Predictive Factors for Delayed Gastric Emptying after Distal Gastrectomy with Roux-en-Y Reconstruction.

Delayed gastric emptying (DGE) after distal gastrectomy (DG) followed by Roux-en-Y (R-Y) reconstruction is one of the most worrisome complications, and the course of DGE has not been completely elucidated. This retrospective study aimed to evaluate the frequency of DGE after DG followed by R-Y reconstruction for gastric cancer and identify the risk factors for its development. This study included 266 patients with gastric cancer who underwent DG followed by R-Y reconstruction between 2005 and 2016. We compared clinicopathological characteristics and surgical procedures between the DGE group and non-DGE group. DGE occurred in 24 of the 266 patients. There were no relationships of gender, age, TNM stage, historical grade, surgical approach, extent of lymphadenectomy, preservation of the vagal nerve, and reconstruction route with DGE development. Body mass index (BMI) was higher in DGE patients than in non-DGE patients (P = 0.053). Univariate analysis revealed that a tumor located in the lower third of the stomach (P = 0.005) and isoperistaltic reconstruction (P = 0.043) were significant factors for DGE. Multivariate analysis showed that a tumor located in the lower third of the stomach (P = 0.007), isoperistaltic reconstruction (P = 0.044), and BMI (P = 0.034) were significant predictors of DGE. Our findings suggest that tumor location, the direction of peristalsis for gastrojejunostomy, and BMI are associated with DGE after R-Y reconstruction.

Prognostic Significance of the Prognostic Nutritional Index in Patients with Recurrent Esophageal Squamous Cell Carcinoma.

The aim of this study was to evaluate the prognostic impact of the prognostic nutritional index (PNI) in patients with recurrent esophageal squamous cell carcinoma (ESCC). We retrospectively reviewed 76 ESCC patients who developed recurrence after curative subtotal esophagectomy at Nara Medical University Hospital between January 2001 and October 2016. The PNI at ESCC recurrence was calculated as 10 × serum albumin (g/dl) + 0.005 × total lymphocyte count (/mm3). The cutoff value of the PNI was set at 45. Multivariate analysis was performed to identify the prognostic factors. The mean PNI was 44.0 ± 5.8, and 42 (55.3%) patients had a PNI <45 at recurrence. The multivariate analysis identified a low PNI (P = 0.047), multiple recurrence sites (P = 0.002), and no treatment for recurrence (P = 0.034) as independent factors for a short survival time after recurrence. A low PNI was significantly associated with a high performance status score, high C-reactive protein level, and short duration of treatment for recurrence. In conclusion, the PNI at recurrence can predict the survival time in patients with recurrent ESCC.

The prognostic significance of inflammation-based markers in patients with recurrent gastric cancer.

PURPOSE: The aim of this study was to evaluate the prognostic impact of inflammation-based markers, including the neutrophil-to-lymphocyte ratio (NLR) and prognostic nutritional index (PNI), in patients with recurrent gastric cancer (RGC). METHODS: This study reviewed 167 patients with RGC. A receiver operating characteristics (ROC) curve analysis was performed to determine the NLR and PNI cutoff values. The prognostic significance of the NLR and PNI was evaluated by a multivariate analysis. RESULTS: The optimal NLR and PNI cutoff values for predicting the 1-year survival after recurrence were 2.2 and 47, respectively. A univariate analysis revealed that the NLR (p < 0.001) and PNI (p < 0.001) were significantly associated with the survival time after recurrence, along with the histology, peritoneal recurrence, carbohydrate antigen 19-9, and chemotherapy for recurrence. In the multivariate analysis, a higher NLR (p < 0.001) and a lower PNI (p = 0.002) were independent predictors of a shorter survival time. Among the patients who underwent chemotherapy, the NLR and PNI were also independent prognostic factors. CONCLUSIONS: Inflammation-based markers, including the NLR and PNI, are simple and useful clinical biomarkers that can be used to predict the survival time of patients with RGC.

Usefulness of computed tomography density of a tumor in predicting the response of advanced esophageal cancer to preoperative chemotherapy.

BACKGROUND: In Japan, preoperative chemotherapy is considered essential for resectable stage II or III esophageal cancers. It is important to identify nonresponders for preoperative chemotherapy because continuing ineffective chemotherapy is not beneficial for them. We investigated the correlation between the computed tomography number of tumor and the effect of preoperative chemotherapy in patients with esophageal cancer. METHODS: This retrospective study included 50 patients receiving preoperative chemotherapy with docetaxel, cisplatin, and 5-fluorouracil for stage II or III esophageal cancer. The computed tomography number of tumor was measured as the mean of Hounsfield Units of the primary lesion on a plain computed tomography measured within a freehand region of interest drawn around the tumor border. For analysis, the patients were classified into responders and nonresponders to chemotherapy, with the pathologic response evaluated using the Japanese and Mandard classification. We analyzed the associations between the computed tomography number of tumor and clinical factors; histopathologic features, including the tumor size, depth of tumor invasion, capillary invasion, Ki-67, p53, and CK5/6 expression; the pathologic response to chemotherapy and prognosis. RESULTS: There was a significant association between the computed tomography number of tumor and the response to chemotherapy. The cut-off value of the computed tomography number of tumor in predicting responders to chemotherapy was 40 Hounsfield Units (area under the receiver operating characteristic curve = 0.73, P = .009); patients with computed tomography number of tumor greater than this value significantly responded to chemotherapy (P = .02 in the Japanese and P = .009 in the Mandard classification) with good postoperative prognosis (P = .04). Only Ki-67 expression among the histopathogic features were associated with the computed tomography number of tumor in histopathologic features (P = .01). CONCLUSION: The computed tomography number of tumor may be useful to predict the efficacy of preoperative chemotherapy and subsequent prognosis for patients with advanced esophageal cancer.

Preoperative Plasma Fibrinogen is Associated with Lymph Node Metastasis and Predicts Prognosis in Resectable Esophageal Cancer.

BACKGROUND: Although it is well known that patients with malignant tumors have abnormal blood coagulation, its clinical significance has not been studied. We investigated the clinicopathological and prognostic impact of plasma fibrinogen, which is the major factor of the coagulation system, in patients with esophageal cancer. METHODS: From February 1995 to December 2006, 100 patients with esophageal cancer who had their plasma fibrinogen measured were enrolled. The associations between plasma fibrinogen, clinicopathological factors, and prognosis were analyzed. A concentration of 2.0-4.0 g/L was defined as normofibrinogenemia, and a concentration higher than 4.0 g/L was described as hyperfibrinogenemia. RESULTS: Patients with large, advanced tumors, and lymph node metastasis had significantly higher plasma fibrinogen than those with small, early tumors, and no lymph node metastasis (p < 0.001, p = 0.002, and p = 0.03, respectively). Plasma fibrinogen was associated with not only the existence of lymph node metastasis but also the extension of lymph node metastasis and lymphatic recurrence. Patients with hyperfibrinogenemia had a significantly poor prognosis as compared to those with normofibrinogenemia, regardless of pathological staging. Plasma fibrinogen was an independent risk factor for overall survival and relapse-free survival as well as tumor depth and lymph node metastasis (p = 0.004 and p = 0.031, respectively). CONCLUSION: Preoperative plasma fibrinogen is a possible biomarker for the prediction of tumor progression, recurrence pattern, and prognosis for esophageal cancer. Preoperative plasma fibrinogen is also associated with lymph node metastasis and may be helpful in adjusting neo-adjuvant therapy.

A decrease in the prognostic nutritional index is associated with a worse long-term outcome in gastric cancer patients undergoing neoadjuvant chemotherapy.

PURPOSE: The aim of this study was to evaluate the prognostic impact of the prognostic nutritional index (PNI) in gastric cancer patients undergoing neoadjuvant chemotherapy (NAC). METHODS: This study reviewed 54 patients with gastric cancer who underwent NAC and a subsequent R0 gastrectomy. The PNI before starting NAC and before gastrectomy were calculated using the following formula: 10 × serum albumin (g/dl) + 0.005 × total lymphocyte count (per mm3). A multivariate analysis was performed to identify the predictors of overall survival (OS). RESULTS: The mean pre-NAC and preoperative PNI were 48.3 ± 5.1 and 48.2 ± 4.7, respectively (p = 0.934). The PNI decreased after NAC in 31 patients (57.4%). The pre-NAC PNI and preoperative PNI were not significantly associated with the OS rate. The 3-year OS rate in patients with the decreased PNI values was significantly lower than that in the patients whose PNI values were either maintained or increased (41 vs. 76.4%, p = 0.003). A multivariate analysis revealed that a decreased PNI value was an independent predictor of a poor OS (p = 0.006). CONCLUSIONS: Decreased PNI values were associated with worse long-term outcomes in gastric cancer patients undergoing NAC.

The anatomical location of the pancreas is associated with the incidence of pancreatic fistula after laparoscopic gastrectomy.

BACKGROUND: Postoperative pancreatic fistula (POPF) is one of the major complications after laparoscopic gastrectomy (LG). We investigated the impact of the anatomical location of the pancreas, especially in relation to the suprapancreatic lymph nodes, on the incidence of POPF after LG. METHODS: We retrospectively reviewed the preoperative computed tomography (CT) images of 246 patients who underwent LG with the suprapancreatic lymph node dissection between November 2008 and November 2015. The length between the levels of the pancreatic body surface and the root of the common hepatic artery (LPC) was measured on a CT image with an axial view. A receiver operating characteristics (ROC) curve analysis was performed to determine the cutoff LPC value. A multivariate analysis was performed to determine the predictive factors for POPF. RESULTS: POPF occurred in 11 patients (4.5 %). The median LPC was significantly longer in the patients with POPF than in those without (26 mm vs. 21 mm, p = 0.026). The ROC curve analysis revealed that the optimal cutoff LPC value for predicting POPF was 25 mm. The POPF rate was significantly higher in the long LPC group than in the short LPC group (10 vs. 1.3 %, p = 0.002). A multivariate analysis demonstrated that a long LPC (p = 0.018) and dissection of the lymph nodes along the distal splenic artery (p = 0.042) were independent predictors of POPF. The amylase level in the drainage fluid on postoperative day 1 was significantly higher in the long LPC group than in the short LPC group. CONCLUSIONS: The LPC is a simple and reliable predictor of POPF after LG. Surgeons should take the anatomical location of the pancreas into consideration when performing LG with suprapancreatic lymph node dissection.

[Long-Term Disease-Free Survival through Postoperative Chemotherapy in a Case of Gastric Cancer with Peritoneal Dissemination].

An 80-year-old man with type 4 gastric cancer in the mid-gastric region underwent total gastrectomy and D2-No.10 lymph-node dissection (cT4a, N0, M0, cStageⅡB). Several nodules were detected under the left diaphragm, some of which were biopsied. Pathological findings indicated a poorly differentiated adenocarcinoma, pT4a (SE), pN3b, pM1 (P1, CY1), pStage Ⅳ. Systemic chemotherapy was initiated, using a regimen of S-1/docetaxel (DOC). After 6 courses of combination therapy, we switched to S-1 alone, which was continued for 1 year. Eighteen months after the surgery the patient discontinued S-1 treatment and has since survived for 5 years with no obvious cancer recurrence.

Evidence for the involvement of double-strand breaks in heat-induced cell killing.

To identify critical events associated with heat-induced cell killing, we examined foci formation of gammaH2AX (histone H2AX phosphorylated at serine 139) in heat-treated cells. This assay is known to be quite sensitive and a specific indicator for the presence of double-strand breaks. We found that the number of gammaH2AX foci increased rapidly and reached a maximum 30 minutes after heat treatment, as well as after X-ray irradiation. When cells were heated at 41.5 degrees C to 45.5 degrees C, we observed a linear increase with time in the number of gammaH2AX foci. An inflection point at 42.5 degrees C and the thermal activation energies above and below the inflection point were almost the same for cell killing and foci formation according to Arrhenius plot analysis. From these results, it is suggested that the number of gammaH2AX foci is correlated with the temperature dependence of cell killing. During periods when cells were exposed to heat, the cell cycle-dependent pattern of cell killing was the same as the cell cycle pattern of gammaH2AX foci formation. We also found that thermotolerance was due to a depression in the number of gammaH2AX foci formed after heating when the cells were pre-treated by heat. These findings suggest that cell killing might be associated with double-strand break formation via protein denaturation.