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1.
J Surg Oncol ; 2022 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-35066881

RESUMO

BACKGROUND: This study explores whether genomic profiles of colorectal liver metastasis (CRLM) patients with early onset (EO, < 50 years old) and screening age (SA) primary diagnosis are associated with overall survival (OS). METHODS: All patients undergoing hepatectomy between 2002 and 2017 were identified and tumor specimens with next-generation sequencing data were cataloged. Gene and signaling-level alterations were checked for association with OS from primary diagnosis accommodating for left-truncated survival. RESULTS: Of 1822 patients, 333 were sequenced-127 (38%) EO-CRLM and 206 (62%) SA-CRLM patients. More aggressive features presented in EO-CRLM patients-synchronous metastatic presentation (83% vs. 75%, p < 0.001) and primary node-positive disease (71% vs. 61%, p < 0.001). The median OS from primary diagnosis was 11.8 years (95% confidence interval = 7.94-NA). Five-year OS did not differ by age (p = 0.702). On multivariable analysis, altered APC (EO-CRLM: [hazard ratio [HR] = 0.37, p = 0.018] vs. SA-CRLM:[HR = 0.61, p = 0.260]), BRAF (EO-CRLM:[HR = 4.38, p = 0.007] vs. SA-CRLM:[HR = 4.78, p = 0.032]), and RAS-TP53 (EO-CRLM:[HR = 2.82, p = 0.011] vs. SA-CRLM:[HR = 2.35, p = 0.003]) associated with OS. CONCLUSIONS: Despite bearing more aggressive features, EO-CRLM patients had similar genomic profiles and survival as SA-CRLM patients. Better performance status in younger patients leading to increased treatment tolerance may partly explain this. As screening and treatment strategies from older patients are applied to younger patients, genomic predictors of biology identified historically in older cohorts could apply to EO patients.

3.
Eur J Surg Oncol ; 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34887165

RESUMO

BACKGROUND: Chyle leak (CL) is a clinically relevant complication after pancreatectomy. Its incidence and the associated risk factors are ill defined, and various treatments options have been described. There is no consensus, however, regarding optimal management. The present study aims to systematically review the literature on CL after pancreatectomy. METHODS: A systematic review from PubMed, Scopus and Embase database was performed. Studies using a clear definition for CL and published from January 2000 to January 2021 were included. The PRISMA guidelines were followed during all stages of this systematic review. The MINORS score was used to assess methodological quality. RESULTS: Literature search found 361 reports, 99 of which were duplicates. The titles and abstracts of 262 articles were finally screened. The references from the remaining 181 articles were manually assessed. After the exclusions, 43 articles were thoroughly assessed. A total of 23 articles were ultimately included for this review. The number of patients varied from 54 to 3532. Incidence of post pancreatectomy CL varied from 1.3% to 22.1%. Main risk factors were the extent of the surgery and early oral or enteral feeding. CL dried up spontaneously or after conservative management within 14 days in 53% to 100% of the cases. CONCLUSIONS: The extent of surgery is the most common predictor of risk of CL. Conservative treatment has been shown to be effective in most cases and can be considered the treatment of choice. We propose a management algorithm based on the current available evidence.

4.
Br J Surg ; 108(12): 1513-1520, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34750608

RESUMO

BACKGROUND: Minimally invasive right posterior sectionectomy (RPS) is a technically challenging procedure. This study was designed to determine outcomes following robotic RPS (R-RPS) and laparoscopic RPS (L-RPS). METHODS: An international multicentre retrospective analysis of patients undergoing R-RPS versus those who had purely L-RPS at 21 centres from 2010 to 2019 was performed. Patient demographics, perioperative parameters, and postoperative outcomes were analysed retrospectively from a central database. Propensity score matching (PSM) was performed, with analysis of 1 : 2 and 1 : 1 matched cohorts. RESULTS: Three-hundred and forty patients, including 96 who underwent R-RPS and 244 who had L-RPS, met the study criteria and were included. The median operating time was 295 minutes and there were 25 (7.4 per cent) open conversions. Ninety-seven (28.5 per cent) patients had cirrhosis and 56 (16.5 per cent) patients required blood transfusion. Overall postoperative morbidity rate was 22.1 per cent and major morbidity rate was 6.8 per cent. The median postoperative stay was 6 days. After 1 : 1 matching of 88 R-RPS and L-RPS patients, median (i.q.r.) blood loss (200 (100-400) versus 450 (200-900) ml, respectively; P < 0.001), major blood loss (> 500 ml; P = 0.001), need for intraoperative blood transfusion (10.2 versus 23.9 per cent, respectively; P = 0.014), and open conversion rate (2.3 versus 11.4 per cent, respectively; P = 0.016) were lower in the R-RPS group. Similar results were found in the 1 : 2 matched groups (66 R-RPS versus 132 L-RPS patients). CONCLUSION: R-RPS and L-RPS can be performed in expert centres with good outcomes in well selected patients. R-RPS was associated with reduced blood loss and lower open conversion rates than L-RPS.

5.
Ann Surg Oncol ; 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34751873

RESUMO

INTRODUCTION: Hepatic arterial infusion (HAI) chemotherapy is associated with improved survival in stage IV colon cancer with liver metastases. Whether simultaneous colon resection and HAI pump (HAIP) placement is associated with increased morbidity has not been specifically studied. The purpose of this study was to compare perioperative outcomes of simultaneous colon resection and HAIP placement versus HAIP placement alone. METHODS: This was a retrospective study of consecutive patients with colon cancer and synchronous liver metastases who underwent HAIP placement between 2007 and 2018. Clinicopathologic characteristics, operative data, complications, and time to first cycle of HAIP chemotherapy were compared between patients who underwent colon resection simultaneously with HAIP placement and those who underwent HAIP placement alone. RESULTS: A total of 258 patients underwent simultaneous colectomy and HAIP placement, and 116 patients underwent HAIP placement alone. Grade 1-2 complications were more common in patients who underwent simultaneous colectomy and HAIP placement (36.8% vs. 19.0%, P < 0.001), but grade 3-4 complications were not observed more frequently (14.3% vs. 12.9%, P = 0.872). The median interval between HAIP placement and start of HAIP chemotherapy did not differ between groups (simultaneous colectomy, 27 days [interquartile range (IQR) 17-34]; HAIP placement alone, 30 days [IQR 21-34]; P = 0.924). Infection of the pump causing either delay of initiation of chemotherapy or explantation of the pump occurred in five patients with simultaneous colectomy and in one patient with HAIP placement alone (P = 0.671). CONCLUSIONS: Simultaneous HAIP implantation and colectomy is safe in patients with liver metastases of colon carcinoma.

6.
Nat Commun ; 12(1): 6821, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34819518

RESUMO

Understanding the molecular and phenotypic profile of colorectal cancer (CRC) in West Africa is vital to addressing the regions rising burden of disease. Tissue from unselected Nigerian patients was analyzed with a multigene, next-generation sequencing assay. The rate of microsatellite instability is significantly higher among Nigerian CRC patients (28.1%) than patients from The Cancer Genome Atlas (TCGA, 14.2%) and Memorial Sloan Kettering Cancer Center (MSKCC, 8.5%, P < 0.001). In microsatellite-stable cases, tumors from Nigerian patients are less likely to have APC mutations (39.1% vs. 76.0% MSKCC P < 0.001) and WNT pathway alterations (47.8% vs. 81.9% MSKCC, P < 0.001); whereas RAS pathway alteration is more prevalent (76.1% vs. 59.6%, P = 0.03). Nigerian CRC patients are also younger and more likely to present with rectal disease (50.8% vs. 33.7% MSKCC, P < 0.001). The findings suggest a unique biology of CRC in Nigeria, which emphasizes the need for regional data to guide diagnostic and treatment approaches for patients in West Africa.

7.
HPB (Oxford) ; 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34844860

RESUMO

BACKGROUND: In patients with perihilar cholangiocarcinoma (PHC), there is concern that transperitoneal (TP) biopsy may seed tumor in the peritoneal cavity, increasing risk of peritoneal metastases (PM). METHODS: A retrospective review of patients undergoing surgery for PHC (1991-2014) was performed. Clinicopathologic characteristics and incidence of PM at the time of index surgery, and one and two years after surgery were compared in patients who did vs. did not undergo TP biopsy. RESULTS: Among 262 patients who underwent surgery, 37 had undergone TP biopsy, and 225 had undergone intraluminal biopsy or had no biopsy. No differences in demographic or clinicopathologic characteristics were noted between groups. The incidence of PM at surgery was not significantly different between TP and non-TP biopsy patients (5.4% vs. 7.6%, p > 0.9). Among 243 patients who did not have PM at surgery, the cumulative incidence of PM in the TP and non-TP biopsy groups were not different at one year (11.4% [95%CI 3.5-24.4] vs. 10.8% [95%CI 7.0-15.5]) or two years (20.3% [95%CI 8.7-35.2] vs. 20.1% [95%CI 14.9-25.9]) (p = 0.7). DISCUSSION: Although PM commonly occurs in patients with PHC, TP biopsy was not associated with higher incidence of PM at surgery or at one or two years after surgery.

8.
Ann Surg ; 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34793354

RESUMO

OBJECTIVE: Prospective evaluation of 2 clinical-molecular models in patients with unknown pathology who underwent endoscopic ultrasound with fine-needle aspiration (EUS-FNA) for a cystic lesion of the pancreas. SUMMARY OF BACKGROUND DATA: Preoperative prediction of histologic subtype (mucinous vs nonmucinous) and grade of dysplasia in patients with pancreatic cystic neoplasms is challenging. Our group has previously published 2 clinical-molecular nomograms for intraductal papillary mucinous neoplasms (IPMN) that incorporated both clinical/radiographic features and cyst fluid protein markers (sFASL, CA72-4, MMP9, IL-4). METHODS: This multiinstitutional study enrolled patients who underwent EUS-FNA for a cystic lesion of the pancreas. Treatment recommendations regarding resection were based on standard clinical, radiographic, and endoscopic features. Predicted probabilities of high-risk IPMN (high-grade dysplasia/invasive cancer) were calculated using the previously developed clinical-molecular nomograms. RESULTS: Cyst fluid was obtained from 100 patients who underwent diagnostic EUS-FNA. Within this group there were 35 patients who underwent resection, and 65 were monitored radiographically. Within the group that underwent resection, 26 had low-risk IPMN or benign non-IPMN lesions, and 9 had high-risk IPMN. Within the surveillance group, no patient progressed to resection or developed cancer after a median follow-up of 12 months (range: 0.5-38). Using the clinical/radiographic nomogram alone, 2 out of 9 patients with high-risk IPMN had a predicted probability >0.5. In the clinical-molecular models, 6 of 9 patients in model 1, and 6 of 9 in model 2, had scores >0.5. CONCLUSIONS: This prospective study of patients with unknown cyst pathology further demonstrates the importance of cyst fluid protein analysis in the preoperative identification of patients with high-risk IPMN. Longer follow-up is necessary to determine if this model will be useful in clinical practice.

9.
Ann Surg ; 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34793355

RESUMO

OBJECTIVE: To determine whether genomic risk groups identified by somatic mutation testing of colorectal liver metastasis (CRLM) can be used for "molecularly-guided" selection for adjuvant systemic chemotherapy and hepatic artery infusion of FUDR (SYS+HAI-FUDR). BACKGROUND: Several genomic biomarkers have been associated with clinical phenotype and survival for patients with resectable CRLM. It is unknown whether prognostication afforded by genomic stratification translates into enhanced patient selection for adjuvant hepatic artery infusion therapy. METHODS: Consecutive patients with resected CRLM and available mutational characterization via Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) were reviewed from a prospective institutional database. Patients were stratified into three genomic risk groups based on previously defined alterations in SMAD4, EGFR and the RAS/RAF pathway. The association between SYS+HAI-FUDR and overall survival (OS), relative to adjuvant chemotherapy alone (SYS), was evaluated in each genomic risk group by Cox proportional hazard regression and propensity score matched analyses. RESULTS: A total of 334 patients (SYS+HAI-FUDR 204; SYS 130) were identified; the rates of RAS/RAF alterations and SMAD4 inactivation were 47.4% and 11.7%, respectively. After a median follow-up of 58 months, adjuvant SYS+HAI-FUDR was independently associated with a reduced risk of death (HR 0.50, 95%CI 0.26-0.98, p=0.045) in the low-risk genomic group, but not in the moderate-risk (HR 1.07, 95%CI 0.5-2.07, p=0.749) or high-risk (HR 1.62, 95%CI 0.29-9.12, p=0.537) cohorts. Following propensity score matching, adjuvant SYS+HAI-FUDR remained associated with significant improvements in long-term survival selectively in the low-risk genomic cohort (5-year actuarial survival: 89% vs. 68%, p=0.019). CONCLUSIONS: Genomic alterations in RAS/RAF, SMAD4 and EGFR may be useful to guide treatment selection in resectable CRLM patients and warrant external validation and integration in future clinical trial design.

10.
Hepatobiliary Surg Nutr ; 10(5): 587-597, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34760963

RESUMO

Background: The application and feasibility of minimally invasive liver resection (MILR) for huge liver tumours (≥10 cm) has not been well documented. Methods: Retrospective analysis of data on 6,617 patients who had MILR for liver tumours were gathered from 21 international centers between 2009-2019. Huge tumors and large tumors were defined as tumors with a size ≥10.0 cm and 3.0-9.9 cm based on histology, respectively. 1:1 coarsened exact-matching (CEM) and 1:2 Mahalanobis distance-matching (MDM) was performed according to clinically-selected variables. Regression discontinuity analyses were performed as an additional line of sensitivity analysis to estimate local treatment effects at the 10-cm tumor size cutoff. Results: Of 2,890 patients with tumours ≥3 cm, there were 205 huge tumors. After 1:1 CEM, 174 huge tumors were matched to 174 large tumors; and after 1:2 MDM, 190 huge tumours were matched to 380 large tumours. There was significantly and consistently increased intraoperative blood loss, frequency in the application of Pringle maneuver, major morbidity and postoperative stay in the huge tumour group compared to the large tumour group after both 1:1 CEM and 1:2 MDM. These findings were reinforced in RD analyses. Intraoperative blood transfusion rate and open conversion rate were significantly higher in the huge tumor group after only 1:2 MDM but not 1:1 CEM. Conclusions: MILR for huge tumours can be safely performed in expert centers It is an operation with substantial complexity and high technical requirement, with worse perioperative outcomes compared to MILR for large tumors, therefore judicious patient selection is pivotal.

11.
Cancer Prev Res (Phila) ; 14(12): 1061-1074, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34507972

RESUMO

Cancer incidence is rising in low- and especially middle-income countries (MIC), driven primarily by four high-burden cancers (breast, cervix, lung, colorectal). By 2030, more than two-thirds of all cancer deaths will occur in MICs. Prevention and early detection are required alongside efforts to improve access to cancer treatment. Successful strategies for decreasing cancer mortality in high-income countries are not always effective, feasible or affordable in other countries. In this review, we evaluate strategies for prevention and early detection of breast, cervix, lung, and colorectal cancers, focusing on modifiable risk factors and high-risk subpopulations. Tobacco taxation, human papilloma virus vaccination, cervical cancer screen-and-treat strategies, and efforts to reduce patient and health system-related delays in the early detection of breast and colorectal cancer represent the highest yield strategies for advancing cancer control in many MICs. An initial focus on high-risk populations is appropriate, with increasing population coverage as resources allow. These strategies can deliver significant cancer mortality gains, and serve as a foundation from which countries can develop comprehensive cancer control programs. Investment in national cancer surveillance infrastructure is needed; the absence of national cancer data to identify at-risk groups remains a barrier to the development of context-specific cancer control strategies.

12.
J Pathol Clin Res ; 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34480530

RESUMO

Histopathological growth patterns (HGPs) are a reliable, reproducible, and strong prognostic biomarker that can be assessed on haematoxylin and eosin-stained sections of resected colorectal liver metastases (CRLM). Assessment estimates the relative fraction of the tumour-liver interface for each of the three growth patterns; the desmoplastic HGP reflects good prognosis. Whether preoperative chemotherapy affects the HGP is currently unclear. The present international multicentre study evaluates this in an original cohort of 877 consecutive patients treated in the Netherlands, an external validation cohort of 1,203 consecutive patients treated in the USA, and a post hoc analysis from the phase III randomised controlled European Organization for Research and Treatment of Cancer (EORTC) 40983 trial (n = 70). All patients underwent resection of CRLM with or without preoperative systemic chemotherapy. Trial patients were randomised between perioperative chemotherapy and resection or resection alone. HGPs were determined according to consensus guidelines and compared for preoperative treatment status. Data from three separate tumour regression grading systems were available for the trial cohort. These were correlated with HGP stratified for treatment arm. In the original cohort, the average presence of desmoplastic HGP was 43% for chemo-naïve versus 67% for preoperatively treated patients (p < 0.001). A significant association between chemotherapy and desmoplastic HGP was found on multivariable analysis (ß [95% confidence interval, CI]: 24.57 [18.28-30.87], p < 0.001). In the validation cohort, the average presence of desmoplastic HGP was 40% for chemo-naïve versus 63% for preoperatively treated patients (p < 0.001). This association remained on multivariable analysis (ß [95% CI]: 24.18 [18.70-29.66], p < 0.001). In the EORTC 40983 trial, the average desmoplastic HGP presence was 33% in the resection arm versus 61% in the chemotherapy arm (p = 0.005). Chemotherapy was independently associated with an increase in desmoplastic HGP (ß [95% CI]: 23.29 [1.78-44.79], p = 0.022). All three tumour regression gradings were significantly associated with the desmoplastic HGP in the chemotherapy arm (all p < 0.04). None were associated in the resection arm (all p > 0.11). Preoperative chemotherapy induces histopathological changes that alter the HGP of CRLM.

13.
World J Surg ; 2021 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-34482410

RESUMO

INTRODUCTION: There are significant differences in the phenotype of CRC by race in the U.S. A similar CRC phenotype-race relationship also appears to exist in South Africa (SA). However, there is a paucity of comparative data on the presentation and survival of CRC in sub-Saharan African by country of origin or race. This study compares clinicopathologic variables between CRC patients in Nigeria and SA. METHODS: From a prospective CRC database, consecutive patients diagnosed between September, 2013 and October, 2018 from the African Research Group for Oncology in South West Nigeria were compared to consecutive patients diagnosed from January, 2016 to October, 2018 from the Colorectal Cancer in South Africa database. Patients with histologically confirmed adenocarcinoma were included. Patients were excluded if they had in-situ disease or no histological diagnosis. Clinical outcomes were calculated from the date of presentation. National census categories were used to define self-reported race in SA. RESULTS: The mean age at presentation in Nigeria (n = 347) was 54.1 years (SD 15.5) compared to 56.8 (SD 13.7) in SA (n = 534). The median age among Black SA (BSA) patients was significantly lower than the median age among White SA (WSA) patients (55 vs. 63, p < 0.001). Right-sided colon cancer was more common in Nigerian (27.4%) and BSA (21.2%) patients compared to WSA patients (15.2%, p < 0.001). Nigerian (39.1%) and BSA (16.7%) patients were also more likely to present with mucinous histology than WSA patients (4.9%, p < 0.001). There was a significant difference in the stage-at-presentation between the cohorts, with a large burden of stage IV disease in the Nigerian cohort (52.6%). Adjusting for stage-at-presentation, there was a significant difference in the median overall survival between country and racial cohorts. CONCLUSION: There are significant differences in the phenotype of CRC between Nigeria and SA. Nigerian and BSA patients, appear to share characteristics that are different than those of WSA patients. Larger series with tissue banking and next-generation sequencing are needed to better delineate these observed differences.

14.
HPB (Oxford) ; 2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34452833

RESUMO

BACKGROUND: To evaluate liver venous deprivation (LVD) outcomes in patients with colorectal liver metastasis (CRLM) heavily pretreated with systemic and hepatic arterial infusion pump (HAIP) chemotherapies that had an anticipated insufficient future liver remnant (FLR) hypertrophy after portal vein embolization (PVE). METHODS: PVE was performed with liquid embolics using a transsplenic or ipsilateral transhepatic approach. Simultaneously and via a trans-jugular approach, the right hepatic vein was embolized with vascular plugs. Liver volumetry was assessed on computed tomography before and 3-6 weeks after LVD. RESULTS: Twelve consecutive CRLM patients that underwent LVD before right hepatectomy or trisectionectomy were included, all previously treated with systemic chemotherapy for a mean of 11.9 months. Six patients had additional HAIP. After embolization, FLR ratio increased from 28.7% ± 5.9 to 42.2% ± 9.0 (P < 0.01). Mean kinetic growth rate (KGR) was 3.56%/week ± 2.3, with a degree of hypertrophy (DH) of 13.8% ± 7.1. In the HAIP subgroup, mean KGR and DH were respectively 3.58%/week ± 2.8 and 14.3% ± 8.7. No severe complications occurred. Ten patients reached surgery after 39 days ± 7.5. CONCLUSION: In heavily pretreated patients, LVD safely stimulated a rapid and effective FLR hypertrophy, with a resultant high rate of resection.

15.
Clin Cancer Res ; 27(21): 5891-5899, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34433650

RESUMO

PURPOSE: The clinical behavior of ampullary adenocarcinoma varies widely. Targeted tumor sequencing may better define biologically distinct subtypes to improve diagnosis and management. EXPERIMENTAL DESIGN: The hidden-genome algorithm, a multilevel meta-feature regression model, was trained on a prospectively sequenced cohort of 3,411 patients (1,001 pancreatic adenocarcinoma, 165 distal bile-duct adenocarcinoma, 2,245 colorectal adenocarcinoma) and subsequently applied to targeted panel DNA-sequencing data from ampullary adenocarcinomas. Genomic classification (i.e., colorectal vs. pancreatic) was correlated with standard histologic classification [i.e., intestinal (INT) vs. pancreatobiliary (PB)] and clinical outcome. RESULTS: Colorectal genomic subtype prediction was primarily influenced by mutations in APC and PIK3CA, tumor mutational burden, and DNA mismatch repair (MMR)-deficiency signature. Pancreatic genomic-subtype prediction was dictated by KRAS gene alterations, particularly KRAS G12D, KRAS G12R, and KRAS G12V. Distal bile-duct adenocarcinoma genomic subtype was most influenced by copy-number gains in the MDM2 gene. Despite high (73%) concordance between immunomorphologic subtype and genomic category, there was significant genomic heterogeneity within both histologic subtypes. Genomic scores with higher colorectal probability were associated with greater survival compared with those with a higher pancreatic probability. CONCLUSIONS: The genomic classifier provides insight into the heterogeneity of ampullary adenocarcinoma and improves stratification, which is dictated by the proportion of colorectal and pancreatic genomic alterations. This approach is reproducible with available molecular testing and obviates subjective histologic interpretation.

16.
Ann Surg ; 274(6): 894-901, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34269717

RESUMO

OBJECTIVE: We sought to compare overall survival (OS) and disease control for patients with localized pancreatic ductal adenocarcinoma (PDAC) treated with ablative dose radiotherapy (A-RT) versus resection. SUMMARY BACKGROUND DATA: Locoregional treatment for PDAC includes resection when possible or palliative RT. A-RT may offer durable tumor control and encouraging survival. METHODS: This was a single-institution retrospective analysis of patients with PDAC treated with induction chemotherapy followed by A-RT [≥98 Gy biologically effective dose (BED) using 15-25 fractions in 3-4.5 Gy/fraction] or pancreatectomy. RESULTS: One hundred and four patients received A-RT (49.8%) and 105 (50.2%) underwent resection. Patients receiving A-RT had larger median tumor size after induction chemotherapy [3.2 cm (undetectable-10.9) vs 2.6 cm (undetectable-10.7), P < 0.001], and were more likely to have celiac or hepatic artery encasement (48.1% vs 11.4%, P <0.001), or superior mesenteric artery encasement (43.3% vs 9.5%, P < 0.001); however, there was no difference in the degree of SMV/PV involvement (P = 0.123). There was no difference in locoregional recurrence/progression at 18-months between A-RT and resection; cumulative incidence was 16% [(95% confidence interval (CI) 10%-24%] versus 21% (95% CI 14%-30%), respectively (P= 0.252). However, patients receiving A-RT had a 19% higher 18-month cumulative incidence of distant recurrence/progression [58% (95% CI 48%-67%) vs 30% (95% CI 30%-49%), P= 0.004]. Median OS from completion of chemotherapy was 20.1 months for A-RT patients (95% CI 16.4-23.1 months) versus 32.9 months (95% CI 29.7-42.3 months) for resected patients (P < 0.001). CONCLUSION: Ablative radiation is a promising new treatment option for PDAC, offering locoregional disease control similar to that associated with resection and encouraging survival.

17.
Cancer ; 127(19): 3566-3578, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34228820

RESUMO

BACKGROUND: Pancreatic cancer is uncommon in patients younger than 50 years, although its incidence is increasing. This study characterizes treatment utilization for early-onset pancreatic cancer (EOPC) versus average-age-onset pancreatic cancer (AOPC) and identifies factors associated with failure to receive treatment. METHODS: The National Cancer Data Base (NCDB) was queried for patients with EOPC (age < 50 years) or AOPC (age ≥ 50 years) from 2004 to 2016. Multinomial regression was used to compare utilization (single modality vs multimodal treatment with or without surgery vs no treatment) between EOPC and AOPC. Kaplan-Meier methods were used to estimate overall survival (OS). RESULTS: Of 248,634 patients, 15,710 (6.3%) had EOPC. There were more male patients (56% vs 50%), non-White patients, and privately insured patients (61% vs 30%) with EOPC versus AOPC, without notable differences in clinical stage distribution. Patients with EOPC received more chemotherapy (38% vs 29%), surgery (9% vs 6.9%), chemoradiation (12% vs 9.2%), and multimodal treatment (21% vs 15%). The odds of receiving multimodal curative therapy were significantly higher for patients with EOPC versus patients with AOPC after adjustments for confounders (odds ratio, 3.89; 95% confidence interval [CI], 3.66-4.15; P < .001). Nineteen percent of patients with EOPC, in contrast to 39% of patients with AOPC, received no treatment. Patients with AOPC more frequently declined chemotherapy (15% vs 9.5%). One-year OS was higher for EOPC versus AOPC across each stage (0/I/II, 72% [95% CI, 71%-74%] vs 53% [95% CI, 53%-54%]; III, 48% [95% CI, 45%-50%] vs 38% [95% CI, 37%-38%]; IV, 25% [95% CI, 24%-26%] vs 15% [95% CI, 15%-15%]) and treated patients (0/I/II, 75% [95% CI, 74%-77%] vs 64% [95% CI, 63%-64%]; III, 51% [95% CI, 49%-54%] vs 47% [95% CI, 47%-48%]; IV, 29% [95% CI, 28%-31%] vs 23% [95% CI, 23%-24%]). CONCLUSIONS: Patients with EOPC receive more oncologic therapy than patients with AOPC, although the intensity, type, and duration of chemotherapy are not available in the NCDB; however, 19% and 39%, respectively, receive no therapy. Underutilization may explain suboptimal oncologic outcomes. Efforts to improve access and treatment utilization in all age groups are warranted.

18.
BMJ Open ; 11(7): e040352, 2021 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-34312189

RESUMO

BACKGROUND/AIMS: Cancer burden is predicted to double by 2030 in sub-Saharan Africa; access to healthcare services for cancer management is a priority in the region. In Nigeria, National Cancer Control Plan aims to ensure >50% cancer screening of eligible populations by 2022 for all Nigerians. We describe healthcare utilisation, cancer screening activities and potential barriers to accessing cancer care within an understudied rural community-based adult population in South West Nigeria. METHODS: In April 2018, we conducted a cross-sectional study of community-based adults (>18 years) ~130 km east of Ibadan, 250 km from Lagos in Osun State, South West Nigeria. Participants completed a face-to-face survey in local dialect. We used a questionnaire to assess demographics, health status, income, medical expenditures, doctor visits and cancer screening history. RESULTS: We enrolled 346 individuals: with median age of 52 years and 75% women. Of the entire cohort, 4% had medical insurance. 46% reported a major medical cost in the last year. Cancer screening activities were infrequent in eligible participants: 1.5% reported having had cervical cancer screening, 3.3% mammogram and 5% colonoscopy screening. Cancer screening assessment was less frequent in those with less income and lower education levels. Using a multivariable logistic regression model including personal income, insurance status and education, higher personal income was associated with more cancer screening activity (OR 2.7, 95% CI 1.3 to 5.7, p<0.01). Despite this, most individuals had contact with a primary healthcare doctor (52% in the last year), and over 70% access to radio and TV suggesting the opportunity to expand community-based screening interventions and awareness exists. CONCLUSIONS: Despite national increases in cancer cases, we highlight a deficiency in cancer screening and universal healthcare coverage within a community-based adult Nigerian population. Subject to availability of governmental resources, increasing financial risk protection, awareness and targeted resource allocation may help expand access in Nigeria.


Assuntos
Detecção Precoce de Câncer , Neoplasias do Colo do Útero , Adulto , África ao Sul do Saara , Estudos Transversais , Feminino , Acesso aos Serviços de Saúde , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Nigéria , Aceitação pelo Paciente de Cuidados de Saúde , População Rural , Neoplasias do Colo do Útero/diagnóstico
19.
J Am Coll Surg ; 233(3): 415-425, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34029677

RESUMO

BACKGROUND: Morbidity after hepatectomy remains a significant, potentially preventable, outcome. Understanding the pattern of complications and rescue pathways is critical for the development of targeted initiatives intended to salvage patients after operative morbidity. STUDY DESIGN: Patients undergoing liver resection from 1991 to 2018 at a single institution were analyzed. Failure to rescue (FTR) was defined as percentage of deaths in patients with a complication within 30 days. Generalized estimating equations with log-link function assessed associations between clinical characteristics and major complications and between complications at fewer than 30 days and 30 to 90 days. Logistic regression assessed associations between complications and FTR. RESULTS: A total of 6,191 patients and 6,668 operations were identified, of which 55.6% were performed for management of metastatic colorectal cancer. Major complications (grade ≥3) occurred in 20.2% of operations (1,346 of 6,668). Ninety-day mortality was 2.2%. The most common complication was intra-abdominal abscess at 9.0% (95% CI, 8.3% to 9.7%). Ten percent of patients with a complication at 30 days had another complication between 30 and 90 days compared with 2% without an early complication (odds ratio [OR] 5.09; 95% CI, 3.97 to 6.54; p < 0.001). FTR for liver failure, cardiac arrest, abscess, and hemorrhage was 36%, 56%, 3%, and 6%, respectively. Risk of 90-day mortality was higher in patients with liver failure (53% vs 2%; OR 61.42; 95% CI, 37.47 to 100.67; p < 0.001), cardiac arrest (69% vs 2%; OR 96.95; 95% CI, 33.23 to 283.80; p < 0.001), hemorrhage (11% vs 2%; OR 5.51; 95% CI, 2.59 to 11.73; p < 0.001), and abscess (7% vs 2%; OR 4.05; 95% CI, 2.76 to 5.94; p < 0.001) compared with those without these complications. CONCLUSIONS: Morbidity after hepatectomy is frequent despite low mortality. This study identifies targets for improvement in morbidity and failure to rescue after hepatectomy. Efforts to improve recognition and intervention for infections and early complications are needed to improve outcomes.


Assuntos
Falha da Terapia de Resgate , Hepatectomia/mortalidade , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Complicações Pós-Operatórias/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Mortalidade Hospitalar , Humanos , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Fatores de Tempo
20.
JNCI Cancer Spectr ; 5(3): pkab026, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34056541

RESUMO

Background: After resection of colorectal cancer liver metastases (CRLM), 2 main histopathological growth patterns can be observed: a desmoplastic and a nondesmoplastic subtype. The desmoplastic subtype has been associated with superior survival. These findings require external validation. Methods: An international multicenter retrospective cohort study was conducted in patients treated surgically for CRLM at 3 tertiary hospitals in the United States and the Netherlands. Determination of histopathological growth patterns was performed on hematoxylin and eosin-stained sections of resected CRLM according to international guidelines. Patients displaying a desmoplastic histopathological phenotype (only desmoplastic growth observed) were compared with patients with a nondesmoplastic phenotype (any nondesmoplastic growth observed). Cutoff analyses on the extent of nondesmoplastic growth were performed. Overall survival (OS) and disease-free survival (DFS) were estimated using Kaplan-Meier and multivariable Cox analysis. All statistical tests were 2-sided. Results: In total 780 patients were eligible. A desmoplastic phenotype was observed in 19.1% and was associated with microsatellite instability (14.6% vs 3.6%, P = .01). Desmoplastic patients had superior 5-year OS (73.4%, 95% confidence interval [CI] = 64.1% to 84.0% vs 44.2%, 95% CI = 38.9% to 50.2%, P < .001) and DFS (32.0%, 95% CI = 22.9% to 44.7% vs 14.7%, 95% CI = 11.7% to 18.6%, P < .001) compared with their nondesmoplastic counterparts. A desmoplastic phenotype was associated with an adjusted hazard ratio for death of 0.36 (95% CI = 0.23 to 0.58) and 0.50 (95% CI = 0.37 to 0.66) for cancer recurrence. Prognosis was independent of KRAS and BRAF status. The cutoff analyses found no prognostic relationship between either OS or DFS and the extent of nondesmoplastic growth observed (all P > .1). Conclusions: This external validation study confirms the remarkably good prognosis after surgery for CRLM in patients with a desmoplastic phenotype. The extent of nondesmoplastic growth does not affect prognosis.

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