Effectiveness and Persistency of Ustekinumab Treatment for Ulcerative Colitis: A Phoenix retrospective Cohort Study.

Background: Real-world data regarding ustekinumab (UST) for ulcerative colitis (UC) particularly in biologics-naïve patients is currently limited. This study aimed to elucidate the real-world effectiveness and safety of UST for UC. Methods: Overall, 150 patients with UC treated with UST from March 2020 to January 2023 were enrolled across 7 referral hospitals. To assess the clinical efficacy and persistence of UST, retrospective analyses were conducted from weeks 8 to 56. Predictive factors concerning the response and persistence of UST were examined through univariate and multivariate analyses. Results: Of the 150 patients, 125 received UST for remission induction, including 36% biologics-naïve. The response and remission rates were 72.8% and 56.0% at week 8 and 73.2% and 63.4% at week 56, respectively. Biologics-naïve patients represented higher response and remission rates at week 8 (84.4% and 73.3%) than those with biologics exposure (66.2% and 46.2%). Patients with prior antitumor necrosis factor (anti-TNF) and vedolizumab (VDZ) exposure had relatively lower response and remission rates (34.5% and 24.1%, respectively). The 1-year cumulative persistence rate was 84.0%. Multivariate analysis revealed that the chronic continuous type and prior anti-TNF and VDZ exposure were negative predictive factors for week 8 responsiveness. Clinical response at week 8 was a predictor of 1-year persistence. Adverse event incidence remained notably low at 6.4%. Conclusions: This study highlights the safety and effectiveness of UST as an induction and maintenance therapy for UC. Chronic continuous type and previous anti-TNF and VDZ exposure negatively contributed to short-term effectiveness, whereas short-term effectiveness provided good persistency.

Risk Factors for Adverse Events of Nanoliposomal Irinotecan Plus 5-Fluorouracil and L-leucovorin.

Background/Aim: The regimen with nanoliposomal irinotecan plus 5-fluorouracil and L-leucovorin (nal-IRI/FL) is used for metastatic pancreatic cancer. A clinical study has indicated that the uridine diphosphate-glucuronosyltransferase (UGT) 1A1 polymorphism is associated with neutropenia during nal-IRI/FL treatment; however, no studies have reported risk factors for the occurrence of adverse events in the clinical setting. This study aimed to explore the risk factors for adverse events of nal-IRI/FL. Patients and Methods: This study included patients with metastatic pancreatic cancer who started nal-IRI/FL treatment. Patient information, including laboratory data before nal-IRI/FL initiation and adverse events during nal-IRI/FL treatment, was retrospectively obtained from medical records. Results: This study consisted of 36 patients, including 16, 16, and 4 with UGT1A1*6 or *28 wild-type (-/-), heterozygous (+/-), and homozygous (+/+), respectively. Patients with UGT1A1*6 or *28 (+/+) exhibited significantly lower nadir counts of white blood cells (p=0.033) and neutrophils (p=0.043). Multiple regression analyses revealed that the decreased white blood cell count was significantly associated with the genotype of UGT1A1*6 or *28 (+/+) (p=0.009), high aspartate aminotransferase (AST) value before the therapy (p=0.019), and pancreatic head cancer (p=0.030). Also, the decreased neutrophil count was significantly related to the genotype of UGT1A1*6 or *28 (+/+) (p=0.017). Conclusion: Patients with UGT1A1*6 or *28 (+/+) should be especially concerned about neutropenia and leukopenia during nal-IRI/FL treatment. Additionally, high AST value and pancreatic head cancer may be risk factors for leukopenia during nal-IRI/FL treatment.

Targeted genetic and small molecule disruption of N-Ras CaaX cleavage alters its localization and oncogenic potential.

Ras GTPases and other CaaX proteins undergo multiple post-translational modifications at their carboxyl-terminus. These events initiate with prenylation of a cysteine and are followed by endoproteolytic removal of the 'aaX' tripeptide and carboxylmethylation. Some CaaX proteins are only subject to prenylation, however, due to the presence of an uncleavable sequence. In this study, uncleavable sequences were used to stage Ras isoforms in a farnesylated and uncleaved state to address the impact of CaaX proteolysis on protein localization and function. This targeted strategy is more specific than those that chemically inhibit the Rce1 CaaX protease or delete the RCE1 gene because global abrogation of CaaX proteolysis impacts the entire CaaX protein proteome and effects cannot be attributed to any specific CaaX protein of the many concurrently affected. With this targeted strategy, clear mislocalization and reduced activity of farnesylated and uncleaved Ras isoforms was observed. In addition, new peptidomimetics based on cleavable Ras CaaX sequences and the uncleavable CAHQ sequence were synthesized and tested as Rce1 inhibitors using in vitro and cell-based assays. Consistently, these non-hydrolyzable peptidomimetic Rce1 inhibitors recapitulate Ras mislocalization effects when modeled on cleavable but not uncleavable CaaX sequences. These findings indicate that a prenylated and uncleavable CaaX sequence, which can be easily applied to a wide range of mammalian CaaX proteins, can be used to probe the specific impact of CaaX proteolysis on CaaX protein properties under conditions of an otherwise normally processed CaaX protein proteome.

Assessment of Patient Characteristics Influencing the Analgesic Effects of Ibuprofen Gargle After Mandibular Third Molar Extractions.

Introduction In our previous work, we investigated the analgesic effects of ibuprofen gargle after mandibular third molar extractions. However, a subsequent detailed review of individual patient data revealed variations in postoperative pain reduction among patients. Consequently, the present study was designed to conduct post-hoc subanalyses that identified factors contributing to variation in the analgesic response to ibuprofen gargle after third molar extractions. Materials and methods This study involved thirty-five Japanese patients from a prior randomized, double-blind, placebo-controlled, crossover study, which focused on the analgesic effects of ibuprofen gargle after mandibular third molar extractions. Participants were categorized as responders (n = 13) and non-responders (n = 22) based on the within-subject difference (ibuprofen-placebo, IP) of visual analog scale (VAS) changes. Baseline characteristics were compared, along with variables, such as age, sex, the reason for extraction, extraction site, Pell Gregory (space and depth) classification, Winter's classification, surgeon's experience, and surgery time. Baseline characteristics predicting responder status were examined using multivariate logistic regression. Results In the univariate analysis, variables such as age, sex, and baseline VAS scores with p-values <0.2 were evaluated using a stepwise approach. This analysis identified age (per -10 years) with an odds ratio of 4.163 (95% confidence interval (CI): 1.170-31.952, p = 0.0233) and sex (female) with an odds ratio of 9.977 (95% CI: 1.336-208.256, p = 0.0213) as significant predictors of responder status. Conclusions In young and female patients, ibuprofen gargle decreased postoperative pain after mandibular third molar extractions.

Radiomics-based prediction of nonalcoholic fatty liver disease following pancreatoduodenectomy.

PURPOSE: Predicting nonalcoholic fatty liver disease (NAFLD) following pancreaticoduodenectomy (PD) is challenging, which delays therapeutic intervention and makes its prevention difficult. We conducted this study to assess the potential application of preoperative computed tomography (CT) radiomics for predicting NAFLD. METHODS: The subjects of this retrospective study were 186 patients with PD from a single institution. We extracted the predictors of NAFLD after PD statistically from conventional clinical and radiomic features of the estimated remnant pancreas and whole liver region on preoperative nonenhanced CT images. Based on these predictors, we developed a machine-learning predictive model, which integrated clinical and radiomic features. A comparative model used only clinical features as predictors. RESULTS: The incidence of NAFLD after PD was 43.5%. The variables of the clinicoradiomic model included one shape feature of the pancreas, two texture features of the liver, and sex; the variables of the clinical model were age, sex, and chemoradiotherapy. The accuracy%, precision%, recall%, F1 score, and area under the curve of the two models were 75.0, 72.7, 66.7, 69.6, and 0.80; and 69.6, 68.4, 54.2, 60.5, and 0.69, respectively. CONCLUSIONS: Preoperative CT-derived radiomic features from the pancreatic and liver regions are promising for the prediction of NAFLD post-PD. Using these features enhances the predictive model, enabling earlier intervention for high-risk patients.

Corticosteroids impair epithelial regeneration in immune-mediated intestinal damage.

Corticosteroid treatment (CST) failure is associated with poor outcomes for patients with gastrointestinal (GI) graft-versus-host disease (GVHD). CST is intended to target the immune system, but the glucocorticoid receptor (GR) is widely expressed, including within the intestines, where its effects are poorly understood. Here, we report that corticosteroids (CS) directly targeted intestinal epithelium, potentially worsening immune-mediated GI damage. CS administered to mice in vivo and intestinal organoid cultures ex vivo reduced epithelial proliferation. Following irradiation, immediate CST mitigated GI damage but delayed treatment attenuated regeneration and exacerbated damage. In a murine steroid-refractory (SR) GVHD model, CST impaired epithelial regeneration, worsened crypt loss, and reduced intestinal stem cell (ISC) frequencies. CST also exacerbated immune-mediated damage in organoid cultures with SR, GR-deficient T cells or IFN-γ. These findings correlated with CS-dependent changes in apoptosis-related gene expression and STAT3-related epithelial proliferation. Conversely, IL-22 administration enhanced STAT3 activity and overcame CS-mediated attenuation of regeneration, reducing crypt loss and promoting ISC expansion in steroid-treated mice with GVHD. Therefore, CST has the potential to exacerbate GI damage if it fails to control the damage-inducing immune response, but this risk may be countered by strategies augmenting epithelial regeneration, thus providing a rationale for clinical approaches combining such tissue-targeted therapies with immunosuppression.

Myeloid spatial and transcriptional molecular signature of ischemia-reperfusion injury in human liver transplantation.

BACKGROUND: Ischemia-reperfusion injury (IRI) is a significant clinical concern in liver transplantation, with a key influence on short-term and long-term allograft and patient survival. Myeloid cells trigger and sustain tissue inflammation and damage associated with IRI, but the mechanisms regulating these activities are unknown. To address this, we investigated the molecular characteristics of intragraft myeloid cells present in biopsy-proven IRI- and IRI+ liver transplants. METHODS: RNA-sequencing was performed on 80 pre-reperfusion and post-reperfusion biopsies from 40 human recipients of liver transplantation (23 IRI+, 17 IRI-). We used transcriptional profiling and computational approaches to identify specific gene coexpression network modules correlated with functional subsets of MPO+, lysozyme+, and CD68+ myeloid cells quantified by immunohistochemistry on sequential sections from the same patient biopsies. RESULTS: A global molecular map showed gene signatures related to myeloid activation in all patients regardless of IRI status; however, myeloid cell subsets differed dramatically in their spatial morphology and associated gene signatures. IRI- recipients were found to have a natural corticosteroid production and response profile from pre-reperfusion to post-reperfusion, particularly among monocytes/macrophages. The pre-reperfusion signature of IRI+ recipients included acute inflammatory responses in neutrophils and increased translation of adaptive immune-related genes in monocytes/macrophages coupled with decreased glucocorticoid responses. Subsequent lymphocyte activation at post-reperfusion identified transcriptional programs associated with the transition to adaptive immunity found only among IRI+ recipients. CONCLUSIONS: Myeloid subset-specific genes and related signaling pathways provide targets for the development of therapeutic strategies aimed at limiting IRI in the clinical setting of liver transplantation.

Impact of radiological and pathological splenic vein involvement in patients with resectable pancreatic body or tail cancer.

PURPOSE: Several studies have reported a negative impact on survival associated with splenic vessel involvement, especially splenic artery (SpA) involvement, in patients diagnosed with pancreatic body or tail cancer. However, there is limited research on splenic vein (SpV) involvement. Therefore, we aimed to elucidate the significance of splenic vessel involvement, especially SpV involvement, in patients with resectable pancreatic body or tail cancer. METHODS: Between January 2007 and December 2021, 116 consecutive patients underwent distal pancreatectomies for pancreatic body or tail cancer. Among them, this study specifically examined 88 patients with resectable pancreatic body or tail cancer to elucidate prognostic factors using a multivariable Cox proportional analysis. The Kaplan-Meier method evaluated the impact of SpV involvement in terms of both radiological and pathological aspects and the efficacy of neoadjuvant therapy. RESULTS: Higher pre-operative carcinoembryonic antigen levels, larger tumour size, pathological SpV invasion, and non-completion of adjuvant therapy were identified as independent poor prognostic factors for overall survival (OS) and recurrence-free survival (RFS). Additionally, patients with radiological SpV encasement had significantly worse prognoses in terms of OS (p = 0.039) and RFS (p < 0.001). The sensitivity and specificity of multidetector-row computed tomography for detecting pathological SpV invasion were 81.0% and 61.2%, respectively. However, the prognostic impact of neoadjuvant therapy could not be determined, regardless of radiological SpV involvement. CONCLUSION: Radiological and pathological SpV involvement is a poor prognostic factor for patients with resectable pancreatic body or tail cancer. New innovative treatments and effective neoadjuvant therapy regimens are required for patients with SpV involvement.

SIRT1 regulates hepatocyte programmed cell death via GSDME - IL18 axis in human and mouse liver transplantation.

Sirtuin 1 (SIRT1) is a histone/protein deacetylase in the cellular response to inflammatory, metabolic, and oxidative stressors. We previously reported that myeloid SIRT1 regulates the inflamed liver's canonical pyroptosis cell death pathway. However, whether/how hepatocyte SIRT1 is engaged in programmed cell death in the cold-stressed liver remains uncertain. Here, we undertook translational studies in human and mouse orthotopic liver transplantation (OLT) to interrogate the significance of hepatocyte-specific SIRT1 in cold-stored donor livers and liver grafts after reperfusion. In the clinical arm of sixty human OLT patients, hepatic SIRT1 levels in cold-preserved donor livers correlated with the anti-apoptotic Bcl-2 expression. After reperfusion, improved OLT function was accompanied by hepatic SIRT1 levels negatively associated with cleaved caspase-3 expression. In the experimental arm, we compared FLOX-control with hepatocyte-specific SIRT1-KO livers after orthotopic transplantation into WT mouse recipients, parallel with primary murine hepatocyte cultures subjected to cold activation with/without knockdown of SIRT1, GSDME, and IL18Rß. Indeed, hepatocyte SIRT1 deficiency upregulated apoptosis and GSDME-mediated programmed cell death, deteriorating hepatocellular function and shortening OLT survival. Augmented GSDME processing, accompanied by increased secretion of IL18 by stressed hepatocytes, was prominent in SIRT1-deficient, cold-stored livers. Hepatocyte SIRT1 expression regulated anti-apoptotic Bcl-2/XIAP proteins, suppressed cold stress-triggered apoptosis, and mitigated GSDME licensing to release IL18. Notably, consistent with the ability of IL18 to depress hepatocyte SIRT1 and Bcl-2/XIAP in vitro, IL18 neutralization in vivo prevented hepatocellular damage and restored the anti-apoptotic phenotype in otherwise injury-prone SIRT1-deficient OLTs. In conclusion, this translational study identifies a novel hepatocyte SIRT1-IL18 molecular circuit as a therapeutic target in the mechanism underpinning hepatocyte death pathways in human and mouse liver transplantation.

Systematic profiling of conditional pathway activation identifies context-dependent synthetic lethalities.

The paradigm of cancer-targeted therapies has focused largely on inhibition of critical pathways in cancer. Conversely, conditional activation of signaling pathways as a new source of selective cancer vulnerabilities has not been deeply characterized. In this study, we sought to systematically identify context-specific gene-activation-induced lethalities in cancer. To this end, we developed a method for gain-of-function genetic perturbations simultaneously across ~500 barcoded cancer cell lines. Using this approach, we queried the pan-cancer vulnerability landscape upon activating ten key pathway nodes, revealing selective activation dependencies of MAPK and PI3K pathways associated with specific biomarkers. Notably, we discovered new pathway hyperactivation dependencies in subsets of APC-mutant colorectal cancers where further activation of the WNT pathway by APC knockdown or direct ß-catenin overexpression led to robust antitumor effects in xenograft and patient-derived organoid models. Together, this study reveals a new class of conditional gene-activation dependencies in cancer.

A tissue-intrinsic IL-33/EGF circuit promotes epithelial regeneration after intestinal injury.

Intestinal stem cells (ISCs) maintain the epithelial lining of the intestines, but mechanisms regulating ISCs and their niche after damage remain poorly understood. Utilizing radiation injury to model intestinal pathology, we report here that the Interleukin-33 (IL-33)/ST2 axis, an immunomodulatory pathway monitored clinically as an intestinal injury biomarker, regulates intrinsic epithelial regeneration by inducing production of epidermal growth factor (EGF). Three-dimensional imaging and lineage-specific RiboTag induction within the stem cell compartment indicated that ISCs expressed IL-33 in response to radiation injury. Neighboring Paneth cells responded to IL-33 by augmenting production of EGF, which promoted ISC recovery and epithelial regeneration. These findings reveal an unknown pathway of niche regulation and crypt regeneration whereby the niche responds dynamically upon injury and the stem cells orchestrate regeneration by regulating their niche. This regenerative circuit also highlights the breadth of IL-33 activity beyond immunomodulation and the therapeutic potential of EGF administration for treatment of intestinal injury.

[Digital Breast Tomosynthesis Quality Control Manual Overview].

Recently, mammography systems equipped with digital breast tomosynthesis (DBT) have become widely used in Japan. Therefore, it is urgently necessary to establish a quality control method for DBTs. So far, we have been studying acceptance tests for DBTs with reference to EUREF. In 2020, IEC 61223-3-6 was published, which provides not only acceptance tests but also constancy test methods. Therefore, we conducted data collection using DBTs sold in Japan and examined the feasibility of conducting constancy tests. Although there were some items that were difficult to implement in each device, we were able to confirm quality control items that could be implemented in many devices. In addition, we were able to confirm routine tests that enable rapid evaluation. Based on these results, we have developed a "Digital Breast Tomosynthesis Quality Control Manual". In this paper, we report an overview of the manual and the results of routine tests.

Long-term effectiveness and safety of infliximab-biosimilar: A multicenter Phoenix retrospective cohort study.

BACKGROUND: Infliximab (IFX) effectively treats patients with inflammatory bowel disease (IBD). IFX-biosimilar (IFX-BS) has the same amino acid sequence as that of the IFX originator, and its increasing use is expected to reduce national healthcare costs. Long-term efficacy and safety of IFX-BS in patients with Crohn's disease (CD) and ulcerative colitis (UC) have not been completely investigated. METHODS: We conducted a retrospective, multicenter observational study of patients with IBD who received IFX-BS treatment at three hospitals between October 2016 and April 2022. Clinical data were collected from electronic medical records and evaluated for achieving clinical remission (CR) using Crohn's disease activity index (CDAI) and partial Mayo (pMayo) score, persistency of long-term IFX-BS administration, and clinical response rate in the bio-naïve and bio-failure groups. RESULTS: A total of 117 patients with IBD (90 CD and 27 UC) were included. The study findings indicated that both bio-naïve and bio-failure groups of patients with UC showed similar effectiveness of IFX-BS. The treatment persistence rate in patients with CD was significantly higher in the bio-naïve (P = 0.042) and switch (P = 0.010) groups than in the bio-failure group. In the former two groups, the treatment persistence rate was high at two years after administration (more than 80%). In patients with UC, the findings indicated higher treatment persistence rate in the switch group than in the bio-naïve group. Univariable and multivariable analyses for treatment persistence rate showed that the albumin level at the initial IFX-BS administration and groups (bio-naïve, bio-failure and switch) were effective factors for patients with CD. Adverse events were reported in 18 patients (15.4%). CONCLUSION: The present study demonstrates the long-term effectiveness and safety of IFX-BS. In addition to the favorable remission induction in the bio-naïve and bio-failure groups, we demonstrated remission maintenance and treatment persistence rates beyond two years. Albumin level and groups were associated with better treatment persistence in patients with CD.

Spleen volume is a predictor of posthepatectomy liver failure and short-term mortality for hepatocellular carcinoma.

BACKGROUND: The study aimed at retrospectively assessing the impact of spleen volume (SpV) on the development of posthepatectomy liver failure (PHLF) in patients who underwent hepatectomy for hepatocellular carcinoma (HCC). METHODS: 152 patients with primary HCC who underwent hepatectomy (sectionectomy or more) were classified into PHLF and non-PHLF groups, and then the relationship between PHLF and SpV was assessed. SpV (cm3) was obtained from preoperative CT and standardized based on the patient's body surface area (BSA, m2). RESULTS: PHLF was observed in 39 (26%) of the 152 cases. SpV/BSA was significantly higher in the PHLF group, and the postoperative 1-year survival rate was significantly worse in the PHLF group than that in the non-PHLF group (p = 0.044). Multivariable analysis revealed SpV/BSA as a significant independent risk factor for PHLF. Using the cut-off value (160 cm3/m2), the 152 cases were divided into small SpV and large SpV groups. The incidence of PHLF was significantly higher in the large SpV group (p = 0.002), the liver failure-related mortality rate was also significantly higher in the large SpV group (p = 0.007), and the 1-year survival rate was significantly worse in the large SpV group (p = 0.035). CONCLUSION: These results suggest SpV as a predictor of PHLF and short-term mortality in patients who underwent hepatectomy for HCC. Moreover, SpV measurement is a simple and potentially useful method for predicting PHLF in patients with HCC.

Safety and efficacy of neoadjuvant chemotherapy based on our resectability criteria for locally advanced perihilar cholangiocarcinoma.

PURPOSE: Neoadjuvant chemotherapy (NAC) is not commonly used for perihilar cholangiocarcinoma (PHC). This study evaluated the safety and efficacy of NAC for PHC. METHODS: Ninety-one PHC patients without metastases were treated at our department. Patients were classified as resectable (R), borderline resectable (BR), or locally advanced unresectable (LA). Upfront surgery (US) was performed for R-PHC patients without regional lymph node metastases (LNM) or those unable to tolerate NAC. The NAC regimen comprised two courses of gemcitabine-based chemotherapy for advanced PHC: R-PHC with LNM, BR, and LA. RESULTS: US and NAC were performed on 32 and 59 patients, respectively. For US, 31 patients underwent curative intent surgery (upfront-CIS). NAC caused adverse effects in 10/59 (17%), allowed 36/59 (61%) to undergo curative intent surgery (NAC-CIS) without impairing liver function, and spared 23/59 (39%) from undergoing resection (NAC-UR). Overall survival was better in the upfront-CIS and NAC-CIS groups than in the NAC-UR group (MST: 74 vs 57 vs 17 months, p < 0.001). In 59 NAC patients, tumour size response occurred in 11/11 (100%) of R, 22/33 (66.7%) of BR, and 9/15 (60.0%) of LA patients. The un-resection rate was the highest in the LA group (27% [3/11] than in R, 30% [10/33] in BR, and 67% [10/15] in LA, p = 0.039). Multivariate analyses revealed that LA and age were independent risk factors for non-resection after NAC. CONCLUSION: was safe and contributed to improving survival in advanced PHC patients. R-PHC was responsive to NAC, but LA remains a risk factor for non-resection through NAC.

Multicenter prospective registration study of efficacy and safety of capsule endoscopy in Crohn's disease in Japan (SPREAD-J study).

BACKGROUND: Evidence of small-bowel capsule endoscopy (SBCE) for evaluating lesions in Crohn's disease (CD) is lacking. We aimed to clarify the effectiveness and safety of SBCE in a large sample of patients with CD. METHODS: This multicenter prospective registration study recorded the clinical information and SBCE results of patients with definitive CD (d-CD) or suspected CD (s-CD). The primary outcomes were the rates of successful assessment of disease activity using SBCE, definitive diagnosis of CD, and adverse events. Secondary outcomes were the assessment of SBCE findings in patients with d-CD and s-CD and factors affecting SBCE incompletion and retention; and tertiary outcomes included the association between clinical disease activity or blood examination, endoscopic disease activity, ileal CD, and the questionnaire assessment of patient acceptance of SBCE. RESULTS: Of 544 patients analyzed, 541 underwent SBCE with 7 (1.3%) retention cases. Of 468 patients with d-CD, 97.6% could be evaluated for endoscopic activity. Of 76 patients with s-CD, 15.8% were diagnosed with 'confirmed CD'. CD lesions were more frequently observed in the ileum and were only seen in the jejunum in 3.4% of the patients. Male sex and stenosis were risk factors for incomplete SBCE, and high C-reactive protein levels and stenosis were risk factors for capsule retention. In L1 (Montreal classification) patients, clinical remission was associated with endoscopic remission but showed low specificity and accuracy. The answers to the acceptability questionnaire showed the minimal invasiveness and tolerability of SBCE. CONCLUSION: SBCE is practical and safe in patients with CD.

Inverted Y-shaped technique for complex superior mesenteric / portal vein reconstruction in pancreatoduodenectomy for locally advanced pancreatic head ductal adenocarcinoma.

Most pancreatoduodenectomy (PD) procedures for locally advanced pancreatic head adenocarcinoma (PDAC) require superior mesenteric/portal vein (SMV/PV) axis resection and reconstruction. Here we describe the inverted Y-shaped as a new technique for complex SMV/PV reconstruction and aimed at evaluating its safety and effectiveness. Among 287 patients who underwent PD for locally advanced PDAC from April, 2007 to December, 2020 at our hospital, 11 patients (3.8%) who underwent PV/SMV reconstruction with this technique were enrolled. Briefly, two distal veins were slit-wedged, sutured, resulting in one orifice, then reconstruction was completed with (n = 6) or without (n = 5) interposed autologous right external iliac vein (REIV) grafts, respectively. Operation time and blood loss were 649 (502-822) min and 1782 (475-6680) mL, respectively. The median length of resected SMV/PV was 40 (20-70) mm, 50 (50-70) mm for REIV grafts, and the splenic vein was resected in eight patients. No patient developed pancreatic fistula; mild leg edema was observed in the six graft patients and the median hospital stay was 36.0 d. PV patency rate at 2 mo after PD was 91% (10/11) and no 90-d mortality was recorded. R0 resection rate was 91% (10/11). It is feasible to safely reconstruct the SMV/PV using the inverted Y-shaped technique in appropriately selected PDAC patients.

Extrapancreatic extension is a better adverse prognostic factor than tumor size in patients with localized pancreatic ductal adenocarcinoma treated with chemoradiotherapy - comparison of T category between the American Joint Committee on Cancer and Japan Pancreas Society.

BACKGROUND: T category classification for pancreatic ductal adenocarcinoma (PDAC) in the Classification of Pancreatic Cancer by the Japan Pancreas Society (JPS) is quite different from that of the American Joint Committee on Cancer (AJCC). The JPS classification focuses on extrapancreatic extension, while the AJCC focuses mainly on tumor size. This study aimed at identifying prognostic factors in PDAC patients undergoing chemoradiotherapy (CRT) by comparing the differences of T categories in these two classifications. METHODS: This retrospective study involved 344 PDAC patients who underwent CRT from 2005 to 2019 and their T-category variables were re-evaluated on computed tomography (CT) images. Disease-specific survival (DSS) was compared based on the JPS and AJCC T categories, while multivariate analysis was performed to identify prognostic factors. RESULTS: Based on the AJCC, 5-year DSS of T3 was better than those of T1 and T2 (57.1% vs. 47.7% and 37.4%). In multivariate analysis, performance status, CEA, the involvement of superior mesenteric vein and superior mesenteric artery, the JPS stage before CRT, and regimen of chemotherapy were identified as independent prognostic factors. CONCLUSIONS: In localized PDAC patients treated with chemoradiotherapy, extrapancreatic extension, as while as biological, conditional and therapeutic factors, is a better prognostic factor than tumor size.

Tumor-Infiltrating CD8-Positive T-Cells Associated with MMR and p53 Protein Expression Can Stratify Endometrial Carcinoma for Prognosis.

BACKGROUND: Inspired by the molecular classification of endometrial carcinoma (EC) proposed by The Cancer Genome Atlas Research Network (TCGA), we investigated tumor-infiltrating CD8-positive T-cell as well as DNA mismatch repair (MMR) protein and p53 protein expression, and we developed a new classification system for ECs to predict patients' prognosis using immunohistochemical methods. METHODS: The study included 128 patients with ECs who underwent surgery. Paraffin-embedded tissue sections of the tumor were stained using antibodies against MMR protein, p53, and CD8. Cases were stratified into four classes by a sequential algorithm. An immunohistochemical classification system for ECs (ICEC) was created, including HCD8, MMR-D, LCD8, and p53 LCD8. RESULTS: In ICEC, 16 cases (12.5%), 27 cases (21.09%), 67 cases (52.34%), and 18 cases (14.06%) belonged to HCD8, MMR-D, LCD8, and p53 LCD8, respectively. ICEC did not show any correlation with clinical stage, lymphovascular space invasion, or lymph node metastasis. However, the p53 LCD8 class contained a significantly higher proportion of G3 ECs and serous carcinoma (p < 0.0001). ICEC showed prognostic significance in overall survival (OS) (p < 0.0001) and disease-free survival (DFS) (p < 0.0001). The class of p53 LCD8 showed the worst prognosis among the classes. CONCLUSIONS: ICEC classification is useful in predicting the prognosis of ECs.

Vascular Normalization Caused by Short-Term Lenvatinib Could Enhance Transarterial Chemoembolization in Hepatocellular Carcinoma.

We describe the clinical effects of short-term lenvatinib administration prior to conventional transarterial chemoembolization (cTACE) on tumor vasculature. Two patients with unresectable hepatocellular carcinoma underwent high-resolution digital subtraction angiography (DSA) and perfusion four-dimensional computed tomography during hepatic arteriography (4D-CTHA) before and after administration of lenvatinib treatment. The doses and periods of lenvatinib administration were, respectively, 12 mg/day for 7 days and 8 mg/day for 4 days. In both cases, high-resolution DSA revealed a decrease in dilatation and tortuosity of the tumor vessels. Furthermore, the tumor staining became more refined, and newly formed tiny tumor vessels were observed. Perfusion 4D-CTHA revealed a decrease in arterial blood flow to the tumor by 28.6% (from 487.9 to 139.5 mL/min/100 mg) and 42.5% (from 288.2 to 122.6 mL/min/100 mg) in the two cases, respectively. The cTACE procedure resulted in good lipiodol accumulation and complete response. Patients have remained recurrence-free for 12 and 11 months after the cTACE procedure, respectively. The administration of short-term lenvatinib in these two cases resulted in the normalization of tumor vessels, which likely led to improved lipiodol accumulation and a favorable antitumor effect.