Is Repeat Resection for Recurrent Intrahepatic Cholangiocarcinoma Warranted? Outcomes of an International Analysis.

BACKGROUND: Recurrence of intrahepatic cholangiocarcinoma (ICC) after liver resection (LR) remains high, and optimal therapy for recurrent ICC is challenging. Herein, we assess the outcomes of patients undergoing repeat resection for recurrent ICC in a large, international multicenter cohort. PATIENTS AND METHODS: Outcomes of adults from six large hepatobiliary centers in North America, Europe, and Asia with recurrent ICC following primary LR between 2001 and 2015 were analyzed. Cox models determined predictors of post-recurrence survival. RESULTS: Of patients undergoing LR for ICC, 499 developed recurrence. The median time to recurrence was 10 months, and 47% were intrahepatic. Overall 3-year post-recurrence survival rate was 28.6%. In total, 121 patients (25%) underwent repeat resection, including 74 (61%) repeat LRs. Surgically treated patients were more likely to have solitary intrahepatic recurrences and significantly prolonged survival compared with those receiving locoregional or systemic therapy alone with a 3-year post-recurrence survival rate of 47%. Independent predictors of post-recurrence death included time to recurrence < 1 year [HR 1.66 (1.32-2.10), p < 0.001], site of recurrence [HR 1.74 (1.28-2.38), p < 0.001], macrovascular invasion [HR 1.43 (1.05-1.95), p = 0.024], and size of recurrence > 3 cm [HR 1.68 (1.24-2.29), p = 0.001]. Repeat resection was independently associated with decreased post-recurrence death [HR 0.58 0.43-0.78), p < 0.001]. CONCLUSIONS: Repeat resection for recurrent ICC in select patients can result in extended survival. Thus, challenging the paradigm of offering these patients locoregional or chemo/palliative therapy alone as the mainstay of treatment.

Metallic Stents for Hepatic Venous Outflow Obstruction After Living-Donor Liver Transplantation and their Therapeutic Effects.

BACKGROUND: Living-donor liver transplantation (LDLT) is established as a standard therapy for end-stage liver disease; however, vessel reconstruction is more demanding due to the short length and small size of the available structures compared with deceased-donor whole liver transplantation. Interventional radiology (IR) has become the first-line treatment for vascular complications after LDLT. Hepatic venous outflow obstruction (HVOO) is a life-threatening complication after LDLT. The aim of this study of 592 adult-to-adult LDLT cases was to investigate the safety and efficacy of stent implantation for HVOO after LDLT. METHODS: Records of patients who developed HVOO requiring any treatment were collected with special reference to the metallic stent implantation. There were 232 left-side grafts and 360 right-side grafts. Sixteen cases developed HVOO after LDLT with an incidence rate of 2.7%, 5 with a left liver graft (2%), and 11 with a right-side graft (3%). The IR was attempted for 14 cases; among those, 8 cases were treated by stent implantation. RESULTS: The technical success rate of the initial stent implantation was 100%. The pressure gradient at the stenotic site significantly improved from 12.2 (range, 10.9-20.4 cm H2O) to 3.9 cm H2O (range, 1.4-8.2 cm H2O; P = .03). The volume of the congested graft liver decreased significantly from 1448 (range, 788-2170 mL) to 1265 mL (range, 748-1665 mL; P = .01), and the serum albumin level improved significantly from 3.3 (range, 1.7-3.7 g/dL) to 3.7 g/dL (range, 2.9-4.1 g/dL; P = .02). No procedure-related complication was noted, and the long-term stent patency was 100%. CONCLUSION: Metallic stent implantation for stenotic venous anastomosis after LDLT is a safe and effective treatment.

The Effect of Renin-Angiotensin System Inhibitors in Patients Undergoing Pancreatic Cancer Resection.

OBJECTIVES: The local renin-angiotensin system promotes angiogenesis and proliferation via vascular endothelial growth factor or epidermal growth factor receptor expression. In this study, we aimed to evaluate the impact of angiotensin system inhibitors (ASIs) on long-term outcomes in patients undergoing surgical resection of pancreatic ductal adenocarcinoma (PDAC). METHODS: A single institutional retrospective analysis was performed using the medical records of patients who underwent pancreatic resection with curative intent for PDAC between January 2005 and December 2018. Patient characteristics and surgical outcomes were compared between patients taking ASIs and those who are not. RESULTS: A total of 272 patients were included in the study and classified into the ASI group (n = 121) and the non-ASI group (n = 151). The median overall survival times in the ASI group and non-ASI group were 38.0 and 34.0 months ( P = 0.250), and the median recurrence-free survival times were 24.0 and 15.0 months ( P = 0.025), respectively. Multivariate analysis for recurrence-free survival identified the use of ASIs ( P = 0.020), CA19-9 level >500 IU/L ( P = 0.010), positive lymph node metastasis ( P < 0.001), and no adjuvant chemotherapy ( P < 0.001) as independent prognostic factors. CONCLUSIONS: The use of ASI may improve long-term outcomes after surgery for PDAC.

Evaluation of pancreatic chymotrypsin activity for on-site prediction of clinically relevant postoperative pancreatic fistula.

OBJECTIVES: Although the risk of complications due to postoperative pancreatic fistula (POPF) have been evaluated based on the amylase level in drained ascitic fluid, this method has much room for improvement regarding diagnostic accuracy and facility of the measurement. This study aimed to investigate the clinical value of measuring pancreatic chymotrypsin activity for rapid and accurate prediction of POPF after pancreaticoduodenectomy. METHODS: In 52 consecutive patients undergoing pancreaticoduodenectomy, the chymotrypsin activity in pancreatic juice was measured by calculating the increase in fluorescence intensity during the first 5 min after activation with an enzyme-activatable fluorophore. The predictive value for clinically relevant POPF (CR-POPF) was compared between this technique and the conventional method based on the amylase level. RESULTS: According to receiver operating characteristic analyses, pancreatic chymotrypsin activity on postoperative day (POD) 3 measured with a multiplate reader had the highest predictive value for CR-POPF (area under the curve [AUC], 0.752; P < 0.001), yielding 77.8 % sensitivity and 68.8 % specificity. The AUC and sensitivity/specificity of the amylase level in ascitic fluid on POD 3 were 0.695 (P = 0.053) and 77.8 %/41.2 %, respectively. Multivariable analysis identified high pancreatic chymotrypsin activity on POD 3 as an independent risk factor for CR-POPF. Measurement of pancreatic chymotrypsin activity with a prototype portable fluorescence photometer could significantly predict CR-POPF (AUC, 0.731; P = 0.010). CONCLUSION: Measurement of pancreatic chymotrypsin activity enabled accurate and rapid prediction of CR-POPF after pancreaticoduodenectomy. This can help surgeons to implement appropriate drain management at the patient's bedside without delay.

Increased expression of TNFRSF14 and LIGHT in biliary epithelial cells of patients with primary sclerosing cholangitis.

BACKGROUND AND AIMS: There is a lack of biliary epithelial molecular markers for primary sclerosing cholangitis (PSC). We analyzed candidates from disease susceptibility genes identified in recent genome-wide association studies (GWAS). METHODS: Expression levels of GWAS genes were analyzed in archival liver tissues of patients with PSC and controls. Immunohistochemical analysis was performed to evaluate expression levels in the biliary epithelia of PSC (N = 45) and controls (N = 12). Samples from patients with primary biliary cholangitis (PBC) were used as disease controls (N = 20). RESULTS: Hepatic expression levels of ATXN2, HHEX, PRDX5, MST1, and TNFRSF14 were significantly altered in the PSC group. We focused on the immune-related receptor, TNFRSF14. Immunohistochemistry revealed that high expression of TNFRSF14 in biliary epithelial cells was observed only in the PSC group. In addition, the expression of LIGHT, which encodes a TNFRSF14-activating ligand, was increased in PSC liver. Immunohistochemistry showed that high expression of LIGHT was more common in PSC biliary epithelia (53%) than in the PBC (15%) or control (0%) groups; moreover, it was positively associated with fibrotic progression, although it was not an independent prognostic factor. CONCLUSIONS: TNFRSF14 and LIGHT are promising candidate markers for PSC.

Exosomes secreted by ST3GAL5high cancer cells promote peritoneal dissemination by establishing a premetastatic microenvironment.

Peritoneal dissemination of cancer affects patient survival. The behavior of peritoneal mesothelial cells (PMCs) and immune cells influences the establishment of a microenvironment that promotes cancer cell metastasis in the peritoneum. Here, we investigated the roles of lactosylceramide alpha-2,3-sialyltransferase (ST3G5; also known as ST3GAL5 and GM3 synthase) in the exosome-mediated premetastatic niche in peritoneal milky spots (MSs). Exosomes secreted from ST3G5high cancer cells (ST3G5high -cExos) were found to contain high levels of hypoxia-inducible factor 1-alpha (HIF1α) and accumulated in MSs via uptake in macrophages (MΦs) owing to increased expression of sialic acid-binding Ig-like lectin 1 (CD169; also known as SIGLEC1). ST3G5high -cExos induced pro-inflammatory cytokines and glucose metabolic changes in MΦs, and the interaction of these MΦs with PMCs promoted mesothelial-mesenchymal transition (MMT) in PMCs, thereby generating αSMA+ myofibroblasts. ST3G5high -cExos also increased the expression of immune checkpoint molecules and T-cell exhaustion in MSs, which accelerated metastasis to the omentum. These events were prevented following ST3G5 depletion in cancer cells. Mechanistically, ST3G5high -cExos upregulated chemokines, including CC-chemokine ligand 5 (CCL5), in recipient MΦs and dendritic cells (DCs), which induced MMT and immunosuppression via activation of signal transducer and activator of transcription 3 (STAT3). Maraviroc, a C-C chemokine receptor type 5 (CCR5) antagonist, prevented ST3G5high -cExo-mediated MMT, T-cell suppression, and metastasis in MSs. Our results suggest ST3G5 as a suitable therapeutic target for preventing cExo-mediated peritoneal dissemination.

A Novel Pathogenic MEN1 Gene Variant Identified in a Family With Multiple Pancreatic Neuroendocrine Tumors.

Multiple endocrine neoplasia type 1 (MEN1) is a hereditary endocrine tumor syndrome caused by pathogenic variants in the MEN1 gene, and most patients with this syndrome initially develop primary hyperparathyroidism (PHPT). Here, we report the case of a family wherein a germline MEN1 variant was detected and multiple pancreatic neuroendocrine tumors (PanNETs) were observed at the initial evaluation. A 40-year-old woman presented with a complaint of abdominal discomfort, and a close examination revealed multiple pancreatic tumors. Distal pancreatectomy with splenectomy was performed, and the diagnosis was nonfunctional PanNETs. Five years later, her 76-year-old mother was referred to the hospital with multiple pancreatic tumors. A genetic test revealed that both patients harbored a previously unreported germline variant in the MEN1 gene. Although it was classified as a variant of uncertain significance, we suspect that it may be associated with the pathogenesis of these lesions. This case report presents a new disease concept-familial isolated pancreatic neuroendocrine tumors, or FIPNETs-in patients harboring a pathogenic variant in the MEN1 gene who experience only pancreatic lesions. We suggest that clinicians consider genetic testing for the MEN1 gene in patients with multiple pancreatic lesions who show no signs of PHPT.

Gastric cancer simultaneously complicated with extrahepatic bile duct metastasis and portal vein tumor thrombus: a case report.

BACKGROUND: Gastric cancer metastatic to the extrahepatic bile duct or accompanied by portal vein tumor thrombus (PVTT) is rare. To our knowledge, there have been no cases complicated with both of these factors. CASE PRESENTATION: A 72-year-old man presented with icterus and melena. A biochemical blood test showed abnormal values for hepatobiliary enzymes and a tumor marker, and abdominal computed tomography scan revealed wall thickening of the lower bile duct with intra- and extra-hepatic bile duct dilatation and PVTT. A biopsy of the lower bile duct during endoscopic retrograde cholangiopancreatography demonstrated a moderately differentiated tubular adenocarcinoma. Moreover, gastroduodenoscopy showed a type 3 tumor at the lesser curvature of the gastric antrum, and an endoscopic biopsy demonstrated a moderately differentiated tubular adenocarcinoma. We diagnosed concomitant gastric cancer and distal bile duct accompanied by PVTT, and pancreatoduodenectomy with combined resection of the portal vein was performed. The resected specimen revealed a tumor in the lesser curvature of the gastric antrum and circumferential wall thickening in the lower bile duct. In pathological findings, infiltration of a moderately differentiated tubular adenocarcinoma from the mucosal layer to the subserosal layer of the stomach was observed. In contrast, a moderately differentiated tubular adenocarcinoma demonstrating the same histological type as the gastric cancer had spread not to the mucosal layer but mainly to the fibromuscular layer of the lower bile duct. Immunohistochemical staining showed identical patterns between gastric cancer and the bile duct tumor: negativity for cytokeratin 7 (CK7), and positivity for CK19 and 20. Therefore, the final diagnosis was extrahepatic bile duct metastasis from gastric cancer with PVTT. Unfortunately, multiple liver metastases occurred in the early postoperative period and chemotherapy was conducted, but the patient died 12 months after the surgery. CONCLUSIONS: In the diagnosis of extrahepatic bile duct metastasis, immunohistochemical staining of gastric cancer and the bile duct tumor was essential and helpful as decisive evidence.

Probe-based confocal laser endomicroscopy for real-time evaluation of colorectal liver metastasis in resected surgical specimens.

Probe-based confocal laser endomicroscopy (pCLE) enables real-time examination of tissue structure. This study investigated pCLE with or without fluorescein sodium for the intraoperative diagnosis of colorectal liver metastasis (CLM) and detection of surgical margins. Thirty-four specimens of CLM and adjacent noncancerous tissue were obtained from 21 patients and examined by pCLE between May 2017 and March 2018. Images were obtained both without and with fluorescein sodium applied to the cut surface and compared with hematoxylin and eosin-stained tissue. Fluorescence intensity (FI) was measured by luminance-analysis software. Without external fluorophores, pCLE visualized 91.2% of CLM tissues as an irregular structure with low autofluorescence and 90.5% of noncancerous liver tissues as a regular structure with high autofluorescence. The median FI was significantly lower in cancer than in benign tissue in patients without chemotherapy [70.4 (51.6-110) vs. 48.3 (39.0-59.4), p = 0.002] and with chemotherapy [67.9 (54.6-89.2) vs. 48.6 (28.8-82.1), p < 0.001]. The border was clearly visible; pCLE with fluorescein sodium clearly showed their morphologies. In summary, our study demonstrated real-time pCLE distinguished CLM and noncancerous tissue by differences in structure and FI regardless of prehepatectomy chemotherapy. Fluorescein spray facilitated clear visualization of differences in the morphology.

Conditional recurrence analysis of intrahepatic cholangiocarcinoma: Changes in recurrence rate and survival after recurrence resection by disease-free interval.

AIM: The prognosis of patients with resected intrahepatic cholangiocarcinoma (ICC) is still unsatisfactory, with a high recurrence rate. We aimed to evaluate risks of recurrence changing over time and the survival benefit of resection for recurrent ICC. METHODS: This study included patients who underwent hepatectomy for ICC during 1995-2020. Risk factors for recurrence-free survival (RFS) in patients undergoing initial resection and overall survival (OS) in patients who developed recurrence after initial resection were analyzed. Conditional cumulative incidence of recurrence was assessed. RESULTS: A total of 169 patients were included in the study and 114 patients (67.5%) developed recurrence. Cumulative analyses showed that the 5-year recurrence rate was 69.3% at the time of initial resection but decreased to 24.8% in patients free from recurrence at 2 years after initial resection and 2.6% in patients free from recurrence at 4 years. Re-resection was carried out in 26 (22.8%) of 114 patients who developed recurrence. Multivariable Cox proportional hazards model analysis indicated re-resection (hazard ratio [HR] 0.19; 95% confidence interval [CI] 0.11-0.40, p < 0.001), microvascular invasion (MVI) (HR 2.39; 95% CI 1.05-5.40, p = 0.037), and disease-free interval (months) (HR 0.97; 95% CI 0.95-1.00, p = 0.067) were significantly associated with longer OS after recurrence. CONCLUSIONS: Although the rate of recurrence remains high, conditional cumulative recurrence rate analysis showed that the rate of recurrence decreased by disease-free interval. Resection of recurrent ICC was associated with improved OS, particularly among patients with longer disease-free interval and absence of MVI after initial hepatectomy.

Lenvatinib recruits cytotoxic GZMK+CD8 T cells in hepatocellular carcinoma.

BACKGROUND: Lenvatinib was expected to enhance the effect of immune checkpoint inhibitors (ICIs) for unresectable HCC; however, their combination therapy failed to show the synergy in the phase III clinical trial. METHODS: To elucidate lenvatinib-induced molecular modulation, we performed bulk RNA-sequencing and digital spatial profiling of 5 surgically resected human HCC specimens after lenvatinib treatment and 10 matched controls without any preceding therapy. FINDINGS: Besides its direct antitumor effects, lenvatinib recruited cytotoxic GZMK+CD8 T cells in intratumor stroma by CXCL9 from tumor-associated macrophages, suggesting that lenvatinib-treated HCC is in the so-called excluded condition that can diminish ICI efficacy.

Post-operative mortality and recurrence patterns in pancreatic cancer according to KRAS mutation and CDKN2A, p53, and SMAD4 expression.

Alterations in KRAS, CDKN2A (p16), TP53, and SMAD4 genes have been major drivers of pancreatic carcinogenesis. The clinical course of patients with pancreatic cancer in relation to these driver alterations has not been fully characterised in large populations. We hypothesised that pancreatic carcinomas with different combinations of KRAS mutation and aberrant expression of CDKN2A, p53, and SMAD4 might show distinctive recurrence patterns and post-operative survival outcomes. To test this hypothesis, we utilised a multi-institutional cohort of 1,146 resected pancreatic carcinomas and assessed KRAS mutations by droplet digital polymerase chain reaction and CDKN2A, p53, and SMAD4 expression by immunohistochemistry. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) for disease-free survival (DFS) and overall survival (OS) were computed according to each molecular alteration and the number of altered genes using the Cox regression models. Multivariable competing risks regression analyses were conducted to assess the associations of the number of altered genes with specific patterns of recurrence. Loss of SMAD4 expression was associated with short DFS (multivariable HR, 1.24; 95% CI, 1.09-1.43) and OS times (multivariable HR, 1.27; 95% CI, 1.10-1.46). Compared to cases with 0-2 altered genes, cases with three and four altered genes had multivariable HRs for OS of 1.28 (95% CI, 1.09-1.51) and 1.47 (95% CI, 1.22-1.78), respectively (ptrend < 0.001). Patients with an increasing number of altered genes were more likely to have short DFS time (ptrend = 0.003) and to develop liver metastasis (ptrend = 0.006) rather than recurrence at local or other distant sites. In conclusion, loss of SMAD4 expression and an increasing number of altered genes were associated with unfavourable outcomes in pancreatic cancer patients. This study suggests that the accumulation of the four major driver alterations can confer a high metastatic potential to the liver, thereby impairing post-operative survival among patients with pancreatic cancer.

Posthepatectomy but not prehepatectomy chemotherapy was associated with a longer time to recurrence in patients with resectable colorectal liver metastases: Inverse probability of treatment weighting analysis.

BACKGROUND: Patients with resectable colorectal liver metastases (CLM) are treated with surgery alone, surgery and posthepatectomy chemotherapy, or prehepatectomy chemotherapy and surgery. The optimal approach in terms of survival is unclear. We compared survival in the three treatment groups using inverse probability of treatment weighting (IPTW) analysis. METHODS: Data from patients undergoing initial CLM resection in 2005-2018 were obtained from a prospectively maintained database. Our group treated resectable CLM with surgery alone but gradually adopted post- and prehepatectomy chemotherapy for patients with CLM number ≥5 after 2015. IPTW analysis was employed to adjust the characteristics of the three groups. RESULTS: Of the 439 patients meeting the inclusion criteria, 175 underwent surgery alone, 135 underwent surgery and posthepatectomy chemotherapy, and 129 underwent prehepatectomy chemotherapy and surgery. After the IPTW adjustment, the demographic and clinicopathological characteristics were well balanced. The IPTW analysis revealed that the recurrence-free survival was better in patients undergoing surgery and posthepatectomy chemotherapy than in patients undergoing surgery alone (median recurrence-free survival, 1.3 years vs 0.7 years; P = .018). Overall survival was not significantly different between the three treatment approaches. CONCLUSION: Posthepatectomy but not prehepatectomy chemotherapy prolongs the time to recurrence after curative-intent resection of CLM.

Clinical Outcomes of Intraductal Papillary Mucinous Neoplasms With Dilatation of the Main Pancreatic Duct.

BACKGROUND & AIMS: Dilatation of the main pancreatic duct (MPD) has been a surgical indication for intraductal papillary mucinous neoplasms (IPMNs). Few studies have investigated long-term outcomes of IPMNs with MPD dilatation. METHODS: Among 3610 patients diagnosed with pancreatic cysts between 1994 and 2021, we identified 2829 IPMN patients, including 282 patients with MPD ≥5 mm, and examined short-term (≤6 months) and long-term risks of pancreatic carcinoma. Utilizing competing risks proportional hazards models, we estimated subdistribution hazard ratios for incidence of pancreatic carcinoma with adjustment for potential confounders. RESULTS: In analyses of short-term outcomes of the 282 patients with MPD dilatation, 72 (26%) patients were diagnosed with pancreatic carcinoma based on surgical or nonsurgical exploration. During long-term follow-up of 168 patients, we documented 24 (14%) patients diagnosed with pancreatic carcinoma (18 with IPMN-derived carcinoma and 6 with concomitant ductal adenocarcinoma). The patients with the MPD = 5-9.9 mm had cumulative incidence rates of pancreatic carcinoma diagnosis of 8.1% (95% confidence interval [CI], 4.3%-13.5%) and 10.0% (95% CI, 5.5%-15.9%) at 2 and 5 years, respectively; and the patients with the MPD ≥10 mm had the corresponding rates of 16.0% (95% CI, 3.6-36.5%) and 33.3% (95% CI, 10.3%-58.8%). The multivariable subdistribution hazard ratios were 2.78 (95% CI, 1.57-4.90) and 7.00 (95% CI, 2.58-19.0) for the MPD = 5-9.9 mm and ≥10 mm (vs <5 mm), respectively. CONCLUSIONS: IPMNs with MPD dilatation at baseline were associated with higher prevalence and incidence of pancreatic carcinoma compared with IPMNs with no MPD dilatation.

New Diagnostic Modality Combining Mass Spectrometry and Machine Learning for the Discrimination of Malignant Intraductal Papillary Mucinous Neoplasms.

BACKGROUND: An intraductal papillary mucinous neoplasm (IPMN) is a pancreatic tumor with malignant potential. Although we anticipate a sensitive method to diagnose the malignant conversion of IPMN, an effective strategy has not yet been established. The combination of probe electrospray ionization-mass spectrometry (PESI-MS) and machine learning provides a promising solution for this purpose. METHODS: We prospectively analyzed 42 serum samples obtained from IPMN patients who underwent pancreatic resection between 2020 and 2021. Based on the postoperative pathological diagnosis, patients were classified into two groups: IPMN-low grade dysplasia (n = 17) and advanced-IPMN (n = 25). Serum samples were analyzed by PESI-MS, and the obtained mass spectral data were converted into continuous variables. These variables were used to discriminate advanced-IPMN from IPMN-low grade dysplasia by partial least square regression or support vector machine analysis. The areas under receiver operating characteristics curves were obtained to visualize the difference between the two groups. RESULTS: Partial least square regression successfully discriminated the two disease classes. From another standpoint, we selected 130 parameters from the entire dataset by PESI-MS, which were fed into the support vector machine. The diagnostic accuracy was 88.1%, and the area under the receiver operating characteristics curve was 0.924 by this method. Approximately 10 min were required to perform each method. CONCLUSION: PESI-MS combined with machine learning is an easy-to-use tool with the advantage of rapid on-site analysis. Here, we show the great potential of our system to diagnose the malignant conversion of IPMN, which would be a promising diagnostic tool in clinical settings.

Transient loss of consciousness immediately after total pancreatectomy for pancreatic metastases from renal cell carcinoma: a case report.

BACKGROUND: Total pancreatectomy (TP) is often selected for treatment of various pancreatic diseases. However, the resultant lack of autoregulation of glycometabolism necessitates careful postoperative management. CASE PRESENTATION: A 77-year-old man who had undergone right nephrectomy for renal cell carcinoma 11 years previously presented with multiple histologically diagnosed pancreatic metastases. The patient had no notable comorbidities, including diabetes. Because no extrapancreatic organ metastasis was identified, he underwent TP as a curative treatment. He awoke from anesthesia and was extubated without any problems in the operating room. However, 15 min after entering the intensive care unit, he suddenly lost consciousness and became apneic, resulting in reintubation. Blood gas analysis revealed an increased glucose concentration (302 mg/dL) and mixed acid-base disorder (pH of 7.21) due to insulin insufficiency and fentanyl administration. After induction of continuous intravenous insulin infusion and termination of fentanyl, the glucose concentration and pH gradually improved. He regained clear consciousness and spontaneous ventilation and was extubated the next day with no difficulties or complications. CONCLUSION: This case highlights the importance of active monitoring of the glycemic state and pH after TP because of the possibility of deterioration due to TP itself as well as the lingering effects of anesthesia.

Safety and usefulness of fluorescence imaging using methylene blue as a fluorophore in a Japanese population with hepatobiliary and pancreatic diseases: A phase I study.

BACKGROUND: Methylene blue (MB) has been used to treat methemoglobinemia. Recently, a fluorescence imaging technique using MB as a fluorophore was used in several region but still not in hepatobiliary and pancreatic surgery; thus, information on the safety of intraoperative fluorescence imaging using MB in a healthy Japanese population is lacking. We aimed to evaluate the usefulness of MB fluorescence imaging in patients undergoing hepatobiliary and pancreatic surgery and the safety of intraoperative administration of MB in patients without methemoglobinemia. METHODS: Eighteen patients undergoing hepatobiliary and pancreatic surgery were enrolled. We developed and used a fluorescence imaging system to visualize MB as fluorescence. The fluorescence intensity of the blood vessels, tumors, liver, and intestine were measured. The primary endpoint was the ability of the MB fluorescence imaging to visualize vessels and tumors with fluorescence. The secondary endpoint was the safety of fluorescence imaging using MB in patients without methemoglobinemia. RESULTS: For the 18 patients undergoing MB fluorescence imaging, no intraoperative and postoperative complications related to MB administration occurred. Seventeen patients (94%) successfully visualized the target object as fluorescence by MB fluorescence imaging, including 100% of neuroendocrine tumors (four tumors) and peripancreatic vessels (n = 13). CONCLUSION: The administration of MB and application of fluorescence imaging using MB can visualize blood vessels and pancreatic neuroendocrine neoplasms. And it also showed the safety of using MB as a fluorophore in Japanese patients without methemoglobinemia.

Venous invasion and lymphatic invasion are correlated with the postoperative prognosis of pancreatic neuroendocrine neoplasm.

BACKGROUND: To determine treatment strategies corresponding to a wide range of pancreatic neuroendocrine neoplasms staging, easier-to-use and detailed prognostic classification is required. METHODS: Patients with pancreatic neuroendocrine neoplasms who underwent curative-intent surgery at the University of Tokyo Hospital between 2000 and 2018 were retrospectively reviewed. The presence or absence of venous and lymphatic invasion was assessed. Multivariable analysis was performed to identify the risk factors of shorter overall survival and recurrence-free survival. Patients were classified into the following 3 groups: a lymphovascular invasion 0 group, whereby both venous and lymphatic invasion were negative; an lymphovascular invasion 1 group, where either of the 2 was positive; and an lymphovascular invasion 2 group, where both were positive. The survival curves and recurrence patterns of the 3 groups were compared. RESULTS: Eighty-nine patients were analyzed. Multivariable analysis revealed that lymphatic invasion and Ki-67 index (≥ 3.0%) were independent prognostic factors of recurrence-free survival (hazard ratio: 5.2 and 3.6). Fifty-three patients were classified as lymphovascular invasion 0, 26 as lymphovascular invasion 1, and 10 as lymphovascular invasion 2. The recurrence-free survival curves of the 3 groups were significantly stratified (10-year recurrence-free survival: 89.1% in lymphovascular invasion 0, 57.1% in lymphovascular invasion 1, and 18.3% in lymphovascular invasion 2). Five-year cumulative liver and lymph node metastasis of lymphovascular invasion 0, lymphovascular invasion 1, and lymphovascular invasion 2 were well stratified at 0% and 3.8%, 15.8% and 23.1%, and 33.3% and 70.0%, respectively. CONCLUSION: Postoperative prognosis of resected pancreatic neuroendocrine neoplasms could be finely classified by venous invasion and lymphatic invasion. Management after curative-intent surgery for pancreatic neuroendocrine neoplasms may be changed by this new classification.

Automated liver tumor detection in abdominal ultrasonography with a modified faster region-based convolutional neural networks (Faster R-CNN) architecture.

Background: Although diagnostic ultrasound can non-invasively capture the image of abdominal viscera, diagnosis of the continuous ultrasound liver images to detect a liver tumor effectively and to determine whether the detected is benign or malignant is nontrivial. In order to minimize the gaps in diagnostic accuracy depending on doctor's proficiency, we built an automated system to support the ultrasonography of liver tumors by employing deep learning technologies. Methods: We constructed a neural network model for the automated detection of tumor tissues and blood vessels from the sequential liver ultrasound images. Faster region-based convolutional neural networks (Faster R-CNN) is employed as a base model for the object detection, which can output the detection results in 4 frames per second and enable the system to be particularly suitable for the real time ultrasonography. Moreover, we proposed a new neural network architecture feeding both the current and previous images into Faster R-CNN. For training the models, intraoperative ultrasound images obtained from one hepatocellular carcinoma (HCC) patient were used. The obtained image was a multifaceted observation of the liver and includes one HCC and some blood vessels. We labeled 91 images with the help of a liver specialist. We compared the tumor detection performance of the plain Faster R-CNN model with that of the proposed model. Results: We find that both the models performed well in detecting HCC and blood vessels, after training with 400 epochs using Adam. However, the mean precision of our model reaches 0.549, which is 0.019 better than that of the plain Faster R-CNN, and the mean sensitivity of our model about HCC reaches 0.623±0.385 for 30 scenes of sequential liver ultrasound images, which is also 0.146 better than that of the plain Faster R-CNN model. Conclusions: The comparison between the proposed model and the plain Faster R-CNN model shows that we achieved better accuracy in tumor detection, in terms of the mean precision as well as the mean sensitivity, with the proposed model.