed at the periphery of the cystic artery. Uninterrupted laparoscopic cholecystectomy was performed. Although laparoscopic cholecystectomy is difficult when bleeding is uncontrolled, it was safely performed following haemostasis using transcatheter arterial embolisation. Laparoscopic cholecystectomy is feasible in haemodynamically stable patients with cystic artery pseudoaneurysms after transcatheter arterial embolisation.

IntroductionWe aimed to explore the effect of gait training using Welwalk on gait patterns by comparing differences in gait patterns between robotic-assisted gait training using Welwalk and gait training using an orthosis in individuals with hemiparetic stroke.MethodsThis study included 23 individuals with hemiparetic stroke who underwent gait training with Welwalk combined with overground gait training using an orthosis. Three-dimensional motion analysis on a treadmill was performed under two conditions for each participant: during gait training with Welwalk and with the ankle-foot orthosis. The spatiotemporal parameters and gait patterns were compared between the two conditions.ResultsThe affected step length was significantly longer, the step width was significantly wider, and the affected single support phase ratio was significantly higher in the Welwalk condition than in the orthosis condition. The index values of abnormal gait patterns were significantly lower while using Welwalk than in the orthosis condition. The following four indices were lower in the Welwalk condition: contralateral vaulting, insufficient knee flexion, excessive hip external rotation during the paretic swing phase, and paretic forefoot contact.DiscussionGait training using Welwalk increased the affected step length, step width, and single support phase while suppressing abnormal gait patterns as compared to gait training using the ankle-foot orthosis. This study suggests that gait training using Welwalk may promote a more efficient gait pattern reacquisition that suppresses abnormal gait patterns.Trial registrationProspectively registered in the Japan Registry of Clinical Trials (https://jrct.niph.go.jp; jRCTs042180152).

Abstract Introduction Club cell secretory protein-16 (CC16) is a major anti-inflammatory protein expressed in the airway; however, the potential role of CC16 on overweight/obese asthma has not been assessed. In this study, we examined whether obesity reduces airway/circulatory CC16 levels using experimental and epidemiological studies. Then, we explored the mediatory role of CC16 in the relationship of overweight/obesity with clinical asthma measures. Methods Circulating CC16 levels were assessed by ELISA in three independent human populations, including two groups of healthy and general populations and asthma patients. The percentage of cells expressing club markers in obese vs. non-obese mice and human airways was determined by immunohistochemistry. A causal mediation analysis was conducted to determine whether circulatory CC16 acted as a mediator between overweight/obesity and clinical asthma measures. Results BMI was significantly and monotonously associated with reduced circulating CC16 levels in all populations. The percentage of CC16-expressing cells was reduced in the small airways of both mice and humans with obesity. Finally, mediation analysis revealed significant contributions of circulatory CC16 in the association between BMI and clinical asthma measures; 21.8% of its total effect in BMI’s association with airway hyperresponsiveness of healthy subjects (p = 0.09), 26.4% with asthma severity (p = 0.030), and 23% with the required dose of inhaled corticosteroid (p = 0.042). In logistic regression analysis, 1-SD decrease in serum CC16 levels of asthma patients was associated with 87% increased odds for high dose ICS requirement (p

Abstract Although neoadjuvant therapy (Nac) is recommended for high-risk resectable pancreatic cancer (R-PDAC), evidence regarding specific regimes is scarce. This report aimed to investigate the efficacy of S-1 Nac for R-PDAC. In a multicenter phase II trial, we investigated the efficacy of Nac S-1 (an oral fluoropyrimidine agent containing tegafur, gimeracil, and oteracil potassium) in R-PDAC patients. The protocol involved two cycles of preoperative S-1 chemotherapy, followed by surgery, and four cycles of postoperative S-1 chemotherapy. Two-year progression-free survival (PFS) rates were the primary endpoint. Overall survival (OS) rates and median survival time (MST) were secondary endpoints. Forty-nine patients were eligible, and 31 patients underwent resection following Nac, as per protocol (31/49; 63.3%). Per-protocol analysis included data from 31 patients, yielding the 2-year PFS rate of 58.1%, and 2-, 3-, and 5-year OS rates of 96.8%, 54.8%, and 44.0%, respectively. MST was 49.2 months. Intention-to-treat analysis involved 49 patients, yielding the 2-year PFS rate of 40.8%, and the 2-, 3-, and 5-year OS rates of 87.8%, 46.9%, and 33.9%, respectively. MST was 35.5 months. S-1 single regimen might be an option for Nac in R-PDAC; however, the high drop-out rate (36.7%) was a limitation of this study.

Abstract Background Replaced right hepatic artery (rRHA) is a common vascular variation, and combined resection of this vessel is sometimes needed for the curative resection of pancreatic head malignancy. Safe surgical management has not been established, and there is a small number of reported cases. Here, we reported five cases, wherein preoperative embolization of rRHA was performed for combined resection. Case presentation All patients had pancreatic head malignancies that were in contact with rRHA. We performed a preoperative embolization of the rRHA before the scheduled pancreaticoduodenectomy for the combined resection. Arterial embolization was safely accomplished, and the communicating arcade from the left hepatic artery via the hilar plate was clearly revealed in all cases. Four patients underwent the operative procedure, except for one patient who had liver metastasis at laparotomy. No patient suffered from a severe abnormal liver function during the management; however, one patient had multiple liver infarctions during the postoperative course. Conclusions Preoperative embolization for the combined resection of rRHA in pancreaticoduodenectomy can be a management option for the precise evaluation of hemodynamics after sacrificing rRHA. In our cases, arterial flow to the right liver lobe was supplied by the left hepatic artery via the bypass route, including the communicating arcade of the hilar plate.

Abstract Background Although endovascular therapy is used to treat chronic limb-threatening ischemia, long chronic total occlusion (CTO) is still challenging to treat. Especially in patients with poor run-off below-the-knee (BTK) arteries, it is difficult to perform a retrograde approach, and even guidewire passage may be difficult. Case presentation We treated two cases of chronic limb-threatening ischemia using our novel extreme antegrade guidewire crossing technique by AnteOwl WR intravascular ultrasound (IVUS)-guided parallel wiring to a BTK artery (EXCAVATOR technique). Case 1 was a 70-year-old man with ulceration of the right toe. The AnteOwl WR IVUS was intentionally advanced into the subintimal space of the posterior tibial artery, and the totally intraplaque route was advanced by IVUS-guided parallel wiring that was successfully passed from the lateral plantar aspect to the true lumen of the digital artery. Case 2 was a 76-year-old woman with rest pain and cyanosis of the right lower limb. Angiography showed total occlusion from the superficial femoral artery to BTK arteries. AnteOwl WR IVUS-guided parallel wiring was repeatedly performed until the distal true lumen of the peroneal artery was reached, and revascularization was successfully achieved via the antegrade approach alone. Conclusions With its excellent crossable performance, good image quality, and high navigational ability within the CTO, the AnteOwl WR can be used to pass parallel wiring into the distal true lumen for BTK CTO.

Abstract The prognosis of pancreatic ductal carcinoma (PDAC) with peritoneal metastasis remains dismal. Systemic chemotherapy alone may not be effective, and the combination of intraperitoneal chemotherapy with systemic chemotherapy is expected to prolong the overall survival in patients with peritoneal metastasis. We have designed a randomized phase III trial to confirm the superiority of intravenous (i.v.) and intraperitoneal (i.p.) paclitaxel (PTX) with S-1 relative to gemcitabine plus nab-PTX (GnP), which is the current standard therapy for patients with metastatic PDAC. A total of 180 patients will be accrued from 30 institutions within 3 years. Patients will be randomly assigned in a 1:1 ratio to receive either i.v. and i.p. PTX with S-1 or GnP (target of 90 patients per group). The primary endpoint is overall survival; secondary endpoints are progression-free survival, response rate, proportion with negative peritoneal washing cytology during chemotherapy, proportion requiring conversion surgery, and adverse event profiles. Japan Registry of Clinical Trials jRCTs051180199 ( https://jrct.niph.go.jp/ ).

Abstract Background The prognosis of pancreatic ductal adenocarcinoma remains very poor. One possible reason for the short survival of patients with this disease is malnutrition, which can be present at the initial diagnosis, and continue after pancreatectomy. Then, it is important to improve nutritional status and to decrease adverse events during neoadjuvant and adjuvant chemotherapy. Active hexose correlated compound (AHCC) is a standardized extract of cultured Lentinula edodes mycelia, and is considered a potent biological response modifier in the treatment of cancer. To evaluate the survival impact of AHCC on the patients with pancreatic ductal adenocarcinoma, we plan to perform this trial. Methods This is a prospective multicenter phase II trial in patients with resectable/borderline resectable pancreatic ductal adenocarcinoma to investigate the efficacy of AHCC regarding survival. Patients will begin taking AHCC or placebo on the first day of neoadjuvant therapy. AHCC or placebo will be continued until 2 years after surgery. The primary endpoint will be 2-year disease-free survival. The secondary endpoints are the completion rate, dose intensity, and adverse event profile of preoperative chemotherapy; response rate to preoperative chemotherapy; rate of decrease in tumor marker (carbohydrate antigen 19-9, carcinoembryonic antigen) concentrations during preoperative chemotherapy; entry rate, completion rate, dose intensity, and adverse event profile of adjuvant chemotherapy; safety of the protocol therapy (adverse effect of AHCC); 2-year overall survival rate; and nutrition score before and after preoperative chemotherapy, and before and after adjuvant chemotherapy. We will enroll 230 patients, and the study involves eight leading Japanese institutions that are all high-volume centers in pancreatic surgery. Discussion AHCC is expected to function as a supportive food in patients with pancreatic ductal adenocarcinoma, to reduce the proportion of severe adverse events related to neoadjuvant chemotherapy, and to increase the completion proportion of multimodal treatments, resulting in improved survival. Trial registration The trial protocol has been registered in the protocol registration system at the Japan Registry of Clinical Trials (Trial ID: jRCTs051200029 ). At the time of the submission of this paper (October 2020), the protocol version is 2.0. The completion date is estimated to be November 2024.

Background: Near-infrared (NIR) fluorescence image-guided surgery (FIGS) introduces a revolutionary new approach to address this basic challenge in minimally invasive surgery. However, current FIGS systems have some limitations – the infrared rays cannot detect and visualise thick tissues with low concentrations of the fluorescent agent. We established a novel laparoscopic fluorescence spectrum (LFS) system using indocyanine green (ICG) fluorescence to overcome these limitations. Materials and Methods: Bovine serum albumin (BSA) was conjugated to ICG, and the mixtures were serially diluted at 5 × 10−8–5 × 10−1 mg/mL. We used the LFS system and a NIR camera system (NLS; SHINKO OPTICAL CO., LTD Tokyo, Japan) to determine the optical dilution for the fluorescence detection. BSA was conjugated to ICG (5.0 × 10−2 mg/mL) and used to coat the clips. We attempted to identify the fluorescence-coated clip from the serosal side of the cadaveric porcine stomach tissues using the LFS system and the NIR camera system. We measured the depth of the cadaveric porcine stomach wall at the thickest part that could be confirmed. Results: We could not visualise fluorescence concentrations

BackgroundThere is an extensive library of language tests, each with excellent psychometric properties; however, many of the tests available take considerable administration time, possibly bearing psychological strain on patients. The Short and Tailored Evaluation of Language Ability (STELA) is a simplified, tablet-based language ability assessment system developed to address this issue, with a reduced number of items and automated testing process. ObjectiveThe aim of this paper is to assess the administration time, internal consistency, and validity of the STELA. MethodsThe STELA consists of a tablet app, a microphone, and an input keypad for clinician’s use. The system is designed to assess language ability with 52 questions grouped into 2 comprehension modalities (auditory comprehension and reading comprehension) and 3 expression modalities (naming and sentence formation, repetition, and reading aloud). Performance in each modality was scored as the correct answer rate (0-100), and overall performance expressed as the sum of modality scores (out of 500 points). ResultsThe time taken to complete the STELA was significantly less than the time for the WAB (mean 16.2, SD 9.4 vs mean 149.3, SD 64.1 minutes; P

Aim Non‐occlusive mesenteric ischemia (NOMI) is a fatal condition with a low survival rate in most cases. The risk factors for perioperative mortality in NOMI cases are unclear. The purpose of this study was to define the risk factors for mortality in patients with NOMI undergoing surgery. Methods Thirty‐eight consecutive patients who underwent surgery for NOMI at Teine Keijinkai Hospital between 2012 and 2020 were included in the study. Patient information, including age, sex, physical findings, comorbidities, laboratory data, and computed tomography and surgical findings were retrospectively analyzed. Results Of the 38 patients, 18 (47%) died before discharge. Significant univariate predictors of mortality were a high Sequential Organ Failure Assessment (SOFA) score, high lactate level, low blood pH, and short intestinal length after surgery. In the multivariate analysis, a high SOFA score (odds ratio 1.33, P = 0.036) and short intestine length after surgery (odds ratio 34.7, P = 0.003) were identified as independent risk factors for perioperative mortality. Conclusion The preoperative SOFA score and postoperative residual intestinal length may be predictors of death in NOMI surgical patients, not age and the content of comorbidities.

IntroductionRobot-assisted gait training has been reported to improve gait in individuals with hemiparetic stroke. Ideally, the gait training program should be customized based on individuals’ gait characteristics and longitudinal changes. However, a gait robot that uses gait characteristics to provide individually tailored gait training has not been proposed. The new gait training robot, “Welwalk WW-2000,” permits modification of various parameters, such as time and load of mechanical assistance for a patient’s paralyzed leg. The robot is equipped with sensors and a markerless motion capture system to detect abnormal hemiparetic gait patterns during robot-assisted gait training. Thus, it can provide individually tailored gait training. This study aimed to investigate the criterion validity of the gait analysis system in the Welwalk WW-2000 in healthy adults.Materials and methodsTwelve healthy participants simulated nine abnormal gait patterns that were often manifested in individuals with hemiparetic stroke while wearing the robot. Each participant was instructed to perform a total of 36 gait trials, with four levels of severity for each abnormal gait pattern. Fifteen strides for each gait trial were recorded using the markerless motion capture system in the Welwalk WW-2000 and a marker-based three-dimensional (3D) motion analysis system. The abnormal gait pattern index was then calculated for each stride from both systems. The correlation of the index values between the two methods was evaluated using Spearman’s rank correlation coefficients for each gait pattern in each participant.ResultsUsing the participants’ index values for each abnormal gait pattern obtained using the two motion analysis methods, the median Spearman’s rank correlation coefficients ranged from 0.68 to 0.93, which corresponded to moderate to very high correlation.ConclusionThe gait analysis system in the Welwalk WW-2000 for real-time detection of abnormal gait patterns during robot-assisted gait training was suggested to be a valid method for assessing gait characteristics in individuals with hemiparetic stroke.Clinical trial registration[https://jrct.niph.go.jp], identifier [jRCT 042190109].

Objective: To compare the functional outcomes of patients with lower limb amputations receiving haemodialysis and those not receiving haemodialysis. Design: A retrospective cohort study. Patients: Patients with lower limb amputation who were admitted to a convalescent rehabilitation ward between January 2018 and December 2021. Methods: The primary outcome was the effectiveness of the Functional Independence Measure (FIM) during hospitalisation in the ward. Secondary outcomes included the total and subtotal (motor/cognitive) FIM scores at discharge, gain in the total and subtotal (motor/cognitive) FIM scores, K-level at discharge, length of hospital stay in the ward, rehabilitation time, and discharge destination. Outcomes were compared between the non-haemodialysis and haemodialysis groups. Results: A total of 28 patients (mean [standard deviation] age, 67.0 [11.9] years; men, 20) were enrolled in this study. Among them, 11 patients underwent haemodialysis. The FIM effectiveness was significantly higher in the non-haemodialysis group than in the haemodialysis group (median [interquartile range], 0.78 [0.72 – 0.81] vs 0.65 [0.28 – 0.75], p = 0.038). The amount of rehabilitation and all secondary outcomes were not significantly different between the groups (p > 0.05). Conclusion: Patients with lower limb amputation who were receiving haemodialysis had poorer FIM effectiveness than those not receiving haemodialysis. LAY ABSTRACT Chronic kidney disease is a risk factor for foot ulcers and lower limb amputation. Thus, patients with lower limb amputation often require maintenance dialysis. However, there is a lack of knowledge on whether patients with lower limb amputation receiving haemodialysis can achieve functional outcomes comparable to those not receiving haemodialysis. This study aimed to compare functional outcomes between patients with lower limb amputations receiving haemodialysis and those not receiving haemodialysis. This retrospective cohort study enrolled 28 patients who underwent amputation surgery and were admitted to a rehabilitation ward, including 11 patients undergoing haemodialysis (8 with diabetic nephropathy, 1 with chronic glomerulonephritis, 1 with rapidly progressive glomerulonephritis, and 1 with acute kidney injury). Although the amount of rehabilitation did not differ between groups, the improvement in the activities of daily living was significantly better in the non-haemodialysis group than in the haemodialysis group. Thus, even the same amount of rehabilitation for patients with lower limb amputations receiving haemodialysis may not lead to functional outcomes comparable to those without haemodialysis.

Abstract Background Pleuroperitoneal communication is a rare disorder that interferes with peritoneal dialysis. Although favorable results of thoracoscopic fistula closure have been reported, there are some cases in which the fistulas cannot be identified by thoracoscopy and the patients are forced to switch to hemodialysis. Case presentation We present two cases of pleuroperitoneal communication in which diaphragmatic fistulas could not be identified thoracoscopically, but could be identified laparoscopically. Patient 1 had difficulty continuing peritoneal dialysis 9 months after its introduction due to right pleural effusion. Although we could not detect the fistula thoracoscopically, we could laparoscopically identify the fistula in the center of the tendon of the right diaphragm and closed the site from the thoracic side. Patient 2 developed dyspnea due to right pleural effusion 6 months after the introduction of peritoneal dialysis. We could not find the fistulas with a thoracoscopic approach, but could identify multiple diaphragmatic fistulas with a laparoscopic approach and close the sites from the thoracic side. Conclusion In the surgical treatment of pleuroperitoneal communication, diaphragmatic fistulas can be identified laparoscopically even when thoracoscopic observation fails to find any fistulas.

Splenic infarction (SI) following gastrectomy is common; severe complications related to SI, such as splenic haemorrhage, abscess formation or rupture, can be fatal. To overcome these problems, we performed real-time vessel navigation using indocyanine green (ICG) fluorescence during robotic distal gastrectomy (RDG). The aim of study is to report the efficacy of robotic real-time vessel navigation for lymph node dissection (LND) along left gastroepiploic vessels (LGEVs). We treated seven patients with gastric cancer who underwent LND along the LGEVs using robotic real-time vessel navigation during RDG at our institution from January 2021 to July 2021. There were no complications (Clavien–Dindo classification II). There were no cases of post-operative SI or spleen-related complications. Robotic real-time vessel navigation using ICG for LND along LGEVs during RDG could help to reduce post-operative spleen-related complications associated with RDG.

Background: Despite recent developments in the methodology for measuring spasticity, the discriminative capacity of clinically diagnosed spasticity has not been well established. This study aimed to develop a simple device for measuring velocity-dependent spasticity with improved discriminative capacity based on an analysis of clinical maneuver and to examine its reliability and validity.Methods: This study consisted of three experiments. First, to determine the appropriate motion of a mechanical device for the measurement of velocity-dependent spasticity, the movement pattern and the angular velocity used by clinicians to evaluate velocity-dependent spasticity were investigated. Analysis of the procedures performed by six physical therapists to evaluate spasticity were conducted using an electrogoniometer. Second, a device for measuring the resistance force against ankle dorsiflexion was developed based on the results of the first experiment. Additionally, preliminary testing of validity, as compared to that of the Modified Ashworth Scale (MAS), was conducted on 17 healthy participants and 10 patients who had stroke with spasticity. Third, the reliability of the measurement and the concurrent validity of mechanical measurement in the best ankle velocity setting were further tested in a larger sample comprising 24 healthy participants and 32 patients with stroke.Results: The average angular velocity used by physical therapists to assess spasticity was 268 ± 77°/s. A device that enabled the measurement of resistance force at velocities of 300°/s, 150°/s, 100°/s, and 5°/s was developed. In the measurement, an angular velocity of 300°/s was found to best distinguish patients with spasticity (MAS of 1+ and 2) from healthy individuals. A measurement of 300°/s in the larger sample differentiated the control group from the MAS 1, 1+, and 2 subgroups (p < 0.01), as well as the MAS 1 and 2 subgroups (p < 0.05). No fixed or proportional bias was observed in repeated measurements.Conclusion: A simple mechanical measurement methodology was developed based on the analysis of the clinical maneuver for measuring spasticity and was shown to be valid in differentiating the existence and extent of spasticity. This study suggest possible requirements to improve the quality of the mechanical measurement of spasticity.

Abstract Objectives In lung cancer, surgery remains the most curative treatment and limited resection is beneficial for patients with low cardiopulmonary function and low malignancy tumors. However, there are no biomarkers of low malignancy to select candidates for limited resection without compromising the outcome of treatments. Recently we identified biglycan (BGN) as a tumor endothelial cell (TEC) marker that is associated with tumor progression in various cancers. In this study, we analyzed the association between BGN expression in TECs in lung cancer and cancer progression in patients. Materials and Methods First, we performed immunohistochemistry of BGN with resected lung tumor tissues of 155 patients who had undergone thoracic surgery and analyzed the correlation between BGN‐positive vessel density in primary lung tumors and clinicopathological factors. Second, we measured the BGN levels in preoperative serum of other 46 patients with lung cancer by ELISA, and analyzed the correlation between BGN expression in tumor tissues and blood BGN levels. Results High BGN expression in the TECs was significantly associated with T factor, and was a significant negative predictor. BGN levels in preoperative serum of 46 patients with lung cancer was significantly correlated with BGN expression in the TECs. Preoperative serum BGN level was significantly lower in healthy volunteers and less invasive adenocarcinoma than in invasive adenocarcinoma and other lung carcinomas. These results suggest that low BGN level in preoperative serum in patients with lung cancer might indicate low malignancy. Conclusions BGN can be a potential biomarker for lung cancer.

Abstract Many clinical trials are being conducted to clarify effective combinations of various drugs for immune checkpoint blockade (ICB) therapy. However, although extensive studies from multiple aspects have been conducted regarding treatments for pancreatic ductal adenocarcinoma (PDAC), there are still no effective ICB-based therapies or biomarkers for this cancer type. A series of our studies have identified that the small GTPase ARF6 and its downstream effector AMAP1 (also called ASAP1/DDEF1) are often overexpressed in different cancers, including PDAC, and closely correlate with poor patient survival. Mechanistically, the ARF6-AMAP1 pathway drives cancer cell invasion and immune evasion, via upregulating β1-integrins and PD-L1, and downregulating E-cadherin, upon ARF6 activation by external ligands. Moreover, the ARF6-AMAP1 pathway enhances the fibrosis caused by PDAC, which is another barrier for ICB therapies. KRAS mutations are prevalent in PDACs. We have shown previously that oncogenic KRAS mutations are the major cause of the aberrant overexpression of ARF6 and AMAP1, in which KRAS signaling enhances eukaryotic initiation factor 4A (eIF4A)-dependent ARF6 mRNA translation and eIF4E-dependent AMAP1 mRNA translation. MYC overexpression is also a key pathway in driving cancer malignancy. MYC mRNA is also known to be under the control of eIF4A, and the eIF4A inhibitor silvestrol suppresses MYC and ARF6 expression. Using a KPC mouse model of human PDAC (LSL-Kras(G12D/+); LSL-Trp53(R172H/+)); Pdx-1-Cre), we here demonstrate that inhibition of the ARF6-AMAP1 pathway by shRNAs in cancer cells results in therapeutic synergy with an anti-PD-1 antibody in vivo; and furthermore, that silvestrol improves the efficacy of anti-PD-1 therapy, whereas silvestrol on its own promotes tumor growth in vivo. ARF6 and MYC are both essential for normal cell functions. We demonstrate that silvestrol substantially mitigates the overexpression of ARF6 and MYC in KRAS-mutated cells, whereas the suppression is moderate in KRAS-intact cells. We propose that targeting eIF4A, as well as mutant KRAS, provides novel methods to improve the efficacy of anti-PD-1 and associated ICB therapies against PDACs, in which ARF6 and AMAP1 overexpression, as well as KRAS mutations of cancer cells are biomarkers to identify patients with drug-susceptible disease. The same may be applicable to other cancers with KRAS mutations. Video abstract

Abstract Background Sarcoid-like reaction (SLR) is a histological pattern of granulomatous inflammation that is clinically differentiated from sarcoidosis. Since SLR is known to occur in several neoplasias and occasionally causes lymphadenopathy and mimics metastatic malignancy, it needs to be considered whether lymphadenopathy is due to metastasis or SLR for the choice of cancer treatment. Few cases of hepatocellular carcinoma (HCC) with SLR have been reported. Here, a case of HCC with lymphadenopathy diagnosed as SLR without metastasis is presented. Case presentation A 69-year-old woman was admitted to our hospital because of upper abdominal pain. She tested positive for hepatitis C virus ribonucleic acid. Imaging modalities showed an 81 × 65-mm-sized tumor with multiple nodules in segment 3 and a 17 × 12-mm-sized tumor in segment 5 with a common HCC enhancement pattern. In addition, a lymph node in the hepatoduodenal ligament was enlarged at 13 mm in size, suggesting the metastasis of HCC. Hepatectomy of the lateral segment and segment 5 and lymph node dissection in the hepatoduodenal ligament were performed. Both tumors in segments 3 and 5 were pathologically diagnosed as HCC without vessel invasion. The tumors contained necrotic cells and epithelioid cell granulomas with multinucleated giant cells, which is typically observed in sarcoidosis. The dissected lymph nodes also contained epithelioid cell granulomas, as well as giant cells with asteroid bodies. There was no malignancy in the lymph nodes. The pathological findings suggested the coexistence of malignancy and sarcoidosis. However, since the patient did not show any typical findings of pulmonary or cardiac sarcoidosis, the case was diagnosed as HCC with SLR in the primary lesion and regional lymph nodes. Conclusions SLR needs to be considered in the differential diagnosis when a cancer patient develops lymphadenopathy. However, lymphadenopathy due to SLR is indistinguishable from that due to metastasis even when using multiple imaging modalities. Pathological examinations may be helpful for the diagnosis.

Abstract Background Surgical endarterectomy for common femoral artery (CFA) disease is still considered the gold standard for treatment. Development of various techniques and devices has improved the clinical results of endovascular therapy (EVT) for CFA. However, severe conditions remain, especially for occlusive lesions owing to calcified plaque. We developed a useful technique for passing a lesion by directly penetrating the calcified plaque of the CFA using a bare metal needle and then passing through a balloon or dilating it. We named this technique “direct bare metal needle puncture and balloon angioplasty in calcified plaques of the common femoral artery guided by angiography” or “BAMBOO SPEAR.” Main text This report describes our technique for crossing a lesion by directly penetrating the calcified plaque of the CFA using a needle. We report a case of a 73-year-old male with hemodialysis who presented with cyanosis and ischemic rest pain of both lower limbs. Control angiography showed total occlusion of the left CFA with a calcified plaque. We advanced a 21-G metal needle that was slightly curved into the blood vessel from where the lumen of the distal CFA was located. The needle was advanced into the center of the calcified plaque, while observing from multiple directions with a fluoroscopic guide. We succeeded in advancing the needle into the lumen of the distal external iliac artery. After guidewire crossing, intravascular ultrasound (IVUS) showed that guidewire was able to completely pass through the center of the calcified plaque. We could dilate the lesion by scoring balloon and drug-coated balloon. The final angiography showed sufficient results. We named this technique “direct BAre Metal needle puncture and BallOOn angioplaSty in calcified PlaquEs of the common femoral ARtery guided by angiography” (BAMBOO SPEAR). Conclusions The BAMBOO SPEAR technique may be considered a useful option in EVT for occlusive CFA with calcified plaques.

Background: Laparoscopic-Warshaw technique (lap-WT) may be selected as a function-preserving operation for malignant border lesions in the tail region of the pancreas. However, previous reports showed that there are complications such as infection and abscess formation due to lack of blood flow to the spleen after surgery. To overcome the problems, we have performed real-time vessel navigation by using indocyanine green (ICG) fluorescence during lap-WT. Materials and Methods: We report our experience of three patients with pancreatic tumour who underwent real-time vessel navigation during lap-WT at Hokkaido University from May 2017 to September 2018. Results: The median operating time was 339 min (174–420). The median intraoperative bleeding was 150 ml (0–480). There were no incidences of complications. There were no cases with post-operative spleen ischaemia or abscess formation and varices formation. Conclusion: We believe that laparoscopic real-time vessel navigation using indocyanine green fluorescence during lap-WT could contribute in reducing the post-operative spleen-related complications.

A considerable percentage of morbidity and mortality after oesophagectomy is due to leakage of oesophagogastrostomy, which is mainly caused by ischaemia of the gastric tube. Therefore, we performed laparoscopic real-time vessel navigation (LRTVN) using indocyanine green fluorescence (ICG) during laparoscopy-assisted gastric tube reconstruction (LAGR) to evaluate gastric tube blood flow and avoid vascular injury. This study included five oesophageal cancer patients who underwent video-assisted thoracoscopic oesophagectomy and LAGR. We confirmed the presence of the left gastroepiploic artery (LGEA) in all cases, and no findings such as post-operative gastric tube ischaemia were observed. In all cases, no vascular injury was observed, and the vascularization of LGEA was confirmed. This report is the first to consider the usefulness of LRTVN using ICG during LAGR. LRTVN using ICG during LAGR was considered to be useful for evaluating gastric tube blood flow and avoiding vascular injury around the splenic hiatus.

Abstract Background In melanoma, completely resectable metastases are surgically resected to expect to prolong relapse-free survival and overall survival. However, distant metastases of melanoma are rarely indicated for surgery because multiple metastases are often observed at diagnosis. We report a case of a man in his 50s who underwent laparoscopic-assisted distal gastrectomy and central pancreatectomy for gastric metastases, lymph node metastases, and pancreatic invasion that could be completely resected. Case presentation A 50-year-old man was diagnosed with malignant melanoma of the left parietal region. After diagnosis, tumor resection and left cervical lymph node dissection were performed, and interferon-β treatment was added as adjuvant therapy. Seventeen months after adjuvant therapy, metastasis of stomach and abdominal lymph nodes from melanoma was diagnosed. And the pancreatic invasion of lymph nodes was suspected. Laparoscopic-assisted distal gastrectomy and the central pancreatectomy were performed because pancreatic invasion of melanoma was intraoperatively found. After 9 months of relapse-free survival, abdominal recurrence was observed. Nivolumab and ipilimumab were administered, and recurrent lesions are currently controlled. The patient has survived more than 3 years since metastasis resection. Conclusion In conclusion, laparoscopic-assisted distal gastrectomy and the central pancreatectomy were performed for gastric and perigastric lymph node metastases and pancreatic invasion due to malignant melanoma, and the negative surgical margin was achieved. Although patient selection is required, the central pancreatectomy was a good indication for maintaining exocrine and endocrine function. The development of immune checkpoint inhibitors and molecular-targeted agents may increase gastrointestinal surgery for metastatic melanoma in the future.

Abstract Background Not merely the onset of immune evasion, but other factors, such as acidosis and fibrosis, are also major barriers in cancer therapeutics. Dense fibrosis is a hallmark of pancreatic ductal carcinoma (PDAC), in which hyperactivation of focal adhesion kinase (FAK) in tumor cells was shown to be crucial. Double mutations of KRAS/ TP53 are characteristic to PDAC. We previously showed that high protein expression of ARF6 and its downstream effector AMAP1, as well as processes involved in the ARF6 activation by cell surface tyrosine kinase receptors, are major targets of the KRAS/TP53 mutations to promote PDAC invasion, metastasis, and immune evasion. This notion was recaptured by KPC mouse model of human PDAC (LSL-Kras(G12D/+); LSL-Trp53(R172H/+)); Pdx-1-Cre). Mechanistically, the ARF6-AMAP1 pathway is primarily involved in cellular dynamics of PD-L1, β1-integrins, and E-cadherin; and hence modulates cell-adhesion properties when ARF6 is activated. Here, with an aim to understand whether the ARF6-AMAP1 pathway is critically involved in the elevated levels of PD-L1 and fibrosis of PDAC, we analyzed relationship between AMAP1 and these malignant phenotypes. Moreover, because the ARF6 pathway may closely be related to focal adhesion dynamics and hence to FAK, we also investigated whether AMAP1 employs FAK in fibrosis. Methods Clinical specimens, as well as KPC cells/tumors and their shAMAP1 or shFAK derivatives were analyzed. Results Elevated levels of PD-L1 and fibrosis correlated with poor outcome of our patient cohort, to be consistent with previous reports; in which high AMAP1 expression statistically correlated with the elevated PD-L1 and fibrosis. To be consistent, silencing of AMAP1 (shAMAP1) in KPC cells resulted in reduced PD-L1 expression and fibrosis in their tumors. On the other hand, shAMAP1 only slightly affected FAK activation in KPC cells, and phosphorylated FAK did not correlate with enhanced fibrosis or with poor outcome of our patients. Conclusions Together with our previous data, our results collectively indicated that the ARF6-AMAP1 pathway, empowered by the KRAS/TP53 mutations, is closely associated with elevated PD-L1 expression and fibrosis of human PDACs, to be recaptured in the KPC mouse model. The ARF6 pathway may promote fibrosis independent of FAK. Video abstract

Abstract Background Lymphangioma is a benign malformation of the lymphatic system and is often found in the neck and axilla, the orbit, the mediastinum, etc. However, isolated splenic lymphangioma is a rare disease in young women, and its treatment is controversial. We report a case of laparoscopic partial splenectomy for isolated splenic lymphangioma in a young woman. Case presentation An 18-year-old woman with mild epigastralgia was admitted to a nearby hospital. Abdominal ultrasound detected a 6-cm mass confined to the upper pole of the spleen; thereafter, she was referred to our department for surgical treatment. Although a benign tumor, we decided to resect it because of her symptoms. To preserve part of the normal spleen, laparoscopic partial splenectomy was performed with a co-axial approach using four ports and a liver retractor in the lithotomy position. After dissection around the spleen hilum, we identified that the tumor was being fed from the splenic vessels of the upper pole and severed the branch. Postoperatively, the patient showed no complications and was discharged on postoperative day 8 without symptoms. Pathological examination revealed splenic lymphangioma, which is rare in young women. No recurrence was seen 1 year after surgery, and a computed tomography scan showed no problems with the remaining spleen. Conclusions In our experience of laparoscopic partial splenectomy for a young woman with an isolated splenic lymphangioma, we determined that laparoscopic partial splenectomy is a safe, effective, and valuable option for the treatment of benign splenic tumors.

Abstract Background Biliary bleeding is a condition reported by Sandblom as hemobilia. The most common cause of hemobilia is iatrogenicity. But it has also been reported as a rare complication after laparoscopic cholecystectomy (LC). Case presentation A man in his 60s underwent a LC. He was taking a direct Xa inhibitor for paroxysmal atrial fibrillation (pAf) and had a history of thrombectomy. There was variation in the bifurcation of the hepatic artery and cystic artery. The right hepatic artery branches from the common hepatic artery by itself, and the cystic artery is double. He complained of right upper quadrant pain, nausea, and vomiting on the third postoperative day (3POD). Non-contrast computed tomography (CT) showed that a high absorption area was found to fill the common bile duct. Contrast CT showed no pseudoaneurysm formation. Ultimately, he was diagnosed with postoperative hemobilia. Angiographic examination selective for the cystic artery branching from the middle hepatic artery revealed leakage of the contrast agent and a micro-pseudoaneurysm. Conclusions We encountered a case of hemobilia after LC. In this case, it was presumed that in addition to the chronic inflammatory changes of the gallbladder wall, extraordinary bifurcation of the hepatic artery and the cystic arteries and easy bleeding due to resumption of a direct Xa inhibitor synergistically caused a micro-pseudoaneurysm and postoperative hemobilia. It was difficult to identify the cause of hemobilia by contrast CT alone. Angiographic examination was useful for identifying and treating the causative artery and needs to perform aggressively.

Neoadjuvant chemotherapy/neoadjuvant chemoradiotherapy (NAC/NACRT) can be performed in patients with pancreatic cancer to improve survival. We aimed to clarify the clinical outcomes of biliary drainage with a metal stent (MS) or a plastic stent (PS) during NAC/NACRT. Between October 2013 and April 2016, 96 patients with pancreatic cancer were registered for NAC/NACRT. Of these, 29 patients who underwent biliary drainage with MS or PS before NAC/NACRT and a subsequent pancreatoduodenectomy were retrospectively analyzed with regard to patient characteristics, preoperative recurrent biliary obstruction rate, NAC/NACRT delay or discontinuation rate, and operative characteristics. The median age of the patients was 67 years. NAC and NACRT were performed in 14 and 15 patients, respectively, and MS and PS were used in 17 and 12 patients, respectively. Recurrent biliary obstruction occurred in 6% and 83% of the patients in the MS and PS groups, respectively (p