Postoperative Delayed Emptying after Total, Subtotal, or Distal Gastrectomy for Gastric Cancer - a Population-based Study.

BACKGROUND: To examine the rate of delayed emptying and other 90-day postoperative complications after total, subtotal, and distal gastrectomy for gastric adenocarcinoma in a population-based setting. METHODS: This study included all patients undergoing total, subtotal, or distal gastrectomy for gastric cancer in Finland in 2005-2016, with follow-up until December 31, 2019. Logistic regression provided odds ratios with 95% confidence intervals of 90-day mortality. Results were adjusted for age, sex, year of surgery, comorbidities, pathological stage, surgical approach, and neoadjuvant therapy. RESULTS: A total of 2,058 patients underwent total (n=1,227), subtotal (n=450), or distal (n=381) gastrectomy. The rate of delayed emptying was 1.7% vs. 1.3% vs. 2.1% in the whole cohort and 1.6% vs. 1.8% vs. 3.5% in the subgroup analysis of R0 resections, respectively. Resection type was not associated to the risk of delayed emptying. Subtotal gastrectomy was associated with lower risk of major complications and re-operations and distal gastrectomy was associated with lower risk of anastomotic leak. CONCLUSIONS: The extent of resection did not affect delayed emptying while less postoperative complications were seen after subtotal or distal gastrectomy compared to total gastrectomy.

Toll-like receptors 1-9 in small bowel neuroendocrine tumors-Clinical significance and prognosis.

Toll-like receptors (TLRs) are pattern recognition receptors of the innate immunity. TLRs are known to mediate both antitumor effects and tumorigenesis. TLRs are abundant in many cancers, but their expression in small bowel neuroendocrine tumors (SB-NETs) is unknown. We aimed to characterize the expression of TLRs 1-9 in SB-NETs and lymph node metastases and evaluate their prognostic relevance. The present study included 125 patients with SB-NETs, of whom 95 had lymph node metastases, from two Finnish hospitals. Tissue samples were stained immunohistochemically for TLR expression, assessed based on cytoplasmic and nucleic staining intensity and percentage of positively stained cells. Statistical methods for survival analysis included Kaplan-Meier method and Cox regression adjusted for confounding factors. Disease-specific survival (DSS) was the primary outcome. TLRs 1-2 and 4-9 were expressed in SB-NETs and lymph node metastases. TLR3 showed no positive staining. In primary SB-NETs, TLRs 1-9 were not associated with survival. For lymph node metastases, high cytoplasmic TLR7 intensity associated with worse DSS compared to low cytoplasmic intensity (26.4% vs. 84.9%, p = 0.028). Adjusted mortality hazard (HR) was 3.90 (95% CI 1.07-14.3). The expression of TLRs 1-6 and 8-9 in lymph node metastases were not associated with survival. SB-NETs and their lymph node metastases express cytoplasmic TLR 1-2 and 4-9 and nucleic TLR5. High TLR7 expression in SB-NET lymph node metastases was associated with worse prognosis. The current research has future perspective, as it can help create base for clinical drug trials to target specific TLRs with agonists or antagonists to treat neuroendocrine tumors.

Stapled vs handsewn anastomosis and anastomotic leaks in gastric cancer surgery-a population-based nationwide study in Finland.

BACKGROUND: There is a lack of evidence regarding anastomotic technique and postoperative complications in gastric cancer surgery. This study aimed to evaluate whether there are differences between stapled and handsewn anastomosis and anastomotic leaks. METHODS: This was a population-based, retrospective, nationwide cohort study in Finland using the Finnish National Esophago-Gastric Cancer Cohort. Patients undergoing gastrectomy with available postoperative complication data were included. Logistic regression analysis was used to calculate the odds ratios with 95% CIs, adjusted for calendar period of surgery, age at surgery, sex, comorbidity, tumor stage, neoadjuvant therapy, minimally invasive surgery, type of gastrectomy, radical resection, and type of anastomosis. RESULTS: Of the 2164 patients, 472 of all patients (21.8%) had handsewn anastomosis and 1692 of all patients (78.2%) had stapled anastomosis. In the unadjusted analysis, anastomotic leaks were significantly lower in the handsewn group (hazard ratio [HR], 0.42; 95% CI, 0.22-0.79) than the stapled group, but after adjustment for known prognostic factors, this association was no longer significant (HR, 0.57; 95% CI, 0.27-1.21). In the analysis stratified by gastrectomy type (distal or total), no differences in anastomotic leaks were observed between anastomotic techniques. CONCLUSION: In this population-based nationwide study, anastomotic technique (stapled or handsewn) was not associated with anastomotic leaks in any, distal or total, gastrectomy.

Postoperative Complications After Neoadjuvant Chemotherapy Versus Upfront Surgery in Gastric Adenocarcinoma: A Population-Based Nationwide Study in Finland.

BACKGROUND: To date, no large population-based studies have compared complications and short-term outcomes between neoadjuvant chemotherapy and upfront surgery in gastric cancer. More nationwide studies with standardized reporting on complications are needed to enable international comparison between studies. This study aimed to compare postoperative complications between neoadjuvant therapy and upfront surgery after gastrectomy for gastric adenocarcinoma in a population-based setting. METHODS: This population-based study based on the Finnish National Esophago-Gastric Cancer Cohort included all patients 18 years of age or older undergoing gastrectomy for gastric adenocarcinoma in Finland during 2005-2016. Logistic regression provided odds ratios (ORs) with 95% confidence intervals (CIs), both crude and adjusted for key confounders. Different types of complications were graded based on the Esophagectomy Complications Consensus Group definitions, and major complications were assessed by the Clavien-Dindo scale. RESULTS: This study analyzed 769 patients. Neoadjuvant chemotherapy did not increase major postoperative complications after gastrectomy for gastric cancer compared with upfront surgery (OR, 1.12; 95% CI 0.81-1.56). Furthermore, it did not increase pneumonia, anastomotic complications, wound complications, or other complications. CONCLUSIONS: Neoadjuvant therapy is not associated with increased postoperative complications, reoperations, or short-term mortality compared with upfront surgery in gastric adenocarcinoma.

Population-based nationwide incidence of complications after gastrectomy for gastric adenocarcinoma in Finland.

BACKGROUND: The incidence of postoperative complications after gastrectomy for gastric cancer is not well known. More population-based studies using established complication classifications are needed for international comparison. The aim of this study was to evaluate the population-based incidence of postoperative complications after gastrectomy for gastric cancer. METHODS: This population-based study based on the Finnish National Esophago-Gastric Cancer Cohort included all patients at least 18 years of age undergoing gastrectomy for gastric adenocarcinoma in Finland during 2005-2016. The occurrence of complications 30 and 90 days after surgery was graded based on the Esophagectomy Complications Consensus Group definitions and the severity of complications was assessed using the Clavien-Dindo scale. RESULTS: This study included a total of 2196 patients. Postoperative complications occurred in 906 (41.3 per cent) of patients during 30 days after surgery and in 946 (43.1 per cent) during 90 days after surgery. Clavien-Dindo grade III or higher complications occurred in 375 (17.1 per cent) of patients. The most common complications 90 days after surgery by Esophagectomy Complications Consensus Group upper-level categories were gastrointestinal (n = 438; 19.9 per cent), including anastomotic leak, infectious (n = 377; 17.2 per cent) and pulmonary (n = 335; 15.3 per cent) complications. Postoperative mortality rate was occurred in 72 (3.3 per cent) patients within 30 days and in 161 (7.3 per cent) patients within 90 days after surgery. The median duration of postoperative hospital stay was 9 days (interquartile range 4-14). CONCLUSIONS: Postoperative complications are common across all types of gastrectomy and the majority occur during the first 30 postoperative days. This study informs the patients and caregivers of the expected outcomes of gastrectomy.

Toll-like receptors 1, 2, 4, 5, and 6 in gastric cancer.

Toll-like receptors (TLRs) are expressed on both immune cells and tumor cells, triggering both anti-tumor and pro-tumor responses. Therefore, TLRs have potential as prognostic biomarkers and immunotherapeutic targets. The aim of this study was to investigate TLR1, TLR2, TLR4, TLR5, and TLR6 expression and association with clinicopathological variables and survival in gastric cancer. Immunohistochemical study on cancer specimens from 564 resected gastric cancer patients was performed using tissue microarrays. The association between patient survival and TLR expression was calculated with Cox regression adjusted for confounding factors. Patients with high cytoplasmic TLR2 expression had significantly poorer 5-year survival than the low cytoplasmic TLR2 expression group in multivariate analysis (adjusted HR 1.38, 95% CI 1.11-1.71), and this estimate was similar in intestinal type (adjusted HR 1.33, 95% CI 0.98-1.80) and diffuse type (adjusted HR 1.48, 95% CI 1.06-2.05) histology subgroups. Patients with high cytoplasmic TLR6 expression group had significantly better 5-year survival compared with low cytoplasmic TLR6 expression group in multivariate analysis (adjusted HR 0.74, 95% CI 0.60-0.91). In the subgroup analysis of diffuse type of histology, the 5-year survival was better in high cytoplasmic TLR6 expression group in multivariable analysis (HR 0.62, 95% CI 0.46-0.83). In the intestinal type of histology subgroup, no significant differences between the groups were present. TLR1, TLR4, and TLR5 expression were not associated with 5-year survival. In conclusion, cytoplasmic TLR2 and TLR6 expression seem to have independent prognostic impact in gastric cancer, while TLR1, TLR4, and TLR5 do not.

Preoperative Esophageal Stenting and 5-Year Survival in Patients Undergoing Esophagectomy for Esophageal Cancer: a Population-Based Nationwide Study from Finland.

BACKGROUND: Preoperative esophageal stenting is proposed to have a negative effect on outcomes. The aim was to compare a 5-year survival in patients undergoing esophagectomy for esophageal cancer with and without preoperative esophageal stent in a population-based nationwide cohort from Finland. The secondary outcome was 90-day mortality. METHODS: This study included curatively intended esophagectomies for esophageal cancer in Finland between 1999 and 2016, with follow-up until December 31, 2019. Cox proportional hazards models provided hazard ratios (HRs) with 95% confidence intervals (CIs) of overall 5-year and 90-day mortality. Model 1 was adjusted for age, sex, year of the surgery, comorbidities, histology, pathological stage, and neoadjuvant therapy. Model 2 included also albumin level and BMI. RESULT: Of 1064 patients, a total of 134 patients underwent preoperative stenting and 930 did not. In both adjusted models 1 and 2, higher 5-year mortality was seen in patients with preoperative stent with HRs of 1.29 (95% CI 1.00-1.65) and 1.25 (95% CI 0.97-1.62), respectively, compared to no stenting. The adjusted HR of 90-day mortality was 2.49 (95% CI 1.27-4.87) in model 1 and 2.49 (95% CI 1.25-4.99) in model 2. When including only neoadjuvant-treated patients, those with preoperative stent had a 5-year survival of 39.2% compared to 46.4% without stent (adjusted HR 1.34, 95% CI 1.00-1.80), and a 90-day mortality rate of 8.5% and 2.5% (adjusted HR 3.99, 95% CI 1.51-10.50). DISCUSSION: This nationwide study reports worse 5-year and 90-day outcomes in patients with preoperative esophageal stent. Since residual confounding remains possible, observed difference could be only an association rather than the cause.

Evolution of pancreatic surgery over time and effects of centralization-a single-center retrospective cohort study.

Background: Short-term outcomes of pancreatic surgery have improved globally during the last two decades. Long-term survival of resectable pancreatic ductal adenocarcinoma (PDAC) has also shown slight improvement. We describe a cohort of 566 consecutive pancreatectomies performed at a Northern Finnish tertiary center. We analyze the trends in short-term outcomes of all-cause pancreatic surgery and long-term survival of PDAC patients. Methods: All pancreatic resections performed at the Oulu University Hospital during years 2000-2020 were included. Patient data was analyzed in four time periods (2000-2005, 2006-2010, 2011-2015 and 2016-2020). Clinicopathological parameters of patients and tumors, complication data and short-term mortality were recorded for all patients and compared between time quartiles. Long-term survival and administration rates of neo-, and/or adjuvant therapy of PDAC patients were analyzed. Results: A total of 566 pancreatectomies were performed during the study period: 359 (63%) pancreatoduodenectomies (PDs), 130 (23.0%) open left pancreatectomies (LPs), 45 (8.0%) laparoscopic LPs, 26 (5.1%) total pancreatectomies (TPs), and 6 (1.1%) enucleations. Median age of patients was 63 [57-71] years, and 49% [267] of patients were men. Number of pancreatectomies per time period increased from 67 in 2000-2005 to 266 in 2016-2020. American Society of Anesthesiologists (ASA) Physical Classification III patients and T3 tumors were more frequently operated on in later time periods. Complication rates remained at constant low levels throughout the study period, but reoperation rate increased from 9.4% in 2000-2010 to 16.2% in 2011-2020. Short-term (90-day) mortality after pancreatectomy decreased from 3.1% to 0.74%, while 5-year survival improved from 14.3% in 2006-2011 to 21.4% in 2011-2015. Resection rate of diagnosed PDAC cases, as reported by the Finnish Cancer Registry (FCR) for the catchment area, increased from 3.2% to 14.9% over the study period. Conclusions: The hospital volume of pancreatectomies has increased substantially, while complications and postoperative mortality have remained at acceptable levels. Long-term survival and resection rate of PDAC patients showed notable improvement over two decades.

Toll-like receptors 3, 7, 8, and 9 in gastric cancer.

Toll-like receptors (TLRs) have been shown to have anti-tumor, pro-tumor, or even dual effects in cancer, and are thus potential prognostic biomarkers and immunotherapeutic targets. The present study aimed to evaluate associations between endosomal TLRs, namely TLR3, TLR7, TLR8, and TLR9, expression and clinicopathological variables and survival in gastric cancer. A total of 564 gastric adenocarcinoma patients were included in this retrospective cohort study. Samples and clinicopathological data were retrieved and organized into tissue microarray blocks. Protein expressions were detected by immunohistochemical staining. The patients were divided into low expression and high expression groups by median values of expression. Cox regression provided hazard ratios (HR) with 95% confidence intervals (CI), adjusted for confounders. Patients with high nuclear TLR3 expression had significantly poorer 5-year survival than the low nuclear TLR3 expression group in the univariable analysis (crude HR 1.31, 95% CI 1.07-1.60). With radically resected patients, poor prognosis was also seen in the multivariable analysis (adjusted HR 1.38, 95% CI 1.08-1.77). Cytoplasmic TLR3, TLR7, TLR8, and TLR9 were not associated with 5-year survival. In conclusion, high nuclear TLR3 expression seems to have prognostic impact in gastric cancer, while TLR7, TLR8, and TLR9 do not.

Five-year Survival after McKeown Compared to Ivor-Lewis Esophagectomy for Esophageal Cancer: A Population-based Nationwide Study in Finland.

OBJECTIVE: The aim of study was to compare overall 5-year survival of esophageal cancer patients undergoing transthoracic esophagectomy with either neck or intrathoracic anastomosis, that is, McKeown and Ivor-Lewis esophagectomy. BACKGROUND: No national studies comparing long-term survival after McKeown and ivor-Lewis esophagectomies in the West exist. METHODS: This population-based nationwide study included all curatively intended transthoracic esophagectomies for esophageal adenocarcinoma or squamous cell carcinoma in Finland in 1987 to 2016, with follow-up until December 31, 2019. Cox proportional hazard models provided hazard ratios (HR) with 95% confidence intervals (ci) of all-cause 5-year mortality. The results were adjusted for age, sex, year of the operation, comorbidities, histology, stage, and neoadjuvant treatment. Adjusted model 2 included also tumor location and lymph node yield. RESULTS: A total of 990 patients underwent McKeown (n = 278) or Ivor-Lewis (n = 712) esophagectomy The observed overall 5-year survival was 43.1% after McKeown, and 45.9% after Ivor-Lewis esophagectomy. McKeown esophagectomy was not associated with the overall 5-year mortality (adjusted HR 1.11, 95% CI: 0.89-1.38), compared to Ivor-Lewis esophagectomy. Additional adjustment for tumor location and lymphadenectomy further attenuated the point estimate (HR 1.06, 95% CI: 0.85-1.33). Surgical approach was not associated with 90-day mortality rate (adjusted HR 1.15, 95% CI: 0.67-1.97). CONCLUSIONS: This population-based nationwide study suggests that overall 5-year survival or 90-day survival with McKeown and Ivor-Lewis esopha-gectomy for esophageal cancer are comparable.

Long-Term Survival After Transhiatal Versus Transthoracic Esophagectomy: A Population-Based Nationwide Study in Finland.

BACKGROUND: No population-based studies comparing long-term survival after transhiatal esophagectomy (THE) and transthoracic esophagectomy (TTE) exist. This study aimed to compare the 5-year survival of esophageal cancer patients undergoing THE or TTE in a population-based nationwide setting. METHODS: This study included all curatively intended THE and TTE for esophageal cancer in Finland during 1987-2016, with follow-up evaluation until 31 December 2019. Cox proportional hazard models provided hazard ratios (HRs) with 95% confidence intervals (CIs) of 5-year and 90-day mortality. The results were adjusted for age, sex, year of operation, comorbidities, histology, neoadjuvant treatment, and pathologic stage. RESULTS: A total of 1338 patients underwent THE (n = 323) or TTE (n = 1015). The observed 5-year survival rate was 39.3% after THE and 45.0% after TTE (p = 0.072). In adjusted model 1, THE was not associated with greater 5-year mortality (HR 0.99; 95% CI 0.82-1.20) than TTE. In adjusted model 2, including T stage instead of pathologic stage, the 5-year mortality hazard rates after THE (HR 0.87, 95% CI 0.72-1.05) and TTE were comparable. The 90-day mortality rate for THE was higher than for TTE (adjusted HR 0.72; 95% CI 0.45-1.14). In subgroup analyses, no differences between THE and TTE were observed in Siewert II gastroesophageal junction cancers, esophageal cancers, or pN0 tumors, nor in the comparison of THE and TTE with two-field lymphadenectomy. The sensitivity analysis, including patients with missing patient records, who underwent surgery during 1996-2016 mirrored the main analysis. CONCLUSIONS: This Finnish population-based nationwide study suggests no difference in 5-year or 90-day mortality after THE and TTE for esophageal cancer.

Predictive value of p53, Ki67 and TLR5 in neoplastic progression of Barrett's esophagus: a matched case-control study.

Barrett's esophagus progresses to high-grade dysplasia or cancer along the well-established metaplasia-dysplasia-adenocarcinoma sequence. The aim of this study was to evaluate the value of p53, Ki67, and toll-like receptor 5 (TLR5) in prediction of malignant progression of Barrett's metaplasia and low-grade dysplasia. This was a retrospective matched case-control study based on Northern and Central Finland population. Patients diagnosed with esophageal high-grade dysplasia or adenocarcinoma were included. From these patients, all previous endoscopy samples were obtained along with original diagnostic HE-slides and clinical data. Age- and sex-matched patients with non-progressing Barrett's metaplasia and low-grade dysplasia confirmed with follow-up endoscopies were used as controls. Two gastrointestinal pathologist re-reviewed all original HE-slides, and newly made sections to confirm representative tissue material blinded from clinical data. p53, Ki67, and TLR5 were immunohistochemically stained. Final cohort included 45 patients with progressive Barrett's metaplasia (n = 21) or low-grade dysplasia (n = 24), and 92 patients with non-progressive Barrett's metaplasia (n = 52) or low-grade dysplasia (n = 40). In Barrett's metaplasia, aberrant p53 expression was observed in 6% of samples in progressors and 0% in non-progressors. In low-grade dysplasia, aberrant p53 was seen in 56% of samples in progressors and 17% in non-progressors (Odd's ratio 6.7, 95% CI 1.8-24.6). Ki67 or TLR5 showed no association with disease progression. In this matched case-control study, p53 expression associated with a high risk of malignant progression in Barrett's low-grade dysplasia. Routine staining of p53 is indicated in expert confirmed low-grade dysplasia.

Monocarboxylate Transporters 1 and 4 and Prognosis in Small Bowel Neuroendocrine Tumors.

Monocarboxylate transporters (MCTs) are cell membrane proteins transporting lactate, pyruvate, and ketone bodies across the plasma membrane. The prognostic role of MCTs in neuroendocrine tumors is unknown. We aimed to analyze MCT1 and MCT4 expression in small bowel neuroendocrine tumors (SB-NETs). The cohort included 109 SB-NETs and 61 SB-NET lymph node metastases from two Finnish hospitals. Tumor samples were immunohistochemically stained with MCT1 and MCT4 monoclonal antibodies. The staining intensity, percentage of positive cells, and stromal staining were assessed. MCT1 and MCT4 scores (0, 1 or 2) were composed based on the staining intensity and the percentage of positive cells. Survival analyses were performed with the Kaplan-Meier method and Cox regression, adjusted for confounders. The primary outcome was disease-specific survival (DSS). A high MCT4 intensity in SB-NETs was associated with better DSS when compared to low intensity (85.7 vs. 56.6%, p = 0.020). A high MCT4 percentage of positive cells resulted in better DSS when compared to a low percentage (77.4 vs. 49.1%, p = 0.059). MCT4 scores 0, 1, and 2 showed DSS of 52.8 vs. 58.8 vs. 100% (p = 0.025), respectively. After adjusting for confounders, the mortality hazard was lowest in the patients with a high MCT4 score. MCT1 showed no association with survival. According to our study, a high MCT4 expression is associated with an improved prognosis in SB-NETs.

Risk of progression in Barrett's esophagus based on diagnoses of general and gastrointestinal pathologists. A retrospective case-control study from Northern and Central Finland.

BACKGROUND: Esophageal adenocarcinoma (EAC) is the sixth leading cause of cancer-related death worldwide. It develops through Barrett's metaplasia - dysplasia sequence. However, the effectiveness of endoscopic surveillance is limited, since diagnosis of low-grade dysplasia (LGD) is known to be challenging for pathologists. Our aim was to compare the risk of Barrett's progression based on diagnoses of general and expert gastrointestinal (GI) pathologists in a population-based cohort. METHODS: A total of 60 patients with non-dysplastic metaplasia (BE) or LGD progressing to high grade dysplasia (HGD) or EAC during follow-up could be identified in the population. For comparison, series representing non-progressive BE (n = 56) and LGD cases (n = 54), matched for age, gender, and length of follow-up were collected. All available original HE stained slides (n = 292) were blindly re-evaluated by two experienced GI pathologists and patient groups of progressive non-progressive BE and LGD were formed according to revised diagnoses. RESULTS: Original diagnosis for each sample was changed in 25% of BE, 59% of LGD, and 33% of HGD diagnoses. Of the original LGD diagnoses, 53% were downgraded to BE or indefinite for dysplasia (ID). Of LGD diagnoses made by an expert GI pathologist, 61% were in the progressive LGD group, whereas only 42% of general pathologists' LGD diagnoses were in the progressive LGD group. CONCLUSION: Based on this retrospective case-control study, LGD is strongly over-diagnosed among general pathologists. LGD diagnosed by expert GI pathologists predicts progressive disease. Recommendation for consensus diagnosis by expert GI pathologists is justified also in the Finnish population-based setting.

Increasing Use of PET-CT, Neoadjuvant Treatment, Minimally Invasive Approach and Surgical Radicality in Esophageal Cancer Surgery are Associated with Improved Short- and Long-term Outcomes in Real-World Setting.

BACKGROUND: Guideline adherence has improved outcomes in several cancers. Our aim was to evaluate whether the rate of PET-CT, neoadjuvant treatment, minimally invasive approach, and surgical radicality, suggested also by recent guidelines, would improve short- and long-term operative outcomes in esophageal cancer in real-world setting. METHODS: This retrospective study in two Finnish Hospitals between 2010 and 2020 included 296 esophageal cancer patients. Grouping factors based on four factors with annual cut-offs by center were 90% rate in PET-CT-based staging, 70% in neoadjuvant therapy usage, 80% in minimally invasive approach, and 20 in annual mean lymph node yield. If none of factors were reached, all patients operated in that year were classified into group 1. With one to three cut-offs reached, grouping was into group 2. If all annual cut-offs were reached, patients were classified into group 3. Primary end points were major complication rate and overall 1-, 3-, and 5-year survival. RESULTS: Major complication rate decreased significantly from 38.2% in group 1 (p < 0.001) and 34.2% in group 2 (p < 0.001) to 10.2% in group 3. Overall 1-, 3-, and 5-year survival rates between groups 1-3 were 77.9% vs. 80.3% vs. 94.2% (p = 0.004), 51.5% vs. 51.1% vs. 67.3% (p = 0.022), and 44.1% vs. 47.4% vs. 55.5% (p = 0.065), respectively. Adjusted 5-year overall mortality was reduced significantly in group 3 compared to group 1 (HR 0.46, 95% CI 0.28-0.75). CONCLUSION: This study suggests that increasing rate of PET-CT, neoadjuvant treatment, minimally invasive surgery, and surgical radicality improves short- and long-term outcomes in operated esophageal cancer patients.

Carbonic Anhydrases II, IX, and XII in Reflux Esophagitis.

BACKGROUND: The pathogenesis of gastroesophageal reflux disease (GERD) has not been resolved in detail. Esophageal epithelial cells provide resistance to acidic reflux via several mechanisms, many of which involve buffering acid with bicarbonate and transporting protons. Carbonic anhydrases (CAs) are enzymes that control the acid-base balance by catalyzing the reversible hydration of carbon dioxide to produce bicarbonate and hydrogen ions. AIMS: We aimed to determine the immunohistochemical expression patterns of CAII, CAIX, and CAXII in the normal esophageal squamous epithelium and in patients with GERD. METHODS: We evaluated 82 biopsy samples, including 26 with a histologically normal esophagus, 26 with histologically mild esophagitis, and 30 with severe esophagitis. Expression patterns of CAII, CAIX, and CAXII in the esophageal squamous epithelium were determined by immunohistochemical staining. RESULTS: Cytoplasmic CAII expression was predominantly detected in the upper luminal part of the squamous epithelium and was significantly (p < 0.01) increased in GERD. Expression of CAIX was essentially membranous. The isozyme was constantly present in the peripapillary cells. In the interpapillary areas, clustered expression was observed to emerge and increase significantly (p < 0.01) in esophagitis. CAXII expression was the most abundant of the isozymes and was mainly membranous. In the normal squamous epithelium, CAXII expression was confined to the basal layer; in severe esophagitis, CAXII expression increased significantly in both basal (p < 0.05) and superficial (p < 0.01) halves of the epithelium. CONCLUSIONS: We demonstrate upregulated expression of CAII, CAIX, and CAXII in GERD. The increase in expression likely contributes to esophageal epithelial resistance to acidic reflux.

Hospital volume and outcomes of pancreatic cancer: a Finnish population-based nationwide study.

BACKGROUND: Pancreatic cancer surgery is associated with high incidence of short- and long-term morbidity and mortality. The aim of this study was to assess whether the hospital volume of pancreatic surgery is associated with better survival in a population-based setting. METHODS: All patients who underwent pancreatic resection for cancer in Finland during 1997-2016 were identified from nationwide registries. The follow-up ended on 31 December 2019. Patients were divided into quintiles based on annual hospital volume (4-year moving average): ≤4, 5-9, 10-18, 19-36 and ≥ 37 resections per year. Cox regression provided hazard ratios (HR) and 95% confidence intervals (CI), adjusted for age, sex, comorbidity and year of surgery. RESULTS: The number of diagnosed pancreatic cancers was 22,724. Of these, 1514 underwent pancreatic surgery due to pancreatic ductal adenocarcinoma. The 5-year survival ranged from 12% to 28%, increasing with higher annual operative volume. Adjusted 5-year mortality was higher in all other quintiles compared to the highest annual volume quintile (HR 1.43, 95% CI 1.16-1.75). Thirty and 90-day mortality were higher in the three lowest volume, compared to the highest quintile. CONCLUSION: Higher annual hospital volume of pancreatic surgery for pancreatic ductal adenocarcinoma is associated with improved short- and long-term survival.

Carbonic Anhydrases II and IX in Non-ampullary Duodenal Adenomas and Adenocarcinoma.

Non-ampullary duodenal adenocarcinoma (DAC) is a rare malignancy. Little information is available concerning the histopathological prognostic factors associated with DAC. Carbonic anhydrases (CAs) are metalloenzymes catalyzing the universal reaction of CO2 hydration. Isozymes CAII, CAIX, and CAXII are associated with prognosis in various cancers. Our aim was to analyze the immunohistochemical expressions of CAII, CAIX, and CAXII in normal duodenal epithelium, duodenal adenomas, and adenocarcinoma and their associations with clinicopathological variables and survival. Our retrospective study included all 27 DACs treated in Oulu University Hospital during years 2000-2020. For comparison, samples of 42 non-ampullary adenomas were collected. CAII expression was low in duodenal adenomas and adenocarcinoma. CAIX expression in adenomas and adenocarcinoma was comparable with the high expression of normal duodenal crypts. Expression patterns in carcinomas were largely not related to clinicopathological features. However, low expression of CAII associated with poorer differentiation of the tumor (p=0.049) and low expression of CAIX showed a trend for association with nodal spread, although statistical significance was not reached (p=0.091). CAII and CAIX lost their epithelial polarization and staining intensity in adenomas. CAXII expression was not detected in the studied samples. CAs were not associated with survival. The prognostic value of CAII and CAIX downregulation should be further investigated. Both isozymes may serve as biomarkers of epithelial dysplasia in the duodenum.

Thirty years of esophageal cancer surgery in Oulu University Hospital.

BACKGROUND: Esophagectomy is the mainstay of surgical treatment of esophageal cancer, but involves high operative risk. The aim of this study was to review the evolution surgical treatment of esophageal cancer in Northern Finland, with introduction of minimally invasive techniques. METHODS: All elective esophagectomies performed in Oulu University Hospital between years 1987 and 2020 were included. Treatment strategies were compared to current guidelines including staging and use of neoadjuvant therapy, and benchmark values including postoperative morbidity, hospital stay, readmissions and 90-day mortality. Long-term survival was compared to previous national studies. RESULTS: Between years 1987 and 2020 a total of 341 underwent an esophagectomy. Transhiatal resection was performed to 167 (49.3%), Ivor Lewis to 129 (38.1%) and McKeown to 42 (12.4%) patients. MIE was performed to 49 (14.5%) patients. During the past four years 83.7% of locally advanced diseases received neoadjuvant treatment. Since 1987, gradual improvements have occurred especially in incidence of pleural effusion requiring additional drainage procedure (highest in 2011-2013 and in last four years 14.0%), recurrent nerve injuries (highest in 2008-2010 29.4% and lowest in 2017-2020 1.8%) and in 1-year survival rate (1987-1998 68.4% vs. 2017-2020 82.1%). No major changes in comorbidity, complication rate, anastomosis leaks, hospital stay or postoperative mortality were seen. CONCLUSIONS: Esophageal cancer surgery has gone through major changes over three decades. Current guideline-based treatment has resulted with progressive improvement in mid- and long-term survival. However, despite modern protocol, no major improvement has occurred for example in major complications, anastomosis leak rates or hospital stay.