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Purpose: Acoustic radiation force impulse (ARFI) elastography and contrast-enhanced ultrasonography (CEUS) are emerging techniques that are becoming common in ultrasound examinations. We previously reported that ARFI (push pulse) induced lung hemorrhage in rabbits, indicating that greater risks are associated with ARFI than with conventional ultrasound. In this study, we assessed the risk of lung hemorrhage under a combination of ARFI elastography and CEUS, considering potential exacerbation of ARFI-induced lung hemorrhage as a result of the ultrasound contrast agent (UCA) used in CEUS., Methods: Twenty-three rabbits were divided into non-UCA and UCA groups. ARFI exposure parameters were set at six mechanical index (MI) levels (0.29, 0.45, 0.60, 0.88, 1.0, 1.39) in non-UCA groups and five MI levels (0.29, 0.66, 0.88, 0.97, 1.25) in UCA groups. Lung exposure was performed bilaterally through the intercostal space in each rabbit. Lung damage was assessed through macroscopic and microscopic observation post euthanasia., Results: Lung hemorrhage was detected at MI 0.3 levels of 0.88 or higher. Logistic regression analyses showed that MI 0.3 was a statistically significant factor for occurrence of lung hemorrhage in both non-UCA and UCA groups, and the MI 0.3 threshold (ED 05 ) for inducing lung hemorrhage was 0.68 and 0.71, respectively. However, multivariate logistic regression and linear regression analyses across all samples indicated that UCA did not significantly affect the occurrence or area of lung hemorrhage., Conclusion: This study demonstrates that UCA does not significantly worsen ARFI-induced lung hemorrhage in terms of occurrence or severity. However, risks and benefits of ARFI elastography on the lung should be considered, irrespective of UCA administration., Competing Interests: Declarations Conflict of interest The authors declare that they do not have any conflict of interest. Ethical approval All institutional and national guidelines for the care and use of laboratory animals were followed., (© 2024. The Author(s), under exclusive licence to The Japan Society of Ultrasonics in Medicine.)

Background: Globally, prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing, and there is an urgent need to develop innovative therapies that promote liver regeneration following hepatectomy for this disease. Surgical excision is a key therapeutic approach with curative potential for liver tumors. However, hepatic steatosis can lead to delayed liver regeneration and higher post-operative complication risk. Mesenchymal stem cells-conditioned medium (MSC-CM) is considered a rich source of paracrine factors that can repair tissues and restore function of damaged organs. Meanwhile, hydrogels have been widely recognized to load MSC secretome and achieve sustained release. This study aimed to evaluate the therapeutic effect of hydrogel-encapsulated MSC-CM on liver regeneration following partial hepatectomy (PHx) in a rodent model of diet-induced hepatic steatosis., Methods: Male Lewis rats were fed with a methionine and choline-deficient diet. After 3 weeks of feeding, PHx was performed and rats were randomly allocated into two groups that received hydrogel-encapsulated MSC-CM or vehicle via the intra-mesenteric space of the superior mesenteric vein (SMV)., Results: The regeneration of the remnant liver at 30 and 168 h after PHx was significantly accelerated, and the expressions of proliferating cell nuclear antigen were significantly enhanced in the MSC-CM group. MSC-CM treatment significantly increased hepatic ATP and β-hydroxybutyrate content at 168 h after PHx, indicating that MSC-CM fosters regeneration not only in volume but also in functionality. The number of each TUNEL- and cleaved caspase-3 positive nuclei in hepatocytes at 9 h after PHx were significantly decreased in the MSC-CM group, suggesting that MSC-CM suppressed apoptosis. MSC-CM increased serum immunoregulatory cytokine interleukin-10 and interleukin-13 at 30 h after PHx. Additionally, mitotic figures and cyclin D1 expression decreased and hepatocyte size increased in the MSC-CM group, implying that this mode of regeneration was mainly through cell hypertrophy rather than cell division., Conclusions: MSC-CM represents a novel therapeutic approach for patients with MASLD requiring PHx., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

RNA-DNA hybrid is a part of the R-loop which is an important non-standard nucleic acid structure. RNA-DNA hybrid/R-loop causes genomic instability by inducing DNA damages or inhibiting DNA replication. It also plays biologically important roles in regulation of transcription, replication, recombination and repair. Here, we have employed catalytically inactive human RNase H1 mutant (D145N) to visualize RNA-DNA hybrids and map their genomic locations in fission yeast cells. The RNA-DNA hybrids appear as multiple nuclear foci in rnh1∆rnh201∆ cells lacking cellular RNase H activity, but not in the wild-type. The majority of RNA-DNA hybrid loci are detected at the protein coding regions and tRNA. In rnh1∆rnh201∆ cells, cells with multiple Rad52 foci increase during S-phase and about 20% of the RNA-DNA hybrids overlap with Rad52 loci. During S-phase, more robust association of Rad52 with RNA-DNA hybrids was observed in the protein coding region than in M-phase. These results suggest that persistent RNA-DNA hybrids in the protein coding region in rnh1∆rnh201∆ cells generate DNA damages during S-phase, potentially through collision with DNA replication forks., (© 2024 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.)

Background: This study aimed to morphologically and histologically examine whether pig is useful as models for rotator cuff tear (RCT)., Methods: The morphology of the scapula and humerus bones was evaluated by taking X-ray and three-dimensional computed tomography (3D CT) scans of the right shoulders of five female pigs (age: 4 months). The rotator cuff (RC) footprint at the humeral insertion of these was observed and its shape was measured. Next, they underwent general anesthesia and an acute rotator cuff tear/rotator cuff repair (RCT/RCR) model was created using a deltoid split approach. Four weeks after surgery, the animals were euthanized, the shoulder joints were harvested, and the repaired RC was evaluated by hematoxylin and eosin staining and toluidine blue staining., Results: The scapula of the pig had a vestigial acromion, in contrast to that in humans. The supraspinatus and infraspinatus tendons were connected so as to overlap each other and attached to the postero-superior part of the greater tuberosity. These tendons were located extra-articularly, separate from the joint capsule. The average antero-posterior length of the foot print was 17.4 ± 0.7 mm on the medial margin and 19.1 ± 2.2 mm on the lateral margin. The maximum medial-to-lateral width of it was 5.1 ± 0.5 mm. In all RCT/RCR models at 4 weeks after surgery, the repaired RC compound tendon was visually confirmed to be continuous with the footprint. Histologically, it was confirmed that regeneration of the four-layer structure of the bone-tendon junction had occurred., Conclusion: Porcine supraspinatus and infraspinatus attachment to the greater tuberosity have a structure similar to that of sheep and dogs, which is advantageous for creating the RCT/RCR model. It might be used for future in vivo studies of shoulder joint diseases., The Translational Potential of This Article: Pigs could potentially serve as a viable model for rotator cuff tears., Competing Interests: Declaration of competing interest The authors have no conflicts of interest directly relevant to the content of this article., (Copyright © 2023 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

A 50-year-old man was diagnosed with type 1 autoimmune pancreatitis (AIP) following endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) and a histopathological examination. After six months of untreated follow-up, the serum IgG4 level decreased, and the diffuse pancreatic enlargement improved; however, a pancreatic head mass became apparent. EUS-FNA of this mass revealed pancreatic ductal adenocarcinoma (PDAC) with IgG4-positive plasma cells. In addition, the resected specimen revealed PDAC, without any features of AIP. After pancreatoduodenectomy, AIP did not recur. The development of AIP in this case could be related to paraneoplastic syndrome.

Objective: This study aimed to clarify the molecular mechanism of remnant pancreatic cancer (PC) development after primary PC resection., Summary Background Data: Molecular mechanisms of the development of remnant PCs following primary PC resection are largely unknown., Methods: Forty-three patients undergoing remnant PC resection after primary PC resection between 2001 and 2017 at 26 institutes were retrospectively analyzed. Clinicopathological features and molecular alterations detected by targeted amplicon sequencing of 36 PC-associated genes were evaluated., Results: These patients showed significantly lower body mass indices and higher hemoglobin A1c values at remnant PC resection than at primary PC resection. A comparison of the molecular features between primary and remnant PCs indicated that remnant PCs were likely to develop via three different molecular pathways: successional, showing identical and accumulated alterations (n=14); phylogenic, showing identical and distinct alterations (n=26); and distinct, showing independent distinctive alterations (n=3). The similarity of gene alterations was associated with time to the remnant PC development (r=－0.384, P=0.0173). Phylogenic pathways were significantly associated with the intraductal spread of carcinoma (P=0.007). Patient survival did not differ significantly depending on these molecular pathways., Conclusion: Molecular profiling uncovered three pathways for the development of remnant PCs, namely, successional, phylogenic, and distinct pathways. The vast majority of remnant PCs are likely to be molecularly associated with primary PCs either in the successional or phylogenic way. This information could impact the design of a strategy for monitoring and treating remnant PCs., Competing Interests: Disclosures: All authors disclose no personal and financial conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The prognosis of patients with peritoneal metastases from pancreatic cancer is poor, largely due to massive ascites, which precludes systemic treatment. Two patients with a poor performance status and malignant ascites were treated with cell-free and concentrated ascites reinfusion therapy followed by combined chemotherapy with intraperitoneal paclitaxel, intravenous gemcitabine, and nab-paclitaxel. These patients achieved a survival of 19 and 36 weeks with a relatively good quality of life. Combined intraperitoneal paclitaxel and systemic chemotherapy may provide effective palliative management for some patients with peritoneal metastases from pancreatic cancer.

Background: Osteopenia is a well-known risk factor for survival in patients with hepatocellular carcinoma; however, it is unclear whether osteopenia can apply to both genders and how osteopenia is associated with cancer progression. The aim of this study was to elucidate whether osteopenia predicts reduced survival in regression models in both genders and whether osteopenia is associated with the pathological factors associated with reduced survival., Methods: This study included 188 consecutive patients who underwent hepatectomy. Bone mineral density was assessed using computed tomography (CT) scan images taken within 3 months before surgery. Non-contrast CT scan images at the level of the 11th thoracic vertebra were used. The cutoff value of osteopenia was calculated using a threshold value of 160 Hounsfield units. Overall survival (OS) curves and recurrence-free survival (RFS) were constructed using the Kaplan-Meier method, as was a log-rank test for survival. The hazard ratio and 95% confidence interval for overall survival were calculated using Cox's proportional hazard model., Results: In the regression analysis, age predicted bone mineral density. The association in females was greater than that in males. The OS and RFS of osteopenia patients were shorter than those for non-osteopenia patients. According to univariate and multivariate analyses, osteopenia was an independent risk factor for OS and RFS. The sole pathological factor associated with osteopenia was microvascular portal vein invasion., Conclusion: Models suggest that osteopenia may predict decreased OS and RFS in patients undergoing resection of hepatocellular carcinoma due to the mechanisms mediated via microvascular portal vein invasion.

RecA protein and RecA/Rad51 orthologues are required for homologous recombination and DNA repair in all living creatures. RecA/Rad51 catalyzes formation of the D-loop, an obligatory recombination intermediate, through an ATP-dependent reaction consisting of two phases: homology recognition between double-stranded (ds)DNA and single-stranded (ss)DNA to form a hybrid-duplex core of 6-8 base pairs and subsequent hybrid-duplex/D-loop processing. How dsDNA recognizes homologous ssDNA is controversial. The aromatic residue at the tip of the β-hairpin loop (L2) was shown to stabilize dsDNA-strand separation. We tested a model in which dsDNA strands were separated by the aromatic residue before homology recognition and found that the aromatic residue was not essential to homology recognition, but was required for D-loop processing. Contrary to the model, we found that the double helix was not unwound even a single turn during search for sequence homology, but rather was unwound only after the homologous sequence was recognized. These results suggest that dsDNA recognizes its homologous ssDNA before strand separation. The search for homologous sequence with homologous ssDNA without dsDNA-strand separation does not generate stress within the dsDNA; this would be an advantage for dsDNA to express homology-dependent functions in vivo and also in vitro., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

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  < 0.001)., Conclusion: Postoperative AT might benefit selected patients with invasive IPMC, especially those at high risk of poor survival. NAT might improve the survivability of BR invasive IPMC. Any treatment for recurrence after surgery for invasive IPMC might improve survival., Competing Interests: Author SH was supported by grants from the Japan Pancreas Society. Author MU was supported by grants from Taiho Pharma, however, the funding source had no role in the design, practice, or analysis of this study. Author SS was supported by grants from Nihon Servier, Amino‐Up co, however, the funding source had no role in the design, practice, or analysis of this study. Authors HN, KH, and HY are editorial board members of Annals of Gastroenterological Surgery. Authors SH, IE, and AH are associate editors of Annals of Gastroenterological Surgery., (© 2024 The Authors. Annals of Gastroenterological Surgery published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Gastroenterological Surgery.)

Intestinal adaptation does not necessarily recover absorptive capacity in short bowel syndrome (SBS), sometimes resulting in intestinal failure-associated liver disease (IFALD). Additionally, its therapeutic options remain limited. Polyamines (spermidine and spermine) are known as one of the autophagy inducers and play important roles in promoting the weaning process; however, their impact on intestinal adaptation is unknown. The aim of this study was to investigate the impact of polyamines ingestion on adaptation and hepatic lipid metabolism in SBS. We performed resection of two-thirds of the small intestine in male Lewis rats as an SBS model. They were allocated into three groups and fed different polyamine content diets (0%, 0.01%, 0.1%) for 30 days. Polyamines were confirmed to distribute to remnant intestine, whole blood, and liver. Villous height and number of Ki-67-positive cells in the crypt area increased with the high polyamine diet. Polyamines increased secretory IgA and mucin content in feces, and enhanced tissue Claudin-3 expression. In contrast, polyamines augmented albumin synthesis, mitochondrial DNA copy number, and ATP storage in the liver. Moreover, polyamines promoted autophagy flux and activated AMP-activated protein kinase with suppression of lipogenic gene expression. Polyamines ingestion may provide a new therapeutic option for SBS with IFALD., (© 2024. The Author(s).)

Acetaldehyde, a chemical that can cause DNA damage and contribute to cancer, is prevalently present in our environment, e.g. in alcohol, tobacco, and food. Although aldehyde potentially promotes crosslinking reactions among biological substances including DNA, RNA, and protein, it remains unclear what types of DNA damage are caused by acetaldehyde and how they are repaired. In this study, we explored mechanisms involved in the repair of acetaldehyde-induced DNA damage by examining the cellular sensitivity to acetaldehyde in the collection of human TK6 mutant deficient in each genome maintenance system. Among the mutants, mismatch repair mutants did not show hypersensitivity to acetaldehyde, while mutants deficient in base and nucleotide excision repair pathways or homologous recombination (HR) exhibited higher sensitivity to acetaldehyde than did wild-type cells. We found that acetaldehyde-induced RAD51 foci representing HR intermediates were prolonged in HR-deficient cells. These results indicate a pivotal role of HR in the repair of acetaldehyde-induced DNA damage. These results suggest that acetaldehyde causes complex DNA damages that require various types of repair pathways. Mutants deficient in the removal of protein adducts from DNA ends such as TDP1 -/- and TDP2 -/- cells exhibited hypersensitivity to acetaldehyde. Strikingly, the double mutant deficient in both TDP1 and RAD54 showed similar sensitivity to each single mutant. This epistatic relationship between TDP1 -/- and RAD54 -/- suggests that the protein-DNA adducts generated by acetaldehyde need to be removed for efficient repair by HR. Our study would help understand the molecular mechanism of the genotoxic and mutagenic effects of acetaldehyde.

REV7 is an abundant, multifunctional protein that is a known factor in cell cycle regulation and in several key DNA repair pathways including Trans-Lesion Synthesis (TLS), the Fanconi Anemia (FA) pathway, and DNA Double-Strand Break (DSB) repair pathway choice. Thus far, no direct role has been studied for REV7 in the DNA damage response (DDR) signaling pathway. Here we describe a novel function for REV7 in DSB-induced p53 signaling. We show that REV7 binds directly to p53 to block ATM-dependent p53 Ser15 phosphorylation. We also report that REV7 is involved in the destabilization of p53. These findings affirm REV7's participation in fundamental cell cycle and DNA repair pathways. Furthermore, they highlight REV7 as a critical factor for the integration of multiple processes that determine viability and genome stability.

Background: International guidelines on intraductal papillary mucinous neoplasm (IPMN) recommend a formal oncological resection including splenectomy when distal pancreatectomy is indicated. This study aimed to compare oncological and surgical outcomes after distal pancreatectomy with or without splenectomy in patients with presumed IPMN., Methods: An international, retrospective cohort study was undertaken in 14 high-volume centres from 7 countries including consecutive patients after distal pancreatectomy for IPMN (2005-2019). Patients were divided into spleen-preserving distal pancreatectomy (SPDP) and distal pancreatectomy with splenectomy (DPS). The primary outcome was lymph node metastasis (LNM). Secondary outcomes were overall survival, duration of operation, blood loss, and secondary splenectomy., Results: Overall, 700 patients were included after distal pancreatectomy for IPMN; 123 underwent SPDP (17.6%) and 577 DPS (82.4%). The rate of malignancy was 29.6% (137 patients) and the overall rate of LNM 6.7% (47 patients). Patients with preoperative suspicion of malignancy had a LNM rate of 17.2% (23 of 134) versus 4.3% (23 of 539) among patients without suspected malignancy (P < 0.001). Overall, SPDP was associated with a shorter operating time (median 180 versus 226 min; P = 0.001), less blood loss (100 versus 336 ml; P = 0.001), and shorter hospital stay (5 versus 8 days; P < 0.001). No significant difference in overall survival was observed between SPDP and DPS for IPMN after correction for prognostic factors (HR 0.50, 95% c.i. 0.22 to 1.18; P = 0.504)., Conclusion: This international cohort study found LNM in 6.7% of patients undergoing distal pancreatectomy for IPMN. In patients without preoperative suspicion of malignancy, SPDP seemed oncologically safe and was associated with improved short-term outcomes compared with DPS., (© The Author(s) 2024. Published by Oxford University Press on behalf of BJS Foundation Ltd.)

Background Achilles tendinopathy is a common ankle disorder in both the general population and athletes. This condition can alter the mechanical characteristics of the Achilles tendon (AT) by decreasing tendon stiffness. Achilles tendinopathy is primarily treated conservatively; however, few monitoring tools exist for evaluating the condition of the AT. The Myoton PRO (Myoton AS, Tallinn, Estonia) device is a handheld tool used to evaluate tissue stiffness. However, no basic studies have examined the validity of Myoton PRO for assessing the AT. This study aimed to assess the validity of Myoton PRO using animal ATs and to examine its clinical applicability. Methods We used 28 fresh porcine ankles and evaluated AT stiffness at the calcaneus insertion site (AT0) and 2.0 cm above the calcaneus (AT2) using Myoton PRO. We also measured changes in the AT length using a tensile testing machine during the cyclic loading test. We investigated the correlation between dynamic stiffness and length change. Furthermore, we assessed the difference in stiffness between AT0 and AT2. Results The dynamic stiffness was 717.6 ± 183.1 N/m at AT0 and 467.4 ± 152.3 N/m at AT2. The change in length during the cyclic loading test was 1.8 ± 0.7 mm. The correlation between dynamic stiffness and length change was as follows: AT0, r=-0.61; AT2, r=-0.64 (P<0.001). The dynamic stiffness at AT0 was significantly greater than that at AT2 (P<0.001). Conclusions AT assessment using Myoton PRO has potential clinical utility as an indicator of tissue stiffness., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Kurashina et al.)

Background: This study compared the clinical results of fracture stems and conventional stems using the same glenoid component in reverse shoulder arthroplasty for proximal humerus fractures in the elderly., Methods: This retrospective study included 35 patients who underwent Grammont-type reverse shoulder arthroplasty for proximal humerus fractures from 2014 to 2020. The average age at surgery was 79.2 (range, 65-92) years, with 33 female shoulders. Fracture types per Neer classification were 3-part fracture, 4-part fracture, in 13 and 22 shoulders, respectively. The final follow-up period was 35 (range, 24-81) months. The Constant score, American Shoulder and Elbow Surgeons score, shoulder range of motion, and healing of greater tuberosities at the final follow-up of AEQUALIS™ REVERSED (Conventional stem group: n = 15) and AEQUALIS™ REVERSED FX (Fractured stem group: n = 20) were retrospectively investigated., Results: There were no statistically significant differences in age at surgery, sex, body mass index, fracture type, waiting time from injury to surgery, or preoperative general condition between the groups. The Constant and American Shoulder and Elbow Surgeons scores of the fractured stem group were significantly higher than those of the conventional stem group (P = 0.038 and P = 0.023, respectively). The anterior elevation and external rotation at the side of the fractured stem group also showed significantly higher values than those of the conventional stem group (fractured stem group vs. conventional stem group: anterior elevation 127° ± 25° vs. 105° ± 35°, P = 0.041; external rotation 28° ± 13° vs. 13° ± 12°, P = 0.015). The greater tuberosity healing rate was 46.7% (7/15) in the conventional stem group and 85.0% (17/20) in the fractured stem group (P＝0.027)., Conclusions: The findings suggest that use of a fracture-specific stem rather than a conventional stem in Grammont-type reverse shoulder arthroplasty for proximal humerus fractures improves tuberosity healing, postoperative range of motion, and clinical scores., Competing Interests: Declaration of competing interest The authors have no conflicts of interest directly relevant to the content of this article., (Copyright © 2022. Published by Elsevier B.V.)

Background: Acute superior mesenteric artery (SMA) occlusion is an uncommon condition associated with high mortality. If extensive bowel resection is performed for patients with acute SMA occlusion and the patient survives, long-term total parenteral nutrition (TPN) may be needed due to short bowel syndrome. This study examined factors associated with the need for long-term TPN after the treatment of acute SMA occlusion., Methods: We retrospectively analyzed 78 patients with acute SMA occlusion. Patients were abstracted from a Japanese database from institutions with at least 10 patients with acute SMA occlusive disease from January 2015 through December 2020 RESULTS: Among the initial cohort there were 41/78 survivors. Of these, 14/41 (34%) required permanent TPN who were compared with those who did not require long-term TPN (27/41, 66%). Compared to patients in the non-TPN group, those in the TPN group had significantly shorter remaining small intestine (90.7 cm vs. 218 cm, P<0.01), more patients with time from onset to intervention >6 hours (P=0.02), pneumatosis intestinalis on enhanced computed tomography scan (P=0.04), ascites (Odds Ratio 11.6, P<0.01), and a positive smaller superior mesenteric vein sign (P= 0.03). These were considered significant risk factors for needing long-term TPN. Age, gender, underlying disease, presence of peritoneal sign, presence of shock requiring vasopressors, site of obstruction (proximal vs. distal), and initial treatment (surgery vs. interventional radiology vs. thrombolytic therapy) were not significantly different between the two groups. Long-term TPN was significantly associated with longer hospital stay (52 vs. 35 days, P=0.04). Multivariate analysis identified the presence of ascites as an independent risk factor for needing long-term TPN., Conclusion: The need for permanent TPN after treatment of acute SMA occlusion is significantly associated with longer hospital stay, longer time to intervention, and characteristic imaging findings (pneumatosis intestinalis, ascites, Smaller SMV sign). Ascites is an independent risk factor., Level of Evidence: III., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

It is important to assess the prognosis and intervene before and after surgery in patients with hepatocellular carcinoma. This study aims to elucidate the association of outcomes and residual liver function after hepatectomy. A total of 176 patients who underwent the initial resection for hepatocellular carcinoma between January 2011 and March 2021 at Jichi Medical University were included. Hepatic clearance of the remnant liver was measured using 99mTc-galactosyl serum albumin scintigraphy. The log-rank test was used to analyze survival using the Kaplan-Meier method. Hazard ratios (HR) and 95% confidence intervals (CI) for overall survival were calculated using Cox's proportional hazard model. In multivariate analysis, microvascular invasion, intraoperative blood loss, and hepatic clearance of the remnant liver were independently associated with overall survival. Hepatic clearance of the remnant liver was independently associated with recurrence free survival. This is the first report to show that lower residual liver function is associated with shorter survival in patients with hepatocellular carcinoma undergoing hepatectomy. Preoperative determination of remnant liver function may allow assessment of prognosis in patients planned to undergo resection of hepatocellular carcinoma. Preservation of liver functional reserve may be crucial for improved long-term outcomes after hepatectomy., (© 2023. Springer Nature Limited.)

CRISPR/Cas9-mediated gene editing has great potential utility for treating genetic diseases. However, its therapeutic applications are limited by unintended genomic alterations arising from DNA double-strand breaks and random integration of exogenous DNA. In this study, we propose NICER, a method for correcting heterozygous mutations that employs multiple nicks (MNs) induced by Cas9 nickase and a homologous chromosome as an endogenous repair template. Although a single nick near the mutation site rarely leads to successful gene correction, additional nicks on homologous chromosomes strongly enhance gene correction efficiency via interhomolog homologous recombination (IH-HR). This process partially depends on BRCA1 and BRCA2, suggesting the existence of several distinct pathways for MN-induced IH-HR. According to a genomic analysis, NICER rarely induces unintended genomic alterations. Furthermore, NICER restores the expression of disease-causing genes in cells derived from genetic diseases with compound heterozygous mutations. Overall, NICER provides a precise strategy for gene correction., (© 2023. Springer Nature Limited.)

Background: Frozen shoulder (FS) is a pathological condition that involves a painful and stiff shoulder joint, most commonly in people aged 40-60 years. Most literature supports treatment with physical therapy (PT), although some studies have demonstrated years of continuing pain and functional deficits. Manipulation under anesthesia is effective at eliminating the contracture of intra-articular lesions for refractory FS. This study aimed to compare whether manipulation under anesthesia or PT is a more effective treatment in refractory FS., Methods: This study was a prospective observational study. A total of 102 patients with refractory FS were enrolled in this study in the medical records, all of whom had severe and multidirectional loss of motion and thickening of the joint capsule and coracohumeral ligament on magnetic resonance imaging. Fifty-one patients were in the manipulation under brachial plexus block (MUB) group (34 females, median age: 57 years), and 51 patients were in the PT group (34 females, median age: 59 years). The MUB procedure consisted of the conventional method with additional adduction manipulation, in which one examiner initially abducted the shoulder joint as much as possible. We recorded the visual analog scale, shoulder range of motion, and American Shoulder and Elbow Surgeons and Constant Scores at the initial baseline visit and at the 1-, 3-, 6-, and 12-month follow-ups. The total cost was calculated from the medical records, and cost-effectiveness was evaluated using quality-adjusted life year and incremental cost-effectiveness ratio., Results: Visual analog scale ( P  < .001), range of motion ( P  < .001), and American Shoulder and Elbow Surgeons and Constant Scores ( P  < .001) in the MUB group were significantly superior to those in the PT group at 1, 3, 6, and 12 months after treatment. The median cost and total quality-adjusted life year in the MUB and PT groups were $1375 versus $2751 and 2.95 versus 2.68, respectively, and the cost-effectiveness ratio between the MUB and PT groups was calculated as -$560., Conclusions: The new MUB procedure provides a shorter treatment period, better clinical outcomes, and higher cost-effectiveness in patients with refractory FS compared to PT., (© 2023 The Author(s).)

Background: A frozen shoulder (FS) is characterized by pain and limited range of motion (ROM). Although physical assessment of ROM is important for diagnosing and staging FS, ROM cannot be accurately assessed in clinical practice because of pain and muscle contraction. This study aimed to measure changes in shoulder joint ROM before and after anesthesia (ΔROM) in patients with FS and investigate the factors affecting these changes., Methods: This study included 54 patients (age, 55.6 ± 9.4 years; 17 males; disease duration, 6.6 ± 3.4 months) with FS before manipulation under transmission anesthesia. FS was defined as having a ROM in external rotation (ER) that was less than 50% of that in the unaffected shoulder. Pain at night and during motion was assessed using a numerical rating scale. Before anesthesia, the passive ROM of forward flexion (FF), abduction (AD), and ER were measured in the supine position. After confirming that the anesthesia was effective, passive ROM was measured again., Results: The ROM in the FF, AD, and ER after anesthesia was significantly higher than that before anesthesia ( P  < .001). ΔROM in the FF, AD, and ER was significantly correlated with pain at night (r = 0.51, P  < .001; r = 0.45, P  < .001; and r = 0.39, P  = .004, respectively). Furthermore, ΔROM in the ER was significantly correlated with pain during motion (r = 0.31, P  = .023) and disease duration (r = -0.31, P  = .021)., Conclusion: The ROM of the FS is susceptible to pain and muscle contraction. Interventions, such as physical therapy, may be recommended after pain relief., (© 2023 The Author(s).)

Adult T-cell leukemia (ATL) is a peripheral T-cell malignancy caused by human T-cell leukemia virus type 1 (HTLV-1). Microsatellite instability (MSI) has been observed in ATL cells. Although MSI results from impaired mismatch repair (MMR) pathway, no null mutations in the genes encoding MMR factors are detectable in ATL cells. Thus, it is unclear whether or not impairment of MMR causes the MSI in ATL cells. HTLV-1 bZIP factor (HBZ) protein interacts with numerous host transcription factors and significantly contributes to disease pathogenesis and progression. Here we investigated the effect of HBZ on MMR in normal cells. The ectopic expression of HBZ in MMR-proficient cells induced MSI, and also suppressed the expression of several MMR factors. We then hypothesized that the HBZ compromises MMR by interfering with a transcription factor, nuclear respiratory factor 1 (NRF-1), and identified the consensus NRF-1 binding site at the promoter of the gene encoding MutS homologue 2 (MSH2), an essential MMR factor. The luciferase reporter assay revealed that NRF-1 overexpression enhanced MSH2 promoter activity, while co-expression of HBZ reversed this enhancement. These results supported the idea that HBZ suppresses the transcription of MSH2 by inhibiting NRF-1. Our data demonstrate that HBZ causes impaired MMR, and may imply a novel oncogenesis driven by HTLV-1., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Masao Matsuoka reports a relationship with Kyowa Kirin Co Ltd that includes: speaking and lecture fees. Masao Matsuoka reports a relationship with Meiji Seika Pharma Co Ltd that includes: speaking and lecture fees. Masao Matsuoka reports a relationship with Bristol Myers Squibb Co that includes: speaking and lecture fees. Masao Matsuoka reports a relationship with Chugai Pharmaceutical Co Ltd that includes: speaking and lecture fees. Akifumi Takaori-Kondo reports a relationship with Ono Pharmaceutical Co Ltd that includes: funding grants., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: The safety of acoustic radiation force impulse (ARFI) elastography, which applies higher acoustic power with a longer pulse duration (PD) than conventional diagnostic ultrasound, is yet to be verified. We assessed the ARFI-induced lung injury risk and its relationship with peak rarefactional pressure amplitude (PRPA) and mechanical index (MI)., Methods: Eighteen and two rabbits were included in the ARFI (0.3-ms push pulses) and sham groups, respectively. A 5.2-MHz linear probe was applied to the subcostal area and aimed at both lungs through the liver for 30 ARFI emissions. The derated PRPA varied among the six ARFI groups-0.80 MPa, 1.13 MPa, 1.33 MPa, 1.70 MPa, 1.91 MPa, and 2.00 MPa, respectively., Results: The occurrence of lung hemorrhage and the mean lesion area among all samples in the seven groups were 0/6, 0/6, 1/6 (1.7 mm 2 ), 4/6 (8.0 mm 2 ), 4/6 (11.2 mm 2 ), 5/6 (23.8 mm 2 ), and 0/4 (sham), respectively. Logistic regression analysis showed that derated PRPA was significantly associated with lung injury occurrence (odds ratio: 207, p < 0.01), with the threshold estimated to be 1.1 MPa (MI, 0.5). Spearman's rank correlation showed a positive correlation between derated PRPA and lesion area (r = 0.671, p < 0.01)., Conclusion: This study demonstrated that the occurrence and severity of ARFI-induced lung hemorrhage increased with a rise in PRPA under clinical conditions in rabbits. This indicates a potential risk of lung injury due to ARFI elastography, especially when ARFI is unintentionally directed to the lungs during liver, heart, or breast examinations., (© 2023. The Author(s), under exclusive licence to The Japan Society of Ultrasonics in Medicine.)

Background: The prognostic importance of osteopenia in patients with intrahepatic cholangiocarcinoma (ICC) undergoing hepatectomy is unclear. The aim of this study was to evaluate the impact of osteopenia on survival in patients with ICC., Methods: A total of 71 patients who underwent hepatectomy at Jichi Medical University between July 2008 and June 2022 were included in this study. Non-contrast computed tomography scan images at the eleventh thoracic vertebra were used to assess bone mineral density. The cutoff value was calculated using a threshold value of 160 Hounsfield units. Overall survival curves were made using the Kaplan-Meier method and the log-rank test was used to evaluate survival. The hazard ratio (HR) and 95% confidence interval (CI) for overall survival were calculated using Cox's proportional hazard model., Results: In multivariable analysis, osteopenia (HR 3.66, 95%CI 1.16-14.1, p = 0.0258) and the platelet-lymphocyte ratio (HR 6.26, 95%CI 2.27-15.9, p = 0.0008) were significant independent factors associated with overall survival. There were no significant independent prognostic factors for recurrence-free survival., Conclusions: Preoperative osteopenia is significantly associated with postoperative survival in patients with ICC undergoing hepatectomy.

Background: The role of various serum tumor markers (TMs) has been reported in non-small cell lung cancer (NSCLC). However, the prognosis of patients with multiple TM-negative NSCLC remain unclear., Aims: This study aimed to describe the characteristics and outcomes of patients with NSCLC undergoing surgery and to investigate their prognostic association with preoperative serum TM-negative cases., Methods and Results: We retrospectively evaluated 442 patients who underwent complete resection of stage I NSCLC between January 2004 and December 2019. These 442 patients were classified into a group whose preoperative serum levels of carcinoembryonic antigen (CEA), cytokeratin-19 fragment (CYFRA21-1), carbohydrate antigen 19-9 (CA19-9), and squamous cell carcinoma antigen (SCC Ag) were all negative (TM-negative group; n = 249, 56%) and a group with at least one positive marker (TM-positive group; n = 193, 44%). Among all patients, the TM-negative group showed higher 5-year recurrence-free survival (RFS) (92.6% vs. 79.1%; p < .01), and overall survival (OS) rates (86.3% vs. 68.6%; p < .01). After propensity score matching, patients in the TM-negative group still exhibited good 5-year RFS (92.1% vs. 81.4%; p = .01) and OS rates (87.6% vs. 72.6%; p < .01)., Conclusion: Our study suggests that NSCLC patients who are preoperatively negative for all serum TMs, such as CEA, CYFRA21-1, CA19-9, and SCC Ag, represent a subgroup with a particularly good prognosis., (© 2022 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

ATM gene mutation carriers are predisposed to estrogen-receptor-positive breast cancer (BC). ATM prevents BC oncogenesis by activating p53 in every cell; however, much remains unknown about tissue-specific oncogenesis after ATM loss. Here, we report that ATM controls the early transcriptional response to estrogens. This response depends on topoisomerase II (TOP2), which generates TOP2-DNA double-strand break (DSB) complexes and rejoins the breaks. When TOP2-mediated ligation fails, ATM facilitates DSB repair. After estrogen exposure, TOP2-dependent DSBs arise at the c-MYC enhancer in human BC cells, and their defective repair changes the activation profile of enhancers and induces the overexpression of many genes, including the c-MYC oncogene. CRISPR/Cas9 cleavage at the enhancer also causes c-MYC overexpression, indicating that this DSB causes c-MYC overexpression. Estrogen treatment induced c-Myc protein overexpression in mammary epithelial cells of ATM-deficient mice. In conclusion, ATM suppresses the c-Myc-driven proliferative effects of estrogens, possibly explaining such tissue-specific oncogenesis., Competing Interests: Declaration of interests The authors have no conflicts of interest directly relevant to the content of this article., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background/purpose: Metal stents (MS) are recommended for preoperative biliary drainage (PBD) in patients with periampullary cancer, but whether MS are superior in terms of re-intervention and direct cost is debatable. This study aimed to compare the effects of MS and PS on the outcomes of patients with periampullary cancer., Methods: For this random-effects meta-analysis, electronic databases were screened for randomized controlled trials (RCTs) published until January 2022. Subgroup analyses were performed basis on the center type and presence of NAC., Results: In this meta-analysis, seven RCTs (440 participants) were included. MS reduced re-interventions (risk ratio [RR] = 0.42, 95% confidence interval [CI] = 0.25-0.72) and direct costs (mean difference = -474 USD, 95% CI = -656 to -292). PBD-related complications (RR = 0.74, 95% CI = 0.32-1.71) and postoperative complications (RR = 0.73, 95% CI = 0.45-1.17) did not differ between MS and PS. Compared PS, MS reduced postoperative complications in high-volume centers (RR = 0.64, 95% CI = 0.49-0.84) and PBD-related complications in patients receiving NAC (RR = 0.29, 95% CI = 0.08-1.08)., Conclusions: Metal stents likely reduces re-interventions and direct costs. Further studies are needed to confirm the effects of MS on the outcomes., (© 2022 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Steroid hormones induce the transcription of target genes by activating nuclear receptors. Early transcriptional response to various stimuli, including hormones, involves the active catalysis of topoisomerase II (TOP2) at transcription regulatory sequences. TOP2 untangles DNAs by transiently generating double-strand breaks (DSBs), where TOP2 covalently binds to DSB ends. When TOP2 fails to rejoin, called "abortive" catalysis, the resulting DSBs are repaired by tyrosyl-DNA phosphodiesterase 2 (TDP2) and non-homologous end-joining (NHEJ). A steroid, cortisol, is the most important glucocorticoid, and dexamethasone (Dex), a synthetic glucocorticoid, is widely used for suppressing inflammation in clinics. We here revealed that clinically relevant concentrations of Dex and physiological concentrations of cortisol efficiently induce DSBs in G 1 phase cells deficient in TDP2 and NHEJ. The DSB induction depends on glucocorticoid receptor (GR) and TOP2. Considering the specific role of TDP2 in removing TOP2 adducts from DSB ends, induced DSBs most likely represent stalled TOP2-DSB complexes. Inhibition of RNA polymerase II suppressed the DSBs formation only modestly in the G 1 phase. We propose that cortisol and Dex frequently generate DSBs through the abortive catalysis of TOP2 at transcriptional regulatory sequences, including promoters or enhancers, where active TOP2 catalysis occurs during early transcriptional response., (© 2022 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.)

Background: Many non-small cell lung cancer (NSCLC) tumors present complex histology with various components. The effects of the lepidic growth component (LGC) on the prognosis of NSCLC have not been investigated. Here, we investigated whether an LGC is a relevant prognostic factor for NSCLC., Methods: This study retrospectively investigated the clinicopathologic characteristics of 379 patients with NSCLC ≤3 cm who underwent complete surgical resection between 2004 and 2016 at the University of Yamanashi Hospital. The histologic subtypes were classified into NSCLC with or without an LGC. We evaluated the effect of an LGC on the clinicopathologic features and 5-year overall survival of patients with NSCLC., Results: On final pathology, 214 (56%) of 379 patients had an LGC, and 165 (44%) did not. Sex, smoking history, ground-glass opacity component, pathologic invasive size, lymph node metastasis, pleural invasion, vessel invasion, pathologic stage, and histologic type were significantly different between the groups. Multivariate analysis of 5-year overall survival, identified age (hazard ratio [HR], 1.07; 95% confidence interval [CI], 1.035-1.105; p < 0.001), pathologic invasive size (HR, 1.548; 95% CI, 1.088-2.202; p = 0.015) and LGC (HR, 2.11; 95% CI, 1.099-4.051; p = 0.025) as independent prognostic factors. When the pathologic invasive size was matched, the 5-year overall survival of the LGC and non-LGC groups was 93% and 77%, respectively (p = 0.006)., Conclusions: LGC is a significantly favorable prognostic factor for NSCLC with a pathologic invasive size of ≤3 cm., (© 2022 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

DNA-protein cross-links (DPCs) are generated by internal factors such as cellular aldehydes that are generated during normal metabolism and external factors such as environmental mutagens. A nucleoside analog, 5-aza-2'-deoxycytidine (5-azadC), is randomly incorporated into the genome during DNA replication and binds DNA methyltransferase 1 (DNMT1) covalently to form DNMT1-DPCs without inducing DNA strand breaks. Despite the recent progress in understanding the mechanisms of DPCs repair, how DNMT1-DPCs are repaired is unclear. The metalloprotease SPRTN has been considered as the primary enzyme to degrade protein components of DPCs to initiate the repair of DPCs. In this study, we showed that SPRTN-deficient ( SPRTN -/- ) human TK6 cells displayed high sensitivity to 5-azadC, and the removal of 5-azadC-induced DNMT1-DPCs was significantly slower in SPRTN -/- cells than that in wild-type cells. We also showed that the ubiquitination-dependent proteasomal degradation, which was independent of the SPRTN-mediated processing, was also involved in the repair of DNMT1-DPCs. Unexpectedly, we found that cells that are double deficient in tyrosyl DNA phosphodiesterase 1 and 2 ( TDP1 -/- TDP2 -/- ) were also sensitive to 5-azadC, although the removal of 5-azadC-induced DNMT1-DPCs was not compromised significantly. Furthermore, the 5-azadC treatment induced a marked accumulation of chromosomal breaks in SPRTN -/- as well as TDP1 -/- TDP2 -/- cells compared to wild-type cells, strongly suggesting that the 5-azadC-induced cell death was attributed to chromosomal DNMT1-DPCs. We conclude that SPRTN protects cells from 5-azadC-induced DNMT1-DPCs, and SPRTN may play a direct proteolytic role against DNMT1-DPCs and TDP1/TDP2 also contributes to suppress genome instability caused by 5-azadC in TK6 cells.

Background/purpose: Previous systematic reviews have shown that radical antegrade modular pancreatosplenectomy (RAMPS) had favorable outcomes including prognosis. However, recent large studies have shown opposite results, thus necessitating clarification of RAMPS efficacy. We aimed to update existing evidence on the clinical outcomes of RAMPS for left-sided pancreatic cancer by comparing them to those of the conventional approach., Methods: Electronic databases and registries were searched until August 2021 to perform random-effect meta-analysis. Methodological quality was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation approach. The protocol was registered at protocols.io (https://doi.org/10.17504/protocols.io.bxhfpj3n)., Results: Thirteen cohort studies (1641 patients) and four ongoing randomized controlled trials (RCTs) were identified. RAMPS increased disease-free survival (hazard ratio [HR] 0.62, 95% confidence interval [CI] = 0.42-0.91), but it had little effect on overall survival (HR 0.92, 95% CI = 0.79-1.09) and recurrence-free survival (HR 0.72, 95% CI = 0.37-1.38) with low certainty of evidence., Conclusion: The meta-analysis of recent studies suggests that RAMPS may have little effect on clinical outcomes. These findings highlight the necessity of further studies, including RCTs to determine the efficacy and subsequent indication of RAMPS in clinical cases., (© 2022 The Authors. Journal of Hepato-Biliary-Pancreatic Sciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: Estimation of the functional reserve of the remnant liver is important to reduce morbidity and mortality., Aim: To estimate the functional reserve of the remnant liver in patients with hepatocellular carcinoma (HCC)., Methods: We reviewed the medical records of 199 patients who underwent resection of HCC. Hepatic clearance of the remnant liver was calculated using fusion images of 99m Tc-labelled galactosyl-human serum albumin liver scintigraphy and computed tomography. Posthepatectomy liver failure (PHLF) was classified according to the International Study Group of Liver Surgery. Complications was classified according to Clavien-Dindo classification. We analyzed by the risk factors for PHLF, morbidity and mortality with multivariate analysis., Results: Twenty-seven (30%) patients had major complications and 23 (12%) developed PHLF. The incidence of major complications increased with increasing albumin-bilirubin (ALBI) grade. The area under the curve values for hepatic clearance of the remnant liver, liver to heart-plus-liver radioactivity at 15 min (LHL15), and ALBI score predicting PHLF were 0.868, 0.629, and 0.655, respectively. The area under the curve for hepatic clearance of the remnant liver, LHL15, and ALBI score predicting major complications were 0.758, 0.594, and 0.647, respectively. The risk factors for PHLF and major complications were hepatic clearance of the remnant liver and intraoperative bleeding., Conclusion: The measurement of hepatic clearance may predict PHLF and major complications for patients undergoing resection of HCC., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest for this study., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Adhesive capsulitis (AC) is characterized by pain and limited range of motion, caused by stiffness of the joint capsule and coracohumeral ligament. On the other hand, there have been few reports on muscle stiffness in AC. The purpose of this study was to assess muscle stiffness in patients of AC with a portable and noninvasive device, Myoton PRO. We hypothesized that muscle stiffness around shoulder joint increases in AC., Methods: At first, we surveyed correlation between Myoton PRO and shear wave elastography with phantoms. Second, reproducibility and repeatability of healthy volunteers with Myoton PRO were evaluated. Finally, muscle stiffness was measured in 40 patients who were diagnosed with AC. Muscle stiffness was quantitatively measured with Myoton PRO. We compared the stiffness of the anterior deltoid (AD), pectoralis major, and latissimus dorsi (LD) in AC patients on both the affected and nonaffected sides., Results: Correlation coefficient in shear wave elastography and Myoton PRO was 0.99( P  = .001). Reliability of intraoperator and interoperator with Myoton PRO was 0.9 or higher. Muscle stiffness values (N/m) of the AD, pectoralis major, and LD were 355 ± 61, 252 ± 54, 207 ± 51 in the affected sides and 328 ± 50, 252 ± 41, 186 ± 37 in the nonaffected sides, and the differences were significant in the AD and LD ( P  = .005, P  = .002, respectively)., Conclusions: We used Myoton PRO to evaluate muscle stiffness in AC. The AD and LD muscles of AC patients were significantly stiffer on the affected side compared to the nonaffected side., (© 2022 The Authors.)

Acoustic radiation force impulse (ARFI) imaging and shear wave elastography use a "push pulse." The push pulse, which is referenced as an ARFI in this study, has a longer duration than that of conventional diagnostic pulses (several microseconds). Therefore, there are concerns regarding thermal safety in vivo. However, few in vivo studies have been conducted using living animals. In this study, to suggest a concept for deciding an ARFI output and cooling time while considering thermal safety, the liver (with and without an ultrasound contrast agent) and femur bone surface of living rabbits were exposed to an ARFI, and the maximum temperature rise, temperature rise for 5-min duration, and cooling time were measured via a thermocouple. While testing within the regulation limits of diagnostic ultrasound outputs, a maximum temperature rise on the femur bone surface exceeded the allowable temperature rise (1.5°C) in the British Medical Ultrasound Society (BMUS) statement. However, using the linear relationships between the pulse intensity integral (PII) of a single pulse and the above three temperature parameters, PII may be determined so that the maximum temperature rise is within the allowable temperature rise in the BMUS statement. The cooling time can be estimated from the PII., Competing Interests: Conflict of interest disclosure— The authors have no potential conflicts of interest to disclose., (Copyright © 2022 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Background: Partial-thickness rotator cuff tears are commonly found in the articular-side tendon of the supraspinatus; however, isolated lesions, except those occurring in the supraspinatus tendons, are rare. We report three cases of isolated bursal-side infraspinatus tears that were difficult to detect by magnetic resonance imaging but could be visualized by computed tomography bursography., Case Presentation: Three Asian patients (59-71 years old) with shoulder pain ranging from 1 month to 3 years in duration were each diagnosed with shoulder impingement syndrome. Magnetic resonance imaging studies failed to show a tear of the rotator cuff tendon complex. However, computed tomography bursography showed a longitudinal infraspinatus partial-thickness tear on the bursal side in each case. Arthroscopic decompression of the subacromial space and debridement of the infraspinatus tendon tear successfully alleviated the shoulder pain in two of the three patients; the third patient did not undergo surgery and remained symptomatic at follow-up., Conclusions: In patients with chronic shoulder pain but normal magnetic resonance imaging findings, computed tomography bursography should be considered, as bursal-side infraspinatus tears may be found in these patients. Furthermore, our findings provide a basis for larger studies to further establish the accuracy of computed tomography bursography for these lesions., (© 2022. The Author(s).)

Base excision repair (BER) removes damaged bases by generating single-strand breaks (SSBs), gap-filling by DNA polymerase β (POLβ), and resealing SSBs. A base-damaging agent, methyl methanesulfonate (MMS) is widely used to study BER. BER increases cellular tolerance to MMS, anti-cancer base-damaging drugs, temozolomide, carmustine, and lomustine, and to clinical poly(ADP ribose)polymerase (PARP) poisons, olaparib and talazoparib. The poisons stabilize PARP1/SSB complexes, inhibiting access of BER factors to SSBs. PARP1 and XRCC1 collaboratively promote SSB resealing by recruiting POLβ to SSBs, but XRCC1 -/- cells are much more sensitive to MMS than PARP1 -/- cells. We recently report that the PARP1 loss in XRCC1 -/- cells restores their MMS tolerance and conclude that XPCC1 facilitates the release of PARP1 from SSBs by maintaining its autoPARylation. We here show that the PARP1 loss in XRCC1 -/- cells also restores their tolerance to the three anti-cancer base-damaging drugs, although they and MMS induce different sets of base damage. We reveal the synthetic lethality of the XRCC1 -/- mutation, but not POLβ -/- , with olaparib and talazoparib, indicating that XRCC1 is a unique BER factor in suppressing toxic PARP1/SSB complex and can suppress even when PARP1 catalysis is inhibited. In conclusion, XRCC1 suppresses the PARP1/SSB complex via PARP1 catalysis-dependent and independent mechanisms., (© 2022 The Authors. Genes to Cells published by Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.)

Introduction and Importance: Intussusception is invagination of the bowel and is rare in adults, representing only 5% of all cases of intussusception. Duodenal intussusception is also very rare. To the best of our knowledge, there is only one previous report of a malignant tumor in the fourth portion of the duodenum as the lead point of intussusception (Vaibhav et al., 2021 [1]). This reports a duodenal-duodenal intussusception caused by a malignant tumor in the third portion of the duodenum., Case Presentation: A 36-year-old woman with abdominal pain was diagnosed with duodenal intussusception by abdominal ultrasonography and computed tomography scan. Double balloon endoscopy showed that the intussusception had spontaneously reduced, and a tumor was found in the third portion of the duodenum. Open resection was performed because of the tumor location. Pathologic examination revealed adenocarcinoma with an adenoma of the duodenum. The patient had no evidence of recurrence for 4 years after resection., Clinical Discussion: This patient had a primary duodenal malignancy and presented with intussusception, Duodenal intussusception is a rare condition requiring prompt intervention, usually requiring surgery. In this patient, since endoscopic resection was difficult, partial resection of duodenum was performed by open surgery assisted by double balloon enteroscopy. The pathological diagnosis of the resected specimen was primary duodenal malignancy., Conclusion: This is a report of adult duodenal intussusception caused by a primary duodenal malignancy. This rare condition posed an intriguing challenge for the optimal operative approach., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Osteopenia is defined as low bone mineral density (BMD) and has been shown to be associated with outcomes of patients with various cancers. The association between osteopenia and perihilar cholangiocarcinoma is unknown. The aim of this study was to evaluate osteopenia as a prognostic factor in patients with perihilar cholangiocarcinoma. Methods: A total of 58 patients who underwent surgery for perihilar cholangiocarcinoma were retrospectively analyzed. The BMD at the 11th thoracic vertebra was measured using computed tomography scan within one month of surgery. Patients with a BMD < 160 HU were considered to have osteopenia and b BMD ≥ 160 did not have osteopenia. The log-rank test was performed for survival using the Kaplan−Meier method. After adjusting for confounding factors, overall survival was assessed by Cox′s proportional-hazards model. Results: The osteopenia group had 27 (47%) more females than the non-osteopenia group (p = 0.036). Median survival in the osteopenia group was 37 months and in the non-osteopenia group was 61 months (p = 0.034). In multivariable analysis, osteopenia was a significant independent risk factor associated with overall survival in patients with perihilar cholangiocarcinoma (hazard ratio 3.54, 95% confidence interval 1.09−11.54, p = 0.036), along with primary tumor stage. Conclusions: Osteopenia is associated with significantly shorter survival in patients with perihilar cholangiocarcinoma.

Acoustic radiation force impulse (ARFI) elastography has been used to diagnose acute pancreatitis (AP). The present study aimed to assess the effectiveness of ARFI elastography in the diagnosis of AP. Studies examining the efficacy of ARFI elastography in AP were selected by searching MEDLINE, EMBASE, CENTRAL, ICTRP, and ClinicalTrial.gov. until September 2021. Meta-analyses were performed using random effects models. The Grading of Recommendations, Assessment, Development, and Evaluation approach was used to assess the certainty of the evidence. Eight case-control studies (994 patients) were included in the meta-analysis. The ARFI-Virtual Touch Quantification value (or ARFI shear wave propagation velocity) of the AP patient group was 0.83 m/s higher (95% confidence interval [CI]: 0.36-1.3) than that in the control group (95% CI: 1.0-1.28). The sensitivity and specificity of ARFI elastography for diagnosing AP were 98.3% (95% CI: 92.6-96.6%) and 95.5% (95% CI: 87.5-98.5%), respectively. The results showed that physicians could use ARFI elastography to accurately diagnose patients with AP. Additional well-designed studies are necessary to validate the efficacy of ARFI elastography in patients with AP., Competing Interests: Conflict of interest disclosure The authors declare no conflicts of interest., (Copyright © 2021 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Background: Sarcopenia, as assessed by body composition, can affect morbidity and survival in several gastrointestinal cancer. However, the impact of sarcopenia, referring to both quantity and quality of skeletal muscle, in biliary tract cancer (BTC) is debatable. We aimed to investigate the impact of sarcopenia on morbidity and mortality in patients with BTC., Methods: Electronic databases and trial registries were searched through July 2021 to perform random-effects meta-analyses. Study selection, data abstraction and quality assessment were independently performed using the Grading of Recommendations, Assessment, Development, and Evaluation approach., Results: Twenty-nine studies (4443 patients) were included; 28 used computed tomography and one used dual-energy X-ray absorptiometry to assess body composition. Eighteen studies reported the impact of pre-operative sarcopenia on postoperative outcomes; namely, sarcopenia increased postoperative complications (risk ratio = 1.23, 95% confidence interval [CI] = 1.07 to 1.41; I 2  = 2%), and decreased recurrence-free survival (hazard ratio [HR] = 2.20, 95% CI = 1.75 to 2.75; I 2  = 0%) in multivariable analyses. Low muscle quantity (HR = 2.26, 95% CI = 1.75 to 2.92; I 2  = 66%) and quality (HR = 1.75, 95% CI = 1.33 to 2.29; I 2  = 50%) decreased overall survival in multivariable analyses. The certainty of the evidence was low because of heterogeneity and imprecision., Conclusions: In sarcopenia, low muscle quantity and quality by body composition conferred an independent risk of morbidity and mortality in patients with BTC. Further studies are needed to confirm these findings and mitigate risk., Competing Interests: Conflict of interest The authors declare no conflict of interest., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: We previously reported a characteristic dynamic magnetic resonance imaging (MRI) change in patients with frozen shoulder (FS) and named this abnormal blood flow pattern the "burning sign". In this study, a semiquantitative method was used to evaluate changes in this abnormal blood flow pattern on dynamic MRI after shoulder manipulation under ultrasound-guided cervical nerve root block (MUC) in patients with FS., Methods: Nineteen patients with FS underwent MUC, with dynamic MRI performed before and after. We used dynamic MRI to semiquantitatively assess changes in the burning sign at the axillary pouch (AP) and rotator interval (RI) by examining the enhancement rate in the signal intensity and the enhancement velocity. Functional assessments included a numeric rating scale score, the range of shoulder motion, the American Shoulder and Elbow Surgeons score, and the Constant score., Results: The burning sign in the AP and RI was observed with dynamic MRI in all patients before MUC. The average interval from MUC until dynamic MRI was 8.2 months (range, 6-12). Clinical results for all patients improved after MUC. The before and after MUC enhancement rates (%) were 217 ± 51 and 85 ± 36 in the AP and 233 ± 61 and 73 ± 40 in the RI, respectively (both P  < .001). The before and after MUC enhancement velocities (ms/s) were 902 ± 335 and 203 ± 125 in the AP and 1249 ± 634 and 213 ± 146 in the RI, respectively (both P  < .001)., Conclusion: Dynamic MRI semiquantitatively demonstrated a reduction in abnormal blood flow and improvement in clinical results after MUC in patients with FS., (© 2022 The Authors.)

Introduction: Shoulder manipulation under ultrasound-guided cervical nerve root block (MUC) gives good clinical results in patients with frozen shoulder 1 week after the procedure. However, some patients are refractory to MUC. The present study was performed to investigate the prognostic factors of MUC for frozen shoulder., Methods: We evaluated 73 frozen shoulders (70 patients) to investigate the prognostic factors of MUC. The patients' mean age was 56.6 years, and 60% were female. The mean duration of symptoms before MUC was 8.6 months. We assessed pain using a numeric rating scale (NRS), range of motion (ROM), and the American Shoulder and Elbow Surgeons (ASES) score before and 1 year after MUC. We compared patients with an ASES score of <80 (defined as a poor clinical result) with those with an ASES score of ≥80 (good clinical result). To identify the risk factors for a poor clinical result, multiple logistic regression analysis was performed using the following variables: age, sex, duration of symptoms before MUC, diabetes mellitus (DM), initial NRS score, and initial ROM., Results: The initial NRS score and the prevalence of DM were significantly greater in the poor clinical results group. Multiple logistic regression analysis revealed that DM was the only independent risk factor for a poor clinical result after MUC (odds ratio, 51; 95% confidence interval, 10.9-237; p = .01)., Conclusions: DM is a negative prognostic factor of MUC for frozen shoulder, and patients with DM should be informed of this before they undergo treatment for frozen shoulder., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction and Importance: Shoulder stiffness in postoperative breast cancer causes a decrease in their quality of life. However, the underlying pathology is not fully understood, and no study has investigated the dynamic magnetic resonance imaging (MRI) findings in these patients. Therefore, the current preliminary study aimed to investigate the dynamic MRI findings in patients with shoulder stiffness occurring after breast cancer surgery., Methods: We retrospectively analyzed the electronic medical records of postoperative breast cancer patients with shoulder stiffness, dated from January 2015 to December 2020. The baseline characteristics, breast cancer treatment methods, range of active shoulder motion, and location of the abnormal enhancement on dynamic MRI were assessed., Results: The mean age of the patients was 57.8 ± 6.1 years (range, 47-63 years) and the mean duration of shoulder symptoms was 5.6 ± 3.6 months (range, 2-12 months). An abnormal enhancement of the rotator interval and axillary pouch was observed on dynamic MRI of all the included patients., Conclusion: This study presents the first case reports of the dynamic MRI findings in postoperative breast cancer patients with shoulder stiffness. All patients had abnormal enhancement of the rotator interval and axillary pouch., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Germline mutations in the mismatch repair (MMR) genes MSH2 , MSH6 , MLH1 , and PMS2 are linked to cancer of the colon and other organs, characterized by microsatellite instability and a large increase in mutation frequency. Unexpectedly, mutations in EXO1 , encoding the only exonuclease genetically implicated in MMR, are not linked to familial cancer and cause a substantially weaker mutator phenotype. This difference could be explained if eukaryotic cells possessed additional exonucleases redundant with EXO1. Analysis of the MLH1 interactome identified FANCD2-associated nuclease 1 (FAN1), a novel enzyme with biochemical properties resembling EXO1. We now show that FAN1 efficiently substitutes for EXO1 in MMR assays and that this functional complementation is modulated by its interaction with MLH1. FAN1 also contributes to MMR in vivo ; cells lacking both EXO1 and FAN1 have an MMR defect and display resistance to N -methyl- N -nitrosourea (MNU) and 6-thioguanine (TG). Moreover, FAN1 loss amplifies the mutational profile of EXO1-deficient cells, suggesting that the two nucleases act redundantly in the same antimutagenic pathway. However, the increased drug resistance and mutator phenotype of FAN1/EXO1-deficient cells are less prominent than those seen in cells lacking MSH6 or MLH1. Eukaryotic cells thus apparently possess additional mechanisms that compensate for the loss of EXO1.