Fabrication of a three-dimensional scaffold-free trachea with horseshoe-shaped hyaline cartilage.

OBJECTIVES: Tracheal regeneration is challenging owing to its unique anatomy and low blood supply. Most tracheal regeneration applications require scaffolds. Herein, we developed bio-three-dimensional-printed scaffold-free artificial tracheas. METHODS: We fabricated bio-three-dimensional-printed artificial tracheas. Their anterior surface comprised hyaline cartilage differentiated from mesenchymal stem cells, and their posterior surface comprised smooth muscle. Human bone marrow-derived mesenchymal stem cells were cultured and differentiated into chondrocytes using fibroblast growth factor-2 and transforming growth factor-beta-3. Initially, horseshoe-shaped spheroids were printed to cover the anterior surface of the artificial trachea, followed by the application of human bronchial smooth muscle cells for the posterior surface. After a 3-week maturing process, the artificial trachea was subjected to histological and immunohistochemical analyses. RESULTS: The anterior surface of the artificial trachea comprised well-differentiated hyaline cartilage from human bone marrow-derived mesenchymal stem cells. Immunohistochemistry revealed that the smooth muscle expressed α-smooth muscle actin and smooth muscle myosin heavy chain 11. CONCLUSIONS: A bio-three-dimensional-printed scaffold-free artificial trachea comprising different tissues at the front and back was successfully fabricated.

Heteromeric amyloid filaments of ANXA11 and TDP-43 in FTLD-TDP Type C.

Neurodegenerative diseases are characterised by the abnormal filamentous assembly of specific proteins in the central nervous system1. Human genetic studies established a causal role for protein assembly in neurodegeneration2. However, the underlying molecular mechanisms remain largely unknown, which is limiting progress in developing clinical tools for these diseases. Recent advances in electron cryo-microscopy (cryo-EM) have enabled the structures of the protein filaments to be determined from patient brains1. All diseases studied to date have been characterised by the self-assembly of proteins in homomeric amyloid filaments, including that of TAR DNA-binding protein 43 (TDP-43) in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) Types A and B3,4. Here, we used cryo-EM to determine filament structures from the brains of individuals with FTLD-TDP Type C, one of the most common forms of sporadic FTLD-TDP. Unexpectedly, the structures revealed that a second protein, annexin A11 (ANXA11), co-assembles with TDP-43 in heteromeric amyloid filaments. The ordered filament fold is formed by TDP-43 residues G282/284-N345 and ANXA11 residues L39-Y74 from their respective low-complexity domains (LCDs). Regions of TDP-43 and ANXA11 previously implicated in protein-protein interactions form an extensive hydrophobic interface at the centre of the filament fold. Immunoblots of the filaments revealed that the majority of ANXA11 exists as a ~22 kDa N-terminal fragment (NTF) lacking the annexin core domain. Immunohistochemistry of brain sections showed the co-localisation of ANXA11 and TDP-43 in inclusions, redefining the histopathology of FTLD-TDP Type C. This work establishes a central role for ANXA11 in FTLD-TDP Type C. The unprecedented formation of heteromeric amyloid filaments in human brain revises our understanding of amyloid assembly and may be of significance for the pathogenesis of neurodegenerative diseases.

The C-reactive protein-albumin-lymphocyte (CALLY) index is a useful predictor of postoperative complications in patients with a colonic stent for obstructive colorectal cancer: a Japanese multicenter study.

PURPOSE: The C-reactive protein-albumin-lymphocyte (CALLY) index is a novel score that offers a good reflection of nutritional status, inflammatory response, and immune system status. The CALLY index is reported to correlate with the prognosis of various carcinomas. The purpose of the present study was to investigate the association between the CALLY index and the short-term prognosis of obstructive colorectal cancer managed with a colonic stent. METHODS: The subjects of this retrospective study were 263 patients who underwent colorectal resection after colonic stenting for obstructive colorectal cancer between 2016 and 2023. Patients were classified into a group with a low CALLY index (CALLY-L group, n = 85) and a group with a high (CALLY-H group, n = 178) CALLY index. RESULTS: The CALLY-L group had greater blood loss (53 mL vs 20 mL, p = 0.002) and higher poor performance status (PS3; 20% vs 10.1%, p = 0.033), open surgery (21.2% vs 7.3%, p = 0.001), distant metastases (41.2% vs 20.8%, p = 0.01), and postoperative complications (30.6% vs. 18.5%, p = 0.039) than the CALLY-H group. Multivariate analysis identified a prolonged operative time (odds ratio 1.983, 95% confidence interval 1.013-3.881; p = 0.045), greater blood loss (odds ratio 2.572, 95% confidence interval 1.291-5.129; p = 0.007) and a low CALLY index (odds ratio 1.961, 95% confidence interval 1.013-3.795; p = 0.045) as independent predictors of complications. CONCLUSION: The CALLY index may be a useful predictor of postoperative complications of obstructive colorectal cancer.

Heteromeric amyloid filaments of ANXA11 and TDP-43 in FTLD-TDP Type C.

Neurodegenerative diseases are characterised by the abnormal filamentous assembly of specific proteins in the central nervous system 1 . Human genetic studies established a causal role for protein assembly in neurodegeneration 2 . However, the underlying molecular mechanisms remain largely unknown, which is limiting progress in developing clinical tools for these diseases. Recent advances in electron cryo-microscopy (cryo-EM) have enabled the structures of the protein filaments to be determined from patient brains 1 . All diseases studied to date have been characterised by the self-assembly of a single intracellular protein in homomeric amyloid filaments, including that of TAR DNA-binding protein 43 (TDP-43) in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) Types A and B 3,4 . Here, we used cryo-EM to determine filament structures from the brains of individuals with FTLD-TDP Type C, one of the most common forms of sporadic FTLD-TDP. Unexpectedly, the structures revealed that a second protein, annexin A11 (ANXA11), co-assembles with TDP-43 in heteromeric amyloid filaments. The ordered filament fold is formed by TDP-43 residues G282/284-N345 and ANXA11 residues L39-L74 from their respective low-complexity domains (LCDs). Regions of TDP-43 and ANXA11 previously implicated in protein-protein interactions form an extensive hydrophobic interface at the centre of the filament fold. Immunoblots of the filaments revealed that the majority of ANXA11 exists as a ∼22 kDa N-terminal fragment (NTF) lacking the annexin core domain. Immunohistochemistry of brain sections confirmed the co-localisation of ANXA11 and TDP-43 in inclusions, redefining the histopathology of FTLD-TDP Type C. This work establishes a central role for ANXA11 in FTLD-TDP Type C. The unprecedented formation of heteromeric amyloid filaments in human brain revises our understanding of amyloid assembly and may be of significance for the pathogenesis of neurodegenerative diseases.

Effect of the lymphocyte-to-monocyte ratio on the prognosis of patients with obstructive colorectal cancer with a colonic stent: a retrospective multicenter study in Japan.

PURPOSE: The prognostic value of the lymphocyte-to-monocyte (LMR) ratio has been reported for various cancers, including colorectal cancer (CRC). The insertion of colonic stents is considered effective for patients with surgically indicated obstructive CRC, but their LMR can vary depending on factors such as inflammation associated with stent dilation and improvement of obstructive colitis. However, the usefulness of the LMR in patients with obstructive CRC and colonic stents and the optimal timing for its measurement remain unclear. We conducted this study to investigate the relationship between the pre-stent LMR and the mid-term prognosis of patients with obstructive CRC and stents as a bridge to surgery (BTS). METHODS: The subjects of this retrospective multicenter study were 175 patients with pathological stage 2 or 3 CRC. Patients were divided into a low pre-stent LMR group (n = 87) and a high pre-stent LMR group (n = 83). RESULTS: Only 3-year relapse-free survival differed significantly between the low and high pre-stent LMR groups (39.9% vs. 63.6%, respectively; p = 0.015). The pre-stent LMR represented a prognostic factor for relapse-free survival in multivariate analyses (hazard ratio 2.052, 95% confidence interval 1.242-3.389; p = 0.005), but not for overall survival. CONCLUSIONS: A low pre-stent LMR is a prognostic factor for postoperative recurrence in patients with obstructive CRC and a colonic stent as a BTS.

Risk factors for pulmonary complications after colorectal cancer surgery: a Japanese multicenter study.

PURPOSE: Pulmonary complications (PC) are a serious condition with a 20% mortality rate. However, few reports have examined risk factors for PC after colorectal surgery. This study investigated the frequency, characteristics, and risk factors for PC after colorectal cancer surgery. METHODS: Between January 2016 and December 2022, we retrospectively reviewed 3979 consecutive patients who underwent colorectal cancer surgery in seven participating hospitals. Patients were divided into patients who experienced PC (PC group, n = 54) and patients who did not (non-PC group, n = 3925). Clinical and pathological features were compared between groups. RESULTS: Fifty-four patients (1.5%) developed PC, of whom 2 patients (3.7%) died due to PC. Age was greater (80 years vs 71 years; p < 0.001), frequency of chronic obstructive pulmonary distress was greater (9.3% vs 3.2%; p = 0.029), performance status was poorer (p < 0.001), the proportion of underweight was higher (42.6% vs 13.4%, p < 0.001), frequency of open surgery was greater (24.1% vs 9.3%; p < 0.001), and blood loss was greater (40 mL vs 22 mL; p < 0.001) in the PC group. Multivariate analysis revealed male sex (odds ratio (OR) 2.165, 95% confidence interval (CI) 1.176-3.986; p = 0.013), greater age (OR 3.180, 95%CI 1.798-5.624; p < 0.001), underweight (OR 3.961, 95%CI 2.210-7.100; p < 0.001), and poorer ASA-PS (OR 3.828, 95%CI 2.144-6.834; p < 0.001) as independent predictors of PC. CONCLUSION: Our study revealed male sex, greater age, underweight, and poorer ASA-PS as factors associated with development of PC, and suggested that pre- and postoperative rehabilitation and pneumonia control measures should be implemented for patients at high risk of PC.

Short- and Long-term Outcomes After Colonic Stent Insertion as a Bridge to Surgery in Elderly Colorectal Cancer Patients.

BACKGROUND/AIM: Colonic stents have been inserted as a bridge to surgery in patients with resectable colorectal cancer, allowing bowel decompression for systemic assessment and better preparation to avoid stoma construction. However, reports of short- and long-term prognoses for elderly patients remain limited. PATIENTS AND METHODS: This retrospective study reviewed 175 consecutive patients who underwent colonic stent insertion for bowel obstruction followed by curative colectomy. Patients were divided into those >80 years old (Old, n=49) and those <80 years old (Young, n=126). After propensity score matching, 41 patients in each group matched. RESULTS: Before matching, performance status was poorer (p<0.001), postoperative complication rate was higher (p=0.009), adjuvant chemotherapy rate was lower (p<0.001), and hospital stay was longer (p<0.001) in the Old group. After matching, adjuvant chemotherapy rate was lower (9.8% vs. 39.0%; p=0.003) and hospital stay was longer (14 vs. 12 days; p=0.029) in the Old group. Five-year relapse-free survival (42.9% vs. 68.8%; p=0.200), overall survival (66.3% vs. 87.7%; p=0.081), and cancer-specific survival (68.2% vs. 87.7%; p=0.129) rates were comparable between groups. CONCLUSION: Colorectal resection after colonic stent insertion is useful for elderly patients, with potential to reduce postoperative complication rates and achieve good long-term results with appropriate case selection.

A case of chylous ascites caused by reflux from the cisterna chyli to the disrupted common iliac lymphatic vessel: fluoroscopic records during intranodal lymphangiography.

A 40-year-old woman underwent laparoscopic common iliac lymphadenectomy for metastasis from rectal cancer. Two weeks after the surgery, she was found to have massive chylous ascites. After failure of conservative treatment, bilateral inguinal intranodal lymphangiography was performed. No definite extravasation was observed while lipiodol injected through the left inguinal node was ascending. When we punctured the right inguinal lymph nodes and started the injection of lipiodol, extravasation of diluted lipiodol was noted at the level of the first sacrum. Careful observation revealed that the ascending lipiodol became diluted in the cisterna chyli, refluxed through the median paraaortic route, leaked from the excised left common iliac lymph vessel, and flowed into the abdominal cavity. Lipiodol used in lymphangiography did not reduce chylous ascites at all. Twenty-seven days after lymphangiography, laparoscopic lymphatic ligation was performed, and the chylous ascites disappeared completely. CT obtained 40 days after surgical repair revealed disappearance of ascites and enlargement of the thoracic duct, which had not been observed on preoperative lymphangiography. Notably, lymphatic reflux from the cisterna chili can occur without obstruction of the thoracic duct and may result in chylous ascites.

Impact of institutional volume on short- and long-term outcomes after laparoscopic colectomy.

INTRODUCTION: The impact of institutional volume on postoperative outcomes after laparoscopic colectomy is still being debated. This study aimed to investigate whether differences in postoperative outcomes of laparoscopic colon resection exist between high- and low-volume centers. METHODS: Data were reviewed for 1360 patients who underwent laparoscopic colectomy for colon cancer between 2016 and 2022. Patients were divided according to whether they were treated at a high-volume center (≥100 colorectal surgeries annually; n = 947) or a low-volume center (<100 colorectal surgeries annually; n = 413). Propensity score matching was applied to balance covariates and minimize selection biases that could affect outcomes. Finally, 406 patients from each group were matched. RESULTS: After matching, patients from high-volume centers showed a higher number of retrieved lymph nodes (19 vs. 17, p < .001) and more frequent involvement of expert surgeons (98.3% vs. 88.4%, p < .001). Postoperative complication rates were similar between groups (p = .488). No significant differences between high- and low-volume centers were seen in relapse-free survival (88.8% each, p = .716) or overall survival (85.7% vs. 82.8%, p = .480). CONCLUSION: The present study suggests that in appropriately educated organizations, relatively safe procedures and good prognosis may be obtained for laparoscopic colectomy cases, regardless of institutional volume.

Intestinal Behçet's and suspected intestinal Behçet's disease: a report of four surgical cases.

BACKGROUND: Intestinal Behçet's disease (BD) is often associated with ulceration that requires surgery, including perforation and abscess formation. However, no consensus has been reached on the optimal extent of resection or treatment strategy. This study reviewed four cases of intestinal or suspected intestinal BD. CASE PRESENTATIONS: In Case 1, a 74-year-old woman diagnosed with BD 2 years earlier was treated with anti-tumor necrosis factor α antibody (Infliximab) and steroids. She had oral and pubic ulcers. After close investigation of abdominal pain, perforation of the gastrointestinal tract was suspected and surgery was performed. Multiple perforating ulcers and abscesses were found in the distal ileum, and the small intestine was resected. Postoperatively, the patient was treated with an increased steroid dose and symptoms have remained stable. Case 2 involved a 69-year-old woman with oral and pubic ulcers, ocular ulcer, and skin lesions. She experienced sudden onset of abdominal pain during treatment for lymphoma. She showed multiple perforating ulcers throughout the ileum and underwent resection of the small intestine and ileostomy. Upper abdominal pain appeared during postoperative treatment for high-output syndrome. The patient underwent omentoplasty after perforation of the upper gastrointestinal tract was diagnosed. Postoperatively, anti-interleukin-1 beta antibodies (canakinumab) was administered to control the disease. Case 3 involved an 81-year-old, previously healthy woman. She presented to her previous physician with complaints of pubic ulcer, hemorrhage and abdominal pain. Colonoscopy showed multiple ulcers throughout the entire colon. Steroid therapy was started, but bleeding proved difficult to control and total proctocolectomy was performed. Histopathology revealed multiple perforating ulcers and BD was diagnosed. Postoperatively, the patient remains under steroid control. Case 4 involved a 43-year-old man with abdominal pain who showed abscess formation in the ileocecal region. After excision of the ileocecal area, multiple ulcers were diagnosed. Two years later, abdominal pain recurred and free air was found in the abdomen on close imaging. Emergency anastomotic resection was performed due to ulceration and perforation of the anastomosis. CONCLUSIONS: Intestinal BD may flare up after surgical treatment and require multiple surgeries. Introducing pharmacotherapy as soon as possible after surgical treatment is important to control the disease.

Prognostic value of lymph node distribution after laparoscopic colectomy with Japanese D3 dissection.

PURPOSE: Positive pathologic lymph nodes in colorectal cancer represent an important prognostic indicator. Whether lymph node distribution or the number of metastatic nodes is more strongly associated with survival prediction remains controversial. METHODS: Among 3449 colorectal cancer surgeries performed at Nagasaki University Hospital and five affiliated institutions from April 2016 to March 2022, we investigated 604 patients who underwent laparoscopic radical resection and were diagnosed with pathological stage III cancer. Patients were divided into two groups according to whether they had central vessel metastasis (LND3 group, n=42) or not (LND1/2 group, n=562). After adjusting for background factors using propensity score matching, the LND3 group included 42 patients and the LND1/2 group included 40 patients. Patient background characteristics and prognosis were compared between these two groups. RESULTS: Before matching, frequencies of right-side colon cancer (64.3% vs 38.1%, p=0.001), multivisceral resection (11.9% vs 4.4%, p=0.039), clinical N2 status (40.5% vs 22.6%, p=0.032), and pathological N2 (73.8% vs 22.6%, p<0.001) were all greater, and the number of lymph nodes retrieved was higher (24 vs 19, p=0.042) in the LND3 group. After matching, no differences in any clinical factors were evident between groups. Five-year RFS (44.8% vs 77.1%, p=0.004) and OS (43.1% vs 83.2%, p<0.001) were worse in the LND3 group. Adjuvant chemotherapy improved RFS (adjuvant chemotherapy (+) vs adjuvant chemotherapy (-): 62.1% vs 27.7%, p=0.047) in the LND3 group. CONCLUSION: LND3-positive patients show poorer prognosis than LND1/2 patients and should be treated with an appropriate perioperative treatment strategy.

Short-term outcomes after laparoscopic colorectal cancer surgery in patients over 90 years old: a Japanese multicenter study.

BACKGROUND: The effect of laparoscopic surgery on short-term outcomes in colorectal cancer patients over 90 years old has remained unclear. METHODS: We reviewed 87 colorectal cancer patients aged over 90 years who underwent surgery between 2016 and 2022. Patients were divided into an open surgery group (n = 22) and a laparoscopic surgery group (n = 65). The aim of this study was to investigate the effect of laparoscopic surgery on postoperative outcome in elderly colorectal cancer patients, as compared to open surgery. RESULTS: Seventy-eight patients (89.7%) had comorbidities. Frequency of advanced T stage was lower with laparoscopic surgery (p = 0.021). Operation time was longer (open surgery 146 min vs. laparoscopic surgery 203 min; p = 0.002) and blood loss was less (105 mL vs. 20 mL, respectively; p < 0.001) with laparoscopic surgery. Length of hospitalization was longer with open surgery (22 days vs. 18 days, respectively; p = 0.007). Frequency of infectious complications was lower with laparoscopic surgery (18.5%) than with open surgery (45.5%; p = 0.021). Multivariate analysis revealed open surgery (p = 0.026; odds ratio, 3.535; 95% confidence interval, 1.159-10.781) as an independent predictor of postoperative infectious complications. CONCLUSIONS: Laparoscopic colorectal resection for patients over 90 years old is a useful procedure that reduces postoperative infectious complications.

A case of pancreaticoduodenal artery bleeding after laparoscopic right colectomy requiring open hemostasis.

BACKGROUND: Pancreatic and duodenal-related complications after right colectomy carry a higher risk of mortality. CASE PRESENTATION: A 64-year-old woman underwent laparoscopic right colectomy for a laterally spreading tumor in the cecum. On postoperative day 10, she experienced sudden hematemesis. Contrast-enhanced computed tomography (CT) of the abdomen showed a large amount of hemorrhage in the stomach, but no obvious extravasation. In addition, free air was observed near the duodenal bulb. Despite blood transfusion, vital signs remained unstable and emergency surgery was performed. The abdomen was opened through midline incisions in the upper and lower abdomen. A fragile wall and perforation were observed at the border of the left side of the duodenal bulb and pancreas, with active bleeding observed from inside. As visualization of the bleeding point proved difficult, the duodenum was divided circumferentially to confirm the bleeding point and hemostasis was performed using 4-0 PDS. The left posterior wall of the duodenum was missing, exposing the pancreatic head. For reconstruction, the jejunum was elevated via the posterior colonic route and the duodenal segment and elevated jejunum were anastomosed in an end-to-side manner. Subsequently, gastrojejunal and Brown anastomoses were added. Drains were placed before and after the duodenojejunal anastomosis. Postoperative vital signs were stable and the patient was extubated on postoperative day 1. Follow-up contrast-enhanced CT of the abdomen showed no active bleeding, and the patient was discharged home on postoperative day 21. As of 6 months postoperatively, the course of recovery has been uneventful. CONCLUSIONS: We encountered a case of pancreaticoduodenal artery hemorrhage after laparoscopic right colectomy. Bleeding at this site can prove fatal, so treatment plans should be formulated according to the urgency of the situation.

Correlations of age with clinicopathological features, perioperative outcomes and the prognosis in patients with colorectal cancer: a Japanese multicenter study.

PURPOSE: Colorectal cancer is not common in patients under 40 years old, and its associations with clinical features and the prognosis remain uncertain. METHODS: Using a multicenter database, we retrospectively reviewed 3015 patients who underwent colorectal surgery between 2016 and 2021. Patients were divided by age into those < 40 years old (young; n = 52), 40-54 years old (middle-aged; n = 254) and > 54 years old (old; n = 2709). We then investigated age-related differences in clinicopathological features, perioperative outcomes and the prognosis. RESULTS: The proportion of young patients increased annually from 0.63% in 2016 to 2.10% in 2021. Female patients were more frequent, the performance status was better, tumors were larger, clinically node-positive and poorly differentiated adenocarcinomas were more frequent, postoperative complications were less frequent, and the hospital stay was shorter in young patients than in older patients. Young age was an independent predictor of a low risk of postoperative complications (odds ratio, 0.204; 95% confidence interval, 0.049-0.849; p = 0.028). With pathologically node-positive status, adjuvant chemotherapy was more frequent in young patients (100%) than in middle-aged (73.7%) or old (51.8%) patients (p < 0.001), and the 3-year relapse-free survival was better in the young group than in others. CONCLUSION: Despite higher rates of advanced tumors in younger patients, adequate adjuvant chemotherapy appears to improve the relapse-free survival.

Feasibility and efficacy of newly developed eco-friendly, automatic washer for endoscope using electrolyzed alkaline and acidic water.

INTRODUCTION: As well as preventing nosocomial and healthcare-associated infections, a reliable and eco-friendly washer for medical equipment would also be safe for the global environment. The aim of this study was to evaluate the efficacy of a newly developed automatic washing system (Nano-washer) that uses electrolyzed water and ultrasonication without detergent for washing endoscopes. METHODS: Patients who underwent laparoscopic lobectomy or laparoscopic colectomy at Nagasaki University between 2018 and 2022 were included. A total of 60 cases of endoscope use were collected and classified according to endoscope washing method into the Nano-washer group (using no detergent) (n = 40) and the manual washing group (n = 20). Protein and bacterial residues were measured before and after washing, using absorbance spectrometry and 16S rRNA polymerase chain reaction. The effectiveness of protein and bacterial removal and endoscope surface damage after washing were compared under specular vision between the groups. RESULTS: Nano-washer did not use detergent unlike manual washing. There was no difference in demographic or clinical characteristics between the groups except for the presence of comorbidities in the lobectomy group (Nano-washer, 85%; manual washing, 40%, P = .031). Compared with the manual washing group, residual protein levels in the Nano-washer group were significantly reduced after washing (lobectomy, 0.956 mg/mL vs 0.016 mg/mL, P < .001; colectomy, 0.144 mg/mL vs 0.002 mg/mL, P = .008). Nano-washer group showed a significant reduction in bacteria between before and after lobectomy (9437 copies/cm2 vs 4612 copies/cm2 , P = .024). CONCLUSION: Nano-washer is a promising, effective, and eco-friendly automatic washing device that is safer and more efficient than manual washing.

Risk factors for reoperation within 30 days in laparoscopic colorectal cancer surgery: A Japanese multicenter study.

INTRODUCTION: Thirty-day reoperation rate reflects short-term surgical outcomes following surgery. Laparoscopic surgery for colorectal cancer reportedly has positive effects on postoperative complications. This retrospective study investigated risk factors for 30-day reoperation rate among patients after laparoscopic colorectal cancer surgery using a multicenter database. METHODS: Participants comprised 3037 patients who had undergone laparoscopic resection of colorectal cancer between April 2016 and December 2022 at the Nagasaki University and six affiliated centers, classified into those who had undergone reoperation within 30 days after surgery (RO group; n = 88) and those who had not (NRO group; n = 2949). Clinicopathological characteristics were compared between groups. RESULTS: In the RO group, anastomotic leakage occurred in 57 patients (64.8%), intestinal obstruction in 12 (13.6%), and intraabdominal abscess in 5 (5.7%). Female patients were more frequent, preoperative treatment less frequent, body mass index (BMI) lower, operation time longer, blood loss greater, and hospital stay longer in the RO group (p < .05 each). Multivariate analysis revealed BMI (odds ratio, 0.415; 95% confidence interval, 0.218-0.787; p = .021) and poor performance status (odds ratio, 1.966; 95% confidence interval, 1.106-3.492; p = .021) as independent predictors of reoperation. CONCLUSION: Perioperative measures are warranted for patients with low BMI and poor performance status undergoing laparoscopic colorectal surgery.

A surgical training system designed to help trainees acquire laparoscopic surgical skills at a rural Japanese institute.

PURPOSE: The Endoscopic Surgical Skill Qualification System was established in Japan to evaluate safe endoscopic surgical techniques and teaching skills. Trainee surgeons obtaining this certification in rural hospitals are disadvantaged by the limited number of surgical opportunities. To address this problem, we established a surgical training system to educate trainee surgeons. METHODS: Eighteen certified expert surgeons affiliated with our department were classified into an experienced training system group (E group, n = 9) and a non-experienced group (NE group, n = 9). Results of the training system were then compared between the groups. RESULTS: The number of years required to become board certified was shorter in the E group (14 years) than that in the NE group (18 years). Likewise, the number of surgical procedures performed before certification was lower in the E group (n = 30) than that in the NE group (n = 50). An expert surgeon was involved in the creation of the certification video of all the E group participants. A questionnaire to board-certified surgeons revealed that guidance by a board-certified surgeon and trainee education (surgical training system) was useful for obtaining certification. CONCLUSIONS: Continuous surgical training, starting with trainee surgeons, appears useful for expediting their acquisition of technical certification in rural areas.

The new missense G376V-TDP-43 variant induces late-onset distal myopathy but not amyotrophic lateral sclerosis.

TDP-43-positive inclusions in neurons are a hallmark of several neurodegenerative diseases including familial amyotrophic lateral sclerosis (fALS) caused by pathogenic TARDBP variants as well as more common non-Mendelian sporadic ALS (sALS). Here we report a G376V-TDP-43 missense variant in the C-terminal prion-like domain of the protein in two French families affected by an autosomal dominant myopathy but not fulfilling diagnostic criteria for ALS. Patients from both families presented with progressive weakness and atrophy of distal muscles, starting in their 5th-7th decade. Muscle biopsies revealed a degenerative myopathy characterized by accumulation of rimmed (autophagic) vacuoles, disruption of sarcomere integrity and severe myofibrillar disorganization. The G376 V variant altered a highly conserved amino acid residue and was absent in databases on human genome variation. Variant pathogenicity was supported by in silico analyses and functional studies. The G376 V mutant increased the formation of cytoplasmic TDP-43 condensates in cell culture models, promoted assembly into high molecular weight oligomers and aggregates in vitro, and altered morphology of TDP-43 condensates arising from phase separation. Moreover, the variant led to the formation of cytoplasmic TDP-43 condensates in patient-derived myoblasts and induced abnormal mRNA splicing in patient muscle tissue. The identification of individuals with TDP-43-related myopathy but not ALS implies that TARDBP missense variants may have more pleiotropic effects than previously anticipated and support a primary role for TDP-43 in skeletal muscle pathophysiology. We propose to include TARDBP screening in the genetic work-up of patients with late-onset distal myopathy. Further research is warranted to examine the precise pathogenic mechanisms of TARDBP variants causing either a neurodegenerative or myopathic phenotype.

Long-term outcomes and early recurrence after resection for metachronous pulmonary metastases from colorectal cancer.

PURPOSE: Properly selecting patients for aggressive curative resection for pulmonary metastases (PMs) from colorectal cancer (CRC) is desirable. We purposed to clarify prognostic factors and risk factors for early recurrence after metachronous PM resection. METHODS: Clinical data of 151 patients who underwent R0 resection for metachronous PMs from CRC at two institutions between 2008 and 2021 were reviewed. RESULTS: Seventy-six patients (50.3%) were male, and the median age was 71 (42-91) years. The numbers of colon/rectal cancers were 76/75, with pStage I/II/III/IV/unknown in 15/34/86/13/3. The duration from primary surgery to PM was 19.7 (1.0-106.4) months. The follow-up period was 41.9 (0.3-156.2) months. The 1-, 3-, and 5-year recurrence-free survival (RFS) rates were 75.1%, 53.7%, and 51.1%, and the 1-, 3-, and 5-year overall survival (OS) rates were 97.7%, 87.5%, and 68.2%. On multivariate analysis, lymph node metastasis of the primary lesion (HR 1.683, 95%CI 1.003-2.824, p = 0.049) was an independent predictor of poor RFS, and history of resection for extrapulmonary metastasis (e-PM) (HR 2.328, 95%CI 1.139-4.761, p = 0.021) was an independent predictor of poor OS. Patients who experienced early recurrence (< 6 months) after PM resection showed poorer OS than others (3-year OS 50.8% vs. 90.2%, p = 0.002). On multivariate analysis, e-PM was an independent predictor of early recurrence after PM resection (OR 3.989, 95%CI 1.002-15.885, p = 0.049). CONCLUSION: Since a history of e-PM was a predictor of early recurrence and poor OS after R0 resection for PM, surgical treatment of patients with a history of e-PM should be considered carefully.

Effects of bathing-induced changes in body temperature on sleep.

BACKGROUND: Passive body heating before sleep is well known to lead to improved sleep. However, the effects of the degree of change in body temperature by bathing on sleep quality are unclear. The present study aimed to clarify the effects on sleep of bathing-induced changes in body temperature. METHODS: Twenty-three healthy males and females in their 20 s to 50 s bathed in their homes 1.5-2 h before bedtime under three bathing conditions: showering only; short bathing in a bathtub; and long bathing in a bathtub. Sublingual and skin temperatures and thermal sensation before and after bathing, sleep indices such as sleep onset latency, time in bed, sleep efficiency, and wake after sleep onset, all of which were evaluated using an actimeter, and subjective evaluations of sleep were compared among conditions. RESULTS: Sublingual temperature just after bathing was significantly higher with long bathing than with other conditions, and the fall in sublingual temperature from after bathing to before sleep was significantly larger with long bathing than with short bathing. Sleep onset latency by actimeter was significantly reduced with long bathing compared to showering. In addition, subjective evaluations of falling asleep and sleep quality were better with long bathing than with showering or short bathing. CONCLUSIONS: In conclusion, bathing conditions that produce a 0.9 °C increase in sublingual temperature appear effective for falling asleep and sleep quality, because core temperature shows a greater drop to before sleep than those producing an increase of about 0.3 °C increase in sublingual temperature.