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.

Brain-derived neurotrophic factor from microglia regulates neuronal development in the medial prefrontal cortex and its associated social behavior.

Microglia and brain-derived neurotrophic factor (BDNF) are essential for the neuroplasticity that characterizes critical developmental periods. The experience-dependent development of social behaviors-associated with the medial prefrontal cortex (mPFC)-has a critical period during the juvenile period in mice. However, whether microglia and BDNF affect social development remains unclear. Herein, we aimed to elucidate the effects of microglia-derived BDNF on social behaviors and mPFC development. Mice that underwent social isolation during p21-p35 had increased Bdnf in the microglia accompanied by reduced adulthood sociability. Additionally, transgenic mice overexpressing microglial Bdnf-regulated using doxycycline at different time points-underwent behavioral, electrophysiological, and gene expression analyses. In these mice, long-term overexpression of microglial BDNF impaired sociability and excessive mPFC inhibitory neuronal circuit activity. However, administering doxycycline to normalize BDNF from p21 normalized sociability and electrophysiological function in the mPFC, whereas normalizing BDNF from later ages (p45-p50) did not normalize electrophysiological abnormalities in the mPFC, despite the improved sociability. To evaluate the possible role of BDNF in human sociability, we analyzed the relationship between adverse childhood experiences and BDNF expression in human macrophages, a possible proxy for microglia. Results show that adverse childhood experiences positively correlated with BDNF expression in M2 but not M1 macrophages. In summary, our study demonstrated the influence of microglial BDNF on the development of experience-dependent social behaviors in mice, emphasizing its specific impact on the maturation of mPFC function, particularly during the juvenile period. Furthermore, our results propose a translational implication by suggesting a potential link between BDNF secretion from macrophages and childhood experiences in humans.

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.

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.

Prostaglandin E2 Induces Long-Lasting Inhibition of Noradrenergic Neurons in the Locus Coeruleus and Moderates the Behavioral Response to Stressors.

Neuronal activity is modulated not only by inputs from other neurons but also by various factors, such as bioactive substances. Noradrenergic (NA) neurons in the locus coeruleus (LC-NA neurons) are involved in diverse physiological functions, including sleep/wakefulness and stress responses. Previous studies have identified various substances and receptors that modulate LC-NA neuronal activity through techniques including electrophysiology, calcium imaging, and single-cell RNA sequencing. However, many substances with unknown physiological significance have been overlooked. Here, we established an efficient screening method for identifying substances that modulate LC-NA neuronal activity through intracellular calcium ([Ca2+]i) imaging using brain slices. Using both sexes of mice, we screened 53 bioactive substances, and identified five novel substances: gastrin-releasing peptide, neuromedin U, and angiotensin II, which increase [Ca2+]i, and pancreatic polypeptide and prostaglandin D2, which decrease [Ca2+]i Among them, neuromedin U induced the greatest response in female mice. In terms of the duration of [Ca2+]i change, we focused on prostaglandin E2 (PGE2), since it induces a long-lasting decrease in [Ca2+]i via the EP3 receptor. Conditional knock-out of the receptor in LC-NA neurons resulted in increased depression-like behavior, prolonged wakefulness in the dark period, and increased [Ca2+]i after stress exposure. Our results demonstrate the effectiveness of our screening method for identifying substances that modulate a specific neuronal population in an unbiased manner and suggest that stress-induced prostaglandin E2 can suppress LC-NA neuronal activity to moderate the behavioral response to stressors. Our screening method will contribute to uncovering previously unknown physiological functions of uncharacterized bioactive substances in specific neuronal populations.SIGNIFICANCE STATEMENT Bioactive substances modulate the activity of specific neuronal populations. However, since only a limited number of substances with predicted effects have been investigated, many substances that may modulate neuronal activity have gone unrecognized. Here, we established an unbiased method for identifying modulatory substances by measuring the intracellular calcium signal, which reflects neuronal activity. We examined noradrenergic (NA) neurons in the locus coeruleus (LC-NA neurons), which are involved in diverse physiological functions. We identified five novel substances that modulate LC-NA neuronal activity. We also found that stress-induced prostaglandin E2 (PGE2) may suppress LC-NA neuronal activity and influence behavioral outcomes. Our screening method will help uncover previously overlooked functions of bioactive substances and provide insight into unrecognized roles of specific neuronal populations.

The gut microbiota-induced kynurenic acid recruits GPR35-positive macrophages to promote experimental encephalitis.

The intricate interplay between gut microbes and the onset of experimental autoimmune encephalomyelitis (EAE) remains poorly understood. Here, we uncover remarkable similarities between CD4+ T cells in the spinal cord and their counterparts in the small intestine. Furthermore, we unveil a synergistic relationship between the microbiota, particularly enriched with the tryptophan metabolism gene EC:1.13.11.11, and intestinal cells. This symbiotic collaboration results in the biosynthesis of kynurenic acid (KYNA), which modulates the recruitment and aggregation of GPR35-positive macrophages. Subsequently, a robust T helper 17 (Th17) immune response is activated, ultimately triggering the onset of EAE. Conversely, modulating the KYNA-mediated GPR35 signaling in Cx3cr1+ macrophages leads to a remarkable amelioration of EAE. These findings shed light on the crucial role of microbial-derived tryptophan metabolites in regulating immune responses within extraintestinal tissues.

Incidence of and risk factors for postoperative ileus between right and left laparoscopic colectomy using propensity-score-matched analysis: A retrospective multicenter study.

INSTRUCTION: In colon cancer, the incidence of postoperative ileus is reportedly higher for the right-side than for the left-side colon, but those studies included small numbers of subjects and contained several biases. Furthermore, risk factors for postoperative ileus remain unclear. METHODS: This multicenter study reviewed 1986 patients who underwent laparoscopic colectomy between 2016 and 2021 for right-side (n = 907) and left-side (n = 1079) colon cancer. After propensity score matching, 803 patients in each group were matched. RESULTS: Postoperative ileus occurred in 97 patients. Before matching, the proportion of female patients and median age were higher and frequency of preoperative stent insertion was lower with right colectomy (P < .001 each). After matching, the number of retrieved lymph nodes (17 vs 15, P < .001) and greater rates of undifferentiated adenocarcinoma (10.6% vs 5.1%, P < .001) and postoperative ileus (6.4% vs 3.2%, P = .004) were higher in right colectomy. Multivariate analysis revealed male gender (hazard ratio, 1.798; 95% confidence interval, 1.049-3.082; P = .32) and history of abdominal surgery (hazard ratio, 1.909; 95% confidence interval, 1.073-3.395; P = .027) as independent predictors of postoperative ileus in right-side colon cancer. CONCLUSION: This study revealed a higher risk of postoperative ileus after right colectomy with laparoscopic surgery. Male gender and history of abdominal surgery were risk factors for postoperative ileus after right colectomy.

Usefulness of the endoscopic surgical skill qualification system for laparoscopic colectomy for transverse colon cancer: a Japanese multicenter analysis.

PURPOSE: Laparoscopic colectomy for transverse colon cancer (TCC) can be technically demanding due to the anatomical complexity of the region. In Japan, the Endoscopic Surgical Skill Qualification System (ESSQS) was established to improve the skill of laparoscopic surgeons and further develop surgical teams. We examined the safety and feasibility of laparoscopic colectomy for TCC and evaluated the effects of the Japanese ESSQS in facilitating this approach. METHODS: We retrospectively reviewed 136 patients who underwent laparoscopic colectomy for TCC between April 2016 and December 2021. Patients were divided into an ESSQS-qualified surgeon group (surgery performed by an ESSQS-qualified surgeon, n = 52) and a non ESSQS-qualified surgeon (surgery performed by a non ESSQS-unqualified surgeon, n = 84). Clinicopathological and surgical features were compared between groups. RESULTS: Postoperative complications occurred in 37 patients (27.2%). The proportion of patients who developed postoperative complications was lower in the ESSQS-qualified surgeon group (8.0%) than that in the non ESSQS-qualified surgeon group (34.5%; p < 0.017). Multivariate analysis revealed "Operation by ESSQS-qualified surgeon surgeon" (odds ratio (OR) 0.360, 95% confidence interval (CI) 0.140-0.924; p = 0.033), blood loss (OR 4.146, 95% CI 1.688-10.184; p = 0.002), and clinical N status (OR 4.563, 95% CI 1.814-11.474; p = 0.001) as factors independently associated with postoperative complications. CONCLUSION: The present multicenter study confirmed the feasibility and safety of laparoscopic colectomy for TCC and revealed that ESSQS-qualified surgeon achieved better surgical outcomes.

Feasibility and Safety of Adjuvant Chemotherapy for Resected Colorectal Cancer in Patients With Renal Insufficiency: A Pooled Analysis of Individual Patient Data from Five Japanese Large-scale Clinical Trials.

BACKGROUND/AIM: The incidence of chemotherapy-related adverse events in colorectal cancer patients with renal insufficiency has been compared to patients with normal renal function in only a few studies. The purpose of this analysis was to verify the feasibility and safety of adjuvant chemotherapy for postoperative colorectal cancer patients with renal insufficiency. PATIENTS AND METHODS: Adverse events and discontinuation of adjuvant chemotherapy for patients with curatively resected locally advanced colorectal cancer were examined using a combined database of individual patient data obtained from five large-scale clinical trials (n=4,106). The renal function of patients was classified into Level (L) 1-2: ≥60 ml/min and L3-4: <60 ml/min. RESULTS: As Grade 3 adverse events, hematological toxicities, such as neutropenia and anemia, and gastrointestinal disorders, such as diarrhea and vomiting, were significantly more frequent in the L3-4 group. Moreover, the time-to-treatment discontinuation in the L3-4 group was higher (hazard ratio=1.21, p=0.0012). T factor, N factor, and creatinine clearance level were found to be independent risk factors for the discontinuation of adjuvant chemotherapy. In the subgroup analysis of FOLFOX, neutropenia and diarrhea were significantly common in the L3-4 group, but neurotoxicities were not different. There was no significant difference in the discontinuation of adjuvant FOLFOX. CONCLUSION: Adverse events of adjuvant chemotherapy in patients with resected colorectal cancer were associated with renal insufficiencies. Since adverse events have the potential to shorten the duration of treatment, especially when using chemotherapy without oxaliplatin, careful management, including dose reduction, may be important in patients with renal insufficiency.

Efficacy of left colic artery preservation with D3 lymph node dissection in laparoscopic surgery for advanced sigmoid and rectal cancer.

PURPOSE: For advanced left colon cancer, lymph node dissection at the root of the inferior mesenteric artery is recommended. Whether the left colic artery (LCA) should be preserved or resected remains contentious. METHODS: The 367 patients who underwent laparoscopic sigmoidectomy or anterior resection and who were pathologically node-positive were reviewed. Patients were divided into LCA-preserving group (LCA-P, n = 60) and LCA-non-preserving group (LCA-NP, n = 307). Propensity score matching was applied to minimize selection bias and 59 patients were matched. RESULTS: Before matching, the rates of poor performance status and cardiovascular disease were higher in the LCA-P group (p < 0.001). After matching, operation time was longer (276 vs. 240 min, p = 0.001), the frequency of splenic flexure mobilization (62.7% vs. 33.9%, p = 0.003) and lymphovascular invasion (84.7% vs. 55.9%, p = 0.001) was higher in the LCA-P group. Severe postoperative complications (CD ≥ 3) occurred only in the LCA-NP group (0% vs. 8.4%, p = 0.028). The median follow-up period was 38.5 months (range 2.0-70.0 months). The 5-year RFS rates (67.8% vs. 66.0%, p = 0.871) and OS rates (80.4% vs. 74.9%, p = 0.308) were comparable between the groups. CONCLUSIONS: Laparoscopic LCA-sparing surgery for left-sided colorectal cancer reduces the risk of severe complications and offers a favorable long-term prognosis.

Effect of adjuvant chemotherapy after curative resection of colorectal cancer peritoneal metastasis.

PURPOSE: Several guidelines have recommended surgical resection for localized peritoneal metastases, but the prognosis remains poor. In addition, the efficacy of adjuvant chemotherapy (AC) after curative resection is under debate. The present study compared long-term outcomes between curative and non-curative resection and evaluated the effects of AC after curative resection. METHODS: Using a multicenter database, we retrospectively reviewed 123 colorectal cancer patients with peritoneal metastases between April 2016 and December 2021. Of these patients, 49 underwent curative resection, and 74 underwent non-curative resection. RESULTS: The frequency of broad metastases was lower in the curative resection group (8.2%) than in the non-curative resection group (43.2%, p < 0.001). Among all patients, 5-year overall survival rate was higher in the curative resection group (43.0%) than in the non-curative resection group (7.3%, p = 0.004). Among patients who underwent curative resection, 5-year overall survival rate was significantly higher in the AC group (48.2%) than in the non-AC group (38.1%, p = 0.037). Multivariate analysis of all patients revealed pathological N status and non-curative resection as independent predictors of overall survival. In patients who underwent curative resection, advanced age was an independent predictor of relapse-free survival, and AC was an independent predictor of overall survival. CONCLUSION: This multicenter study of colorectal cancer patients with peritoneal metastases revealed that prognosis was more favorable for curable cases than for non-curable cases. Prognosis was more favorable in the AC group than in the non-AC group after curative resection.

Pupil Dynamics-derived Sleep Stage Classification of a Head-fixed Mouse Using a Recurrent Neural Network.

The standard method for sleep state classification is thresholding the amplitudes of electroencephalography (EEG) and electromyography (EMG) data, followed by manual correction by an expert. Although popular, this method has some shortcomings: (1) the time-consuming manual correction by human experts is sometimes a bottleneck hindering sleep studies, (2) EEG electrodes on the skull interfere with wide-field imaging of the cortical activity of a head-fixed mouse under a microscope, (3) invasive surgery to fix the electrodes on the thin mouse skull risks brain tissue injury, and (4) metal electrodes for EEG and EMG recording are difficult to apply to some experimental apparatus such as that for functional magnetic resonance imaging. To overcome these shortcomings, we propose a pupil dynamics-based vigilance state classification method for a head-fixed mouse using a long short-term memory (LSTM) model, a variant of a recurrent neural network, for multi-class labeling of NREM, REM, and WAKE states. For supervisory hypnography, EEG and EMG recording were performed on head-fixed mice. This setup was combined with left eye pupillometry using a USB camera and a markerless tracking toolbox, DeepLabCut. Our open-source LSTM model with feature inputs of pupil diameter, pupil location, pupil velocity, and eyelid opening for 10 s at a 10 Hz sampling rate achieved vigilance state estimation with a higher classification performance (macro F1 score, 0.77; accuracy, 86%) than a feed-forward neural network. Findings from a diverse range of pupillary dynamics implied possible subdivision of the vigilance states defined by EEG and EMG. Pupil dynamics-based hypnography can expand the scope of alternatives for sleep stage scoring of head-fixed mice.

Novel Bruton's tyrosine kinase inhibitor TAS5315 suppresses the progression of inflammation and joint destruction in rodent collagen-induced arthritis.

Rheumatoid arthritis is an inflammatory autoimmune disease, characterized by autoantibody production, synovial inflammation, and joint destruction. Its pathogenesis is due to environmental factors and genetic backgrounds. Bruton's tyrosine kinase is a cytoplasmic non-receptor tyrosine kinase, expressed in most hematopoietic cell lineages, except T cells and plasma cells, and regulates various immune-related signaling pathways, thereby playing a crucial role in pathogenesis. Thus, inhibiting Bruton's tyrosine kinase may prove beneficial in treating autoimmune diseases. In the present study, we characterized Bruton's tyrosine kinase inhibitor, TAS5315, in vitro and evaluated its therapeutic effects in experimental arthritis models. TAS5315 markedly inhibited Bruton's tyrosine kinase enzyme activity and suppressed the B-cell receptor signaling pathway in Ramos cells. Moreover, it suppressed the expression of CD69, CD86, and MHC class II in mouse B lymphocytes and the production of TNF-α and MIP-1α in mouse macrophages and decreased bone resorption activity in mouse osteoclasts. Furthermore, it ameliorated the pathological changes in two rodent models of collagen-induced arthritis in vivo. TAS5315 improved bone mineral density and bone intensity. Thus, these results suggest that TAS5315 could be a promising therapeutic option for the treatment of rheumatoid arthritis.

Mid-term outcomes of laparoscopic vs open colectomy for pathological T4 and/or N2 colon cancer patients: Multicenter study using propensity score matched analysis.

OBJECTIVES: We aimed to assess mid-term outcomes after laparoscopic surgery (LAP) vs open surgery (OP) for pathological T4 (pT4) and/or N2 (pN2) colon cancer. METHODS: We retrospectively reviewed 255 primary tumor resections for pT4 and/or pN2 colon cancer performed from 2015 to 2020 at six hospitals, divided into LAP (n = 204) and OP groups (n = 51). After propensity score matching to minimize selection bias, 47 matched patients per group were assessed. RESULTS: Before matching, the rate of males (53.9% vs. 37.3%, P = .042), left sided colon cancer (53.9% vs 37.3%, P = .042), D3 lymph node dissection (90.7% vs 68.6%, P < .001) and body mass index (kg/m2 ) (22.3 vs 21.8, P = .039) were significantly greater in the LAP group. The rate of pT4b (7.8% vs 40.4%, P < .001) was lower and pN2 was higher (57.4% vs 37.3%, P = .012) in the LAP group. After matching, preoperative characteristics and pathologic status were equivalent between the groups. The LAP and OP groups showed comparable overall survival (OS) (2-year OS, 84.5% vs 76.8%, P = .055) and recurrence-free survival (RFS) (2-year RFS, 73.9% vs 52.8%, P = .359). In the patients with pT4, OS (2-year OS, 79.4% vs 75.7%, P = .359) and RFS (2-year RFS, 71.3% vs 58.7%) were comparable. In the patients with pN2, OS (2-year OS, 83.4% vs 76.3%) and RFS (2-year RFS, 69.6% vs 36.2%) were also comparable. CONCLUSIONS: LAP for pT4 and/or pN2 colon cancer showed comparable mid-term outcomes compared with OP. LAP was an acceptable surgical approach in this cohort.

Laparoscopic resection of an intra-abdominal esophageal duplication cyst in the ileum: a case report.

BACKGROUND: Esophageal duplication cyst (EDC) is a type of gastrointestinal duplication cyst that involves congenital malformations of the gastrointestinal tract. EDCs are frequently found in the mediastinum and thoracoabdominal region, but rarely occur in the abdominal cavity. However, intra-abdominal EDCs are frequently found in the upper abdomen near the abdominal esophagus. Here, we report, for the first time, a case of intra-abdominal EDC that occurred in the ileum. CASE PRESENTATION: A 14-year-old female patient presented to our hospital with complaints of epigastric pain and vomiting. Abdominal computed tomography (CT) revealed a cystic tumor in the pelvis, suspected of ovarian origin. She was admitted to our gynecology department and underwent emergency surgery. The laparoscopic examination revealed that both ovaries were intact and that a primary tumor had developed from the ileal mesentery. Since the patient's condition was not urgent at the time of the gynecological surgery, the procedure was completed by only performing exploratory laparotomy; the patient was admitted to our department after the surgery. Pelvic magnetic resonance imaging performed on the next day revealed a cystic mass measuring 90 × 65 mm with a smooth margin and homogeneous signal intensity, arising posterior to the uterus. The mass was suspected as an intestinal duplication cyst. On another day, after the examinations were completed, we resected the portion of the small intestine containing the tumor by laparoscopy. The patient had a successful postoperative course and was discharged on the 5th postoperative day. Histological examination showed that the cyst was lined by stratified squamous epithelium, contained esophageal glands, and had a two-layer muscularis propria. Therefore, a diagnosis of intra-abdominal EDC was performed. CONCLUSIONS: An intra-abdominal EDC cyst is relatively rare; this is the first case reported at the distal ileum.

Effect of oxaliplatin in elderly colon cancer patients with pathological T4 and/or N2 disease: a multicenter, propensity score-matched analysis.

PURPOSE: Although adjuvant chemotherapy (AC) using fluoro-pyrimidine and oxaliplatin (FU + oxaliplatin) is recommended after curative resection for locally advanced colon cancer patients, several randomized controlled trials have shown no additional effect of oxaliplatin in patients aged ≥ 70 years. Here, we examined the effectiveness of FU + oxaliplatin on the long-term outcome of old patients with a high risk of recurrence. METHODS: This multicenter, retrospective study included 346 colon cancer patients diagnosed with pathological T4 and/or N2 disease from 2016 to 2020. They were divided into an old group (≥ 70 years, n = 197) and a young group (< 70 years, n = 167). Propensity score matching was used to minimize selection bias, and 126 patients per group were matched. RESULTS: Before matching, the rates of poor performance status (p < 0.001) and the presence of comorbidities (76.1% vs. 47.9%, p < 0.001) were higher in the old group. Although all baseline factors were similar between groups, after matching, the AC rate was lower in the old group (45.2% vs. 65.1%, p = 0.002). In the old group, relapse-free (82.2% vs. 55.6% and 69.6%, p < 0.05) and overall survival (83.1% vs. 80.0% and 44.4%, p < 0.05) rates were significantly higher in the AC patients with FU + oxaliplatin than in the AC patients with only FU and the non-AC patients. CONCLUSION: The selected old colon cancer patients with a high risk of recurrence gained an additional benefit with respect to prognosis from FU + oxaliplatin as AC.

Short- and long-term outcomes of single-incision laparoscopic surgery for right colon cancer: A multicenter propensity score-matched analysis.

INTRODUCTION: Single-incision laparoscopic surgery (SILS) for colon cancer is a recent innovation in minimally invasive surgery that can improve short-term outcome. However, several biases exist in current favorable comparisons of SILS with conventional laparoscopic (CL) surgery. Moreover, the oncological outcomes in SILS remain unclear. The aim of this study was to identify outcomes following SILS and CL for right colectomy using a propensity score-matched analysis. METHODS: A total of 553 patients underwent curative resection for right colon cancer (58 SILS and 495 CL). After propensity score matching, 58 patients in each group were matched. RESULTS: Before matching, median age was younger (p = 0.037) and clinical stage was lower (p < 0.001) in the SILS group. After matching, operation time was shorter (172 versus 193 min, p = 0.007) and blood loss was less (12 versus 20 mL, p = 0.037) in the SILS group. Most of the SILS cases were performed (43.1%) or supervised (51.7%) by an expert surgeon. Median follow-up duration was 30 and 37 mo in the SILS and CL groups, respectively. Three-year relapse-free survival was 92.5% and 92.4% (p = 0.781); and overall survival was 100% versus 98.1% (p = 0.177). CONCLUSIONS: Under the control of expert surgeons, SILS appeared to be a safe and feasible approach and had similar oncological outcomes compared with CL in a propensity score-matched cohort of patients with right-sided colon cancer.

Dysfunction of parvalbumin-expressing cells in the thalamic reticular nucleus induces cortical spike-and-wave discharges and an unconscious state.

Spike-and-wave discharges and an accompanying loss of consciousness are hallmarks of absence seizure, which is a childhood generalized epilepsy disorder. In absence seizure, dysfunction of the cortico-thalamo-cortico circuitry is thought to engage in abnormal cortical rhythms. Previous studies demonstrated that the thalamic reticular nucleus has a critical role in the formation of normal cortical rhythms; however, whether thalamic reticular nucleus dysfunction leads directly to abnormal rhythms, such as epilepsy, is largely unknown. We found that expressing the inhibitory opsin, archaerhodopsin, including in the thalamic reticular nucleus, caused abnormal cortical rhythms in Pvalb-tetracycline transactivator::tetO-ArchT (PV-ArchT) double transgenic mice. We validated the PV-ArchT line as a new mouse model of absence seizure through physiological and pharmacological analyses, as well as through examining their behavioural features. We then discovered that archaerhodopsin expression exclusively in thalamic reticular nucleus parvalbumin-positive neurons was sufficient to induce cortical spike-and-wave discharges using adeno-associated virus-mediated thalamic reticular nucleus targeting. Furthermore, we found that archaerhodopsin expression impaired rebound burst firing and T-current in thalamic reticular nucleus parvalbumin-positive cells by slice physiology. Although T-current in the thalamic reticular nucleus was impaired, the T-current blocker ethosuximide still had a therapeutic effect in PV-ArchT mice, suggesting a gain of function of T-type calcium channels in this absence seizure model. However, we did not find any over- or misexpression of T-type calcium channel genes in the thalamus or the cortex. Thus, we demonstrated that thalamic reticular nucleus dysfunction led to an absence seizure-like phenotype in mice. In a final set of experiments, we showed that the archaerhodopsin-mediated absence seizure-like phenotype disappeared after the removal of archaerhodopsin by using a time-controllable transgenic system. These data may provide a hint as to why many absence seizures naturally regress.

Effect of Neoadjuvant Chemotherapy in Patients With Locally Advanced Rectal Cancer: A Multicenter Propensity Score-matched Analysis.

BACKGROUND/AIM: The effect of neoadjuvant chemotherapy (NAC) and adjuvant chemotherapy (AC) for locally advanced rectal cancer (LARC) is not fully understood. This study aimed to identify outcomes following NAC plus AC for LARC. PATIENTS AND METHODS: We reviewed 252 patients who underwent curative resection for LARC. Propensity score matching matched 51 patients in NAC and non-NAC groups. RESULTS: Operative time (443 min vs. 286 min, p<0.001), blood loss (279 ml vs. 124 ml p<0.001), and number of patients who received AC were higher in the NAC group (74.5% vs. 33.3%, p<0.001). The Disease control rate of NAC group was 98.1%. The NAC group showed better 3-year RFS (86.5% vs. 62.1%, p=0.021). Patients who received both NAC and AC displayed better 3-year RFS (90.2%) compared to the non-NAC group both with (63.8%) and without (60.4%) AC (p<0.05). CONCLUSION: NAC and AC for LARC have the potential to improve oncological outcomes.

Hybrid Repair with Reversed Sequence Supra-aortic Debranching in Ruptured Arch Aneurysm.

Aortic arch pathology in a high-risk patient in whom the resternotomy approach is unfeasible due to treated mediastinitis after ascending aortic replacement presents a unique challenge for hybrid arch repair (HAR) because of the need for supra-aortic debranching from unusual inflow sites other than the ascending aorta. This report describes a "reversed sequence" extra-anatomical supra-aortic debranching procedure as a salvage technique performed to enable HAR. An 83-year-old woman with a history of ascending aortic replacement for type A aortic dissection, mediastinitis complicated by sternal osteomyelitis, and a chest wall reconstructed with a rectus abdominis myocutaneous flap presented with chest pain because of a contained dissecting arch aneurysm rupture. The patient underwent supra-aortic debranching from the bilateral common femoral arteries and thoracic endovascular aortic repair to the ascending aorta under cerebral near-infrared spectroscopy (NIRS) monitoring. Completion imaging by angiography demonstrated successful exclusion of the ruptured aneurysm. The regional cerebral oxygen saturation level, monitored by NIRS, did not change markedly during surgery. The patient was neurologically intact with adequate cerebral blood flow assessed postoperatively by 123 I-IMP single photon emission computed tomography. Total debranching of the supra-aortic vessels from the common femoral artery for inflow is feasible and provides adequate cerebral perfusion. This procedure may offer an alternative treatment option in patients with complex conditions involving aortic arch pathology.