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.

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.

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.

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.

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.

Severe thrombocytopenia caused by cytomegalovirus infection in an immunocompetent adult: A case report.

A 53-year-old otherwise healthy man was referred to our hospital with a fever of unknown origin, headache, and arthralgia. Four days earlier, he had a fever with chills. Treatment with antibiotics and acetaminophen proved ineffective, with the patient subsequently developing headache and joint pain. Blood analysis revealed elevated inflammatory markers, liver impairment, and severe thrombocytopenia (platelet count, 19,000/µL). Subsequent tests revealed elevated levels of anti-cytomegalovirus IgM and IgG. Based on these findings, the patient was diagnosed with severe thrombocytopenia associated with cytomegalovirus infection. Platelet counts increased spontaneously without antiviral therapy. Forty-five days after the initial visit, the symptoms improved, and blood tests revealed resolution of the inflammatory findings, with the platelet count recovering to 155,000/µL. Although the disease may resolve spontaneously, cytomegalovirus infection should be considered as a differential diagnosis in case of severe thrombocytopenia in immunocompetent adults.

Risk factors for recurrent biliary obstruction following suprapapillary placement of a plastic stent as preoperative biliary drainage for perihilar biliary malignancy.

BACKGROUND/PURPOSE: The usefulness of endoscopic biliary stenting by deploying a plastic stent suprapapillary, called inside-stent (IS) placement, as preoperative biliary drainage (PBD) for perihilar biliary malignancy (PHBM) has been demonstrated. This study investigated risk factors for recurrent biliary obstruction (RBO) after IS placement. METHODS: Consecutive patients with potentially resectable PHBM treated with IS placement as PBD between 2017 and 2023 at Nagoya University Hospital were retrospectively reviewed. RESULTS: A total of 157 patients were included, with RBO occurring in 34 (22%) patients. The non-RBO rates were 83% at 30 days, 77% at 60 days, and 57% at 90 days. The most common cause of RBO was stent occlusion (n = 14), followed by segmental cholangitis (n = 12) and stent migration (n = 8). Stent migration and occlusion occurred more frequently within and after 1 week post-stenting, respectively. In multivariate analysis, biliary infection before IS was the sole risk factor for RBO, with a hazard ratio of 2.404 (95% confidence interval 1.163-4.972; p = .018). This risk was reduced by temporary endoscopic nasobiliary drainage prior to definitive IS placement. CONCLUSIONS: Biliary infection before IS was identified as an independent risk factor for RBO in patients with PHBM with IS as PBD. CLINICAL TRIAL REGISTER: Clinical trial registration number: UMIN000025631.

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.