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Purpose:This study examined whether abdominal plain computed tomography (CT) can predict surgical difficulty in acute cholecystitis., Methods:We retrospectively analyzed 84 consecutive patients who underwent laparoscopic cholecystectomy for acute cholecystitis between January 2015 and December 2018. We distinguished three degrees of surgical difficulty based on the operative time and blood loss: difficult, both ≥120 minutes and ≥ 100 mL, respectively (n = 27); moderate, either ≥120 minutes or ≥ 100 mL, respectively (n = 30); and easy, both, Results:Mean age, albumin levels, C-reactive protein levels, and the CT attenuation around the gallbladder (P < .001) were significantly different between groups. The surgical difficulty was unrelated to the timing of surgery. The postoperative complications were more frequent in operations more than 72 hours after disease onset (P = .04) and with CT attenuation around the gallbladder of ≥1.4 (P = .036)., Conclusion:High attenuation around the gallbladder on plain CT predicted a high surgical difficulty of laparoscopic cholecystectomy. We recommend measuring the CT attenuation around the gallbladder in patients with acute cholecystitis.

Cancer cells in intraoperative peritoneal washings (PW) indicate increased peritoneal recurrence. Detection of CEA or CK20 genes indicates poor prognosis. We assessed long-term prognosis of patients with amplification of cancer-related genes in PW obtained intraoperatively during curative gastric cancer surgery.PW was collected before and immediately after curative gastrectomy. CEA, CK20, TFF1, MUC2, and FABP1-mRNA were selected as marker genes for reverse transcription polymerase chain reaction. Peritoneal recurrence-free survival (PRFS) and overall survival (OS) after7-year follow-up were examined using the Kaplan-Meier method.Of 138 patients who underwent gastrectomy with negative cytological findings at laparotomy, 80 patients showed negative cancer-related gene amplification in preoperative PW. Fifty-eight patients were excluded due to positive gene amplification, which suggested presence of preoperative peritoneal cancer cells. The 80 patients had mRNA amplification in PW after surgery. Amplification of multiple and single cancer-related marker genes was observed in 38 and 21 patients; 21 cases had marker-negative results. Five-year PRFS was 69.1%, 95.2%, and 100% in multi-marker-positive, single marker-positive, and marker-negative cases, respectively. Multi-marker-positive patients had significantly worse PRFS than the other groups (p 0.05). Multivariate analysis in the Cox proportional hazards model identified multi-marker-positivity as an independent prognostic factor for PRFS (hazard ratio, 7.6; 95% confidence interval, 1.07-62.63; p = 0.046), and multi-marker-positive patients had significantly worse OS than other groups (p 0.01).Multi-marker cancer-related gene amplification in PW is associated with worse prognosis in PRFS and OS even after a long follow-up; PRFS can be stratified by the number of genes amplified.

Adoptive cell transfer (ACT) is an emerging and promising cancer immunotherapy that has been improved through various approaches. Here, we described the distinctive characteristics and functions of tumor Ag-specific effector CD8+ T-cells, co-cultured with a tumor-specific peptide and a stimulatory anti-OX40 antibody, before being used for ACT therapy in tumor-bearing mouse recipients. Splenic T-cells were obtained from wild-type FVB/N mice that had been injected with a HER2/neu (neu)-expressing tumor and a neu-vaccine. The cells were then incubated for 7 days in vitro with a major histocompatibility complex (MHC) class I peptide derived from neu, in the presence or absence of an agonistic anti-OX40 monoclonal antibody, before CD8+ T cells were isolated for use in ACT therapy. The proliferative ability of OX40-driven tumor Ag-specific effector CD8+ T-cells in vitro was less than that of non-OX40-driven tumor Ag-specific effector CD8+ T-cells, but they expressed significantly more early T-cell differentiation markers, such as CD27, CD62L and CCR7, and significantly higher levels of Bcl-2, an anti-apoptotic protein. These OX40-driven tumor Ag-specific effector CD8+ T-cells, when transferred into tumor-bearing recipients, demonstrated potent proliferation capability and successfully eradicated the established tumor. In addition, these cells exhibited long-term antitumor function, and appeared to be established as memory T-cells. Our findings suggest a possible in vitro approach for improving the efficacy of ACT, which is simple, requires only a small amount of modulator, and can potentially avoid several toxicities associated with co-stimulation in vivo.

Background: The invasive tumour front may provide prognostic information. We examined the relationship between the presence of cancer stem cells (CSCs) at the invasive tumour front and prognosis in gastric cancer (GC). Methods: CD44 is a CSC marker; accordingly, CD44 standard (CD44s), CD44 variant-6 (CD44v6), and CD44 variant-9 (CD44v9) expression were examined in 123 resected primary GCs and the clinical significance of CSCs at the invasive tumour front was analysed. Results: Thirteen (10.6%), 79 (64.2%), and 47 (38.2%) GCs were CD44s-, CD44v6-, and CD44v9-positive, respectively. Patients with CD44-positive expression at the invasive tumour front had significantly poorer disease-specific survival than those with negative expression (CD44s: P

The mechanisms underlying peritoneal metastasis (PM) after curative gastrectomy for gastric cancer (GC) are not well elucidated. This study assessed whether viable cancer cells, including cancer stemlike cells (CSCs), were present in the remnant stomach immediately before gastrointestinal (GI) tract reconstruction because these could be a source of PM after gastrectomy.Saline fluid used for remnant stomach lumen irrigation before GI reconstruction was prospectively collected from 142 consecutive patients undergoing distal gastrectomy for GC and cytologically examined. Proliferative activity (Ki67 staining) and stemness (expression of the CSC surface markers CD44s or CD44v6) were evaluated in detected cancer cells.Viable cancer cells were detected in 33 (23.2 %) of the 142 remnant stomachs. These cells formed clusters and stained positively for Ki67, indicating proliferation. Cancer cells in remnant stomachs and surface cancer cells in primary GCs from 10 (30.3 %) of these 33 cases also stained positively for CD44s or CD44v6. In a multiple logistic regression analysis, advanced cancer (odds ratio [OR], 4.65; 95 % confidence interval [CI], 1.32-16.4; P = 0.017), tumor size of 40 mm or larger (OR, 3.78; 95 % CI, 1.12-12.8; P = 0.033), and histologic differentiation (OR, 3.10; 95 % CI, 1.30-7.40; P = 0.011) were associated independently with the presence of cancer cells in the remnant stomach.Viable, proliferative, and clustered cancer cells, including CSCs, were found in remnant gastric lumens immediately before GI reconstruction, indicating a possible cellular source of PM after curative gastrectomy for GC. Dissemination of gastric contents into the peritoneal cavity should be avoided during GI reconstruction.

Adoptive cell transfer (ACT) is an emerging and promising cancer immunotherapy that has been improved through various approaches. Here, we described the distinctive characteristics and functions of tumor Ag-specific effector CD8

e16191Background: To elucidate recurrence pathophysiology after gastrointestinal cancer surgery, the prognostic effect of peritoneal cancer cell spillage during surgery was evaluated in patients (p...

A synthesis of 1,1-disubstituted 1,2,3,4-tetrahydroisoquinolines (6) was achieved in a highly efficient manner via Pictet-Spengler reaction of arylethylamines (1) and acyclic and cyclic ketones (2) using titanium (IV) isopropoxide and acetic-formic anhydride. The cyclization of the in situ formed acyliminium ion (4) to N-formyl 1,2,3,4-tetrahydroisoquinoline (5) was greatly facilitated by using trifluoroacetic acid as an additional reagent. The Pictet-Spengler reaction was carried out by one pot procedure, providing a convenient and effective method for preparing various 1,2,3,4-tetrahydroisoquinolines.

4050 Background: We recently showed that cancer cells, with proliferative and tumorigenic potential, can spill into the peritoneal cavity during curative (R0) gastric cancer (GC) surgery, which is associated with peritoneal recurrence (PM). To elucidate the pathophysiology of PM, the relationship between spilled cancer cells and cancer stem cells was evaluated. Furthermore, to identify a therapeutic strategy for PM, the prognostic impact of hyperthermic intraperitoneal chemotherapy (HIPEC) following GC surgery with spillage of cancer cells was evaluated. Methods: Patients with advanced GC (≥pT2 [MP]) who underwent R0 gastrectomy between 2010 and 2015 were enrolled. Ninety-four consecutive patients with negative results in peritoneal cytology and cancer cell culture (CCC [-]) following peritoneal washing (PW) before GC surgery were included. Spilled cancer cells in PW after GC surgery (PW-Post) were examined to identify any CD44-positive cancer stem-like cells associated with cancer metastasis. Based on the PW-Post CCC results, associations between HIPEC and recurrence-free survival (RFS), or overall survival (OS) were evaluated. HIPEC was performed following GC surgery using CDDP, MMC, and 5-FU in 5 L saline maintained at 42˚C for 30 min. Results: Spilled cancer cells included CD44+ cancer stem-like cells. In 48 patients with PW-Post positive CCC (CCC [+]), the number of patients with pStage I, II, and III were 4, 7, and 15, respectively, in those who received HIPEC (n = 26), and 3, 9, and 10, respectively, in those who did not (n = 22). Among patients with CCC (+), the 5-year peritoneal RFS, hepatic RFS, and lymph node RFS rates were 93.3%, 100%, and 68.5%, respectively, in patients who received HIPEC, and 56.7%, 35.6%, and 66.7%, respectively, in those who did not ( P = 0.008, P = 0.008, and P= 0.24, respectively). Among patients with PW-Post CCC (-), none developed recurrence, regardless of whether they received HIPEC (n = 28) or not (n = 18). Conclusions: The results show that PW-Post CCC is a promising predictive biomarker for recurrence after R0 GC surgery. Adjuvant HIPEC performed with R0 GC surgery showed preventive effects on peritoneal and hepatic recurrence and survival benefits for patients with PW-Post CCC (+).

4056Background: Prevention of recurrence after curative (R0) surgery is one of the most important subjects to be resolved for gastrointestinal (GI) cancers. We have previously shown that hypertherm...

A synthesis of 1,1-disubstituted 1,2,3,4-tetrahydroisoquinolines (6) was achieved in a highly efficient manner via Pictet-Spengler reaction of arylethylamines (1) and acyclic and cyclic ketones (2) using titanium (IV) isopropoxide and acetic-formic anhydride. The cyclization of the in situ formed acyliminium ion (4) to N-formyl 1,2,3,4-tetrahydroisoquinoline (5) was greatly facilitated by using trifluoroacetic acid as an additional reagent. The Pictet-Spengler reaction was carried out by one pot procedure, providing a convenient and effective method for preparing various 1,2,3,4-tetrahydroisoquinolines.

The renoprotective effect of cilnidipine ((±)-2-methoxyethyl 3-phenyl-2(E)-pro-penyl 1,4-dihydro-2,6-dimethyl-4-(3-ni-trophenyl)-3,5-pyridinedicarboxylate, CAS 132203-70-4), a L/N-type calcium channel antagonist, on puromycin aminonucleoside (PAN)-induced nephrosis was investigated in rats. In the Experiment I, rats were given an intravenous injection of PAN (70 mg/kg). Cilnidipine (3 mg/kg/day) and enalapril (CAS 75847-73-3, 5mg/kg/day) were administered orally from 6 days after treatment with PAN (day 6) to day 26, and urinary analysis was performed on days 9, 15, 20 and 27. In the Experiment II, nephrosis was also induced by intravenous injection of PAN (70 or 100 mg/kg) in rats which were treated with cilnidipine and enalapril from days 6 to 10. Systolic blood pressure was measured on day 7 and urinary analysis was performed on day 10. On day 11, serum was collected and the kidneys were removed for immunofluorescence staining for nephrin and podocin proteins. In PAN-treated rats, the daily urinary protein excretion was dramatically elevated on day 5, reached a peak on day 9 and gradually returned to a normal level from days 15 to 27. Cilnidipine (3 mg/kg/day) significantly suppressed the increase in proteinuria on day 9 and also improved the decrease in creatinine clearance without evident effect on the blood pressure. Furthermore, the elevations in serum total cholesterol and triglyceride tended to be suppressed by cilnidipine. The expression of nephrin and podocin proteins in PAN-treated rats showed the granular pattern in the glomeruli, while the intensity of staining seemed to be dependent on the urinary protein excretion level in the cilnidipinetreated rats. The results obtained in this study suggest a renoprotective effect of cilnidipine in PAN-induced nephrosis in rats.

e15003 Background: Recently, we have shown that viable cancer cells (CCs) spilled into the peritoneal cavity during curative gastrectomy for gastric cancer (GC) were tumorigenic and showed the clin...

A synthesis of 1,1-disubstitued 1,2,3,4-tetrahydro-β-carbolines (13) was achieved in a highly effective manner via the trifluoroacetic acid catalyzed Pictet-Spengler reaction of the keto imines (9) prepared from tryptamine (8) with acyclic and cyclic ketones using titanium(IV) isopropoxide as the imination reagent under one pot procedure. This reaction provides a convenient and general method for preparing various 1,2,3,4-tetrahydro-β-carbolines derivatives.

Surface processes in GaAs digital etching using alternating incidence of Cl radicals and a low energy Ar ion beam are discussed. For Cl feed time greater than 0.3 s, etching of GaAs does not proceed for short Ar ion irradiation times. This etching delay time is about 3 and 7 s for Cl feed time of 0.5 and 0.7 s, respectively. After etching starts, the etch rate increases and finally saturates during Ar ion irradiation. Since the same saturation value was obtained for Cl feed times between 0.5 and 0.7 s, digital etching involves a self-limiting mechanism. Rate equation analysis can explain these unique characteristics of digital etching on the assumption that physisorbed Cl layers prevent the sample surface from etching during short Ar ion irradiation times.

Characteristics o digital etching using an electron-beam-excited plasma system in GaAs are reported. In digital etching, etchant gas pulses and Ar ions are sequentially impinged onto the substrate surface to be etched. When the energy of Ar ion is -17 eV, etch rates which correspond to the 0.5 monolayer (ML) per cycle of GaAs (0.142 nm) are obtained between 0.3 and 0.5 seconds of Cl2 feed time by using Cl radicals as etchants. With these etching parameters, a rectangular cross-sectional etch profile with smooth surface is obtained. Damages induced in digital etching was characterized by current-voltage measurement of the diode fabricated after the etching.