Effects of robot-assisted gait training using the Welwalk on gait independence for individuals with hemiparetic stroke: an assessor-blinded, multicenter randomized controlled trial.

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.

Factors Affecting Nonfunctioning Small Pancreatic Neuroendocrine Neoplasms and Proposed New Treatment Strategies.

BACKGROUND & AIMS: Despite previously reported treatment strategies for nonfunctioning small (≤20 mm) pancreatic neuroendocrine neoplasms (pNENs), uncertainties persist. We aimed to evaluate the surgically resected cases of nonfunctioning small pNENs (NF-spNENs) in a large Japanese cohort to elucidate an optimal treatment strategy for NF-spNENs. METHODS: In this Japanese multicenter study, data were retrospectively collected from patients who underwent pancreatectomy between January 1996 and December 2019, were pathologically diagnosed with pNEN, and were treated according to the World Health Organization 2019 classification. Overall, 1490 patients met the eligibility criteria, and 1014 were included in the analysis cohort. RESULTS: In the analysis cohort, 606 patients (59.8%) had NF-spNENs, with 82% classified as grade 1 (NET-G1) and 18% as grade 2 (NET-G2) or higher. The incidence of lymph node metastasis (N1) by grade was significantly higher in NET-G2 (G1: 3.1% vs G2: 15.0%). Independent factors contributing to N1 were NET-G2 or higher and tumor diameter ≥15 mm. The predictive ability of tumor size for N1 was high. Independent factors contributing to recurrence included multiple lesions, NET-G2 or higher, tumor diameter ≥15 mm, and N1. However, the independent factor contributing to survival was tumor grade (NET-G2 or higher). The appropriate timing for surgical resection of NET-G1 and NET-G2 or higher was when tumors were >20 and >10 mm, respectively. For neoplasms with unknown preoperative grades, tumor size >15 mm was considered appropriate. CONCLUSIONS: NF-spNENs are heterogeneous with varying levels of malignancy. Therefore, treatment strategies based on tumor size alone can be unreliable; personalized treatment strategies that consider tumor grading are preferable.

[A Case of Advanced Gastric Cancer Treated with Conversion Surgery followed by Nivolumab Combination Chemotherapy].

The use of nivolumab as first-line therapy for unresectable advanced gastric cancer has now become a standard practice, and its efficacy has been established. This is the first report of a patient with advanced gastric cancer who underwent conversion surgery after first-line nivolumab combination chemotherapy. The patient was a 58-year-old woman. Her medical history included hypertension and dyslipidemia. She had advanced gastric cancer with extensive lymph node metastasis in the left supraclavicular fossa and around the abdominal aorta. After confirming the HER2-negative status and the PD-L1 CPS score to be ≥5, nivolumab was administered in combination with chemotherapy. After the treatment, she underwent a total gastrectomy with D2 dissection, combined splenectomy and pancreatic tail resection for adhesions, and para-aortic lymph node sampling as a conversion surgery. There was no obvious cancerous remnant in the resected specimen, and the pathological response was Grade 3. The patient was alive and recurrence-free at 4 months postoperatively.

Prognostic value of combined psoas muscle mass and controlling nutritional status in patients with pancreatic ductal adenocarcinoma: a retrospective cohort study.

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 < 0.001). The poor general condition group had a significantly worse prognosis than the good and moderate general condition groups (p = 0.012 and p = 0.037). The 5-year survival rates were 10.9%, 22.3%, and 36.1% in the poor, moderate, and good general condition groups, respectively. In multivariate analysis, poor general condition, with both low PMI and malnutrition status, was an independent poor prognostic factor for postoperative OS (hazard ratio 2.161, p = 0.031). CONCLUSIONS: The combination of PMI and CONUT scores may be useful for predicting the prognosis of patients with PDAC after radical surgery.

Aldehyde Dehydrogenese-1 High Cancer Stem-like Cells/Cancer-initiating Cells Escape from Cytotoxic T Lymphocytes due to Lower Expression of Human Leukocyte Antigen Class 1.

BACKGROUND/AIM: Human gastric cancer stem-like cells (CSCs)/cancer-initiating cells can be identified as aldehyde dehydrogenase-high (ALDHhigh) cells. Cancer immunotherapy employing immune checkpoint blockade has been approved for advanced gastric cancer cases. However, the effectiveness of cancer immunotherapy against gastric CSCs/CICs remains unclear. This study aimed to investigate the susceptibility of gastric CSCs/CICs to immunotherapy. MATERIALS AND METHODS: Gastric CSCs/CICs were isolated as ALDHhigh cells using the human gastric cancer cell line, MKN-45. ALDHhigh clone cells and ALDHlow clone cells were isolated using the ALDEFLUOR assay. ALDH1A1 expression was assessed via qRT-PCR. Sphere-forming ability was evaluated to confirm the presence of CSCs/CICs. A model neoantigen, AP2S1, was over-expressed in ALDHhigh clone cells and ALDHlow clone cells, and susceptibility to AP2S1-specific TCR-T cells was assessed using IFNγ ELISPOT assay. RESULTS: Three ALDHhigh clone cells were isolated from MKN-45 cells. ALDHhigh clone cells exhibited a stable phenotype in in vitro culture for more than 2 months. The High-36 clone cells demonstrated the highest sphere-forming ability, whereas the Low-8 cells showed the lowest sphere-forming ability. High-36 cells exhibited lower expression of HLA-A24 compared to Low-8 cells. TCR-T cells specific for AP2S1 showed lower reactivity to High-36 cells compared to Low-8 cells. CONCLUSION: High-36 cells and Low-8 cells represent novel gastric CSCs/CICs and non-CSCs/CICs, respectively. ALDHhigh CSCs/CICs evade T cells due to lower expression of HLA class 1.

Transabdominal impalement injury by an iron pipe - A case report.

Impalement injuries are rare and complex problems, often involving multiple organ injuries. An 18-year-old male was admitted to our emergency department after a car accident. Positioned in the right-side recumbent position, he had a 4.5 cm diameter pipe penetrating from his left abdomen to his back. Given the pipe's length exceeding the CT gantry's capacity, further imaging tests were not feasible. Consequently, the patient proceeded directly to the operating room without preoperative imaging. Before laparotomy, a left thoracotomy was conducted for aortic cross-clamping, anticipating uncontrollable bleeding during pipe removal. The subsequent laparotomy, with the patient in the right-side recumbent position, revealed the pipe impaling through the mesentery of the descending colon without evident major vessel injury. The pipe was cautiously extracted. The patient was subsequently discharged on day 26. The absence of imaging feasibility emphasized that current hemodynamic stability does not rule out the potential for significant vessel injury. Therefore, the sequential approach of left thoracotomy for aortic cross-clamping followed by laparotomy emerges as a potentially beneficial strategy in cases of transabdominal impalement. The impalement injury requires our preparedness and flexibility, which should be tailored to the individual case.

Acute onset of constrictive pericarditis due to acute myelomonocytic leukemia: A case and literature review.

We herein present a fatal case of constrictive pericarditis (CP) due to acute myelomonocytic leukemia (AMML) in a patient who initially complained of an acute onset of chest pain two days after COVID-19 vaccination. An autopsy revealed pericardial infiltration of leukemic cells. CP is rarely associated with leukemia and only 14 cases have been reported in the literature. The etiology of CP in previous reports included leukemic infiltration, graft-versus-host disease, drug-induced, post-radiation, autoimmune, and otherwise unidentified. This case indicates that leukemic infiltration can cause CP and that clinicians should include leukemia in the differential diagnosis of CP.

Concurrent targeting of GSK3 and MEK as a therapeutic strategy to treat pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies worldwide. However, drug discovery for PDAC treatment has proven complicated, leading to stagnant therapeutic outcomes. Here, we identify Glycogen synthase kinase 3 (GSK3) as a therapeutic target through a whole-body genetic screening utilizing a '4-hit' Drosophila model mimicking the PDAC genotype. Reducing the gene dosage of GSK3 in a whole-body manner or knocking down GSK3 specifically in transformed cells suppressed 4-hit fly lethality, similar to Mitogen-activated protein kinase kinase (MEK), the therapeutic target in PDAC we have recently reported. Consistently, a combination of the GSK3 inhibitor CHIR99021 and the MEK inhibitor trametinib suppressed the phosphorylation of Polo-like kinase 1 (PLK1) as well as the growth of orthotopic human PDAC xenografts in mice. Additionally, reducing PLK1 genetically in 4-hit flies rescued their lethality. Our results reveal a therapeutic vulnerability in PDAC that offers a treatment opportunity for patients by inhibiting multiple targets.

Incidence of atrial fibrillation after esophageal cancer surgery with L-carnitine use: a preliminary single-group interventional study.

PURPOSE: We aimed to investigate the POAF rate and blood FABP4 levels after perioperative L-carnitine administration in patients with esophageal cancer. METHODS: L-carnitine (3 g in three divided doses) was administered to 15 patients 2 days before and 3 days after surgery. POAF during the study period and blood FABP4 levels (ELISA) before and after L-carnitine administration were evaluated. Accurate 95% confidence intervals (CI) for POAF incidence and changes in blood FABP4 levels were calculated. The preoperative predicted POAF rate was calculated using an application for esophageal cancer. The correlation between FABP4 levels and the predicted POAF rate was analyzed using Pearson's coefficient (r). RESULTS: Thirteen patients completed this study. The predicted POAF rate was 24% (17%, 34%) (median; interquartile range). The actual incidence of POAF was 7.7% (95% CI: 0.2-36%). Blood FABP4 levels changed from 10.3 to 7.0 ng/mL; the average change was - 3.3 (95% CI: - 6.6 to - 0.1). A positive correlation was found between preoperative FABP4 levels and the predicted POAF rates (r = 0.564). CONCLUSIONS: The POAF rate after esophageal surgery was 7.7% for L-carnitine. L-carnitine may reduce blood FABP4 levels. This preliminary study will contribute to the planning of sample sizes in future randomized trials.

Esophageal perforation due to soft coagulation heat injury after right lower lobectomy: A case report.

INTRODUCTION: Soft coagulation is a hemostatic system of electrosurgical units that automatically regulates its output to avoid carbonization or incision. This system is widely used in invasive procedures, including thoracic surgery. Few reports exist on the harmful effects of these devices. Herein, we encountered a case of an esophagopleural fistula caused by soft coagulation. PRESENTATION OF CASE: A 74-year-old man with a history of bladder cancer was diagnosed with a tumor in the right lower lung lobe 2.5 cm in diameter. A thoracoscopic right lower lobectomy with lymph node dissection was performed. During surgery, hemostasis using soft coagulation was performed on the right wall of the lower esophagus. Eight days after surgery, thoracoscopic empyema curettage and drainage were performed. Three days after the second surgery, an esophageal fistula was identified. Suturing for the esophageal fistula and omentoplasty were performed. Suture failure occurred and an esophagobronchial fistula developed after the third surgery, which was reduced by drainage, antibiotics, and enteral nutrition. The fistula was finally addressed by fibrin glue filling in its cavity. DISCUSSION: Soft coagulation helps manage hemostasis and contributes to safe surgery. However, it may cause severe complications owing to the unpredictable spread of heat denaturation. It is suspected that delayed esophageal perforation was caused by an unnoticed heat injury to the deeper layer of the esophageal wall. CONCLUSION: There have been no reports of esophagus injury caused by soft coagulation exept for our experience. Although soft coagulation is a useful device owing to its excellent hemostatic capacity, the spread of heat denaturation may cause unpredictable tissue damage. Extra caution should be observed when using this device for hemostasis.

Long-term outcomes of single-incision laparoscopic colectomy for right-sided colon cancer utilising a craniocaudal approach.

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.

Ensuring communication redundancy and establishing a telementoring system for robotic telesurgery using multiple communication lines.

Assuring communication redundancy during the interruption and establishing appropriate teaching environments for local surgeons are essential to making robotic telesurgery mainstream. This study analyzes robotic telesurgery with telementoring using standard domestic telecommunication carriers. Can multiple carriers guarantee redundancy with interruptions? Three commercial optical fiber lines connected Hirosaki University and Mutsu General Hospitals, 150 km apart. Using Riverfield, Inc. equipment, Hirosaki had a cockpit, while both Mutsu used both a cockpit and a surgeon's console. Experts provided telementoring evaluating 14 trainees, using objective indices for operation time and errors. Subjective questionnaires addressed image quality and surgical operability. Eighteen participants performed telesurgery using combined lines from two/three telecommunication carriers. Manipulation: over 30 min, lines were cut and restored every three minutes per task. Subjects were to press a switch when noticing image quality or operability changes. Mean time to task completion was 1510 (1186-1960) seconds: local surgeons alone and 1600 (1152-2296) seconds for those under remote instructor supervision, including expert intervention time. There was no significant difference (p = 0.86). The mean error count was 0.92 (0-3) for local surgeons and 0.42 (0-2) with remote instructors. Image quality and operability questionnaires found no significant differences. Results communication companies A, B, and C: the A/B combination incurred 0.17 (0-1) presses of the environment change switch, B/C had 0, and C/A received 0.67 (0-3), showing no significant difference among provider combinations. Combining multiple communication lines guarantees communication redundancy and enables robotic telementoring with enhanced communication security.

Effects of communication delay in the dual cockpit remote robotic surgery system.

PURPOSE: To evaluate the impact of dual cockpit telesurgery on proctors and operators, and acceptable levels of processing delay for video compression and restoration. METHODS: Eight medical advisors and eight trainee surgeons, one highly skilled per group, performed gastrectomy, rectal resection, cholecystectomy, and bleeding tasks on pigs. Using the Medicaroid surgical robot hinotori™, simulated delay times (0 ms, 50 ms, 100 ms, 150 ms, and 200 ms) were inserted mid-surgery to evaluate the tolerance level. Operative times and dual cockpit switching times were measured subjectively using 5-point scale questionnaires (mSUS [modified System Usability Scale], and Robot Usability Score). RESULTS: No significant difference was observed in operative times between proctors and operators (proctor: p = 0.247, operator: p = 0.608) nor in switching times to the dual cockpit mode (p = 0.248). For each survey setting, proctors tended to give lower ratings to delays of ≥ 150 ms. No marked difference was observed in the operator evaluations. On the postoperative questionnaires, there were no marked differences in the mSUS or Robot Usability Score between the proctors and operators (mSUS: p = 0.779, Robot Usability Score: p = 0.261). CONCLUSION: Telesurgery using a dual cockpit with hinotori™ is practical and has little impact on surgical procedures.

The shortage of surgeons in Japan: Results of an online survey of qualified teaching hospitals that take part in the surgical training programs for board certification by the Japan Surgical Society.

PURPOSE: A collapse in regional healthcare through the maldistribution of physicians has been a long-debated issue in Japan and amidst this situation, a new system of board certification was initiated. The Japan Surgical Society (JSS) conducted a nation-wide survey to grasp the current distribution of surgeons in Japan, and their roles. METHODS: All 1976 JSS-certified teaching hospitals were invited to respond to a web-based questionnaire. The responses were analyzed to seek a solution to the current issues. RESULTS: Responses to the questionnaire were received from 1335 hospitals. The surgical departments of medical universities serve as an internal labor market and were the source of surgeons for most hospitals. More than 50% of teaching hospitals throughout the country claimed a shortage of surgeons even in well-populated prefectures such as Tokyo and Osaka. Hospitals rely on surgeons to cover the deficits in medical oncology, anesthesiology, and emergency medicine. These additional responsibilities were identified as significant predictors of a shortage of surgeons. CONCLUSIONS: Surgeon shortage is a serious issue throughout Japan. Given the limited number of surgeons and surgical trainees, hospitals should make every effort to recruit specialists in the additional fields where surgeons are filling the gaps and allow surgeons to engage more in surgery.

Tele-robotic distal gastrectomy with lymph node dissection on a cadaver.

The purpose of this study is to evaluate the performance of tele-robotic distal gastrectomy (tele-RDG) with lymph node dissection (LND) using a novel Japanese-made surgical robot hinotori™ (Medicaroid, Kobe, Japan) in a cadaver with a presumptive gastric cancer. The Cadaveric Anatomy and Surgical Training Laboratory (CAST-Lab.) at Hokkaido University and Kushiro City General Hospital (KCGH) are connected by a guaranteed type line (1 Gbps), and the distance between the two facilities is 250 km. A patient cart was installed at CAST-Lab, and a surgeon cockpit was installed at KCGH. Tele-RDG with D2 LND was performed on an adult human cadaver. In all surgical processes, the communication environment was stable without image degradation, and the mean round trip time was 40 milliseconds (36.5-55 milliseconds). For tele-RDG with D2 LND, the operation time was 199 minutes without any technical problems. Tele-RDG using hinotori™ was feasible and similar to local robotic RDG.

Field experiment of a telesurgery system using a surgical robot with haptic feedback.

PURPOSE: To verify the usefulness of haptic feedback in telesurgery and improve the safety of telerobotic surgery. METHODS: The surgeon's console was installed at two sites (Fukuoka and Beppu; 140 km apart), and the patient cart was installed in Fukuoka. During the experiment, the surgeon was blinded to the haptic feedback levels and asked to grasp the intestinal tract in an animal model. The surgeon then performed the tasks at each location. RESULTS: No marked differences in task accuracy or average grasping force were observed between the surgeon locations. However, the average task completion time was significantly longer, and the system usability scale (SUS) was significantly lower rating for remote operations than for local ones. No marked differences in task accuracy or task completion time were observed between the haptic feedback levels. However, with haptic feedback, the organ was grasped with a significantly weaker force than that without it. Furthermore, with haptic feedback, experienced surgeons in robotic surgery tended to perform an equivalent task with weaker grasping forces than inexperienced surgeons. CONCLUSION: The haptic feedback function is a tool that allows the surgeon to perform surgery with an appropriate grasping force, both on site and remotely. Improved safety is necessary in telesurgery; haptic feedback will thus be an essential technology in robotic telesurgery going forward.

Impact of Neutrophil Extracellular Traps Identified by Citrullinated Histone H3 Immunohistochemistry for Postoperative Prognosis in Patients with Extrahepatic Cholangiocarcinomas.

BACKGROUND: Neutrophil extracellular traps (NETs) are extracellular chromatin structures composed of cytoplasmic, granular, and nuclear components of neutrophils. Recently, NETs have received much attention for their role in tumor biology; however, their impact on the postoperative prognosis of patients with extrahepatic cholangiocarcinomas (EHCCs) remains unclear. The purpose of this study was to clarify the impact of NETs identified by immunohistochemical citrullinated histone H3 (Cit-H3) staining on postoperative overall survival (OS) in patients with perihilar cholangiocarcinoma (PHCC) and distal cholangiocarcinoma (DCC). METHODS: This study included 318 patients with EHCC (PHCC, n = 192; DCC, n = 126) who underwent surgical resection with curative intent. Neutrophils and NETs were identified by immunohistochemistry using antibodies against CD15 and Cit-H3, respectively. Based on the distribution of CD15 and Cit-H3 expression in the tumor bed, the patients were classified into four groups: one negative group and three subgroups of the positive group (diffuse, intermediate, and focal subgroups). RESULTS: No significant difference was found in the postoperative OS rate depending on the distribution of CD15 expression in patients with PHCC or DCC. However, the three subgroups with positive Cit-H3 expression had significantly poorer OS than the negative group for both PHCC and DCC. Moreover, positive Cit-H3 was an independent OS factor in the multivariable analyses of PHCC (hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.11-2.59, P = 0.0115) and DCC (HR 2.03; 95% CI 1.21-3.42, P = 0.0057). CONCLUSIONS: The presence of NETs in the tumor microenvironment may have adverse prognostic effects in patients with EHCCs.

The Short- and Long-Term Surgical Results of Consecutive Hepatopancreaticoduodenectomy for Wide-Spread Biliary Malignancy.

BACKGROUND: Cancer-free resection (R0) is one of the most important factors for the long-term survival of biliary carcinoma. For some patients with widespread invasive cancer located between the hilar and intrapancreatic bile duct, hepatopancreaticoduodenectomy (HPD) is considered a radical surgery for R0 resection. However, HPD is associated with high morbidity and mortality rates. Furthermore, previous reports have not shown lymph node metastasis (LNM) status, such as the location or number, which could influence the prognosis after HPD. In this study, first, we explored the prognostic factors for survival, and second, we evaluated whether the LNM status (number and location of LNM) would influence the decision on surgical indications in patients with widely spread biliary malignancy. METHODS: We retrospectively reviewed the medical records of 54 patients who underwent HPD with hepatectomy in ≥2 liver sectors from January 2003 to December 2021 (HPD-G). We also evaluated 54 unresectable perihilar cholangiocarcinoma patients who underwent chemotherapy from January 2010 to December 2021 (CTx-G). RESULTS: R0 resection was performed in 48 patients (89%). The median survival time (MST) and 5-year overall survival rate of the HPD-G and CTx-G groups were 36.9 months and 31.1%, and 19.6 months and 0%, respectively. Univariate and multivariate analyses showed that pathological portal vein involvement was an independent prognostic factor for survival (MST: 18.9 months). Additionally, patients with peripancreatic LNM had worse prognoses (MST: 13.3 months) than CTx-G. CONCLUSIONS: Patients with peripancreatic LNM or PV invasion might be advised to be excluded from surgery-first indications for HPD.

Feasibility of S-1 adjuvant chemotherapy after major hepatectomy for biliary tract cancers: An exploratory subset analysis of JCOG1202.

INTRODUCTION: Major hepatectomy (MH) may produce the impaired liver function and affect the feasibility of adjuvant chemotherapy in terms of early period after the surgery, but there have not been detailed investigations. JCOG1202 (UMIN000011688) is a randomized phase III trial demonstrating the superiority of adjuvant S-1 chemotherapy for biliary tract cancer (BTC). The aim of this study is to examine the influence of MH for BTC on adjuvant S-1. MATERIALS AND METHODS: Of the total 424 patients, 207 received S-1 (S-1 arm) while the remaining 217 were not. We compared MH with non-major hepatectomy (NMH) for BTC. RESULTS: In the S-1 arm, 42 had undergone MH, and 165 had undergone NMH. MH had similar pretreatment features to NMH, including the proportion of biliary reconstruction, to NMH, except for a lower platelet count (17.7 vs. 23.4 × 104/mm3, p < 0.0001) and lower serum albumin level (3.5 vs. 3.8 g/dL, p < 0.0001). The treatment completion proportion tended to be lower for MH than for NMH (59.5 % vs. 75.8 %; risk ratio, 0.786 [95 % confidence interval, 0.603-1.023], p = 0.0733), and the median dose intensity was lower as well (88.7 % vs. 99.6 %, p = 0.0358). The major reasons for discontinuation were biliary tract infections and gastrointestinal disorders after MH. The frequency of grade 3-4 biliary tract infection was 19.0 % in MH vs. 4.2 % in NMH. CONCLUSION: The treatment completion proportion and dose intensity were lower in MH than in NMH. Caution should be exercised against biliary tract infections and gastrointestinal disorders during adjuvant S-1 after MH for BTC.