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.

Comparison of Postoperative Complications After Gastrectomy for Gastric Cancer with Antecolic Versus Retrocolic Reconstruction: A Population-Based Study.

BACKGROUND: The purpose of this study was to examine the rates of 90-day anastomotic complications and other postoperative complications after total or partial gastrectomy with antecolic versus retrocolic reconstruction in a population-based setting. METHODS: This population-based nationwide retrospective cohort study included all patients undergoing total or partial gastrectomy for gastric adenocarcinoma in Finland in 2005-2016, with follow-up until 31 December 2019. Logistic regression provided odds ratios (ORs) with 95% confidence intervals (CIs) of 90-day mortality. Results were adjusted for age, sex, year of the surgery, comorbidities, tumor locations, pathological stage, and neoadjuvant therapy. RESULTS: A total of 2063 patients having gastrectomy with antecolic (n = 814) or retrocolic (n = 1249) reconstruction were identified from the registries. The anastomotic complication rate was 3.8% with antecolic reconstruction and 5.0% with retrocolic reconstruction. Antecolic reconstruction was not associated with a higher risk of anastomotic complications compared with retrocolic reconstruction in the adjusted analysis (OR 0.69, 95% CI 0.44-1.09) of the whole cohort or in the predefined subgroups. The reoperation rate was 8.2% with antecolic reconstruction and 7.7% with retrocolic reconstruction, without statistical significance. In subgroup analysis of total gastrectomy patients, the risk of major complications was lower with antecolic reconstruction compared with retrocolic reconstruction (OR 0.62, 95% CI 0.45-0.86). CONCLUSIONS: The rate of anastomotic complications did not differ after antecolic versus retrocolic reconstruction after total or partial gastrectomy. In total gastrectomies, the risk of major complications was lower after antecolic compared with retrocolic reconstruction.

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.

Immunophenotype based on inflammatory cells, PD-1/PD-L1 signalling pathway and M2 macrophages predicts survival in gastric cancer.

BACKGROUND: Immune response against cancer has prognostic impact but its role in gastric cancer is poorly known. The aim of the study was to assess the prognostic significance of immune cell score (CD3+, CD8+), tumour immune escape (PD-L1, PD-1) and immune tolerance (Clever-1). METHODS: After exclusion of Epstein-Barr virus positive (n = 4) and microsatellite instable (n = 6) tumours, the study included 122 patients with GC undergoing D2 gastrectomy. CD3+ and CD8+ based ICS, PD-L1, PD-1 and Clever-1 expressions were evaluated. Differences in survival were examined using Cox regression adjusted for confounders. The primary outcome was 5-year survival. RESULTS: The 5-year overall survival rate was 43.4%. High ICS was associated with improved overall survival (adjusted HR 0.48 (95% CI 0.26-0.87)) compared to low ICS. In the high ICS group, patients with PD-L1 expression (5-year survival 69.2 vs. 53.1%, p = 0.317), high PD-1 (5-year survival 70.6 vs. 55.3% p = 0.312) and high Clever-1 (5-year survival 72.0% vs. 45.5% (p = 0.070) had poor prognosis. CONCLUSIONS: High ICS was associated with improved survival. In the high ICS group, patients with high PD-L1, PD-1 and Clever-1 had poor prognosis highlighting the importance of immune escape and immune tolerance in GC.

Impact of splenectomy on long-term outcomes after gastrectomy for gastric cancer: a population-based study.

BACKGROUND: No national studies comparing long-term survival after total or partial gastrectomy with splenectomy due to injury or oncologic reasons or spleen preservation exist. This study aimed to examine the 5-year overall survival (OS) of patients with gastric adenocarcinoma who underwent total or partial gastrectomy with splenectomy due to injury or oncologic reasons or spleen preservation in a population-based nationwide setting. METHODS: This study included all patients undergoing total or partial gastrectomy with splenectomy or spleen preservation for gastric adenocarcinoma in Finland from 2005 to 2016, with follow-up until December 31, 2019. A total of 2196 patients with gastric cancer diagnosis and total or partial gastrectomy were identified in the registries. Of these patients, 2118 were applicable for this study. Cox proportional hazard models provided hazard ratios (HRs) with 95% CIs of 5-year OS. The results were adjusted for age, sex, year of operation, comorbidities, tumor location, pathologic stage, and neoadjuvant therapy. RESULTS: The observed 5-year OS rates were 38.7% in patients with no or minor spleen injury, 39.7% in patients with splenectomy due to injury, and 30.8% in patients with splenectomy due to oncologic reasons (P = .032). Patients who underwent R0 gastrectomy with splenectomy due to oncologic reasons had higher 5-year mortality (the adjusted model HR, 1.26; 95% CI, 1.01-1.56) than patients who underwent spleen preservation. CONCLUSION: The OS was worst in patients who underwent gastrectomy with splenectomy due to oncologic reasons, highlighting the poor prognosis in patients with advanced gastric cancer. Splenectomy due to injury does not compromise the prognosis.

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 delayed emptying after total, subtotal, or distal gastrectomy for gastric cancer: a population-based study.

BACKGROUND: This study aimed to examine the rate of delayed emptying and other 90-day postoperative complications after total, subtotal, and distal gastrectomies for gastric adenocarcinoma in a population-based setting. METHODS: This study included all patients who underwent total, subtotal, or distal gastrectomy for gastric cancer in Finland in 2005-2016, with follow-up until December 31, 2019. Logistic regression provided the odds ratios with 95% CIs of 90-day mortality. The results were adjusted for age, sex, year of surgery, comorbidities, pathologic stage, and neoadjuvant therapy. RESULTS: A total of 2058 patients underwent total (n = 1227), subtotal (n = 450), or distal (n = 381) gastrectomy. In the total, subtotal, and distal gastrectomy groups, the rates of 90-day delayed emptying were 1.7%, 1.3%, and 2.1% in the whole cohort and 1.6%, 1.8%, and 3.5% in the subgroup analysis of R0 resections, respectively. The resection type was not associated with the risk of delayed emptying. Subtotal gastrectomy was associated with a lower risk of major complications and reoperations, whereas distal gastrectomy was associated with a lower risk of anastomotic complications. CONCLUSION: The extent of resection did not affect delayed emptying, whereas fewer postoperative complications were observed after subtotal or distal gastrectomy than after total gastrectomy.

Tertiary lymphoid structures and gastric cancer prognosis.

Tertiary lymphoid structures (TLSs) are part of immune response against cancer. Their high density and high diameter have been shown to be associated with prognosis in different cancer types. The aim of this study was to examine the prognostic significance of TLS density and diameter in gastric cancer and reproducibility of their assessments. TLS densities and maximal TLS diameter were assessed from hematoxylin-eosin (HE) stained slides of 721 surgically treated gastric cancer patients from two hospitals in Finland. Mortality hazard ratios (HRs) for TLS densities and maximal TLS diameter were analyzed. TLS densities and maximal TLS diameter were assessed with moderate interobserver agreement (Cohen's kappa 0.50-0.62). Maximal TLS density was not associated with survival (adjusted HR 0.85, 95% CI 0.70-1.02) and neither was hotspot TLS density (adjusted HR 0.85, 95% CI 0.70-1.02). High maximal TLS diameter was associated with longer survival in overall study population (adjusted HR 0.74, 95% CI 0.61-0.89) and in diffuse type subgroup (adjusted HR 0.65, 95% CI 0.50-0.85). In conclusion, high maximal TLS diameter is associated with improved survival in gastric cancer and can be assessed from HE-stained slides. Its prognostic value might be limited to diffuse histological type.

Exercise capacity in the stair-climbing test predicts outcomes of operable esophageal cancer in minimally invasive era.

INTRODUCTION: The risk of complications after esophagectomy highlights the need for careful preoperative assessment. Aim was to assess whether stair-climbing test (SCT) could predict outcomes of patients with operable esophageal cancer in minimally invasive era. MATERIALS AND METHODS: Patients with esophageal cancer were evaluated for surgical treatment in Central Finland Central Hospital from 2012 to March 2021. Of evaluated 162 patients, 138 were scheduled to eventually undergo surgery. The exercise capacity was evaluated with symptom limited SCT. Patients were divided into four study groups on intent-to-treat basis: surgery and the SCT >14 m (Group 1), surgery and the SCT <11 m (Group 2), non-surgical therapy and the SCT <11 m (Group 3) and non-surgical therapy and the SCT >14 m (Group 4). Results were adjusted for confounders. RESULTS: Major complication rate was 10.1% vs 40.0% between Group 1 and 2 (p = 0.006), and 90-day mortality 0% vs 20.0% (p < 0.001). Overall survival rates in Groups 1-4 at 1-year were 92.3% vs 72.2% vs 46.8% vs 81.8%, at 3-year 68.5% vs 52.7% vs 15.6% vs 27.3% and at 5-year 58.7% vs 39.5% vs 0% vs 0%, respectively (p < 0.001). In adjusted analysis when compared to Group 1, other groups had increased 5-year mortality hazard (Group 2 HR 2.88 (95% CI 1.25-6.63), Group 3 HR 15.6 (95% CI 5.57-43.5) and Group 4 HR 5.35 (95% CI 2.08-13.7)). CONCLUSION: Exercise capacity measured with SCT in esophageal cancer patients is a strong predictor of complications and survival, and is a potential parameter to be included in any risk or prognostic models.

Implementation of Multimodality Therapy and Minimally Invasive Surgery: Short- and Long-term Outcomes of Gastric Cancer Surgery in Medium-Volume Center.

BACKGROUND: Multimodal treatment of gastric cancer includes careful preoperative staging, perioperative oncological treatment, and selective minimally invasive approach. The aim was to evaluate whether this approach improves short- and long-term outcomes in operable gastric cancer. METHODS: This study included 181 gastric cancer patients who underwent curative intent surgery in Central Finland Central Hospital between years 2005 and 2021 for gastric or esophagogastric junction adenocarcinoma. Those 65 patients in group 1 operated between years 2005-2010 had open surgery with possible adjuvant therapy. During the second period including 58 patients (2011-2015), perioperative chemotherapy and minimally invasive surgery were implemented. The period, when these treatments were standard practise, was years 2016-2021 including 58 patients (group 3). Outcomes were lymph node yield, major complications and 1- and 3-year survival rates. RESULTS: Median lymph node yield increased from 17 in group 1 and 20 in group 2 to 23 in group 3 (p < 0.001). Major complication rates in groups 1-3 were 12.3%, 32.8%, and 15.5% (group 1 vs. group 2, p = 0.007; group 2 vs. group 3, p = 0.018), respectively. Overall 1-year survival rates between study groups 1-3 were 78.5% vs. 69.0% vs. 90.2% (p = 0.018) and 3-year rates 44.6% vs. 44.8% vs. 68.1% (p = 0.016), respectively. For overall 3-year mortality, adjusted hazard ratio (HR) was 1.02 (95%CI 0.63-1.66) in group 2 and HR 0.37 (95%CI 0.20-0.68) in group 3 compared to group 1. CONCLUSIONS: In medium-volume center, modern multimodal therapy in operable gastric cancer combined with minimally invasive surgery increased lymph node yield and improved long-term survival without increasing postoperative morbidity.

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.

Laparoscopic treatment of small bowel strangulation caused by an intramesosigmoid hernia and review of literature.

An internal hernia is defined as a protrusion of an abdominal viscera through the defects of the gastrointestinal mesentery or peritoneum-lined fossa. Sigmoid mesocolic hernias are an uncommon type of internal hernias, accounting for only 6% of all internal hernias. Furthermore, intramesosigmoid hernia is one of the three subtypes of the sigmoid mesocolic hernias. Internal hernias are potentially fatal conditions with diagnostic challenges. Patients presenting with acute obstruction, no surgical history and no external hernia should receive an urgent CT scan to facilitate early surgery and to minimise the risk of strangulation and bowel resection. Here, we report a case of strangulated small bowel obstruction secondary to an intramesosigmoid hernia with a successful laparoscopic repair. We also present a literature review of all reported cases so far and give an up-to-date perspective on intramesosigmoid hernia.

Immune Cell Infiltrate and Prognosis in Gastric Cancer.

PURPOSE: To examine and compare the prognostic value of immune cell score (ICS) and Klintrup-Mäkinen (KM) grade in gastric cancer. METHODS: Gastric adenocarcinoma tissues from samples of 741 patients surgically treated in two hospitals in Finland were assessed for ICS and KM grade. Cox regression with adjustment for confounders provided hazard ratios (HRs) and 95% CIs. Subgroup analyses were performed in intestinal and diffuse type subgroups. The primary outcome was 5-year overall survival. RESULTS: High ICS was associated to longer 5-year survival (adjusted HR 0.70, 95% CI 0.52-0.94), compared to low ICS. The difference was significant in intestinal type subgroup (adjusted HR 0.54, 95% CI 0.36-0.81) but not in diffuse type subgroup (adjusted HR 0.92, 95% CI 0.58-1.46). High KM grade was an independent prognostic factor for longer 5-year overall survival (adjusted HR 0.59, 95% CI 0.45-0.77) in both intestinal (adjusted HR 0.61, 95% CI 0.44-0.85) and diffuse subgroups (adjusted HR 0.52, 95% CI 0.31-0.86). ICS and KM grade were moderately correlated (ρ = 0.425). When both immune cell score and KM grade were included in the regression analysis, only KM grade remained prognostic. CONCLUSIONS: Both ICS and KM grade are prognostic factors in gastric adenocarcinoma, but immunohistochemistry-based ICS might not have additional prognostic value over hematoxylin-eosin-based KM grade.

Amyand's hernia: acute appendicitis and abscess in the inguinal canal.

Amyand's hernia is a rare entity where the appendix is trapped within inguinal canal. For even rarer are the cases where the appendix has perforated and caused an abscess into inguinal canal. Here we report a case where a male patient had Amyand's hernia, acute appendicitis and abscess which were treated by laparotomy. We present the diagnostic process and intraoperative finding leading to diagnosis of Amyand's hernia.

Cerebrospinal Fluid TDP-43 in Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis Patients with and without the C9ORF72 Hexanucleotide Expansion.

BACKGROUND: TDP-43 is the main protein component of ubiquitinated inclusions in a subgroup of frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) patients. The C9ORF72 hexanucleotide expansion is one of the main mutations associated with TDP-43 pathology in FTLD and ALS. Our aim was to analyze cerebrospinal fluid (CSF) TDP-43 levels and Alzheimer's disease biomarkers in FTLD and ALS patients and to test whether the C9ORF72 expansion carrier status affects these variables. METHODS: The patient cohort consisted of 90 clinically well-characterized FTLD (n = 69) and ALS (n = 21) patients. There were 30 patients with the C9ORF72 expansion and 60 patients without the expansion. CSF TDP-43, AΒ1-42, t-tau, and phospho-tau levels were measured using commercial ELISA kits. RESULTS: There was no difference in CSF TDP-43 levels between the C9ORF72 expansion carriers and the noncarriers. CSF TDP-43 levels were higher in ALS patients than in FTLD patients, and this finding was independent of the C9ORF72 expansion carrier status. Males had significantly higher TDP-43 levels than females (p = 0.008 in the total cohort). CONCLUSION: CSF TDP-43 does not seem to distinguish the C9ORF72 expansion carriers from noncarriers. However, higher CSF TDP-43 levels were detected in ALS than in FTLD, which might be an indicator of a more rapid progression of TDP-43 pathology in ALS.