Equal short-term outcomes of intracorporeal mechanical gastrogastrostomy in laparoscopic pylorus-preserving gastrectomy for cT1N0 gastric cancer in the middle stomach compared with the extracorporeal hand-sewing method.

BACKGROUND: Intracorporeal mechanical gastrogastrostomy (IMG) techniques have recently been developed and their short-term safety was presented in their initial evaluation. However, whether they are comparable to extracorporeal hand-sewing gastrogastrostomy (EHG) remains unclear. The aim of the study is to establish the safety of IMG in totally laparoscopic pylorus-preserving gastrectomy (TLPPG) compared to EHG in laparoscopy-assisted pylorus-preserving gastrectomy (LAPPG). METHODS: We retrospectively analyzed the short-term outcomes of patients with middle-third early gastric cancer who underwent LAPPG or TLPPG between 2005 and 2022. The primary objective of this study was to evaluate the non-inferiority of IMG to EHG in terms of safety, with the primary endpoint being the risk difference in anastomosis-related complications (ARCs). The sample size required to achieve a statistical power of 80% for the non-inferiority test was 971 with a one-sided alpha level of 5% and non-inferiority of 5%. RESULTS: The analysis included a total of 1,021 patients who underwent LAPPG or TLPPG during the study period. Among them, 488 patients underwent EHG, while 533 underwent IMG. The incidences of ARCs were 11.3% and 11.4% in EHG and IMG, respectively. The observed difference in incidence was 0.0017 (90% confidence interval - 0.0313 to 0.0345), which statistically demonstrated the non-inferiority of IMG to EHG in the incidence of ARCs. Among other complications, the incidence of wound infection in IMG was lower than that in EHG. CONCLUSION: IMG is safe regarding ARCs compared with EHG. These results will encourage surgeons to introduce IMG for patients with early middle gastric cancer.

Adequate gross resection margin length ensuring pathologically complete resection in gastrectomy for gastric cancer: A systematic review and meta-analysis.

Aim: A positive resection margin (RM) is associated with poor survival after gastrectomy for gastric cancer (GC). However, the adequate RM length to avoid a positive RM remains controversial. We performed a systematic review to examine the RM length required to avoid a positive RM in gastrectomy for GC. Methods: This systematic review involved all relevant articles identified in PubMed, the Cochrane Library, Web of Science, and ClinicalTrials.gov until August 2023. The incidence of a positive RM related to the RM length and the possible incidence of a positive RM estimated from the discrepancy between the gross and pathological RM length were evaluated. The Newcastle-Ottawa Scale was used to quantify study quality. Results: Thirteen studies involving 8983 patients were analyzed. Investigation of the incidence of a positive RM in relation to the RM length showed that a proximal RM length of 6 cm guaranteed a negative RM in gastrectomy. Analyses of the possible incidence of a positive RM revealed that a negative RM would be guaranteed if the proximal RM length was 6 cm in distal gastrectomy, if the esophageal resection length was 2 cm in total gastrectomy for GC without esophageal invasion and 2.5 cm in total or proximal gastrectomy for GC with esophageal invasion or esophagogastric junction cancer, and if the distal RM length was 4 cm in proximal gastrectomy for early GC. Conclusions: The adequate RM lengths to ensure a pathologically negative RM in each type of gastrectomy for GC were herein suggested.

Clinical utility of the carcinoembryonic antigen level in patients with stage III colon cancer after surgery and adjuvant chemotherapy.

PURPOSE: The association between perioperative and post-adjuvant carcinoembryonic antigen (CEA) levels and recurrence and prognosis remains unclear. We aimed to evaluate whether perioperative CEA levels are an integral component of the assessment of recurrence and prognosis of patients with stage III colon cancer (CC). METHODS: This retrospective study was conducted at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research from 2005 to 2013. We enrolled patients with stage III CC who underwent complete resection of a primary tumor and received adjuvant chemotherapy. We analyzed the association between perioperative and post-adjuvant CEA levels and recurrence-free survival (RFS) and overall survival (OS). RESULTS: A total of 564 consecutive patients were included in the analysis. The RFS and OS of patients with high postoperative CEA levels were significantly worse than those of patients with normal postoperative CEA levels. In the multivariate analysis, high postoperative CEA levels were associated with shorter RFS and OS. The number of risk factors, postoperative CEA levels, and T/N-stage all had a cumulative effect on RFS and OS. CONCLUSIONS: High postoperative CEA levels and the number of risk factors are associated with recurrence and worse prognosis for patients with stage III CC.

Retrospective study of the efficacy and safety of docetaxel/carboplatin combination therapy as postoperative adjuvant chemotherapy for nonsquamous cell carcinoma of the cervix.

OBJECTIVE: Optimal adjuvant chemotherapy for nonsquamous cervical carcinoma has not yet been established. This study investigated the efficacy and safety of docetaxel/carboplatin (DC) for early-stage nonsquamous cell cervical carcinoma after radical hysterectomy (RH). METHODS: We evaluated 157 patients with stage IB-IIB nonsquamous cervical carcinoma with intermediate risk and high risk treated at our institution with DC after type II or III RH from 2007 to 2021. Patients received docetaxel (60-70 mg/m2) and carboplatin (area under the curve 5-6) every 3 weeks for six cycles. The primary endpoint was 2 year recurrence-free survival (RFS) and the secondary endpoint was adverse events (AEs). RESULTS: There were 106 intermediate-risk and 51 high-risk patients. The high-risk patients included 11 with positive parametrial involvement, 20 with pelvic lymph node metastases, and 20 with both parametrial involvement and pelvic lymph node metastases. The 2 year RFS rates for intermediate-risk, high-risk, and positive pelvic lymph nodes were 94.8% (95% confidence interval [CI], 87.9-97.8), 80.1% (95% CI, 64.1-89.5), and 74.5% (95% CI, 55.4-86.4), respectively. Sixteen patients had recurrence, including local recurrence (n = 6), distant metastasis (n = 9), and local and distant metastasis (n = 1). Hematologic toxicity was the most frequent AE, especially leukopenia and neutropenia. Nausea and constipation were the most frequent nonhematologic toxicities. CONCLUSION: DC therapy at our institution showed good 2 year RFS, and postoperative adjuvant therapy with DC therapy is suggested as a useful strategy for patients with nonsquamous cervical carcinoma.

Efficacy of intra-abdominal cytoreductive surgery in advanced endometrial cancer with distant metastasis.

OBJECTIVE: The efficacy of intra-abdominal cytoreductive surgery in patients with endometrial cancer and distant metastasis is equivocal. We investigated the effectiveness of such surgical treatment and whether it should be performed before or after chemotherapy (CT). METHODS: This study included patients with an International Federation of Gynecology and Obstetrics stage IVB endometrial cancer who received initial treatment at our hospital between January 2006 and December 2017. RESULTS: We retrospectively reviewed 67 patients with stage IVB endometrial cancer with distant metastases and classified them into preceding surgery (PS, n=23), chemotherapy followed by a surgery (CS, n=27), and CT (n=17) groups. We examined the achievement of resection with [R (1)] or without [R (0)] intra-abdominal macroscopic residue and survival. The median survival time for R (0) was 44 (95% confidence interval [CI]=9-not available [NA]) months in the PS group and 27 (95% CI=11-NA) months in the CS group. The median survival time for R (1) was 9 (95% CI=0-24) months in the PS group and 12 (95% CI=7-19) months in the CS group. The similar prognosis in both groups was worse with R (1) than with R (0). The survival curve for R (1) in the resection groups was similar to that of the CT group. CONCLUSION: Achieving resection without intra-abdominal macroscopic residue for endometrial cancer with distant metastases, whether before or after CT, could extend patients' survival.

Directly Reprogrammed Neurons as a Tool to Assess Neurotoxicity of the Contaminant 4-Hydroxy-2',3,5,5'-tetrachlorobiphenyl (4'OH-CB72) in Melon-Headed Whales.

Whales accumulate high levels of environmental pollutants. Exposure to polychlorinated biphenyls (PCBs) and their metabolites (OH-PCBs) could be linked to abnormal behavior, which may lead to mass stranding of marine mammals. Whales may thus suffer from adverse effects such as neuronal dysfunction, yet testing the neurotoxicity of these compounds has never been feasible for these species. This study established neurons chemically reprogrammed from fibroblasts of mass stranded melon-headed whales (Peponocephala electra) and used them for in vitro neurotoxicity assays. Exposure to 4-hydroxy-2',3,5,5'-tetrachlorobiphenyl (4'OH-CB72), a metabolite of PCBs, caused apoptosis in the reprogrammed neurons. Transcriptome analysis of 4'OH-CB72-treated whale neurons showed altered expressions of genes associated with oxidative phosphorylation, chromatin degradation, axonal transport, and neurodegenerative diseases. These results suggest that 4'OH-CB72 exposure may induce neurodegeneration through disrupted apoptotic processes. A comparison of the results with human reprogrammed neurons revealed the specific effects on the whale neurons. Our noninvasive approach using fibroblast-derived neurons is useful for hazard and risk assessments of neurotoxicity in whales.

Short- and long-term oncological outcomes of totally laparoscopic gastrectomy versus laparoscopy-assisted gastrectomy for clinical stage I gastric cancer.

BACKGROUND: Totally laparoscopic gastrectomy (TLG), which involves a complete intracorporeal gastric transection and the creation of an anastomosis, has been gradually adopted. However, a potential limitation of intracorporeal transection is the lack of tactile feedback, and whether this limitation influences oncological outcomes is unclear. The aim of this study is to evaluate the short- and long-term oncological safety of TLG using endoscopy-guided intracorporeal gastric transection for clinical stage (cStage) I gastric cancer. METHODS: A total of 1875 consecutive patients who underwent laparoscopic gastrectomy for cStage I gastric cancer between January 2007 and March 2015 were enrolled in this study. Marking clips were preoperatively placed and a transection line was determined by perceiving it tactually in laparoscopy-assisted gastrectomy (LAG) or endoscopically in TLG. After propensity score matching, 1366 patients (683 each for LAG and TLG groups) were selected to primarily test the non-inferiority of TLG to that of LAG for relapse-free survival (RFS). RESULTS: In the propensity-matched population, the 5-year RFS rates of the LAG and TLG groups were 94.3% (95% confidence interval (CI) 92.2-95.8%), and 95.6% (95% CI 93.8-96.9%), respectively. The hazard ratio (TLG/LAG) was 0.77 (95% CI 0.48-1.24, P for non-inferiority < 0.01). There were no significant differences in the recurrence profiles. The incidence of the remnant of marking clips or tumor tissue did not differ (LAG: 1.0% vs. TLG: 1.9%, P = 0.177). CONCLUSIONS: TLG using preoperative markings and intraoperative endoscopic guidance provides cStage I gastric cancer patients with comparable oncological outcomes to the conventional method.

In Vitro Cytotoxicity and Risk Assessments of Environmental Pollutants Using Fibroblasts of a Stranded Finless Porpoise (Neophocaena asiaeorientalis).

Cetaceans accumulate high levels of environmental pollutants, yet their toxicological studies have been difficult due to technical and ethical issues. It is essential to identify and fill the current knowledge gaps in the in vitro assays available for cetaceans. The present study establishes a novel in vitro assay that uses the fibroblasts of a finless porpoise (Neophocaena asiaeorientalis) (FF) stranded in the Seto Inland Sea (SIS) to answer questions about the cytotoxicity and risks of environmental pollutants. FF were treated with 17 compounds including polychlorinated biphenyls (PCBs) and dichlorodiphenyltrichloroethane and their metabolites (DDTs) and evaluated for cytotoxicity, viability, and apoptosis. The results of FF were compared with those of human fibroblasts (HF). The relative potencies of the test compounds were comparable between the two species, as EC50 of these compounds significantly correlated for FF and HF. Exposure-activity ratios (EARs) revealed that accumulation of PCBs and DDTs are likely to pose adverse effects at the cellular level in the SIS finless porpoises, as their tissue concentrations exceeded EC50 values obtained in this study. This study successfully evaluated the risks of environmental pollutants using cetacean fibroblasts isolated by a non-invasive method that may be applied to various cetacean species and compounds.

What is the taxonomic status of East Asian otter species based on molecular evidence?: focus on the position of the Japanese otter holotype specimen from museum.

The Japanese otter (Lutra nippon), once inhabited in most islands of Japan, is now considered as an extinct species. Although the Japanese otter is regarded as a distinct species from the Eurasian otter (L. lutra), its phylogeny and taxonomic status are based on limited information on morphological and genetic data, and thus further clarification is required. Here, we assessed the phylogenetic relationship among the genus Lutra and taxonomic status of L. nippon by using the complete sequences of cytochrome b gene of its holotype. The present phylogenic trees supported that the genus Lutra specimens largely formed monophyletic group, with L. sumatrana as a basal to other Lutra species. Within Lutra species, L. nippon was distantly related with L. lutra. The European otter population of L. l. lutra were clustered together with its subspecies, L. l. chinensis rather than the same subspecies, Korean otter population. The discrepancy between the genetic data and traditional taxonomy justifies the necessity of reexamination of the current subspecific classification system of Eurasian otters. Level of genetic divergence between the holotype of L. nippon and L. lutra was two to three-fold lower than those among the other sister species of the Lutrinae. Based on the level of divergence between the L. nippon and L. lutra, and insufficient evidence of morphological difference between them, it is suggested that designation of Japanese otter as a separate species from L. lutra will be reconsidered.

Innervation of wing membrane in Japanese little horseshoe bats, Rhinolophus cornutus.

The spinal nerves supplying the wing membranes of Japanese little horseshoe bats, Rhinolophus cornutus were studied. The wing membrane was innervated by nerve branches of the radial, ulnar, and median nerves, showing that the membrane was formed from the skin of the forelimb rather than that of the thoracolumbar skin. The radial nerve was mainly composed of the ventral rami of C7-T1, the ulnar nerve by C8-T2, and the median nerve by C8-T1. These components of R. cornutus tended to be from a narrower range of spinal nerves and to position more caudally than those of humans. In addition, the ulnar nerve showed a distribution pattern different from that of other mammals.

Description of the karyotypes of Stejneger's beaked whale (Mesoplodon stejnegeri) and Hubbs' beaked whale (M. carlhubbsi)

Abstract The genus Mesoplodon (Cetacea: Odontoceti: Ziphiidae) is one of the few cetacean genera with the karyotype 2n = 42. The 2n = 42 karyotype of M. europaeus and M. carlhubbsi is largely consistent with the general cetacean karyotype 2n = 44, although other 2n = 42 karyotypes do not exhibit clear homologies with the general cetacean karyotype. Therefore, the chromosomes of Mesoplodon species may be the key to understanding cetacean karyological evolution. In the present study, the male karyotypes of M. stejnegeri and M. carlhubbsi were examined. In both species, the diploid number of the male karyotype was 42. Both species had the following characteristics: 1) a huge subtelocentric X chromosome with a large C-block; 2) a small metacentric Y chromosome; 3) nucleolus organizer regions (NORs) in the terminal regions of a large autosome and one or two small metacentric autosomes; 4) small metacentric autosomes; 5) large submetacentric and subtelocentric autosomes; 6) less accumulated C-heterochromatin in the centromeric region; and 7) heteromorphism in C-heterochromatin accumulation between homologues. Characteristics 1 and 3 are peculiar to only the karyotypes of Mesoplodon species, whereas characteristics 4, 5, 6, and 7 are also found in the species with the general cetacean karyotype 2n = 44.

Description of the karyotypes of Stejneger's beaked whale (Mesoplodon stejnegeri) and Hubbs' beaked whale (M. carlhubbsi).

The genus Mesoplodon (Cetacea: Odontoceti: Ziphiidae) is one of the few cetacean genera with the karyotype 2n = 42. The 2n = 42 karyotype of M. europaeus and M. carlhubbsi is largely consistent with the general cetacean karyotype 2n = 44, although other 2n = 42 karyotypes do not exhibit clear homologies with the general cetacean karyotype. Therefore, the chromosomes of Mesoplodon species may be the key to understanding cetacean karyological evolution. In the present study, the male karyotypes of M. stejnegeri and M. carlhubbsi were examined. In both species, the diploid number of the male karyotype was 42. Both species had the following characteristics: 1) a huge subtelocentric X chromosome with a large C-block; 2) a small metacentric Y chromosome; 3) nucleolus organizer regions (NORs) in the terminal regions of a large autosome and one or two small metacentric autosomes; 4) small metacentric autosomes; 5) large submetacentric and subtelocentric autosomes; 6) less accumulated C-heterochromatin in the centromeric region; and 7) heteromorphism in C-heterochromatin accumulation between homologues. Characteristics 1 and 3 are peculiar to only the karyotypes of Mesoplodon species, whereas characteristics 4, 5, 6, and 7 are also found in the species with the general cetacean karyotype 2n = 44.

Control of the 1,2-rearrangement process by oxidosqualene cyclases during triterpene biosynthesis.

Oxidosqualene cyclases (OSCs) catalyze the cyclization of an acyclic substrate into various polycyclic triterpenes through a series of cation-π cyclization and 1,2-rearrangement processes. The mechanisms by which OSCs control the fate of intermediate carbocation to generate each specific triterpene product have not yet been determined. The formation of ubiquitous sterol precursors in plants, cycloartenol and Cucurbitaceae-specific cucurbitadienol, only differs by the extent of the 1,2-rearrangement of methyl and hydride. In the present study, we identified critical residues in cycloartenol synthase and cucurbitadienol synthase that were primarily responsible for switching product specificities between the two compounds. The mutation of tyrosine 118 to leucine in cycloartenol synthase resulted in the production of cucurbitadienol as a major product, while the mutation of the corresponding residue leucine 125 to tyrosine in cucurbitadienol synthase resulted in the production of parkeol. Our discovery of this "switch" residue will open up future possibilities for the rational engineering of OSCs to produce the desired triterpenes.

Improving importance estimation in pool-based batch active learning for approximate linear regression.

Pool-based batch active learning is aimed at choosing training inputs from a 'pool' of test inputs so that the generalization error is minimized. P-ALICE (Pool-based Active Learning using Importance-weighted least-squares learning based on Conditional Expectation of the generalization error) is a state-of-the-art method that can cope with model misspecification by weighting training samples according to the importance (i.e., the ratio of test and training input densities). However, importance estimation in the original P-ALICE is based on the assumption that the number of training samples to gather is small, which is not always true in practice. In this paper, we propose an alternative scheme for importance estimation based on the inclusion probability, and show its validity through numerical experiments.

Iteratively-reweighted local model fitting method for adaptive and accurate single-shot surface profiling.

The local model fitting (LMF) method is one of the useful single-shot surface profiling algorithms. The measurement principle of the LMF method relies on the assumption that the target surface is locally flat. Based on this assumption, the height of the surface at each pixel is estimated from pixel values in its vicinity. Therefore, we can estimate flat areas of the target surface precisely, whereas the measurement accuracy could be degraded in areas where the assumption is violated, because of a curved surface or sharp steps. In this paper, we propose to overcome this problem by weighting the contribution of the pixels according to the degree of satisfaction of the locally flat assumption. However, since we have no information on the surface profile beforehand, we iteratively estimate it and use this estimation result to determine the weights. This algorithm is named the iteratively-reweighted LMF (IRLMF) method. Experimental results show that the proposed algorithm works excellently.