Multiplexed analysis of macrophage polarisation in pulmonary metastases of microsatellite stable colorectal cancer.

Tumour-associated macrophages (TAMs) express a continuum of phenotypes ranging from an anti-tumoural M1-like phenotype to a pro-tumoural M2-like phenotype. During cancer progression, TAMs may shift to a more M2-like polarisation state, but the role of TAMs in CRC metastases is unclear. We conducted a comprehensive spatial and prognostic analysis of TAMs in CRC pulmonary metastases and corresponding primary tumours using multiplexed immunohistochemistry and machine learning-based image analysis. We obtained data from 106 resected pulmonary metastases and 74 corresponding primary tumours. TAMs in the resected pulmonary metastases were located closer to the cancer cells and presented a more M2-like polarised state in comparison to the primary tumours. Higher stromal M2-like macrophage densities in the invasive margin of pulmonary metastases were associated with worse 5-year overall survival (HR 3.19, 95% CI 1.35-7.55, p = 0.008). The results of this study highlight the value of multiplexed analysis of macrophage polarisation in cancer metastases and might have clinical implications in future cancer therapy.

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.

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.

Area-based disparities in non-small-cell lung cancer survival.

BACKGROUND: In the Nordic countries, universal healthcare access has been effective in reducing socioeconomic disparities in non-small-cell lung cancer (NSCLC) management. However, other factors, such as proximity to healthcare facilities, may still affect access to care. This study aimed at investigating the influence of residential area on NSCLC survival. METHODS: This population-based study utilized hospital records to identify NSCLC patients who underwent their initial treatment at Vaasa Central Hospital between January 1, 2016, and December 31, 2020. Patients were categorized based on their postal codes into urban areas (≤50 km from the hospital) and rural areas (>50 km from the hospital). Survival rates between these two groups were compared using Cox regression analysis. RESULTS: A total of 321 patients were included in the study. Patients residing in rural areas (n = 104) exhibited poorer 12-month survival rates compared to their urban counterparts (n = 217) (unadjusted Hazard Ratio [HR]: 1.38; 95% Confidence Interval [CI]: 1.01-1.89; p = 0.042). After adjusting for factors such as performance status, frailty, and stage at diagnosis in a multivariate Cox regression model, the adjusted HR increased to 1.47 (95% CI: 1.07-2.01; p = 0.017) for patients living in rural areas compared to those in urban areas. INTERPRETATION: The study findings indicate that the distance to the hospital is associated with increased lung cancer mortality. This suggests that geographical proximity may play a crucial role in the disparities observed in NSCLC survival rates. Addressing these disparities should involve strategies aimed at improving healthcare accessibility, particularly for patients residing in rural areas, to enhance NSCLC outcomes and reduce mortality.

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.

Standard Lymphadenectomy for Esophageal and Lung Cancer: Variability in the Number of Examined Lymph Nodes Among Pathologists and Its Survival Implication.

AIM: We compared variability in number of examined lymph nodes between pathologists and analyzed survival implications in lung and esophageal cancer after standardized lymphadenectomy. METHODS: Outcomes of 294 N2 dissected lung cancer patients and 132 2-field dissected esophageal cancer patients were retrospectively examined. The primary outcome was difference in reported lymph node count among pathologists. Secondary outcomes were overall and disease-specific survival related to this count and survival related to the 50% probability cut-off value of detecting metastasis based on the number of examined lymph nodes. RESULTS: The median number of examined lymph nodes in lung cancer was 13 (IQR 9-17) and in esophageal cancer it was 22 (18-29). The pathologist with the highest median number of examined nodes had > 50% higher lymph node yield compared with the pathologist with the lowest median number of nodes in lung (15 vs. 9.5, p = 0.003), and esophageal cancer (28 vs. 17, p = 0.003). Survival in patients stratified by median reported lymph node count in both lung (adjusted RMST ratio < 14 vs. ≥ 14 lymph nodes 0.99, 95% CI 0.88-1.10; p = 0.810) and esophageal cancer (adjusted RMST ratio < 25 vs. ≥ 25 lymph nodes 0.95, 95% CI 0.79-1.15, p = 0.612) was similar. The cut-off value for 50% probability of detecting metastasis by number of examined lymph nodes in lung cancer was 15.7 and in esophageal cancer 21.8. When stratified by this cut-off, no survival differences were seen. CONCLUSION: The quality of lymphadenectomy based on lymph node yield is susceptible to error due to detected variability between pathologists in the number of examined lymph nodes. This variability in yield did not have any survival effect after standardized lymphadenectomy.

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.

Preoperative esophageal stenting and short-term outcomes of surgery for esophageal cancer in a population-based study from Finland and Sweden.

Population-based studies examining whether preoperative esophageal stenting influences the short-term outcomes after esophagectomy for esophageal cancer are lacking. This nationwide cohort combining data from Finland and Sweden was conducted to cover this gap. Patients with locally advanced esophageal cancer (T ≥ 3 and/or N ≥ 1, M0) who underwent esophagectomy between 2007 and 2014 were identified from nationwide registries in Finland and Sweden. The study exposure was preoperative stenting. The primary outcomes were 30- and 90-day mortality. Secondary outcomes were length of hospital stay and 30- and 90-day readmission rates. Multivariable Cox and linear regression analyses provided hazard ratios (HRs) with 95% confidence intervals (CIs) adjusted for age, sex, comorbidity, tumor histology, year of surgery, and country. Of all 1029 participating patients who underwent surgery for locally advanced esophageal cancer, 127 (12.3%) had an esophageal stent inserted preoperatively. The absolute 30-day mortality rates were higher in stented patients (3.9%) than in those without a stent (1.6%), but the HR was not statistically significantly increased (HR 2.42; 95% CI 0.85-6.92). Similarly, the absolute 90-day mortality rates were increased after preoperative stenting (11.8%) compared to no stenting (7.0%), but again the HR was not statistically significantly increased (HR 1.68; 95% CI 0.95-2.98). Preoperative stenting did not influence length of hospital stay or readmission rates. The possibly increased short-term mortality after preoperative stenting in patients who undergo esophagectomy for esophageal cancer indicated in this study suggests a cautious approach to preoperative stenting until future research or meta-analyses provide a more definite answer.

Laryngo-tracheal resections in the Nordic countries: an option for further centralization?

PURPOSE: We aimed to obtain information on the number of Nordic centers performing tracheal resections, crico-tracheal resections, and laryngo-tracheal reconstructions, as well as the patient volume and the standard regimens associated with these procedures. METHODS: Consultants at all Departments of Otorhinolaryngology-Head and Neck Surgery (ORL-HNS, n = 22) and Thoracic Surgery (n = 21) in the five Nordic countries were invited (April 2018-January 2019) to participate in an online survey. RESULTS: All 43 departments responded to the survey. Twenty departments declared to perform one or more of the three types of tracheal resections. At five hospitals, departments of ORL-HNS and Thoracic Surgery perform these operations in collaboration. Hence, one or more of the tracheal operations in question are carried out at 15 centers. The median annual number of tracheal operations per center is five (range 1-20). Great variations were found regarding contraindications (relative and absolute) for surgery, the use of guardian sterno-mental sutures (all patients, 33%; selected cases, 40% of centers), prophylactic antibiotic therapy (cefuroxime +/- metronidazole, penicillin +/- metronidazole, clindamycin, imipenem, or none), post-operative follow-up time (range: children: 3-120 months; adults: 0-60 months), and the performance of post-operative bronchoscopy. CONCLUSIONS: Fifteen centers each perform a low number of annual operations with significant variations in the selection of patients and the clinical setup, which raises the question if a higher degree of collaboration and centralization would be warranted. We encourage Nordic transnational collaboration, pursuing alignment on central management issues, and establishment of a common prospective database for future tracheal resection surgery.

Short-Term Outcomes Following Minimally Invasive and Open Esophagectomy: A Population-Based Study from Finland and Sweden.

BACKGROUND: Population-based studies comparing minimally invasive esophagectomy (MIE) and open esophagectomy (OE) relative to 90-day postoperative mortality are needed. OBJECTIVE: The aim of this study was to compare short-term outcomes following these two techniques for esophageal cancer. METHODS: Patients undergoing MIE (n = 217) or OE (n = 1397) for esophageal cancer between 2007 and 2014 were identified from nationwide complete registries in Finland and Sweden. The primary outcome was 90-day mortality, and secondary outcomes were 30-day mortality, length of hospital stay, and 30- and 90-day readmission rate. Results were adjusted for age, sex, comorbidity, tumor histology, surgery year, and country. RESULTS: Ninety-day mortality rates were 4.1% (n = 9 of 217) for MIE and 6.8% (n = 95 of 1397) for OE; 90-day mortality was halved after MIE [adjusted hazard ratio (HR) 0.49, 95% confidence interval (CI) 0.24-0.99]. There was no difference in 30-day mortality (adjusted HR 0.87, 95% CI 0.29-2.66). Median hospital stay was 15 days for MIE and 16 days for OE (adjusted ß -0.17, standard error 0.08, p = 0.030). The 30-day readmission rates were 8.9% after MIE and 12.0% after OE (adjusted HR 0.57, 95% CI 0.34-0.94), while the 90-day readmission rates were 28.8% and 33.6%, respectively, without a statistically significant difference (adjusted HR 0.82, 95% CI 0.61-1.10). CONCLUSIONS: This population-based study from Finland and Sweden revealed lower 90-day mortality, shorter hospital stay, and lower 30-day readmission rates after MIE compared with OE for esophageal cancer. These findings support the use of minimally invasive approaches.

Catheter-Directed Thrombolysis Versus Pharmacomechanical Thrombectomy for Upper Extremity Deep Venous Thrombosis: A Cost-Effectiveness Analysis.

BACKGROUND: Upper extremity deep vein thrombosis represents (UEDVT) 2-3% of all deep vein thrombosis. Catheter directed thrombolysis (CDT) was replaced largely by pharmacomechanical thrombolysis (PMT) in our institution. In this study we compared the immediate and 1-year results as well as the total hospital costs between CDT and PMT in the treatment of UEDVT. METHODS: From 2006 to 2013, 55 patients with UEDVT were treated with either CDT or PMT at Helsinki University Hospital. Of them, 43 underwent thoracoscopic rib resection later to relieve phlebography-confirmed vein compression. This patient cohort was prospectively followed up with repeated phlebographies. CDT was performed to 24 patients, and 19 had PMT with a Trellis™ device. Clinical evaluation and vein patency assessment were performed with either phlebography or ultrasound 1 year after the thrombolysis. Primary outcomes were immediate technical success, 1-year vein patency, and costs of the initial treatment. RESULTS: The immediate overall technical success rate, defined as recanalization of the occluded vein and removal of the fresh thrombus, was 91.7% in the CDT group and 100% in the PMT group (n.s.). The median thrombolytic time was significantly longer in CDT patients than that in PMT patients (21.1 vs. 0.33 hr, P < 0.00001). There were no procedure-related complications. The 1-year primary assisted patency rate was similar in both the groups (91.7% and 94.7%). There were no recurrences of clinical DVT. The hospital costs for the acute period were significantly lower in the PMT group than those in the CDT group (medians: 11,476 € and 5,975 € in the CDT and PMT groups, respectively [P < 0.00001]). CONCLUSIONS: The clinical results of the treatment of UEDVT with CDT or PMT were similar. However, PMT required shorter hospital stay and less intensive surveillance, leading to lower total costs.

Diagnostics and current care of myasthenia gravis.

Myasthenia gravis (MG) is the most common neuromuscular transmission disorder, causing weakness of skeletal muscles on exertion. The course of the disease is highly variable, symptoms and signs may change rapidly due to infection or pregnancy. MG is classified using serological, electrophysiological and pharmaceutical tools. A precise diagnosis allows for the choice of right treatment, predicts the course of disease and hence helps with the follow-up. In this review we present Finnish guidelines for diagnostics, treatment and follow-up of MG patients.

[Developing surgical options for lung cancer]. / Keuhkosyövän kehittyvät leikkaushoitomahdollisuudet.

The selection of correct treatment for lung cancer is multidisciplinary collaboration and requires careful assessment of the extent of the tumor and the condition of the patient. In localized non-small cell lung cancer, mere surgery or surgery in combination with adjuvant therapies are the best options for curing the disease. The trend in modern surgery is mini-invasiveness and preservation of lung tissue. Accordingly, any unit conducting lung cancer operations should have access to all modern techniques in order to provide each patient with optimal, patient-tailored surgical therapy.

Esophageal Ulcer as a Cause of Death: A Population-Based Study. Mortality of Esophageal Ulcer Disease.

BACKGROUND: This study aimed at defining the mortality and the nature of fatal complications that arise out of esophageal ulcer for one clearly defined geographical area. METHODS: In this national, population-based study, the occurrence of fatal esophageal ulcer or ulcer requiring hospital treatment between January 1987 and December 2000 was assessed by the use of Finland's administrative databases. Medical records provided etiology of fatal ulcer and agonal symptoms. RESULTS: Due to an esophageal ulcer, 2,242 patients received treatment in Finnish hospitals, at an annual frequency of 3.2/100,000. Ulcer with hemorrhage (53.5%), perforation (38.4%), or aspiration pneumonia (2.3%) was the cause of death in 86 patients for an annual mortality of 0.12/100,000. Based on the number of ulcers treated, 3.8% cases ended fatally. Gastroesophageal reflux disease (GERD) seemed to be the etiologic factor for ulcer in 68 (79.0%) patients. The most common agonal symptoms were hematemesis (41.8%), abdominal pain (25.6%), melaena (22.1%), and dyspnea (17.4%). Twenty (23.3%) patients were found dead at home. CONCLUSION: The rarity of the disease, related disorders, and the diversity of symptoms make the complicated esophageal ulcer a diagnostic challenge. Effective monitored treatment for severe GERD may be an important step to prevent fatal outcome.

Open versus minimally invasive esophagectomy: clinical outcomes for locally advanced esophageal adenocarcinoma.

BACKGROUND: We compared oncologic and surgical outcome between minimally invasive esophagectomy (MIE) and the Ivor Lewis-type open approach (OE) in the treatment of locally advanced esophageal adenocarcinoma (EAC). MATERIALS AND METHODS: Of 284 patients undergoing surgery for EAC between 2003 and 2013, the 153 selected with locally advanced EAC were 74 MIEs and 79 OEs [median age, 66 for MIE, 63 for OE (p = 0.009)]. Neoadjuvant therapy was given to 82% of MIEs and 78% of OEs. In the OE group, 86% was male, and in the MIE group, 78%. Data assessed were oncologic, intraoperative, and postoperative. RESULTS: Mortality at 30 days was 3% for MIE and 1% for OE; and 90-day mortality was 4% for MIE and 5% for OE. The complication rate for MIE was 50%, and 60% for OE (p = 0.181). The pneumonia rate was 18% for MIE and 19% for OE; leak rate was 7% for MIE and 6% for OE; conduit necrosis was 0 for MIE and 3% for OE; and rate of airway-conduit fistula was 3% for MIE and 1 % for OE. Median blood loss (MIE 300 vs. OE 800, p < 0.0001), overall stay (MIE 13 vs. OE 14, p = 0.040), and harvested lymph nodes (MIE 20 vs. OE 22, p = 0.021) all were in favor of MIE. Median ICU stay and operative time did not differ. Neither did overall (OS) nor recurrence-free (RFS) 3-year survival differs significantly (MIE 64% vs. OS OE 49%, MIE 57% vs. RFS OE 53%). CONCLUSIONS: In our institution, MIE appears to produce oncologic and survival results similar to those of OE. Shorter length of stay and less operative blood loss may reduce costs for MIE.

[Treatment of adult tracheal stenosis]. / Aikuisten henkitorven ahtaumien kirurginen hoito.

Tracheal stenosis is a rare condition with symptoms mimicking asthma or COPD. The most frequent benign tracheal stenosis is caused by lesions related either to intubation or tracheostomy. Primary tracheal tumors or secondary malignancies such as locally advanced esophageal cancer are rare causes. As a rare disease the diagnosis and treatment are often delayed. Endoscopic therapy is the primary treatment for tracheal stenosis. Tracheal resection is indicated in resectable malignant tumors and in benign stenosis which do not respond to endoscopic treatment or require repeated therapy. In these situations, surgery provides a safe and a long-term solution. Currently, surgery is rarely an option in long-segment tracheal lesions. Advances in stem cell technology, tracheal transplantation and tissue engineering may, however, provide a solution for these problems in the future.

[Endoscopic surgery accelerates recovery from empyema]. / Tähystyskirurgia nopeuttaa empyeemasta toipumista.

The incidence of thoracic empyema is increasing. Early treatment of empyema should focus on optimal drainage and antibiotics. If conventional therapy fails, surgical intervention has to be considered and approximately 30% of all patients require surgery. In a three-year period (2011-2013), 182 patients were operated at Helsinki University Hospital due to pleural empyema. Thoracoscopic decortication was performed on 44% of the patients and 56% underwent open surgery. After thoracoscopy, the patients had a shorter hospital stay and fewer reoperations. Thoracoscopic decortication should therefore be the first-line procedure in the surgical treatment of pleural empyema.