Impact of body mass index on complications following pancreatectomy:Ten-year experience at National Cancer Center in China

AIM: To examine the impact of body mass index(BMI)on outcomes following pancreatic resection in the Chinese population.METHODS: A retrospective cohort study using prospectively collected data was conducted at the Cancer Hospital of the Chinese Academy of Medical Sciences, China National Cancer Center. Individuals who underwent pancreatic resection between January2004 and December 2013 were identified and included in the study. Persons were classified as having a normal weight if their BMI was < 24 kg/m2 and overweight/obese if their BMI was ≥ 24 kg/m2 as defined by the International Life Sciences Institute Focal Point in China. A χ 2 test(for categorical variables) or a t test(for continuous variables) was used to examine the differences in patients' characteristics between normal weight and overweight/obese groups. Multiple logistic regression models were used to assess the associationsof postoperative complications, operative difficulty,length of hospital stay, and cost with BMI, adjusting for age, sex, and type of surgery procedures.RESULTS: A total of 362 consecutive patients with data available for BMI calculation underwent pancreatic resection for benign or malignant disease from January1, 2004 to December 31, 2013. Of the 362 patients,156 were overweight or obese and 206 were of normal weight. One or more postoperative complications occurred in 35.4% of the patients following pancreatic resection. Among patients who were overweight or obese, 42.9% experienced one or more complications,significantly higher than normal weight(29.6%)individuals(P = 0.0086). Compared with individuals who had normal weight, those with a BMI ≥ 24.0kg/m2 had higher delayed gastric emptying(19.9% vs5.8%, P < 0.0001) and bile leak(7.7% vs 1.9%, P =0.0068). There were no significant differences seen in pancreatic fistula, gastrointestinal hemorrhage, reoperation,readmission, or other complications. BMI did not show a significant association with intraoperative blood loss, operative time, length of hospital stay, or cost.CONCLUSION: Higher BMI increases the risk for postoperative complications after pancreatectomy in the Chinese population. The findings require replication in future studies with larger sample sizes.

Anorectal malignant melanomas: Retrospective experience with surgical management

AIM: To present the experience and outcomes of the surgical treatment for the patients with anorectal melanoma from the Cancer Hospital, Chinese Academy of Medical Sciences. METHODS: Medical records of the diagnosis, surgery, and follow-up of 56 patients with anorectal melanoma who underwent surgery between 1975 and 2008 were retrospectively reviewed. The factors predictive for the survival rate of these patients were identified using multivariate analysis. RESULTS: The 5-year survival rate of the 56 patients with anorectal melanoma was 20%, 36 patients underwent abdominoperineal resection (APR) and 20 patients underwent wide local excision (WLE). The rates of local recurrence of the APR and WLE groups were 16.13% (5/36) and 68.75% (13/20), (P = 0.001), and the median survival time was 22 mo and 21 mo, respectively (P = 0.481). Univariate survival analysis demonstrated that the number of tumor and the depth of invasion had significant effects on the survival (P < 0.05). Multivariate analysis showed that the number of tumor [P = 0.017, 95% confidence interval (CI) = 1.273-11.075] and the depth of invasion (P = 0.015, 95% CI = 1.249-7.591) were independent prognostic factors influencing the survival rate. CONCLUSION: Complete or R0 resection is the first choice of treatment for anorectal melanoma, prognosis is poor regardless of surgical approach, and early diagnosis is the key to improved survival rate for patients with anorectal melanoma.

Tumors of the angle of Treitz: A single-center experience

AIM:To explore the feasibility and oncologic outcomes of segmental jejunal resection on the left side of the mesenteric vessels in patients with tumors of the angle of Treitz using data from a single center.METHODS:Thirteen patients with tumors of the angle of Treitz who underwent surgery at our institution were prospectively followed.A segmental jejunal resection on the left side of the mesenteric vessels was performed in all patients.Formalin-fixed and paraffin-embedded tumor samples were examined.The primary end point of this analysis was disease-free survival.RESULTS:In this study,there were 8 males and 5females(mean age,50.1 years;range,36-74 years).The mean tumor size was 8.1 cm(range,3.2-15 cm).Histologic examination showed 11 gastrointestinal stromal tumors(GISTs)and 2 adenocarcinomas.Five of the GIST patients presented with potential low risk,and 6presented with intermediate and high risk,according to the National Institutes of Health criteria.One potentially high-risk patient showed tumor progression at 46 mo and died 52 mo after surgery.One patient with locally advanced adenocarcinoma received neoadjuvant chemotherapy and adjuvant radiotherapy,but the disease progressed,and the patient died 9 mo after surgery.One GIST patient without progression died 16 mo after surgery because of a postoperative intestinal obstruction.The median overall survival rate was 84.6 mo,and the median disease-free survival rate was 94.5 mo.CONCLUSION:The overall survival of patients with tumors of the angle of Treitz was encouraging even when the tumor size was relatively large.A segmental resection on the left side of the mesenteric vessels is considered to be a reliable and curative option for tumors of the angle of Treitz.

G-CSF is a key modulator of MDSC and could be a potential therapeutic target in colitis-associated colorectal cancers

Granulocyte colony-stimulating factor （G-CSF） is an essential regulator of neutrophil trafficking and is highly expressed in multiple tumors. Myeloid derived suppressor cells （MDSCs） promote neoplastic progression through multiple mechanisms by immune suppression. Despite the findings of G-CSF function in colon cancer progression, the precise mechanism of G-CSF on MDSCs regulation and its blockade effects on tumor growth remains a worthy area of investigation. In this study we observed an overexpression of G-CSF in a mouse colitis-associated cancer （CAC） model, which was consistent with the accumulation of MDSCs in mouse colon tissues. Further in vitro studies demonstrated that G-CSF could promote MDSCs survival and activation through signal transducer and activator of transcription 3 （STAT3） signaling pathway. Moreover, compared with isotype control, anti-G-CSF mAb treatment demonstrated reduced MDSC accumulation, which led to a marked decrease in neoplasm size and number in mice. Our results indicated that G-CSF is a critical regulating molecule in the migration, proliferation and function maintenance of MDSCs, which could be a potential therapeutic target for cancer.

Surgical management for carcinoma of the gallbladder： a single-institution experience in 25 years

Background Gallbladder carcinoma is rare and associated with dismal outcomes. Radical surgery is the only curative treatment, and options for adjuvant therapy remain limited. This study aimed to determine the factors influencing outcome of treatment in patients with gallbladder carcinoma, and to identify the patients who might benefit from radical surgery and adjuvant therapy. Methods Medical records and follow-up histories of 150 patients with gallbladder carcinoma who had undergone surgery between April 1980 and December 2005 were retrospectively reviewed. The factors predictive for the survival of the patients were identified using multivariate analysis. Results Surgery for gallbladder cancer was associated with an overall 5-year survival rate of 26.2%. After curative resection （40% of the patients）, the 5-year survival rate was 60.3%. The patients who underwent R0 resection had a significantly longer median survival （97.3 months） than those who had R1/R2 resection （8.3 months） or only laparotomy （3.7 months） （P 〈0.0001）. Univariate analysis showed that resectability, American Joint Committee on Cancer staging, tumor grade, adjuvant therapy, jaundice at presentation, depth of tumor invasion, lymph node involvement, distant metastasis, and carcinoembryonic antigen level were statistically significant predictors for survival. Multivariate analysis revealed American Joint Committee on Cancer staging and resectability were independent prognostic factors for survival. The patients who underwent noncurative resection might benefit from adjuvant therapy （median survival, 12.4 months vs 7.2 months, P=-0.006）. Conclusions Favorable survival rate can be achieved after curative resection, even for selected patients with advanced disease. Adjuvant therapy may improve the survival of patients with gallbladder carcinoma.

Mismatch repair, minichromosome maintenance complex component 2, cyclin A, and transforming growth factor β receptor type Ⅱ as prognostic factors for colorectal cancer： results of a 10-year prospective study using tissue microarray analysis

Background The expression of genes encoding a number of pathogenetic pathways involved in colorectal cancer could potentially act as prognostic markers. Large prospective studies are required to establish their relevance to disease prognosis.Methods We investigated the relevance of 19 markers in 790 patients enrolled in a large randomised trial of 5-fluorouracil using immunohistochemistry and chromogenic in situ hybridisation. The relationship between overall 10-year survival and marker status was assessed.Results Minichromosome maintenance complex component 2 （MCM2） and cyclin A were significantly associated with overall survival. Elevated MCM2 expression was associated with a better prognosis （HR=0.63, 95%CI： 0.46-0.86）.Cyclin A expression above the median predicted an improved patient prognosis （HR=0.71, 95%CI： 0.53-0.95）. For mismatch repair deficiency and transforming growth factor β receptor type Ⅱ （TGFBRII） overexpression there was a borderline association with a poorer prognosis （HR=0.69, 95%C/： 0.46-1.04 and HR=2.11, 95%CI： 1.02-4.40,respectively）. No apparent associations were found for other markers.Conclusion This study identified cell proliferation and cyclin A expression as prognostic indicators of patient outcome in colorectal cancer.

D)iagnosis of colon cancer with Fourier transform infrared ;pectroscopy on the malignant colon tissue samples

Background Fourier transform infrared spectroscopy （FT-IR） combined with chemometrics discriminant analysis technology could improve diagnosis. The present study aimed to evaluate the effects of FT-IR on malignant colon tissue samples in diagnosis of colon cancer. Methods Principal component analysis （PCA） and support vector machine classification were used to discriminate FT-IR spectra from malignant and normal tissue. Colon tissues samples from 85 patients were used to demonstrate the procedure. Results For this set of colon spectral data, the sensitivity and specificity of the support vector machine （SVM） classification were found both higher than 90%. Conclusions FT-IR provided important information about cancerous tissue, which could be used to discriminate malignant from normal tissues. The combination of PCA and SVM classification indicated that FT-IR has a potential clinical application in diagnosis of colon cancer.

Clinicopathological and prognostic features of hepatoid adenocarcinoma of the stomach

Background Hepatoid adenocarcinoma of the stomach （HAS） is a rare type of gastric carcinoma, which has its unique clinicopathological features and poorer prognosis than that of the ordinary gastric adenocarcinoma. At present, there is still a lack of understanding about this disease. The current study aimed to summarize and discuss the clinical,pathological, immunohistochemical, and prognostic features of this disease.Methods A total of 20 patients of HAS were retrospectively studied. All the patients were treated in Cancer Hospital of Chinese Academy of Medical Sciences between March 1998 and October 2009. Statistical analysis, including the Kaplan-Meier method, log-rank test and Cox model, were performed by the SPSS 15.0 software.Results Seventeen patients （85%） had at least 1 lymph node metastases; 17 patients （85%） received postoperative immunohistochemical examinations, with an alpha-fetoprotein （AFP） positive rate of 94.1% （16/17）; 14 patients had distant metastases （including 12 liver metastases, 1 lung metastasis, and 1 celiac widespread metastases）, and one simultaneously had anastomotic recurrence and liver metastases. The overall survival time was 2-99 months （median：12.0 months）. The 3-year survival rate of the 20 patients was 17.2%. The 3-year survival rate of patients with complete hepatocyte-like regions and those with both hepatocellular carcinoma and adenocarcinoma regions was 20.0% and 17.5%, respectively （P=0.361）. The survival difference among the radical surgery group, palliative surgery group and no surgery group was statistically significant （P=0.022）. The Kaplan-Meier method and log-rank test showed that surgery,pTNM stages, and adjuvant chemotherapy were associated with prognosis （P 〈0.05）. The Cox model only confirmed that the pTNM stages and adjuvant chemotherapy had statistical significance for the prognosis of HAS （P〈0.05） due to the limited cases.Conclusions HAS is a special type of gastric carcinoma and has a poor prognosis. The pTNM stage is an independent risk factor for HAS. Multidisciplinary therapy, including surgery and chemotherapy, may improve the prognosis of HAS.

Excision Repair Cross-complementation Group 1 is a Prognostic Biomarker in Patients with Colorectal Cancer Receiving Chemotherapy

Background：Conflicting results about the association between expression level of excision repair cross-complementation group 1 （ERCC1） and clinical outcome in patients with colorectal cancer （CRC） receiving chemotherapy have been reported.Thus,we searched the available articles and performed the meta-analysis to elucidate the prognostic role of ERCC1 expression in patients with CRC.Methods：A thorough literature search using PubMed （Medline）,Embase,Cochrane Library,Web of Science databases,and Chinese Science Citation Database was conducted to obtain the relevant studies.Pooled hazard ratios （HRs） or odds ratios （ORs） with 95% confidence intervals （CIs） were calculated to estimate the results.Results：A total of 11 studies were finally enrolled in this meta-analysis.Compared with patients with lower ERCC1 expression,patients with higher ERCC1 expression tended to have unfavorable overall survival （OS） （HR =2.325,95% CI：1.720-3.143,P 〈 0.001）,progression-free survival （PFS） （HR =1.917,95% CI：1.366-2.691,P 〈 0.001） and poor response to chemotherapy （OR =0.491,95% CI：0.243-0.990,P =0.047）.Subgroup analyses by treatment setting,ethnicity,HR extraction,detection methods,survival analysis,and study design demonstrated that our results were robust.Conclusions：ERCC1 expression may be taken as an effective prognostic factor predicting the response to chemotherapy,OS,and PFS.Further studies with better study design and longer follow-up are warranted in order to gain a deeper understanding of ERCC 1＇s prognostic value.

Risk factors associated with postoperative hospital stay after pancreaticoduodenectomy： a retrospective study

Background Postoperative hospital stay after pancreaticoduodenectomy （PD） is relatively longer than after other gastrointestinal operations.The aim of the current study was to investigate the risk factors associated with prolonged hospital stay after PD.Methods Patients who had PD at the Cancer Hospital of Chinese Academy of Medical Sciences between December 2008 and November 2012 were selected for this retrospective study.Clinical and pathological data were collected and analyzed.The primary outcome was postoperative length of stay.Normal discharge or recovery was defined as a postoperative hospital stay of no more than 10 days; otherwise it was defined as delayed discharge or recovery （including hospital death）.Results Atotal of 152 patients were enrolled in the present study.Postoperative hospital stay was （19.7±7.7） days （range 7-57）.Of the 152 patients,67 were discharged within the normal time and 85 had delayed discharge.Postoperative complications occurred in 62.5% （95/152）,and the mortality rate was 3.29% （5/152）.Multiple regression analysis showed that delayed discharge was significantly associated with postoperative complications （adjusted odds ratio （OR） 10.40,95% confidence interval （CI） 3.58-30.22）,age （adjusted OR 4.09,95% CI 1.16-14.39）,body mass index （BMI） （adjusted OR 4.40,95% CI 1.19-16.23）,surgical procedure （adjusted OR 26.14,95% CI 4.94-153.19）,blood transfusion （adjusted OR 7.68,95% Cl 2.09-28.27）,and fluid input （adjusted OR 3.47,95% CI 1.24-11.57）.Conclusions Postoperative complications increase the time to postoperative hospital discharge.The length of hospital stay after PD is also associated with age,BMI,blood transfusion,surgical procedure,and fluid input.Further studies with more patients are needed in future.

BRCA2 promoter polymorphism is associated with breast cancer prognosis in Chinese women

Background Breast cancer 2 （BRCA2） is an important breast cancer-susceptibility gene.Promoter polymorphisms in BRCA2 may affect its transcription and be associated with cancer prognosis.Methods We identified five polymorphisms of the BRCA2 promoter region by in silico searching and direct sequencing：-254A/G （rs3092989）,-908A/G （rs206117）,-1134A/G （rs206115）,-1144C/T （rs206116）,and-1260CTTAGA/-（rs3072036）.The-908A/G,-1134A/G,-1144C/T,and-1260CTTAGA/-polymorphisms were genotyped by direct sequencing in 491 breast cancer patients,and the-254A/G polymorphism was genotyped by Sequenom.Results The-1144C/T polymorphism was associated with clinical outcome.Carriers of the TT genotype had longer disease-free intervals （DFIs,P=0.029）,especially among patients with sporadic unilateral breast cancer （P=0.010）.Linkage disequilibrium （LD） analysis showed that all the five single nucleotide polymorphisms （SNPs） were in LD （D＇〉0.8）.Carriers of haplotypes containing the-1144T allele showed longer DFIs （P=0.049）,and the result was more significant in patients with sporadic unilateral cancer （P=0.018）.There were no significant associations between the other polymorphisms and DFI.Conclusions The results of this study suggest that homozygosity for the BRCA2 T（-1144） allele is associated with a longer DFI in Chinese women with breast cancer.Further functional studies are warranted to clarify this relationship.