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.

Malpractice claims after antireflux surgery and paraesophageal hernia repair: a population-based analysis.

BACKGROUND: The complication rate of modern antireflux surgery or paraesophageal hernia repair is unknown, and previous estimates have been extrapolated from institutional cohorts. METHODS: A population-based retrospective cohort study of patient injury cases involving antireflux surgery and paraesophageal hernia repair from the Finnish National Patient Injury Centre (PIC) register between Jan 2010 and Dec 2020. Additionally, the baseline data of all the patients who underwent antireflux and paraesophageal hernia operations between Jan 2010 and Dec 2018 were collected from the Finnish national care register. RESULTS: During the study period, 5734 operations were performed, and the mean age of the patients was 54.9 ± 14.7 years, with 59.3% (n = 3402) being women. Out of all operations, 341 (5.9%) were revision antireflux or paraesophageal hernia repair procedures. Antireflux surgery was the primary operation for 79.9% (n = 4384) of patients, and paraesophageal hernia repair was the primary operation for 20.1% (n = 1101) of patients. A total of 92.5% (5302) of all the operations were laparoscopic. From 2010 to 2020, 60 patient injury claims were identified, with half (50.0%) of the claims being related to paraesophageal hernia repair. One of the claims was made due to an injury that resulted in a patient's death (1.7%). The mean Comprehensive Complication Index scores were 35.9 (± 20.7) and 47.6 (± 20.8) (p = 0.033) for antireflux surgery and paraesophageal hernia repair, respectively. Eleven (18.3%) of the claims pertained to redo surgery. CONCLUSIONS: The rate of antireflux surgery has diminished and the rate of paraesophageal hernia repair has risen in Finland during the era of minimally invasive surgery. Claims to the PIC remain rare, but claims regarding paraesophageal hernia repairs and redo surgery are overrepresented. Additionally, paraesophageal hernia repair is associated with more serious complications.

Western European Variation in the Organization of Esophageal Cancer Surgical Care.

Reasons for structural and outcome differences in esophageal cancer surgery in Western Europe remain unclear. This questionnaire study aimed to identify differences in the organization of esophageal cancer surgical care in Western Europe. A cross-sectional international questionnaire study was conducted among upper gastrointestinal (GI) surgeons from Western Europe. One surgeon per country was selected based on scientific output and active membership in the European Society for Diseases of the Esophagus or (inter)national upper GI committee. The questionnaire consisted of 51 structured questions on the structural organization of esophageal cancer surgery, surgical training, and clinical audit processes. Between October 2021 and October 2022, 16 surgeons from 16 European countries participated in this study. In 5 countries (31%), a volume threshold was present ranging from 10 to 26 annual esophagectomies, in 7 (44%) care was centralized in designated centers, and in 4 (25%) no centralizing regulations were present. The number of centers performing esophageal cancer surgery per country differed from 4 to 400, representing 0.5-4.9 centers per million inhabitants. In 4 countries (25%), esophageal cancer surgery was part of general surgical training and 8 (50%) reported the availability of upper GI surgery fellowships. A national audit for upper GI surgery was present in 8 (50%) countries. If available, all countries use the audit to monitor the quality of care. Substantial differences exist in the organization and centralization of esophageal cancer surgical care in Western Europe. The exchange of experience in the organizational aspects of care could further improve the results of esophageal cancer surgical care in Europe.

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.

Paraconduit hernia after minimally invasive esophagectomy - incidence and risk factors.

BACKGROUND: Paraconduit hernia is a relatively common long-term complication after esophagectomy which has the potential to cause great morbidity and even mortality. The aim of this study is to examine the risk factors and incidence of paraconduit hernia after minimally invasive esophagectomy (MIE) in esophageal adenocarcinoma patients who have received neoadjuvant treatment. METHODS: Minimally invasive esophagectomies done for patients with neoadjuvant-treated esophageal or esophagogastric junction adenocarcinoma at our institution between 2008 and 2018 were included in this study. All patients with symptomatic or incidentally found paraconduit hernias on computed tomography scans were identified. Patient demographics were analyzed using logistic and Cox regression. RESULTS: The incidence of paraconduit hernia was 14 out of 171 patients (8.2%). The hernia was surgically repaired in 10 (71.4%) of patients. Laparoscopic approach was used in 90% of the repairs, with one (11.1%) conversion to laparotomy. Emergency operations accounted for three (30%) of the operations. The complication rate was 10% (n = 1) and 90-day mortality was 10% (n = 1). Neither sarcopenia nor muscle mass loss was not associated with paraconduit hernia development, whereas preoperative radiotherapy (OR = 8.57, CI = 1.98-33.8, p = .002) was a strong risk factor for paraconduit hernia. Higher BMI had a protective effect (OR = 0.83 per point, 95% CI = 0.69-0.97, p = .027). CONCLUSIONS: Paraconduit hernia is a relatively common complication after MIE for neoadjuvant-treated adenocarcinoma patients. Preoperative radiotherapy was associated with a higher risk of paraconduit hernia. Minimally invasive repair of paraconduit hernia after esophagectomy is efficient and has a low complication rate both in elective and emergency cases.

An International Cohort Study of Prognosis Associated With Pathologically Complete Response Following Neoadjuvant Chemotherapy Versus Chemoradiotherapy of Surgical Treated Esophageal Adenocarcinoma.

OBJECTIVE: To compare overall (OS) and recurrence-free survival (RFS) in esophageal adenocarcinoma patients with a pathologically complete response (pCR) following neoadjuvant chemotherapy (nCT) or neoadjuvant chemoradiotherapy (nCRT). BACKGROUND: In the absence of survival differences in several prior studies comparing nCT with nCRT, the higher rate of pCR after nCRT has been suggested as reason to prefer this modality over nCT. METHODS: An international cohort study included data from 8 high-volume centers. Inclusion criteria was patients with esophageal adenocarcinoma, between 2008 and 2018, who had a pCR after nCT or nCRT. Univariate analysis was used to compare demographic factors, and Kaplan-Meier survival analysis used to compare 5-year OS and RFS between groups. RESULTS: In all, 465 patients with pCR following neoadjuvant treatment were included; 132 received nCT and 333 received nCRT. There was no statistically significant difference in 5-year OS between groups (78.8% (nCT) vs 65.5% (nCRT), P =0.099), with a similar result demonstrated in multivariate analysis (HR=1.19, 95% CI 0.77-1.84). 5-year RFS was significantly reduced in patients with a pCR following neoadjuvant chemoradiotherapy (75.3% (nCRT) vs 87.1% (nCT), P =0.026). Multivariate analysis confirmed nCRT was associated with a poorer 5-year RFS (HR=1.70, 95% CI 1.22-2.99). nCRT associated with a significantly greater prevalence of 5-year distant recurrence (odds ratio=2.50, 95% CI 1.25-4.99). CONCLUSIONS: The results of this international cohort study show that the prognosis of pCR following different neoadjuvant regimes differs, bringing into question the validity of this measure as an oncological surrogate when comparing neoadjuvant treatment schemes for esophageal adenocarcinoma.

Learning Curves of Ivor Lewis Totally Minimally Invasive Esophagectomy by Hospital and Surgeon Characteristics: A Retrospective Multinational Cohort Study.

OBJECTIVE: To describe the pooled learning curves of Ivor Lewis totally minimally invasive esophagectomy (TMIE) in hospitals stratified by predefined hospital- and surgeon-related factors. BACKGROUND: Ivor Lewis (TMIE is known to have a long learning curve which is associated with considerable learning associated morbidity. It is unknown whether hospital and surgeon characteristics are associated with more efficient learning. METHODS: A retrospective analysis of prospectively collected data of consecutive Ivor Lewis TMIE patients in 14 European hospitals was performed. Outcome parameters used as proxy for efficient learning were learning curve length, learning associated morbidity, and the plateau level regarding anastomotic leakage and textbook outcome. Pooled incidences were plotted for the factor-based subgroups using generalized additive models and 2-phase models. Casemix predicted outcomes were plotted and compared with observed outcomes. The investigated factors included annual volume, TMIE experience, clinic visits, courses and fellowships followed, and proctor supervision. RESULTS: This study included 2121 patients. The length of the learning curve was shorter for centers with an annual volume >50 compared to centers with an annual volume <50. Analysis with an annual volume cut-off of 30 cases showed similar but less pronounced results. No outcomes suggesting more efficient learning were found for longer experience as consultant, visiting an expert clinic, completing a minimally invasive esophagectomy fellowship or implementation under proctor supervision. CONCLUSIONS: More efficient learning was observed in centers with higher annual volume. Visiting an expert clinic, completing a fellowship, or implementation under a proctor's supervision were not associated with more efficient learning.

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.

Congenital diaphragmatic hernia in adults: a decade of experience from a single tertiary center.

INTRODUCTION: Congenital diaphragmatic hernias (CDHs) in adults remain rare, with limited data on them available. However, CDHs can cause respiratory and gastrointestinal symptoms in adults, even resulting in the strangulation of the bowel when incarcerated. Here, we aimed to analyze surgical outcomes among adult patients. The primary outcome of interest was the complication rate, reoperations and 90-day mortality after laparoscopic and open hernia repair. METHODS: We identified all adult patients diagnosed with a Morgagni or Bochdalek hernia treated operatively between 2010 and 2019 in a single tertiary care hospital. Data on patient demographics, surgical characteristics, mortality and morbidity were collected. RESULTS: In total, we identified 37 patients (67.6% female; average age, 57 years). Overall, 78.4% patients underwent minimally invasive operations, while 35.1% underwent emergency operations. A Clavien-Dindo grade II-V complication was experienced by 18.9% of patients. No deaths occurred within 90 days of surgery, and we detected no recurrences in short-term or long-term follow-up. A minimally invasive technique correlated with a shorter hospital stay of 3.6 days versus 6.8 days in the open surgery group (p = .007, t = 3.3, 95% confidence interval = 1.04-5.21). CONCLUSION: Our findings indicate that the laparoscopic repair of a congenital diaphragmatic hernia is safe and effective, offering short hospital stay and a low amount of complications.

The Effect of Postoperative Complications After Minimally Invasive Esophagectomy on Long-term Survival: An International Multicenter Cohort Study.

BACKGROUND: Esophagectomy is a technically challenging procedure, associated with significant morbidity. The introduction of minimally invasive esophagectomy (MIE) has reduced postoperative morbidity. OBJECTIVE: Although the short-term effect on complications is increasingly being recognized, the impact on long-term survival remains unclear. This study aims to investigate the association between postoperative complications following MIE and long-term survival. METHODS: Data were collected from the EsoBenchmark Collaborative composed by 13 high-volume, expert centers routinely performing MIE. Patients operated between June 1, 2011 and May 31, 2016 were included. Complications were graded using the Clavien-Dindo (CD) classification. To correct for short-term effects of postoperative complications on mortality, patients who died within 90 days postoperative were excluded. Primary endpoint was 5-year overall survival. RESULTS: A total of 915 patients were included with a mean follow-up time of 30.8 months (standard deviation 17.9). Complications occurred in 542 patients (59.2%) of which 50.2% had a CD grade ≥III complication [ie, (re)intervention, organ dysfunction, or death]. The incidence of anastomotic leakage (AL) was 135 of 915 patients (14.8%) of which 84 patients were classified as a CD grade ≥III. Multivariable analysis showed a significantly deteriorated long-term survival in all patients with AL [hazard ratio (HR) 1.68, 95% confidence interval (CI) 1.25-2.24]. This inverse relation was most distinct when AL was scored as a CD grade ≥III (HR 1.83, 95% CI 1.30-2.58). For all other complications, no significant association with long-term survival was found. CONCLUSION: The occurrence and severity of AL, but not overall complications, after MIE negatively affect long-term survival of esophageal cancer patients.

Percutaneous endoscopic gastrostomy: a dislodgement complication due to a moving hiatal hernia.

Objectives: Frail patients with malnourishment due to an esophageal condition and dysphagia are often unamenable to safe surgery. Thus, in high-risk patients, less invasive techniques such as percutaneous endoscopic gastrostomy (PEG) are regarded as a safer choice. Nevertheless, as described here, PEG insertion can have rare serious complications.Materials and methods: We report the case of a frail patient with dysphagia due to a large Zenker's diverticulum and concomitant giant hiatal hernia. To improve her nutrinitional status before surgery she received a PEG after endoscopic repositioning of the hernia.Results: Within 48 hours after hernia repositioning and PEG insertion, a severe adverse event ensued: dislodgement of the PEG due to stomach reherniation.Conclusions: This case challenges the use of PEG as an only means for gastric fixation for hiatal hernia.

Long-Term Health-Related Quality of Life (HRQoL) After Redo-Fundoplication.

BACKGROUND: We aim to shed light on long-term subjective outcomes after re-operations for failed fundoplication. METHODS: 1809 patients were operated on for hiatal hernia and/or gastroesophageal reflux disease (GERD) at the Helsinki University Hospital between 2000 and 2017. 111 (6%) of these had undergone a re-operation for a failed antireflux operation. Overall, HRQoL was assessed in 89 patients at the latest follow-up using the generic 15D© instrument. The results were compared to a sample of the general population, weighted to reflect the age and gender distribution of patients. Disease-specific HRQoL was assessed using the GERD-HRQoL questionnaire. We studied variation in the overall HRQoL with respect to disease-specific HRQoL and known patients' parameters using univariate and multivariable linear regression models. RESULTS: The median postoperative follow-up period was 9.3 years. All patients were operated on laparoscopically (6% conversion rate), and 87% were satisfied with the re-operation. Postoperative complications were minimal (5%). Twelve patients (11%) underwent a second re-operation. The median GERD-HRQoL score was nine. In multivariable analysis, four variables were independently associated with the 15D score, suggesting a decrease in the 15D score with increasing GERD-HRQoL score, increasing Charlson Comorbidity Index (CCI) and the presence of chronic pain syndrome (CPS) and depression. CONCLUSION: Re-do LF is a safe procedure in experienced hands and may offer acceptable long-term alleviation in patients with recurring symptoms after antireflux surgery. Decreased HRQoL in the long run is related to recurring GERD and co-morbidities.

Technique of open and minimally invasive intrathoracic reconstruction following esophagectomy-an expert consensus based on a modified Delphi process.

BACKGROUND: In recent years, minimally invasive Ivor Lewis (IL) esophagectomy with high intrathoracic anastomosis has emerged as surgical standard of care for esophageal cancer in expert centers. Alongside this process, many divergent technical aspects of this procedure have been devised in different centers. This study aims at achieving international consensus on the surgical steps of IL reconstruction using Delphi methodology. METHODS: The expert panel consisted of specialized esophageal surgeons from 8 European countries. During a two-round Delphi process, a detailed analysis and consensus on key steps of intrathoracic gastric tube reconstruction (IL esophagectomy) was performed. RESULTS: Response rates in Delphi rounds 1 and 2 were 100% (22 of 22 experts) and 83.3% (20 of 24 experts), respectively. Three essential technical areas of intrathoracic gastric tube reconstruction were identified: first, vascularization of the gastric conduit, second, gastric mobilization, tube formation and pull-up, and third, anastomotic technique. In addition, 3 main techniques for minimally invasive intrathoracic anastomosis are currently practiced: (i) end-to-side circular stapled, (ii) end-to-side double stapling, and (iii) side-to-side linear stapled technique. The step-by-step procedural analysis unveiled common approaches but also different expert practice. CONCLUSION: This precise technical description may serve as a clinical guideline for intrathoracic reconstruction after esophagectomy. In addition, the results may aid to harmonize the technical evolution of this complex surgical procedure and thereby facilitate surgical training.

Health-related quality of life after laparoscopic repair of giant paraesophageal hernia: how does recurrence in CT scan compare to clinical success?

BACKGROUND: Computed tomography (CT) is widely used in the diagnosis of giant paraesophageal hernias (GPEH) but has not been utilised systematically for follow-up. We performed a cross-sectional observational study to assess mid-term outcomes of elective laparoscopic GPEH repair. The primary objective of the study was to evaluate the radiological hernia recurrence rate by CT and to determine its association with current symptoms and quality of life. METHODS: All non-emergent laparoscopic GPEH repairs between 2010 to 2015 were identified from hospital medical records. Each patient was offered non-contrast CT and sent questionnaires for disease-specific symptoms and health-related quality of life. RESULTS: The inclusion criteria were met by 165 patients (74% female, mean age 67 years). Total recurrence rate was 29.3%. Major recurrent hernia (> 5 cm) was revealed by CT in 4 patients (4.3%). Radiological findings did not correlate with symptom-related quality of life. Perioperative mortality occurred in 1 patient (0.6%). Complications were reported in 27 patients (16.4%). CONCLUSIONS: Successful laparoscopic repair of GPEH requires both expertise and experience. It appears to lead to effective symptom relief with high patient satisfaction. However, small radiological recurrences are common but do not affect postoperative symptom-related patient wellbeing.

Anastomotic Techniques and Associated Morbidity in Total Minimally Invasive Transthoracic Esophagectomy: Results From the EsoBenchmark Database.

OBJECTIVE: The aim of this study was to describe anastomotic techniques used for total minimally invasive transthoracic esophagectomy (ttMIE) and to analyze the associated morbidity. BACKGROUND: ttMIE faces increasing application in surgical treatment of esophageal cancer. For esophagogastric reconstruction, different anastomotic techniques are currently used, but their effect on postoperative anastomotic leakage and morbidity has not been investigated. PATIENTS AND METHODS: Patients were selected from a basic dataset, collected during a 5-year period from 13 international surgical high-volume centers. Endpoints were anastomotic leakage rate and postoperative morbidity in correlation to anastomotic techniques, measured by the Clavien-Dindo classification and the Comprehensive Complication Index (CCI). RESULTS: Five anastomotic techniques were identified in 966 patients after ttMIE: intrathoracic end-to-side circular-stapled technique in 427 patients (double-stapling n = 90, purse-string n = 337), intrathoracic (n = 109) or cervical (n = 255) side-to-side linear-stapled, and cervical end-to-side hand-sewn (n = 175). Leakage rates were similar in intrathoracic and cervical anastomoses (15.9% vs 17.2%, P = 0.601), but overall complications (56.7%% vs 63.7%, P = 0.029) and median 90-day CCI {21 [interquartile range (IQR) 0-36] vs 29 [IQR 0-40], P = 0.019} favored intrathoracic reconstructions. Leakage rates after intrathoracic end-to-side double-stapling (23.3%) and cervical end-to-side hand-sewn (25.1%) techniques were significantly higher compared with intrathoracic side-to-side linear (15.6%), end-to-side purse-string (13.9%), and cervical side-to-side linear-stapled esophagogastrostomies (11.8%) (P < 0.001). Multivariable analysis confirmed anastomotic technique as independent predictor of leakage after ttMIE. CONCLUSION: Results of this analysis present the current status of the technical evolution of ttMIE with anastomotic leakage as predominant surgical complication. However, technique-related morbidity requires cautious interpretation considering the long learning curve of this complex surgical procedure.

Distribution of lymph node metastases in esophageal carcinoma [TIGER study]: study protocol of a multinational observational study.

BACKGROUND: An important parameter for survival in patients with esophageal carcinoma is lymph node status. The distribution of lymph node metastases depends on tumor characteristics such as tumor location, histology, invasion depth, and on neoadjuvant treatment. The exact distribution is unknown. Neoadjuvant treatment and surgical strategy depends on the distribution pattern of nodal metastases but consensus on the extent of lymphadenectomy has not been reached. The aim of this study is to determine the distribution of lymph node metastases in patients with resectable esophageal or gastro-esophageal junction carcinoma in whom a transthoracic esophagectomy with a 2- or 3-field lymphadenectomy is performed. This can be the foundation for a uniform worldwide staging system and establishment of the optimal surgical strategy for esophageal cancer patients. METHODS: The TIGER study is an international observational cohort study with 50 participating centers. Patients with a resectable esophageal or gastro-esophageal junction carcinoma in whom a transthoracic esophagectomy with a 2- or 3-field lymphadenectomy is performed in participating centers will be included. All lymph node stations will be excised and separately individually analyzed by pathological examination. The aim is to include 5000 patients. The primary endpoint is the distribution of lymph node metastases in esophageal and esophago-gastric junction carcinoma specimens following transthoracic esophagectomy with at least 2-field lymphadenectomy in relation to tumor histology, tumor location, invasion depth, number of lymph nodes and lymph node metastases, pre-operative diagnostics, neo-adjuvant therapy and (disease free) survival. DISCUSSION: The TIGER study will provide a roadmap of the location of lymph node metastases in relation to tumor histology, tumor location, invasion depth, number of lymph nodes and lymph node metastases, pre-operative diagnostics, neo-adjuvant therapy and survival. Patient-tailored treatment can be developed based on these results, such as the optimal radiation field and extent of lymphadenectomy based on the primary tumor characteristics. TRIAL REGISTRATION: NCT03222895 , date of registration: July 19th, 2017.

Long-term results of surgical resection of lung metastases from soft tissue sarcoma: A single center experience.

BACKGROUND: A single-institution experience of pulmonary metastasectomy in soft tissue sarcoma (STS) was retrospectively reviewed. Our specific aim was to examine, whether the resection of pulmonary metastases could be curative. We also compared overall survival (OS) of patients after complete or incomplete pulmonary resection and nonsurgical treatment. METHODS: Between 1987 and 2016, 1580 patients were treated for STS with curative intent by Soft Tissue Sarcoma Group at Helsinki University Hospital, Finland. Three hundred forty-seven patients (22%) developed advanced disease and 130 STS patients (9%) developed pulmonary metastases as first systemic relapse. Seventy four patients (5%) were operated for lung metastases. RESULTS: Fifty-five patients (42%) had a complete and 19 (15%) incomplete resection. Fifty-six (43%) were unoperated. Median OS after complete or incomplete metastasectomy, chemotherapy, or best supportive care was 22, 18, 8, and 5 months, respectively. Twelve patients (9%) developed no further metastases and are alive with no evidence of disease. Disease-free survival (DFS) for completely resected patients was 17% at 5 years. All long-term survivors had oligometastatic disease and they underwent one to three complete metastasectomies. CONCLUSIONS: Complete pulmonary metastasectomy in STS results in 5 years DFS in nearly one-fifth of patients. Most of these patients are probably cured.

Malignant pleural mesothelioma in Finland: regional and gender variation.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare occupational cancer with a poor prognosis. Even with a multimodality treatment approach, the treatment outcomes remain unsatisfactory. The use of asbestos has been banned in most developed countries, but MPM continues to be a significant occupational disease also in these countries. Aim of this study is to identify modern epidemiology and assess equality in care. METHODS: Our study cohort consists of 1010 patients diagnosed with MPM in Finland during 2000-2012. The data were collected from the Finnish Cancer Registry, the National Workers' Compensation Center Registry and the National Registry of Causes of Death, Statistics Finland. RESULTS: Women were diagnosed a mean of 4.5 years later than males (p = .001), but survival did not differ (overall median survival 9.7 months). A workers' compensation claim was more common in males (OR 11.0 [95% CI 7.5-16.2]) and in regions with a major asbestos industry (OR 1.7 [95% CI 1.3-2.2]). One-year and three-year survivals did not differ regionally. Patients without chemotherapy treatment had an inferior survival (RR 1.8 [95% CI 1.5-2.0]). The initial survival benefit gained with pemetrexed was diluted at 51 months. CONCLUSIONS: MPM is a disease with a poor prognosis, although chemotherapy appears to improve survival time. Significant gender and regional variation exists among patients, with notable differences in diagnostic and treatment practices. Long-term outcomes with pemetrexed remain indeterminate. IMPACT: Emphasize centralized consult services for the diagnosis, treatment and support that patients receive for MPM, facilitating equal outcomes and compensation.

Spatial aspects of oncogenic signalling determine the response to combination therapy in slice explants from Kras-driven lung tumours.

A key question in precision medicine is how functional heterogeneity in solid tumours informs therapeutic sensitivity. We demonstrate that spatial characteristics of oncogenic signalling and therapy response can be modelled in precision-cut slices from Kras-driven non-small-cell lung cancer with varying histopathologies. Unexpectedly, profiling of in situ tumours demonstrated that signalling stratifies mostly according to histopathology, showing enhanced AKT and SRC activity in adenosquamous carcinoma, and mitogen-activated protein kinase (MAPK) activity in adenocarcinoma. In addition, high intertumour and intratumour variability was detected, particularly of MAPK and mammalian target of rapamycin (mTOR) complex 1 activity. Using short-term treatment of slice explants, we showed that cytotoxic responses to combination MAPK and phosphoinositide 3-kinase-mTOR inhibition correlate with the spatially defined activities of both pathways. Thus, whereas genetic drivers determine histopathology spectra, histopathology-associated and spatially variable signalling activities determine drug sensitivity. Our study is in support of spatial aspects of signalling heterogeneity being considered in clinical diagnostic settings, particularly to guide the selection of drug combinations. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.