Reconsideration of indications for third hepatectomy for colorectal liver metastases.

BACKGROUND: It is unclear which patients with recurrence after a second hepatectomy will benefit from a third hepatectomy. METHODS: Patients who underwent hepatectomy for colorectal liver metastasis (CRLM) between April 2005 and July 2021 were included. Factors affecting recurrence after each hepatectomy were analyzed. RESULTS: Sixty-four of the 167 patients who had recurrence after the first hepatectomy underwent a second hepatectomy. Then, 46 patients had recurrence and 18 patients did not have recurrence after the second hepatectomy. Sixteen patients who underwent a third hepatectomy had better overall survival (OS) than those who did not (52 vs. 31 months, p = 0.043). However, the multivariate analysis demonstrated that only tumor size (>5 cm) during the second hepatectomy (p = 0.022) and carbohydrate antigen 19-9 (CA 19-9) level (>50 U/ml) (p = 0.041) at recurrence after the second hepatectomy were poor prognostic factors for OS. CONCLUSION: While a third hepatectomy can be performed if it is technically and oncologically appropriate, tumor size >5 cm and CA 19-9 >50 U/ml should be considered in terms of long-term outcomes before proceeding to surgery.

Clinicopathological Features and Surgical Outcomes of Small Bowel Metastasis from Renal Cell Carcinoma.

Small bowel metastasis from renal cell carcinoma (RCC) is rare, and its clinicopathological characteristics are unclear; thus, we revisited the concept of this tumor and reviewed its diagnostic and treatment modalities. We filtered MEDLINE searches of articles published in English between 1950 and 2019, and identified 100 patients who had undergone treatment, including 1 patient from our clinic. We extracted patient characteristics, treatment, and prognostic data, resulting in clinicopathological data on 100 patients (83 men, 17 women). Mean age was 63 years (range, 16-86 years). Tumor sites were duodenum, jejunum, ileum, and multiple sites in 30, 37, 25, and 7 patients, respectively. The 1-, 3-, and 5-year overall survival rates after diagnosis were 53.0%, 36.0%, and 36.0%. Curative resection patients showed 62.1% 5-year survival after surgery, vs. 27.5% in noncurative surgical management cases. Good prognoses can be expected if these tumors are identified early for complete removal. Surgery is the only curative option. To determine the best management strategy and improve prognostic accuracy, we continue to collect and analyze epidemiological and pathological data. Although this condition is rare, surgery should be considered if curative resection is expected. Prognosis after curative resection is not poor, but recurrence is not unlikely.

A proposal to modify the 8th edition of the UICC staging system for pancreatic adenocarcinoma.

PURPOSE: The aim of this study was to validate and improve the 8th edition of the Union for International Cancer Control (UICC) staging system for pancreatic ductal adenocarcinoma (PDAC). METHODS: Prognostic impact of the pathological tumor (pT) and lymph node (pN) stages between the 7th and 8th editions were compared using a single-center cohort of 311 patients who underwent curative pancreatic resection for PDAC. RESULTS: Applying the 7th edition T staging system resulted in a clustering of pT3 cases (92.3%) and failed to show significant prognostic differences between the three pT stages. However, applying the 8th edition T staging system yielded a more even distribution and resulted in an excellent prognostic separation between the pT stages based on decreases in median survival (month [pT1: 69.4, pT2: 27.6, pT3: 16.7], p=0.001). In pN staging system, the 8th edition provided more precise prognostication in median survival (month [pN0: 41.7, pN1: 25.6, pN2: 14.4], p<0.001). Moreover, in the 8th edition pT2 category, patients with portal vein invasion (PVI) showed significantly worse survival than those without PVI (median survival months [without PVI: 38.2, with PVI: 17.1], p<0.001). CONCLUSIONS: The 8th edition provides a more even distribution among stages and better stage discriminations compared to the 7th edition. The 8th edition pT2 category should be subdivided according to PVI status of the patient to allow for more precise patient prognostication.

Effect of Neoadjuvant Chemotherapy in Patients with Colorectal Cancer Liver Metastases.

BACKGROUND: This study was performed to evaluate the relationships between potential prognostic factors and post-surgery survival in patients with colorectal cancer liver metastasis (CRLM). In particular, this study investigated the value of neoadjuvant chemotherapy as an independent predictor of cancer-specific survival. METHODS: The study participants included 147 patients who underwent resection for CRLM. Demographics, treatments, and relationships between potential prognostic factors and the survival rate were analyzed using a prospective database. RESULTS: The overall 1-, 3- and 5-year cancer-specific survival rates for post-surgery CRLM patients were 94.3%, 71.2%, and 53.5%, respectively. Multivariate analysis revealed that a positive surgical margin and extrahepatic metastasis were independent negative prognostic factors. The administration of neoadjuvant chemotherapy prior to liver surgery did not significantly improve post-surgery outcomes of patients with CRLM. In a subgroup analysis, the time to recurrence in the remnant liver after hepatectomy for CRLM was significantly less in the neoadjuvant group than in the upfront surgery group. CONCLUSIONS: Neoadjuvant chemotherapy was not predictive of cancer-specific survival. The achievement of macroscopically and microscopically negative resection remains the main aim of surgery.

A Novel Physiobiological Parameter-Based Grading System for Resectable Pancreatic Cancer.

BACKGROUND: Preoperative methods to estimate disease-specific survival (DSS) for resectable pancreatic cancer are limited. OBJECTIVE: The aim of this study was to develop and validate a pretreatment physiobiological prognostic model in patients with radiologically resectable pancreatic cancer. METHODS: A retrospective review of a prospectively maintained institutional database was undertaken to identify patients who underwent potentially curative resection for radiologically resectable pancreatic cancer. Demographics, treatments, and relationships between the potential prognostic factors and survival rate were analyzed, and prognostic nomograms were established. RESULTS: We identified 240 patients who fulfilled our eligible criteria. The 1-, 3-, and 5-year DSS rates after surgery were 77.8, 40.9, and 31.3%, respectively. On multivariate analysis, increased neutrophil/lymphocyte ratio [hazard ratio (HR) 1.60, 95% confidence interval (CI) 1.17-2.17; p < 0.01], reduced Prognostic Nutritional Index (HR 2.08, 95% CI 1.68-3.20; p < 0.01), and elevated preoperative serum carbohydrate antigen 19-9 level (HR 2.12, 95% CI 1.55-2.88; p < 0.01) were associated with worse DSS. Although curative resection was the operative aim for all patients, 131 (54.6%) patients had recurrence within 12 months after curative resection of resectable pancreatic cancer. There was a significant correlation between recurrence pattern and physiobiological characteristics. CONCLUSION: We developed a new grading system for radiologically resectable pancreatic cancer. This system is simple and reliably predicts differences in survival after pancreatic resection.

Correlation between the skeletal muscle index and surgical outcomes of pancreaticoduodenectomy.

PURPOSES: Sarcopenia is known to be associated with a worse prognosis following abdominal operations; however, the relationship between sarcopenia and the outcomes of pancreaticoduodenectomy remains unclear. MATERIALS: We measured body composition parameters, including total abdominal muscle area, using preoperative staging computed tomography (CT), in patients undergoing pancreaticoduodenectomy for periampullary cancer. The incidence of sarcopenia among these patients was evaluated and multivariable analysis was performed to identify independent predictors of postoperative pancreatic fistula. RESULTS: We identified 335 consecutive patients who were eligible for the study. Patients with sarcopenia had significantly poorer 5-year survival rates than those without sarcopenia (32.4 vs. 51.6%, respectively, P = 0.009). Interestingly, the incidence of Grade B/C pancreatic fistula was significantly lower in the sarcopenia group than in the non-sarcopenia group. Multivariate analysis identified high body mass index and soft pancreatic texture as independent predictors of postoperative pancreatic fistula. CONCLUSION: Sarcopenia may have an independent prognostic effect on the survival of patients with periampullary cancer. Preoperative nutritional intervention and rehabilitation may improve the postoperative outcomes of pancreaticoduodenectomy for periampullary cancer.

Randomised controlled trial of long-term maintenance corticosteroid therapy in patients with autoimmune pancreatitis.

OBJECTIVE: Corticosteroid has been established as the standard therapy for autoimmune pancreatitis (AIP), but the requirement for maintenance corticosteroid therapy is controversial. We conducted a randomised controlled trial to clarify the efficacy of maintenance corticosteroid therapy in patients with AIP. DESIGN: We conducted a multicentre, tertiary setting, randomised controlled trial. After the induction of remission with the initial oral prednisolone (PSL) treatment, maintenance therapy with PSL at 5-7.5 mg/day was continued for 3 years or withdrawn at 26 weeks. The primary endpoint was relapse-free survival over 3 years and the secondary endpoint was serious corticosteroid-related complications. All analyses were performed on an intention-to-treat basis. RESULTS: Between April 2009 and March 2012, 49 patients with AIP were randomly assigned to the maintenance therapy group (n=30) or the cessation group (n=19). Baseline characteristics were not different between the two groups. Relapses occurred within 3 years in 11 out of 19 (57.9%) patients assigned to the cessation group, and in 7 of 30 (23.3%) patients in the maintenance therapy group. The relapse rate over 3 years was significantly lower in the maintenance therapy group than that in the cessation group (p=0.011). The relapse-free survival was significantly longer in the maintenance therapy group than that in the cessation group (p=0.007). No serious corticosteroid-related complications requiring discontinuation of PSL were observed. CONCLUSIONS: Maintenance corticosteroid therapy for 3 years may decrease relapses in patients with AIP compared with those who discontinued the therapy at 26 weeks. TRIAL REGISTRATION NUMBER: UMIN000001818; Results.

Safety and Efficacy of the Surgical Management of Hemodialysis Patients with Gastric Cancer.

This retrospective study evaluated the short- and long-term outcomes after surgical management for gastric cancer in hemodialysis patients compared to non-dialysis patients. Twelve hemodialysis patients were compared with a propensity score-matched cohort of 39 gastric cancer patients who had not undergone hemodialysis. Short- and long-term outcomes along with scores estimating physiological ability and surgical stress were evaluated in both groups. The incidence of postoperative morbidity according to the Clavien-Dindo classification was higher in the hemodialysis gastric cancer group than in the non-dialysis gastric cancer group. The 5-year overall survival rate in the non-dialysis group was 69.2% after surgical resection for gastric cancer and 22.2% in the hemodialysis group. Patients with preoperative risk scores≥0.48 had significantly poorer survival outcomes compared to those with preoperative risk scores<0.48 (5-year survival rate, 83.3% vs. 39.4%, respectively). Our analyses suggest that hemodialysis patients undergoing surgery for gastric cancer have a significantly poorer postoperative prognosis and an elevated risk of postoperative complications.

Surgical Management in Patients with Gastrointestinal Stromal Tumors: A Single-Center Experience.

BACKGROUND: We have revisited prognostic outcomes and recurrence patterns in patients with gastrointestinal stromal tumors (GISTs) who underwent complete surgical resection at a single institution. PATIENTS AND METHODS: Patients who underwent curative surgical treatment were divided into two groups: those with high-risk GISTs (high-risk group) and those with very low-, low-, and intermediate-risk GISTs (lower-risk group). RESULTS: A total of 109 patients who underwent surgery as an initial treatment for GIST were studied. The overall 5- and 10-year survival rates after surgery were 90.3 and 71.1%, respectively. The 5-year survival rate in high-risk group patients was 88.1%, and their overall survival rate did not vary significantly from that of the lower-risk group (5-year survival rate, 91.3%). The recurrence rate in patients with high-risk GISTs gradually increased without reaching a plateau, with a cumulative rate of GIST recurrence of 26.4 and 48.9% at 5 and 10 years after surgical treatment, respectively. CONCLUSIONS: Our data suggest that the repeat surgical management in metastatic GIST is of clinical usefulness whatever the risk and improves survival.

Differentiation of infiltrative cardiomyopathy from hypertrophic cardiomyopathy using high-sensitivity cardiac troponin T: a case-control study.

BACKGROUND: Because infiltrative cardiomyopathy and hypertrophic cardiomyopathy (HCM) share clinical and hemodynamic features of left ventricular (LV) hypertrophy and abnormal diastolic function, it is often difficult to distinguish these entities. METHODS: We investigated the potential role of high-sensitivity cardiac troponin T (hs-cTnT) for differentiation of infiltrative cardiomyopathy from HCM. RESULTS: The study group consisted of 46 consecutive patients with infiltrative cardiomyopathies or HCM in whom sarcomere protein gene mutations were identified at Kochi Medical School Hospital; of these, there were 11 patients with infiltrative cardiomyopathy (cardiac amyloidosis in 8 patients and Fabry disease in 3 patients) and 35 HCM patients. Serum hs-cTnT level was significantly higher in patients who had infiltrative cardiomyopathy than in those who had HCM (0.083 ± 0.057 ng/ml versus 0.027 ± 0.034 ng/ml, p < 0.001), whereas brain natriuretic peptide levels did not differ between the two groups. In two age-matched the 2 cohorts (patients evaluated at > 40 years at age), hs-cTnT level, maximum LV wall thickness, posterior wall thickness, peak early (E) transmitral filling velocity, peak early diastolic (Ea) velocity of tissue Doppler imaging at the lateral corner and E/Ea ratios at both the septal and lateral corners were significantly different between the two groups. As for diagnostic accuracy to differentiate the two groups by using receiver operating characteristic analysis, hs-cTnT was the highest value of area under the curve (0.939) and E/Ea (lateral) was second highest value (0.914). CONCLUSIONS: Serum hs-cTnT is a helpful diagnostic indicator for accurate differentiation between infiltrative cardiomyopathy and HCM.

Reconsideration about the aggressive surgery for resectable pancreatic cancer: a focus on real pathological portosplenomesenteric venous invasion.

BACKGROUND: Some clinicians have argued that combining pancreatic and portomesenteric venous resection could improve the rates of long-term survival. However, whether resection of the portosplenomesenteric vein could provide an acceptable survival benefit to patients with pancreatic cancer involving the portosplenomesenteric system remains controversial. The purpose of this study was to determine the significance of pathological portosplenomesenteric venous invasion on survival in patients who underwent surgical management for pancreatic adenocarcinoma. METHODS: Patients who underwent curative surgical treatment were divided into two subgroups: those with pathological invasion to the portosplenomesenteric vein (PV-positive group) and those without invasion (PV-negative group). RESULTS: Of 160 studied patients, the median overall survival was 48.0 months after pancreatic surgery in the PV-negative group and 18.0 months in the PV-positive group. The incidence of postoperative peritoneal dissemination was significantly lower in the PV-negative group than in the PV-positive group. Accordingly, patients in the PV-negative group showed a cumulative rate of pancreatic cancer recurrence at 2 years after pancreatic surgery of 54.4%, while this rate was 89.4% in the PV-positive group. Finally, an elevated presurgical serum CA19-9 level (>700 IU/mL) was found to be significantly associated with a poor outcome after surgery in pancreatic cancer patients with pathological portosplenomesenteric venous invasion. CONCLUSIONS: Pancreatic cancer carries a high risk of recurrence even if surgical resection is technically possible. The current study suggested that portosplenomesenteric involvement and preoperative high serum CA19-9 are poor prognostic indications; however, the findings provided little insight into the role of neoadjuvant therapy in such patients.

Donepezil can improve ischemic muscle atrophy by activating angiomyogenic properties of satellite cells.

BACKGROUND: Saving more limbs of patients with peripheral arterial disease (PAD) from amputation by accelerating angiogenesis in affected limbs has been anticipated for years. We hypothesized that an anti-Alzheimer drug, donepezil (DPZ), can activate angiomyogenic properties of satellite cells, myogenic progenitors, and thus be an additional pharmacological therapy against PAD. METHODS AND RESULTS: In a murine hindlimb ischemia model, we investigated the angiogenic effects of a clinical dose of DPZ (0.2 mg·kg(-1)·day(-1)) and its combination with cilostazol, a platelet aggregation inhibitor and a conventional therapeutic drug against PAD. The combination therapy most effectively improved skin coldness and most effectively upregulated vascular endothelial growth factor (VEGF)-producing satellite cells in ischemic hindlimbs. Computed tomography revealed that DPZ remarkably attenuated ischemic muscle atrophy and induced super-restoration in affected hindlimbs. The in vitro study with human aortic endothelial cells showed that DPZ or its combination with cilostazol effectively upregulated the expression of pAkt, hypoxia inducible factor-1α, and VEGF protein. Likewise, in primary cultured satellite cells, DPZ, alone or in combination, upregulated the expression of VEGF, interleukin-1ß, and fibroblast growth factor 2 protein. CONCLUSIONS: The present results suggest that a clinical dosage of DPZ accelerates angiomyogenesis by directly acting on both endothelial and satellite cells. Therefore, DPZ is a potential additional choice for conventional drug therapy against PAD.

Extrahepatic stem cells mobilized from the bone marrow by the supplementation of branched-chain amino acids ameliorate liver regeneration in an animal model.

BACKGROUND AND AIMS: In recent years, bone marrow (BM)-derived stem cell repopulation of injured organs has been increasingly observed; however, the extent to which it occurs and its clinical relevance remain unclear. Here, we investigated on the potential of extrahepatic stem cells to become hepatocytes using the treatment of the oral supplementation of branched-chain amino acids (BCAA). METHODS: In the first, Sprague-Dawley (SD) rats were administered BCAA to promote liver regeneration; in the second, syngenic liver transplantations using wild-type SD rats that do not express green fluorescent protein (GFP) as syngenic donors and GFP-transgenic SD rats as recipients to confirm that an extrahepatic source of cells (GFP(+)) could repopulate the transplanted (GFP(-)) liver were performed. RESULTS: Treatment of the oral supplementation of BCAA for 2-3 weeks before transplantation to promote liver regeneration resulted in greater than 7 days graft volume, with extensive spotty conversion of a small wild-type graft to the recipient GFP(+) genotype. The treatment by oral supplementation of BCAA resulted in higher levels of CD34+SDF+c-kit+ stem cells in the blood and liver after liver transplantation. Liver repopulation could be achieved with hepatocytes that bone marrow-derived from stem cells proliferated. CONCLUSIONS: We have identified extrahepatic stem cell migration from the BM to the injured liver as a mechanism underlying liver regeneration that supports hepatocyte proliferation in diseased liver. Our results suggested that BCAA is able to mobilize a population of BM-derived cells that contribute to hepatic regeneration.

S-1 vs. gemcitabine as an adjuvant therapy after surgical resection for ductal adenocarcinoma of the pancreas.

BACKGROUND: Pancreatectomy with regional lymphadenectomy remains the only curative treatment option for pancreatic cancer. There is no clear consensus on what type of adjuvant therapy should be used for patients with pancreatic cancer. OBJECTIVE: Our objective was to retrospectively evaluate whether postoperative adjuvant chemotherapy using S-1 is clinically beneficial in managing resectable pancreatic cancer. METHODS: Patients were divided into three groups: those undergoing surgery alone, those receiving gemcitabine infusion, and those receiving S-1 orally. RESULTS: Of 189 studied patients, the median overall survival was 15.0 months after surgery alone, 33.0 months in the gemcitabine group, and 45.0 months in patients receiving S-1. A multivariate analysis identified regional lymph node metastasis, positive surgical margins, and absence of adjuvant chemotherapy as independent negative prognostic factors. S-1 was not inferior to gemcitabine in terms of survival outcomes and showed a favorable hazard ratio compared with gemcitabine in the subsets of patients with positive vascular invasion. CONCLUSIONS: There was no difference between adjuvant chemotherapy with S-1 and gemcitabine in overall survival for patients with curative pancreatic cancer. Our results suggested that S-1 can be used as a second agent to gemcitabine after surgical resection for ordinary adenocarcinoma of the pancreas.

The Clinical Features of Late Postoperative Cholangitis After Hepaticojejunostomy Brought on by Conditions other than Cancer Recurrence.

PURPOSE: Postoperative cholangitis and anastomotic strictures (AS) are long-term complications of biliary-enteric anastomosis (BEA). METHODS: We retrospectively reviewed data of patients who underwent bile duct resection with or without hepatectomy and investigated the risk factors for postoperative cholangitis, benign AS, and incidence of Clavien-Dindo (C-D) >Grade III complications. RESULTS: Overall, data of 189 patients (115 men and 74 women) were retrospectively analyzed. The median patient age was 73 years. Thirty-five patients (18.5%) developed postoperative cholangitis, and 16 (8.4%) developed postoperative AS. Male sex and serious postoperative complications (C-D ≥ Grade III) were independent risk factors for cholangitis. The incidence of serious postoperative complications was 32.3%. Hypertension, preoperative biliary drainage, C-reactive protein-albumin ratio ≥.22, and bile duct resection with hepatectomy were potential risk factors for serious postoperative complications. CONCLUSIONS: The incidence rates of postoperative cholangitis and AS after BEA were 18.5% and 8.4%, respectively. Male sex and serious postoperative complications (C-D ≥ Grade III) were independent risk factors for postoperative cholangitis.

Serum level of soluble (pro)renin receptor is modulated in chronic kidney disease.

BACKGROUND: Prorenin, the precursor of renin, binds to the (pro)renin receptor [(P)RR] and triggers intracellular signaling. The ligand binding sites of (P)RR are disconnected and are present in the soluble form of the receptor in serum. Given that the clinical significance of serum prorenin and soluble (P)RR in chronic kidney disease (CKD) is unclear, we investigated the relationship between serum prorenin, soluble (P)RR, and various clinical parameters in patients with CKD. METHODS: A total of 374 patients with CKD were enrolled. Serum samples were collected, and the levels of soluble (P)RR and prorenin were measured using ELISA kits. Serum creatinine (Cr), blood urea nitrogen (BUN), uric acid (UA), hemoglobin (Hb), soluble secreted α-Klotho, and the urine protein/Cr ratio were also measured. Similarly, clinical parameters were also evaluated using serum and urine sample collected after 1 year (n = 204). RESULTS: Soluble (P)RR levels were positively associated with serum Cr (P < 0.0001, r = 0.263), BUN (P < 0.0001, r = 0.267), UA (P < 0.005, r = 0.168) levels, CKD stage (P < 0.0001, r = 0.311) and urine protein/Cr ratio (P < 0.01, r = 0.157), and inversely with estimated glomerular infiltration rate (eGFR) (P < 0.0001, r = -0.275) and Hb (P < 0.005, r = -0.156). Soluble (P)RR levels were inversely associated with α-Klotho levels (P < 0.001, r = -0.174) but did not correlate with prorenin levels. With respect to antihypertensive drugs, soluble (P)RR levels were significantly lower in patients treated with an angiotensin II receptor blocker (ARB) than in those without ARB therapy (P < 0.005). Soluble (P)RR levels were significantly lower in CKD patients with diabetes mellitus or primary hypertension than in those without these conditions (P < 0.05). In contrast, serum levels of prorenin did not correlate with parameters related to renal function. Serum prorenin levels were significantly higher in CKD patients with diabetes mellitus than in nondiabetic patients (P < 0.05), but not in CKD patients with hypertension (P = 0.09). Finally, with respect to the relationship between basal soluble (P)RR levels and the progression rates of renal function, soluble (P)RR levels were positively associated with ΔCr (P < 0.05, r = 0.159) and inversely associated with ΔeGFR (P < 0.05, r = -0.148). CONCLUSION: Serum levels of soluble (P)RR correlated with the stage of CKD. Our findings suggest that soluble (P)RR may be involved in renal injury and influence the progression of CKD.

Oral supplementation of branched-chain amino acids reduces early recurrence after hepatic resection in patients with hepatocellular carcinoma: a prospective study.

PURPOSES: The long-term outcomes of branched-chain amino acids (BCAA) administration after hepatic resection in patients with hepatocellular carcinoma (HCC) remain unclear. This study assessed the effect of oral supplementation with BCAA on the development of liver tumorigenesis after hepatic resection in HCC patients. METHODS: Fifty-six patients were randomly assigned to receive either BCAA supplementation (Livact group, n = 26) or a conventional diet (Control group, n = 30). Twenty-six patients in the BCAA group were treated orally for 2 weeks before and 6 months after hepatic resection. Postoperative tumor recurrence was continuously evaluated in all patients by measuring various clinical parameters. RESULTS: There was no significant difference in the overall survival rate between the two patient groups; however, the recurrence rate at 30 months after surgery was significantly better in the Livact group in comparison to the Control group. Interestingly, the tumor markers, such as AFP and PIVKA-II, significantly decreased at 36 months after liver resection in the Livact group in comparison to the Control group. CONCLUSIONS: Oral supplementation of BCAA reduces early recurrence after hepatic resection in patients with HCC. This treatment regimen offers potential benefits for clinical use in such patients, even in cases with a well-preserved preoperative liver function.

Evolving partnership: A National Center for Global Health and Medicine Resilient Training Model for clinical research professionals during the COVID-19 pandemic.

The clinical trial industry has encountered challenging circumstances in which the increasing number of trials outpaces the number of trial specialists. For instance, there has been an unprecedented demand for clinical trials following the Covid-19 pandemic, which has worsened the global shortage of qualified personnel. It is therefore imperative to produce more qualified clinical trial professionals. An adaptive and collaborative training model was implemented by the National Center for Global Health and Medicine through the Department of International Trials. This aimed at building capacity among health workers in developing countries and providing them with the skills to be able to conduct all phases of the clinical trial from protocol design to publication of results. It also seeks to foster collaboration and partnership between local health workers and international experts. Since 2016, we have implemented a Japan-led training program, and since 2020, the COVID-19 pandemic has ushered in a shift from a single Train-the-trainer model (ToT) to a mixed model, the Evolving Partnership Training (ePT). In this model, we applied four different methods: train-the-trainer, needs-oriented training, open symposiums, and advanced learning. The total number of training participants increased exponentially from a total of 41 between 2016-2020 to 2,810 in 2021. Our experience has proven that despite the constraint of the pandemic, the ePT is a viable approach compared to a single method for providing quality training and increasing the number of participants.

Comparison between intravesical and oral administration of 5-aminolevulinic acid in the clinical benefit of photodynamic diagnosis for nonmuscle invasive bladder cancer.

BACKGROUND: This study was undertaken to evaluate the clinical value of photodynamic diagnosis (PDD) with intravesical and oral instillation of 5-aminolevulinic acid (ALA) (ALA-PDD), and transurethral resection of bladder tumor (TURBT) guided by ALA-PDD (PDD-TURBT) for nonmuscle invasive bladder cancer. METHODS: Of all 210 cases, 75 underwent PDD with intravesically applied ALA, and 135 cases underwent PDD with orally applied ALA. Diagnostic accuracy was evaluated by comparing the level on images of ALA-induced fluorescence with the pathological result. PDD-TURBT was performed in 99 completely resectable cases corresponding to 210 ALA-PDD cases. To evaluate the abilities of PDD-TURBT, survival analysis regarding intravesical recurrence was retrospectively compared with the historical control cases that underwent conventional TURBT. RESULTS: The diagnostic accuracy and capability of ALA-PDD were significantly superior to those of conventional endoscopic examination. Moreover, 72.1% of flat lesions, including dysplasia and carcinoma in situ, could be detected only by ALA-PDD. The recurrence-free survival rate in the cases that underwent PDD-TURBT was significantly higher than that of conventional TURBT. Moreover, multivariate analysis revealed that the only independent factor contributing to improving prognosis was PDD-TURBT (hazard ratio, 0.578; P = .012). Regardless of the ALA administration route, there was no significant difference in diagnostic accuracy, ability of PDD, or recurrence-free survival. All procedures were well tolerated by all patients without any severe adverse events. CONCLUSIONS: This multicenter study is likely to be biased, because it is limited by the retrospective analysis. This study suggests that regardless of the ALA administration route, ALA-PDD and PDD-TURBT are remarkably helpful in detection and intraoperative navigation programs.

Influences of donepezil on cardiovascular system--possible therapeutic benefits for heart failure--donepezil cardiac test registry (DOCTER) study.

To study prospectively influences of donepezil, an acetylcholinesterase inhibitor against Alzheimer disease, on cardiovascular system, we evaluated cardiovascular changes occurring during new initialized treatment with donepezil in 49 dementia patients over 6 months. No patient suffered from cardiovascular events. In clinical changes between baseline and the first evaluation after donepezil treatment, heart rate and plasma brain natriuretic peptide (BNP) levels as a marker for heart failure did not change (BNP: 59.62 ± 62.71 pg/mL at baseline to 53.18 ± 42.34 pg/mL at first evaluation; P = 0.262). We further examined plasma BNP levels in 2 groups into which the patients were divided at baseline according to the cut-off plasma BNP level of 60 pg/mL. In patients with high level of BNP, the BNP levels decreased after administration of donepezil (116.39 ± 76.58 pg/mL at baseline to 82.24 ± 46.64 pg/mL at first evaluation; P = 0.011) with the tendency to be reduced in the follow-up period. BNP did not change in patients with low level of BNP. Donepezil seemed to be safe in patients with dementia without symptomatic heart disease and significantly decreased plasma BNP levels in patients with subclinical chronic heart failure.