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Asymptotic expansion in far-field for the incompressible Navier–Stokes flow are established. It is well known that a velocity decays slowly in far-field. This property prevents classical procedure giving asymptotic expansions of solutions with high-order. In this paper, under natural settings and moment conditions on the initial vorticity, technique of renormalization together with Biot–Savart law derives an asymptotic expansion for velocity with high-order. Especially scalings and large-time behaviors of the expansions are clarified. By employing them, time evolution of velocity in far-field is drawn. As an appendix, asymptotic behavior of solutions as time variable tends to infinity is given. In this assertion, large-time behavior of velocity is discovered clearly.

Analysis of operative data with convolutional neural networks (CNNs) is expected to improve the knowledge and professional skills of surgeons. Identification of objects in videos recorded during surgery can be used for surgical skill assessment and surgical navigation. The objectives of this study were to recognize objects and types of forceps in surgical videos acquired during colorectal surgeries and evaluate detection accuracy. Images (n = 1818) were extracted from 11 surgical videos for model training, and another 500 images were extracted from 6 additional videos for validation. The following 5 types of forceps were selected for annotation: ultrasonic scalpel, grasping, clip, angled (Maryland and right-angled), and spatula. IBM Visual Insights software was used, which incorporates the most popular open-source deep-learning CNN frameworks. In total, 1039/1062 (97.8%) forceps were correctly identified among 500 test images. Calculated recall and precision values were as follows: grasping forceps, 98.1% and 98.0%; ultrasonic scalpel, 99.4% and 93.9%; clip forceps, 96.2% and 92.7%; angled forceps, 94.9% and 100%; and spatula forceps, 98.1% and 94.5%, respectively. Forceps recognition can be achieved with high accuracy using deep-learning models, providing the opportunity to evaluate how forceps are used in various operations.

Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal-dominant disorder characterized by progressive and profoundly disabling heterotopic ossification (HO). Here we show that fibro/adipogenic progenitors (FAPs) are a major cell-of-origin of HO in an accurate genetic mouse model of FOP ( Acvr1 tnR206H ). Targeted expression of the disease-causing type I bone morphogenetic protein (BMP) receptor, ACVR1(R206H), to FAPs recapitulates the full spectrum of HO observed in FOP patients. ACVR1(R206H)-expressing FAPs, but not wild-type FAPs, activate osteogenic signaling in response to activin ligands. Conditional loss of the wild-type Acvr1 allele dramatically exacerbates FAP-directed HO, suggesting that mutant and wild-type ACVR1 receptor complexes compete for activin ligands or type II BMP receptor binding partners. Finally, systemic inhibition of activin A completely blocks HO and restores wild-type-like behavior to transplanted Acvr1 R206H/+ FAPs. Understanding the cells that drive HO may facilitate the development of cell-specific therapeutic approaches to inhibit catastrophic bone formation in FOP. Fibrodysplasia ossificans progressiva is a severe disorder characterized by heterotopic ossification, and is caused by mutations in ACVR1. Here, the authors show that expression of mutant ACVR1 in fibro/adipogenic progenitors recapitulates disease progression, and that this can be halted by systemic inhibition of activin A in mice.

Intraductal papillary mucinous neoplasm (IPMN) is a common pancreatic cystic neoplasm that is often invasive and metastatic, resulting in a poor prognosis. Few molecular alterations unique to IPMN are known. We performed whole-exome sequencing for a primary IPMN tissue, which uncovered somatic mutations in KCNF1, DYNC1H1, PGCP, STAB1, PTPRM, PRPF8, RNASE3, SPHKAP, MLXIPL, VPS13C, PRCC, GNAS, KRAS, RBM10, RNF43, DOCK2 and CENPF . We further analyzed GNAS mutations in archival cases of 118 IPMNs and 32 pancreatic ductal adenocarcinomas (PDAs), which revealed that 48 (40.7%) of the 118 IPMNs but none of the 32 PDAs harbored GNAS mutations. G-protein alpha-subunit encoded by GNAS and its downstream targets, phosphorylated substrates of protein kinase A, were evidently expressed in IPMN; the latter was associated with neoplastic grade. These results indicate that GNAS mutations are common and specific for IPMN and activation of G-protein signaling appears to play a pivotal role in IPMN.

BackgroundTo date, postoperative prognostic factors for intraductal papillary neoplasm of the bile duct (IPNB) have not been well-established. This study aimed to examine the histopathologic features and postoperative prognosis of the two IPNB subclassifications, as well as factors affecting prognosis, based on the authors’ experience at a single institution.MethodsThe study enrolled 83 patients who underwent surgical resection for pathologically diagnosed IPNB at the authors’ institution. The clinicopathologic features and postoperative outcomes for these patients were examined. The study also investigated postoperative prognostic factors for IPNB using uni- and multivariate analyses.ResultsMore than half of the tumors (64%) diagnosed as IPNB were early-stage cancer (UICC Tis or T1). However, none were diagnosed as benign. The multivariate analysis showed that lymph node metastasis (hazard ratio [HR], 5.78; p = 0.002) and bile duct margin status with carcinoma in situ (D-CIS; HR, 5.10; p = 0.002) were independent prognostic factors, whereas MUC6 expression showed only a marginal influence on prediction of prognosis (HR, 0.32; p = 0.07). The tumor recurrence rate and the proportion of locoregional recurrence were significantly greater among the patients with D-CIS than among those with negative bile duct margins, including those patients with low-grade dysplasia. The patients with D-CIS showed a significantly poorer prognosis than those with negative bile duct margins (5-year survival, 38% versus 87%; p = 0.0002).ConclusionsEvaluation of resected IPNBs showed cancer in all cases. Avoiding positive biliary stumps during surgery, including resection of carcinoma in situ, would improve the prognosis for patients with IPNB.

Background Non-occlusive mesenteric ischemia (NOMI) has a high mortality rate, but the analyses of preoperative prognostic factors for improving survival in patients suspected of having NOMI are scarce. We aimed to analyze the prognostic factors of preoperative examinations for NOMI. Methods The clinical data of 224 patients with NOMI were retrospectively collected for a multicenter survey. Clinicophysiological factors were compared between the survivors and non-survivors ( N  = 107/117) and between the operative and non-operative cases ( N  = 180/44) by univariate analysis using chi-square test and multivariate analysis using Cox proportional hazard models. In the operative cases, the prognostic operative factors were also analyzed. Results The overall mortality rate for NOMI was 52.2%. There were 129 male and 95 female patients. The mean age was 71.23 (14–94) years. Univariate analysis showed that cardiovascular complication, shock, abdominal pain, average blood pressure, systemic inflammatory response syndrome, aspartic aminotransferase, alanine transaminase, creatine phosphokinase, lactate dehydrogenase, base excess, prothrombin time-international normalized ratio, D-dimer, and fibrinogen degradation products were independent prognostic factors. Multivariate analysis showed that average blood pressure and base excess were independent prognostic factors. Among patients undergoing surgery, those with bowel resection had better prognosis than those without bowel resection, but those with long bowel resection had worse prognosis than those with short resection. Additional postoperative treatment was not effective compared with operation alone ( P  = 0.011). Conclusions Prognostic factors of preoperative examinations for NOMI were average blood pressure and base excess. Patients with long bowel resection should be carefully monitored owing to their poor prognosis.

Mutations in genes of the breast cancer susceptibility gene (BRCA) pathway, namely, BRCA1 , BRCA2 , and PALB2 , can provide useful information for the efficacy of platinum-based or poly ADP-ribose polymerase inhibitors chemotherapeutic regimens. Pancreatic ductal adenocarcinoma (PDAC) is an important target for such precision chemotherapies because of its dismal prognosis. We analyzed mutations in the entire coding regions of the BRCA pathway genes, expression of breast cancer 2 (BRCA2), and mutations in hotspots of 50 cancer-associated genes in 42 surgically resected PDACs, and evaluated their associations with clinicopathological features. We identified 13 rare germline mutations in the BRCA pathway genes; 68 somatic mutations in KRAS , TP53 , SMAD4 , CDKN2A , GNAS , SMARCB1 , and RB1 ; and 2 germline variations in MLH1 . Among them, BRCA2 S2148fs was known to be pathogenic. BRCA2 R18H and BRCA2 G2044V were enriched in tumor tissues. BRCA2 K799R and BRCA2 R2964T were novel germline variations. Patients harboring potentially deleterious mutations in the BRCA pathway genes showed significantly better prognosis than those with benign mutations or no mutation. These results indicate that rare germline variations in BRCA pathway genes could be found more frequently than previously anticipated and, more importantly, potentially deleterious mutations of them could be a favorable prognostic factor in patients with resectable PDACs.

PurposeTo investigate the risk factors for post-pancreatectomy hemorrhage (PPH).MethodsThe incidence, outcome, and risk factors for PPH were evaluated in 1169 patients who underwent pancreatectomy.ResultsThe incidence and mortality rates of PPH were 3% and 11% in all pancreatectomies, 4% and 11% in pancreatoduodenectomy, 1% and 20% in distal pancreatectomy, and 3% and 0% in total pancreatectomy, respectively. Male sex [odds ratio (OR) 2.32], body mass index (BMI) ≥ 25 kg/m2 (OR 3.70), absence of diabetes mellitus (DM; HbA1c ≤ 6.2%; OR 3.62), and pancreatoduodenectomy (OR 3.06) were risk factors for PPH after all pancreatectomies. The PPH incidence was 0%, 1%, 2%, 6%, and 20% in patients with risk scores of 0 (n = 65), 1 (n = 325), 2 (n = 455), 3 (n = 299), and 4 (n = 25), respectively. The differences between risk-score groups 0–2 (2%) and 3–4 (7%) were significant (P < 0.05, OR 4.7). In patients who had undergone pancreatoduodenectomy, postoperative pancreatic fistula (POPF; OR 31.7) and absence of DM (OR 3.45) were risk factors for PPH. There was no significant association between POPF and PPH after distal pancreatectomy (P = 0.28). The incidence of POPF post-pancreatoduodenectomy was 20%. BMI ≥ 25 kg/m2 (OR 3.17), serum albumin < 3.5 g/dl (OR 1.77), absence of DM (OR 1.75), distal extrahepatic bile duct carcinoma (OR 4.05), and carcinoma of the papilla of Vater (OR 5.19) were risk factors for POPF post-pancreatoduodenectomy.ConclusionOur study clarified the preoperative risk factors for PPH and recommends using a risk scoring system that includes “absence of DM” for predicting PPH.

PurposeArtificial intelligence-enabled techniques can process large amounts of surgical data and may be utilized for clinical decision support to recognize or forecast adverse events in an actual intraoperative scenario. To develop an image-guided navigation technology that will help in surgical education, we explored the performance of a convolutional neural network (CNN)-based computer vision system in detecting intraoperative objects.MethodsThe surgical videos used for annotation were recorded during surgeries conducted in the Department of Surgery of Tokyo Women’s Medical University from 2019 to 2020. Abdominal endoscopic images were cut out from manually captured surgical videos. An open-source programming framework for CNN was used to design a model that could recognize and segment objects in real time through IBM Visual Insights. The model was used to detect the GI tract, blood, vessels, uterus, forceps, ports, gauze and clips in the surgical images.ResultsThe accuracy, precision and recall of the model were 83%, 80% and 92%, respectively. The mean average precision (mAP), the calculated mean of the precision for each object, was 91%. Among surgical tools, the highest recall and precision of 96.3% and 97.9%, respectively, were achieved for forceps. Among the anatomical structures, the highest recall and precision of 92.9% and 91.3%, respectively, were achieved for the GI tract.ConclusionThe proposed model could detect objects in operative images with high accuracy, highlighting the possibility of using AI-based object recognition techniques for intraoperative navigation. Real-time object recognition will play a major role in navigation surgery and surgical education.

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder characterized by debilitating heterotopic ossification (HO). The retinoic acid receptor gamma agonist, palovarotene, and antibody-mediated activin A blockade have entered human clinical trials, but how these therapeutic modalities affect the behavior of pathogenic fibro/adipogenic progenitors (FAPs) is unclear. Using live-animal luminescence imaging, we show that transplanted pathogenic FAPs undergo rapid initial expansion, with peak number strongly correlating with HO severity. Palovarotene significantly reduced expansion of pathogenic FAPs, but was less effective than activin A inhibition, which restored wild-type population growth dynamics to FAPs. Palovarotene pretreatment did not reduce FAPs’ skeletogenic potential, indicating that efficacy requires chronic administration. Although palovarotene inhibited chondrogenic differentiation in vitro and reduced HO in juvenile FOP mice, daily dosing resulted in aggressive synovial joint overgrowth and long bone growth plate ablation. These results highlight the challenge of inhibiting pathological bone formation prior to skeletal maturation.