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Abstract Background Surgical resection is standard treatment for invasive intraductal papillary mucinous carcinoma (IPMC); however, impact of multidisciplinary treatment on survival including postoperative adjuvant therapy (AT), neoadjuvant therapy (NAT), and treatment for recurrent lesions is unclear. We investigated the effectiveness of multidisciplinary treatment in prolonging survival of patients with invasive IPMC. Methods This retrospective multi‐institutional study included 1183 patients with invasive IPMC undergoing surgery at 40 academic institutions. We analyzed the effects of AT, NAT, and treatment for recurrence on survival of patients with invasive IPMC. Results Completion of the planned postoperative AT for 6 months improved the overall survival (OS), disease‐specific survival (DSS), and recurrence‐free survival (RFS) of patients with stage IIB and stage III resected invasive IPMC, elevated preoperative carbohydrate antigen 19–9 level, lymphovascular invasion, perineural invasion, serosal invasion, and lymph node metastasis on un‐matched and matched analyses. Of the patients with borderline resectable (BR) invasive IPMC, the OS (p = 0.001), DSS (p = 0.001), and RFS (p = 0.001) of patients undergoing NAT was longer than that of those without on the matched analysis. Of the 484 invasive IPMC patients (40.9%) who developed recurrence after surgery, the OS of 365 patients who received any treatment for recurrence was longer than that of those without treatment (40.6 vs. 22.4 months, p

Abstract The differentiation of B cells into plasma cells is associated with substantial transcriptional and epigenetic remodeling. H3.3 histone variant marks active chromatin via replication-independent nucleosome assembly. However, its role in plasma cell development remains elusive. Herein, we show that during plasma cell differentiation, H3.3 is downregulated, and the deposition of H3.3 and chromatin accessibility are dynamically changed. Blockade of H3.3 downregulation by enforced H3.3 expression impairs plasma cell differentiation in an H3.3-specific sequence-dependent manner. Mechanistically, enforced H3.3 expression inhibits the upregulation of plasma cell-associated genes such as Irf4, Prdm1, and Xbp1 and maintains the expression of B cell-associated genes, Pax5, Bach2, and Bcl6. Concomitantly, sustained H3.3 expression prevents the structure of chromatin accessibility characteristic for plasma cells. Our findings suggest that appropriate H3.3 expression and deposition control plasma cell differentiation.

Abstract The capability of focus control has been central to optical technologies that require both high temporal and spatial resolutions. However, existing varifocal lens schemes are commonly limited to the response time on the microsecond timescale and share the fundamental trade-off between the response time and the tuning power. Here, we propose an ultrafast holographic focusing method enabled by translating the speed of a fast 1D beam scanner into the speed of the complex wavefront modulation of a relatively slow 2D spatial light modulator. Using a pair of a digital micromirror device and a resonant scanner, we demonstrate an unprecedented refresh rate of focus control of 31 MHz, which is more than 1,000 times faster than the switching rate of a digital micromirror device. We also show that multiple micrometer-sized focal spots can be independently addressed in a range of over 1 MHz within a large volume of 5 mm × 5 mm × 5.5 mm, validating the superior spatiotemporal characteristics of the proposed technique – high temporal and spatial precision, high tuning power, and random accessibility in a three-dimensional space. The demonstrated scheme offers a new route towards three-dimensional light manipulation in the 100 MHz regime.

Summary: Background: Gallbladder cancer (GBC) is rare but aggressive. The extent of surgical intervention for different GBC stages is non-uniform, ranging from cholecystectomy alone to extended resections including major hepatectomy, resection of adjacent organs and routine extrahepatic bile duct resection (EBDR). Robust evidence here is lacking, however, and survival benefit poorly defined. This study assesses factors associated with recurrence-free survival (RFS), overall survival (OS) and morbidity and mortality following GBC surgery in high income countries (HIC) and low and middle income countries (LMIC). Methods: The multicentre, retrospective Operative Management of Gallbladder Cancer (OMEGA) cohort study included all patients who underwent GBC resection across 133 centres between 1st January 2010 and 31st December 2020. Regression analyses assessed factors associated with OS, RFS and morbidity. Findings: On multivariable analysis of all 3676 patients, wedge resection and segment IVb/V resection failed to improve RFS (HR 1.04 [0.84–1.29], p = 0.711 and HR 1.18 [0.95–1.46], p = 0.13 respectively) or OS (HR 0.96 [0.79–1.17], p = 0.67 and HR 1.48 [1.16–1.88], p = 0.49 respectively), while major hepatectomy was associated with worse RFS (HR 1.33 [1.02–1.74], p = 0.037) and OS (HR 1.26 [1.03–1.53], p = 0.022). Furthermore, EBDR (OR 2.86 [2.3–3.52], p

Abstract Background Gallbladder cancer (GBC) with liver metastasis is considered unresectable. However, there have been infrequent reports of long-term survival in patients with GBC and liver metastases. Therefore, we examined the characteristics of long-term survivors of gallbladder cancer with liver metastasis. Methods A retrospective multicenter study of 462 patients with GBC (mean age, 71 years; female, 51%) was performed. Although patients with pre-operatively diagnosed GBC and liver metastasis were generally excluded from resection, some cases identified during surgery were resected. Result In patients with resected stage III/IV GBC (n = 193), the period 2007–2013 (vs. 2000–2006, hazard ratio 0.63), pre-operative jaundice (hazard ratio 1.70), ≥ 2 liver metastases (vs. no liver metastasis, hazard ratio 2.11), and metastasis to the peritoneum (vs. no peritoneal metastasis, hazard ratio 2.08) were independent prognostic factors for overall survival, whereas one liver metastasis (vs. no liver metastasis) was not. When examining the 5-year overall survival and median survival times by liver metastasis in patients without peritoneal metastasis or pre-operative jaundice, those with one liver metastasis (63.5%, not reached) were comparable to those without liver metastasis (40.4%, 33.0 months), and was better than those with ≥ 2 liver metastases although there was no statistical difference (16.7%, 9.0 months). According to the univariate analysis of resected patients with GBC and liver metastases (n = 26), minor hepatectomy, less blood loss, less surgery time, papillary adenocarcinoma, and T2 were significantly associated with longer survival. Morbidity of Clavien–Dindo classification ≤ 2 and received adjuvant chemotherapy were marginally not significant. Long-term survivors (n = 5) had a high frequency of T2 tumors (4/5), had small liver metastases near the gallbladder during or after surgery, underwent minor hepatectomy without postoperative complications, and received postoperative adjuvant chemotherapy. Conclusions Although there is no surgical indication for GBC with liver metastasis diagnosed pre-operatively, minor hepatectomy and postoperative chemotherapy may be an option for selected patients with T2 GBC and liver metastasis identified during or after surgery who do not have other poor prognostic factors.

Abstract Background Ring calcification in hepatocellular carcinoma is extremely rare. Untreated hepatocellular carcinoma occasionally includes calcified lesions. Here, we report a case of ring-calcified hepatocellular carcinoma. Case presentation A 60-year-old man with a hepatic tumor was referred to Tokyo Women’s Medical University Hospital. He had a history of chronic hepatitis C. Computed tomography showed a liver tumor 20 mm in diameter in segment 6 of the Couinaud classification, with ring calcification. Based on this uncommon imaging presentation and the patient’s past exposure to the definitive hosts of Echinococcus multilocularis, he was preoperatively diagnosed with echinococcosis. Partial hepatectomy was performed as a radical treatment for echinococcosis. A final diagnosis of hepatocellular carcinoma was confirmed based on pathological findings. The patient was discharged uneventfully. Conclusion The presentation of an extremely rare hepatocellular carcinoma with ring calcification may be disguised as hydatid disease.

The subloading surface model has been formulated and applied to the prediction of cyclic loading behavior of metals. However, the existing formulation of this model is limited to metals exhibiting only the cyclic hardening. In the present paper, the material functions prescribing the elastic-plastic transition are extended so as to describe the inverse and reloading behavior and the strain accumulation in cyclic loading more accurately for metals exhibiting not only the cyclic hardening but also the cyclic softening behavior. The experiments on the uniaxial cyclic loading of the seamless steel pipe P110 which exhibits the cyclic softening are performed for the mechanical ratcheting and the constant strain amplitudes. The simulations to the test data are performed by using the same set of material constants. Then, the validity of the extended model for the description of cyclic loading behavior of the seamless steel pipe is verified by comparisons with the test data.

The capability of focus control has been central to optical technologies that require both high temporal and spatial resolutions. However, existing varifocal lens schemes are commonly limited to the response time on the microsecond timescale and share the fundamental trade-off between the response time and the tuning power. Here, we propose an ultrafast holographic focusing method enabled by translating the speed of a fast 1D beam scanner into the speed of the complex wavefront modulation of a relatively slow 2D spatial light modulator. Using a pair of a digital micromirror device and a resonant scanner, we demonstrate an unprecedented refresh rate of focus control of 31 MHz, which is more than 1,000 times faster than the switching rate of a digital micromirror device. We also show that multiple micrometer-sized focal spots can be independently addressed in a range of over 1 MHz within a large volume of 5 mm × 5 mm × 5.5 mm, validating the superior spatiotemporal characteristics of the proposed technique – high temporal and spatial precision, high tuning power, and random accessibility in a three-dimensional space. The demonstrated scheme offers a new route towards three-dimensional light manipulation in the 100 MHz regime. [ABSTRACT FROM AUTHOR]

Background: Distal pancreatectomy with en bloc coeliac axis resection (DP-CAR) for pancreatic body cancer has been reported increasingly. However, its large-scale outcomes remain undocumented. This study aimed to evaluate DP-CAR volume and mortality, preoperative arterial embolization for ischaemic gastropathy, the oncological benefit for resectable tumours close to the bifurcation of the splenic artery and coeliac artery using propensity score matching, and prognostic factors in DP-CAR. Methods: In a multi-institutional analysis, 626 DP-CARs were analysed retrospectively and compared with 1325 distal pancreatectomies undertaken in the same interval. Results: Ninety-day mortality was observed in 7 of 21 high-volume centres (1 or more DP-CARs per year) and 1 of 41 low-volume centres (OR 20.00, 95 per cent c.i. 2.26 to 177.26). The incidence of ischaemic gastropathy was 19.2 per cent in the embolization group and 7.9 per cent in the no-embolization group (OR 2.77, 1.48 to 5.19). Propensity score matching analysis showed that median overall survival was 33.5 (95 per cent c.i. 27.4 to 42.0) months in the DP-CAR and 37.9 (32.8 to 53.3) months in the DP group. Multivariable analysis identified age at least 67 years (HR 1.40, 95 per cent c.i. 1.12 to 1.75), preoperative tumour size 30 mm or more (HR 1.42, 1.12 to 1.80), and preoperative carbohydrate antigen 19-9 level over 37 units/ml (HR 1.43, 1.11 to 1.83) as adverse prognostic factors. Conclusion: DP-CAR can be performed safely in centres for general pancreatic surgery regardless of DP-CAR volume, and preoperative embolization may not be required. This procedure has no oncological advantage for resectable tumour close to the bifurcation of the splenic artery, and should be performed after appropriate patient selection. [ABSTRACT FROM AUTHOR]

Abstract Background/purpose  Natural orifice translumenal endoscopic surgery (NOTES) is a novel concept using an endoscope via a translumenal access for abdominal surgery. This study was designed to evaluate the feasibility and technical aspects of NOTES cholecystectomy from our experience on humans and animals. Methods  NOTES cholecystectomies were performed in 12 animal experiments, including 8 pigs (6 by transgastric and 2 by transvaginal accesses) and 4 dogs (4 transvaginal accesses), and a human female cadaver. Results  The entire gallbladder could be removed under direct vision in all experiments. The average time was 60 min by transgastric and 40 min by transvaginal in animals. It was 87 min for human transvaginal cholecystectomy. In all animal and human procedures, there was no major complication concerning the operation. Discussion  The transvaginal route may be the easiest route for abdominal NOTES. Percutaneous endoscopic gastrostomy (PEG) allowed the safe performance of a controlled gastric perforation and shortened the time. The hybrid method allowed performance of a safe procedure and shortened the time. Conclusions  Transvaginal and transgastric NOTES cholecystectomy is technically feasible and safe in both humans and animals. New instrumentation needs to be developed to perform a pure NOTES cholecystectomy without transabdominal assistance. [ABSTRACT FROM AUTHOR]