Prognostic significance of preoperative osteosarcopenia on patient' outcomes after emergency surgery for gastrointestinal perforation.

PURPOSE: Sarcopenia is a prognostic predictor in emergency surgery. However, there are no reports on the relationship between osteopenia and in-hospital mortality. This study clarified the effect of preoperative osteosarcopenia on patients with gastrointestinal perforation after emergency surgery. METHODS: We included 216 patients with gastrointestinal perforations who underwent emergency surgery between January 2013 and December 2022. Osteopenia was evaluated by measuring the pixel density in the mid-vertebral core of the 11th thoracic vertebra. Sarcopenia was evaluated by measuring the area of the psoas muscle at the level of the third lumbar vertebra. Osteosarcopenia is defined as the combination of osteopenia and sarcopenia. RESULTS: Osteosarcomas were identified in 42 patients. Among patients with osteosarcopenia, older and female patients and those with an American Society of Anesthesiologists Physical Status of ≥ 3 were significantly more common, and the body mass index, hemoglobin value, and albumin level were significantly lower in these patients than in patients without osteosarcopenia. Furthermore, the osteosarcopenia group presented with more postoperative complications than patients without osteosarcopenia (P < 0.01). In the multivariate analysis, age ≥ 74 years old (P = 0.04) and osteosarcopenia (P = 0.04) were independent and significant predictors of in-hospital mortality. CONCLUSION: Preoperative osteosarcopenia is a risk factor of in-hospital mortality in patients with gastrointestinal perforation after emergency surgery.

The real-world data of immune-checkpoint inhibitor combination therapy for unresectable or metastatic esophageal cancer: a multi-institutional cohort study.

BACKGROUND: The real-world efficacy, feasibility, and prognostic factors of immune-checkpoint inhibitor combination therapy for unresectable or metastatic esophageal cancer are not fully established. METHODS: This multi-institutional retrospective cohort study evaluated 71 consecutive patients treated with immune-checkpoint inhibitor combination therapy for esophageal cancer between March 2021 and December 2022. We assessed tumor response, safety, and long-term survival. RESULTS: In patients with measurable lesions, the response rate was 58%, and the disease control rate for all enrolled patients was 80%. Five patients (7.0%) underwent successful conversion surgery. Grade 3 or higher immune-related adverse events occurred in 13% of patients, and one patient (1.4%) died due to cholangitis. Median progression-free survival was 9.7 (95% confidence interval: 6.5-not reached). C-reactive protein levels and performance status were identified as significant predictors of progression-free survival through Cox proportional hazards analysis. CONCLUSIONS: Immune-checkpoint inhibitor combination therapy for esophageal cancer demonstrated comparable tumor response, safety, and long-term survival to previous randomized clinical trials. Patients with good performance status and low C-reactive protein levels may be suitable candidates for this treatment.

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

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

Prognostic significance of the preoperative C-reactive protein-albumin-lymphocyte (CALLY) index on outcomes after gastrectomy for gastric cancer.

PURPOSE: Systemic inflammatory response markers are reported to be prognostic for patients with cancer. The C-reactive protein (CRP)-albumin-lymphocyte (CALLY) index has been established as an immuno-nutritional scoring system. The aim of this study was to clarify the impact of the preoperative CALLY index on the outcome of patients undergoing gastrectomy for gastric cancer. METHODS: We analyzed the data of 826 patients who underwent gastrectomy for stage I, II, or III gastric cancer between 2010 and 2017. The CALLY index was defined as (albumin × lymphocyte)/(CRP × 104). RESULTS: The cut-off of the CALLY index was 2. The 147 patients with a preoperative CALLY index < 2 had significantly worse overall survival (OS) and relapse-free survival (RFS) than those with a CALLY index ≥ 2 (P < 0.01, P < 0.01, respectively). Multivariate analysis identified that a CALLY index < 2 (P = 0.02), intraoperative blood loss (P < 0.01), and stage II or III disease (P < 0.01) were independent and significant predictors of worse RFS. A CALLY index < 2 (P = 0.01), intraoperative blood loss (P < 0.01), postoperative complications (P = 0.02), and stage II or III disease (P < 0.01) were independent and significant predictors of worse OS. CONCLUSION: The preoperative CALLY index was independently associated with a poor prognosis for patients after gastrectomy for gastric cancer.

Laparoscopic sleeve gastrectomy combined with Toupet fundoplication (T-sleeve): A short report of a Japanese obesity patient with gastroesophageal reflux disease.

Laparoscopic sleeve gastrectomy (LSG) is the most frequently performed procedure in bariatric-metabolic surgery (BMS) worldwide, accounting for approximately 90% of BMS procedures in Japan. While numerous studies have reported on the safety and efficacy of LSG, gastroesophageal reflux disease (GERD) remains a major postoperative complication. Although Roux-en-Y gastric bypass (RYGB) is preferred for severe obesity with GERD, it is less suitable for Japanese patients who have a higher risk of gastric cancer due to the remnant stomach which is difficult to observe with esophago-gastro-duodenoscopy. To address de novo and exacerbation GERD after LSG, we conducted LSG with Toupet fundoplication (T-sleeve) for Japanese patients with severe obesity. In our first T-sleeve case, the patient demonstrated sufficient weight loss and improved GERD following surgery. Hence, we suggest that T-sleeve is a feasible option for Japanese patients with obesity and concurrent GERD.

Role of modified Glasgow Prognostic Score in patients with achalasia who underwent laparoscopic Heller-myotomy with Dor-fundoplication.

BACKGROUND: Systemic inflammatory response is significant prognostic indicator in patients with various diseases. The relationship between prognostic scoring systems based on the modified Glasgow Prognostic Score (mGPS) and achalasia in patients treated with laparoscopic Heller­myotomy with Dor­fundoplication (LHD) remains uninvestigated. This study aimed to examine the role of mGPS in patients with achalasia. METHODS: 457 patients with achalasia who underwent LHD as the primary surgery between September 2005 and December 2020 were included. We divided patients into the mGPS 0 and mGPS 1 or 2 groups and compared the patients' background, pathophysiology, symptoms, surgical outcomes, and postoperative course. RESULTS: mGPS was 0 in 379 patients and 1 or 2 in 78 patients. Preoperative vomiting and pneumonia were more common in patients with mGPS of 1 or 2. There were no differences in surgical outcomes. Postoperative upper gastrointestinal endoscopy revealed that severe esophagitis was more frequently observed in patients with mGPS of 1 or 2 (P < 0.01). The clinical success was 91% and 99% in the mGPS 0 and mGPS 1 or 2 groups, respectively (P < 0.01). CONCLUSIONS: Although severe reflux esophagitis was more common in patients with achalasia with a high mGPS, good clinical success was obtained regardless of the preoperative mGPS.

Evaluation of the Usefulness of Contrast-Enhanced Computed Tomography for the Early Detection of Anastomotic Leakage After Esophagectomy.

OBJECTIVE: Anastomotic leakage is one of the most severe complications after esophagectomy. However, a diagnostic gold standard for anastomotic leakage has not been established yet. This retrospective cohort study aimed to evaluate the potential use of routine postoperative contrast-enhanced computed tomography findings as an early predictor of anastomotic leakage in patients who underwent esophagectomy for esophageal cancer. METHODS: This study included 75 patients who underwent Mckeown esophagectomy, of whom 22 developed anastomotic leakage after surgery. The computed tomography findings for this patient cohort were categorized into 3 grades based on mural enhancement patterns observed at the anastomotic site. Both semiquantitative and quantitative analyses were performed, and the interobserver agreement between the 2 experienced radiologists was assessed. RESULTS: It was found that poor enhancement in both the early and portal venous phases (grade 2) had a robust association with the occurrence of anastomotic leakage. The computed tomography enhancement ratio that is used to estimate wall degeneration and ischemia was significantly higher in patients with anastomotic leakage. CONCLUSIONS: Routine postoperative contrast-enhanced computed tomography could be beneficial for the early detection of anastomotic leakage, even in asymptomatic patients, after esophagectomy.

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

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

A novel combined C-reactive protein-albumin ratio and modified albumin-bilirubin score can predict long-term outcomes in patients with hepatocellular carcinoma after hepatic resection.

Background: Systemic inflammatory response represented by C-reactive protein and albumin ratio (CAR) and modified albumin-bilirubin (mALBI) grade both have been associated with long-term outcome in patients with hepatocellular carcinoma (HCC). In this study, we investigated the prognostic utility of combined score of CAR and mALBI score to predict the prognosis of HCC patients after hepatic resection. Methods: This study included 214 patients who had undergone primary hepatic resection for HCC between 2008 and 2018. Systemic inflammatory response and mALBI were evaluated preoperatively and patients were classified into three groups based on the combination of CAR and mALBI score: low CAR and low mALBI grade (score 0), either high CAR or high mALBI grade (score 1), and both high CAR and high mALBI grade ≥2b (score 2). Multivariate Cox proportional hazard models were conducted to assess disease-free and overall survival. Results: In multivariate analysis, sex (p < 0.01), HBsAg positivity (p < 0.01), serum AFP level ≥20 ng/mL (p < 0.01), microvascular invasion (p = 0.02), multiple tumors (p < 0.01), type of resection (p < 0.01), and CAR-mALBI score ≥2 (HR 2.19, 95% CI 1.39-3.44, p < 0.01) were independent prognostic factors of disease-free survival, while sex (p = 0.01), HBsAg positivity (p < 0.01), poor tumor differentiation (p = 0.03), multiple tumors (p < 0.01), CAR-mALBI score ≥2 (HR 2.70, 95% CI 1.51-4.83, p < 0.01) were independent prognostic factors of overall survival. Conclusions: CAR-mALBI score is associated with disease-free and overall survival in patients with HCC after hepatic resection, suggesting the importance of evaluating both hepatic functional reserve and host-inflammatory state in the risk assessment of HCC patients.

Decoupling power and type I error rate considerations when incorporating historical control data using a test-then-pool approach.

To accelerate a randomized controlled trial, historical control data may be used after ensuring little heterogeneity between the historical and current trials. The test-then-pool approach is a simple frequentist borrowing method that assesses the similarity between historical and current control data using a two-sided test. A limitation of the conventional test-then-pool method is the inability to control the type I error rate and power for the primary hypothesis separately and flexibly for heterogeneity between trials. This is because the two-sided test focuses on the absolute value of the mean difference between the historical and current controls. In this paper, we propose a new test-then-pool method that splits the two-sided hypothesis of the conventional method into two one-sided hypotheses. Testing each one-sided hypothesis with different significance levels allows for the separate control of the type I error rate and power for heterogeneity between trials. We also propose a significance-level selection approach based on the maximum type I error rate and the minimum power. The proposed method prevented a decrease in power even when there was heterogeneity between trials while controlling type I error at a maximum tolerable type I error rate larger than the targeted type I error rate. The application of depression trial data and hypothetical trial data further supported the usefulness of the proposed method.

RNA Foci in Two bi-Allelic RFC1 Expansion Carriers.

Cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) is a late-onset, autosomal recessive neurodegenerative disorder caused by biallelic AAGGG/ACAGG repeat expansion (AAGGG-exp/ACAGG-exp) in RFC1. The recent identification of patients with CANVAS exhibiting compound heterozygosity for AAGGG-exp and truncating variants supports the loss-of-function of RFC1 in CANVAS patients. We investigated the pathological changes in 2 autopsied patients with CANVAS harboring biallelic ACAGG-exp and AAGGG-exp. RNA fluorescence in situ hybridization of the 2 patients revealed CCTGT- and CCCTT-containing RNA foci, respectively, in neuronal nuclei of tissues with neuronal loss. Our findings suggest that RNA toxicity may be involved in the pathogenesis of CANVAS. ANN NEUROL 2024;95:607-613.

Is it meaningful to add mesh reinforcement to laparoscopic fundoplication for esophageal hiatal hernias in the patients with high risk of hiatal hernia recurrence?

BACKGROUND: While laparoscopic fundoplication is a standard surgical procedure for patients with esophageal hiatal hernias, the postoperative recurrence of esophageal hiatal hernias is a problem for patients with giant hernias, elderly patients, or obese patients. Although there are some reports indicating that reinforcement with mesh is effective, there are differing opinions regarding the use thereof. The aim of this study is to investigate whether mesh reinforcement is effective for laparoscopic fundoplication in patients with esophageal hiatus hernias. METHODS: The subjects included 280 patients who underwent laparoscopic fundoplication as the initial surgery for giant esophageal hiatal hernias, elderly patients aged 75 years or older, and obese patients with a BMI of 28 or higher, who were considered at risk of recurrent hiatal hernias based on the previous reports. Of the subject patients, 91 cases without mesh and 86 cases following the stabilization of mesh use were extracted to compare the postoperative course including the pathology, symptom scores, surgical outcome, and recurrence of esophageal hiatus hernias. RESULTS: The preoperative conditions indicated that the degree of esophageal hiatal hernias was high in the mesh group (p = 0.0001), while the preoperative symptoms indicated that the score of heartburn was high in the non-mesh group (p = 0.0287). Although the surgical results indicated that the mesh group underwent a longer operation time (p < 0.0001) and a higher frequency of intraoperative complications (p = 0.037), the rate of recurrence of esophageal hiatal hernia was significantly low (p = 0.049), with the rate of postoperative reflux esophagitis also tending to be low (p = 0.083). CONCLUSIONS: Mesh reinforcement in laparoscopic fundoplication for esophageal hiatal hernias contributes to preventing the recurrence of esophageal hiatal hernias when it comes to patient options based on these criteria.

Tumor-infiltrating lymphocytes in patients undergoing esophagectomy following neoadjuvant DCF therapy.

BACKGROUND: Accumulating evidence suggests that expression levels of tumor-infiltrating (TI) cells may play a prognostic role in patients with esophageal cancer who have undergone esophagectomy. However, its effect on patients undergoing neoadjuvant docetaxel, cisplatin, and 5-fluorouracil (DCF) therapy followed by esophagectomy for esophageal squamous cell carcinoma (ESCC) remains unclear. Therefore, this study aimed to elucidate the prognostic impact of TI cells in patients who underwent esophagectomy following neoadjuvant DCF therapy. METHODS: Overall, 81 patients with ESCC who underwent curative esophagectomy following neoadjuvant DCF therapy were included. The number of TI CD8+ cells was determined using light microscopy at ×400 in tumor invasive margins. Receiver operative characteristic curve was used to determine the cutoff values for mortality for continuous variables; the patients were separated into high and low TI CD8+ cell groups and their backgrounds and clinical outcomes were compared. RESULTS: Overall and relapse-free survival were significantly worse in the TI CD8+-low group than that in the TI CD8+-high group (p < 0.01). Multivariate analysis revealed that positive ypN (hazard ratio [HR], 3.12; 95% confidence interval [CI], 1.08-9.02) and low TI CD8+ cell levels (HR, 2.77; 95% CI, 1.31-5.85) were independent prognostic factors for overall survival. Furthermore, positive venous invasion (HR, 2.63; 95% CI, 1.29-5.35) and low TI CD8+ cell levels (HR, 2.77; 95% CI, 1.70-5.46) were significant prognostic factors for relapse-free survival. CONCLUSIONS: Low TI CD8+ cell level was a prominent prognostic factor for patients with ESCC undergoing neoadjuvant DCF therapy followed by esophagectomy.

Lateral olfactory tract usher substance (LOTUS), an endogenous Nogo receptor antagonist, ameliorates disease progression in amyotrophic lateral sclerosis model mice.

Nogo-Nogo receptor 1 (NgR1) signaling is significantly implicated in neurodegeneration in amyotrophic lateral sclerosis (ALS). We previously showed that lateral olfactory tract usher substance (LOTUS) is an endogenous antagonist of NgR1 that prevents all myelin-associated inhibitors (MAIs), including Nogo, from binding to NgR1. Here we investigated the role of LOTUS in ALS pathogenesis by analyzing G93A-mutated human superoxide dismutase 1 (SOD1) transgenic (Tg) mice, as an ALS model, as well as newly generated LOTUS-overexpressing SOD1 Tg mice. We examined expression profiles of LOTUS and MAIs and compared motor functions and survival periods in these mice. We also investigated motor neuron survival, glial proliferation in the lumbar spinal cord, and neuromuscular junction (NMJ) morphology. We analyzed downstream molecules of NgR1 signaling such as ROCK2, LIMK1, cofilin, and ataxin-2, and also neurotrophins. In addition, we investigated LOTUS protein levels in the ventral horn of ALS patients. We found significantly decreased LOTUS expression in both SOD1 Tg mice and ALS patients. LOTUS overexpression in SOD1 Tg mice increased lifespan and improved motor function, in association with prevention of motor neuron loss, reduced gliosis, increased NMJ innervation, maintenance of cofilin phosphorylation dynamics, decreased levels of ataxin-2, and increased levels of brain-derived neurotrophic factor (BDNF). Reduced LOTUS expression may enhance neurodegeneration in SOD1 Tg mice and ALS patients by activating NgR1 signaling, and in this study LOTUS overexpression significantly ameliorated ALS pathogenesis. LOTUS might serve as a promising therapeutic target for ALS.

Predicting the daily gastrointestinal doses of stereotactic body radiation therapy for pancreatic cancer based on the shortest distance between the tumor and the gastrointestinal tract using daily computed tomography images.

Objectives: We aimed to investigate whether daily computed tomography (CT) images could predict the daily gastroduodenal, small intestine, and large intestine doses of stereotactic body radiation therapy (SBRT) for pancreatic cancer based on the shortest distance between the gross tumor volume (GTV) and gastrointestinal (GI) tract. Methods: Twelve patients with pancreatic cancer received SBRT of 40 Gy in five fractions. We recalculated the reference clinical SBRT plan (PLANref) using daily CT images and calculated the shortest distance from the GTV to each GI tract. The maximum dose delivered to 0.5 cc (D0.5cc) was evaluated for each planning at-risk volume of the GI tract. Spearman's correlation test was used to determine the association between the daily change in the shortest distance (Δshortest distance) and the ratio of ΔD0.5cc dose to D0.5cc dose in PLANref (ΔD0.5cc/PLANref) for quantitative analysis. Results: The median shortest distance in PLANref was 0 mm in the gastroduodenum (interquartile range, 0-2.7), 16.7 mm in the small intestine (10.0-23.7), and 16.7 mm in the large intestine (8.3-28.1 mm). The D0.5cc of PLANref in the gastroduodenum was >30 Gy in all patients, with 10 (83.3%) having the highest dose. A significant association was found between the Δshortest distance and ΔD0.5cc/ PLANref in the small or large intestine (p < 0.001) but not in the gastroduodenum (p = 0.404). Conclusions: The gastroduodenum had a higher D0.5cc and predicting the daily dose was difficult. Daily dose calculations of the GI tract are recommended for safe SBRT. Advances in knowledge: This study aimed to predict the daily doses in SBRT for pancreatic cancer from the shortest distance between the GTV and the gastrointestinal tract.Daily changes in the shortest distance can predict the daily dose to the small or large intestines, but not to the gastroduodenum.

Anatomical and anastomotic viability indexes for stratifying the risk of anastomotic leakage in esophagectomy with retrosternal reconstruction.

Background: Risk prediction of anastomotic leakage using anatomical and vascular factors has not been well established. This study aimed to assess the anatomical and vascular factors affecting the hemodynamics of the gastric conduit and develop a novel risk stratification system in patients undergoing esophagectomy with retrosternal reconstruction. Methods: This retrospective cohort study analyzed 202 patients with esophageal cancer who underwent subtotal esophagectomy with gastric tube retrosternal reconstruction between January 2008 and December 2020. Risk factors for anastomotic leakage (AL), including the anatomical index (AI) and anastomotic viability index (AVI), were evaluated using a logistic regression model. Results: According to the logistic regression model, the independent risk factors for AL were preoperative body mass index ≥23.6 kg/m2 (odds ratio [OR], 7.97; 95% confidence interval [CI], 2.44-26.00; P < 0.01), AI <1.4 (OR, 23.90; 95% CI, 5.02-114.00; P < 0.01), and AVI <0.62 (OR, 8.02; 95% CI, 2.57-25.00; P < 0.01). The patients were stratified into four AL risk groups using AI and AVI as follows: low-risk group (AI ≥1.4, AVI ≥0.62 [2/99, 2.0%]), intermediate low-risk group (AI ≥1.4, AVI <0.62 [2/29, 6.9%]), intermediate high-risk group (AI <1.4, AVI ≥0.62 [8/53, 15.1%]), and high-risk group (AI <1.4, AVI <0.62 [11/21, 52.4%]). Conclusion: The combination of AI and AVI strongly predicted AL. Additionally, the use of AI and AVI enabled the stratification of the risk of AL in patients who underwent esophagectomy with retrosternal reconstruction.

Preoperative Therapy for Unresectable Locally Advanced Pancreatic Cancer for ≥6 Months Improves Prognosis After Pancreatectomy.

BACKGROUND/AIM: This study aimed to identify the optimal duration of pretreatment for unresectable locally advanced (UR-LA) pancreatic cancer and analyze its effect on the prognosis. PATIENTS AND METHODS: This retrospective study included 39 patients with UR-LA pancreatic cancer after pancreatectomy. The cutoff period of preoperative therapy was determined using a receiver operating characteristic curve. We investigated the relationship between preoperative and intraoperative clinical variables and overall survival (OS) in univariate and multivariate analyses. The relationship between the preoperative therapy duration and the clinicopathological variables was investigated. OS was compared according to preoperative therapy duration and the presence or absence of adjuvant surgery. RESULTS: After pretreatment, 15 patients underwent adjuvant surgery and 24 patients continued on chemotherapy without surgery. The multivariate analysis demonstrated preoperative therapy duration ≥6 months was an independent prognostic factor [hazard ratio (HR)=0.10, p=0.04]. No significant difference in the clinicopathological variables was observed between the two groups according to preoperative therapy duration. The OS was significantly better in patients who underwent adjuvant surgery after preoperative therapy duration ≥6 months than in those after preoperative therapy duration <6 months and in those without adjuvant surgery (5-year OS rates: 80% vs. 0%; p=0.01 and 5-year OS rates: 80% vs. 0%; p=0.004, respectively). The OS was not significantly better in patients with adjuvant surgery after preoperative therapy duration <6 months than in those without adjuvant surgery (2-year OS rates: 45.7% vs. 38.1%; p=0.98). CONCLUSION: Preoperative therapy for UR-LA pancreatic cancer for ≥6 months is necessary to improve prognosis after adjuvant surgery.

Characterization of epitopes of human monoclonal antibodies against cytomegalovirus glycoprotein B for neutralization and antibody-dependent phagocytosis.

As congenital cytomegalovirus (CMV) infections are the leading non-genetic cause of sensorineural hearing loss and significant neurological disabilities in children, the development of CMV vaccines should be given the highest public health priority. Although MF59-adjuvanted glycoprotein B (gB) vaccine (gB/MF59) is safe and immunogenic, its efficacy in terms of protection from natural infection was around 50 % in clinical trials. Although gB/MF59 induced high antibody titers, anti-gB antibodies contributed little to the neutralization of infection. Recent studies have found that non-neutralizing functions, including antibody-dependent phagocytosis of virions and virus-infected cells, are likely to play important roles in pathogenesis and vaccine design. Previously, we isolated human monoclonal antibodies (MAbs) that reacted with the trimeric form of gB ectodomain and found that preferential epitopes for neutralization were present on Domains (Doms) I and II of gB, while there were abundant non-neutralizing antibodies targeting Dom IV. In this study, we analyzed the phagocytosis activities of these MAbs and found the following: 1) MAbs effective for phagocytosis of the virions targeted Doms I and II, 2) the MAbs effective for phagocytosis of the virions and those of virus-infected cells were generally distinct, and 3) the antibody-dependent phagocytosis showed little correlation with neutralizing activities. Taking account of the frequency and levels of neutralization and phagocytosis, incorporation of the epitopes on Doms I and II into developing vaccines is considered desirable for the prevention of viremia.

The comparison of postoperative analgesic requirements between modified thoracoabdominal nerve block through perichondrial approach versus wound infiltration analgesia in patients undergoing gynecological laparoscopic surgery: a retrospective, exploratory study.

INTRODUCTION: Recently, modified thoracoabdominal nerve block through perichondrial approach (M-TAPA) has been introduced as a novel trunk block. To date, studies comparing its clinical advantages with those of existing local anesthetic techniques are scarce. We aimed to compare the analgesic efficacy of M-TAPA to that of wound infiltration analgesia (WIA) in patients who underwent gynecological laparoscopic surgeries. METHODS: We studied medical records from January 2020 to July 2021 at Hokkaido University Hospital. The primary outcome was the number of analgesic requirements in the first 24 h postoperatively. Secondary outcomes were the time until the first analgesic requirement and adverse events regarding local anesthetic techniques. To address confounding, a regression model was used. RESULTS: Data from 90 of 231 patients were analyzed (M-TAPA group, n = 40; WIA group, n = 50). For the primary outcome, means and 95% confidence intervals for each group and between-group differences were as follows: 2.25 (1.74, 2.76), 2.28 (1.81, 2.75), and -0.03 (-0.72, 0.66), respectively. Adjusted mean difference was 0.39 (-0.32, 1.11). There were no significant differences in means between groups, with or without adjustment for covariates (p = 0.93, 0.28). Furthermore, no significant difference was detected in the time until the first analgesic requirement and adverse events related to local anesthesia. CONCLUSION: Our results demonstrate that M-TAPA did not reduce postoperative analgesic requirements compared to WIA. In a future clinical trial, sufficient visceral pain control may be required to evaluate the effectiveness of M-TAPA over WIA in patients undergoing laparoscopic gynecological surgery.