Ecological study of gastric cancer in Brazil:Geographic and time trend analysis

AIM:To investigate the geographic distributions and time trends of gastric cancer(GC)incidence and mortality in Brazil.METHODS:An ecological study of the DATASUS registry was conducted by identifying hospitalizations for GC between January 2005 and December 2010.The data included information on the gender,age,and town of residence at the time of hospital admission and death.RESULTS:The GC rates,adjusted according to available hospital beds,decreased from 13.8 per 100000in 2005 to 12.7 per 100000 in 2010.The GC rates decreased more among the younger age groups,in which the male-to-female difference also decreased in comparison to the older age groups.Although the lethality rates tended to increase with age,young patients were proportionally more affected.The spatial GC distribution showed that the rates were higher in the south and southeast.However,while the rates decreased in the central-west and south,they increased in the northern regions.A geographic analysis showed higher rates of GC in more urbanized areas,with a coast-toinland gradient.Geographically,GC lethality overlapped greatly with the hospital admission rates.CONCLUSION:The results of this study support the hypothesis of a critical role for environmental factors in GC pathogenesis.The declining rates in young patients,particularly males,suggest a relatively recent decrease in the exposure to risk factors associated with GC.The spatial distribution of GC indicates an ongoing dynamic change within the Brazilian environment.     

Comparison of laparoscopic versus open pancreaticoduodenectomy in patients with resectable pancreatic ductal adenocarcinoma: A propensity score-matching analysis of long-term survival

BackgroundMany studies have shown the short-term feasibility and effectiveness of laparoscopic pancreaticoduodenectomy (LPD) are comparable to open pancreaticoduodenectomy (OPD). However, the long-term oncological safety of LPD in patients with pancreatic ductal adenocarcinoma (PDAC) remains to be elucidated.MethodsPatients who underwent LPD or OPD between July 2014 and July 2018 at our institution were identified, and those with resectable, pathologically diagnosed PDAC were analyzed. The primary outcome was overall survival (OS). Propensity score-matching (PSM) analysis was performed to balance the baseline characteristics between groups. Cox proportional hazards model was constructed to determine independent predictors of OS.ResultsThe original cohort consisted of 64 LPD and 80 OPD cases, in which, the laparoscopic group had a significantly longer median OS (25 vs. 17 months; P = 0.034). A higher proportion of laparoscopic patients received adjuvant therapy (51.6 vs. 32.5%; P = 0.021). PSM analysis identified 47 patient pairs. No significant differences in OS (21 vs. 17 months; P = 0.220) or adjuvant therapy utilization (53.2 vs. 38.3%; P = 0.248) were observed between the matched groups. Multivariate Cox analyses showed that receiving adjuvant therapy (HR = 0.44; 95% CI, 0.28–0.68), histopathological differentiation (poor vs. moderate-to-well differentiation; HR = 1.93; 95% CI, 1.26–2.95), and sex (female vs. male, HR = 0.47, 95% CI, 0.30–0.75) were independent predictors of OS.ConclusionsLPD can be comparable to OPD in terms of long-term safety for patients with resectable pancreatic ductal adenocarcinoma when performed in a high-volume center.     

Prehabilitation prior to surgery for pancreatic cancer: A systematic review

IntroductionPrehabilitation aims to improve fitness and outcomes of patients undergoing major surgery. This systematic review aimed to appraise current available evidence regarding the role of prehabilitation in patients undergoing oncological pancreatic resection.MethodsA systematic literature search of PUBMED, MEDLINE, EMBASE databases identified articles describing prehabilitation programmes before pancreatic resection for malignancy. Data collected included timing of prehabilitation, programme type, duration, adherence and post-operative outcome reporting.ResultsSix studies, including 193 patients were included in the final analysis. Three studies included patients undergoing neoadjuvant therapy followed by resection and 3 studies included patients undergoing upfront resection. Time from diagnosis to surgery ranged between 2 and 22 weeks across all studies. Two studies reported a professionally supervised exercise programme, and four described unsupervised programmes. Exercise programmes varied from 5 days to 6 months in duration. Adherence to exercise programmes was better with supervised programmes (99% reaching weekly activity goal vs 85%) and patients not undergoing neoadjuvant therapy (90% reaching weekly activity goal vs 82%). All studies reported improvement in muscle mass or markers of muscle function following prehabilitation. Two studies reported the impact of Prehabilitation on postoperative outcomes and Prehabilitation was associated with lower delayed gastric emptying and a shorter hospital stay with no impact on other postoperative outcomes.ConclusionEarly evidence demonstrates that Prehabilitation programmes may improve postoperative outcomes following pancreatic surgery. However current Prehabilitaton programmes for patients undergoing pancreatic resection report diverse exercise regimens with no consensus regarding timing or length of Prehabilitation, warranting a need for standardisation of Prehabilitation programmes in pancreatic surgery.     

浙江省绍兴市2009年至2013年甲状腺癌检出率及时间趋势分析

目的 分析绍兴市2009年至2013年甲状腺癌的检出率及其时间变化趋势.方法 利用2009年至2013年绍兴市居民甲状腺癌数据资料,计算甲状腺癌的检出率、中国人口标化率(中标率)、世界人口标化率(世标率)及变化百分比;采用对数直线因归法估箅枪出率的年度变化百分比(APC)进行趋势分析.结果 2009年至2013年绍兴市甲状腺癌检出数为3 290例,男性、女性比例为1∶3.69,甲状腺癌检出率为14.98/10万(男性6.39/10万,女性23.59/10万),中标率为9.13/10万(男性3.94/10万,女性14.31/10万),世标率为10.39/10万(男性4.47/10万,女性16.32/10万);2009年至2013年甲状腺癌枪出率由7.26/10万上升至27.26/10万,APC值为39.65％(P＜0.05),中标率和世标率的APC值分别为52.96％(P＜0.05)和49.48％(P＜0.05);其中男性检出率由2.42/10万上升至12.65/10万,APC值为48.44％(P＜0.05),女性检出率由12.15/10万上升至41.96/10万,APC值为37.58％ (P＜0.05).绍兴市甲状腺癌主要在25～ 59岁年龄段好发,在50 ～54岁组达到高峰(29.08/10万),各年龄组检出率女性均高于男性,且基本在2倍以上.结论 绍兴市甲状腺癌检出率较高,且呈逐年上升趋势,中青年人群尤其女性好发,应针对性地加强控制甲状腺癌的危险因素.     

Treatment strategy for pancreatic head cancer with celiac axis stenosis in pancreaticoduodenectomy: A case report and review of literature

BACKGROUND During pancreaticoduodenectomy in patients with celiac axis(CA)stenosis due to compression by the median arcuate ligament(MAL),the MAL has to be divided to maintain hepatic blood flow in many cases.However,MAL division often fails,and success can only be determined intraoperatively.To overcome this problem,we performed endovascular CA stenting preoperatively,and thereafter safely performed pancreaticoduodenectomy.We present this case as a new preoperative treatment strategy that was successful.CASE SUMMARY A 77-year-old man with a diagnosis of pancreatic head cancer presented to our department for surgery.Preoperative assessment revealed CA stenosis caused by MAL.We performed endovascular stenting in the CA preoperatively because we knew that going into the operation without a strategy could lead to ischemic complications.Double-antiplatelet therapy(DAPT)–which is needed when a stent is inserted–was then administered in parallel with neoadjuvant chemotherapy(NAC).This allowed us to administer DAPT for a sufficient period before the main pancreaticoduodenectomy procedure while obtaining therapeutic effects from NAC.Subtotal stomach-preserving pancreaticoduodenectomy was thenperformed.The operation did not require any unusual techniques and was performed safely.Postoperatively,the patient progressed well,without any ischemic complications.Histopathologically,curative resection was confirmed,and the patient had no recurrence or complications due to ischemia up to six months postoperatively.CONCLUSION Preoperative endovascular stenting,with NAC and DAPT,is effective and safe prior to pancreaticoduodenectomy in potentially resectable pancreatic cancer.     

Residual pancreatic function after pancreaticoduodenectomy is better preserved with pancreaticojejunostomy than pancreaticogastrostomy: A long-term analysis

BackgroundPancreatico-enteric anastomosis after pancreaticoduodenectomy can be performed using either a pancreaticojejunostomy (PJ) or pancreaticogastrostomy (PG). Differences in surgical outcomes are still a matter of debate, and less is known about long-term functional outcomes.MethodsTwelve years after the conclusion of a comparative study evaluating the surgical outcomes of PJ and PG (Bassi et al., Ann Surg 2005), available patients underwent morphological and functional pancreatic assessment: pancreatic volume and duct diameter measured by MRI, impaired secretion after secretin, fecal fat, fecal elastase-1 (FE-1), serum vitamin D and endocrine function. Quality of life and symptom scores were evaluated with the EORTC QLQ-C30 questionnaire.ResultsOnly 34 patients were available for assessment. No differences were found in terms of BMI variation, endocrine function, quality of life or symptoms. Exocrine function was more severely impaired after PG than after PJ (fecal fats 26.6 ± 4.1 vs 18.2 ± 3.6 g/day; FE-1 121.4 ± 6.7 vs 170.2 ± 25.5 μg/g, vitamin D 18.1 ± 1.8 vs. 23.2 ± 3.1 ng/mL). MRI assessment identified a lower pancreatic volume (26 ± 3.1 vs. 36 ± 4.1 cm³) and a more dilated pancreatic duct (4.6 ± 0.92 vs. 2.4 ± 0.18 mm) in patients with PG compared to those with PJ.ConclusionCompared to PJ, PG is associated with a more severely impaired exocrine function long-term, but they result similar endocrine function and quality of life. In patients with a long life expectancy, this should be taken into account.     

Sorafenib does not improve efficacy of chemotherapy in advanced pancreatic cancer: A GISCAD randomized phase II study

BackgroundThe RAF–MEK–ERK pathway is commonly activated in pancreatic cancer because of a high frequency of KRAS-BRAF mutations. A phase II randomized trial was designed to investigate the activity of sorafenib in combination with chemotherapy in advanced pancreatic cancer.MethodsLocally advanced or metastatic pancreatic adenocarcinoma patients were randomized in a 1:1 ratio to receive cisplatin plus gemcitabine with sorafenib 400 mg bid (arm A) or without sorafenib (arm B).ResultsOne hundred and fourteen patients were enrolled; of these, 43 (74.6%) patients progressed in arm A and 44 (82.4%) in arm B. Median progression-free survival was 4.3 months (95% CI: 2.7–6.5) and 4.5 months (95% CI: 2.5–5.2), respectively (HR = 0.92; 95% CI: 0.62–1.35). Median overall survival was 7.5 (95% CI: 5.6–9.7) and 8.3 months (95% CI: 6.2–8.7), respectively (HR = 0.95; 95% CI: 0.62–1.48). Response rates were 3.4% in arm A and 3.6% in arm B.ConclusionsSorafenib does not significantly enhance activity of chemotherapy in advanced pancreatic cancer patients, and therefore should not be assessed in phase III trials.     

胰腺癌关键基因的筛选和分析:多数据联合生物信息学分析

目的 通过多数据联合生物信息学分析,明确候选基因与胰腺癌发生发展以及预后的相关关系.方法 从Gene Expression Omnibus(GEO)下载芯片数据集GSE15471、GSE16515、GSE28735,筛选差异表达基因.通过功能富集分析,利用STRING和Cytoscape软件构建蛋白质相互作用(prot...     

Impact of vascular abnormality on contrast-enhanced CT and high C-reactive protein levels on postoperative pancreatic hemorrhage after pancreaticoduodenectomy: A multi-institutional,retrospective analysis of 590 consecutive cases

Background/Objectives: This study aimed to elucidate the efficacy of CT findings and perioperative characteristics to predict post-pancreatectomy hemorrhage (PPH): a critical complication after pancreaticoduodenectomy.MethodsThe records of 590 consecutive patients who underwent pancreaticoduodenectomy at three institutes between 2012 and 2018 were included. The presence of a vascular wall abnormality or ascites with high density (vascular abnormality) on postoperative day (POD) 5–10 contrast-enhanced CT (early CT), perioperative characteristics, and any PPH or pseudoaneurysm formation (PPH events) were analyzed through a multivariate analysis.ResultsPPH events occurred in 48 out of 590 patients (8%). The vascular abnormality on early CT and the C-reactive protein (CRP) value on POD 3 were independent risk factors for PPH events after POD5 (vascular abnormality: odds ratio 6.42, p = 0.001; CRP on POD 3: odds ratio 1.17, p = 0.016). The sensitivity of vascular abnormality for PPH events was 24% (7/29), and the positive predictive value was 30% (7/23). The combination of vascular abnormality and a high CRP value (≥15.5 mg/dL) on postoperative day 3 had a higher positive predictive value of 64% (7/11) than the vascular abnormality alone. None of the seven PPH events that occurred more than one month after surgery were foreseen via early CT.ConclusionThe combination of vascular abnormality and high CRP value was associated with increasing risk of PPH events after pancreaticoduodenectomy, but the low sensitivity of early CT must be noted as an important shortcoming. The normal findings on early CT could not eliminate the risk of late PPH.     

Selection criteria in resectable pancreatic cancer: A biological and morphological approach

Pancreatic ductal adenocarcinoma (PDA) remains one of the most aggressive tumors with a low rate of survival. Surgery is the only curative treatment for PDA, although only 20% of patients are resectable at diagnosis. During the last decade there was an improvement in survival in patients affected by PDA, possibly explained by the advances in cancer therapy and by improve patient selection by pancreatic surgeons. It is necessary to select patients not only on the basis of surgical resectability, but also on the basis of the biological nature of the tumor. Specific preoperative criteria can be identified in order to select patients who will benefit from surgical resection. Duration of symptoms and level of carbohydrate antigen 19.9 in resectable disease should be considered to avoid R1 resection and early relapse. Radiological assessment can help surgeons to distinguish resectable disease from borderline resectable disease and locally advanced pancreatic cancer. Better patient selection can increase survival rate and neoadjuvant treatment can help surgeons select patients who will benefit from surgery.     

Pain sensation in pancreatic diseases is not uniform: The different facets of pancreatic pain

AIM: To systematically characterize specific pain patterns in the most frequent pancreatic diseases.METHODS: Pain in patients with chronic pancreatitis (n = 314), pancreatic cancer (n = 469), and other pancreatic tumors (n = 249) including mucinous (n = 20) and serous cystadenoma (n = 31), invasive (n = 37) and non-invasive intraductal papillary mucinous neoplasia (IPMN; n = 48), low stage (n = 18) and high stage neuroendocrine neoplasia (n = 44), and ampullary cancer (n = 51) was registered and correlated with clinicopathological data. Survival times were estimated by the Kaplan-Meier method. Patients alive at the follow-up time were censored. Survival curves were compared statistically using the log-rank test.RESULTS: Forty-nine point one percent of pancreatic cancer patients revealed no pain, whereas in chronic pancreatitis only 18.3% were pain free. In contrary, moderate/severe pain was registered in 15.1% in pancreatic cancer patients that was increased in chronic pancreatitis with up to 34.2%. Serous cystadenoma was asymptomatic in most cases (58.1%), whereas 78.9% of all mucinous cystadenoma patients suffered pain. In neuroendocrine neoplasia pain was not a key clinical symptom since 64% of low stage neuroendocrine neoplasia and 59% of high stage neuroendocrine neoplasia patients were pain free. Cancer localization in the pancreatic body and patients with malignant pancreatic neoplasms were associated with more severe pain. Tumor grading and stage did not show any impact on pain. Only in pancreatic cancer, pain was directly associated with impaired survival.CONCLUSION: Pancreatic pain depicts different patterns of abdominal pain sensation according to the respective pancreatic disorder and does not allow a unification of the term pancreatic pain.     

Autoantibody-targeted TAAs in pancreatic cancer: A comprehensive analysis

BackgroundPancreatic cancer is one of the leading causes of cancer mortality and lacks efficient biomarkers for early diagnosis. In the early stages of pancreatic cancer, humoral immunity can respond to a certain amount of tumor-associated antigens (TAAs) with the production of corresponding autoantibodies. Such autoantibody-targeted TAAs (autoTAAs) are highly likely to indicate early events during pancreatic carcinogenesis. Herein, we performed a comprehensive analysis of these autoTAAs to explore their physiological function and their involvement and prognostic value in pancreatic cancer.MethodsWe first searched the literature to identify the autoTAAs. A PPI network of these autoTAAs was constructed, and core network modules were extracted by Cytoscape software. GO annotation and KEGG pathway analysis were performed to analyze the main physiological functions of these autoTAAs. The prognostic value of autoTAAs in pancreatic cancer was analyzed by using RNA-seq data generated by TCGA.ResultsThe PPI network including 98 autoTAAs was constructed, and 2 subgroups were extracted as core modules. GO and KEGG analysis revealed that key functions and pathways of these autoTAAs were significantly enriched in nucleotide repair, protein synthesis, and cancer-associated events. MSH2, EZR, PGK1, VCL and ANXA2 have prognostic value in pancreatic cancer, and high mRNA expression of these 5 proteins is associated with unfavorable prognosis in pancreatic cancer.ConclusionsAutoTAAs may be associated with early events in the carcinogenesis of pancreatic cancer. MSH2, EZR, PGK1, VCL and ANXA2 predict poor prognosis in pancreatic cancer. Some autoTAAs also have prognostic value in other cancers.     

A prospective multicenter trial evaluating diagnostic validity of multivariate analysis and individual serum marker in differential diagnosis of pancreatic cancer from benign pancreatic diseases

Summary Conclusion: A multivariate analysis of CAMPAS-PX2 can increase its diagnostic accuracy in differential diagnosis of pancreatic cancer from benign pancreatic or extrapancreatic disease, when compared with CA19-9 alone. However, the improvement in diagnostic accuracy is still not satisfactory in spite of an elaborate combination of serum markers in diagnosis for pancreatic cancer. Optimal combination of a sensitive serum marker and another diagnostic modality, such as ultrasonography, can be a practical way to improve important diagnostic and cost-effectiveness in diagnosis for pancreatic cancer. Background: No specific biological test has yet been developed for diagnosis of pancreatic cancer, although increasing numbers of tumor markers become available. For improvement in the diagnostic and cost effectiveness, it is important to select optimal combination of several serum markers relatively independent of each other. Methods: A new model of discriminant function, computer-aided multivariate and pattern analysis system for pancreatic cancer examination 2 (CAMPAS-PX2), was developed based on the data of the 23 serum tumor markers from the first prospective trial (1) to differentiate between pancreatic cancer and benign pancreatobiliary disease by logistic regression analysis using a stepwise selection method. In 243 patients suspected of having pancreatic cancer by a multicenter prospective study, the diagnostic value of the multivariate analysis, CAMPAS-PX2, was compared with the 23 markers. Results: Pancreatic cancer was subsequently identified in 27 patients. Positive in disease, negative in health, and area under receiver operating characteristic curve were significantly higher by CAMPAS-PX2 (89, 87, 91%) than by CA19-9 (78, 82, 84%), the most sensitive marker among the 23 markers.     

Update on the management of pancreatic cancer:Surgery is not enough

Pancreatic ductal adenocarcinoma(PDAC) represents the fourth cause of death in cancer and has a 5-year survival of < 5%.Only about 15% of the patients present with a resectable PDAC with potential to undergo "curative" surgery.After surgery,local and systemic recurrence,is though very common.The median survival of resected patients with adjuvant chemotherapy after surgery is only 20-23 mo.This underscores the significant need to improve PDAC management strategies.Increased survival rate is dependent on new breakthroughs in our understanding of not at least tumor biology.The aim of this review is to update and comment on recent knowledge concerning PDAC biology and new diagnostics and treatment modalities.One fundamental approach to improve survival rates is by earlier and improved diagnosis of the disease.In recent years,novel blood-based biomarkers have emerged based on genetic,epigenetic and protein changes in PDAC with very promising results.For biomarkers to enter clinical practice they need to have been developed using adequate control groups and provide high sensitivity and specificity and by this identify patients at risk already in a pre-symptomatic stage.Another way to improve outcomes,is by employing neoadjuvant treatments thereby increasing the number of resectable cases.Novel systemic treatment regimes like FOLFIRINOX and nab-paclitaxel have demonstrated improvements in prolonging survival in advanced cases,but long-term survival is still scarce.The future improved understanding of PDAC biology will inevitably render new treatment options directed against both the cancer cells and the surrounding microenvironment.     

Elderly patients had more severe postoperative complications after pancreatic resection:A retrospective analysis of 727 patients

AIM To examine the impact of aging on the short-term outcomes following pancreatic resection(PR) in elderly patients.METHODS A retrospective cohort study using prospectively collected data was conducted at the China National Cancer Center. Consecutive patients who underwent PR from January 2004 to December 2015 were identifiedand included. ‘Elderly patient' was defined as ones age 65 and above. Comorbidities, clinicopathology, perioperative variables, and postoperative morbidity and mortality were compared between the elderly and young patients. Univariate and multivariate analyses were performed using the Cox proportional hazard model for severe postoperative complications(grades Ⅲb-Ⅴ).RESULTS A total of 454(63.4%) patients were 65-yearsold and 273(36.6%) patients were ≥ 65-yearsold, respectively. Compared to patients 65-yearsold, elderly patients had worse American Society of Anesthesiologists scores(P = 0.007) and more comorbidities(62.6% vs 32.4%, P 0.001). Elderly patients had more severe postoperative complications(16.8% vs 9.0%, P = 0.002) and higher postoperative mortality rates(5.5% vs 0.9%, P 0.001). In the multivariate Cox proportional hazards model for severe postoperative complications, age ≥ 65 years [hazard ratio(HR) = 1.63; 95% confidence interval(CI): 1.18-6.30], body mass index ≥ 24 kg/m~2(HR = 1.20, 95%CI: 1.07-5.89), pancreaticoduodenectomy(HR = 4.86, 95%CI: 1.20-8.31) and length of operation ≥ 241 min(HR = 2.97; 95%CI: 1.04-6.14) were significant(P = 0.010, P = 0.041, P = 0.017 and P = 0.012, respectively).CONCLUSION We found that aging is an independent risk factor for severe postoperative complications after PR. Our results might contribute to more informed decision-making for elderly patients.     

Telomerase activity in pancreatic juice differentiates pancreatic cancer from chronic pancreatitis: A meta-analysis

Background/objectiveTo evaluate the usefulness of genetic markers in pancreatic juice (PJ), and the combination of these markers with telomerase activity in the differential diagnosis of pancreatic ductal adenocarcinoma (PDAC) from chronic pancreatitis.MethodsWe conducted a meta-analysis for the diagnostic utility of the four major altered genes in PDAC (KRAS, CDKN2A/p16, TP53, and SMAD4/DPC4), telomerase activity, and a combination assay using PJ samples. A literature search was conducted in MEDLINE, Cochrane Library, and Web of Science. Data were pooled and presented as diagnostic sensitivity and specificity with 95% confidence intervals (CIs).ResultsThirty-nine studies fulfilled the inclusion criteria. Pooled estimates of KRAS analysis were as follows: sensitivity was 0.67 (95% CI, 0.63–0.71) and specificity, 0.82 (95% CI, 0.79–0.85). For telomerase activity analysis, sensitivity was 0.82 (95% CI, 0.76–0.87) and specificity, 0.96 (95% CI, 0.90–0.99). The other three tumor suppressors demonstrated low sensitivity. The data did not suggest any publication bias. A combined analysis of KRAS and telomerase activity showed a higher diagnostic sensitivity (0.94; 95% CI, 0.83–0.99) than KRAS alone. A combined analysis of telomerase activity and cytology revealed more reliable diagnostic accuracy than telomerase activity alone, with high sensitivity (0.88; 95% CI, 0.74–0.96) and specificity (1.00; 95% CI, 0.91–1.00).ConclusionsThe most reliable marker in PJ samples for diagnosis of PDAC was telomerase activity. Telomerase activity can play a central role in diagnostic analysis using PJ samples, and can increase diagnostic accuracy when combined with KRAS mutations or cytological examination.     

Statin use is associated to a reduced risk of pancreatic cancer: A meta-analysis

Background

Previous studies investigating the association between statin use and pancreatic cancer (PDAC) risk for a possible chemopreventive effect gathered heterogeneous results.