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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.
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Procedimientos Quirúrgicos del Sistema Digestivo , Hernia Hiatal , Laparoscopía , Mala Praxis , Humanos , Femenino , Adulto , Persona de Mediana Edad , Anciano , Masculino , Hernia Hiatal/cirugía , Hernia Hiatal/complicaciones , Estudios Retrospectivos , Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Resultado del TratamientoRESUMEN
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.
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Adenocarcinoma , Neoplasias Esofágicas , Hernia Hiatal , Humanos , Esofagectomía/efectos adversos , Esofagectomía/métodos , Incidencia , Estudios Retrospectivos , Complicaciones Posoperatorias/etiología , Hernia Hiatal/epidemiología , Hernia Hiatal/cirugía , Factores de Riesgo , Neoplasias Esofágicas/cirugía , Neoplasias Esofágicas/complicaciones , Procedimientos Quirúrgicos Mínimamente Invasivos/efectos adversos , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Resultado del TratamientoRESUMEN
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.
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Adenocarcinoma , Neoplasias Esofágicas , Adenocarcinoma/patología , Quimioradioterapia/métodos , Estudios de Cohortes , Neoplasias Esofágicas/patología , Esofagectomía/métodos , Humanos , Terapia Neoadyuvante/métodos , Estadificación de Neoplasias , Pronóstico , Estudios RetrospectivosRESUMEN
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.
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Hernias Diafragmáticas Congénitas , Laparoscopía , Adulto , Humanos , Femenino , Persona de Mediana Edad , Masculino , Hernias Diafragmáticas Congénitas/cirugía , Hernias Diafragmáticas Congénitas/diagnóstico , Laparoscopía/efectos adversos , Laparoscopía/métodos , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Reoperación , Tiempo de InternaciónRESUMEN
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.
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Trastornos de Deglución , Hernia Hiatal , Trastornos de Deglución/etiología , Endoscopía , Femenino , Gastrostomía/efectos adversos , Gastrostomía/métodos , Hernia Hiatal/complicaciones , Hernia Hiatal/cirugía , Humanos , Estómago/cirugíaRESUMEN
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.
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Hernia Hiatal/cirugía , Laparoscopía/métodos , Calidad de Vida , Anciano , Estudios Transversales , Procedimientos Quirúrgicos Electivos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Satisfacción del Paciente , Recurrencia , Encuestas y Cuestionarios , Tomografía Computarizada por Rayos XRESUMEN
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.
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Neoplasias Pulmonares/epidemiología , Mesotelioma/epidemiología , Neoplasias Pleurales/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Finlandia/epidemiología , Humanos , Incidencia , Masculino , Mesotelioma Maligno , Persona de Mediana Edad , Sistema de Registros , Distribución por SexoRESUMEN
BACKGROUND: Pulmonary carcinoids (PC) are rare malignant neoplasms that cover approximately 1% of all lung cancers. PCs are classified by histological criteria as either typical (TC) or atypical (AC). Histological subtype is the most studied prognostic factor. The aim of this study was to evaluate if other tissue or clinical features are associated with patient outcomes. MATERIAL AND METHODS: We retrospectively reviewed clinical records of 133 PC patients who underwent operation in the Helsinki University Hospital between 1990 and 2013. Tissue specimens were re-evaluated, processed into tissue microarray format and stained immunohistochemically with serotonin, calcitonin, adrenocorticotropic hormone (ACTH), thyroid transcription factor-1 (TTF-1) and Ki-67. Survival and risk analyses were performed. RESULTS: Based on histology, 75% (n = 100) of the tumors were TCs and 25% (n = 33) ACs. TCs had higher 10-year disease-specific survival (DSS) rate than ACs (99% (95% CI, 93-100%) for TCs vs. 82% (95% CI, 61-92%) for ACs). Hormonally active tumors expressing serotonin, calcitonin or ACTH were noted in 53% of the specimens but hormonal expression was not associated with DSS. TTF-1 was positive in 78% of the specimens but was not associated with DSS. Ki-67 index varied between <1% and 15%. Ki-67 ≥ 2.5% was associated with shorter DSS (p = .004). The presence of metastatic disease (p = .001), tumor size ≥30 mm (p = .021) and atypical histology (p = .011) were also associated with disease-specific mortality. CONCLUSIONS: We conclude that PCs are uncommon tumors. When resected, the long-term survival is in general favorable. In this consecutive, single-institution cohort of patients, presence of metastatic disease, tumor size, histological subtype and Ki-67 index were associated with shorter disease-specific survival. As TC and AC have different clinical behaviors, the correct tumor classification at the time of diagnosis is a necessity.
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Tumor Carcinoide/mortalidad , Tumor Carcinoide/patología , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Hormona Adrenocorticotrópica/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/metabolismo , Calcitonina/metabolismo , Tumor Carcinoide/cirugía , Supervivencia sin Enfermedad , Femenino , Humanos , Antígeno Ki-67/metabolismo , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Serotonina/metabolismoRESUMEN
BACKGROUND: Nutritional deficits, cachexia, and sarcopenia are extremely common in esophageal cancer. The aim of this article was to assess the effect of loss of skeletal muscle mass during neoadjuvant treatment on the prognosis of esophageal cancer patients. METHODS: Esophageal cancer patients (N = 115) undergoing neoadjuvant therapy and surgery between 2010 and 2014 were identified from our surgery database and retrospectively analyzed. Computed tomography imaging of the total cross-sectional muscle tissue measured at the third lumbar level defined the skeletal muscle index, which defined sarcopenia (SMI < 52.4 cm2/m2 for men and < 38.5 cm2/m2 for women). Images were collected before and after neoadjuvant treatments. RESULTS: Sarcopenia in preoperative imaging was prevalent in 92 patients (80%). Median overall survival was 900 days (interquartile range 334-1447) with no difference between sarcopenic (median = 900) and non-sarcopenic (median = 914) groups (p = 0.872). Complication rates did not differ (26.1% vs 32.6%, p = 0.725). A 2.98% decrease in skeletal muscle index during neoadjuvant treatment correlated with poor 2-year survival (log-rank p = 0.04). CONCLUSION: Loss of skeletal muscle tissue during neoadjuvant treatment correlates with worse overall survival.
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Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Caquexia/etiología , Neoplasias Esofágicas/terapia , Esofagectomía/efectos adversos , Músculo Esquelético/patología , Terapia Neoadyuvante/efectos adversos , Sarcopenia/etiología , Terapia Combinada , Estudios Transversales , Neoplasias Esofágicas/patología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/cirugía , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
Background and study aims Upper gastrointestinal endoscopy (EGD) is one of the most common diagnostic procedures done to examine the foregut, but it can also be used for therapeutic interventions. The main objectives of this study were to investigate trends in EGD utilization and mortality related to it in a national low-threshold healthcare system, assess perioperative safety, and identify and describe patient-reported malpractice claims from the national database. Patients and methods We retrospectively identified patients from the Finnish Patient Care Registry who underwent diagnostic or procedural EGD between 2010 and 2018. In addition, patient-reported claims for malpractice were analyzed from the National Patient Insurance Center (PIC) database. Patient survival data were gathered collectively from the National Death Registry from Statistics Finland. Results During the study period, 409,153 EGDs were performed in Finland for 298,082 patients, with an annual rate of 9.30 procedures per 1,000 inhabitants, with an annual increase of 2.6%. Thirty-day all-cause mortality was 1.70% and 90-day mortality was 3.84%. For every 1,000 patients treated, 0.23 malpractice claims were filed. Conclusions The annual rate of EGD increased by 2.6% during the study, while the rate of interventional procedures remained constant. Also, while the 30-day mortality rate declined over the study period, it is an unsuitable quality metric for EGDs in comprehensive centers because a patient's underlying disease plays a larger role than the procedure in perioperative mortality. Finally, there were few malpractice claims, with self-evident causes prevailing.
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Lung cancer is the most significant cause of cancer-related deaths in Finland. The diagnosis is still a challenge in outpatient settings. With early diagnosis, patients may receive curable treatment. We describe a young female lung cancer patient with prolonged upper airway infection as a symptom of the disease.
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Neoplasias Pulmonares/diagnóstico , Infecciones del Sistema Respiratorio/diagnóstico , Diagnóstico Diferencial , Diagnóstico Precoz , Femenino , Humanos , Adulto JovenRESUMEN
Importance: The association of the surgical approach, surgical specialty, and other factors with the outcomes of surgical treatment of Zenker diverticulum (ZD) have been debated in the literature. Objectives: To explore the outcomes of 3 different surgical methods used in the management of ZD and determine the associations between patient characteristics, such as preoperative comorbidities and treatment outcomes. Design, Setting, and Participants: This retrospective, population-based cohort study examined patient records of patients who underwent surgical treatment for ZD from the Care Register for Healthcare database in Finland between January 1996 and December 2015. Data review and analysis were completed in 2021. Exposure: Surgical treatment for ZD. Main Outcome and Measures: Complications of surgical procedures used in the management of ZD. Results: In this study, 1044 patients (median [IQR] age, 70.0 [22.0-98.0] years; 416 female individuals [39.8%]) surgically treated for ZD were identified. Most patients (606 [58.0%]) had no preoperative comorbidities. A total of 67 (6.4%) complications were recorded, with a mortality rate of 0.9%. The likelihood of complications was associated with patient age (t [1042] = 2.28; Cohen d, 0.29; 95%, CI 0.04, 0.54), surgical approach (Cramer V = 0.14 [95% CI 0.07-0.21]), and surgical specialty (Cramer V, 0.16; 95% CI, 0.06-0.28). The median (IQR) length of stay in association with the primary surgical intervention was 3.0 (0-85.0) days. Length of stay was associated with patient age (Cramer V, 0.14; 95% CI, 0.06-0.25), especially in patients older than 90 years, surgical approach (F [2, 466.2] = 26.9; ηp2 = 0.08; 95% CI, 0.05-0.11), and surgical specialty (F [4, 22.1] = 11.0; ηp2 = 0.07; 95% CI, 0.04-0.10). Reoperation was associated with the initial surgical approach (Cramer V, 0.18; 95% CI, 0.12-0.23) and surgical specialty (Cramer V, 0.14; 95% CI, 0.09-0.21). Conclusions and Relevance: The results of this cohort study suggest that the outcomes of surgical management depended on the surgical approach, surgical specialty, and patient age. Overall, surgical treatment may be considered safe and may be considered for all patients with symptomatic ZD.
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Esofagoscopía , Divertículo de Zenker , Humanos , Femenino , Anciano , Esofagoscopía/métodos , Divertículo de Zenker/cirugía , Reoperación , Estudios Retrospectivos , Estudios de Cohortes , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/cirugía , Resultado del TratamientoRESUMEN
OBJECTIVES: Pleural mesothelioma (PM) is an aggressive malignancy with limited treatment options. The first-line therapy has remained unchanged for two decades and consists of pemetrexed in combination with cisplatin. Immune-checkpoint inhibitors (nivolumab plus ipilimumab) have high response rates, resulting in recent updates in treatment recommendations by the U.S. Food and Drug Administration. However, the overall benefits of combination treatment are modest, suggesting that other targeted therapy options should be investigated. MATERIALS AND METHODS: We employed high-throughput drug sensitivity and resistance testing on five established PM cell lines using 527 cancer drugs in a 2D setting. Drugs of the greatest potential (n = 19) were selected for further testing in primary cell models derived from pleural effusions of seven PM patients. RESULTS: All established and primary patient-derived PM cell models were sensitive to the mTOR inhibitor AZD8055. Furthermore, another mTOR inhibitor (temsirolimus) showed efficacy in most of the primary patient-derived cells, although a less robust effect was observed when compared with the established cell lines. Most of the established cell lines and all patient-derived primary cells exhibited sensitivity to the PI3K/mTOR/DNA-PK inhibitor LY3023414. The Chk1 inhibitor prexasertib showed activity in 4/5 (80%) of the established cell lines and in 2/7 (29%) of the patient-derived primary cell lines. The BET family inhibitor JQ1 showed activity in four patient-derived cell models and in one established cell line. CONCLUSION: mTOR and Chk1 pathways had promising results with established mesothelioma cell lines in an ex vivo setting. In patient-derived primary cells, drugs targeting mTOR pathway in particular showed efficacy. These findings may inform novel treatment strategies for PM.
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Antineoplásicos , Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurales , Humanos , Preparaciones Farmacéuticas , Inhibidores mTOR , Neoplasias Pulmonares/patología , Mesotelioma Maligno/tratamiento farmacológico , Mesotelioma/patología , Antineoplásicos/uso terapéutico , Neoplasias Pleurales/patología , Serina-Treonina Quinasas TOR/metabolismo , Línea Celular TumoralRESUMEN
Objective: The objective of this study was to assess procedure markup (charge-to-cost ratio) across lung resection procedures and examine variability by geographic region. Methods: Provider-level data for common lung resection operations was obtained from the 2015 to 2020 Medicare Provider Utilization and Payment Data datasets using Healthcare Common Procedure Coding System codes. Procedures studied included wedge resection; video-assisted thoracoscopic surgery; and open lobectomy, segmentectomy, and mediastinal and regional lymphadenectomy. Procedure markup ratio and coefficient of variation (CoV) was assessed and compared across procedure, region, and provider. The CoV, a measure of dispersion defined as the ratio of the SD to the mean, was likewise compared across procedure and region. Results: Median markup ratio across all procedures was 3.56 (interquartile range, 2.87-4.59) with right skew (mean, 4.13). Median markup ratio was 3.59 for lymphadenectomy (CoV, 0.51), 3.13 for open lobectomy (CoV, 0.45), 3.55 for video-assisted thoracoscopic surgery lobectomy (CoV, 0.59), 3.77 for segmentectomy (CoV, 0.74), and 3.80 for wedge resection (CoV, 0.67). Increased beneficiaries, services, and Healthcare Common Procedure Coding System score (total) were associated with a decreased markup ratio (P < .0001). Markup ratio was highest in the Northeast at 4.14 (interquartile range, 3.09-5.56) and lowest in the South (Markup ratio 3.26; interquartile range, 2.68-4.02). Conclusions: We observe geographic variation in surgical billing for thoracic surgery.
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Malignant pleural mesothelioma (MPM) is an aggressive tumor with a poor prognosis. As the available therapeutic options show a lack of efficacy, novel therapeutic strategies are urgently needed. Given its T-cell infiltration, we hypothesized that MPM is a suitable target for therapeutic cancer vaccination. To date, research on mesothelioma has focused on the identification of molecular signatures to better classify and characterize the disease, and little is known about therapeutic targets that engage cytotoxic (CD8+) T cells. In this study we investigate the immunopeptidomic antigen-presented landscape of MPM in both murine (AB12 cell line) and human cell lines (H28, MSTO-211H, H2452, and JL1), as well as in patients' primary tumors. Applying state-of-the-art immuno-affinity purification methodologies, we identify MHC I-restricted peptides presented on the surface of malignant cells. We characterize in vitro the immunogenicity profile of the eluted peptides using T cells from human healthy donors and cancer patients. Furthermore, we use the most promising peptides to formulate an oncolytic virus-based precision immunotherapy (PeptiCRAd) and test its efficacy in a mouse model of mesothelioma in female mice. Overall, we demonstrate that the use of immunopeptidomic analysis in combination with oncolytic immunotherapy represents a feasible and effective strategy to tackle untreatable tumors.
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Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurales , Humanos , Femenino , Animales , Ratones , Neoplasias Pleurales/tratamiento farmacológico , Mesotelioma/tratamiento farmacológico , Inmunoterapia , Péptidos/uso terapéutico , Línea Celular Tumoral , Neoplasias Pulmonares/patologíaRESUMEN
Lung cancer remains among the most difficult-to-treat malignancies and is the leading cause of cancer-related deaths worldwide. The introduction of targeted therapies and checkpoint inhibitors has improved treatment outcomes; however, most patients with advanced-stage non-small cell lung cancer (NSCLC) eventually fail these therapies. Therefore, there is a major unmet clinical need for checkpoint refractory/resistant NSCLC. Here, we tested the combination of aPD-1 and adenovirus armed with TNFα and IL-2 (Ad5-CMV-mTNFα/mIL-2) in an immunocompetent murine NSCLC model. Moreover, although local delivery has been standard for virotherapy, treatment was administered intravenously to facilitate clinical translation and putative routine use. We showed that treatment of tumor-bearing animals with aPD-1 in combination with intravenously injected armed adenovirus significantly decreased cancer growth, even in the presence of neutralizing antibodies. We observed an increased frequency of cytotoxic tumor-infiltrating lymphocytes, including tumor-specific cells. Combination treatment led to a decreased percentage of immunosuppressive tumor-associated macrophages and an improvement in dendritic cell maturation. Moreover, we observed expansion of the tumor-specific memory T cell compartment in secondary lymphoid organs in the group that received aPD-1 with the virus. However, although the non-replicative Ad5-CMV-mTNFα/mIL-2 virus allows high transgene expression in the murine model, it does not fully reflect the clinical outcome in humans. Thus, we complemented our findings using NSCLC ex vivo models fully permissive for the TNFα and IL-2- armed oncolytic adenovirus TILT-123. Overall, our data demonstrate the ability of systemically administered adenovirus armed with TNFα and IL-2 to potentiate the anti-tumor efficacy of aPD-1 and warrant further investigation in clinical trials.
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Carcinoma de Pulmón de Células no Pequeñas , Interleucina-2 , Neoplasias Pulmonares , Factor de Necrosis Tumoral alfa , Animales , Humanos , Ratones , Adenoviridae/genética , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Interleucina-2/genética , Interleucina-2/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/uso terapéutico , Inhibidores de Puntos de Control InmunológicoRESUMEN
The field of thoracic surgery is a rapidly developing field due to exciting developments in technology and oncologic treatments as well as continuous innovation in surgical technique. Although the population of Finland is relatively small, general thoracic surgery is represented at a high level in five centralized university centers, Helsinki University Hospital, Tampere University Hospital, Turku University Hospital, Kuopio University Hospital and Oulu University Hospital. Thus, high case volume and good results are achieved in these centers. Here, we describe a short history, current state and future prospects of the field of cardiothoracic surgery in Finland, with a focus on general thoracic surgery and the perspective of Helsinki University Hospital. From the field's birth in Finland, marked by the first lobectomy, in the late 1930's, it has grown and adapted more and more modern techniques such as totally minimally invasive esophagectomy and robotic lung cancer surgery. Nowadays, most of general thoracic surgery in Helsinki University Hospital is either minimally invasive or robotic and open surgery is the exception to the norm. Helsinki University Hospital has a strong presence in the European general thoracic surgery community and aims to do so in the future by investing on training & education, research and surgical innovation.
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IMPORTANCE: The incidence of Zenker diverticulum has been established; previous estimates have been extrapolated from small institutional cohorts. OBJECTIVE: To describe the population-wide incidence of Zenker diverticulum over a 20-year period and characterize management strategies across specialties and treatment settings. DESIGN, SETTING, AND PARTICIPANTS: This retrospective national cohort study was conducted from January 1, 1996, through December 31, 2015, and reviewed patient records from the Care Register for Healthcare in Finland, from which patients with Zenker diverticulum were identified. The data were analyzed in October 2021. EXPOSURES: Zenker diverticulum. MAIN OUTCOME AND MEASURE: The incidence of Zenker diverticulum per 100â¯000 person-years. RESULTS: A total of 2736 patients (median [IQR] age at diagnosis 72.0 [19-106] years; 1278 women [46.7%]) were identified, making the annual incidence of Zenker diverticulum in Finland 2.9/100â¯000 person-years. Men had higher incidence (3.7/100â¯000 person-years) compared with women (2.3/100â¯000 person-years), with an incidence rate ratio of 1.61 (95% CI, 1.48-1.76; P < .001). Within the study population, 1044 patients (38.2%) underwent surgical treatment and 227 (8.3%) underwent 2 or more surgeries. The choice of initial operative approach depended on the medical specialty (Cramer V = 0.41) and on specific catchment area (Cramer V = 0.41). Overall, endoscopic approaches for initial operations were most popular. CONCLUSIONS AND RELEVANCE: The cohort study results found that the incidence of Zenker diverticulum was 2.9/100â¯000 person-years. Most patients with Zenker diverticulum did not undergo definitive therapy. Some hospital districts and some medical specialties were more likely to opt for conservative treatment than others. The choice of operative approach depended more on physician-level factors rather than patient profiles.
Asunto(s)
Divertículo de Zenker , Estudios de Cohortes , Atención a la Salud , Femenino , Finlandia/epidemiología , Humanos , Masculino , Estudios Retrospectivos , Resultado del Tratamiento , Divertículo de Zenker/epidemiología , Divertículo de Zenker/cirugíaRESUMEN
Follicular dendritic cell sarcoma is a rare, low-grade cancer derived from follicular dendritic cells, which serve as accessory cells to the lymphoid system. Here, we describe the case of a 57-year-old man who had a mediastinal mass with aortic involvement incidentally identified during evaluation for indeterminate pulmonary nodules. The mass, later diagnosed as follicular dendritic cell sarcoma, was successfully treated with surgical resection aided by the placement of an endovascular aortic stent graft.