Optimal treatment strategy for patients with pancreatic cancer having positive peritoneal cytology: A nationwide multicenter retrospective cohort study supervised by the Japanese Society of Hepato-Biliary-Pancreatic Surgery.

BACKGROUND: The aim of this study was to determine the optimal treatment for patients with pancreatic cancer (PaCa) having positive peritoneal cytology (PPC). METHODS: This multicenter retrospective study included patients with PPC treated at 78 high-volume centers between January 2012 and December 2020. Prognoses after resection (S-group) and initiation of nonsurgical treatment (N-group) were compared. Prognostic factors for survival in both groups were analyzed. Detailed characteristics of conversion surgery (CS) in the N-group were evaluated. RESULTS: In total, 568 enrolled patients were classified into an S-group (n = 445) or an N-group (n = 123). Median survival times (MSTs) were 19.0 months and 19.3 months, respectively, with no significant difference in prognosis (p = .845). The intervenable prognostic factors for survival were adjuvant treatment in the S-group (p < .001) and CS in the N-group (p < .001). Following CS, the MST was prolonged to 45.6 months, and peritoneal or liver recurrence decreased considerably. CS can be expected if PPC is diagnosed before neoadjuvant treatment and when combination treatment is initiated. CONCLUSION: Surgical resection may not be beneficial for improving survival when PPC is evident. Chemotherapy aiming for CS may be the optimal treatment for such patients.

Is multidisciplinary treatment effective for invasive intraductal papillary mucinous carcinoma?

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 < 0.001). Conclusion: Postoperative AT might benefit selected patients with invasive IPMC, especially those at high risk of poor survival. NAT might improve the survivability of BR invasive IPMC. Any treatment for recurrence after surgery for invasive IPMC might improve survival.

Toll-Like Receptor 7-Expressed Macrophages Are Involved in the Pathogenesis of Esophageal Achalasia and Esophagogastric Junction Outflow Obstruction.

INTRODUCTION: Esophageal achalasia is a typical esophageal motility disorder (EMD). Although viral infections have been hypothesized to play a role in the pathogenesis of esophageal achalasia, its etiology remains unclear. This study used esophageal muscle layer specimens collected during per-oral endoscopic myotomy (POEM) procedures to investigate the association between esophageal achalasia and esophagogastric junction outflow obstruction (EGJOO) and pattern recognition receptors. METHODS: Patients with esophageal achalasia and EGJOO who underwent POEM were allocated to the EMD group. Biopsies of the inner circular muscle were conducted during the POEM procedure. The control group comprised individuals diagnosed with esophageal squamous cell carcinoma who underwent surgical resection. Expression of pattern recognition receptors, including Toll-like receptor (TLR) 7, was examined by polymerase chain reaction. Immunohistochemical staining was performed to determine TLR7 expression sites in the esophageal muscle layer, and the relationship between TLR7 mRNA expression and clinical score was investigated. RESULTS: Our analysis revealed a notable upregulation of TLR7 mRNA levels within the muscle layer of esophageal achalasia and EGJOO, in contrast to those of control specimens. In contrast, the correlation between TLR7 and clinical score was not significant. Immunohistochemical staining revealed increased numbers of TLR7-expressing macrophages between the muscle layers. CONCLUSIONS: TLR7-expressing macrophages are involved in the innate immune response underlying esophageal achalasia and EGJOO. This result will lead to the elucidation of new pathogenetic mechanisms and the development of novel therapeutic targets.

[A Case of Appendiceal Mucinous Carcinoma with Bladder Invasion Developed from Abscess-Forming Appendicitis, Which Was Curatively Resected after Chemotherapy].

The patient was a 35-year-old man who saw his first doctor with the chief complaint of painful urination. A contrast- enhanced CT scan of the abdomen revealed a diagnosis of abscess-forming appendicitis with inflammatory spread to the bladder, and conservative treatment was decided. Since antibiotic treatment failed to reduce the size of the abscess, he underwent surgery. The bladder wall was highly inflamed, only appendectomy was performed. Pathology revealed appendiceal mucinous carcinoma invading the bladder, so he was referred to our department. Because a total cystectomy was required for curative resection and there was concern about seeding associated with the initial surgery, he was judged to be unresectable, and received chemotherapy. After 6 courses of CAPOX+bevacizumab therapy, he was able to have a bladder- sparing curative resection because of the absence of distant metastasis and shrinkage of the tumor. He remains stable without recurrence 6 months after surgery. We herein report, with some discussion of the literature, this case of bladder-invading appendiceal mucinous carcinoma arising from abscess-forming appendicitis, for which a curative resection was possible after chemotherapy.

Moderate cryptoxanthin intake correlates with maintenance of a proper PINT index in a general Japanese population.

INTRODUCTION: Small fibre neuropathy (SFN) is an early manifestation of diabetic polyneuropathy. Although oxidative stress, inflammation and change of intestinal bacterial population are assumed to be their pathogenesis, the effects of dietary nutrition have not been evaluated. The relationship between dietary nutrition intake and pain sensation was evaluated in the Japanese population. METHODS: We conducted the Iwaki project, a population-based study recruiting 1,028 individuals, in 2018. The relationships between the pain threshold from intraepidermal electrical stimulation (PINT) and the amount of dietary nutrition evaluated by a brief-type self-administered diet history questionnaire were examined. The odds ratio was further explored after categorizing subjects based on low (< 63.7 µg/day), intermediate (63.7-159.2 µg/day), and high cryptoxanthin levels (> 159.2 µg/day). RESULTS: Univariate linear regression analyses showed significant correlations between PINT and cryptoxanthin intake even after adjustments for other nutritional intakes (ß = 0.107, p < 0.01). Multivariate logistic regression analysis revealed low and high cryptoxanthin intake as significant risk factors for abnormal PINT (≥ 0.20 mA). Multivariate linear regression analyses showed significant correlations between PINT and cryptoxanthin intake levels after adjustment for other clinically PINT-related factors (ß = 0.09, p < 0.01). CONCLUSIONS: Adequate intake of cryptoxanthin is recommended to maintain the pain threshold in the Japanese population.

Enhanced cancer cell proliferation and aggressive phenotype counterbalance in breast cancer with high BRCA1 gene expression.

PURPOSE: While comprehensive research exists on the mutation of the DNA repair gene BRCA1, limited information is available regarding the clinical significance of BRCA1 gene expression. Given that cancer cell proliferation is aggrevated by DNA repair, we hypothesized that high BRCA1 gene expression breast cancer (BC) might be linked with aggressive tumor biology and poor clinical outcomes. METHODS: The cohorts: The Cancer Genome Atlas (TCGA, n = 1069), METABRIC (n = 1903), and SCAN-B (n = 3273) were utilzed to obtain data of 6245 BC patients. RESULTS: BC patients without BRCA1 mutation exhibited higher BRCA1 expression, which was associated with DNA repair functionality. However, no such correlation was observed with BRCA2 expression. The association of high BRCA1 expression with cancer cell proliferation was evidenced by significant enrichment of cell proliferation-related gene sets, higher histological grade, and proliferation score. Furthermore, increased levels of homologous recombination deficiency, intratumoral heterogeneity, and altered fractions were associated with high BRCA1 expression. Moreover, BC with high BRCA1 expression exhibited reduced infiltration of dendritic cells and CD8 T-cells, while showing increased infiltration of Th1 cells. Surprisingly, BRCA1 expression was not associated with the survival of BC irrespective of the subtypes. Conversely, BC with low BRCA1 expression enriched cancer aggravating pathway gene sets, such as Cancer Stem Cell-related signaling (NOTCH and HEDGEHOG), Angiogenesis, Epithelial-Mesenchymal Transition, Inflammatory Response, and TGF-beta signaling. CONCLUSION: Despite being linked to heightened proliferation of cancer cells and unassertive phenotype, BRCA1 expression did not show any association with survival in BC.

Three Molecular Developmental Pathways of Remnant Pancreatic Cancer after Resection: A Nationwide Project Study of Japan Pancreas Society.

OBJECTIVE: This study aimed to clarify the molecular mechanism of remnant pancreatic cancer (PC) development after primary PC resection. SUMMARY BACKGROUND DATA: Molecular mechanisms of the development of remnant PCs following primary PC resection are largely unknown. METHODS: Forty-three patients undergoing remnant PC resection after primary PC resection between 2001 and 2017 at 26 institutes were retrospectively analyzed. Clinicopathological features and molecular alterations detected by targeted amplicon sequencing of 36 PC-associated genes were evaluated. RESULTS: These patients showed significantly lower body mass indices and higher hemoglobin A1c values at remnant PC resection than at primary PC resection. A comparison of the molecular features between primary and remnant PCs indicated that remnant PCs were likely to develop via three different molecular pathways: successional, showing identical and accumulated alterations (n=14); phylogenic, showing identical and distinct alterations (n=26); and distinct, showing independent distinctive alterations (n=3). The similarity of gene alterations was associated with time to the remnant PC development (r=－0.384, P=0.0173). Phylogenic pathways were significantly associated with the intraductal spread of carcinoma (P=0.007). Patient survival did not differ significantly depending on these molecular pathways. CONCLUSION: Molecular profiling uncovered three pathways for the development of remnant PCs, namely, successional, phylogenic, and distinct pathways. The vast majority of remnant PCs are likely to be molecularly associated with primary PCs either in the successional or phylogenic way. This information could impact the design of a strategy for monitoring and treating remnant PCs.

Novel insight into nicotinamide adenine dinucleotide and related metabolites in cancer patients undergoing surgery.

Nicotinamide adenine dinucleotide (NAD +) plays a pivotal role in numerous cellular functions. Reduced NAD + levels are postulated to be associated with cancer. As interest in understanding NAD + dynamics in cancer patients with therapeutic applications in mind grows, there remains a shortage of comprehensive data. This study delves into NAD + dynamics in patients undergoing surgery for different digestive system cancers. This prospective study enrolled 99 patients with eight different cancers. Fasting blood samples were obtained during the perioperative period. The concentrations of NAD + , nicotinamide mononucleotide (NMN), and nicotinamide riboside were analyzed using tandem mass spectrometry. After erythrocyte volume adjustment, NAD + remained relatively stable after surgery. Meanwhile, NMN decreased the day after surgery and displayed a recovery trend. Interestingly, liver and pancreatic cancer patients exhibited poor postoperative NMN recovery, suggesting a potential cancer type-specific influence on NAD + metabolism. This study illuminated the behavior of NAD + in surgically treated cancer patients. We identified which cancer types have particularly low levels and at what point depletion occurs during the perioperative period. These insights suggest the need for personalized NAD + supplementation strategies, calibrated to individual patient needs and treatment timelines. Clinical trial registration jRCT1020210066.

Clinical practice guidelines for telesurgery 2022 : Committee for the promotion of remote surgery implementation, Japan Surgical Society.

Telesurgery is expected to improve medical access in areas with limited resources, facilitate the rapid dissemination of new surgical procedures, and advance surgical education. While previously hindered by communication delays and costs, recent advancements in information technology and the emergence of new surgical robots have created an environment conducive to societal implementation. In Japan, the legal framework established in 2019 allows for remote surgical support under the supervision of an actual surgeon. The Japan Surgical Society led a collaborative effort, involving various stakeholders, to conduct social verification experiments using telesurgery, resulting in the development of a Japanese version of the "Telesurgery Guidelines" in June 2022. These guidelines outline requirements for medical teams, communication environments, robotic systems, and security measures for communication lines, as well as responsibility allocation, cost burden, and the handling of adverse events during telesurgery. In addition, they address telementoring and full telesurgery. The guidelines are expected to be revised as needed, based on the utilization of telesurgery, advancements in surgical robots, and improvements in information technology.

The role of lidocaine in cancer progression and patient survival.

Since its development in 1943, lidocaine has been one of the most commonly used local anesthesia agents for surgical procedures. Lidocaine alters neuronal signal transmission by prolonging the inactivation of fast voltage-gated sodium channels in the cell membrane of neurons, which are responsible for action potential propagation. Recently, it has attracted attention due to emerging evidence suggesting its potential antitumor properties, particularly in the in vitro setting. Further, local administration of lidocaine around the tumor immediately prior to surgical removal has been shown to improve overall survival in breast cancer patients. However, the exact mechanisms driving these antitumor effects remain largely unclear. In this article, we will review the existing literature on the mechanism of lidocaine as a local anesthetic, its effects on the cancer cells and the tumor microenvironment, involved pathways, and cancer progression. Additionally, we will explore recent reports highlighting its impact on clinical outcomes in cancer patients. Taken together, there remains significant ambiguity surrounding lidocaine's functions and roles in cancer biology, particularly in perioperative setting.

Postoperative long­term outcomes of acute normovolemic hemodilution in pancreatic cancer: A propensity score matching analysis.

Acute normovolemic hemodilution (ANH) is a useful intraoperative blood conservation technique. However, the impact on long-term outcomes in pancreatic ductal adenocarcinoma (PDAC) remains unclear. The present study investigated the impact of ANH on long-term outcomes in patients with PDAC undergoing radical surgery. Data from 155 resectable PDAC cases were collected. Patients were categorized according to whether or not they had received intraoperative allogeneic blood transfusion (ABT) or ANH. Postoperative complications, recurrence-free survival (RFS) and disease-specific survival (DSS), before and after propensity score matching (PSM), were compared among patients who did and did not receive ANH. A total of 44 patients (28.4%) were included in the ANH group and 30 patients (19.4%) were included in the ABT group; 81 (52.3%) patients, comprising the standard management (STD) group, received neither ANH nor ABT. The ABT group had the worst prognosis among them. Before PSM, ANH was significantly associated with decreased RFS (P=0.043) and DSS (P=0.029) compared with the STD group before applying Bonferroni correction; however, no significant difference was observed after applying Bonferroni correction. Cox regression analysis identified ANH as an independent prognostic factor for RFS [relative risk (RR), 1.696; P=0.019] and DSS (RR, 1.876; P=0.009). After PSM, the ANH group exhibited less favorable RFS [median survival time (MST), 12.1 vs. 18.1 months; P=0.097] and DSS (MST, 32.1 vs. 50.5 months; P=0.097) compared with the STD group; however, these differences were not statistically significant. In conclusion, while ANH was not as harmful as ABT, it exhibited potentially more negative effects on long-term postoperative outcomes in PDAC than STD.

Tryptophan metabolism and small fibre neuropathy: a correlation study.

Small nerve fibres located in the epidermis sense pain. Dysfunction of these fibres decreases the pain threshold known as small fibre neuropathy. Diabetes mellitus is accompanied by metabolic changes other than glucose, synergistically eliciting small fibre neuropathy. These findings suggest that various metabolic changes may be involved in small fibre neuropathy. Herein, we explored the correlation between pain sensation and changes in plasma metabolites in healthy Japanese subjects. The pain threshold evaluated from the intraepidermal electrical stimulation was used to quantify pain sensation in a total of 1021 individuals in the 2017 Iwaki Health Promotion Project. Participants with a pain threshold evaluated from the intraepidermal electrical stimulation index <0.20 mA were categorized into the pain threshold evaluated from the intraepidermal electrical stimulation index-low group (n = 751); otherwise, they were categorized into the pain threshold evaluated from the intraepidermal electrical stimulation index-high group (n = 270). Metabolome analysis of plasma was conducted using capillary electrophoresis time-of-flight mass spectrometry. The metabolite set enrichment analysis revealed that the metabolism of tryptophan was significantly correlated with the pain threshold evaluated from the intraepidermal electrical stimulation index in all participants (P < 0.05). The normalized level of tryptophan was significantly decreased in participants with a high pain threshold evaluated from the intraepidermal electrical stimulation index. In addition to univariate linear regression analyses, the correlation between tryptophan concentration and the pain threshold evaluated from the intraepidermal electrical stimulation index remained significant after adjustment for multiple factors (ß = -0.07615, P < 0.05). These findings indicate that specific metabolic changes are involved in the deterioration of pain thresholds. Here, we show that abnormal tryptophan metabolism is significantly correlated with an elevated pain threshold evaluated from the intraepidermal electrical stimulation index in the Japanese population. This correlation provides insight into the pathology and clinical application of small fibre neuropathy.

Immunohistochemical and molecular profiles of heterogeneous components of metaplastic breast cancer: a squamous cell carcinomatous component was distinct from a spindle cell carcinomatous component.

Metaplastic breast carcinoma (MBC), a category of breast cancer, includes different histological types, which are occasionally mixed and heterogeneous. Considering the heterogeneity of cancer cells in a tumour mass has become highly significant, not only from a biological aspect but also for clinical management of recurrence. This study aimed to analyse the immunohistochemical and molecular profiles of each MBC component of a tumour mass. Twenty-five MBC tumours were histologically evaluated, and the most frequent MBC component (c) was squamous cell carcinoma (SCC), followed by spindle cell carcinoma (SpCC). A total of 69 components of MBC and non-MBC in formalin-fixed paraffin-embedded sections were examined for 7 markers by immunohistochemistry. SCC(c) were significantly PTEN negative and CK14 positive, and SpCC(c) were significantly E-cadherin negative and vimentin positive. Multivariate analyses revealed that immunohistochemical profiles of normal/intraductal (IC)(c), no special type (NST)(c), and MBC(c) differed; moreover, SCC(c) and SpCC(c) were distinctly grouped. PTEN gene mutation was detected only in SCC(c) (2/7), but not in SpCC(c). Next-generation sequence analyses for 2 cases with tumours containing SCC(c) demonstrated that PTEN gene mutation increased progressively from IC(c) to NST(c) to SCC(c). In conclusion, the immunohistochemical and molecular profiles of the SCC(c) of MBC are distinct from those of the SpCC(c).

Revealing the role of early peripancreatic bacterial contamination and Enterococcus faecalis in pancreatic fistula development after pancreaticoduodenectomy: Implications for useful antibiotic prophylaxis-An observational cohort study.

BACKGROUND: Peripancreatic bacterial contamination (PBC) is a critical factor contributing to the development of clinically relevant postoperative pancreatic fistula (CR-POPF) following pancreaticoduodenectomy (PD). Controlling pathogenic bacteria is essential in preventing CR-POPF; however, the precise relationship between specific bacteria and CR-POPF remains unclear. This study aimed to investigate the relationship between PBC and CR-POPF after PD, with a focus on identifying potentially causative bacteria. METHODS: This prospective observational study enrolled 370 patients who underwent PD. Microbial cultures were routinely collected from peripancreatic drain fluid on postoperative days (PODs) 1, 3, and 6. Predictive factors for CR-POPF and the bacteria involved in PBC were investigated. RESULTS: CR-POPF occurred in 86 (23.2%) patients. In multivariate analysis, PBC on POD1 (Odds ratio [OR] = 3.59; P = 0.005) was one of the main independent predictive factors for CR-POPF, while prophylactic use of antibiotics other than piperacillin/tazobactam independently influenced PBC on POD1 (OR = 2.95; P = 0.010). Notably, Enterococcus spp., particularly Enterococcus faecalis, were significantly isolated from PBC in patients with CR-POPF compared to those without CR-POPF on PODs 1 and 3 (P < 0.001), and they displayed high resistance to all cephalosporins. CONCLUSIONS: Early PBC plays a pivotal role in the development of CR-POPF following PD. Prophylactic antibiotic administration, specifically targeting Enterococcus faecalis, may effectively mitigate early PBC and subsequently reduce the risk of CR-POPF. This research sheds light on the importance of bacterial control strategies in preventing CR-POPF after PD.

Follicular dendritic cell sarcoma arising from the lymph node of the pancreatic head: a case report with literature review.

A 72-year-old man was referred to our hospital for the examination of a pancreatic head mass. Abdominal computed tomography revealed a contrasted 8-cm-diameter tumor extending from the dorsal pancreatic head to the porta hepatis. The preoperative diagnosis was challenging due to the absence of specific imaging findings and the inability to perform a biopsy. Positron emission tomography/computed tomography and diffusion-weighted imaging suggested a malignant tumor originating from the organs surrounding the pancreatic head. Subtotal stomach-preserving pancreaticoduodenectomy with regional lymph node dissection was performed, as dissection from the pancreatic head proved unfeasible. Pathological examination identified the tumor as an enlarged lymph node consisting of pleomorphic large cells forming clusters, positive for follicular dendritic cell markers cluster of differentiation (CD) 21 and CD23. No evidence of tumor capsule infiltration, other organ infiltration, or metastasis to other lymph nodes was observed. The final diagnosis was nodal follicular dendritic cell sarcoma (FDCS) originating from the pancreatic head lymph nodes. No recurrence occurred at 3 years postoperatively with no postoperative treatment. Intraperitoneal nodal FDCS is extremely rare, and occasionally, it can lead to postoperative recurrence and progression. It is crucial to differentiate neoplastic lymph node enlargement around the pancreatic head from nodal FDCS.

[A Case of Breast Cancer That Developed Pulmonary Tumor Thrombotic Microangiopathy during Adjuvant Chemotherapy].

A 68-year-old woman underwent neoadjuvant chemotherapy for left breast cancer(triple negative type), cT2N3cM0, cStage ⅢC, and Bt+Ax(Ⅲ). The pathological diagnosis was ypT1aN2aM0, ypStage ⅢA, ER-, PgR-, HER2 score 1+, Ki- 67 25%. Adjuvant radiotherapy(50 Gy/25 Fr)was then administered, followed by capecitabine as adjuvant chemotherapy. Dyspnea occurred during administration of capecitabine, and computed tomography(CT)and blood test results suggested drug-induced interstitial pneumonia and disseminated intravascular coagulation(DIC). The patient was admitted, and steroid pulse therapy, anticoagulant therapy, and antibiotics were administered; however, the treatment was ineffective, and she died 3 days after admission. An autopsy provided a final diagnosis of pulmonary tumor thrombotic microangiopathy(PTTM). There is no established treatment for PTTM, and the prognosis is poor even with anticoagulant therapy and chemotherapy. The definitive diagnosis of PTTM is based on pathological findings; however, during respiratory failure, invasive tests such as lung biopsy are not recommended. Therefore, if a significantly worsening respiratory disorder develops, as in this case, chemotherapy should be considered for suspected PTTM.

Gastric cancer with enhanced myogenesis is associated with less cell proliferation, enriched epithelial-to-mesenchymal transition and angiogenesis, and poor clinical outcomes.

Gastric cancer (GC) remains a lethal disease, with over 26,000 new cases and more than 11,000 deaths annually in the US. Thus, a deeper understanding of GC biology is critical to improve survival. Myogenesis is the formation of muscle fibers, which is a mesodermal tissue. In cancer, epithelial-to-mesenchymal transition (EMT) is a known phenomenon that promotes metastasis and poor survival. Given that myogenesis produces mesenchymal cells, we hypothesized that GC with increased myogenesis is linked to aggressive tumor behaviors and less favorable outcomes. In this study, three GC patient cohorts: TCGA (n=375), GSE26253 (n=432), and GSE84437 (n=482), were analyzed. The "MYOGENESIS" set in the Hallmark collection which comprises 200 myogenesis-related genes was analyzed to perform gene set variation analysis to create a score to quantify the myogenesis activity. Our results showed that T category of AJCC cancer staging that reflects the tumor invasion to stomach wall consistently correlated with myogenesis activity in two GC cohorts. High myogenesis GC was associated with lower cell proliferation, evidenced by reduced proliferation scores, decreased Ki67 gene expression, and less enrichment of E2F Targets, G2M checkpoint, MYC Targets V1, and V2 gene sets. High myogenesis tumors showed increased stromal cells (fibroblasts and adipocytes) infiltration within the tumor microenvironment, as well as less silent and non-silent mutation rates and copy number alterations. Higher lymphocyte infiltration, leukocyte fraction, T-cell receptor richness, and B-cell receptor richness were associated with high myogenesis GC. However, infiltration of CD4 cells, T helper type 1 and 2 cells, Natural Killer cells, regulatory T cells, and plasma cells was lower, with increased infiltration of dendritic cells in high myogenesis GC. High myogenesis GC enriched EMT, Hedgehog, TGF-ß, and KRAS gene sets. Furthermore, it was associated with enhanced angiogenesis, evidenced by enrichment of Angiogenesis, Coagulation, and Hypoxia gene sets, and increased infiltration of microvascular and lymphatic endothelial cells and pericytes. High myogenesis GC consistently correlated with worse overall survival in all three cohorts, and worse disease-specific and progression-free survival in the TCGA cohort. Hence, our findings suggest that GC with enhanced myogenesis is associated with decreased cell proliferation, increased EMT and angiogenesis, and worse prognosis.

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.

Neoadjuvant S-1 and oxaliplatin plus bevacizumab therapy for high-risk locally advanced rectal cancer: A prospective multicenter phase II study.

Aim: We report the short/mid-term results of surgery for high-risk locally advanced rectal cancer (LARC) after neoadjuvant chemotherapy (NAC, four courses of S-1 + oxaliplatin+ bevacizumab) without radiotherapy with the primary aim of ypT0-2. Methods: High-risk LARC was defined as cT4b, mesorectal fascia (MRF) ≤1 mm (MRF+), or lateral lymph node metastasis (cLLN+) on high-resolution MRI. The planned 32 cases from April 2018 to December 2021 were all included. Results: There were 10 patients at cT4b (31.2%), 26 MRF+ (81.3%), and 22 cLLN+ (68.8%). Thirteen (40.6%) underwent NAC after a colostomy for stenosis. NAC was completed in 26 (81.2%) cases. Grade 3 or higher adverse events occurred in six (18.7%). One patient developed progressive disease (3.2%). Eleven were ycT0-3MRF-LLN- (34.3%). Curative-intent surgery was performed on 31, with sphincter-preserving surgery in 20, abdominoperineal resection in nine, total pelvic exenteration in two, and lateral lymph node dissection in 24. Two had R1/2 resection (6.4%). A Grade 3 or higher postoperative complication rate occurred in 3.2%. Pathological complete response and ypT0-2 rates were 12.9% and 45.1%. Three-year disease-free survival rates (3yDFS) for ypT0-2 and ypT ≥3 were 81.2%, 46.6% (p = 0.061), and 3-year local recurrence rates (3yLR) were 0%, 48.8% (p = 0.015). 3yDFS for ycT0-3MRF-LLN- and ycT4/MRF+/LLN+ were 87.5%, 48.0% (p = 0.031) and 3yLR were 0%, 42.8% (p = 0.045). Conclusion: NAC yielded a clinically significant effect in about half of high-risk LARC patients. If NAC alone is ineffective, radiotherapy should be added, even if extended surgery is intended.

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.