The Short- and Long-Term Surgical Results of Consecutive Hepatopancreaticoduodenectomy for Wide-Spread Biliary Malignancy.

BACKGROUND: Cancer-free resection (R0) is one of the most important factors for the long-term survival of biliary carcinoma. For some patients with widespread invasive cancer located between the hilar and intrapancreatic bile duct, hepatopancreaticoduodenectomy (HPD) is considered a radical surgery for R0 resection. However, HPD is associated with high morbidity and mortality rates. Furthermore, previous reports have not shown lymph node metastasis (LNM) status, such as the location or number, which could influence the prognosis after HPD. In this study, first, we explored the prognostic factors for survival, and second, we evaluated whether the LNM status (number and location of LNM) would influence the decision on surgical indications in patients with widely spread biliary malignancy. METHODS: We retrospectively reviewed the medical records of 54 patients who underwent HPD with hepatectomy in ≥2 liver sectors from January 2003 to December 2021 (HPD-G). We also evaluated 54 unresectable perihilar cholangiocarcinoma patients who underwent chemotherapy from January 2010 to December 2021 (CTx-G). RESULTS: R0 resection was performed in 48 patients (89%). The median survival time (MST) and 5-year overall survival rate of the HPD-G and CTx-G groups were 36.9 months and 31.1%, and 19.6 months and 0%, respectively. Univariate and multivariate analyses showed that pathological portal vein involvement was an independent prognostic factor for survival (MST: 18.9 months). Additionally, patients with peripancreatic LNM had worse prognoses (MST: 13.3 months) than CTx-G. CONCLUSIONS: Patients with peripancreatic LNM or PV invasion might be advised to be excluded from surgery-first indications for HPD.

Impact of Neutrophil Extracellular Traps Identified by Citrullinated Histone H3 Immunohistochemistry for Postoperative Prognosis in Patients with Extrahepatic Cholangiocarcinomas.

BACKGROUND: Neutrophil extracellular traps (NETs) are extracellular chromatin structures composed of cytoplasmic, granular, and nuclear components of neutrophils. Recently, NETs have received much attention for their role in tumor biology; however, their impact on the postoperative prognosis of patients with extrahepatic cholangiocarcinomas (EHCCs) remains unclear. The purpose of this study was to clarify the impact of NETs identified by immunohistochemical citrullinated histone H3 (Cit-H3) staining on postoperative overall survival (OS) in patients with perihilar cholangiocarcinoma (PHCC) and distal cholangiocarcinoma (DCC). METHODS: This study included 318 patients with EHCC (PHCC, n = 192; DCC, n = 126) who underwent surgical resection with curative intent. Neutrophils and NETs were identified by immunohistochemistry using antibodies against CD15 and Cit-H3, respectively. Based on the distribution of CD15 and Cit-H3 expression in the tumor bed, the patients were classified into four groups: one negative group and three subgroups of the positive group (diffuse, intermediate, and focal subgroups). RESULTS: No significant difference was found in the postoperative OS rate depending on the distribution of CD15 expression in patients with PHCC or DCC. However, the three subgroups with positive Cit-H3 expression had significantly poorer OS than the negative group for both PHCC and DCC. Moreover, positive Cit-H3 was an independent OS factor in the multivariable analyses of PHCC (hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.11-2.59, P = 0.0115) and DCC (HR 2.03; 95% CI 1.21-3.42, P = 0.0057). CONCLUSIONS: The presence of NETs in the tumor microenvironment may have adverse prognostic effects in patients with EHCCs.

Outcomes of laparoscopic total gastrectomy in elderly patients: a propensity score matching analysis.

PURPOSE: This study evaluated the short-term outcomes and prognosis after laparoscopic total gastrectomy (LTG) in elderly patients aged ≥ 80 years in a multicenter retrospective cohort study using propensity score matching. METHODS: We retrospectively enrolled 440 patients who underwent curative LTG for gastric cancer at six institutions between January 2004 and December 2018. Patients were categorized into an elderly patient group (EG; age ≥ 80 years) and non-elderly patient group (non-EG; age < 80 years). Patients were matched using the following propensity score covariates: sex, body mass index, American Society of Anesthesiologists physical status, extent of lymph node dissection, and Japanese Classification of Gastric Carcinoma stage. Short-term outcomes and prognoses were compared. RESULTS: We identified 37 propensity score-matched pairs. The median operative time was significantly shorter, and postoperative stay was longer in the EG. In terms of postoperative outcomes, the rates of all complications were comparable. The median follow-up period of the EG and non-EG was 11.5 (1-106.4) months and 35.7 (1-110.0) months, respectively; there were significant differences in 5-year overall survival between the two groups (EG, 58.5% vs. non-EG, 91.5%; P = 0.031). However, there were no significant differences in 5-year disease-specific survival (EG, 62.1% vs. non-EG, 91.5%; P = 0.068) or 5-year disease-free survival (EG, 52.9% vs. non-EG, 60.8%; P = 0.132). CONCLUSIONS: LTG seems to be safe and feasible in elderly patients. LTG had a limited effect on morbidity, disease recurrence, and survival in elderly patients. Therefore, age should not prevent elderly patients from benefitting from LTG.

Bacteremia after hepatectomy and biliary reconstruction for biliary cancer: the characteristics of bacteremia according to occurrence time and associated complications.

PURPOSE: Bacteremia occurring after extensive hepatic resection and biliary reconstruction (Hx + Bx) for biliary cancer is a critical infectious complication. This study evaluated postoperative bacteremia and examined the potential usefulness of surveillance cultures. METHODS: We retrospectively reviewed 179 patients who underwent Hx + Bx for biliary cancer from January 2008 to December 2018 in our department. RESULTS: Bacteremia occurred in 41 (23.0%) patients. Patients with bacteremia had a longer operation time and more frequent intraoperative transfusion and more frequently developed organ/space surgical site infection (SSI) than those without bacteremia. The most frequently isolated bacterial species from blood cultures were Enterococcus faecium (29.3%), Enterobacter cloacae (24.4%), and Enterococcus faecalis (22.0%). The SIRS duration of bacteremia associated with organ/space SSI was significantly longer than that of other infectious complications (median 96 h vs. 48 h; p = 0.043). Bacteremia associated with organ/space SSI occurred most often by postoperative day (POD) 30. The concordance rate of bacterial species between blood and surveillance cultures within POD 30 was 67-82%. CONCLUSIONS: Bacteremia associated with organ/space SSI required treatment for a long time and typically occurred by POD 30. Postoperative surveillance cultures obtained during this period may be useful for selecting initial antibiotic therapy because of their high concordance rate with blood cultures.

Clinical and oncological benefits of left hepatectomy for Bismuth type I/II perihilar cholangiocarcinoma.

PURPOSE: This retrospective study aimed to clarify whether the postoperative prognosis differs between right and left hepatectomy for Bismuth type I/II perihilar cholangiocarcinoma. METHODS: Preoperative images of 195 patients with perihilar cholangiocarcinoma were reexamined. Patients with Bismuth type I/II perihilar cholangiocarcinoma without a difference in extraductal tumor invasion between the right and left sides of the hepatic portal region were classified into those undergoing left (L group) or right (R group) hepatectomy. RESULTS: Twenty-three patients (11.8%) were classified into the L group and 33 (16.9%) into the R group. All eight patients with pTis/1 belonged to the L group. The L group had significantly less liver failure than the R group (p = 0.001). One patient (4.3%) in the L group and four patients (12.1%) in the R group died from postoperative complications. Among 48 patients with pT2, the L group tended to have better overall survival (median, 12.2 vs. 5.6 years; p = 0.072), but not recurrence-free survival (median, 9.1 vs. 3.6 years; p = 0.477), in comparison to the R group. CONCLUSIONS: Postoperative survival after left hepatectomy for Bismuth type I/II perihilar cholangiocarcinoma is expected to be as long as that after right hepatectomy.

Targeted amplicon sequencing for primary tumors and matched lymph node metastases in patients with extrahepatic cholangiocarcinoma.

BACKGROUND: Lymph node metastasis (LNM) is one of the most adverse prognostic factors in extrahepatic cholangiocarcinoma (EHCC) cases. As next-generation sequencing technology has become more widely available, the genomic profile of biliary tract carcinoma has been clarified. However, whether LNMs have additional genomic alterations in patients with EHCC has not been investigated. Here, we aimed to compare the genomic alterations between primary tumors and matched LNMs in patients with EHCC. METHODS: Sixteen patients with node-positive EHCCs were included. Genomic DNA was extracted from tissue samples of primary tumors and matched LNMs. Targeted amplicon sequencing of 160 cancer-related genes was performed. RESULTS: Among the 32 tumor samples from 16 patients, 91 genomic mutations were identified. Genomic mutations were noted in 31 genes, including TP53, MAP3K1, SMAD4, APC, and ARID1A. TP53 mutations were most frequently observed (12/32; 37.5%). Genomic mutation profiles were highly concordant between primary tumors and matched LNMs (13/16; 81.3%), and an additional genomic mutation of CDK12 was observed in only one patient. CONCLUSION: Genomic mutations were highly concordant between primary tumors and matched LNMs, suggesting that genotyping of archived primary tumor samples may help predict genomic mutations of metastatic tumors in patients with EHCC.

Stratification of Postoperative Prognosis by Invasive Tumor Thickness in Perihilar Cholangiocarcinoma.

BACKGROUND: The pathological tumor classification of distal cholangiocarcinoma in the American Joint Committee on Cancer (AJCC) Cancer Staging Manual 8th edition is based on invasive depth, whereas that of perihilar cholangiocarcinoma (PHCC) continues to be layer-based. We aimed to clarify whether invasive depth measurement based on invasive tumor thickness (ITT) could help determine postoperative prognosis in patients with PHCC. METHODS: We enrolled 184 patients with PHCC who underwent hepatectomy plus extrahepatic bile duct resection or hepatopancreatoduodenectomy with curative intent. ITT was measured using simple definitions according to the sectioning direction or gross tumor pattern. RESULTS: The median ITT was 5.8 mm (range 0.7-15.5). Using the recursive partitioning technique, ITT was classified into grades A (ITT < 2 mm, n = 9), B (2 mm ≤ ITT < 5 mm, n = 68), C (5 mm ≤ ITT < 11 mm, n = 81), and D (11 mm < ITT, n = 26). The median survival times (MSTs) in patients with grade B, C, or D were 90.8, 44.6, and 21.1 months, respectively (patients with grade A did not reach the MST). There were significant differences in postoperative prognosis between ITT grades (A vs. B, p = 0.027; B vs. C, p < 0.001; C vs. D, p = 0.004). Through multivariate analysis, regional node metastasis, invasive carcinoma at the resected margin, and ITT grade were determined as independent prognostic factors. CONCLUSION: ITT could be measured using simple methods and may be used to stratify postoperative prognosis in patients with PHCC.

A drainage strategy for postoperative pancreatic fistula after left-sided pancreatectomy based on the wall status of collected fluid.

PURPOSE: Postoperative pancreatic fistula (POPF) after pancreatectomy is one of the severe postoperative adverse events. We aimed to clarify the outcomes of a strategy for POPF after left-sided pancreatectomy with one-step endoscopic ultrasonography-guided drainage (EUSD) and percutaneous drainage (PCD) based on the wall status of collected fluid. METHODS: From January 2012 to September 2017, 90 of 336 patients developed grade B/C POPF and were retrospectively analyzed. Primary outcome measures were the technical and clinical success and resolution rates. Secondary outcome measures were time from surgery to intervention, and time from intervention to discharge/resolution or stent/tube removal and adverse events. RESULTS: Seventeen patients underwent EUSD and 73 patients underwent PCD for POPF. The technical success rates were 100% in both the EUSD and PCD groups. The clinical success and resolution rates in the EUSD group were 100%, while those in the PCD group were 98.6%. The time from surgery to intervention was significantly longer in the EUSD group than in the PCD group (20 vs. 11 days, p < 0.001). The time from intervention to discharge/resolution was significantly shorter in the EUSD group than in the PCD group (11 vs. 22 days, p < 0.001/10 vs. 20 days, p < 0.001). The time from intervention to stent/tube removal was significantly shorter in the PCD group than in the EUSD group (20.5 vs. 873 days, p < 0.001). Adverse event rates were similar in the two groups (11.8% vs. 5.5%). CONCLUSION: A drainage strategy for POPF based on the wall status of collected fluid is appropriate.

The assessment of risk factors for postoperative delirium using cubic spline curves in gastroenterological surgery.

PURPOSE: Delirium is associated with longer hospital stays and increased medical costs and mortality. This study explored the risk factors for postoperative delirium in gastroenterological surgery and investigated the association between qualitative changes in risk factors and the incidence of postoperative delirium. METHODS: A total of 418 patients > 18 years old who underwent gastroenterological surgery at our department between April 2018 and September 2019 were included. Risk factors were identified by comparing patients with and without postoperative delirium. Continuous variables were evaluated graphically using cubic spline curves. A logistic regression analysis was performed to assess independent risk factors. RESULTS: The incidence of postoperative delirium was 6.9%. The cubic spline curve showed that the incidence of postoperative delirium began to increase at 50 years old and increased sharply at 70 years old. A multiple logistic regression analysis of patients > 50 years old identified 5 risk factors: age ≥ 70 years, preoperative serum albumin ≤ 3.8 g/dL, psychosis, sedative-hypnotics, and intensive-care unit admission. CONCLUSION: The risk of postoperative delirium increases progressively at 50 years old and sharply at 70 years old. Advanced age, preoperative hypoalbuminemia, psychosis, sedative-hypnotics, and intensive-care unit admission are risk factors for postoperative delirium in patients > 50 years old undergoing gastroenterological surgery.

Laparoscopic real-time vessel navigation using indocyanine green fluorescence during the laparoscopic-Warshaw technique: First clinical experience.

BACKGROUND: Laparoscopic-Warshaw technique (lap-WT) may be selected as a function-preserving operation for malignant border lesions in the tail region of the pancreas. However, previous reports showed that there are complications such as infection and abscess formation due to lack of blood flow to the spleen after surgery. To overcome the problems, we have performed real-time vessel navigation by using indocyanine green (ICG) fluorescence during lap-WT. MATERIALS AND METHODS: We report our experience of three patients with pancreatic tumour who underwent real-time vessel navigation during lap-WT at Hokkaido University from May 2017 to September 2018. RESULTS: The median operating time was 339 min (174-420). The median intraoperative bleeding was 150 ml (0-480). There were no incidences of complications. There were no cases with post-operative spleen ischaemia or abscess formation and varices formation. CONCLUSION: We believe that laparoscopic real-time vessel navigation using indocyanine green fluorescence during lap-WT could contribute in reducing the post-operative spleen-related complications.

Time to Recurrence After Surgical Resection and Survival After Recurrence Among Patients with Perihilar and Distal Cholangiocarcinomas.

BACKGROUND: The differences between perihilar cholangiocarcinoma (PHCC) and distal cholangiocarcinoma (DCC) regarding recurrence and the factors that affect recurrence after surgery are unclear. This study aims to investigate the differences in recurrence patterns between patients with PHCC and those with DCC after surgical resection with curative intent. It also investigates the risk factors associated with recurrence and survival thereafter. PATIENTS AND METHODS: The postoperative courses of 366 patients with extrahepatic cholangiocarcinomas (EHCCs), including 236 with PHCC and 130 with DCC, who underwent surgical resections were investigated retrospectively. RESULTS: During follow-up, tumors recurred in 143 (60.6%) patients with PHCC and in 72 (55.4%) patients with DCC. Overall survival (OS) after surgery, recurrence-free survival (RFS), and OS after recurrence were similar for the patients with PHCC and those with DCC. The cumulative probability of recurrence declined 3 years after surgery in the patients with PHCC and those with DCC. A multivariable analysis determined that, among the patients with PHCC and those with DCC, regional lymph node metastasis was a significant risk factor associated with RFS. Ten patients with PHCC and eight patients with DCC with two or fewer sites of recurrence in a single organ underwent resections. A multivariable analysis determined that recurrent tumor resection was an independent prognostic factor associated with OS after recurrence in the patients with PHCC and those with DCC. CONCLUSIONS: Postoperative survival did not differ between the patients with PHCC and those with DCC. Frequent surveillances for recurrence are needed for 3 years after surgical resection of EHCCs. In selected patients, surgery for recurrent EHCCs might be associated with improved outcomes.

Outcomes of limited resection for patients with intraductal papillary mucinous neoplasm of the pancreas: A single-center experience.

BACKGROUND: /ObjectivesThe aim of this study was to clarify the oncological outcomes of patients with intraductal papillary mucinous neoplasm (IPMN) who underwent limited resection (LR). METHODS: This retrospective study analyzed the data of 110 patients with IPMN. Patients with IPMN without a history of pancreatitis who had neither tumor infiltration nor regional lymph node swelling on imaging findings underwent LR. We assessed the oncological outcomes of LR for patients with IPMN by comparing the surgical outcomes of LR and standard resection. RESULTS: LR was performed in 50 patients (45.5%), including duodenum-preserving pancreatic head resection (n = 31), middle-pancreatectomy (n = 12), spleen-preserving distal pancreatectomy (n = 3), total parenchymal pancreatectomy (n = 3), and partial resection (n = 1). In the LR group, 18 patients had postoperative complications of Clavien-Dindo classification ≥ IIIa. After histopathological examination, the presence of high-grade dysplasia (HGD) and invasive carcinoma (IC) were observed in nine and three patients, respectively, in the LR group, and eight and 22 patients, respectively, in the standard resection group. There was a significant difference in the histopathological diagnosis of IC between the two groups (p < 0.001). Finally, in the LR group, postoperative recurrences occurred in three patients, and the 5-, 10-, and 15-year disease-specific survival rates were all 97.0%. CONCLUSIONS: For patients with IPMN judged to have no infiltrating lesions based on the detailed imaging examination, LR is acceptable and may be considered as an alternative to standard resection.

Pancreatic body and tail cancer and favorable metastatic lymph node behavior on the left edge of the aorta.

BACKGROUND: Lymph node (LN) metastasis in pancreatic body-tail cancer is a poor prognostic factor and the optimal LN dissection area for distal pancreatectomy (DP) remains unclear. Lymphatic flow from the tumors is thought to depend on the tumor sites. We examined LN metastasis frequency based on tumor site and recurrent patterns post-DP. METHODS: With a retrospective, single institutional study, we examined 100 patients who underwent DP as an upfront surgery for pancreatic cancer over 17 years. Tumor sites were classified as tumor confined to pancreatic body (and neck) (Pb(n)); and pancreatic tail (Pt). We compared metastatic LN and recurrence patterns based on tumor site. The median overall survival (OS) and disease-free survival (DFS) were analyzed. RESULTS: LN metastasis occurred in 59/100 (59.0%), with 23 and 25 tumors located in the Pb(n), and Pt, respectively. Those with the tumor in Pt had metastases to #10, #11d/p, and #18 LN mainly. However, the patients with the Pb(n) tumor had metastases to #8a/p, #11p, and #14p/d LN. There was no metastasis to #10 and #11d LN. The OS and DFS were 34 and 15 months, respectively. No significant difference was found in the OS, DFS, and recurrence patterns based on tumor sites. CONCLUSION: Differences in metastatic LN sites were observed in pancreatic body-tail cancer when tumors were confined to the left or right of the left aortic edge. Although it is necessary to validate this finding with a large-scale study, organ-preserving DP might be a treatment option for selected patients depending on the tumor sites.

Elevated chymase-dependent angiotensin II-forming activity in circulating mononuclear leukocytes was observed in the patient of atrial fibrillation.

Chymase is an angiotensin II-forming serine proteinase and elevation of its tissue activity occurs in various cardiovascular diseases. Several authors have suggested that there is an association between the renin-angiotensin system and atrial fibrillation (AF). Chymase-dependent angiotensin II-forming activity in circulating mononuclear leukocytes (CML chymase dAIIFA) was investigated in patients with AF and patients in sinus rhythm. Consecutive outpatients were recruited at our hospital. CML chymase dAIIFA was measured using a Nma/Dnp-type fluorescence-quenching substrate of modified angiotensin I in the presence or absence of a specific serine proteinase inhibitor. To search the independent contributing factor of existence of AF, the analysis between groups was carried out using multivariate analysis after univariate analysis. The patients were classified into a sinus rhythm (SR) group (n = 459) or an AF group (n = 48). CML chymase dAIIFA was significantly higher in the AF group (622 pmol/min/mg) compared with the SR group (488 pmol/min/mg) (p < 0.001). Logistic regression analysis revealed that high CML chymase dAIIFA was an independent determinant of the existence of AF (p < 0.001). Elevation of CML chymase dAIIFA was associated with AF. Activation of chymase might be linked to atrial structural and electrical remodeling.

Efficacy and safety of a combination antihypertensive drug (olmesartan plus azelnidipine): "Issues with hypertension studies in real-world practice".

Background: This study investigated whether a combination drug containing an angiotensin II receptor blocker (ARB) and a calcium channel blocker (CCB) could provide effective antihypertensive therapy.Methods: A multicenter, prospective, open-label study was conducted at the clinics of Clinical Research Network. The subjects had uncontrolled blood pressure (BP) despite ARB or CCB monotherapy. The effect on both office and home BP was examined after patients switched to a combination drug (REZ: containing 20 mg of olmesartan [OL] and 16 mg of azelnidipine [AZ]).Results: A total of 78 patients were enrolled. After switching to REZ, a significant and sustained reduction of office BP was observed. The proportion of patients who achieved the target for both office and home BP was an increase from 0% to 55%. Switching from amlodipine to REZ resulted in a significant and sustained decrease of office and home BP. There was also a significant decrease of home pulse rate (PR), but office PR was unchanged. To determine the accuracy of the BP and PR values reported by patients, the frequency of each number as the first digit was determined. The frequency of "0" was extremely high for both office and home BP values, and the same was noted for home PR values.Conclusion: The results of this study suggested that switching from a single drug to combination therapy with REZ could achieve a stronger antihypertensive effect. However, concern was raised regarding the methods of BP and PR measurement and recording in this clinical trial involving general practitioners.

Multicenter prospective observational study of teneligliptin, a selective dipeptidyl peptidase-4 inhibitor, in patients with poorly controlled type 2 diabetes: Focus on glycemic control, hypotensive effect, and safety Chikushi Anti-Diabetes Mellitus Trial-Teneligliptin (CHAT-T).

Objective: We purpose to confirm the effect of teneligliptin (Tenelia), a selective dipeptidyl peptidase-4 (DPP-4) inhibitor, on glycemic control and non-glucose risk factors for macroangiopathy, including blood pressure, lipid metabolism, and body weight.Methods: In a prospective, multicenter, open-label, observational study, teneligliptin (20 mg/day) was administered to type 2 diabetic patients with poor glycemic control (HbA1c ≥ 6.5% to <10%) at our hospitals. The safety of teneligliptin and its impact on blood glucose, blood pressure, and the lipid profile were assessed after administration for 3 and 6 months.Results: One hundred and sixty-two patients were enrolled between February 2014 and August 2015. HbA1c was 7.6% at baseline and showed significant reduction to 7.1% after 3 months of treatment and to 6.9% after 6 months (both p < 0.01). Patients with poorly controlled hypertension (systolic blood pressure [SBP] ≥130 mmHg and/or diastolic blood pressure [DBP] ≥80 mmHg) at study initiation were extracted to investigate the effect of teneligliptin on blood pressure. SBP showed a significant decrease from 141.2 ± 9.8 mmHg at baseline to 131.1 ± 14.3 mmHg after 3 months and 133.9 ± 11.5 mmHg after 6 months (both p < 0.001). DBP also decreased significantly from 85.8 ± 5.7 mmHg at baseline to 78.4 ± 10.0 mmHg after 3 months and 79.7 ± 10.1 mmHg after 6 months (both p < 0.001). Adverse events were pruritus in four patients, and cerebral infarction was reported as a cerebrovascular event in one patient.Conclusions: Teneligliptin therapy was safe and improved glycemic control irrespective of baseline HbA1c. Blood pressure was also improved in patients with concomitant hypertension.

Add-on aliskiren treatment can decrease blood pressure but requires attention to risks of renal impairment and hyperkalemia Chikushi Anti-Hypertension Trial-Rasilez® (CHAT-Ras).

BACKGROUND: Renin is the starting point of the renin angiotensin (RA) system cycle. Aliskiren (AL), which is a direct renin inhibitor, suppressed the entire RA cycle. In the present study, the efficacy of add-on of AL treatment in patients with essential hypertension (HT) was investigated. METHODS: This study was a multi-center, open-label, prospective, observational study. Study subjects were patients with essential HT and poor blood pressure (BP) control, who had received calcium channel blocker monotherapy or angiotensin II receptor blocker monotherapy or had not received any BP lowering drugs. Following add-on of AL for 12 months, BP and additional laboratory findings were analyzed. RESULTS: A total of 150 subjects were enrolled. There were 50 dropout subjects including discontinuation. Dropouts were the highest in the ARB combination therapy group at 9 subjects due to adverse events, and 3 of them were due to hyperkalemia. A significantly higher number of patients with chronic kidney disease (CKD) dropped out compared to patients without CKD (φ = 0.166, p < .05). BP before add-on of AL was 155/88 mmHg. After add-on of AL, BP was significantly improved and this lowering was sustained for 3 months (136/78 mmHg, p < .001), 6 months (136/77 mmHg, p < .001) and 12 months (134/78 mmHg, p < .001). In contrast, add-on of AL increased the potassium level and decreased the estimated glomerular filtration rate. CONCLUSION: While add-on AL treatment achieved a favorable and sustained decrease of BP in this study, caution is necessary with regard to elevation of potassium levels and renal impairment.

The effect of the body mass index on the short-term surgical outcomes of laparoscopic total gastrectomy: A propensity score-matched study.

PURPOSE: This study aimed to evaluate the relationship between the body mass index (BMI) and the short-term outcomes of laparoscopic total gastrectomy (LTG). SUBJECTS AND METHODS: Data of patients who underwent LTG for gastric cancer at six institutions between 2004 and 2018 were retrospectively collected. The patients were classified into three groups: low BMI (<18.5 kg/m2), normal BMI (≥18.5 and <25 kg/m2) and high BMI (≥25 kg/m2). In these patients, clinicopathological variables were analysed using propensity score matching for age, sex, the American Society of Anaesthesiologists physical state, clinical stage, surgical method, D2 lymph node dissection, combined resection of other organs, anastomosis method and jejunal pouch reconstruction. The surgical results and post-operative outcomes were compared among the three groups. RESULTS: A total of 82 patients were matched in the analysis of the low BMI and normal BMI groups. There were no differences in operative time (P = 0.693), blood loss (P = 0.150), post-operative complication (P = 0.762) and post-operative hospital stay (P = 0.448). In the analysis of the normal BMI and high BMI groups, 208 patients were matched. There were also no differences in blood loss (P = 0.377), post-operative complication (P = 0.249) and post-operative hospital stay (P = 0.676). However, the operative time was significantly longer in the high BMI group (P = 0.023). CONCLUSIONS: Despite the association with a longer operative time in the high BMI group, BMI had no significant effect on the surgical outcomes of LTG. LTG could be performed safely regardless of BMI.

Prognostic relevance of tertiary lymphoid organs following neoadjuvant chemoradiotherapy in pancreatic ductal adenocarcinoma.

The efficacy of preoperative neoadjuvant chemoradiotherapy (NAC) in cases of pancreatic cancer with extremely poor prognoses has been reported. In this study, we aimed to identify novel biomarkers that reflect prognoses following chemoradiotherapy using tertiary lymphoid organs (TLO) expressed in the tumor microenvironment. Resected tumor specimens were obtained from 140 pancreatic cancer patients. We retrospectively investigated the clinical relevance of TLO by categorizing patients into those who underwent upfront surgery (surgery first [SF]) and those who received NAC. The immunological elements within TLO were analyzed by immunohistochemistry (IHC). In the IHC analysis, the proportions of CD8+ T lymphocytes, PNAd+ high endothelial venules, CD163+ macrophages and Ki-67+ cells within the TLO were higher in the NAC group than in the SF group. In contrast, the proportion of programmed cell death-1+ immunosuppressive lymphocytes within TLO was lower in the NAC group than in the SF group. The NAC group demonstrated favorable prognoses compared with the SF group. In the multivariate analysis, the TLO/tumor ratio was determined as an independent predictive prognostic factor. In conclusion, the administration of preoperative chemoradiotherapy may influence the immunological elements in the tumor microenvironment and result in favorable prognoses in pancreatic ductal adenocarcinoma patients.

High Fib4 index in patients with suspected NASH is associated with elevation of chymase-dependent angiotensin II-forming activity in circulating mononuclear leucocytes.

Fatal hepatic disease is closely related to non-alcoholic fatty liver disease, especially non-alcoholic steatohepatitis (NASH). NASH is associated with cardiovascular events because it develops on the background of lifestyle-related diseases. Chymase-dependent angiotensin II-forming activity (dAIIFA) in circulating mononuclear leucocytes (CML) is a marker of local angiotensin II production and inflammation. This study investigated the association between CML chymase dAIIFA and NASH. Cardiovascular outpatients were recruited and the Fib4 index (F4I) was calculated. Patients with an F4I > 2.67 were classified into the high F4I group and these patients were strongly suspected to have NASH, while patients with an F4I < 1.30 were classified into the low F4I group. Patient background factors were compared between these groups. CML chymase dAIIFA was measured by ELISA using Nma/Dnp-modified angiotensin I. Among 499 patients, 16% were classified into the high F4I group. Compared with the low F4I group, the high F4I group had a significantly higher age, pancytopenia, more frequent diabetes mellitus, lower diastolic blood pressure, lower estimated glomerular filtration rate, higher brain natriuretic peptide, lower plasma aldosterone concentration, higher total AIIFA, higher CML chymase dAIIFA, and higher pulse wave velocity. Contrary to expectations, the body mass index, triglycerides, and low-density lipoprotein cholesterol were relatively low in the high F4I group. Many cardiovascular outpatients have a high F4I and can probably be categorized as NASH. The high F4I patients had few features of metabolic syndrome and were suspected to have elevated tissue chymase dAIIFA contributing to inflammation in the liver as well as in cardiovascular organs.