[Laparoscopic Proximal Gastrectomy with Supra-Pancreatic Dissection First Approach].

BACKGROUND: In laparoscopic proximal gastrectomy(LPG)with esophago-gastro anastomosis, the key of obtaining good surgical view is how to exclude the stomach from the supra-pancreatic area. METHODS: We could get good surgical view at the supra-pancreatic area with gastro-ptosis by firstly dissecting lesser curvature. Followed by the supra-pancreatic dissection we could efficiently dissect the gastro-splenic ligament from cranial side. We performed this procedure in 20 cases with upper gastric cancer. We evaluate the surgical outcomes of this procedure(S group)comparing to that of the previous procedure in 14 cases(G group). RESULTS: The median operative time in S group was significantly shorter than that in G group (226 min vs 249 min, p=0.02). Other data were similar in 2 groups. CONCLUSIONS: The short-term clinical outcomes of LPG with supra-pancreatic dissection first approach revealed that this technique is safe and feasible.

Quantification of Structural Heterogeneity Using Fractal Analysis of Contrast-Enhanced CT Image to Predict Survival in Gastric Cancer Patients.

BACKGROUND: Malignant tumor essentially implies structural heterogeneity. Fractal analysis of medical imaging has a potential to quantify this structural heterogeneity in the tumor AIMS: The purpose of this study is to quantify this structural abnormality in the tumor applying fractal analysis to contrast-enhanced computed tomography (CE-CT) image and to evaluate its biomarker value for predicting survival of surgically treated gastric cancer patients. METHODS: A total of 108 gastric cancer patients (77 men and 31 women; mean age: 69.1 years), who received curative surgery without any neoadjuvant therapy, were retrospectively investigated. Portal-phase CE-CT images were analyzed with use of a plug-in tool for ImageJ (NIH, Bethesda, USA), and the fractal dimension (FD) in the tumor was calculated using a differential box-counting method to quantify structural heterogeneity in the tumor. Tumor FD was compared with clinicopathologic features and disease-specific survival (DSS). RESULTS: High FD value of the tumor significantly associated with high T stage and high pathological stage (P = 0.009, 0.007, respectively). In Kaplan-Meier analysis, patients with higher FD tumors (FD > 0.9746) showed a significantly worse DSS (P = 0.009, log rank). Multivariate analysis demonstrated that tumor FD, T stage, and N stage were independent prognostic factors for DSS. In subset analysis of lymph-node positive gastric cancers, only tumor FD was an independent prognostic factor for DSS. CONCLUSION: CT fractal analysis can be a useful biomarker for gastric cancer patients, reflecting survival and clinicopathologic features.

Histogram Analysis of Diffusion-Weighted MR Imaging as a Biomarker to Predict Survival of Surgically Treated Colorectal Cancer Patients.

BACKGROUND: Structural abnormality is a well-recognized feature of malignancy. On the other hand, diffusion-weighted MRI (DWI) has been reported as a tool that can reflect tumor biology. AIMS: The purpose of this study is to apply histogram analysis to DWI to quantify structural abnormality of colorectal cancer, and evaluate its biomarker value. METHODS: This is a retrospective study of 80 (46 men and 34 women; median age: 68.0 years) colorectal cancer patients who underwent DWI followed by curative surgery at the Chiba University Hospital between 2009 and 2011. Median follow-up time was 62.2 months. Histogram parameters including signal intensity of kurtosis and skewness of the tumor were measured on DWI at b = 1000, and mean apparent diffusion coefficient value (ADC) of the tumor was also measured on ADC map generated by DWIs at b = 0 and 1000. Associations of tumor parameters (kurtosis, skewness, and ADC) with pathological features were analyzed, and these parameters were also compared with overall survival (OS) and relapse-free survival (RFS) using Cox regression and Kaplan-Meier analysis. RESULTS: ADC of the tumor did not have significant associations with any pathological factors, but kurtosis and skewness of signal intensity in the tumor was significantly different between tumors with distant metastases and those without (4.23 ± 1.31 vs. 3.24 ± 1.32, p = 0.04; 1.09 ± 0.39 vs. 0.57 ± 0.58, p = 0.03). Kurtosis of the tumor was significantly correlated with OS and RFS (p = 0.04, p = 0.03, respectively), and skewness was significantly correlated with OS (p = 0.03) in Cox regression analysis. Higher kurtosis or higher skewness of the tumor was associated with worse OS in Kaplan-Meier analysis (p = 0.01, p = 0.009, log-rank). In subset analysis, there were 50 patients (32 men and 18 women) of lymph node-negative colorectal cancers (≤ stage II); skewness of signal intensity in the tumor was associated with OS using univariate Cox regression analysis (p = 0.04). CONCLUSIONS: Histogram analysis of DWI can be a prognostic biomarker for colorectal cancer.

Treatment Outcome of Resection of Disseminated Peritoneal Metastases from Colorectal Cancer.

AIM: To show the treatment outcomes of disseminated nodule resection for peritoneal metastasis of colorectal cancer and describe the details of cured cases. PATIENTS AND METHODS: From January 2001 to December 2016, patients who underwent disseminated nodule resection of colorectal adenocarcinoma with no macroscopic residual tumor in our institution were retrospectively analyzed for clinicopathological factors associated with prognosis. RESULTS: Forty-one cases were included in this study. The 3-year relapse-free survival was 12.5%, and the 5-year overall survival was 38.4%. In a multivariate analysis, lack of post-operative adjuvant chemotherapy and pre-operative carbohydrate antigen 19-9 over 100 IU/l were extracted as independent factors associated with short relapse-free survival, respectively. Among 41 cases, 32 were followed-up 5 years after surgery and five (15.6%) survived without relapse and were regarded as 'cured'. CONCLUSION: More than a few cases of colorectal peritoneal metastasis, which is thought to be difficult to cure, were cured by resection of disseminated nodules without resorting to highly invasive treatment.

Volumetric Histogram Analysis of Apparent Diffusion Coefficient as a Biomarker to Predict Survival of Esophageal Cancer Patients.

BACKGROUND: The purpose of this study was to investigate whether histogram analysis of an apparent diffusion coefficient (ADC) can serve as a prognostic biomarker for esophageal squamous cell carcinoma (ESCC). METHODS: This retrospective study enrolled 116 patients with ESCC who received curative surgery from 2006 to 2015 (including 70 patients who received neoadjuvant chemotherapy). Diffusion-weighted magnetic resonance imaging (DWI) was performed prior to treatment. The ADC maps were generated by DWIs at b = 0 and 1000 (s/mm2), and analyzed to obtain ADC histogram-derived parameters (mean ADC, kurtosis, and skewness) of the primary tumor. Associations of these parameters with pathological features were analyzed, and Cox regression and Kaplan-Meier analyses were performed to compare these parameters with recurrence-free survival (RFS) and disease-specific survival (DSS). RESULTS: Kurtosis was significantly higher in tumors with lymphatic invasion (p = 0.005) with respect to the associations with pathological features. In univariate Cox regression analysis, tumor depth, lymph node status, mean ADC, and kurtosis were significantly correlated with RFS (p = 0.047, p < 0.001, p = 0.037, and p < 0.001, respectively), while lymph node status and kurtosis were also correlated with DSS (p = 0.002 and p = 0.017, respectively). Furthermore, multivariate analysis demonstrated that kurtosis was the independent prognostic factor for both RFS and DSS (p < 0.001 and p = 0.015, respectively). In Kaplan-Meier analysis, patients with higher kurtosis tumors (> 3.24) showed a significantly worse RFS and DFS (p < 0.001 and p = 0.006, respectively). CONCLUSIONS: Histogram analysis of ADC may serve as a useful biomarker for ESCC, reflecting pathological features and prognosis.

Volumetric histogram analysis of apparent diffusion coefficient for predicting pathological complete response and survival in esophageal cancer patients treated with chemoradiotherapy.

BACKGROUND: The purpose of the study was to evaluate whether histogram analysis of apparent diffusion coefficient (ADC) can predict pathological complete response (pCR) and survival in patients with esophageal squamous cell carcinoma (ESCC) after chemoradiotherapy (CRT). METHODS: We retrospectively identified 58 patients with ESCC who underwent surgery after CRT between 2007 and 2016. Associations of pretreatment histogram derived ADC parameters with pathological response and survival were analyzed. RESULTS: Tumors achieved pCR (10 patients, 17.2%) showed significant lower ADC, higher kurtosis, and higher skewness than those of non-pCR (p = 0.005, 0.007, <0.001, respectively). Receiver operating characteristics analysis demonstrated skewness was the best predictor for pCR (AUC = 0.86), with a cut off value of 0.50 (accuracy, 86.2%). In Kaplan-Meier analysis, patients with higher skewness tumors (≥0.50) showed a significantly better recurrence free survival (p = 0.032, log-rank). CONCLUSIONS: Histogram analysis of ADC can enable prediction of pCR and survival in ESCC patients treated with preoperative CRT. A SHORT SUMMARY: ADC histogram analysis can be an imaging biomarker for esophageal cancer patients treated with CRT.

[A Case of Gastric Cancer with Necrotic Lymph Node Perforation in the Stomach during Chemotherapy].

A 63-year-old man was diagnosed with gastric cancer. Distal gastrectomywas performed in November 2011. The pathologic finding was pT3N2M0, Stage ⅢA. S-1 was administered as adjuvant chemotherapy. However, in August 2012, computed tomographyrevealed a tumor measuring 3 cm in size in the dorsal pancreas. Based on endoscopic ultrasound-guided fine- needle aspiration, he was diagnosed with lymph node recurrence of gastric cancer. Injection chemotherapy of CDDP/CPT-11 was initiated in November 2012. In January 2013, the patient developed fever owing to a ruptured abscess from the posterior wall in the stomach. In the 6 years since, although the patient has not undergone chemotherapy, recurrence has not been observed.

Preoperative chemoradiotherapy using S-1 combined with celecoxib for advanced lower rectal cancer: Phase I/II study.

OBJECTIVES: To clarify the safety and efficacy of celecoxib combined with chemoradiotherapy using S-1 for lower rectal cancer. METHODS: Twenty-one patients with pathologically proven lower rectal adenocarcinoma (cT3-T4, Tx N+, M0) were included in this study. A total dose of 45 Gy was administered in daily fractions of 1.8 Gy. Celecoxib was given orally twice daily with S-1 on the day of irradiation. The dose of celecoxib was set at 400 mg/day. In Phase I, the S-1 dose was started at 80 mg/m2/day; in Phase II, S-1 was administered in the same dose as Phase I. Patients underwent surgery six to eight weeks after completing chemoradiotherapy, followed by six months of postoperative adjuvant chemotherapy. RESULTS: The S-1 recommended dose was 80 mg/m2/day. The pathological complete remission rate was 15.8%, the rate of protocol completion was 14.3%, and the rate of adverse events exceeding Grade 3 was 19.0%. Surgery was performed in 19 cases, with a sphincter-sparing rate of 31.6%. Postoperative complications exceeding Grade 3 occurred in 52.4% of cases. The three year overall survival and relapse-free survival rates were 89.3% and 67.0%, respectively. CONCLUSIONS: We failed to show a synergistic or additive therapeutic effect of preoperative CRT using S-1, combined with celecoxib, for lower advanced rectal cancer beyond CRT using 5 FU or capecitabine alone. The incidence of complications, evidently involving intestinal ischemia, was relatively high. This treatment strategy is not recommended at present.

Imaging biomarkers for the treatment of esophageal cancer.

Esophageal cancer is known as one of the malignant cancers with poor prognosis. To improve the outcome, combined multimodality treatment is attempted. On the other hand, advances in genomics and other "omic" technologies are paving way to the patient-oriented treatment called "personalized" or "precision" medicine. Recent advancements of imaging techniques such as functional imaging make it possible to use imaging features as biomarker for diagnosis, treatment response, and prognosis in cancer treatment. In this review, we will discuss how we can use imaging derived tumor features as biomarker for the treatment of esophageal cancer.

[Long-Term Control of Metastatic Colon Cancer by Chemotherapy in a Patient on Hemodialysis].

A 54-year-old man receiving dialysis for diabetic nephropathy underwent surgery for sigmoid cancer. Nine months later, he was diagnosed with multiple liver metastases. He underwent 2 courses of FOLFIRI plus panitumumab(Pmab)as first-line therapy, 15courses of capecitabine plus bevacizumab(Bmab)as second-line therapy, and 27 courses of Pmab as third-line therapy. He developed various complications throughout the disease course, such as heart disease, diabetic gangrene in both legs, and abscess of liver metastasis. The tumor marker levels after each event were higher than the previous event and subsequently decreased with the resumption of chemotherapy. However, after 27 courses of Pmab, his liver and para-aortic lymph node metastases exacerbated, and he ultimately died from a poor general condition at 42 months after the initial recurrence of liver metastasis. Evidence regarding the safety and pharmacokinetics of chemotherapy in dialysis patients is insufficient at present. Herein, we report a case of metastatic colon cancer in a patient on hemodialysis along with a literature review.

Heterogeneity of Glucose Metabolism in Esophageal Cancer Measured by Fractal Analysis of Fluorodeoxyglucose Positron Emission Tomography Image: Correlation between Metabolic Heterogeneity and Survival.

BACKGROUND: Intratumoral heterogeneity is a well-recognized characteristic feature of cancer. The purpose of this study is to assess the heterogeneity of the intratumoral glucose metabolism using fractal analysis, and evaluate its prognostic value in patients with esophageal squamous cell carcinoma (ESCC). METHODS: 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) studies of 79 patients who received curative surgery were evaluated. FDG-PET images were analyzed using fractal analysis software, where differential box-counting method was employed to calculate the fractal dimension (FD) of the tumor lesion. Maximum standardized uptake value (SUVmax) and FD were compared with overall survival (OS). RESULTS: The median SUVmax and FD of ESCCs in this cohort were 13.8 and 1.95, respectively. In univariate analysis performed using Cox's proportional hazard model, T stage and FD showed significant associations with OS (p = 0.04, p < 0.0001, respectively), while SUVmax did not (p = 0.1). In Kaplan-Meier analysis, the low FD tumor (<1.95) showed a significant association with favorable OS (p < 0.0001). In wthe multivariate analysis among TNM staging, serum tumor markers, FD, and SUVmax, the FD was identified as the only independent prognostic factor for OS (p = 0.0006; hazards ratio 0.251, 95% CI 0.104-0.562). CONCLUSION: Metabolic heterogeneity measured by fractal analysis can be a novel imaging biomarker for survival in patients with ESCC.

A Case of G-CSF-Producing Histiocytic Sarcoma of the Stomach.

No reports have been published to date regarding primary gastric granulocyte colony-stimulating factor (G-CSF)-producing histiocytic sarcoma. We encountered a case of primary gastric histiocytic sarcoma that also fulfilled the criteria for a G-CSF-producing tumor. A 75-year-old man was diagnosed with gastric cancer with poorly differentiated adenocarcinoma. The patient's white blood cell count was elevated to 20,700/µL, and the G-CSF level was elevated to 380 pg/mL. A computed tomography scan showed hepatic infiltration; therefore, a preoperative diagnosis of T4 (liver) N2H0M0 cStage IV gastric cancer was made, and surgery was performed. No. 11d lymphatic metastasis was noted, resulting in invasion of the pancreatic tail, and combined resection of the liver, pancreas, and spleen was conducted with complete gastrectomy. The results of hematoxylin-eosin and immunohistochemical staining were subsequently assessed. On discharge, the G-CSF level had fallen to 22.7 pg/mL. Currently, the patient is still alive and has experienced no recurrence approximately 4 years after the operation.

Preoperative hepatic CT perfusion as an early predictor for the recurrence of esophageal squamous cell carcinoma: initial clinical results.

Reports suggest that hepatic blood flow may have an association with cancer progression. The aim of the present study was to evaluate whether the hepatic blood flow measured by CT perfusion (CTP) may identify patients at high­risk for postoperative recurrence of esophageal squamous cell carcinoma (ESCC). Prior to surgery, hepatic CTP images were obtained using a 320-row area detector CT. The data were analyzed by a commercially available software based on the dual input maximum slope method, and arterial blood flow (AF, ml/min/100 ml tissue), portal blood flow (PF, ml/min/100 ml tissue) and perfusion index [PI (%) = AF/AF + PF x 100] were measured. These parameters were compared with the pathological stage and outcome of the ESCC patients. Forty-five patients with ESCC were eligible for this study. The median follow-up period was 17 months, and recurrences were observed in 9 patients (20%). The preoperative PI values of the 9 patients with recurrence were significantly higher than those of the 36 patients without recurrence (23.9 vs. 15.9, P=0.0022). Patients were categorized into the following two groups; high PI (>20) and low PI (<20). The recurrence-free survival of the low PI group was significantly better than that of the high PI group (P<0.0001). A multivariate analysis showed that a high PI was an independent risk factor for recurrence (odds ratio, 19.1; P=0.0369).Therefore, the preoperative PI of the liver may be a useful imaging biomarker for predicting the recurrence of patients with esophageal cancer.

S-1 monotherapy as second- or third-line chemotherapy for unresectable and recurrent esophageal squamous cell carcinoma.

PURPOSE: S-1 is widely used for various cancers. It may be useful for esophageal squamous cell carcinoma (ESCC); however, there are insufficient data. The purpose is to provide results of an analysis of S-1 monotherapy for unresectable and recurrent ESCC. PATIENTS AND METHODS: Twenty patients with histologically proven ESCC who were previously treated with other chemo(radio)therapies were treated with S-1 alone as second- or third-line chemotherapy. RESULTS: A complete response (CR) was observed in 1 case (5%). A partial response (PR), stable disease (SD), and progressive disease (PD) were seen in 4 (20.0%), 7 (35.0%), and 8 (40.0%) cases, respectively. Two cases (10%) of anemia, 1 case (5%) of leukopenia, 3 cases (15%) of fatigue, and 3 cases (15%) of diarrhea were observed as grade 3 toxicity; however, there were no cases of grade 4 toxicity. The 1-year progression-free survival (PFS) rate was 10.0%, and the median PFS was 100 days. The 1-year overall survival (OS) was 30.5%, and the median OS was 330 days. The 1-year PFS rate in CR/PR/SD and PD was 16.7 and 0%, and the median survival time was 120 and 40 days. CONCLUSION: S-1 is a promising new drug which can be used as a second- or third-line chemotherapy for ESCC.

[Evaluation of false-negative lymph nodes diagnosed by fludeoxy glucose-positron emission tomography in cases of metastatic esophageal squamous cell carcinoma].

We have encountered many cases wherein the metastatic nest of esophageal squamous cell carcinoma occupied only a small space in the lymph nodes because of which computed tomography( CT) and fludeoxy glucose( FDG)-positron emission tomography( PET) could not detect the lymph node metastasis satisfactorily. The false-negative lymph nodes that were not detected by FDG-PET before surgery were smaller in diameter, rate of occupation, and area of occupation than the true-positive lymph nodes. The smallest area of the cancer nest in the true-positive group was 7.5 mm2, and therefore, it was reasonable to consider a 5-mm diameter area as the criteria for correct diagnosis by FDG-PET. Most of the false-negative lymph nodes with a large area of carcinoma were attached to the primary tumor; therefore, they could not be precisely identified. The detection of false-negative lymph nodes by FDG-PET was not precise because of increases in the quantity of stroma-like cells in poorly differentiated carcinomas and in fibrosis caused by neoadjuvant therapy in the lymph nodes.

Utility of arterial phase of dynamic CT for detection of intestinal ischemia associated with strangulation ileus.

AIM: To clarify the usefulness of arterial phase scans in contrast computed tomography (CT) imaging of strangulation ileus in order to make an early diagnosis. METHODS: A comparative examination was carried out with respect to the CT value of the intestinal tract wall in each scanning phase, the CT value of the content in the intestinal tract, and the CT value of ascites fluid in the portal vein phase for a group in which ischemia was observed (Group I) and a group in which ischemia was not observed (Group N) based on the pathological findings or intra-surgical findings. Moreover, a comparative examination was carried out in Group I subjects for each scanning phase with respect to average differences in the CT values of the intestinal tract wall where ischemia was suspected and in the intestinal tract wall in non-ischemic areas. RESULTS: There were 15 subjects in Group I and 30 subjects in Group N. The CT value of the intestinal tract wall was 41.8 ± 11.2 Hounsfield Unit (HU) in Group I and 69.6 ± 18.4 HU in Group N in the arterial phase, with the CT value of the ischemic bowel wall being significantly lower in Group I. In the portal vein phase, the CT value of the ischemic bowel wall was 60.6 ± 14.6 HU in Group I and 80.7 ± 17.7 HU in Group N, with the CT value of the ischemic bowel wall being significantly lower in Group I; however, no significant differences were observed in the equilibrium phase. The CT value of the solution in the intestine was 18.6 ± 9.5 HU in Group I and 10.4 ± 5.1 HU in Group N, being significantly higher in Group I. No significant differences were observed in the CT value of the accumulation of ascites fluid. The average difference in the CT values between the ischemic bowel wall and the non-ischemic bowel wall for each subject in Group I was 33.7 ± 20.1 HU in the arterial phase, being significantly larger compared to the other two phases. CONCLUSION: This is a retrospective study using a small number of subjects; however, it suggests that there is a possibility that CT scanning in the arterial phase is useful for the early diagnosis of strangulation ileus.