Overexpression of HSP27 and HSP70 is associated with decreased survival among patients with esophageal adenocarcinoma

BACKGROUND Overexpression of heat shock proteins (HSPs) is associated with several malignancies and contributes to the development, progression, and metastasis of cancer, in addition to the inhibition of cellular death. In recent years, there has been active research into using HSP inhibitors in several malignancies. Due to the poor prognosis of esophageal adenocarcinoma (EAC), it would be valuable to find new biomarkers for the development of cancer treatments. AIM To evaluate the expressions of HSP27 and HSP70 and their effect on survival in EAC. METHODS Immunohislochemical analyses and evaluations of HSP27 and HSP70 expression were performed on all available samples from 93 patients diagnosed with EAC between 1990 and 2007 at two university hospitals. Fifteen cases with Barrett's metaplasia and 5 control cases from the same patient population were included in the analysis. HSP expression was quantitatively assessed and classified as high or low. Kaplan-Meier analyses and Cox regression models adjusting for age and sex as well as tumor site, stage, and grade were used to evaluate the effect on survival. RESULTS Tumor stage and surgical treatment were the main prognostic factors. High HSP27 expression in cancer cases was a strong negative predictive factor, with a mean survival of 23 mo compared to the 49 mo in cases with a low expression (P = 0.018). The results were similar for HSP70, with a poorer survival of 17 mo in cases with high HSP70 expression, in contrast to 40 mo (P = 0.006) in cases with a low expression. A Cox regression survival analysis was performed, adjusting for possible confounding factors, and higher HSP27 and HSP70 expressions remained an independent negative prognostic factor. The HSPs' correlation with survival was not affected by cancer treatments. When the analysis was adjusted for all factors, the odds ratios for HSP27 and HSP70 were 3.3 (CI: 1.6-6.6, P = 0.001) and 2.2 (CI: 1.2-3.9, P = 0.02), respectively. CONCLUSION HSP27 and HSP70 overexpression is associated with poor survival in EAC, which is, to the best of our knowledge, reported for the first time.Peer reviewe

Prognostic role of radiological peritoneal cancer index in malignant peritoneal mesothelioma : national cohort study

Malignant peritoneal mesothelioma (MPeM) is a rare cancer of the mesothelial cells of the peritoneum. Computed tomography (CT) is considered the standard for first-line imaging of MPeM, diagnosis and risk stratification remains challenging. Peritoneal cancer index (PCI), as assessed by CT, is utilized in the prognostic assessment of other malignant intra-abdominal conditions; however, there is limited data concerning the utility of PCI in the diagnosis and workup of MPeM. We studied a retrospective cohort of all patients diagnosed with MPeM from 2000 to 2012 in Finland. CT and magnetic resonance imaging (MRI) were reviewed and scored by an experienced and blinded, board-certified abdominal radiologist. Additional clinical data and outcomes were obtained from Finnish Cancer Registry (FCR), the Workers' Compensations Center (WCC), and Statistics Finland (SF). Abdominal CT or MRI was available for 53 of 90 patients. The median radiographic PCI was 25. PCI score was correlated with overall survival (p = 0.004, Exp(B) = 1.064, 95% CI 1.020-1.110). PCI score >= 30 was associated with worse survival (p = 0.002), while PCIPeer reviewe

Appendiceal neoplasm risk associated with complicated acute appendicitisa population based study

PurposeAppendiceal tumors are rare, but high neoplasm rates have been reported at interval appendectomy after periappendicular abscess. Non-operative management of uncomplicated acute appendicitis has shown promising results. The data on appendiceal tumor incidence and presentation among acute appendicitis patients is limited, especially in patient cohorts differentiating between uncomplicated and complicated acute appendicitis. Objective was to assess appendiceal tumor incidence and tumor association to appendicitis in patients with uncomplicated and complicated acute appendicitis.MethodsThis nationwide population-based registry study was conducted from 2007 to 2013. The Finnish Cancer Registry and the National Institute for Health Registry were used to combine data on all appendiceal tumors and acute appendicitis diagnosis with medical reports evaluated at eight study hospitals.ResultsAltogether, 840 appendiceal tumors were identified, and out of these, 504 patient reports were reviewed, including 472 patients in this study. Tumor was diagnosed at appendectomy for suspected acute appendicitis in 276 patients (58%). In the whole study, histologically acute appendicitis and tumor were both present in 53% (n=250), and out of these, 41% (n=102) were complicated and 59% (n=148) uncomplicated acute appendicitis. The associated tumor risk was significantly higher in complicated acute appendicitis compared with uncomplicated cases (3.24% vs. 0.87%, pPeer reviewe

Cohort profile : a nationwide population-based retrospective assessment of oesophageal cancer in the Finnish National Esophago-Gastric Cancer Cohort (FINEGO)

Purpose The Finnish National Esophago-Gastric Cancer Cohort (FINEGO) was established to combine the available registry data with detailed patient information to form a comprehensive, retrospective, population-based research platform of surgically treated oesophageal and gastric cancer in Finland. This cohort profile describes the 2045 surgically treated patients with oesophageal cancer included in the FINEGO cohort. Participants Registry data were collected from the National Cancer, Patient, Education and Death Registries from 1 January 1987 to 31 December 2016. All patients over 18 years of age, who had either curative surgery, palliative surgery or salvage surgery for primary cancer in the oesophagus are included in this study. Findings to date 2045 patients had surgery for oesophageal cancer in the selected time period. 67.2% were man, and the majority had only minor comorbidities. The proportions of adenocarcinomas and squamous cell carcinomas were 43.1% and 44.4%, respectively, and 12.5% had other or missing histology. Only about 23% of patients received neoadjuvant therapy. Oesophagectomy was the treatment of choice and most patients were treated at low-volume centres, but median annual hospital volume increased over time. Median overall survival was 23 months, 5-year survival for all patients in the cohort was 32.9% and cancer-specific survival was 36.5%. Future plans Even though Finland only has a population of 5.5 million, surgery for oesophageal carcinoma has not been centralised and therefore previously reported results have mostly been small, single-centre cohorts. Because of FINEGO, we now have a population-based, unselected cohort of surgically treated patients, enabling research on national trends over time regarding oesophageal cancer, including patient characteristics, tumour histology, stage and neoadjuvant treatment, surgical techniques, hospital volumes and patient mortality. Data collection is ongoing, and the cohort will be expanded to include more detailed data from patient records and national biobanks.Peer reviewe

The association between appendicitis severity and patient age with appendiceal neoplasm histology-a population-based study

Purpose Recent studies have reported alarming appendiceal tumor rates associated with complicated acute appendicitis, especially in patients presenting with a periappendicular abscess. However, the data on histology of appendiceal tumors among acute appendicitis patients is limited, especially in patient cohorts differentiating between uncomplicated and complicated acute appendicitis. We have previously reported the association of increased appendiceal tumor prevalence with complicated acute appendicitis in this population-based study. The objective of this secondary analysis was to evaluate the association of both appendicitis severity and patient age with appendiceal tumor histology. Methods This nationwide population-based registry study (The Finnish Cancer Registry) was conducted from 2007 to 2013. All appendiceal tumors (n = 840) and available medical reports (n = 504) of these patients at eight study hospitals were previously evaluated, identifying altogether 250 patients with both acute appendicitis and appendiceal tumor. Results The severity of acute appendicitis was significantly associated with more malignant tumor histology. The risk of adenocarcinoma or pseudomyxoma was significantly higher among patients with periappendicular abscess (OR 15.05, CI 95% 6.98-32.49, p < 0.001) and patients presenting with perforated acute appendicitis (OR 4.09, CI 95% 1.69-9.90, p = 0.0018) compared to patients with uncomplicated acute appendicitis. Similarly, patient age over 40 years was significantly associated with the risk of adenocarcinoma and pseudomyxoma (OR 26.46, Cl 95% 7.95-88.09, p < 0.001). Patient sex was not associated with a more malignant appendiceal tumor histology (p = 0.67). Conclusion More malignant appendiceal tumor histology of adenocarcinoma or pseudomyxoma was significantly associated with patient age over 40 years and complicated acute appendicitis, especially periappendicular abscess.Peer reviewe

Parastomal Hernia : A Retrospective Nationwide Cohort Study Comparing Different Techniques with Long-Term Follow-Up

Background Parastomal hernia repair is a complex surgical procedure with high recurrence and complication rates. This retrospective nationwide cohort study presents the results of different parastomal hernia repair techniques in Finland. Methods All patients who underwent a primary end ostomy parastomal hernia repair in the nine participating hospitals during 2007-2017 were included in the study. The primary outcome measure was recurrence rate. Secondary outcomes were complications and re-operation rate. Results In total, 235 primary elective parastomal hernia repairs were performed in five university hospitals and four central hospitals in Finland during 2007-2017. The major techniques used were the Sugarbaker (38.8%), keyhole (16.3%), and sandwich techniques (15.4%). In addition, a specific intra-abdominal keyhole technique with a funnel-shaped mesh was utilized in 8.3% of the techniques; other parastomal hernia repair techniques were used in 21.3% of the cases. The median follow-up time was 39.0 months (0-146, SD 35.3). The recurrence rates after the keyhole, Sugarbaker, sandwich, specific funnel-shaped mesh, and other techniques were 35.9%, 21.5%, 13.5%, 15%, and 35.3%, respectively. The overall re-operation rate was 20.4%, while complications occurred in 26.3% of patients. Conclusion The recurrence rate after parastomal hernia repair is unacceptable in this nationwide cohort study. As PSH repair volumes are low, further multinational, randomized controlled trials and hernia registry data are needed to improve the results.Peer reviewe

Finnish National Esophago-Gastric Cancer Cohort (FINEGO) for studying outcomes after oesophageal and gastric cancer surgery: a protocol for a retrospective, population-based, nationwide cohort study in Finland

Introduction: Surgery for oesophageal and gastric cancers is associated with high morbidity, mortality and poor quality of life postoperatively. The Finnish National Esophago-Gastric Cancer Cohort has been established with the aim of identifying factors that could contribute to improved outcomes in oesophago-gastric cancer.Methods and analysis: All patients with oesophageal and gastric cancer diagnosed in Finland between 1987 and 2015 will be identified from the Finnish national registries. The Finnish Cancer Registry and Finnish Patient Registry will be used to identify patients that fulfil the inclusion criteria for the study: (1) diagnosis of oesophageal, gastro-oesophageal junction, or gastric cancer, (2) any surgical treatment for the diagnosed cancer and (3) age of 18 or over at the time of diagnosis. Clinical variables and complication information will be retrieved in extensive data collection from the medical records of the relevant Finnish hospitals and complete follow-up for vital status from Statistics Finland. Primary endpoint is overall all-cause mortality and secondary endpoints include complications, reoperations, medication use and sick leaves. Sub-studies will be implemented within the cohort to investigate specific populations undergoing oesophageal and gastric cancer surgery. The initial estimated sample size is 1800 patients with surgically treated oesophageal cancer and 7500 patients with surgically treated gastric cancer.Ethics and dissemination: The study has been approved by the Ethical Committee in Northern Ostrobothnia, Finland and The National Institute for Health and Welfare, Finland. Study findings will be disseminated via presentations at conferences and publications in peer-reviewed journals.</p

Cost analysis of antibiotic therapy versus appendectomy for treatment of uncomplicated acute appendicitis: 5-year results of the APPAC randomized clinical trial

BackgroundThe efficacy and safety of antibiotic treatment for uncomplicated acute appendicitis hasbeen established at long-term follow-up with the majority of recurrences shown to occurwithin the first year. Overall costs of antibiotics are significantly lower compared with appendectomyat short-term follow-up, but long-term durability of these cost savings is unclear.The study objective was to compare the long-term overall costs of antibiotic therapy versusappendectomy in the treatment of uncomplicated acute appendicitis in the APPAC (APPendicitisACuta) trial at 5 years.Methods and findingsThis multicentre, non-inferiority randomized clinical trial randomly assigned 530 adultpatients with CT-confirmed uncomplicated acute appendicitis to appendectomy or antibiotictreatment at six Finnish hospitals. All major costs during the 5-year follow-up were recorded,whether generated by the initial visit and subsequent treatment or possible recurrent appendicitis.Between November 2009 and June 2012, 273 patients were randomized to appendectomyand 257 to antibiotics. The overall costs of appendectomy were 1.4 times higher(pCI: €3879 to €4463) resulting in cost savings of €1545 per patient (95% CI: €1193 to €1899;ppatients did not undergo appendectomy.ConclusionsAt 5-year follow-up antibiotic treatment resulted in significantly lower overall costs comparedwith appendectomy. As the majority of appendicitis recurrences occur within the first yearafter the initial antibiotic treatment, these results suggest that treating uncomplicated acuteappendicitis with antibiotics instead of appendectomy results in lower overall costs even atlonger-term follow-up.</p

Cohort profile: gastric cancer in the population-based, Finnish National Esophago-Gastric Cancer Cohort (FINEGO) Study

Purpose The Finnish National Esophago-Gastric Cancer Cohort (FINEGO) was established with the aim of identifying factors that could contribute to improved outcomes in oesophago-gastric cancer. The aim of this study is to describe the patients with gastric cancer included in FINEGO. Participants A total of 10 457 patients with gastric cancer or tumour diagnosis in the Finnish Cancer Registry or the Finnish Patient Registry during 1987-2016 were included in the cohort, with follow-up from Causes of Death Registry until 31 December 2016. All of the participants were at least 18 years of age, and had undergone either resectional or endoscopic mucosal surgery with curative or palliative intent. Findings to date Of the 10 457 patients, 90.1% were identified to have cancer in both cancer and patient registries. In all, the median age was 70 at the time of surgery, 54.5% of the patients were men and 64.4% had no comorbidities. Education data were available for 31.1% of the patients, of whom the majority had had Future plans The data in FINEGO can be currently used for registry-based research but is being expanded by data extraction from patient records and scanning of histological samples from the Finnish biobanks. Initially, we are planning on studies on the national trends in treatment and mortality, and studies on the demographic factors and their influence on survival.</div