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BACKGROUND: Immune response against cancer has prognostic impact but its role in gastric cancer is poorly known. The aim of the study was to assess the prognostic significance of immune cell score (CD3+, CD8+), tumour immune escape (PD-L1, PD-1) and immune tolerance (Clever-1). METHODS: After exclusion of Epstein-Barr virus positive (n = 4) and microsatellite instable (n = 6) tumours, the study included 122 patients with GC undergoing D2 gastrectomy. CD3+ and CD8+ based ICS, PD-L1, PD-1 and Clever-1 expressions were evaluated. Differences in survival were examined using Cox regression adjusted for confounders. The primary outcome was 5-year survival. RESULTS: The 5-year overall survival rate was 43.4%. High ICS was associated with improved overall survival (adjusted HR 0.48 (95% CI 0.26-0.87)) compared to low ICS. In the high ICS group, patients with PD-L1 expression (5-year survival 69.2 vs. 53.1%, p = 0.317), high PD-1 (5-year survival 70.6 vs. 55.3% p = 0.312) and high Clever-1 (5-year survival 72.0% vs. 45.5% (p = 0.070) had poor prognosis. CONCLUSIONS: High ICS was associated with improved survival. In the high ICS group, patients with high PD-L1, PD-1 and Clever-1 had poor prognosis highlighting the importance of immune escape and immune tolerance in GC.
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Adenocarcinoma/imunologia , Tolerância Imunológica/imunologia , Macrófagos/imunologia , Neoplasias Gástricas/imunologia , Evasão Tumoral/imunologia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Antígeno B7-H1/imunologia , Feminino , Humanos , Imunofenotipagem/métodos , Masculino , Pessoa de Meia-Idade , Receptor de Morte Celular Programada 1/imunologia , Transdução de Sinais/imunologia , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologiaRESUMO
BACKGROUND: One-stage laparoscopic common bile duct (CBD) stone clearance and laparoscopic cholecystectomy (LCBDE+LC) for cholecystocholedocholithiasis ( CCL) can be performed with similar short and long-term outcomes than two-stage endoscopic retrograde cholangiography followed by subsequent LC (ERCP+LC). This study examined retrospectively the outcome and hospital costs of one-stage versus two-stage treatment of CBD stones. METHODS: From January 1999 and December 2014, 217 consecutive, elective patients underwent one-stage (LCBDE + LC ) or two-stage (ERCP + subsequent LC ) treatment for CBD stones. The data from the one-stage management was collected prospectively, and from the two-stage management retrospectively. The main measure of outcome was hospital costs, with the success of one-stage versus two-stage management, postoperative morbidity and postoperative stay as secondary outcome measures. RESULTS: One-stage laparoscopic transcystic management was the least costly option compared to laparoscopic one-stage transductal approach (TC 5455 versus TD 9364, p < 0.001) or two-stage management (6913 , p = 0.02). Overall success rate of primary intervention (including conversions to open surgery) for CBD stone clearance was 96.9%, 97.0% and 98.3% after transcystic one-stage, transductal one-stage and two-stage approach, p = 0.79. Postoperative morbidity was 15.5% versus 7.5%, p = 0.64, and postoperative hospital stay median 2 days (IQR 2-5) versus 4.5 days ( IQR 3-7), p < 0.001 in the one-stage and two-stage management groups. CONCLUSIONS: Our study shows that laparoscopic one-stage transcystic management of CCL results in high rate of CBD clearance, fewer procedures per patient, shorter hospital and lower costs than the two-stage management. Therefore the one-stage transcystic management seems to be an attractive strategy for the treatment of CCL depending on local resources and surgical expertise .
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Colangiopancreatografia Retrógrada Endoscópica/métodos , Colecistectomia Laparoscópica/métodos , Cálculos Biliares/cirurgia , Adulto , Idoso , Conversão para Cirurgia Aberta , Procedimentos Cirúrgicos Eletivos , Feminino , Custos Hospitalares , Humanos , Laparoscopia/métodos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND AND AIM: To examine the impact of day-care laparoscopic cholecystectomy (LC) with ultrasonic scissors dissection versus diathermy hook dissection method in a randomized setting. METHODS: From April 2012 to September 2014, a total of 169 elective day-care patients were randomized to undergo either laparoscopic cholecystectomy with ultrasonic scissors using fundus-first approach (n = 88) or diathermy hook dissection starting from the triangle of Calot (n = 79). Main measures of outcome were operative time, same-day discharge and intraoperative complications. Secondary outcome measures were postoperative pain (numeric rating scale), postoperative nausea and vomiting (PONV), readmissions and 30-day morbidity. RESULTS: Median operative time was similar in the ultrasonic dissection and diathermy hook dissection groups (45 vs 45 min, p = 0.95). Same-day discharge was possible in 77 patients (87 %) in the ultrasonic dissection group and in 69 patients (87 %) in the diathermy group, p = 0.98. Intraoperative gallbladder perforations, mean intraoperative bleeding, postoperative pain and PONV at 1, 2 and 4 h (p = 0.78) did not differ significantly between the study groups. CONCLUSION: Day-care LC using either diathermy hook or ultrasonic dissection resulted in excellent same-day discharge in both groups (87 %). LC with ultrasonic dissection does not offer any clinical advantages compared to diathermy dissection.
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Procedimentos Cirúrgicos Ambulatórios , Colecistectomia Laparoscópica/métodos , Diatermia , Procedimentos Cirúrgicos Ultrassônicos , Dissecação/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados da Assistência ao Paciente , Procedimentos Cirúrgicos Ultrassônicos/instrumentaçãoRESUMO
BACKGROUND: Prophylactic placement of a mesh has been suggested to prevent parastomal hernia, but evidence to support this approach is scarce. OBJECTIVE: The aim of this study was to evaluate whether laparoscopic placement of a prophylactic, dual-component, intraperitoneal onlay mesh around a colostomy is safe and prevents parastomal hernia formation after laparoscopic abdominoperineal resection. DESIGN: This is a prospective, multicenter, randomized controlled clinical trial. SETTINGS: This study was conducted at 2 university and 3 central Finnish hospitals. PATIENTS: From 2010 to 2013, 83 patients undergoing laparoscopic abdominoperineal resection for rectal cancer were recruited. After withdrawals and exclusions, the outcome of 70 patients, 35 patients in each study group, could be examined. INTERVENTIONS: In the intervention group, an end colostomy was created with placement of a intraperitoneal, dual-component onlay mesh and compared with a group with a traditional stoma. MAIN OUTCOME MEASURES: The main outcome measures were the incidence of clinically and radiologically detected parastomal hernias and their extent 12 months after surgery. Stoma-related morbidity and the need for surgical repair of parastomal hernia were secondary outcome measures. RESULTS: Parastomal hernia was observed by clinical inspection in 5 intervention patients (14.3%) and in 12 control patients (32.3%; p = 0.049). Surgical repair of parastomal hernia was performed in 1 control patient (3.2%) and in none of the patients in the intervention group. CT detected parastomal hernia in 18 intervention patients (51.4%) and in 17 control patients (53.1%; p = 1.00). The extent of hernias was similar according to European Hernia Society classification (p = 0.41). Colostomy-related morbidity (32.3% vs 14.3%; p = 0.140) did not differ between the study groups. LIMITATIONS: The study was limited by its small size and short follow-up time. CONCLUSIONS: Prophylactic laparoscopic placement of intraperitoneal onlay mesh does not significantly reduce the overall risk of radiologically detected parastomal hernia after laparoscopic abdominoperineal resection. However, prophylactic mesh repair was associated with significantly lower risk of clinically detected parastomal hernia.
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Colostomia , Hérnia Ventral , Laparoscopia , Complicações Pós-Operatórias , Neoplasias Retais/cirurgia , Telas Cirúrgicas , Idoso , Colostomia/efeitos adversos , Colostomia/instrumentação , Colostomia/métodos , Feminino , Hérnia Ventral/diagnóstico , Hérnia Ventral/etiologia , Hérnia Ventral/prevenção & controle , Hérnia Ventral/cirurgia , Herniorrafia/métodos , Herniorrafia/estatística & dados numéricos , Humanos , Laparoscopia/instrumentação , Laparoscopia/métodos , Masculino , Pessoa de Meia-Idade , Peritônio/cirurgia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/cirurgia , Procedimentos Cirúrgicos Profiláticos/instrumentação , Procedimentos Cirúrgicos Profiláticos/métodos , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
BACKGROUND AND AIM: To audit short- and long-term outcomes after laparoscopic common bile duct exploration (LCBDE) and factors influencing the success of the laparoscopic treatment. METHODS: From January 1999 to December 2011, 288 patients (93 males) underwent a single-stage laparoscopic cholecystectomy combined with LCBDE in two Finnish Hospitals. Short-term outcome data were collected prospectively. Long-term outcomes were examined retrospectively. The main measures of outcome were the success of laparoscopic CBD stone clearance and recurrence of CBD stones in the long-term, with 30-day mortality, morbidity, and the length of postoperative hospital stay as secondary outcome measures. RESULTS: CBD stones were successfully removed by one-stage laparoscopic procedure in 232 of the 279 patients (83.2%) with verified CBD stones and after conversion to open surgery in additional 28 patients (93.2%). Nineteen patients (6.8%) having residual stones after surgery were successfully treated with postoperative ERCP. On multivariate analysis, the independent factors associated with a failed laparoscopic stone clearance were stone size over 7 mm [OR 3.51 (95% CI 1.53-8.03), p = 0.003], difficult anatomy [OR 18.01 (5.03-64.49), p < 0.001] and transcholedochal approach [OR 2.98 (1.37-4.47), p = 0.006]. Laparoscopic stone clearance also failed in all 11 patients having impacted stones at the ampulla of Vater. Cumulative long-term recurrence rate was 3.6% at 5 years and 6.0 % at 10 years. Thirty-day mortality was 0.3% and morbidity 12.2%. Postoperative hospital stay was median 2 (IQR 1-3) days after transcystic CBD removal and 4 (IQR 3-7) days after transcholedochal CBD removal, p < 0.001. CONCLUSION: Our results show that one-stage LC combined with LCBDE stone clearance is safe and effective in most patients thus reducing the number of additional, potentially dangerous endoscopic procedures. Moreover, large or impacted stones are a risk factor for failed stone clearance.
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Colecistectomia Laparoscópica/métodos , Auditoria Clínica , Cálculos Biliares/cirurgia , Colangiopancreatografia Retrógrada Endoscópica/métodos , Feminino , Finlândia/epidemiologia , Seguimentos , Cálculos Biliares/diagnóstico , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida/tendências , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: There are no prospective studies available on the behavior of extraesophageal and esophageal symptoms and treatment-related side effects in patients without effective antireflux medication, receiving the most effective antireflux medication, and after laparoscopic fundoplication. METHODS: Extraesophageal and esophageal reflux symptoms and treatment-related side effects were assessed in 60 patients while they were on no effective antireflux medication (three-week washout period), after three month of treatment with double-dose esomeprazole, and 3 months after laparoscopic Nissen fundoplication. Esophageal and extraesophageal reflux symptoms, rectal flatulence, and bloating were analyzed with the visual analog scale. In addition, dysphagia, rectal flatulence, and bloating were recorded as none, mild, moderate, or severe. RESULTS: Both extraesophageal and esophageal reflux symptoms decreased after treatment with esomeprazole and were further reduced after fundoplication. Dysphagia and flatulence did not increase from baseline after surgery. Bloating decreased both after treatment with esomeprazole and after fundoplication. In contrast, dysphagia and increased flatus were found more often after surgery than during treatment with esomeprazole. Dysphagia and rectal flatulence were less common during treatment with esomeprazole than at baseline or after surgery. CONCLUSIONS: Both extraesophageal and esophageal reflux symptoms decreased after treatment with esomeprazole and were reduced further after fundoplication. Any treatment-related side effect was not increased after surgery when compared to baseline. However, compared to esomeprazole there was more dysphagia and flatulence after fundoplication.
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Fundoplicatura/métodos , Refluxo Gastroesofágico/fisiopatologia , Refluxo Gastroesofágico/cirurgia , Esomeprazol/uso terapêutico , Feminino , Finlândia , Flatulência/etiologia , Refluxo Gastroesofágico/tratamento farmacológico , Humanos , Laparoscopia/métodos , Masculino , Inibidores da Bomba de Prótons/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: Laparoscopic resection for rectal cancer has remained controversial because of the lack of level 1 evidence regarding oncologic safety and long-term survival. OBJECTIVES: The aim of this study was to assess the impact of laparoscopic versus open resection for rectal cancer on clinical and oncologic outcome in the multimodal setting. DESIGN: This is a review of prospectively gathered data from a single-institution rectal cancer database. SETTINGS: This study was conducted in the Central Hospital of Central Finland. PATIENTS: From January 1999 to December 2006, 191 selected patients were included. INTERVENTIONS: One hundred patients underwent laparoscopic resection, and 91 patients, also suitable for laparoscopic surgery, underwent open major rectal resection in the multimodal setting. MAIN OUTCOME MEASURES: The main measures of outcome were early recovery and short- and long-term morbidity; local recurrence and survival were secondary outcomes. LIMITATIONS: This is not a randomized study. RESULTS: The study groups were balanced for baseline characteristics. Conversion rate to open surgery was 22%. Laparoscopic surgery resulted in significantly less bleeding (175 mL vs 500 mL, p < 0.001), 1 day earlier recovery of normal diet (3 days vs 4 days, p = 0.001), and shorter postoperative hospital stay (7 days vs 9 days, p < 0.001). Postoperative 30-day mortality (1% vs 3%), morbidity (31% vs 43%), readmission (11% vs 15%), and reoperation (6% vs 9%) rates were similar in the 2 groups, but significantly fewer patients in the laparoscopic group had long-term complications (19% vs 36%, p = 0.033). The 5-year disease-free survival (78% vs 80%, p = 0.74) and local recurrence (5% vs 6%, p = 0.66) rates were similar in the laparoscopic and open group for those 175 patients treated for cure. CONCLUSION: Laparoscopic surgery resulted in faster postoperative recovery and fewer long-term complications than open surgery without apparently compromising the long-term oncologic outcome. Our results indicate that laparoscopic rectal resection is an acceptable alternative to open surgery in selected patients with rectal cancer.
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Laparoscopia , Neoplasias Retais/cirurgia , Reto/cirurgia , Idoso , Quimiorradioterapia Adjuvante , Feminino , Seguimentos , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Readmissão do Paciente/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Recuperação de Função Fisiológica , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Neoplasias Retais/terapia , Reoperação/estatística & dados numéricos , Análise de Sobrevida , Resultado do TratamentoRESUMO
PURPOSE: To assess the quality of surgical care and outcome following multimodal treatment for low- and midrectal cancers, focusing on differences between low anterior and abdominoperineal resections. METHODS: From 1999 to 2007, 179 patients underwent low anterior resection (LAR), abdominoperineal resection (APR), or proctocolectomy for low- or midrectal cancers. Preoperative (chemo)radiotherapy was given according to local guidelines and adjuvant postoperative chemotherapy in stage III disease. Outcome together with clinical and histopathological data were analyzed in relation to the type of surgery performed. RESULTS: The postoperative mortality was 2.2%; morbidity, 39.6%; reoperation rate, 8.4%; and readmission rate, 16.0%. Involved circumferential resection margin (CRM ≤ 1 mm) rate was 4.5% (APR 9.1% vs. LAR 2.6%, p = 0.046). Intraoperative bowel perforation occurred in 5.5% of APRs. Anastomotic leak rate was 15.3%. The 5-year overall survival of the 179 patients was 68.5 %; disease-specific survival, 82.2%; and local recurrence rate, 6.3%. The overall, disease-specific, and disease-free survival rates in the 162 patients treated for cure were 73.1%, 84.6%, and 78.3%, and local recurrence rate was 4.4% with no significant differences between LAR and APR. CRM was the only independent predictor of local recurrence and CRM, tumor stage, and level independent predictors of disease-free survival. CONCLUSIONS: Quality of surgical care was in line with the current international standards. CRM was an independent predictor for local recurrence and CRM, tumor stage, and level independent prognostic factors for disease-free survival. Neither the type of surgery (LAR vs. APR) nor the surgical approach (laparoscopic vs. open) influenced the oncologic outcome.
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Recidiva Local de Neoplasia/patologia , Qualidade da Assistência à Saúde/normas , Neoplasias Retais/cirurgia , Idoso , Terapia Combinada , Intervalo Livre de Doença , Feminino , Humanos , MasculinoRESUMO
The fast-track treatment model can be regarded as the second revolution of colorectal surgery after the introduction of laparoscopic surgery. In the gastro-surgical unit of the Central Hospital of Central Finland, results equivalent to international studies in colorectal surgery have been achieved by using fast-track model. In a study setting, this treatment model has resulted in significant decrease of total treatment costs and speeded up discharge of the patients from the hospital. The fast-track treatment model requires both a motivated, trained medical team and a motivated patient.
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Protocolos Clínicos , Cirurgia Colorretal/tendências , Laparoscopia/métodos , Cirurgia Colorretal/economia , Finlândia , HumanosRESUMO
Laparoscopic surgery has established itself in gallbladder, adrenal and colorectal surgery as well as in anti-reflux and buriatric surgery. The technique has also been increasingly applied to hepatic, pancreatic and gastric surgery. The progress has taken place at the price of increased surgery costs, but is compensated by shortened hospitalization. Robot-assisted laparoscopy may facilitate the technical execution of surgery in hepatic and pancreatic surgery and additionally make possible the benefits of preoperative imaging, intraoperative localization of the tumor, and optimal determination of the margins of resection.
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Laparoscopia/tendências , Previsões , Humanos , Laparoscopia/economia , Tempo de Internação/estatística & dados numéricos , RobóticaRESUMO
PURPOSE: To evaluate immune cell infiltration, the programmed death-1/programmed death ligand-1 (PD-1/PD-L1) expression and their prognostic value in a series of mismatch proficient (pMMR) CRC with matched liver and lung metastases. METHODS: Formalin-fixed paraffin-embedded tissue sections stained for CD3, CD8, PD-L1 and PD-1 from 113 primary CRC tumours with 105 liver and 59 lung metastases were analyzed. The amount of CD3 and CD8 positive lymphocytes were combined as immune cell score (ICS). Comparative analyses on immune contexture were performed both between the primary tumour and matched metastases and between the metastatic sites. RESULTS: In liver metastases, immune cell infiltration was increased in general compared to primary tumours but did not correlate case by case. On the contrary, ICS between lung metastases and primary tumours correlated well, but the expression of PD-1/PD-L1 was increased in lung metastases. The proportion of tumours with high ICS together with PD-L1-positivity almost doubled in metastases (39%) compared to primary tumours (20%). High ICS (compared to lowest) in patient's least immune-infiltrated metastasis was an independent prognostic marker for disease-specific (HR 9.14, 95%CI 2.81-29.68) and overall survival (HR 6.95, 95%CI 2.30-21.00). CONCLUSIONS: Our study confirms the prognostic value of high ICS in least immune-infiltrated metastases in pMMR CRC patients. Major differences observed in immune contexture between primary tumours and metastases may have significance for treatment strategies for patients with advanced CRC.
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This retrospective population-based study examined the impact of age and comorbidity burden on multimodal management and survival from colorectal cancer (CRC). From 2000 to 2015, 1479 consecutive patients, who underwent surgical resection for CRC, were reviewed for age-adjusted Charlson comorbidity index (ACCI) including 19 well-defined weighted comorbidities. The impact of ACCI on multimodal management and survival was compared between low (score 0-2), intermediate (score 3) and high ACCI (score ≥ 4) groups. Changes in treatment from 2000 to 2015 were seen next to a major increase of laparoscopic surgery, increased use of adjuvant chemotherapy and an intensified treatment of metastatic disease. Patients with a high ACCI score were, by definition, older and had higher comorbidity. Major elective and emergency resections for colon carcinoma were evenly performed between the ACCI groups, as were laparoscopic and open resections. (Chemo)radiotherapy for rectal carcinoma was less frequently used, and a higher rate of local excisions, and consequently lower rate of major elective resections, was performed in the high ACCI group. Adjuvant chemotherapy and metastasectomy were less frequently used in the ACCI high group. Overall and cancer-specific survival from stage I-III CRC remained stable over time, but survival from stage IV improved. However, the 5-year overall survival from stage I-IV colon and rectal carcinoma was worse in the high ACCI group compared to the low ACCI group. Five-year cancer-specific and disease-free survival rates did not differ significantly by the ACCI. Cox proportional hazard analysis showed that high ACCI was an independent predictor of poor overall survival (p < 0.001). Our results show that despite improvements in multimodal management over time, old age and high comorbidity burden affect the use of adjuvant chemotherapy, preoperative (chemo)radiotherapy and management of metastatic disease, and worsen overall survival from CRC.
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PURPOSE: To compare laparoscopic non-CME colectomy with laparoscopic CME colectomy in two hospitals with similar experience in laparoscopic colorectal surgery. METHODS: Data was collected retrospectively from Päijät-Häme Central Hospital (PHCH, NCME group) and Central Finland Central Hospital (CFCH, CME group) records. Elective laparoscopic resections performed during 2007-2016 for UICC stage I-III adenocarcinoma were included to assess differences in short-term outcome and survival. RESULTS: There were 340 patients in the NCME group and 325 patients in the CME group. CME delivered longer specimens (p < 0.001), wider resection margins (p < 0.001), and more lymph nodes (p < 0.001) but did not result in better 5-year overall or cancer-specific survival (NCME 77.9% vs CME 72.9%, p = 0.528, NCME 93.2% vs CME 88.9%, p = 0.132, respectively). Thirty-day morbidity, mortality, and length of hospital stay were similar between the groups. Conversion to open surgery was associated with decreased survival. DISCUSSION: Complete mesocolic excision (CME) is reported to improve survival. Most previous studies have compared open CME with open non-CME (NCME) or open CME with laparoscopic CME. NCME populations have been historical or heterogeneous, potentially causing bias in the interpretation of results. Studies comparing laparoscopic CME with laparoscopic NCME are few and involve only small numbers of patients. In this study, diligently performed laparoscopic non-CME D2 resection delivered disease-free survival results comparable with laparoscopic CME but was not safer.
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Neoplasias do Colo , Laparoscopia , Mesocolo , Colectomia , Neoplasias do Colo/cirurgia , Finlândia , Hospitais , Humanos , Excisão de Linfonodo , Mesocolo/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Hyaluronan (HA) accumulation has been associated with poor survival in various cancers, but the mechanisms for this phenomenon are still unclear. The aim of this study was to investigate the prognostic significance of stromal HA accumulation and its association with host immune response in pancreatic ductal adenocarcinoma (PDAC). The study material consisted of 101 radically treated patients for PDAC from a single geographical area. HA staining was evaluated using a HA-specific probe, and the patterns of CD3, CD8, CD73 and PD-L1 expression were evaluated using immunohistochemistry. HA staining intensity of tumour stromal areas was assessed digitally using QuPath. CD3- and CD8-based immune cell score (ICS) was determined. High-level stromal HA expression was significantly associated with poor disease-specific survival (p = 0.037) and overall survival (p = 0.013) In multivariate analysis, high-level stromal HA expression was an independent negative prognostic factor together with histopathological grade, TNM stage, CD73 positivity in tumour cells and low ICS. Moreover, high-level stromal HA expression was associated with low ICS (p = 0.017). In conclusion, stromal HA accumulation is associated with poor survival and low immune response in PDAC.
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5'-Nucleotidase/metabolismo , Antígeno B7-H1/metabolismo , Carcinoma Ductal Pancreático/imunologia , Ácido Hialurônico/metabolismo , Imunidade/imunologia , Neoplasias Pancreáticas/imunologia , Células Estromais/imunologia , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/cirurgia , Feminino , Seguimentos , Proteínas Ligadas por GPI/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Prognóstico , Estudos Prospectivos , Células Estromais/metabolismo , Taxa de SobrevidaRESUMO
Immune suppressing molecule CD73 is overexpressed in various cancers and associated with poor survival. Little is so far known about the predictive value of CD73 in pancreatic ductal adenocarcinoma (PDAC). The purpose of this study was to investigate the prognostic significance of CD73 in PDAC. The study material consisted of 110 radically treated patients for PDAC. Tissue microarray blocks were constructed and stained immunohistochemically using CD73 antibody. Staining intensity and numbers of stained tumour cells, inflammatory cells, stroma, and blood vessels were assessed. High-level CD73 expression in tumour cells was positively associated with PD-L1 expression, perineural invasion, and histopathological grade. CD73 positivity in tumour-infiltrating lymphocytes was significantly associated with lymph node metastasis. Lymphocytic CD73 positivity was also associated with staining positivity in both stroma and vascular structures. In addition, CD73 positivity in vascular structures and stroma were associated with each other. There were no significant associations between CD73 positive tumour cells and CD73 positivity in any other cell types. PD-L1 expression was associated with CD73 staining positivity in stroma (p = 0.007) and also with histopathological grade (p = 0.033) and T class (p = 0.016) of the primary tumour. CD73 positivity in tumour cells was significantly associated with poor disease-specific (p = 0.021) and overall survival (p = 0.016). In multivariate analysis, CD73 positivity in tumour cells was an independent negative prognostic factor together with histopathological grade, TNM stage, and low immune cell score. In conclusion, high CD73 expression in tumour cells is associated with poor survival in PDAC independently of the number of tumour-infiltrating lymphocytes or TNM stage.
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5'-Nucleotidase/análise , Antígeno B7-H1/análise , Biomarcadores Tumorais/análise , Carcinoma Ductal Pancreático/enzimologia , Neoplasias Pancreáticas/enzimologia , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal Pancreático/imunologia , Carcinoma Ductal Pancreático/secundário , Carcinoma Ductal Pancreático/terapia , Quimioterapia Adjuvante , Bases de Dados Factuais , Feminino , Proteínas Ligadas por GPI/análise , Humanos , Metástase Linfática , Linfócitos do Interstício Tumoral/química , Linfócitos do Interstício Tumoral/imunologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Pancreatectomia , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/terapia , Pancreaticoduodenectomia , Medição de Risco , Fatores de Risco , Resultado do Tratamento , Microambiente TumoralRESUMO
BACKGROUND: Resection of colorectal cancer (CRC) metastases provides good survival but is probably underused in real-world practice. METHODS: A prospective Finnish nationwide study enrolled treatable metastatic CRC patients. The intervention was the assessment of resectability upfront and twice during first-line therapy by the multidisciplinary team (MDT) at Helsinki tertiary referral centre. The primary outcome was resection rates and survival. FINDINGS: In 2012-2018, 1086 patients were included. Median follow-up was 58 months. Multiple metastatic sites were present in 500 (46%) patients at baseline and in 820 (76%) during disease trajectory. In MDT assessments, 447 (41%) were classified as resectable, 310 (29%) upfront and 137 (18%) after conversion therapy. Six-hundred and ninety curative intent resections or local ablative therapies (LAT) were performed in 399 patients (89% of 447 resectable). Multiple metastasectomies for multisite or later developing metastases were performed in 148 (37%) patients. Overall, 414 liver, 112 lung, 57 peritoneal, and 107 other metastasectomies were performed. Median OS was 80·4 months in R0/1-resected (HR 0·15; CI95% 0·12-0·19), 39·1 months in R2-resected/LAT (0·39; 0·29-0·53) patients, and 20·8 months in patients treated with "systemic therapy alone" (reference), with 5-year OS rates of 66%, 40%, and 6%, respectively. INTERPRETATION: Repeated centralized MDT assessment in real-world metastatic CRC patients generates high resectability (41%) and resection rates (37%) with impressive survival, even when multisite metastases are present or develop later. FUNDING: The funders had no role in the study design, analysis, and interpretation of the data or writing of this report.
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BACKGROUND: Hepatopancreatobiliary surgery is prone to complications. Methods are needed to monitor surgical outcomes and enable comparison between institutions. METHODS: Complications were collected prospectively and reviewed using the modified Accordion Severity Grading System (MASGS) and the Postoperative Morbidity Index (PMI). RESULTS: This study included 527 consecutive patients receiving either pancreatic or liver resection in 2000-2017 in Central Finland Central Hospital. The PMI was 0.177 for all patients, and 0.192, 0.094, 0.285, and 0.129 for patients receiving major pancreatic (n=218), minor pancreatic (n=93), major liver (n=73), and minor liver (n=143) resection, respectively. The rates of postoperative pancreatic fistula (POPF) after pancreaticoduodenectomies (n=200) were 6.5% for grade B and 5.5% for grade C; rates for biliary leak were 1.0% (grade A), 2.5% (grade B), and 0.5% (grade C). Similarly, the rates for delayed gastric emptying (DGE) were 2.8% (grade A), 15.6% (grade B), and 3.7% (grade C). Postoperative hepatic dysfunction occurred in 2.3%, major surgical site bleeding in 2.3%, and biloma in 7.9% of patients after liver resection. Ninety-day mortality rates were 3.7% and 1.1% in major and minor pancreatic resections, and 8.2% and 0.7% in major and minor liver resections. Major complications occurred in 13.3% and 3.3% in pancreatic, and 19.2% and 6.3% in liver resections, respectively. CONCLUSIONS: Major pancreatic and hepatic surgery are associated with significant morbidity and burden in our center, comparable with previous population-based studies. PMI is an informative way to monitor surgical outcomes and enable comparison between institutions.
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The aim of surgical treatment is to anatomically restore rectal prolapse and functionally remedy fecal incontinence and disorder of rectal emptying. There is not yet sufficient evidence-based knowledge of the advantages and disadvantages of various surgical methods, but in practice transabdominal surgery is recommended for patients in good condition and perineal surgery for elderly and frail patients suffering from associated diseases. The progress of laparoscopic surgery has, however, made the transabdominal operation possible for those in increasingly poor condition. With this procedure a significant improvement of defecation disorder is achieved in over 80% of patients.
Assuntos
Prolapso Retal/cirurgia , Incontinência Fecal/etiologia , Incontinência Fecal/cirurgia , Humanos , Laparoscopia , Prolapso Retal/complicaçõesRESUMO
An immune cell score (ICS) was introduced for predicting survival in pancreatic ductal adenocarcinoma (PDAC). Few studies have compared different methods of evaluating immune infiltrate. This study compared ICSs determined in whole sections or tissue microarray-like hotspots for predicting survival after PDAC surgery. We included in 79 consecutive patients from a single geographical area that underwent surgery for PDAC (R0/R1, stages I-III). We performed digital image analyses to evaluate CD3 and CD8 staining. ICSs were classified as low, moderate, or high, based on the numbers of immune cells in the tumour core and invasive margin. We compared ICS groups determined with the hotspot and whole-section techniques. Associations between ICS and survival were analysed with Cox regression models, adjusted for sex, age, tumour stage, differentiation grade, perineural invasion, and resection radicality. In hotspot ICS analysis, 5-year overall survival rates for low, moderate, and high groups were 12.1%, 26.3%, and 26.8%, respectively (p = 0.193). In whole-section analyses, overall survival rates were 5.3%, 26.4%, and 43.8%, respectively (p = 0.030). In the adjusted Cox model, whole-section ICS groups were inversely associated with the overall mortality hazard ratio (HR): low, moderate, and high ICS groups had HRs of 1.00, 0.42 (95% CI 0.20-0.88), and 0.27 (95% CI 0.11-0.67), respectively. The number of immune cells per square millimetre in the tumour core and the invasive margin were significantly higher and had a wider range in hotspots than in whole-tissue sections. Accordingly, ICS could predict survival in patients with PDAC after surgery. Whole tissue section ICSs exhibited better prognostic value than hotspot ICSs.
Assuntos
Adenocarcinoma/patologia , Carcinoma Ductal Pancreático/patologia , Neoplasias Pancreáticas/patologia , Adenocarcinoma/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal Pancreático/imunologia , Feminino , Humanos , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/imunologia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias PancreáticasRESUMO
Increasing evidence suggests that cancer progression is strongly influenced by host immune response, which is represented by immune cell infiltrates. T-lymphocyte-based immunoscore has proved to be a prognostic factor in colon cancer, but its significance in pancreatic cancer is poorly known. Total of 108 patients operated (R0/R1) for pancreatic ductal adenocarcinoma (PDAC) (TNM stage I-II) were included in the study. Immune cell score (IS) was determined by scoring the samples from grade 0 to 4 according to the number of immune cells (CD3+ and CD8+) in tumor core and invasion margin using tissue microarrays, immunohistochemistry, and digital analysis. Tumors with microsatellite instability were identified by MLH1 immunostaining. High IS and low histological grade were significantly associated with better disease-specific survival (DSS) and overall survival (OS). The 5-year DSS rate for low, moderate, and high IS groups were 5.0, 15.2, and 33.4%, respectively (p = 0.007). The 5-year OS rate for the low, moderate, and high IS groups were 4.2, 13.4, and 31.5%, respectively (p = 0.004). In addition, IS and prognosis varied within a single TNM stage. There was no association between IS and any of the clinicopathological variables. IS was shown to be an independent prognostic factor for better DSS and OS in multivariate analysis, together with the histological grade of the tumor and perineural invasion. Five MLH1-negative tumors (4.6%) were found showing no correlation with IS. IS could be a useful prognostic marker in patients with PDAC treated by primary surgery.