Bloodstream infection caused by Wickerhamiella pararugosa in a patient with intestinal obstruction: A case report.

The fungus Wickerhamiella pararugosa (Candida pararugosa) has been detected in various human organs but has rarely caused bloodstream infections. This report presents a case of central venous catheter-related bloodstream infection (CRBSI) of W. pararugosa in an adult. A female patient in her 80s was admitted to our facility for intestinal obstruction caused by colorectal cancer. The patient's ability to consume food was hindered, necessitating the insertion of a central venous catheter (CVC) into the internal jugular vein. On day 3 after admission, the patient developed a fever, prompting blood and CVC tip cultures to be performed. On day 5, yeast-like fungi were discovered in the blood cultures, and fosfluconazole (fluconazole [FLCZ] pro-drug) treatment was initiated. On day 8, yeast-like fungi were identified in both the blood and CVC tip cultures, leading to a diagnosis of CRBSI. The fungus was identified as W. pararugosa through biochemical and genetic characterization. This finding justified the use of micafungin (MCFG) for combination therapy. On day 17, the minimum inhibitory concentrations (MIC) for FLCZ and MCFG were 4-8 and 0.06 µg/mL, respectively. Accordingly, the treatment was changed to monotherapy with MCFG. After a 21-day treatment regimen, the patient was discharged on day 31. We present a case of CRBSI caused by W. pararugosa in an adult with intestinal obstruction. The notable increase in the MIC of FLCZ necessitated monotherapy with MCFG, which resulted in successful recovery of the patient.

CD44-positive Cancer Stem-like Cells as a Potential Source of Peritoneal Metastasis After Surgery.

BACKGROUND/AIM: The role of CD44 in gastric cancer-derived peritoneal metastasis is currently unknown. It was previously shown that viable, tumorigenic cancer cells are spilled into the peritoneal cavity during surgery, providing a potential cause of peritoneal recurrence after surgery. The purpose of this study was to elucidate the mechanism of peritoneal metastasis of gastric cancer through the expression of CD44 and to propose a method for preventing peritoneal recurrence. MATERIALS AND METHODS: Gastric cancer cell line MKN-45 was sorted into CD44+ and CD44- cells and then injected intraperitoneally into NOD/ShiJic-scidJcl mice. Differences in tumor-initiating capacity between the two groups were assessed using in vivo limiting dilution assays. Tumors harvested from both groups were examined for CD44 and ALDH1A1 expression using immunohistochemistry. The effects of CD44 blockade with anti-CD44 antibody on cell invasion and peritoneal metastasis formation in vivo were assessed. RESULTS: CD44+ cells showed significantly higher efficiency in initiating peritoneal tumor than CD44- cells. Blockade of CD44 significantly reduced peritoneal dissemination of CD44+ cells in vivo, indicating that the CD44 function of intraperitoneally disseminated cancer cells helped promote the formation of peritoneal metastasis. The margin of established tumors showed clusters of cells co-expressing CD44 and ALDH1A1. Peritoneally administered CD44- cells resulted in peritoneal metastases consisting of CD44+ and CD44- cancer cells. CONCLUSION: CD44 expressing cells are a potential source of peritoneal metastasis after surgery and could be a promising target for preventing peritoneal recurrence.

Surgical invasiveness and lymphadenectomy in robotic and laparoscopic gastrectomy: A retrospective study with propensity-score matching.

BACKGROUND: There is no consensus amongst comparative studies about the advantages of robotic over laparoscopic surgeries for gastric cancer (GC). We compared invasiveness and lymph node dissection between robotic and laparoscopic gastrectomies (RG and LG). METHODS: We retrospectively reviewed the medical records of 215 consecutive patients with GC who underwent RG or LG with lymphadenectomy from January 2011-December 2020. Propensity score matching analysis was performed to control selection bias. RESULTS: The RG group had less operative blood loss (P = 0.0005) and higher C-reactive protein levels on postoperative day 1 (P = 0.0006) than the LG group. When analyzing the specific sites of dissected lymph nodes, station groups of supra-pancreatic and lesser curvature areas accounted for this difference (P = 0.0073 and 0.0362, respectively). CONCLUSIONS: RG demonstrated lesser intraoperative bleeding, less of a postoperative inflammatory response, and a higher proportion of lymph node removal than LG, suggesting that it is a better surgical and oncological procedure.

Enhancement of antitumor immune response by radiation therapy combined with dual immune checkpoint inhibitor in a metastatic model of HER2-positive murine tumor.

PURPOSE: Treatments for metastatic human epidermal growth factor receptor 2 (HER2)-positive tumors are improving but remain inadequate. We investigated activating antitumor immune response by combining radiation therapy with immune checkpoint inhibitors using mouse tumors overexpressing HER2, a pivotal driver oncogenic antigen, to develop new immunotherapies for metastatic HER2-positive tumors. MATERIALS AND METHODS: NT2.5 cells were inoculated into the two mammary fat pads of FVB/N mice, which were divided into four groups: no treatment (Non), anti-PD-1 and anti-CTLA4 antibodies (P1C4), irradiation of the large tumor (Rad), and combination (R + P1C4) groups. Tumor growth, immunostaining of tumor-infiltrating lymphocytes, and the proportion of HER2-tumor antigen-specific CD8-positive T cells in the spleen and tumor-infiltrating lymphocytes were analyzed. RESULTS: In the Rad group, unirradiated and irradiated tumors shrank after treatment. Besides the directly irradiated tumors, the unirradiated tumors in the R + P1C4 group shrank the most. In the unirradiated tumors, CD8-positive T cells and FOXP3-positive T cells accumulated significantly more in the R + P1C4 group than in the P1C4 and the Rad groups (all p < 0.001). CD4-positive helper T cells accumulated significantly more in the R + P1C4 group than in the Rad group (p < 0.05), but this was not significantly different from the P1C4 group. HER2-specific CD8-positive T cells in the spleen and tumor-infiltrating lymphocytes were significantly increased in the R + P1C4 group compared to the P1C4 and Rad groups (all p < 0.0001). CONCLUSION: Irradiation of HER2-positive tumors induced an antitumor immune effect against the unirradiated tumor, which was enhanced by the combined use of immune checkpoint inhibitors and was mediated by enhanced recruitment of HER2-tumor antigen-specific cytotoxic T lymphocytes at the tumor site in an HER2-positive mouse tumor model. Harnessing the distant antitumor immune response induced by the combination of radiation therapy and immune checkpoint inhibitors could be a promising treatment strategy for metastatic HER2-positive tumors.

Adverse impact of postoperative intra-abdominal infectious complications on cancer recurrence-related survival after curative gastric cancer surgery.

BACKGROUND: This study aimed to evaluate the impact of postoperative intra-abdominal infectious complications (PICs) on survival after surgery for gastric cancer. METHODS: A total of 152 patients who underwent curative gastrectomy for gastric cancer were included. The effect of clinicopathological features and PICs on recurrence-free survival (RFS) and overall survival (OS) were investigated. RESULTS: The median age was 67 years. The pathological stage was stage I (61), II (40), and III (51). Thirty-two patients (21.1%) had PICs: 9, pancreatic fistula; 14, anastomotic leakage; and 17, intra-abdominal abscess. The five-year RFS and OS rates were significantly lower in patients with PICs than in those without PICs (63.4 vs. 85.6%; p < 0.01 and 56.4 vs. 80.3%; p < 0.01, respectively). In multivariate analysis, intraoperative blood loss was an independent prognostic factor for PICs. CONCLUSIONS: Patients with PICs had worse clinical outcomes. Reducing intraoperative bleeding may improve the prognosis of gastric cancer.

Nanoarchitected Tough Biological Composites from Assembled Chitinous Scaffolds.

Over hundreds of millions of years, organisms have derived specific sets of traits in response to common selection pressures that serve as guideposts for optimal biological designs. A prime example is the evolution of toughened structures in disparate lineages within plants, invertebrates, and vertebrates. Extremely tough structures can function much like armor, battering rams, or reinforcements that enhance the ability of organisms to win competitions, find mates, acquire food, escape predation, and withstand high winds or turbulent flow. From an engineering perspective, biological solutions are intriguing because they must work in a multifunctional context. An organism rarely can be optimally designed for only one function or one environmental condition. Some of these natural systems have developed well-orchestrated strategies, exemplified in the biological tissues of numerous animal and plant species, to synthesize and construct materials from a limited selection of available starting materials. The resulting structures display multiscale architectures with incredible fidelity and often exhibit properties that are similar, and frequently superior, to mechanical properties exhibited by many engineered materials. These biological systems have accomplished this feat through the demonstrated ability to tune size, morphology, crystallinity, phase, and orientation of minerals under benign processing conditions (i.e., near-neutral pH, room temperature, etc.) by establishing controlled synthesis and hierarchical 3D assembly of nano- to microscaled building blocks. These systems utilize organic-inorganic interactions and carefully controlled microenvironments that enable kinetic control during the synthesis of inorganic structures. This controlled synthesis and assembly requires orchestration of mineral transport and nucleation. The underlying organic framework, often consisting of polysaccharides and polypeptides, in these composites is critical in the spatial and temporal regulation of these processes. In fact, the organic framework is used not only to provide transport networks for mineral precursors to nucleation sites but also to precisely guide the formation and phase development of minerals and significantly improve the mechanical performance of otherwise brittle materials.Over the past 15 years, we have focused on a few of these extreme performing organisms, (Wang , Adv. Funct. Mater. 2013, 23, 2908; Weaver , Science 2012, 336, 1275; Huang , Nat. Mater. 2020, 19, 1236; Rivera , Nature 2020, 586, 543) investigating not only their ultrastructural features and mechanical properties but in some cases, how these assembled structures are mineralized. In specific instances, comparative analyses of multiscale structures have pinpointed which design principles have arisen convergently; when more than one evolutionary path arrives at the same solution, we have a good indication that it is the best solution. This is required for survival under extreme conditions. Indeed, we have found that there are specific architectural features that provide an advantage toward survival by enabling the ability to feed effectively or to survive against predatory attacks. In this Account, we describe 3 specific design features, nanorods, helicoids, and nanoparticles, as well as the interfaces in fiber-reinforced biological composites. We not only highlight their roles in the specific organisms but also describe how controlled syntheses and hierarchical assembly using organic (i.e., often chitinous) scaffolds lead to these integrated macroscale structures. Beyond this, we provide insight into multifunctionality: how nature leverages these existing structures to potentially add an additional dimension toward their utility and describe their translation to biomimetic materials used for engineering applications.

Long-term prognosis of patients with cancer-related genes detected in postoperative peritoneal washings obtained during curative gastrectomy.

BACKGROUND: 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. METHODS: 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) after >7-year follow-up were examined using the Kaplan-Meier method. RESULTS: 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). CONCLUSION: 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.

BCS1L mutations produce Fanconi syndrome with developmental disability.

Fanconi syndrome is a functional disorder of the proximal tubule, characterized by pan-aminoaciduria, glucosuria, hypophosphatemia, and metabolic acidosis. With the advancements in gene analysis technologies, several causative genes are identified for Fanconi syndrome. Several mitochondrial diseases cause Fanconi syndrome and various systemic symptoms; however, it is rare that the main clinical symptoms in such disorders are Fanconi syndrome without systematic active diseases like encephalomyopathy or cardiomyopathy. In this study, we analyzed two families exhibiting Fanconi syndrome, developmental disability and mildly elevated liver enzyme levels. Whole-exome sequencing (WES) detected compound heterozygous known and novel BCS1L mutations, which affect the assembly of mitochondrial respiratory chain complex III, in both cases. The pathogenicity of these mutations has been established in several mitochondria-related functional analyses in this study. Mitochondrial diseases with isolated renal symptoms are uncommon; however, this study indicates that mitochondrial respiratory chain complex III deficiency due to BCS1L mutations cause Fanconi syndrome with developmental disability as the primary indications.

18F-fluorodeoxyglucose uptake in advanced gastric cancer correlates with histopathological subtypes and volume of tumor stroma.

PURPOSE: The aim of this study was to investigate the correlation between preoperative 18F-fluorodeoxyglucose (FDG) uptake and histological subtypes, amount of tumor stroma in advanced gastric cancer (GC), and clinical outcomes. METHODS: We evaluated 56 patients (male/female, 42:14; mean age, 69 years) with advanced GC who underwent surgical resection at our institution and positron emission tomography-computed tomography with 18F-FDG prior to surgery. We used the maximum standardized uptake value (SUVmax) of the tumor and the tumor-to-liver ratio (TLR) of the SUVmax for the analysis. The SUVmax and TLR correlated with histological subtypes, immunohistochemistry (IHC) for CD34, and recurrence-free survival (RFS). Tumor stroma in GC was evaluated by CD34 expression. GCs were classified according to the Lauren and World Health Organization (WHO) classifications. RESULTS: The average FDG uptakes (SUVmax) were 4.17% and 14.04% in diffuse and intestinal type GCs, respectively, according to the Lauren classification, and 4.17%, 13.87%, 7.70%, 9.71%, and 19.45% in the poorly cohesive, tubular, mucinous, and papillary adenocarcinomas, respectively, according to the WHO classification. The FDG uptake in diffuse type was significantly lower than that in the intestinal type (p = 0.000). The SUVmax and TLR of the CD34(+) group (mean SUVmax, 5.50; TLR, 1.56) were significantly lower than those of the CD34(-) group (mean SUVmax, 14.09; TLR, 4.09). RFS was not associated with TLR or CD34 expression. CONCLUSION: GC, which has abundant tumor stroma characterized by high CD34 expression on IHC, shows low FDG uptake.

Cancer-derived Exosomes Activate Immune Surveillance and Suppress Peritoneal Metastasis of Murine Colonic Cancer.

BACKGROUND: Colonic cancer is associated with a low incidence of peritoneal metastasis compared with gastric cancer; however, the reason for this remains unclear. In this study, a model of peritoneal dissemination using the CT26 murine colon cancer cell line was used to analyze the physiological roles of cancer-derived exosomes. MATERIALS AND METHODS: Exosomes were collected from the supernatant of CT26 cell culture by ultracentrifugation. The number of peritoneal disseminations in two mouse models of colonic cancer pre-administered exosomes or phosphate-buffered saline were compared. RESULTS: Cancer-derived exosomes suppressed peritoneal dissemination compared to phosphate-buffered saline. After administration of exosomes, the number of intraperitoneal macrophages and the expression of inducible nitric oxide synthase increased. Furthermore, cancer-derived exosomes increased activated natural killer cells and interferon-γ expression. CONCLUSION: Tumor-derived exosomes from colonic cancer may suppress peritoneal metastasis via an immunological mechanism.

A Prospective Multicenter Observational Study of Venous Thromboembolism after Gastric Cancer Surgery (SHISA-1601).

INTRODUCTION: This study aimed to clarify the frequency and risk factors of intercurrent venous thromboembolism (VTE) in patients undergoing major curative gastric cancer surgery. METHODS: This prospective, multicenter, observational study included patients with gastric cancer who underwent radical gastrectomy at 5 hospitals between June 2016 and May 2018. Patients who were preoperatively administered anticoagulants were excluded. RESULTS: A total of 126 patients were eligible to participate. VTE occurred within 9 days postoperatively in 5 cases (4.0%; 2 symptomatic and 3 asymptomatic). Postoperative day (POD) 1 plasma D-dimer and soluble fibrin (SF) levels were significantly higher in the VTE group than in the non-VTE group. Receiver-operating characteristic curve (ROC) analysis indicated a statistically significant ability of POD 1 D-dimer and SF levels to predict postoperative VTE development after gastrectomy; this finding was reflected by an area under the curve (AUC) of 0.97 (95% CI 0.92-1.0) and 0.87 (95% CI 0.74-1.0), respectively. Cutoff values of D-dimer (24.6 µg/mL) and SF (64.1 µg/mL) were determined. Intraoperative blood transfusion (odds ratio [OR] 7.86), POD 1 D-dimer ≥24.6 µg/mL (OR 17.35), and POD 1 SF ≥64.1 µg/mL (OR 19.5) were independent predictive factors for postoperative VTE (p < 0.05). CONCLUSION: VTE occurred in 4.0% patients (1.6% symptomatic and 2.4% asymptomatic) after gastric cancer surgery; however, with an early diagnosis and anticoagulant therapy, no patients experienced progression. Careful observation of patients with a high risk for VTE, including intraoperative blood transfusion and high POD 1 D-dimer or SF levels, would contribute to the early detection of VTE.

A Novel Technique to Predict Liver Damage After Laparoscopic Gastrectomy From the Stomach Volume Overlapping the Liver by Preoperative Computed Tomography.

BACKGROUND: During laparoscopic gastrectomy (LG), it is necessary to manipulate the lateral segment of the liver to secure the surgical field. Liver retraction during surgery often causes liver dysfunction after LG. However, no previous studies have used preoperative image evaluations to predict postoperative liver damage associated with surgical retraction. We aimed to predict postoperative liver damage after LG. METHODS: In all, 117 consecutive patients with gastric cancer who underwent LG were included in this study. Using preoperative computed tomography (CT), the volume of the stomach overlapping the liver was integrated and calculated as the liver projecting stomach volume (LPSV). The liver projection ratio (LPR) was calculated by dividing the LPSV by the volume of the whole stomach. The relationships among liver damage, the LPSV and LPR were evaluated. RESULTS: A total of 112 patients were divided into two groups as follows: 33 patients in the liver dysfunction group (D group) and 79 patients in the non-dysfunction group (N group). The LPSV was significantly larger in the D group than in the N group (median 77.1 vs 50.1 cm3; p = 0.0061). Similarly, LPR values in the D group were significantly higher than those in the N group (median 33.6 vs 26.2%; p = 0.003). Receiver operating characteristic curve analysis indicated a statistically significant ability of the LPSV and LPR to predict postoperative liver damage (area under the curve; 0.705 and 0.735, respectively). Furthermore, multivariate logistic regression analysis revealed that the increase in the LPR was an independent predictor of postoperative liver damage (odds ratio: 1.042; 95% confidence interval: 1.009-1.078; p = 0.019). CONCLUSIONS: We have developed a novel technique for predicting postoperative liver damage associated with surgical liver retraction following LG. This method confirms the degree of the LPSV and LPR of the stomach via preoperative CT.

Infiltration of CD4, CD8, CD56, and Fox-P3-positive lymphocytes in breast carcinoma tissue after neoadjuvant chemotherapy with or without trastuzumab.

BACKGROUND: Trastuzumab (Tz) is assumed to prime antibody-dependent cellular cytotoxicity (ADCC); however, it remains unclear whether Tz therapy can clinically induce adaptive cellular immunity. OBJECTIVE: Adaptive Cellular Immune Effect of Tz Therapy. METHODS: This study included 29 surgical invasive breast carcinomas administered neoadjuvant chemotherapy with Tz (15 cases) or without Tz (14 cases). The numbers of immunoreactive cells (CD4, CD8, CD56, and Fox-P3) in three different compartments (intratumoral, adjacent stromal, and distant stromal) were determined. RESULTS: The average number of adjacent stromal CD4-positive, CD8-positive, and Fox-P3-positive cells in the Tz+ group was significantly greater than that in the Tz- group (p = 0.036, 0.0049, and 0.043, respectively). However, the number of Fox-P3-positive cells was much less than that of CD4-positive cells. Moreover, distant stromal CD4-positive and CD8-positive cells in the Tz+ group was also significantly greater than that of the Tz- group (p = 0.029 and 0.032, respectively). Only a small number of CD56-positive natural killer cells, playing a main role in ADCC, accumulated at the tumor site after Tz therapy. CONCLUSIONS: The results suggest that Tz therapy induces adaptive cellular immunity, including infiltration of both CD4-positive helper T cells and CD8-positive cytotoxic T cells into the breast carcinoma lesion.

[Study of Eight Cases of Retroperitoneal Liposarcoma].

Retroperitoneal liposarcoma is a relatively rare disease, with a high recurrence rate and poor prognosis. We encountered 8 patients with retroperitoneal liposarcoma who underwent surgery in Shiga University of Medical Science Hospital. We often encounter elderly male patients without symptoms. Of the 8 patients, 6 received extensive resection that included the surrounding organs or tissues; however, 3 patients demonstrated positive surgical margins, which resulted in liposarcoma recurrence. Despite the additional resection in the 3 recurrent cases, all the patients had a tumor relapse. One patient with an unresectable tumor received chemotherapy. The other patients received surgical treatment 3 times. One patient developed an unresectable relapse after receiving chemotherapy. Another patient attained long-term survival by adjuvant chemoradiotherapy combined with 3 surgeries. Aggressive surgical resection to achieve a negative surgical margin and careful postoperative follow-up seem important for the treatment of retroperitoneal liposarcoma. This study suggests that postoperative adjuvant therapy may contribute to the improvement of prognosis. Further findings must be accumulated to clarify the significance of postoperative adjuvant therapies in the future.

Presence of cancer cells in the periarterial tissues of patients with advanced gastric cancer.

Lymphadenectomy with gastrectomy is considered a curative surgical treatment for gastric cancer. Periarterial connective tissue-preserving lymphadenectomy has become a common procedure following developments in laparoscopic surgery. However, the presence of cancer cells in the periarterial tissue, including neural invasion, has not been examined. In the present study, the periarterial tissues from the vessel roots of the left gastric artery (LGA) and right gastroepiploic artery (RGEA) after gastrectomy were evaluated for the presence of cancer cells. The study included 28 consecutive patients who underwent gastrectomy for gastric cancer. The vessel roots of the RGEA and LGA were obtained from surgically resected specimens and examined by two independent pathologists to determine the presence of cancer cells in the periarterial tissues. The collected specimens included 23 RGEA roots and 26 LGA roots from 28 patients. In 8 cases of early gastric cancer, no cancer cells were indicated in the periarterial tissues. By contrast, cancer cells, including neural invasion in 2 cases, were identified in the periarterial tissues from the roots of examined gastric arteries in 3/20 (15%) cases of advanced gastric cancer. Notably, all 3 cases featured multiple regional lymph node (LN) metastases. Cancer cells were detected in the perivascular tissue of the major gastric arteries from cases with advanced gastric cancer with LN metastases, suggesting the requirement for oncologic evaluation to ensure adequate vascular tissue margins and an adequate periarterial layer during lymphadenectomy.

Classification of remnant stomach shape after distal gastrectomy with Billroth-I reconstruction and a comparison of the postoperative outcomes.

PURPOSE: To classify the shape of the remnant stomach after Billroth-I (B-I) reconstruction and evaluate the relationship between the shape of the remnant stomach and the postoperative clinical outcomes. METHODS: One hundred and ninety-five consecutive patients with gastric cancer underwent distal gastrectomy with B-I reconstruction between May 2006 and October 2014. We retrospectively reviewed their medical records and radiological findings. Finally, the shapes of the remnant stomach of 150 patients were classified as either straight type (type A) or stagnant type (type B). The clinical outcomes were compared with respect to the types of remnant stomach. RESULTS: The incidence of anastomotic leakage was significantly higher in the type A group than in the type B group (9.4 vs. 1.5%, p = 0.044). The body weight change ratio after surgery was significantly lower in the type B group than in the type A group [p = 0.0068, two-way repeated measures analysis of variance (ANOVA)], while the serum albumin levels showed marginally significant improvement in the type B group compared with the type A group (p = 0.0542, two-way repeated measures ANOVA). CONCLUSION: The shape of the remnant stomach after distal gastrectomy with B-I reconstruction might influence the degree of anastomotic leakage and long-term nutritional status.

[A Case of Gastric Cancer Underwent Two-Stage Gastrectomy after Chemotherapy-Induced Perforation].

A 70's man presenting with a chief complaint of stomachache was found to have advanced gastric cancer with a deep ulcer and some lymph-node metastases. We decided performing a curative operation after 2 courses of S-1 plus cisplatin. On the first course day 13 of chemotherapy, he complained of severe epigastralgia, and we diagnosed as generalized peritonitis due to perforation of gastric cancer. We performed an urgent laparoscopic operation, which made perforation simple closure and omentopexy. Curative distal gastrectomy with D2 lymph node dissection was successfully performed on postoperative day 16.

In vivo antitumor function of tumor antigen-specific CTLs generated in the presence of OX40 co-stimulation in vitro.

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.