Antibody acquisition after second and third SARS-CoV-2 vaccinations in Japanese kidney transplant patients: a prospective study.

BACKGROUND: Kidney transplant patients have lower antibody acquisition after SARS-CoV-2 vaccination. The efficacy of vaccines in Japanese kidney transplant patients with specific characteristics, such as predominant living-donor, ABO-incompatible kidney transplant, and low-dose immunosuppression, requires verification. METHODS: We conducted a prospective study to estimate anti-SARS-CoV-2 antibody levels in 105 kidney transplant patients and 57 controls. Blood samples were obtained before vaccination, 1, 3, and 6 months after second vaccination, and 1 month after third vaccination. We investigated antibody acquisition rates, antibody levels, and factors associated with antibody acquisition. RESULTS: One month after second vaccination, antibody acquisition was 100% in the controls but only 36.7% in the kidney transplant group (P < 0.001). Antibody levels in positive kidney transplant patients were also lower than in the controls (median, 4.9 arbitrary units vs 106.4 arbitrary units, respectively, P < 0.001). Years after kidney transplant (odds ratio 1.107, 95% confidence interval 1.012-1.211), ABO-incompatible kidney transplant (odds ratio 0.316, 95% confidence interval 0.101-0.991) and mycophenolate mofetil use (odds ratio 0.177, 95% confidence interval 0.054-0.570) were significant predictors for antibody acquisition after second vaccination. After third vaccination, antibody positivity in the kidney transplant group increased to 75.3%, and antibody levels in positive patients were 71.7 arbitrary units. No factors were associated with de novo antibody acquisition. CONCLUSIONS: In Japanese kidney transplant patients, years after kidney transplant, ABO-incompatible kidney transplant and mycophenolate mofetil use were predictors for antibody acquisition after second vaccination. Third vaccination improves antibody status even in patients who were seronegative after the second vaccination.

Impact of Abdominal Fat Distribution on Mortality and Its Changes Over Time in Patients Undergoing Hemodialysis: A Prospective Cohort Study.

OBJECTIVE: Measures of fat distribution and visceral fat accumulation maintain a direct association with mortality in the general population. However, among patients undergoing hemodialysis (HD), there are few reports of this association. This study aimed to investigate the impact of computed tomography (CT)-measured abdominal fat levels, including the visceral fat area (VFA) and subcutaneous fat area (SFA), on all-cause mortality in patients undergoing HD and investigate whether there are sex-specific particularities regarding the associations between the abovementioned parameters. METHODS: A total of 258 participants were selected from the population of patients undergoing stable HD. The baseline characteristics were collected by records and interviews. The following variables were assessed at baseline and every year: body mass index, abdominal circumference, VFA, and SFA. Abdominal circumference and body fat distribution were assessed at the level of the umbilicus via CT. All CT scans were performed on a nondialysis day with the subject in a supine position. The primary end point was the 5-year all-cause mortality. RESULTS: This prospective cohort study revealed that age, cardiothoracic ratio, %VFA (VFA/[VFA + SFA]), and albumin were independent predictors of death via multivariable analyses. Regarding the %VFA, its area under the curve (0.599), which did not suffice to predict mortality, was higher than that of VFA, SFA, and body mass index. Also, the effect was recognized mainly in male patients. The %VFA of patients who survived for 60 months increased over time. CONCLUSION: These data suggest that patients (especially men) with a high VFA-to-abdominal fat ratio have a high risk of death. Thus, more attention should be paid to such patients.

Maoto, a traditional herbal medicine, for post-exposure prophylaxis for Japanese healthcare workers exposed to COVID-19: A single center study.

BACKGROUND: Little research has been done on post-exposure prophylaxis (PEP) for COVID-19. This study was done to determine if maoto, a traditional herbal medicine commonly used for diseases with symptoms similar to those of COVID-19, can be repurposed for post-exposure prophylaxis to prevent the spread of nosocomial infection with SARS-CoV-2. METHODS: A cohort analysis was done of the data of 55 health care workers (HCWs) whether to get infected with SARS-CoV-2 in a Japanese hospital experiencing a COVID-19 cluster in April of 2021. Of these subjects, maoto granules for medical use were prescribed for PEP to 42 HCWs and taken for three days in mid-April. Controls were 13 HCWs who rejected the use of maoto. Polymerase chain reaction was performed routinely once or twice a week or when a participant presented with symptoms of COVID-19. RESULT: There were no background differences between the maoto and control groups by profession, sex, or mean age. No severe adverse reactions were observed. During the observation period of 1 week, significantly fewer subjects were diagnosed with COVID-19 in the maoto group (N = 3, 7.1%) than in the control group (N = 6, 46.2%). The prophylactic effectiveness of maoto was 84.5%. CONCLUSION: Oral administration of maoto is suggested to be effective as PEP against nosocomial COVID-19 infection.

Effects of L- and N-Type Ca Channel Blocker Cilnidipine on Changes in Heart Rate and QT Interval During Dialysis.

BACKGROUND/AIMS: Hemodialysis patients have poor prognosis due to increased prevalence of cardiovascular diseases. Treatment to suppress increases in sympathetic nerve activity and QT prolongation may have the potential to reduce the occurrence of these events. The L/N-type Calcium (Ca) channel blocker cilnidipine has unique inhibitory action to inhibit sympathetic nerve activity and in a canine model ameliorates QT prolongation. In this study, we investigated whether cilnidipine has inhibitory effects on heart rate, an index of sympathetic nerve activity, and QT prolongation in patients undergoing dialysis. METHODS: An L-type Ca channel blocker amlodipine was administered for 4 weeks followed by cilnidipine treatment for 4 weeks. On the last day of each period, heart rate and corrected QT interval were estimated and compared between the two periods. RESULTS: Cilnidipine showed greater suppression of heart rate during dialysis than did amlodipine. The corrected QT interval in one dialysis session was significantly increased, and 3 of 17 patients showed prominent QT prolongation during administration of amlodipine but not cilnidipine. CONCLUSION: These data suggested that cilnidipine may inhibit increases in heart rate and QT interval. Cilnidipine may have beneficial effects in reducing cardiovascular events, resulting from increased sympathetic nerve activity and lethal arrhythmias in hemodialysis patients.

Effects of nocturnal oxygen therapy on heart function in SDB patients undergoing dialysis.

There is a close relationship between sleep disordered breathing (SDB) and heart failure. We performed home oxygen therapy (HOT) in patients with SAS undergoing dialysis, and investigated its effects on the heart function. The subjects were 10 SDB patients on dialysis. On retiring at night, oxygen was transnasally administered at 1.0 L/min. The human atrial natriuretic peptide (hANP), brain natriuretic peptide (BNP), total protein, Alb, cholesterol and phosphorus levels were measured before the start of oxygen therapy and after 6 weeks. The mean SpO2 increased from 93.5% [91.5, 97.0] to 96.3% [94.8, 97.4] (median [interquartile range]) (p = 0.015). The hANP (p = 0.0039), BNP (p = 0.0098) and serum Alb (p = 0.015) levels significantly improved. There were no significant changes in the cholesterol, phosphorus or total protein levels. These results suggest that nocturnal oxygen therapy improves indices of heart failure, contributing to the prevention and treatment of heart failure in dialysis patients with SDB.

[Myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) -associated glomerulonephritis with acute pancreatitis: a case report].

We report here a case of a 64-year-old woman with myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) -associated glomerulonephritis who developed acute pancreatitis. The patient was admitted to our hospital because of abnormal urinalysis findings, edema, and progressive renal failure. Laboratory studies showed a high white blood cell count (11,570/µL), anemia (hemoglobin 7.8 g/dL), and elevated serum creatinine (2.36 mg/dL) and C-reactive protein (12.20 mg/dL) levels. Furthermore, the MPO-ANCA titer was very high (1,625 U/mL, normal range < 10 U/mL). Histopathological findings of the renal biopsy were consistent with microscopic polyangiitis. Accordingly, we diagnosed MPO-ANCA-associated glomerulonephritis. On the day after the renal biopsy, the patient complained of low back pain. Computed tomography (CT) revealed postbiopsy hemorrhage. Thereafter, the patient's symptoms and laboratory studies gradually worsened. A repeat CT performed a few days later revealed no changes in the perirenal hematoma; however, an enlarged pancreas head was incidentally observed. There was no obvious cause of acute pancreatitis, and MPO-ANCA-associated vasculitis, although rare, was suspected as the cause. We initiated prednisolone pulse therapy for vasculitis along with the administration of nafamostat mesilate and ulinastatin for acute pancreatitis. Subsequently, the levels of pancreatic enzymes gradually increased, but several days later, abdominal magnetic resonance imaging showed improvement in the pancreas head. The pancreatitis gradually resolved over time. Acute pancreatitis occurring concurrently with MPO-ANCA-associated glomerulonephritis is extremely rare. To our knowledge, only a few such cases have been reported and have suggested that steroid therapy may play a role in triggering pancreatic involvement. In our case, however, an enlarged pancreas head was observed before steroid therapy was initiated. Therefore, we consider our case to be very rare.

Antitumor immune response of dendritic cells (DCs) expressing tumor-associated antigens derived from induced pluripotent stem cells: in comparison to bone marrow-derived DCs.

It is generally accepted that the difficulty in obtaining a sufficient number of functional dendritic cells (DCs) is a serious problem in DC-based immunotherapy. Therefore, we used the induced pluripotent stem (iPS) cell-derived DCs (iPSDCs). If the therapeutic efficacy of iPSDCs is equivalent to that of bone marrow-derived DCs (BMDCs), then the aforementioned problems may be solved. In our study, we induced iPSDCs from iPS cells and examined the capacity for maturation of iPSDCs compared to that of BMDCs in addition to the capacity for migration of iPSDCs to regional lymph nodes. We adenovirally transduced the hgp100 gene, natural tumor antigens, into DCs and immunized mice once with the genetically modified DCs. The cytotoxic activity of CD8 (+) cytotoxic T lymphocytes (CTLs) was assayed using a (51) Cr-release assay. The therapeutic efficacy of the vaccination was examined in a subcutaneous tumor model. Our results showed that iPSDCs have an equal capacity to BMDCs in terms of maturation and migration. Furthermore, hgp100-specific CTLs were generated in mice immunized with genetically modified iPSDCs. These CTLs exhibited as high a level of cytotoxicity against B16 cells as BMDCs. Moreover, vaccination with the genetically modified iPSDCs achieved as high a level of therapeutic efficacy as vaccination with BMDCs. Our study clarified experimentally that genetically modified iPSDCs have an equal capacity to BMDCs in terms of tumor-associated antigen-specific therapeutic antitumor immunity. This vaccination strategy may therefore be useful for future clinical application as a cancer vaccine.

Is preoperative colonoscopy necessary for patients undergoing gastric cancer surgery?

PURPOSE: The aim of this study was to evaluate the necessity of preoperative colonoscopy (CS) in gastric cancer (GC) patients and to assess the outcomes of different treatments in patients with synchronous GC and colorectal neoplasms (CRN). We also determined the risk factors influencing the comorbidity of colorectal cancer (CRC) in patients with GC. METHODS: This retrospective study included 1891 consecutive GC patients who underwent CS before surgery from January 1, 1999, through June 30, 2012. RESULTS: There was a high prevalence of concurrent CRN (28.4 %) and CRC (3.2 %) in our patients with GC. Sixty-one patients with GC had synchronous CRC. Twenty-three of the 61 tumors were perioperatively treated by endoscopic resection. The other 38 tumors were treated by simultaneous surgery for the GC and CRC. Surgical complications were not found in either the endoscopic or surgical resection group. The multivariate logistic regression analysis indicated that the prevalence of synchronous CRC in patients with GC was significantly associated with the incidence of multiple GCs [P < 0.0001; odds ratio (OR) 15.3], having anemia (P = 0.002; OR 3.0), and having a smoking history (P = 0.021; OR 1.9). CONCLUSIONS: We recommend preoperative CS screening for GC patients. In particular, preoperative CS screening is indispensable for patients with multiple GCs. In addition, simultaneous treatments for patients with synchronous GC and CRN are safe and feasible procedures.

Endoscopic submucosal dissection for gastric tumors in various types of remnant stomach.

BACKGROUND AND STUDY AIMS: The aim of this study was to examine the clinical outcomes of endoscopic submucosal dissection (ESD) for gastric tumors in various types of remnant stomach. PATIENTS AND METHODS: Between January 2002 and March 2013, ESD was performed for 750 gastric tumors. Of these lesions, 49 were in a remnant stomach, and were included in the study. RESULTS: The en bloc resection rate was 100 %. The curative resection rate was 82 %. The rate of perforation was high in patients with gastric conduits (28.6 %). Perforation was significantly more common in patients with lesions located on the suture line (4.9 % vs. 50.0 %; P = 0.0043). CONCLUSION: ESD for gastric tumors in the remnant stomach can be considered feasible and safe in clinical practice. However, the procedure is technically more difficult in patients with a gastric conduit, due to the increased risk of perforation at the suture line.

Atrial fibrillation after esophageal cancer surgery: an analysis of 207 consecutive patients.

PURPOSE: The aim of this study was to identify perioperative risk factors that are associated with postoperative atrial fibrillation (AF) and the outcomes of different pharmacological interventions in esophageal cancer patients who underwent transthoracic esophagectomy. METHODS: This study included 207 patients who underwent a transthoracic esophagectomy for esophageal cancer resection by a single surgeon from January 1, 2004, through December 31, 2010. RESULTS: Postoperative AF occurred in 19 patients (9.2 %), all of whom received antiarrhythmic drug therapy at the early stage. Antiarrhythmic treatment was effective in 12 cases (63.2 %). In this study, landiolol hydrochloride, an ultrashort-acting ß1-selective ß-blocker, was the first-line therapy for postoperative AF. A multivariate logistic regression analysis showed that postoperative AF was significantly associated with the use of an ileo-colon for reconstruction after esophagectomy (P = 0.0023, odds ratios [OR] = 13.6) and with the presence of tachycardia with a heart rate of >100 bpm on postoperative day (POD) 1 (P = 0.0004, OR = 18.4). CONCLUSIONS: Postoperative AF is associated with the use of a colon conduit for reconstruction after esophagectomy and with tachycardia with a heart rate >100 bpm on POD 1. Identifying patients at high risk for postoperative AF will allow for more direct application of pharmacological methods of prophylaxis.

Clinical benefits of thoracoscopic esophagectomy in the prone position for esophageal cancer.

PURPOSES: The clinical benefits of thoracoscopic radical esophagectomy in the prone position compared to conventional open esophagectomy have not been fully documented. METHODS: Forty-six patients with esophageal cancer who underwent MIE in the prone position (MIE-P group) were enrolled, and 46 case-matched controls that underwent open esophagectomy (OE group) were identified using propensity score methods to achieve a valid comparison of outcomes between MIE and open esophagectomy. RESULTS: The duration of systemic inflammatory response syndrome was shorter in the MIE-P group than in OE group (P = 0.005). The time to first walking was earlier in the MIE-P group (P < 0.001). Although the vital capacity ratio (%VC) declined after the operation in both groups, the change ratio of the %VC was 85.3% in the MIE-P group and 69.6% in the OE group (P < 0.001). No mortality occurred in either group. The postoperative morbidity rate was lower in the MIE-P group (13%) than in the OE group (30.4%) (P = 0.020). Two patients (4.3%) in the OE group and one patient in the MIE-P group (2.2%) had pneumonia. CONCLUSIONS: MIE in the prone position was associated with less impairment of the pulmonary function, earlier recovery of activity and lower subsequent morbidity compared to open esophagectomy. Further investigation of the long-term outcomes is, therefore, needed.

New prognostic score for the survival of patients with esophageal squamous cell carcinoma.

PURPOSE: Recent studies have shown that the modified Glasgow Prognostic Score (mGPS), which is an inflammation-based prognostic score, is useful as a prognostic index for some cancer cases. The purpose of this study was to create a prognostic scoring system for patients with esophageal squamous cell carcinoma (ESCC) that was more independent and sensitive than the mGPS. METHODS: One hundred sixty-eight patients who had undergone esophagectomy for ESCC were included in the study. The new mGPS (NmGPS) was calculated based on the following cutoff values: CRP >0.75 mg/dL indicated NmGPS 1 or 2, depending on the absence or presence of hypoalbuminemia (<3.5 g/dL); and CRP ≤0.75 mg/dL indicated NmGPS 0. We also performed an analysis based on cutoff values of 0.5 and 0.25 mg/dL for CRP. RESULTS: Only the NmGPS with a cutoff CRP value of 0.5 mg/dL was able to divide into three independent patient groups in the survival curves. In the multivariate analyses, a NmGPS (CRP cutoff; 0.5 mg/dL) of 2 was a more significant independent prognostic factor (HR 4.437, 95 % CI 2.000-9.844, p = 0.0002) than a mGPS of 2 (HR 2.726, 95 % CI 1.021-7.112, p = 0.0449). CONCLUSIONS: The new prognostic score NmGPS (CRP cutoff; 0.5 mg/dL) was more independent and sensitive than the mGPS for patients with ESCC.

Effects of daily teriparatide, weekly high-dose teriparatide, or bisphosphonate on cortical and trabecular bone of vertebra and proximal femur in postmenopausal women with fragility fracture: Sub-analysis by quantitative computed tomography from the TERABIT study.

PURPOSE: The effects of daily teriparatide (D-PTH, 20 µg/day), weekly high-dose teriparatide (W-PTH, 56.5 µg/week), or bisphosphonate (BP) on the vertebra and proximal femur were investigated using quantitative computed tomography (QCT). METHODS: A total of 131 postmenopausal women with a history of fragility fractures were randomized to receive D-PTH, W-PTH, or bisphosphonate (oral alendronate or risedronate). QCT were evaluated at baseline and after 18 months of treatment. RESULTS: A total of 86 participants were evaluated by QCT (Spine: D-PTH: 25, W-PTH: 21, BP: 29. Hip: PTH: 22, W-PTH: 21, BP: 32. Dropout rate: 30.5 %). QCT of the vertebra showed that D-PTH, W-PTH, and BP increased total vBMD (+34.8 %, +18.2 %, +11.1 %), trabecular vBMD (+50.8 %, +20.8 %, +12.2 %), and marginal vBMD (+20.0 %, +14.0 %, +11.5 %). The increase in trabecular vBMD was greater in the D-PTH group than in the W-PTH and BP groups. QCT of the proximal femur showed that D-PTH, W-PTH, and BP increased total vBMD (+2.8 %, +3.6 %, +3.2 %) and trabecular vBMD (+7.7 %, +5.1 %, +3.4 %), while only W-PTH and BP significantly increased cortical vBMD (-0.1 %, +1.5 %, +1.6 %). Although there was no significant increase in cortical vBMD in the D-PTH group, cortical bone volume (BV) increased in all three treatment groups (+2.1 %, +3.6 %, +3.1 %). CONCLUSIONS: D-PTH had a strong effect on trabecular bone of vertebra. Although D-PTH did not increase cortical BMD of proximal femur, it increased cortical BV. W-PTH had a moderate effect on trabecular bone of vertebra, while it increased both cortical BMD and BV of proximal femur. Although BP had a limited effect on trabecular bone of vertebra compared to teriparatide, it increased both cortical BMD and BV of proximal femur.

An armed oncolytic herpes simplex virus expressing thrombospondin-1 has an enhanced in vivo antitumor effect against human gastric cancer.

Advanced gastric cancer is a common disease, but the conventional treatments are unsatisfactory because of the high recurrence rate. One of the promising new therapies is oncolytic virotherapy, using oncolytic herpes simplex viruses (HSVs). Thrombospondin-1 (TSP-1) suppresses tumor progression via multiple mechanisms including antiangiogenesis. Our approach to enhance the effects of oncolytic HSVs is to generate an armed oncolytic HSV that combines the direct viral oncolysis with TSP-1-mediated function for gastric cancer treatment. Using the bacterial artificial chromosome (BAC) system, a 3rd generation oncolytic HSV (T-TSP-1) expressing human TSP-1 was constructed for human gastric cancer treatment. The enhanced efficacy of T-TSP-1 was determined in both human gastric cancer cell lines in vitro and subcutaneous tumor xenografts of human gastric cancer cells in vivo. In addition, we examined the apoptotic effect of T-TSP-1 in vitro, and the antiangiogenic effect of T-TSP-1 in vivo compared with a non-armed 3rd generation oncolytic HSV, T-01. No apparent apoptotic induction by T-TSP-1 was observed for human gastric cancer cell lines TMK-1 cells but for MKN1 cells in vitro. Arming the viruses with TSP-1 slightly inhibited their replication in some gastric cancer cell lines, but the viral cytotoxicity was not attenuated. In addition, T-TSP-1 exhibited enhanced therapeutic efficacy and inhibition of angiogenesis compared with T-01 in vivo. In this study, we established a novel armed oncolytic HSV, T-TSP-1, which enhanced the antitumor efficacy by providing a combination of direct viral oncolysis with antiangiogenesis. Arming oncolytic HSVs may be a useful therapeutic strategy for gastric cancer therapy.

[Cancer vaccine therapy using genetically modified induced pluripotent stem cell-derived dendritic cells expressing the TAA gene].

It is generally accepted that the difficulty in obtaining a sufficient number of functional dendritic cells (DCs) poses a serious problem in DC-based immunotherapy. Therefore, we used induced pluripotent stem (iPS) cell-derived DCs (iPSDCs) instead. If the therapeutic efficacy of iPSDCs was equivalent to that of bone marrow-derived DCs( BMDCs), then the above-mentioned problems may be solved. In this study, we generated iPSDCs from iPS cells and compared their capacity to mature and migrate to the regional lymph nodes with that of BMDCs. We adenovirally transduced the hgp100 gene, which codes for a natural tumor antigen, into the DCs and immunized the mice with these genetically modified DCs. The cytotoxic activity of CD8( +) cytotoxic T lymphocytes( CTLs) was assayed using a 51Cr-release assay. The therapeutic efficacy of the vaccination was examined in a subcutaneous tumor model. Our results demonstrated that iPSDCs equaled BMDCs in terms of their maturation and migration capacity. Furthermore, hgp100-specific CTLs were generated in mice that were immunized with the genetically modified iPSDCs. These CTLs exhibited a high level of cytotoxicity against B16 cells, which is similar to that exhibited by CTLs generated in BMDCs immunized mice. Moreover, vaccination with genetically modified iPSDCs elicited a high level of therapeutic efficacy equaling that of vaccination with BMDCs. This study clarified experimentally that genetically modified iPSDCs are equivalent to BMDCs in terms of tumor-associated antigen-specific therapeutic antitumor immunity. This vaccination strategy may therefore be useful for future clinical application as a cancer vaccine.

The evaluation of surgical treatment for gastric cancer patients with noncurative resection.

PURPOSE: This study aims to analyze the results of treatment in a series of 233 gastric cancer patients who underwent a noncurative resection. METHODS: We performed a retrospective study of patients with noncurative treatment for advanced gastric cancer who were divided into three treatment groups: total gastrectomy (TG, n=150), distal gastrectomy (DG, n=44), and nonresection (NR, bypass procedure or chemotherapy only, n=39). RESULTS: In multivariate analysis, surgical treatment (TG) and an absence of chemotherapy were significant independent prognostic factors for a poor survival. In the late period, the overall survival rate was significantly lower in the TG group than in the DG group (p=0.005) and was marginally lower than in the NR group (p=0.054). The resection group had a poorer compliance for chemotherapy than the NR group, and the TG group had a poorer compliance than the DG group (p<0.01). The morbidity rate was higher in the TG group than in the DG group (p<0.05). CONCLUSIONS: TG is considered to be inappropriate for the treatment of noncurative gastric cancer because of the poor prognosis, high morbidity rates, and poor compliance for chemotherapy associated with the procedure. However, noncurative DG was acceptable and postoperative chemotherapy should be used in selected patients.

The impact of abdominal shape index of patients on laparoscopy-assisted distal gastrectomy for early gastric cancer.

PURPOSE: The aim of this study was to explore the effects of the abdominal shape index on gastric cancer patients' short-term surgical outcomes of laparoscopy-assisted distal gastrectomy (LADG) in both genders. METHODS: This retrospective study included 231 consecutive patients with early gastric cancer who underwent LADG with Billroth I anastomosis between 1998 and 2009. The abdominal shape index of patients was calculated using preoperative abdominal computed tomography scans and the Fat Scan software program. RESULTS: In male patients, the duration of surgery was longer in patients with a body mass index ≥25 kg/m(2) (P = 0.016), with the anterior to posterior diameter ≥200 mm (P < 0.0001), with the transverse diameter (TD) ≥300 mm (P = 0.030), with the waist ≥85 cm (P = 0.039), and with the visceral fat area (VFA) ≥100 cm(2) (P = 0.029). The intraoperative blood loss was higher in the large TD group (P = 0.049), in the high waist group (P = 0.006), and in the large VFA group (P = 0.007). In female patients, the correlations between these surgical outcomes and this abdominal shape index were not found. No significant relationships between each body shape index and the number of lymph nodes retrieved were found in either gender. Postoperative complications were not associated with the fat volume and abdominal shape index. CONCLUSIONS: Accumulation of fat did not affect short-term surgical outcomes except for the duration of surgery and intraoperative blood loss in male patients.

[Peptide vaccine therapy with TLR-9 agonist for patients with esophageal squamous cell carcinoma].

Patients with advanced carcinoma are thought to have an impaired immune surveillance system. Therefore, the potent helper action is required for the induction of an antitumor immune response in such patients. We evaluated the efficacy of CpG-ODN, which is TLR-9 agonist, as cancer vaccine adjuvant through in vitro experiments. We also conducted a phase I clinical trial for patients with advanced esophageal squamous cell carcinoma (ESCC) using peptide vaccine in combination with CpG-B. In vitro experiments showed that CpG-ODN caused various immune-modifications, suggesting an efficacy of CpG-ODN as peptide vaccine adjuvant. Moreover, the immune monitoring data in phase I clinical trial suggested that CpG-B augmented the generation of antigen-specific T cell responses and innate immunity. These data indicated that the vaccination with cancer-testis antigen derived peptide in combination with CpG-B may be useful as a new immunotherapy for patients with advanced ESCC.

Serum soluble (pro)renin receptor level as a prognostic factor in patients undergoing maintenance hemodialysis.

The (pro)renin receptor [(P)RR)] is a multifunctional protein that is cleaved to generate the soluble (P)RR [s(P)RR], reflecting the status of the tissue renin-angiotensin system and/or activity of the (P)RR. The serum s(P)RR level is associated with arteriosclerosis, independent of other risk factors, in patients undergoing hemodialysis (HD). This study was conducted to investigate whether the s(P)RR level was associated with new-onset cardiovascular events or malignant diseases and poor prognosis in patients undergoing HD. Overall, 258 patients [70 (61-76) years, 146 males] undergoing maintenance HD were prospectively followed up for 60 months. We investigated the relationships between s(P)RR levels and new-onset cardiovascular events/ malignant diseases and mortality during the follow-up period using Cox proportional hazard analyses. The cumulative incidence of new-onset cardiovascular events (P = 0.009) and deaths (P < 0.001), but not of malignant diseases, was significantly greater in patients with higher serum s(P)RR level (≥ 29.8 ng/ml) than in those with lower s(P)RR level (< 29.8 ng/ml). A high serum s(P)RR level was independently correlated with cardiovascular mortality (95% CI 1.001-1.083, P = 0.046). The serum s(P)RR level was associated with cardiovascular events and mortality, thus qualifying as a biomarker for identifying patients requiring intensive care.

Vaccination with peptides derived from cancer-testis antigens in combination with CpG-7909 elicits strong specific CD8+ T cell response in patients with metastatic esophageal squamous cell carcinoma.

Potent helper action is necessary for peptide-based vaccines to efficiently induce antitumor immune responses against advanced cancer. A phase I trial for advanced esophageal squamous cell carcinoma was carried out for patients with HLA-A*2402 using epitope peptides derived from novel cancer-testis antigens, LY6K and TTK, in combination with CpG-7909 (NCT00669292). This study investigated the feasibility and the toxicity as well as induction of tumor antigen-specific immune responses. Nine patients were vaccinated on days 1, 8, 15, and 22 of each 28-day treatment cycle with peptide LY6K-177, peptide TTK-567, and CpG-7909 (level-1; 0, level-2; 0.02, level-3; 0.1 mg/kg) and all were tolerated by this treatment. LY6K-specific T cell responses in PBMCs were detected in two of the three patients in each level. In particular, two patients in level-2/3 showed potent LY6K-specific T cell responses. In contrast, only two patients in level-2/3 showed TTK-567-specific T cell responses. The frequency of LY6K-177 or TTK-567-specific CD8+ T cells increased in patients in level-2/3 (with CpG). The vaccination with peptides and CpG-7909 increased and activated both plasmacytoid dendritic cells and natural killer cells, and increased the serum level of α-interferon. There were no complete response (CR) and partial response (PR), however, one of three patients in level-1, and four of six patients in level-2/3 showed stable disease (SD). In conclusion, vaccination with LY6K-177 and TTK-567 in combination with CpG-7909 successfully elicited antigen-specific CD8+ T cell responses and enhanced the innate immunity of patients with advanced esophageal squamous cell carcinoma. This vaccine protocol is therefore recommended to undergo further phase II trials.