TLK1 Inhibition Enhances the Anticancer Effect of Deep UV Irradiation Through CHK1 Activation.

BACKGROUND/AIM: A deep ultraviolet (DUV) light-emitting diode (LED) is a device that can irradiate electromagnetic waves from 250 nm to 350 nm. Tousled-like kinase 1 (TLK1) encodes a nuclear serine/threonine kinase, which is thought to influence the effects of DUV irradiation in cancer. The aim of this study was to clarify the interaction of TLK1 with DUV irradiation-induced DNA damage in cancer cells. MATERIALS AND METHODS: Pancreatic cancer cell lines were treated with or without DUV. TLK1 expression and phosphorylation in the two groups were examined. Then, these cancer cell lines were treated with thioridazine (THD), DUV or both. Thereafter, cytomorphology and apoptosis were assessed. Several proteins related to DNA damage, were analyzed in cancer cells treated with DUV and THD. Tumors in a subcutaneous xenograft model were treated with THD, DUV, or both for six weeks. RESULTS: DUV irradiation induced the phosphorylation of TLK1 in pancreatic cancer cell lines. Cytomorphology was significantly changed in pancreatic cancer cells treated with DUV and THD. TLK1 inhibition enhanced DUV irradiation-induced apoptosis in cancer cells. Interestingly, CHK1 and pCHK1 expression was suppressed after TLK1 inhibition. In addition, inhibition of MRE11 led to a decrease in the expression of CHK1 and pCHK1, accompanied by a notable increase in apoptosis. In the subcutaneous xenograft models, the tumor volume in the DUV and THD groups was lower than that in the other groups. CONCLUSION: TLK1 phosphorylation is an important event in DUV irradiation. DUV irradiation combined with TLK1 inhibition has therapeutic potential in pancreatic cancer cells.

Trefoil factor 1 suppresses stemness and enhances chemosensitivity of pancreatic cancer.

BACKGROUND AND AIMS: Pancreatic cancer is one of the most lethal malignancies, partly due to resistance to conventional chemotherapy. The chemoresistance of malignant tumors is associated with epithelial-mesenchymal transition (EMT) and the stemness of cancer cells. The aim of this study is to investigate the availability and functional mechanisms of trefoil factor family 1 (TFF1), a tumor-suppressive protein in pancreatic carcinogenesis, to treat pancreatic cancer. METHODS: To investigate the role of endogenous TFF1 in human and mice, specimens of human pancreatic cancer and genetically engineered mouse model of pancreatic cancer (KPC/TFF1KO; Pdx1-Cre/LSL-KRASG12D/LSL-p53R172H/TFF1-/-) were analyzed by immunohistochemistry (IHC). To explore the efficacy of extracellular administration of TFF1, recombinant and chemically synthesized TFF1 were administered to pancreatic cancer cell lines, a xenograft mouse model and a transgenic mouse model. RESULTS: The deficiency of TFF1 was associated with increased EMT of cancer cells in mouse models of pancreatic cancer, KPC. The expression of TFF1 in cancer cells was associated with better survival rate of the patients who underwent chemotherapy, and loss of TFF1 deteriorated the benefit of gemcitabine in KPC mice. Extracellular administration of TFF1 inhibited gemcitabine-induced EMT, Wnt pathway activation and cancer stemness, eventually increased apoptosis of pancreatic cancer cells in vitro. In vivo, combined treatment of gemcitabine and subcutaneous administration of TFF1 arrested tumor growth in xenograft mouse model and resulted in the better survival of KPC mice by inhibiting EMT and cancer stemness. CONCLUSION: These results indicate that TFF1 can contribute to establishing a novel strategy to treat pancreatic cancer patients by enhancing chemosensitivity.

A clinical assessment of three-dimensional-printed liver model navigation for thrice or more repeated hepatectomy based on a conversation analysis.

PURPOSES: We performed a conversation analysis of the speech conducted among the surgical team during three-dimensional (3D)-printed liver model navigation for thrice or more repeated hepatectomy (TMRH). METHODS: Seventeen patients underwent 3D-printed liver navigation surgery for TMRH. After transcription of the utterances recorded during surgery, the transcribed utterances were coded by the utterer, utterance object, utterance content, sensor, and surgical process during conversation. We then analyzed the utterances and clarified the association between the surgical process and conversation through the intraoperative reference of the 3D-printed liver. RESULTS: In total, 130 conversations including 1648 segments were recorded. Utterance coding showed that the operator/assistant, 3D-printed liver/real liver, fact check (F)/plan check (Pc), visual check/tactile check, and confirmation of planned resection or preservation target (T)/confirmation of planned or ongoing resection line (L) accounted for 791/857, 885/763, 1148/500, 1208/440, and 1304/344 segments, respectively. The utterance's proportions of assistants, F, F of T on 3D-printed liver, F of T on real liver, and Pc of L on 3D-printed liver were significantly higher during non-expert surgeries than during expert surgeries. Confirming the surgical process with both 3D-printed liver and real liver and performing planning using a 3D-printed liver facilitates the safe implementation of TMRH, regardless of the surgeon's experience. CONCLUSIONS: The present study, using a unique conversation analysis, provided the first evidence for the clinical value of 3D-printed liver for TMRH for anatomical guidance of non-expert surgeons.

Evaluation of 4D Flow MRI-Derived Relative Residence Time as a Marker for Cirrhosis Associated Portal Vein Thrombosis.

BACKGROUND: Portal vein thrombosis (PVT) is thought to arise from stagnant blood flow, yet conclusive evidence is lacking. Relative residence time (RRT) assessed using 4D Flow MRI may offer insight into portal flow stagnation. PURPOSE: To explore the relationship between RRT values and the presence of PVT in cirrhotic participants. STUDY TYPE: Prospective. POPULATION: Forty-eight participants with liver cirrhosis (27 males, median age 67 years [IQR: 57-73]) and 20 healthy control participants (12 males, median age 45 years [IQR: 40-54]). FIELD STRENGTH/SEQUENCE: 3 T/4D Flow MRI. ASSESSMENT: Laboratory (liver and kidney function test results and platelet count) and clinical data (presence of tumors and other imaging findings), and portal hemodynamics derived from 4D Flow MRI (spatiotemporally averaged RRT [RRT-mean], flow velocity, and flow rate) were analyzed. STATISTICAL TESTS: We used multivariable logistic regression, adjusted by selected covariates through the Lasso method, to explore whether RRT-mean is an independent risk factor for PVT. The area under the ROC curve (AUC) was also calculated to assess the model's discriminative ability. P < 0.05 indicated statistical significance. RESULTS: The liver cirrhosis group consisted of 16 participants with PVT and 32 without PVT. Higher RRT-mean values (odds ratio [OR] 11.4 [95% CI: 2.19, 118]) and lower platelet count (OR 0.98 per 1000 µL [95% CI: 0.96, 0.99]) were independent risk factors for PVT. The incorporation of RRT-mean (AUC, 0.77) alongside platelet count (AUC, 0.75) resulted in an AUC of 0.84. When including healthy control participants, RRT-mean had an adjusted OR of 12.4 and the AUC of the combined model (RRT-mean and platelet count) was 0.90. DATA CONCLUSION: Prolonged RRT values and low platelet count were significantly associated with the presence of PVT in cirrhotic participants. RRT values derived from 4D Flow MRI may have potential clinical relevance in the management of PVT. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Intraductal papillary neoplasms of the bile ducts: a comparative study of a rare disease in Europe and Nagoya, Japan.

BACKGROUND: Intraductal papillary neoplasm of the bile ducts (IPNB) is a rare disease in Western countries. The aim of this study was to compare tumor characteristics, management strategies, and outcomes between Western and Eastern patients who underwent surgical resection for IPNB. METHODS: A multi-institutional retrospective series of patients with IPNB undergoing surgery between January 2010 and December 2020 was gathered under the auspices of the European-African Hepato-Pancreato-Biliary Association (E-AHPBA), and at Nagoya University Hospital, Japan. RESULTS: A total of 85 patients (51% male; median age 66 years) from 28 E-AHPBA centers were compared to 91 patients (64% male; median age 71 years) from Nagoya. Patients in Europe had more multiple lesions (23% vs 2%, P < .001), less invasive carcinoma (42% vs 85%, P < .001), and more intrahepatic tumors (52% vs 24%, P < .001) than in Nagoya. Patients in Europe experienced less 90-day grade >3 Clavien-Dindo complications (33% vs 68%, P < .001), but higher 90-day mortality rate (7.0% vs 0%, P = .03). R0 resections (81% vs 82%) were similar. Overall survival, excluding 90-day postoperative deaths, was similar in both regions. DISCUSSION: Despite performing more extensive resections, the low perioperative mortality rate observed in Nagoya was probably influenced by a combination of patient-, tumor-, and surgery-related factors.

Utility of modified pancreaticoduodenectomy (Hi-cut PD) for middle-third cholangiocarcinoma: an alternative to hepatopancreaticoduodenectomy.

BACKGROUND: The standard procedure for middle-third cholangiocarcinoma (MCC) is pancreaticoduodenectomy (PD); hepatopancreaticoduodenectomy (HPD) is often performed despite its high risk. There is no clear selection guidance for these procedures. METHODS: Patients with MCC who underwent HPD or PD were retrospectively evaluated. The conventional PD was modified (mPD) to transect the bile duct beyond or close to the cranial level of the portal bifurcation. RESULTS: The mPD group (n = 55) was characterized by older age, shorter operation time, less blood loss, and less frequent complications than were observed in the HPD group (n = 34). The median grossly tumor-free margin of the proximal bile duct (GM) was 13 mm vs 20 mm (P = 0.006). Overall survival did not differ significantly between groups (48% vs 53% at 5 years, P = 0.399). Multivariate analysis identified positive surgical margin as a sole independent prognostic factor (hazard ratio, 1.89; P = 0.043), which was statistically associated with GM length. Five-year survival for mPD patients with GM ≥15 mm was significantly better than that for those who had GM <15 mm (69% vs 33%, P = 0.011) and comparable to that of HPD patients (53%, P = 0.450). CONCLUSION: The mPD may be recommended in patients with MCC, provided that GM ≥15 mm is expected from the preoperative radiological imaging. Otherwise, HPD should be considered.

Liver remnant volume to body weight ratio of 0.65% as a lower limit in right hepatic trisectionectomy with bile duct resection.

BACKGROUND: Previous studies have suggested the utility of an indocyanine green plasma clearance rate of the future liver remnant (FLR) (ICGK-F) ≥0.05 in hepatobiliary resection to reduce the surgical risk. The present study aimed to verify whether future liver remnant size rather than ICGK-F matters in extended hepatobiliary resection. METHODS: Between 2004 and 2021, patients who underwent right hepatic trisectionectomy with bile duct resection were included. The effect of the FLR volume-to-body weight ratio (FLR/BW) and ICGK-F on posthepatectomy liver failure was evaluated along with other parameters. RESULTS: Among 91 study patients, the median ICGK-F, FLR, and FLR/BW were 0.057 (range, 0.027-0.099), 392 mL (145-705), and 0.78% (0.40-1.37), respectively. Posthepatectomy liver failure occurred in 23 patients. The incidence was 10 (40%) in 25 patients with an ICGK-F <0.05 and 12 (18%) in 65 patients with an ICGK-F ≥0.05 (P = .053); 13 (52%) in 25 patients with a FLR/BW <0.65% and 10 (15%) in 66 patients with a FLR/BW ≥0.65% (P = .001). Multivariate analysis showed that a FLR/BW <0.65% (odds ratio, 11.7; P = .005), age ≥65 years (odds ratio, 31.7; P < .001), and blood loss ≥25 mL/kg (odds ratio, 22.1; P = .004) were independent predictors of posthepatectomy liver failure, but ICGK-F <0.05 was not (P = .499). According to the meeting number of 3 factors, posthepatectomy liver failure incidence was 0 of 22 (0%) in patients with 0 factors, 6 of 43 (14%) in patients with 1, and 17 of 26 (65%) in patients with 2 or 3 (P < .001). CONCLUSION: A FLR/BW ≥0.65% may serve as a volumetric basis to reduce posthepatectomy liver failure after extended hepatobiliary resection.

Saturation of Percutaneous Oxygen Decreases with Meal Consumption in Patients with Acute Pneumonia.

OBJECTIVE: This study aimed to investigate how respiratory status may be affected during meal consumption in patients with acute pneumonia, mainly aspiration pneumonia, using percutaneous oxygen saturation (SpO2) and pulse rate (PR) measurements. METHODS: We recruited 44 inpatients at the Towada City Hospital and divided them into 'pneumonia' and 'control' groups. Generalized linear mixed effects model was used for analysis. The pneumonia group comprised 22 patients (mean age 81.2 ± 7.0 years, body mass index [BMI] 21.1 ± 4.0 kg/m2) with 1-3 points A-DROP scores. The control group comprised 22 patients (mean age 80.5 ± 4.9 years, BMI 20.9 ± 2.9 kg/m2) with no obvious respiratory diseases. SpO2 and PR were measured 30 min before, during, and 30 min after meals. RESULTS: SpO2 was significantly lower during meals in the pneumonia group (-1.60%; 95% confidence interval = -2.76 to -0.44). There were no significant changes in PR during or after meals in the pneumonia group. CONCLUSIONS: This study suggests pneumonia may worsen respiratory status during meal intake. Patients with pneumonia may be unable to eat adequately due to worsened oxygenation during meals, even in the absence of aspiration. Therefore, it is important to observe whether there is a decrease in respiratory status during meals.

Four-dimensional Flow MRI Assessment of Portal Hemodynamics and Hepatic Regeneration after Portal Vein Embolization.

Background Percutaneous transhepatic portal vein (PV) embolization (PVE) is a standard preoperative procedure for advanced biliary cancer when the future liver remnant (FLR) is insufficient, yet the effect of this procedure on portal hemodynamics is still unclear. Purpose To assess whether four-dimensional (4D) MRI flowmetry can be used to estimate FLR volume and to identify the optimal time for this measurement. Materials and Methods This prospective single-center study enrolled consecutive adult patients with biliary cancer who underwent percutaneous transhepatic PVE for the right liver between June 2020 and November 2022. Portal hemodynamics were assessed using 4D flow MRI before PVE and within 1 day (0-day group) or 3-4 days (3-day group) after PVE. FLR volume was measured using CT before PVE and after PVE but before surgery. Blood flow changes were analyzed with the Wilcoxon signed rank test, and correlations with Spearman rank correlation. Results The 0-day group included 24 participants (median age, 72 years [IQR, 69-77 years]; 17 male participants), and the 3-day group included 13 participants (median age, 71 years [IQR, 68-78 years]; eight male participants). Both groups showed increased left PV (LPV) flow rate after PVE (0-day group: from median 3.72 mL/sec [IQR, 2.83-4.55 mL/sec] to 9.48 mL/sec [IQR, 8.12-10.7 mL/sec], P < .001; 3-day group: from median 3.65 mL/sec [IQR, 2.14-3.79 mL/sec] to 8.16 mL/sec [IQR, 6.82-8.98 mL/sec], P < .001). LPV flow change correlated with FLR volume change relative to the number of days from PVE to presurgery CT only in the 3-day group (ρ = 0.62, P = .02; 0-day group, P = .11). The output of the regression equation for estimating presurgery FLR volume correlated with CT-measured volume (ρ = 0.78; P = .002). Conclusion Four-dimensional flow MRI demonstrated increased blood flow in residual portal branches 3-4 days after PVE, offering insights for estimating presurgery FLR volume. Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Roldán-Alzate and Oechtering in this issue.

Renal Dysfunction after Rectal Cancer Surgery: A Long-term Observational Study.

Objectives: Despite the high incidence of urinary dysfunction (UD) after rectal surgery, it remains questionable whether UD causes future chronic kidney disease (CKD). This study aimed to clarify the long-term trends in renal function and risk factors for future CKD after rectal resection. Methods: For comparison, patients who underwent rectal resection (n = 129) and colectomy (n = 127) between 2006 and 2017 were identified. The estimated glomerular filtration rate (eGFR) ratio was calculated as the ratio to the baseline. "eGFR ratio < 0.75 at 3-year" was adopted as a surrogate indicator of future CKD. Results: eGFR ratio significantly decreased in the rectal cohort compared with the colon cohort at 1.5 years (0.9 vs. 0.95, p = 0.008) and at 3 years (0.85 vs. 0.94, p < 0.001). Although the preoperative prevalence of CKD was lower in the rectal than the colon cohort (13.9% vs. 23.6%, p = 0.055), it was similar at 3 years (29.5% vs. 30.7%). In multivariate analysis, females, and cT4 were independent risk factors for future CKD, but UD itself was not. Conclusions: Postoperative eGFR significantly decreased after rectal cancer surgery compared to colectomy. The prevalence of CKD more than doubled at 3 years after rectal resection. The female sex and cT4 tumor, instead of the UD, were independent risk factors for future CKD.

Clinical value of fluorescent cholangiography for the infraportal type of right posterior bile duct.

BACKGROUND: The infraportal type of the right posterior bile duct (infraportal RPBD) is a well-known anatomical variation that increases the potential risk of intraoperative biliary injury. The aim of this study is to clarify the clinical value of fluorescent cholangiography during single-incision laparoscopic cholecystectomy (SILC) for patients with infraportal RPBD. MATERIAL AND METHODS: Our procedure for SILC utilized the SILS-Port, and another 5-mm forceps was inserted via an umbilical incision. A laparoscopic fluorescence imaging system developed by Karl Storz Endoskope was utilized for fluorescent cholangiography. Between July 2010 and March 2022, 41 patients with infraportal RPBD underwent SILC. We conducted retrospective reviews of patient data, focusing on the clinical value of fluorescent cholangiography. RESULTS: Thirty-one patients underwent fluorescent cholangiography during SILC, but the remaining ten did not. Only one patient who did not undergo fluorescent cholangiography developed an intraoperative biliary injury. The detectability of infraportal RPBD before and during the dissection of Calot's triangle was 16.1% and 45.2%, respectively. These visible infraportal RPBDs were characterized as connections to the common bile duct. The confluence pattern of infraportal RPBD significantly influenced its detectability during the dissection of Calot's triangle (p < 0.001). CONCLUSIONS: The application of fluorescent cholangiography can lead to safe SILC, even for patients with infraportal RPBD. Its benefit is emphasized when infraportal RPBD is connected to the common bile duct.

The Goal of Intraoperative Blood Loss in Major Hepatobiliary Resection for Perihilar Cholangiocarcinoma: Saving Patients From a Heavy Complication Burden.

OBJECTIVE: To determine the goal of intraoperative blood loss in hepatectomy for perihilar cholangiocarcinoma. BACKGROUND: Although massive bleeding can negatively affect the postoperative course, the target value of intraoperative bleeding to reduce its adverse impact is unknown. METHODS: Patients who underwent major hepatectomy for perihilar cholangiocarcinoma between 2010 and 2019 were included. Intraoperative blood loss was adjusted for body weight [adjusted blood loss (aBL)], and the overall postoperative complications were evaluated by the comprehensive complication index (CCI). The impact of aBL on CCI was assessed by the restricted cubic spline regression. RESULTS: A total of 425 patients were included. The median aBL was 17.8 (interquartile range, 11.8-26.3) mL/kg, and the CCI was 40.6 (33.7-49.5). Sixty-three (14.8%) patients had an aBL<10 mL/kg, nearly half (45.4%) of the patients were in the range of 10 ≤aBL<20 mL/kg, and 37 (8.7%) patients had an aBL >40 mL/kg. The spline regression analysis showed a nonlinear incremental association between aBL and CCI; CCI remained flat with an aBL under 10 mL/kg; increased significantly with an aBL ranging from 10 to 20 mL/kg; grew gradually with an aBL over 20 mL/kg. These inflection points of ~10 and 20 mL/kg were almost consistent with the cutoff values identified by the recursive partitioning technique. After adjusting for other risk factors for the postoperative course, the spline regression identified a similar model. CONCLUSIONS: aBL had a nonlinear aggravating effect on CCI after hepatectomy for perihilar cholangiocarcinoma. The primary goal of aBL should be <10 mL/kg to minimize CCI.

Two-step arterial reconstruction technique for en bloc resection of a large retroperitoneal liposarcoma involving the common iliac artery.

Retroperitoneal liposarcoma (RPLS) is a rare but challenging neoplasm, which is frequently associated with iliac vessel invasion. We describe how we used a two-step arterial reconstruction technique to perform en bloc resection of a large RPLS involving the iliac arteries in three patients. A temporal long in situ graft bypass was established using a prosthetic vascular graft during dissection of the tumor. This bypass provided an unobscured surgical field, while maintaining blood flow in the lower limb during the operation. After removal of the tumor and washing out the abdominal cavity, the new prosthetic vascular graft of a suitable length was placed. No graft-related complications, including vascular graft infection or graft occlusion, occurred during the follow-up period. This novel technique appears to provide a safe and effective way to remove large RPLSs involving the retroperitoneal major vessels.

Impact of skeletal muscle mass on the prognosis of patients undergoing neoadjuvant chemotherapy for resectable or borderline resectable pancreatic cancer.

BACKGROUND: Neoadjuvant chemotherapy is a common therapeutic procedure for patients with pancreatic cancer. This study aimed to investigate the association between the total psoas area (TPA) and prognosis in patients undergoing neoadjuvant chemotherapy for resectable or borderline resectable pancreatic cancer. STUDY DESIGN: This retrospective study included patients who underwent neoadjuvant chemotherapy for pancreatic cancer. TPA was measured at the level of the L3 vertebra using computed tomography. The patients were divided into low-TPA and normal-TPA groups. These dichotomizations were separately performed in patients with resectable and those with borderline resectable pancreatic cancer. RESULTS: In total, 44 patients had resectable pancreatic cancer and 71 patients had borderline resectable pancreatic cancer. Overall survival among patients with resectable pancreatic cancer did not differ between the normal- and low-TPA groups (median, 19.8 vs. 21.8 months, p = 0.447), whereas among patients with borderline resectable pancreatic cancer, the low-TPA group had shorter overall survival than the normal-TPA group (median, 21.8 vs. 32.9 months, p = 0.006). Among patients with borderline resectable pancreatic cancer, the low-TPA group was predictive of poor overall survival (adjusted hazard ratio, 2.57, p = 0.037). CONCLUSION: Low TPA is a risk factor of poor survival in patients undergoing neoadjuvant chemotherapy for borderline resectable pancreatic cancer. TPA evaluation could potentially suggest the treatment strategy in this disease.

Cyclodextrin Conjugated α-Bisabolol Suppresses FAK Phosphorylation and Induces Apoptosis in Pancreatic Cancer.

BACKGROUND/AIM: α-Bisabolol is an essential oil component extracted from plants, such as chamomile. We have previously reported that α-bisabolol suppressed proliferation, invasion, and motility of pancreas cancer. Cyclodextrin improved the solubility of α-bisabolol, therefore it enabled to administer intravenously. The aim of this study was to clarify the effect of cyclodextrin conjugated α-bisabolol (CD-BSB) and the signals pathways associated with α-bisabolol for pancreatic cancer. MATERIALS AND METHODS: Human pancreatic cancer cell lines were treated with or without CD-BSB. Cytomorphology and apoptosis were assessed in these treated groups. In addition, several phosphorylated proteins were analyzed to clarify the signal pathway concerning CD-BSB. In subcutaneous xenograft model, tumor volume and Ki-67 expression were evaluated among Control (untreated), CD-BSB, or Gemcitabine (GEM). RESULTS: CD-BSB significantly changed cytomorphology and induced apoptosis in pancreatic cancer cells. CD-BSB suppressed phosphorylation of focal adhesion kinase (FAK). In addition, pFAK 397 was inhibited by CD-BSB in a concentration-dependent manner in cancer cells. In the subcutaneous xenograft models, the tumor volume in the CD-BSB groups was lower than Control groups. Ki67-positive cells in CD-BSB treated group were lower than the GEM-treated groups. CONCLUSION: We clarified the efficiency of CD-BSB in xenograft tumor using intravenous administration. α-Bisabolol suppresses phosphorylation of FAK 397 and impairs cytoskeletal polymerization in a pancreatic cancer cell line. Further investigations are required to reveal the precise mechanisms of the antitumor effects of solubilized α-bisabolol to facilitate its clinical application. Our data indicate that solubilized α-bisabolol has therapeutic potential and could improve the prognosis of cancer patients.

Antitumor Effects of Deep Ultraviolet Irradiation for Pancreatic Cancer.

BACKGROUND/AIM: Deep ultraviolet (DUV) light spans within the 250 nm to 350 nm invisible wavelength range. Although it strongly damages various cells, the efficacy of DUV irradiation on pancreatic cancer cells has never been clarified. The purpose of this study was to reveal the antitumor effects of DUV irradiation on pancreatic cancer cells. MATERIALS AND METHODS: Human pancreatic cancer cell lines were eradicated with DUV or ultraviolet A (UVA) for 5 s. Several angiogenesis-related proteins were studied in cancer cells after DUV irradiation using a protein antibody array. A subcutaneous xenograft model was established by inoculation of pancreatic cancer cells into mice. Tumors in this model were irradiated with DUV or UVA once or twice for two weeks. Tumor volumes in these groups (DUV×1: one irradiation, DUV×2: two irradiations, and untreated) were analyzed one week after the second irradiation. RESULTS: DUV irradiation significantly changed the cytomorphology of pancreatic cancer cells. In addition, DUV irradiation induced apoptosis on pancreatic cancer cells more strongly than UVA irradiation and no irradiation. Interestingly, lower expression of thrombospondin 1 (TSP1) and tissue inhibitor of metalloproteinase 1 (TIMP1) was identified after DUV treatment. The tumor volume in the DUV-treated groups (DUV×1 and DUV×2) was smaller than that in the untreated group. CONCLUSION: Further investigations are required to reveal the precise mechanisms of the antitumor effects of DUV irradiation and to facilitate its clinical application as a new therapy for pancreatic cancer. Overall, DUV irradiation can be potentially used as a therapeutic option of pancreatic malignancy.

Assessing the Complicated Venous Hemodynamics and Therapeutic Outcomes of Budd-Chiari Syndrome with Respiratory-gated 4D Flow MR Imaging During the Expiratory and Inspiratory Phases.

A man in his 50s with Budd-Chiari syndrome diagnosed with the suprahepatic inferior vena cava (IVC) obstruction on CT was assessed using 4D Flow MRI before and after balloon angioplasty. 4D Flow MRI acquired in two respiratory phases, depicted complex hemodynamic and respiratory variability, and a jet stream at the narrowed channel of the membranous IVC. Post-interventional 4D Flow MRI showed that the IVC blood flow increased with corrected flow directions in the infrarenal IVC.

Early Prediction of a Serious Postoperative Course in Perihilar Cholangiocarcinoma: Trajectory Analysis of the Comprehensive Complication Index.

OBJECTIVE: The aim of this study was to visualize the postoperative clinical course using the comprehensive complication index (CCI) and to propose an early alarming sign for subsequent serious outcomes in perihilar cholangiocarcinoma. BACKGROUND: Surgery for this disease carries a high risk of morbidity and mortality. The developmental course of the overall morbidity burden and its clinical utility are unknown. METHODS: Patients who underwent major hepatectomy for perihilar cholan-giocarcinoma between 2010 and 2019 were reviewed retrospectively. All postoperative complications were evaluated according to the Clavien-Dindo classification (CDC), and the CCI was calculated on a daily basis until postoperative day 14 to construct an accumulating graph as a trajectory. Group-based trajectory modeling was conducted to categorize the trajectory into clinically distinct patterns and the predictive power of early CCI for a subsequent serious course was assessed. RESULTS: A total of 4230 complications occurred in the 484 study patients (CDC grade I, n = 27; II, n = 132; IlIa, n = 290; IIIb, n = 4; IVa, n = 21; IVb, n = 1; and V, n = 9). The trajectory was categorized into 3 patterns: mild (n = 209), moderate (n = 235), and severe (n = 40) morbidity courses. The 90-day mortality rate significantly differed among the courses: 0%, 0.9%, and 17.5%, respectively (P<0.001). The cutoff values of the CCI on postoperative days 1, 4, and 7 for predicting a severe morbidity course were 15.0, 28.5, and 40.6 with areas under the curves of 0.780, 0.924, and 0.984, respectively. CONCLUSIONS: The CCI could depict the chronological increase in the overall morbidity burden, categorized into 3 patterns. Early CCI potentially predicted sequential progression to serious outcomes.

Efficacy of Extended Modification in Left Hemihepatectomy for Advanced Perihilar Cholangiocarcinoma: Comparison Between H12345'8'-B-MHV and H1234-B.

OBJECTIVE: The aim of this study was to verify the prognostic impact of the tumor exposure at the liver transection margin (LTM) in left-sided perihilar cholangiocarcinoma and the impact of middle hepatic vein (MHV) resection on this exposure. BACKGROUND: In perihilar cholangiocarcinoma, tumors are unexpectedly exposed at the LTM during left hemihepatectomy (LH). METHODS: Patients who underwent LH for perihilar cholangiocarcinoma during 2002 to 2018 were retrospectively evaluated. LH was classified into conventional and extended types, which preserved and resected the MHVs, respectively. Positive LTM was defined as the involvement of invasive carcinoma at the liver transection plane and/or the adjacent Glissonean pedicle exposed. The clinicopathologic features and survival outcomes were compared between procedures. RESULTS: Among 236 patients, conventional and extended LHs were performed in 198 and 38 patients, respectively. The LTM was positive in 31 (13%) patients, with an incidence of 14% versus 8% ( P = 0.432) and 24% versus 0% in advanced tumors ( P = 0.011). Tumor size ≥ 18 mm ( P = 0.041), portal vein invasion ( P = 0.009), and conventional LH ( P = 0.028) independently predicted positive LTM. In patients with negative LTM, the survival was comparable between the two groups: 60.4% versus 59.2% at 3 years ( P = 0.206), which surpassed 17.7% for those with positive LTM in the conventional group ( P < 0.001). Multivariable analysis demonstrated that LTM status was an independent prognostic factor ( P = 0.009) along with ductal margin status ( P = 0.030). CONCLUSIONS: The LTM status is an important prognostic factor in perihilar cholangiocarcinoma. Extended LH reduced the risk of tumor exposure at the LTM with a subsequent improvement in the survival, particularly in advanced tumors.