Treatment and Prognosis for Pancreatic Duct Disruption Associated With Pancreatic Cancer: A Case Series of 15 Patients.

Background Pancreatic duct (PD) disruption can occasionally be attributed to pancreatic cancer. Therapeutic interventions for PD disruption due to pancreatic cancer and their influence on pancreatic cancer prognosis remain unclear. This study investigated the therapeutic modalities and prognostic implications of PD disruption in pancreatic cancer. Methods This retrospective study included 15 patients with PD disruption concomitant with pancreatic cancer between April 2011 and March 2023. As an endoscopic intervention for PD disruption, endoscopic pancreatic stenting (EPS) or endoscopic ultrasonography-guided pancreatic fluid collection drainage (EUS-PFD) was performed. Technical success was defined as stent placement and clinical success was defined as an improvement in PD disruption. Results Of the 15 cases of PD disruption, two involved only pancreatic juice leakage without symptoms, four involved pancreatic pseudocyst (PPC) without infection, and nine involved PPC with infection. Four patients underwent EPS, nine underwent EUS-PFD, and two underwent lumen-apposing metal stent placement. All patients achieved both technical and clinical success without complications. The clinical stage of pancreatic cancer ranged from carcinoma in situ to the metastatic phase. For the treatment of pancreatic cancer, five patients underwent surgical resection, and eight underwent chemotherapy. There was no obvious recurrence of peritoneal sowing. The median overall survival from the diagnosis of pancreatic cancer in the resected and non-resected cases was 74 and 9.6 months, respectively. Conclusion Endoscopic intervention was effective in all cases of PD disruption due to pancreatic cancer. Furthermore, even in cases of pancreatic cancer after PD disruption, survival rates were similar to those in cases without PD disruption and were achieved through surgical resection or chemotherapy.

Association of pancreatic atrophy patterns with intraductal extension of early pancreatic ductal adenocarcinoma: a multicenter retrospective study.

BACKGROUND: Focal pancreatic parenchymal atrophy (FPPA) and upstream pancreatic atrophy (UPA) may indicate the presence of early pancreatic cancer. In early pancreatic cancer, the tumor occasionally spreads laterally along the main pancreatic duct, presenting challenges in determining the extent of surgical resection. This study aimed to investigate the association of pancreatic atrophy pattern and intraductal cancer extension. METHODS: Thirty-two patients with early-stage pancreatic cancer who underwent surgery at five participating centers were enrolled. Pancreatic atrophy was defined as the narrowing of parenchyma compared to the surrounding parenchyma and was classified as either FPPA (partial atrophy surrounding the pancreatic duct stenosis) or UPA (global atrophy caudal to the site of duct stenosis). Intraductal cancer extension was defined as an extension exceeding 10 mm. RESULTS: Preoperative computed tomography revealed FPPA, UPA, and no parenchymal atrophy in 13, 13, and 6 patients. Cases with FPPA or UPA showed significantly longer cancer extensions than those without atrophy (P = 0.005 and P = 0.03, respectively). Intraductal cancer extension was present in all but one case of FPPA. 69% (9/13) of the cases with UPA showed intraductal cancer extension, whereas cases without atrophy showed no intraductal cancer extension. Importantly, two patients with FPPA or UPA showed positive resection margins during surgery and three patients with FPPA or UPA showed recurrence in the remnant pancreas. CONCLUSIONS: The presence of FPPA and UPA indicates lateral cancer extension in early-stage pancreatic cancer. Preoperative assessment of the pancreatic parenchyma may provide valuable insights for determining the extent of surgical resection.

Assessment of the biliary branching pattern of the caudate lobe in perihilar cholangiocarcinoma using ENBD-CT cholangiography.

BACKGROUND: Preoperative recognition of the anatomy of caudate biliary branches is important for the safe and complete resection of perihilar cholangiocarcinoma (PHC). In the present study, we identified these branches using an endoscopic nasobiliary drainage tube (ENBD). METHODS: Between January 2012 and October 2022, 89 patients with suspected PHC underwent computed tomographic (CT) cholangiography through ENBD and caudate biliary branching patterns were examined. Multidetector raw CT (MDCT) scans on 85 patients with PHC without biliary drainage were also investigated. The caudate biliary branches detected by each modality were evaluated. RESULTS: ENBD-CT cholangiography detected 206 caudate branches (2.44 branches/patient), while MDCT identified 62 branches (0.78 branches/patient). ENBD-CT cholangiography showed that 89 caudate branches drained into the left hepatic duct (LHD), 87 into the posterior hepatic duct (Bpost), and 30 into the right hepatic duct. LHD and Bpost were the common roots of the caudate branches. Some branches (20%) joined the contralateral hepatic duct across the left-right border, but not the anterior hepatic duct or infraportal-type Bpost. CONCLUSIONS: ENBD-CT cholangiography clearly showed the caudate biliary branches in patients with PHC after biliary drainage.

Preoperative level of serum transthyretin as a novel biomarker predicting survival in resected pancreatic ductal adenocarcinoma with neoadjuvant therapy.

BACKGROUND: Systemic inflammation and altered metabolism are essential hallmarks of cancer. We hypothesized that the rapid turnover protein transthyretin (TTR) (half-life: 2-3 days), compared with the conventional marker albumin (21 days), better reflects the inflammatory/metabolic dynamics of pancreatic ductal adenocarcinoma (PDAC) after neoadjuvant therapy (NAT) and is a useful prognostic marker. METHODS: Serum TTR and albumin levels were measured in 104 consecutive post-NAT PDAC patients before curative resection. The associations of preoperative TTR and albumin levels with overall survival (OS) after pancreatectomy were retrospectively analyzed. RESULTS: The mean (SD) TTR and albumin levels were 21.6 (6.4) mg/dL (normal range: ≥22.0 mg/dL) and 3.9 (0.55) g/dL. A low (<22.0 mg/dL) post-NAT TTR level was associated with an advanced tumor stage and higher CEA and CRP levels. Patients with low TTR levels showed significantly worse OS compared with normal levels (3-year OS 39 % vs. 54 %, P = 0.037), although albumin levels did not. We modified prognostic biomarkers of systemic inflammation/metabolism, such as GPS, PNI, and CONUT scores, using the serum TTR instead of albumin level and successfully showed that modified scores were better associated with OS compared with original scores using serum albumin level. CONCLUSIONS: Our data suggest that the TTR level is a promising prognostic biomarker for PDAC patients after NAT.

Comparison of laparoscopic liver resection for the ventral versus the dorsal areas of segment 8.

PURPOSE: The technical difficulties of laparoscopic liver resection (LLR) are greatly associated with the location of liver tumors. Since segment 8 (S8) contains a wide area, the difficulty of LLR for S8 tumors may vary depending on the location within the segment, such as the ventral (S8v) and dorsal (S8d) area, but the difference is unclear. METHODS: We retrospectively investigated 30 patients who underwent primary laparoscopic partial liver resection for liver tumors in S8 at Kobe University Hospital between January 2018 and June 2023. RESULTS: Thirteen and 17 patients underwent LLR for S8v and S8d, respectively. The operation time was significantly longer (S8v 203[135-259] vs. S8d 261[186-415] min, P = 0.002) and the amount of blood loss was significantly higher (10[10-150] vs. 10[10-200] mL, P = 0.034) in the S8d group than in the S8v group. No significant differences were observed in postoperative complications or postoperative length of hospital stay. Additionally, intraoperative findings revealed that the rate at which the case performed partial liver mobilization in the S8d group was higher (2[15.4%] vs. 8[47.1%], P = 0.060) and the median parenchymal transection time of the S8d group was longer (102[27-148] vs. 129[37-175] min, P = 0.097) than those in the S8v group, but there were no significant differences. CONCLUSION: The safety of LLR for the S8d was comparable to that of LLR for S8v, although LLR for S8d resulted in longer operative time and more blood loss. THE TRIAL REGISTRATION NUMBER: B230165 (approved at December 26, 2023).

[A Case of Radical Hepatectomy in a Patient with Recurrent Liver Metastasis of Gallbladder Cancer after Successful Chemotherapy with GC+Durvalumab].

A 49-year-old man underwent an open cholecystectomy for advanced gallbladder cancer in 2021. Three months after surgery, the patient underwent an additional resection, which showed no malignant findings, but 12 months after surgery, contrast-enhanced CT and MRI showed a new mass lesion in segment 8 of the liver, and the patient was diagnosed with postoperative hepatic metastatic recurrence of gallbladder cancer. After referral to our institution, he received 1 course of gemcitabine+cisplatin(GC)therapy and 8 courses of gemcitabine+cisplatin+durvalumab(GCD)therapy. Contrast- enhanced CT and MRI showed that the metastases had shrunk, and PET scan showed no FDG accumulation. Two months after completion of chemotherapy, there was no evidence of metastatic enlargement and new metastasis including distant metastasis, and the patient was referred to our department. Since curative resection was expected, a laparoscopic partial hepatectomy of segment 8 of the liver was performed. Pathological diagnosis revealed no residual tumor. If the metastases could be well controlled by systemic chemotherapy, hepatectomy for hepatic metastases of biliary tract cancer could be a treatment option.

Evaluation of Interaction With Bio-absorbable Polyglycolic Acid Spacer and Anti-adhesive Agents Using a Rat Experimental Model.

BACKGROUND/AIM: Neskeep®, an absorbable polyglycolic acid spacer, has been developed as the optimal material for spacer placement surgery. However, preventing its severe adhesion is a crucial concern. Therefore, we aimed to identify an effective anti-adhesion agent for Neskeep® using rat models. MATERIALS AND METHODS: Animal experiments were performed using 60 rats, which underwent Neskeep® placement on the abdominal wall. Three types of anti-adhesion agents were employed, establishing four subgroups: Seprafilm®, INTERCEED®, AdSpray®, and only Neskeep® (control) groups. Rats were sacrificed on postoperative days 7, 14, and 28 to assess adhesion levels around the Neskeep® Macroscopic visual assessment with the Lauder score and histopathological evaluation were performed to assess the degree of adhesion. RESULTS: There were no significant differences in the proportion of Lauder scores on days 7 and 14 between the four groups. Histological evaluation revealed no significant differences between groups at any observation time. However, the mean Lauder scores at day 28 were 5.0, 1.6, 4.0, and 4.8 in the Neskeep®, Seprafilm®, INTERCEED®, and AdSpray® groups, respectively. The proportion of milder Lauder score was significantly higher in the Seprafilm® group on day 28. CONCLUSION: Seprafilm® may exhibit an anti-adhesive effect when used with Neskeep®.

Impact of bile leak on the prognosis of patients with hepatocellular carcinoma who have undergone liver resection.

PURPOSE: The impact of postoperative bile leak on the prognosis of patients with hepatocellular carcinoma who underwent liver resection is controversial. This study aimed to investigate the prognostic impact of bile leak for patients with hepatocellular carcinoma who underwent liver resection. METHODS: Patients with hepatocellular carcinoma who underwent liver resection between 2009 and 2019 at Kobe University Hospital and Hyogo Cancer Center were included. After propensity score matching between the bile leak and no bile leak groups, differences in 5-year recurrence-free and overall survival rates were evaluated using the Kaplan-Meier method. RESULTS: A total of 781 patients, including 43 with postoperative bile leak, were analyzed. In the matched cohort, 40 patients were included in each group. The 5-year recurrence-free survival rates after liver resection were 35% and 32% for the bile leak and no bile leak groups, respectively (P = 0.857). The 5-year overall survival rates were 44% and 54% for the bile leak and no bile leak groups, respectively (P = 0.216). CONCLUSION: Overall, bile leak may not have a profound negative impact on the prognosis of patients with hepatocellular carcinoma who have undergone liver resection.

Complete response to tremelimumab plus durvalumab treatment in hepatocellular carcinoma with a bile duct tumor thrombus: A case report.

Tremelimumab plus durvalumab (Dur/Tre) is the first-line treatment for advanced hepatocellular carcinoma (HCC) worldwide. The present report describes the case of a 68-year-old man diagnosed with advanced HCC and a bile duct tumor thrombus (BDTT) who achieved a complete response to Dur/Tre therapy. The BDTT progressed to the bifurcation of the left and right hepatic ducts. Over time, both the tumors and BDTT progressively decreased in size, and a complete response was confirmed using the Response Evaluation Criteria in Solid Tumors (version 1.1.) 6 months after treatment administration. Subsequently, immune-related adverse events, including type 1 diabetes mellitus and diabetic ketoacidosis, emerged, leading to treatment discontinuation. The patient was undergoing outpatient follow-up in a drug-free state with no signs of recurrence 290 days after the initial administration of Dur/Tre. Although long-term and meticulous observations are required, the present findings could influence the choice of systemic chemotherapy for advanced HCC.

Rim Enhancement on Contrast-Enhanced CT as a Predictor of Prognosis in Patients with Pancreatic Ductal Adenocarcinoma.

This study investigated the utility of imaging features, such as rim enhancement on contrast-enhanced CT (CECT), in predicting the prognosis of pancreatic ductal adenocarcinoma (PDAC). This retrospective study included 158 patients (84 men; mean age, 68 years) with pathologically confirmed PDAC. The following imaging features were evaluated on CECT by two radiologists: tumor size, tumor attenuation, and the presence of rim enhancement. Cox proportional hazards analysis was performed to identify the imaging and clinicopathological features for predicting disease-free survival (DFS) and overall survival (OS). Pathological features were compared with the presence of rim enhancement. Among the 158 patients, 106 (67%) underwent curative surgery (surgery group) and 52 (33%) received conservative treatment (non-surgery group). Rim enhancement was observed more frequently in the non-surgery group than in the surgery group (44% vs. 20%; p < 0.001). Rim enhancement showed significant associations with shorter DFS and OS in the surgery group (hazard ratios (HRs), 3.03 and 2.99; p < 0.001 and p = 0.003, respectively), whereas tumor size showed significant associations with shorter OS (HR per 1 mm increase, 1.08; p < 0.001). PDACs with rim enhancement showed significant associations with higher histological tumor grades (p < 0.001). PDAC with rim enhancement on CECT could predict poorer prognosis and more aggressive tumor grades.

Current Roles of Ramucirumab in the Sequential Treatment of Unresectable Hepatocellular Carcinoma.

BACKGROUND/AIM: The treatment algorithm for systemic therapies for advanced hepatocellular carcinoma (HCC) has changed dramatically; however, the therapeutic landscape for sequential second-line or later-line treatments, including ramucirumab, remains controversial. This study aimed to investigate the role of ramucirumab for treating HCC. PATIENTS AND METHODS: We retrospectively analyzed data from 17 patients with advanced HCC who received ramucirumab, and 8 of them who received lenvatinib re-administration after ramucirumab treatment failure. RESULTS: The median overall survival of 17 patients treated with ramucirumab was 11.5 months. The median ratios of the 1-month post-treatment α-fetoprotein (AFP) levels and albumin-bilirubin (ALBI) scores to the pre-treatment AFP levels and ALBI scores following ramucirumab treatment were 0.880 and 0.965, respectively. The median ratios of the 1-month post-treatment AFP and ALBI levels to the pre-treatment levels were 1.587 and 0.970 for mALBI grade 1/2a, and 1.313 and 0.936 for mALBI grade 2b/3, respectively. Six of the eight patients who received lenvatinib rechallenge treatment exhibited a decrease in AFP levels one month post-lenvatinib treatment. Deterioration of liver function 3 months post-lenvatinib treatment was noted in five of the eight patients who received lenvatinib rechallenge treatment after ramucirumab. CONCLUSION: Ramucirumab may be equally useful in patients with unresectable HCC who have poor liver function or whose liver function is aggravated by other therapies. Rechallenge treatment with lenvatinib after ramucirumab may be a valid treatment option for HCC.

The Albumin-bilirubin Grade as Prognostic Indicator for Recurrent Hepatocellular Carcinoma Needing Repeat Liver Resection.

BACKGROUND/AIM: This study aimed to evaluate the utility of the albumin-bilirubin grade for predicting the prognosis after repeat liver resection for patients with recurrent hepatocellular carcinoma. PATIENTS AND METHODS: Ninety patients with intrahepatic recurrent hepatocellular carcinoma who underwent repeat liver resection at our institution between 2005 and 2019 were retrospectively analyzed. Cox proportional-hazards regression models evaluated independent preoperative prognostic factors, including the albumin-bilirubin grade. Prognosis differences between patients with albumin-bilirubin grades 1 and 2 were analyzed using the Kaplan-Meier method. RESULTS: Cox proportional-hazards regression analysis revealed that albumin-bilirubin grade 2 (p=0.003) and early recurrence within one year from the initial surgery (p=0.001) were independently associated with poor recurrence-free survival, and albumin-bilirubin grade 2 (p=0.020) was independently associated with poor overall survival. The five-year recurrence-free (31% and 17%, respectively) and overall (86% and 60%, respectively) survival rates after repeat liver resection for patients with albumin-bilirubin grades 1 and 2 were significantly different between groups (both p=0.003). CONCLUSION: The albumin-bilirubin grade is useful for preoperatively predicting favorable survival rates after repeat liver resection for patients with recurrent hepatocellular carcinoma. Patients with an albumin-bilirubin grade 1 are better candidates for surgical treatment of recurrent hepatocellular carcinoma.

Novel concept of "sequential particle radiotherapy" with atezolizumab plus bevacizumab for hepatocellular carcinoma with portal vein tumor thrombus.

Owing to the high objective response rate of atezolizumab plus bevacizumab (Atez/Bev) for hepatocellular carcinoma (HCC), the concept of sequential conversion to local treatment has recently become mainstream. The conversion concept is mainly applied to Barcelona Clinic for Liver Cancer (BCLC) stage B cases, and radiotherapy is rarely considered as a conversion local treatment. We herein report three patients who were treated with the novel concept of "sequential particle radiotherapy," consisting of Atez/Bev therapy followed by particle radiotherapy (PRT) for HCC with advanced portal vein tumor thrombus (Vp3/4 PVTT). All patients achieved partial response radiologically and were switched to PRT. All patients were recurrence free at 1 year after the introduction of Atez/Bev therapy without any additional treatment. This upcoming combination strategy includes the advocacy of sequential concepts for BCLC stage C cases and the introduction of PRT as a local treatment after Atez/Bev.

Temporal progression of pancreatic cancer computed tomography findings until diagnosis: A large-scale multicenter study.

BACKGROUND: Focal parenchymal atrophy and main pancreatic duct (MPD) dilatation have been identified as early signs of pancreatic ductal adenocarcinoma. However, limited evidence exists regarding their temporal progression due to previous study limitations with restricted case numbers. OBJECTIVE: To ascertain a more precise frequency assessment of suspicious pancreatic ductal adenocarcinoma findings as well as delineate the temporal progression of them. METHODS: A multicenter retrospective study was conducted on patients diagnosed with pancreatic ductal adenocarcinoma between 2015 and 2021. We included patients who had undergone at least one computed tomography (CT) scan ≥6 months before diagnosing pancreatic ductal adenocarcinoma. The temporal progression of suspicious pancreatic ductal adenocarcinoma findings on CT was investigated. RESULTS: Out of 1832 patients diagnosed with pancreatic ductal adenocarcinoma, 320 had a previous CT before their diagnosis. Suspicious pancreatic ductal adenocarcinoma findings were detected in 153 cases (47.8%), with focal parenchymal atrophy (26.6%) being the most common followed by MPD dilatation (11.3%). Focal parenchymal atrophy was the earliest detectable sign among all suspicious findings and became visible on average 2.7 years before diagnosis, and the next most common, MPD dilatation, 1.1 years before diagnosis. Other findings, such as retention cysts, were less frequent and appeared around 1 year before diagnosis. Focal parenchymal atrophy followed by MPD dilatation was observed in 10 patients but not in reverse order. Focal parenchymal atrophy was more frequently detected in the pancreatic body/tail. No significant relationship was found between the pathological pancreatic ductal adenocarcinoma differentiation or tumor stage and the time course of the CT findings. All cases of focal parenchymal atrophy progressed just prior to diagnosis, and the atrophic area was occupied by tumor at diagnosis. Main pancreatic duct dilatation continued to progress until diagnosis. CONCLUSION: This large-scale study revealed that the temporal progression of focal parenchymal atrophy is the earliest detectable sign indicating pancreatic ductal adenocarcinoma. These results provide crucial insights for early pancreatic ductal adenocarcinoma detection.

Optimal cutoff values of drain amylase for predicting pancreatic fistula are different between open and laparoscopic distal pancreatectomy.

BACKGROUND: Drainage fluid amylase (DFA) is useful for predicting clinically relevant postoperative pancreatic fistula (CR-POPF) after distal pancreatectomy (DP). However, difference in optimal cutoff value of DFA for predicting CR-POPF between open DP (ODP) and laparoscopic DP (LDP) has not been investigated. This study aimed to identify the optimal cutoff values of DFA for predicting CR-POPF after ODP and LDP. METHODS: Data for 294 patients (ODP, n = 127; LDP, n = 167) undergoing DP at Kobe University Hospital between 2010 and 2021 were reviewed. Propensity score matching was performed to minimize treatment selection bias. Receiver operating characteristic (ROC) analysis was performed to determine the optimal cutoff values of DFA for predicting CR-POPF for ODP and LDP. Logistic regression analysis for CR-POPF was performed to investigate the diagnostic value of DFA on postoperative day (POD) three with identified cutoff value. RESULTS: In the matched cohort, CR-POPF rates were 24.7% and 7.9% after ODP and LDP, respectively. DFA on POD one was significantly lower after ODP than after LDP (2263 U/L vs 4243 U/L, p < 0.001), while the difference was not significant on POD three (543 U/L vs 1221 U/L, p = 0.171). ROC analysis revealed that the optimal cutoff value of DFA on POD one and three for predicting CR-POPF were different between ODP and LDP (ODP, 3697 U/L on POD one, 1114 U/L on POD three; LDP, 10564 U/L on POD one, 6020 U/L on POD three). Multivariate analysis showed that DFA on POD three with identified cutoff value was the independent predictor for CR-POPF both for ODP and LDP. CONCLUSIONS: DFA on POD three is an independent predictor for CR-POPF after both ODP and LDP. However, the optimal cutoff value for it is significantly higher after LDP than after ODP. Optimal threshold of DFA for drain removal may be different between ODP and LDP.

Spontaneous rupture of splenic hilar lymph node metastasis from hepatocellular carcinoma.

Spontaneous rupture of a primary hepatocellular carcinoma (HCC) is a frequently observed and fatal complication. However, the rupture of lymph node (LN) metastases from HCC is rare. A 79 year-old male with hepatitis B underwent three liver resections for HCC. Two years and 6 months after the last liver resection, enhanced computed tomography (CT) revealed a nodule with a diameter of 3 cm in the lower pole of the spleen. Splenic metastasis of HCC was suspected, and splenectomy was scheduled. During our hospital stay for a urinary tract infection before the scheduled operation, he complained of acute left-sided abdominal pain, and CT showed intra-abdominal hemorrhage due to rupture of the splenic tumor. Emergency splenectomy was performed, and the postoperative course was uneventful. Histopathological examination revealed a poorly differentiated HCC in the lower splenic pole lesion, which contained LN structures. The ruptured lesion was diagnosed as splenic hilar LN metastasis of HCC. Although laparoscopic partial liver resection was performed for intrahepatic recurrence, and atezolizumab plus bevacizumab therapy was administered for peritoneal metastases, the patient was alive 25 months after the splenectomy. Our case suggests that emergency surgery for LN metastatic rupture can achieve hemostasis and lead to improved survival outcomes.

Association between tumor morphology and efficacy of atezolizumab plus bevacizumab for advanced hepatocellular carcinoma.

AIM: The IMbrave150 trial revealed that atezolizumab plus bevacizumab (AtezoBv) showed a higher objective response rate (ORR) in patients with advanced hepatocellular carcinoma (HCC). Although conversion therapy after AtezoBv has been recently reported, markers predictive of its efficacy, particularly radiological imaging markers, have not yet been identified. The present study focused on tumor morphological appearance on radiological imaging and evaluated whether it could be associated with AtezoBv efficacy. METHODS: Ninety-five intrahepatic lesions in 74 patients who were given AtezoBv for advanced HCC were recruited for evaluation. The lesions were divided into two groups, simple nodular (SN group) and non-simple nodular (non-SN group), based on the gross morphology on pretreatment imaging, and retrospectively evaluated for treatment response and other relevant clinical outcomes. RESULTS: Assessing the size of individual tumors after treatment, waterfall plots showed that tumor shrinkage in the non-SN group including 56 lesions was higher than that in the SN group comprising 39 lesions. The ORR was significantly higher in the non-SN group (39.3% vs. 15.4%, p = 0.012). Additionally, the median time to nodular progression was longer in the non-SN group (21.0 months vs. 8.1 months, p = 0.119) compared to the SN group. Six patients with non-SN lesions underwent sequential local therapy. CONCLUSIONS: Atezolizumab plus bevacizumab may show increased therapeutic efficacy in patients with tumors with a higher potential for aggressive oncological behavior, such as non-SN lesions. Treatment strategies focusing on conversion therapy may be crucial in patients with non-SN lesions.

Utility of plasma D-dimer for diagnosis of venous thromboembolism after hepatectomy.

BACKGROUND: Venous thromboembolism (VTE) is a potentially fatal complication of hepatectomy. The use of postoperative prophylactic anticoagulation in patients who have undergone hepatectomy is controversial because of the risk of postoperative bleeding. Therefore, we hypothesized that monitoring plasma D-dimer could be useful in the early diagnosis of VTE after hepatectomy. AIM: To evaluate the utility of monitoring plasma D-dimer levels in the early diagnosis of VTE after hepatectomy. METHODS: The medical records of patients who underwent hepatectomy at our institution between January 2017 and December 2020 were retrospectively analyzed. Patients were divided into two groups according to whether or not they developed VTE after hepatectomy, as diagnosed by contrast-enhanced computed tomography and/or ultrasonography of the lower extremities. Clinicopathological factors, including demographic data and perioperative D-dimer values, were compared between the two groups. Receiver operating characteristic curve analysis was performed to determine the D-dimer cutoff value. Univariate and multivariate analyses were performed using logistic regression analysis to identify significant predictors. RESULTS: In total, 234 patients who underwent hepatectomy were, of whom (5.6%) were diagnosed with VTE following hepatectomy. A comparison between the two groups showed significant differences in operative time (529 vs 403 min, P = 0.0274) and blood loss (530 vs 138 mL, P = 0.0067). The D-dimer levels on postoperative days (POD) 1, 3, 5, 7 were significantly higher in the VTE group than in the non-VTE group. In the multivariate analysis, intraoperative blood loss of > 275 mL [odds ratio (OR) = 5.32, 95% confidence interval (CI): 1.05-27.0, P = 0.044] and plasma D-dimer levels on POD 5 ≥ 21 µg/mL (OR = 10.1, 95%CI: 2.04-50.1, P = 0.0046) were independent risk factors for VTE after hepatectomy. CONCLUSION: Monitoring of plasma D-dimer levels after hepatectomy is useful for early diagnosis of VTE and may avoid routine prophylactic anticoagulation in the postoperative period.

Impact of intratumoral microbiome on tumor immunity and prognosis in human pancreatic ductal adenocarcinoma.

BACKGROUND: Recent evidence suggests that the presence of microbiome within human pancreatic ductal adenocarcinoma (PDAC) tissue potentially influences cancer progression and prognosis. However, the significance of tumor-resident microbiome remains unclear. We aimed to elucidate the impact of intratumoral bacteria on the pathophysiology and prognosis of human PDAC. METHODS: The presence of intratumoral bacteria was assessed in 162 surgically resected PDACs using quantitative polymerase chain reaction (qPCR) and in situ hybridization (ISH) targeting 16S rRNA. The intratumoral microbiome was explored by 16S metagenome sequencing using DNA extracted from formalin-fixed paraffin-embedded tissues. The profile of intratumoral bacteria was compared with clinical information, pathological findings including tumor-infiltrating T cells, tumor-associated macrophage, fibrosis, and alterations in four main driver genes (KRAS, TP53, CDKN2A/p16, SMAD4) in tumor genomes. RESULTS: The presence of intratumoral bacteria was confirmed in 52 tumors (32%) using both qPCR and ISH. The 16S metagenome sequencing revealed characteristic bacterial profiles within these tumors, including phyla such as Proteobacteria and Firmicutes. Comparison of bacterial profiles between cases with good and poor prognosis revealed a significant positive correlation between a shorter survival time and the presence of anaerobic bacteria such as Bacteroides, Lactobacillus, and Peptoniphilus. The abundance of these bacteria was correlated with a decrease in the number of tumor-infiltrating T cells positive for CD4, CD8, and CD45RO. CONCLUSIONS: Intratumoral infection of anaerobic bacteria such as Bacteroides, Lactobacillus, and Peptoniphilus is correlated with the suppressed anti-PDAC immunity and poor prognosis.

Efficacy of S-1 Adjuvant Chemotherapy for Resected Biliary Tract Cancer: A Retrospective Propensity-Matched Analysis.

INTRODUCTION: Surgical resection is considered an effective cure for biliary tract cancer (BTC); however, the prognosis is unsatisfactory despite improved surgical techniques and perioperative management. The recurrence rate remains high even after curative resection. The efficacy of adjuvant chemotherapy in pancreatic and gastric cancers has been previously reported, and the feasibility of adjuvant therapy with S-1 has recently been reported in patients with resected BTC. We aimed to retrospectively investigate the effects of adjuvant chemotherapy with S-1 on resected advanced BTC. METHODS: We included data from 438 BTC patients who underwent resection between 2001 and 2020. After excluding patients with pTis-pT1 (n = 112) and other exclusion criteria, 266 patients were included in the analysis. RESULTS: After propensity score matching, 48 patients received S-1 adjuvant chemotherapy (S-1 group), and 48 patients received non-S1 adjuvant chemotherapy or underwent surgery alone (Non-S-1 group). The patients in the S-1 group had significantly better overall survival (OS) than those in the non-S-1 group (MST 51 vs 37 months, hazard ratio [HR]:.54, 95% confidence interval [CI]:.30-.98, P = .04). The S-1 group had a significantly better recurrence-free survival (RFS) than the non-S-1 group (94 vs 21 months, HR: .57, 95% CI: .33-.97, P = .03). Subgroup analyses for OS and RFS exhibited the benefits of S-1 in patients aged <75 years and in patients with primary sites of extrahepatic and perineural invasion and curability of R0. DISCUSSION: S-1 adjuvant therapy is promising for improving the postoperative survival of patients with resected advanced BTC, positive nerve invasion, and R0 resection.