ABSTRACT
PURPOSE: To evaluate the prognostic significance of circulating tumour cell (CTC) number determined on the Epic Sciences platform in men with metastatic castration-resistant prostate cancer (mCRPC) treated with an androgen receptor signalling inhibitor (ARSI). PATIENTS AND METHODS: A pre-treatment blood sample was collected from men with progressing mCRPC starting either abiraterone or enzalutamide as a first-, second- or third-line systemic therapy at Memorial Sloan Kettering Cancer Center (Discovery cohort, N = 171) or as a first- or second-line therapy as part of the multicenter PROPHECY trial (NCT02269982) (Validation cohort, N = 107). The measured CTC number was then associated with overall survival (OS) in the Discovery cohort, and progression-free survival (PFS) and OS in the Validation cohort. CTC enumeration was also performed on a concurrently obtained blood sample using the CellSearch® Circulating Tumor Cell Kit. RESULTS: In the MSKCC Discovery cohort, CTC count was a statistically significant prognostic factor of OS as a dichotomous (<3 CTCs/mL versus ≥ 3 CTCs/mL; hazard ratio [HR] = 1.8 [95% confidence interval {CI} 1.3-3.0]) and a continuous variable when adjusting for line of therapy, presence of visceral metastases, prostate-specific antigen, lactate dehydrogenase and alkaline phosphatase. The findings were validated in an independent datas et from PROPHECY (HR [95% CI] = 1.8 [1.1-3.0] for OS and 1.7 [1.1-2.9] for PFS). A strong correlation was also observed between CTC counts determined in matched samples on the CellSearch® and Epic platforms (r = 0.84). CONCLUSION: The findings validate the prognostic significance of pretreatment CTC number determined on the Epic Sciences platform for predicting OS in men with progressing mCRPC starting an ARSI.
Subject(s)
Neoplastic Cells, Circulating/pathology , Prostatic Neoplasms, Castration-Resistant/pathology , Adult , Aged , Aged, 80 and over , Androgen Antagonists/therapeutic use , Androstenes/therapeutic use , Benzamides/therapeutic use , Biomarkers, Tumor/blood , Cell Count , Clinical Decision-Making , Humans , Keratins/blood , Leukocyte Common Antigens/blood , Male , Middle Aged , Neoplasm Metastasis , Neoplastic Cells, Circulating/chemistry , Neoplastic Cells, Circulating/drug effects , Nitriles/therapeutic use , Phenylthiohydantoin/therapeutic use , Predictive Value of Tests , Progression-Free Survival , Prostatic Neoplasms, Castration-Resistant/blood , Prostatic Neoplasms, Castration-Resistant/drug therapy , Prostatic Neoplasms, Castration-Resistant/mortality , Reproducibility of ResultsABSTRACT
OBJECTIVES: We aimed to develop a prospective prediction tool on Crimean-Congo haemorrhagic fever (CCHF) to identify geographic regions at risk. The tool could support public health decision-makers in implementation of an effective control strategy in a timely manner. METHODS: We used monthly surveillance data between 2004 and 2015 to predict case counts between 2016 and 2017 prospectively. The Turkish nationwide surveillance data set collected by the Ministry of Health contained 10 411 confirmed CCHF cases. We collected potential explanatory covariates about climate, land use, and animal and human populations at risk to capture spatiotemporal transmission dynamics. We developed a structured Gaussian process algorithm and prospectively tested this tool predicting the future year's cases given past years' cases. RESULTS: We predicted the annual cases in 2016 and 2017 as 438 and 341, whereas the observed cases were 432 and 343, respectively. Pearson's correlation coefficient and normalized root mean squared error values for 2016 and 2017 predictions were (0.83; 0.58) and (0.87; 0.52), respectively. The most important covariates were found to be the number of settlements with fewer than 25 000 inhabitants, latitude, longitude and potential evapotranspiration (evaporation and transpiration). CONCLUSIONS: Main driving factors of CCHF dynamics were human population at risk in rural areas, geographical dependency and climate effect on ticks. Our model was able to prospectively predict the numbers of CCHF cases. Our proof-of-concept study also provided insight for understanding possible mechanisms of infectious diseases and found important directions for practice and policy to combat against emerging infectious diseases.
Subject(s)
Hemorrhagic Fever, Crimean/epidemiology , Hemorrhagic Fever, Crimean/transmission , Animals , Climate , Epidemiological Monitoring , Geography , Hemorrhagic Fever Virus, Crimean-Congo , Hemorrhagic Fever, Crimean/prevention & control , Humans , Machine Learning , Normal Distribution , Predictive Value of Tests , Prospective Studies , Public Health/methods , Spatio-Temporal Analysis , Ticks , Turkey/epidemiologyABSTRACT
AIM: To determine whether antegrade or retrograde methods should be preferred for double-J stent placement in patients with malignant ureteral obstruction (MUO). MATERIAL AND METHODS: The medical records of patients treated for MUO in the Urology and Interventional Radiology Clinic, Konya Training and Research Hospital, were reviewed retrospectively. Patients with benign aetiology were excluded from the study. Reports of the procedures, ultrasonography findings, computed tomography (CT), angiography, and pyelography images and the follow-up records of patients with MUO were assessed. A total of 111 patients and 114 ureteral stenting treatments were included in the study; 63 (55.3%) were operated on using the antegrade ureteral stenting (AUS) method, whereas 51 (44.7%) were operated on using the retrograde ureteral stenting (RUS), method, and the characteristics of these groups were evaluated. The presence of hydroureteronephrosis and ureteral tortuosity were determined. RESULTS: Overall success rates were found to be 95.2% using the AUS method and 47.1% using the RUS method. The technical success of the antegrade method was significantly higher in patients with or without tortuosity (respectively: p=0.005, Z shape p=0.001, pigtail shape p=0.035â³). The technical success of the antegrade method was significantly higher in patients with hydroureteronephrosis (p=0.001). CONCLUSION: The AUS technique should be the first choice for double-J stent placement in patients with MUO.
Subject(s)
Prosthesis Implantation/methods , Stents , Ureteral Obstruction/surgery , Adult , Aged , Aged, 80 and over , Colonic Neoplasms/complications , Female , Humans , Male , Middle Aged , Operative Time , Retrospective Studies , Tomography, X-Ray Computed , Ureteral Obstruction/diagnostic imaging , Ureteral Obstruction/etiology , UrographyABSTRACT
AIM: Significant recent changes in management of locally advanced rectal cancer (LARC) include preoperative staging, use of extended neoadjuvant therapies and minimally invasive surgery (MIS). This study was aimed at characterizing these changes and associated short-term outcomes. METHOD: We retrospectively analysed treatment and outcome data from patients with T3/4 or N+ LARC ≤ 15 cm from the anal verge who were evaluated at a comprehensive cancer centre in 2009-2015. RESULTS: In total, 798 patients were identified and grouped into five cohorts based on treatment year: 2009-2010, 2011, 2012, 2013 and 2014-2015. Temporal changes included increased reliance on MRI staging, from 57% in 2009-2010 to 98% in 2014-2015 (P < 0.001); increased use of total neoadjuvant therapy, from 17% to 76% (P < 0.001); and increased use of MIS, from 33% to 70% (P < 0.001). Concurrently, median hospital stay decreased (from 7 to 5 days; P < 0.001), as did the rates of Grade III-V complications (from 13% to 7%; P < 0.05), surgical site infections (from 24% to 8%; P < 0.001), anastomotic leak (from 11% to 3%; P < 0.05) and positive circumferential resection margin (from 9% to 4%; P < 0.05). TNM downstaging increased from 62% to 74% (P = 0.002). CONCLUSION: Shifts toward MRI-based staging, total neoadjuvant therapy and MIS occurred between 2009 and 2015. Over the same period, treatment responses improved, and lengths of stay and the incidence of complications decreased.
Subject(s)
Disease Management , Neoadjuvant Therapy/trends , Patient Care Team/trends , Proctectomy/trends , Rectal Neoplasms/therapy , Aged , Female , Humans , Length of Stay/trends , Male , Margins of Excision , Middle Aged , Neoplasm Grading , Neoplasm Staging , Rectal Neoplasms/pathology , Retrospective Studies , Time Factors , Treatment OutcomeABSTRACT
Escherichia coli ST131 is a cause for global concern because of its high multidrug resistance and several virulence factors. In this study, the contribution of acrAB-TolC efflux system of E. coli ST131 to fluoroquinolone resistance was evaluated. A total of nonrepetitive 111 ciprofloxacin-resistant E. coli isolates were included in the study. Multilocus sequence typing was used for genotyping. Expressions of acrA, acrB, and TolC efflux pump genes were measured by RT-PCR. Mutations in marA, gyrA, parC, and aac(6')-lb-cr positivity were studied by Sanger sequencing. Sixty-four (57.7%) of the isolates were classified as ST131, and 52 (81.3%) of the ST131 isolates belonged to H30-Rx subclone. In ST131, CTX-M 15 positivity (73%) and aac(6')-lb-cr carriage (75%) were significantly higher than those in non-ST131 (12.8% and 51%, respectively) (P < 0.05). The ampicillin-sulbactam (83%) resistance was higher, and gentamicin resistance (20%) was lower in ST131 than that in non-ST131 (64% and 55%, respectively) (P = 0.001 and P = 0.0002). Numbers of the isolates with MDR or XDR profiles did not differ in both groups. Multiple in-dels (up to 16) were recorded in all quinolone-resistant isolates. However, marA gene was more overexpressed in ST131 compared to that in non-ST131 (median 5.98 vs. 3.99; P = 0.0007). Belonging to H30-Rx subclone, isolation site, ciprofloxacin MIC values did not correlate with efflux pump expressions. In conclusion, the marA regulatory gene of AcrAB-TolC efflux pump system has a significant impact on quinolone resistance and progression to MDR profile in ST131 clone. Efflux pump inhibitors might be alternative drugs for the treatment of infections caused by E. coli ST131 if used synergistically in combination with antibiotics.
Subject(s)
Carrier Proteins/genetics , Drug Resistance, Multiple, Bacterial/genetics , Escherichia coli Proteins/genetics , Escherichia coli/drug effects , Escherichia coli/genetics , Quinolones/pharmacology , Anti-Bacterial Agents/pharmacology , Escherichia coli Infections/drug therapy , Humans , Microbial Sensitivity Tests/methods , Multilocus Sequence Typing/methods , Virulence Factors/geneticsABSTRACT
BACKGROUND: Surgical-site infection (SSI) is associated with significant healthcare costs. To reduce the high rate of SSI among patients undergoing colorectal surgery at a cancer centre, a comprehensive care bundle was implemented and its efficacy tested. METHODS: A pragmatic study involving three phases (baseline, implementation and sustainability) was conducted on patients treated consecutively between 2013 and 2016. The intervention included 13 components related to: bowel preparation; oral and intravenous antibiotic selection and administration; skin preparation, disinfection and hygiene; maintenance of normothermia during surgery; and use of clean instruments for closure. SSI risk was evaluated by means of a preoperative calculator, and effectiveness was assessed using interrupted time-series regression. RESULTS: In a population with a mean BMI of 30 kg/m2 , diabetes mellitus in 17·5 per cent, and smoking history in 49·3 per cent, SSI rates declined from 11·0 to 4·1 per cent following implementation of the intervention bundle (P = 0·001). The greatest reductions in SSI rates occurred in patients at intermediate or high risk of SSI: from 10·3 to 4·7 per cent (P = 0·006) and from 19 to 2 per cent (P < 0·001) respectively. Wound care modifications were very different in the implementation phase (43·2 versus 24·9 per cent baseline), including use of an overlying surface vacuum dressing (17·2 from 1·4 per cent baseline) or leaving wounds partially open (13·2 from 6·7 per cent baseline). As a result, the biggest difference was in wound-related rather than organ-space SSI. The median length of hospital stay decreased from 7 (i.q.r. 5-10) to 6 (5-9) days (P = 0·002). The greatest reduction in hospital stay was seen in patients at high risk of SSI: from 8 to 6 days (P < 0·001). SSI rates remained low (4·5 per cent) in the sustainability phase. CONCLUSION: Meaningful reductions in SSI can be achieved by implementing a multidisciplinary care bundle at a hospital-wide level.
Subject(s)
Patient Care Bundles/standards , Patient Care Team/standards , Surgical Wound Infection/prevention & control , Female , Humans , Length of Stay/statistics & numerical data , Male , Middle Aged , Patient Readmission/statistics & numerical data , Risk Factors , Treatment Outcome , Wound Closure Techniques/standardsABSTRACT
PURPOSE: To review outcomes following microwave ablation (MWA) of colorectal cancer pulmonary metastases and assess predictors of oncologic outcomes. METHODS: Technical success, primary and secondary technique efficacy rates were evaluated for 50 patients with 90 colorectal cancer pulmonary metastases at immediate, 4-8 weeks post-MWA and subsequent follow-up CT and/or 18F-FDG PET/CT. Local tumor progression (LTP) rate, LTP-free survival (LTPFS), cancer-specific and overall survivals were assessed. Complications were recorded according to SIR classification. RESULTS: Median follow-up was 25.6 months. Median tumor size was 1 cm (0.3-3.2 cm). Technical success, primary and secondary technique efficacy rates were 99, 90 and 92%, respectively. LTP rate was 10%. One-, 2- and 3-year LTPFS were: 93, 86 and 86%, respectively, with median LTPFS not reached. Median overall survival was 58.6 months, and median cancer-specific survival (CSS) was not reached. One-, 2- and 3-year overall and CSS were 94% and 98, 82 and 90%, 61 and 70%, respectively. On univariate analysis, minimal ablation margin (p < 0.001) and tumor size (p = 0.001) predicted LTPFS, with no LTP for minimal margin ≥ 5 mm and/or tumor size < 1 cm. Pleural-based metastases were associated with increased LTP risk (p = 0.002, SHR = 7.7). Pre-MWA CEA level > 10 ng/ml (p = 0.046) and ≥ 3 prior chemotherapy lines predicted decreased CSS (p = 0.02). There was no 90-day death. Major complications rate was 13%. CONCLUSIONS: MWA with minimal ablation margin ≥ 5 mm is essential for local control of colorectal cancer pulmonary metastases. Pleural-based metastases and larger tumor size were associated with higher risk of LTP. CEA level and pre-MWA chemotherapy impacted CSS.
Subject(s)
Catheter Ablation/methods , Colorectal Neoplasms/surgery , Lung Neoplasms/secondary , Microwaves/therapeutic use , Adult , Aged , Colorectal Neoplasms/diagnostic imaging , Female , Fluorodeoxyglucose F18 , Follow-Up Studies , Humans , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/surgery , Male , Middle Aged , Positron Emission Tomography Computed Tomography , Retrospective Studies , Tomography, X-Ray Computed , Treatment OutcomeABSTRACT
OBJECTIVES: To assess safety and efficacy of 90Y resin microspheres administration using undiluted non-ionic contrast material (UDCM) {100% Omnipaque-300 (Iohexol)} in both the "B" and "D" lines. MATERIALS AND METHODS: We reviewed all colorectal cancer liver metastases patients treated with 90Y resin microspheres radioembolization (RAE) from 2009 to 2017. As of April 2013, two experienced operators started using UDCM (study group) instead of standard sandwich infusion (control group). Occurrence of myelosuppression (leukopenia, neutropenia, erythrocytopenia or/and thrombocytopenia), stasis, nontarget delivery (NTD), median fluoroscopy radiation dose (FRD), median infusion time (IT), liver progression-free (LPFS) and overall survivals (OS) was evaluated. Complications within 6 months post-RAE were reported according to CTCAE v3.0 criteria. RESULTS: Study and control groups comprised 23(28%) and 58(72%) patients, respectively. Median follow-up was 9.1 months. There was no statistically significant difference in myelosuppression incidence within 6 months post-RAE between groups. Median FRD and IT for study and control groups were 44.6 vs. 97.35 Gy/cm2 (p = 0.048) and 31 vs. 39 min (p = 0.006), respectively. A 38% lower stasis incidence in study group was not significant (p = 0.34). NTD occurred in 1/27(4%) study vs. 5/73(7%) control group procedures (p = 1). Grade 1-2 and grade 3-4 toxicities between study and control group patients were 36%(8/22) vs. 45%(26/58), p = 0.61 and 9%(2/22) vs. 16%(9/58), p = 0.72, respectively. There was no difference in LPFS and OS between groups. CONCLUSION: Administration of 90Y resin microspheres using UDCM in both lines is safe and effective, resulting in lower fluoroscopy radiation dose and shorter infusion time, without evidence of myelosuppression or increased stasis incidence.
Subject(s)
Brachytherapy/methods , Colorectal Neoplasms/radiotherapy , Embolization, Therapeutic/methods , Liver Neoplasms/radiotherapy , Liver Neoplasms/secondary , Microspheres , Yttrium Radioisotopes/therapeutic use , Adult , Aged , Brachytherapy/adverse effects , Colorectal Neoplasms/mortality , Embolization, Therapeutic/adverse effects , Female , Follow-Up Studies , Humans , Iohexol , Liver Neoplasms/mortality , Male , Middle Aged , Prospective Studies , Survival Analysis , Treatment Outcome , Yttrium Radioisotopes/adverse effectsABSTRACT
Cancer is the leading cause of morbidity and mortality worldwide. Some studies have shown that high heat kills cancer cells. Irisin is a protein involved in heat production by converting white into brown adipose tissue, but there is no information about how its expression changes in cancerous tissues. We used irisin antibody immunohistochemistry to investigate changes in irisin expression in gastrointestinal cancers compared to normal tissues. Irisin was found in human brain neuroglial cells, esophageal epithelial cells, esophageal epidermoid carcinoma, esophageal adenocarcinoma and neuroendocrine esophageal carcinoma, gastric glands, gastric adenosquamous carcinoma, gastric neuroendocrine carcinoma, gastric signet ring cell carcinoma, neutrophils in vascular tissues, intestinal glands of colon, colon adenocarcinoma, mucinous colon adenocarcinoma, hepatocytes, hepatocellular carcinoma, islets of Langerhans, exocrine pancreas, acinar cells and interlobular and interlobular ducts of normal pancreas, pancreatic ductal adenocarcinoma, and intra- and interlobular ducts of cancerous pancreatic tissue. Histoscores (area × intensity) indicated that irisin was increased significantly in gastrointestinal cancer tissues, except liver cancers. Our findings suggest that the relation of irisin to cancer warrants further investigation.
Subject(s)
Fibronectins/genetics , Fibronectins/metabolism , Gastrointestinal Neoplasms/physiopathology , Immunohistochemistry , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , HumansABSTRACT
BACKGROUND: The objective of this study was to derive and validate a prognostic nomogram to predict disease-specific survival (DSS) after a curative intent resection of perihilar cholangiocarcinoma (PHC). PATIENTS AND METHODS: A nomogram was developed from 173 patients treated at Memorial Sloan Kettering Cancer Center (MSKCC), New York, USA. The nomogram was externally validated in 133 patients treated at the Academic Medical Center (AMC), Amsterdam, The Netherlands. Prognostic accuracy was assessed with concordance estimates and calibration, and compared with the American Joint Committee on Cancer (AJCC) staging system. The nomogram will be available as web-based calculator at mskcc.org/nomograms. RESULTS: For all 306 patients, the median overall survival (OS) was 40 months and the median DSS 41 months. Median follow-up for patients alive at last follow-up was 48 months. Lymph node involvement, resection margin status, and tumor differentiation were independent prognostic factors in the derivation cohort (MSKCC). A nomogram with these prognostic factors had a concordance index of 0.73 compared with 0.66 for the AJCC staging system. In the validation cohort (AMC), the concordance index was 0.72, compared with 0.60 for the AJCC staging system. Calibration was good in the derivation cohort; in the validation cohort patients had a better median DSS than predicted by the model. CONCLUSIONS: The proposed nomogram to predict DSS after curative intent resection of PHC had a better prognostic accuracy than the AJCC staging system. Calibration was suboptimal because DSS differed between the two institutions. The nomogram can inform patients and physicians, guide shared decision making for adjuvant therapy, and stratify patients in future randomized, controlled trials.
Subject(s)
Klatskin Tumor/mortality , Klatskin Tumor/surgery , Nomograms , Adult , Aged , Aged, 80 and over , Algorithms , Female , Humans , Male , Middle Aged , Models, Theoretical , Neoplasm Staging , PrognosisSubject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers, Tumor/genetics , Drug Resistance, Neoplasm/genetics , Gene Expression Profiling , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/mortality , Adolescent , Adult , Cohort Studies , Cytarabine/administration & dosage , Daunorubicin/administration & dosage , Female , Follow-Up Studies , Humans , Leukemia, Myeloid, Acute/genetics , Male , Middle Aged , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/mortality , Neoplasm Staging , Prognosis , Survival Rate , Young AdultABSTRACT
BACKGROUND: Pelvic lymph node dissection in patients undergoing radical prostatectomy for clinically localised prostate cancer is not without morbidity and its therapeutical benefit is still a matter of debate. The objective of this study was to develop a model that allows preoperative determination of the minimum number of lymph nodes needed to be removed at radical prostatectomy to ensure true nodal status. METHODS: We analysed data from 4770 patients treated with radical prostatectomy and pelvic lymph node dissection between 2000 and 2011 from eight academic centres. For external validation of our model, we used data from a cohort of 3595 patients who underwent an anatomically defined extended pelvic lymph node dissection. We estimated the sensitivity of pathological nodal staging using a beta-binomial model and developed a novel clinical (preoperative) nodal staging score (cNSS), which represents the probability that a patient has lymph node metastasis as a function of the number of examined nodes. RESULTS: In the development and validation cohorts, the probability of missing a positive lymph node decreases with increase in the number of nodes examined. A 90% cNSS can be achieved in the development and validation cohorts by examining 1-6 nodes in cT1 and 6-8 nodes in cT2 tumours. With 11 nodes examined, patients in the development and validation cohorts achieved a cNSS of 90% and 80% with cT3 tumours, respectively. CONCLUSIONS: Pelvic lymph node dissection is the only reliable technique to ensure accurate nodal staging in patients treated with radical prostatectomy for clinically localised prostate cancer. The minimum number of examined lymph nodes needed for accurate nodal staging may be predictable, being strongly dependent on prostate cancer characteristics at diagnosis.
Subject(s)
Prostatic Neoplasms/pathology , Aged , Aged, 80 and over , Cohort Studies , Humans , Lymph Node Excision , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Staging , Prostatectomy , Prostatic Neoplasms/surgery , Risk AssessmentABSTRACT
OBJECTIVE: To explore whether pre-reoperative dynamic contrast-enhanced (DCE)-MRI findings correlate with clinical outcome in patients who undergo surgical treatment for recurrent rectal carcinoma. METHODS: A retrospective study of DCE-MRI in patients with recurrent rectal cancer was performed after obtaining an IRB waiver. We queried our PACS from 1998 to 2012 for examinations performed for recurrent disease. Two radiologists in consensus outlined tumour regions of interest on perfusion images. We explored the correlation between K(trans), Kep, Ve, AUC90 and AUC180 with time to re-recurrence of tumour, overall survival and resection margin status. Univariate Cox PH models were used for survival, while univariate logistic regression was used for margin status. RESULTS: Among 58 patients with pre-treatment DCE-MRI who underwent resection, 36 went directly to surgery and 18 had positive margins. K(trans) (0.55, P = 0.012) and Kep (0.93, P = 0.04) were inversely correlated with positive margins. No significant correlations were noted between K(trans), Kep, Ve, AUC90 and AUC180 and overall survival or time to re-recurrence of tumour. CONCLUSION: K(trans) and Kep were significantly associated with clear resection margins; however overall survival and time to re-recurrence were not predicted. Such information might be helpful for treatment individualisation and deserves further investigation.
Subject(s)
Image Enhancement/methods , Neoplasm Recurrence, Local/diagnosis , Neoplasm Recurrence, Local/surgery , Rectal Neoplasms/diagnosis , Rectal Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Chemoradiotherapy , Contrast Media , Female , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Neoadjuvant Therapy , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Preoperative Care , Prognosis , Proportional Hazards Models , Rectal Neoplasms/mortality , Rectal Neoplasms/pathology , Reoperation , Retrospective Studies , Survival Rate , Treatment OutcomeABSTRACT
BACKGROUND: Perioperative outcomes, such as blood loss, transfusions, and morbidity, have been linked to cancer-specific survival, but this is largely unsupported by prospective data. METHODS: Patients from a previous, randomized trial that evaluated acute normovolemic hemodilution during major hepatectomy (≥3 segments) were reevaluated and those with metastatic colorectal cancer (n = 90) were selected for analysis. Survival data were obtained from the medical record. Disease extent was measured using a clinical-risk score (CRS). Log-rank test and Cox proportional hazard model were used to evaluate recurrence-free survival (RFS) and overall survival (OS). RESULTS: Median follow-up was 71 months. The CRS was ≥3 in 45 % of patients; 59 % had extrahepatic procedures. Morbidity and mortality were 33 and 2 %, respectively. Postoperative chemotherapy was given to 87 % of patients (78/90) starting at a median of 6 weeks. RFS and OS were 29 and 60 months, respectively. Postoperative morbidity significantly reduced RFS (23 vs. 69 months; P < 0.001) and OS (28 vs. 74 months; P < 0.001) on uni- and multi-variate analysis; positive resection margins and high CRS also were significant factors. Delayed initiation of postoperative chemotherapy (≥8 weeks) was common in patients with complications (37 vs. 12 %; P = 0.01). CONCLUSIONS: In this selected cohort of patients from a previous RCT, perioperative morbidity was strongly (and independently) associated with cancer-specific outcome. It also was associated with delayed initiation of postoperative chemotherapy, the impact of which on survival is unclear.
Subject(s)
Blood Loss, Surgical , Colorectal Neoplasms/pathology , Hemodilution , Hepatectomy/adverse effects , Liver Neoplasms/surgery , Transfusion Reaction , Abdominal Abscess/etiology , Chemotherapy, Adjuvant , Disease-Free Survival , Equipment Failure , Female , Hospital Mortality , Humans , Ileus/etiology , Infusion Pumps, Implantable/adverse effects , Length of Stay , Liver Neoplasms/drug therapy , Liver Neoplasms/secondary , Male , Middle Aged , Multivariate Analysis , Myocardial Ischemia/etiology , Neoplasm, Residual , Recurrence , Risk Assessment , Surgical Wound Infection/etiology , Survival Rate , Tachycardia/etiology , Time Factors , Venous Thrombosis/etiologyABSTRACT
BACKGROUND: The hepatic artery lymph node (HALN) is frequently sampled during pancreaticoduodenectomy (PD). Data suggest that survival in the setting of HALN metastases is similar to that of stage IV pancreatic ductal adenocarcinoma (PDAC). The objectives of this study were to describe the prognostic significance of HALN metastases and to assess the predictive performance of HALN compared to peripancreatic lymph node status. METHODS: Patients undergoing PD for PDAC from January 2000-October 2010 were identified from a prospectively maintained database. Patients were included if during PD the HALN was submitted for pathologic evaluation. Patients were excluded if margins were macroscopically positive, if pathology was found to be consistent with a diagnosis other than PDAC. Overall (OS) and disease-free survival (DFS) were estimated by Kaplan-Meier methods. RESULTS: Of the 671 patients who underwent PD for PDAC, HALN status was analyzed for 147 patients. HALN was positive in 23 patients (16 %), 38 were peripancreatic lymph node (PPLN) and HALN negative, and 86 were PPLN+/HALN-. Median follow-up for survivors was 10 months. In a multivariable model, lymph node status and tumor differentiation predicted OS and DFS. Hazard of death and relapse/death were highest among the HALN+ patients (hazard ratio [HR] 2.94; p = 0.017 and HR 2.66; p = 0.011, respectively). Kaplan-Meier analysis revealed significant differences in OS (p = 0.017) and DFS (p = 0.013) based on lymph node status. CONCLUSIONS: OS and DFS are significantly reduced in patients with a positive HALN. Differentiation and lymph node status were predictors of OS and DFS. In the multivariate models, differentiation and lymph node status remain independent predictors of OS and DFS.
Subject(s)
Carcinoma, Pancreatic Ductal/secondary , Lymph Nodes/pathology , Pancreatic Neoplasms/pathology , Aged , Carcinoma, Pancreatic Ductal/surgery , Disease-Free Survival , Female , Hepatic Artery , Humans , Kaplan-Meier Estimate , Lymphatic Metastasis , Male , Middle Aged , Pancreas , Pancreatic Neoplasms/surgery , Pancreaticoduodenectomy , Predictive Value of Tests , Retrospective StudiesABSTRACT
PURPOSE: To examine the association between positive resection margins and survival and local recurrence in patients with gastric cancer undergoing resection with curative intent. METHODS: Patients who underwent curative intent resection for gastric carcinoma from 1985 to 2010 were identified from a prospectively maintained database. Positive margins were defined as disease present at the line of luminal transection. Clinicopathological features and outcome of patients undergoing gastrectomy with negative and positive margins were compared. RESULTS: Among 2384 patients undergoing curative intent resection, 108 (4.5 %) had positive margins. Positive margins were associated with higher American Joint Committee on Cancer (AJCC) stage, T stage, N stage, median number of positive nodes, diffuse Lauren type, and poorly differentiated tumors. Treatment of positive margins consisted of: observation (39 %), chemoradiotherapy (26 %), chemotherapy (20 %), repeat resection (10 %), radiotherapy (4 %), and unknown (1 %). Multivariate analysis of the entire cohort demonstrated margin status, T stage, N stage, grade, and perineural invasion to be independent predictors of survival. Margin status was an independent predictor of survival in patients with ≤3 positive nodes or T1-2 disease but was not in patients with >3 positive nodes or T3-4 disease. Local recurrence occurred in 16 % of patients with a positive margin. We identified no factors predictive of local recurrence in patients with positive margins. CONCLUSIONS: Positive resection margin is associated with advanced AJCC stage and aggressive tumor biology but remains an independent predictor of worse survival. The significance of a positive margin in gastric cancer is confined to patients with nontransmural disease and/or limited nodal involvement.
Subject(s)
Carcinoma/secondary , Carcinoma/therapy , Neoplasm Recurrence, Local/etiology , Stomach Neoplasms/pathology , Stomach Neoplasms/therapy , Adult , Aged , Aged, 80 and over , Chemoradiotherapy, Adjuvant , Chemotherapy, Adjuvant , Female , Gastrectomy , Humans , Kaplan-Meier Estimate , Lymphatic Metastasis , Male , Middle Aged , Multivariate Analysis , Neoplasm Grading , Neoplasm Invasiveness , Neoplasm Staging , Neoplasm, Residual , Proportional Hazards Models , Radiotherapy, Adjuvant , Reoperation , Retrospective Studies , Young AdultABSTRACT
BACKGROUND: Splenectomy is performed for a variety of indications in haematological disorders. This study was undertaken to analyse outcomes, and morbidity and mortality rates associated with this procedure. METHODS: Patients undergoing splenectomy for the treatment or diagnosis of haematological disease were included. Indications for operation, preoperative risk, intraoperative variables and short-term outcomes were evaluated. RESULTS: From January 1997 to December 2010, 381 patients underwent splenectomy for diagnosis or treatment of haematological disease. Some 288 operations were performed by an open approach, 83 laparoscopically, and there were ten conversions. Overall 136 patients (35·7 per cent) experienced complications. Postoperative morbidity was predicted by age more than 65 years (odds ratio (OR) 1·63, 95 per cent confidence interval 1·05 to 2·55), a Karnofsky performance status (KPS) score lower than 60 (OR 2·74, 1·35 to 5·57) and a haemoglobin level of 9 g/dl or less (OR 1·74, 1·09 to 2·77). Twenty-four patients (6·3 per cent) died within 30 days of surgery. Postoperative mortality was predicted by a KPS score lower than 60 (OR 16·20, 6·10 to 42·92) and a platelet count of 50,000/µl or less (OR 3·34, 1·25 to 8·86). The objective of the operation was achieved in 309 patients (81·1 per cent). The success rate varied for each indication: diagnosis (106 of 110 patients, 96·4 per cent), thrombocytopenia (76 of 115, 66·1 per cent), anaemia (10 of 16, 63 per cent), to allow further treatment (46 of 59, 78 per cent) and primary treatment (16 of 18, 89 per cent). CONCLUSION: Splenectomy is an effective procedure in the diagnosis and treatment of haematological disease in selected patients.
Subject(s)
Hematologic Diseases/surgery , Splenectomy/methods , Adolescent , Adult , Aged , Aged, 80 and over , Blood Loss, Surgical/statistics & numerical data , Child , Child, Preschool , Conversion to Open Surgery/statistics & numerical data , Female , Hemoglobins/metabolism , Humans , Infant , Laparotomy/methods , Laparotomy/mortality , Male , Middle Aged , Operative Time , Platelet Count , Postoperative Complications/etiology , Risk Factors , Splenectomy/mortality , Treatment Outcome , Young AdultABSTRACT
AIMS: The choice of insulin at initiation in type 2 diabetes remains controversial. The aim of this study was to assess the occurrence of self-reported severe hypoglycaemia associated with premixed insulin analogues in routine clinical care. METHODS: A 12-month, prospective, observational, multicentre study in patients starting a commonly prescribed premixed insulin analogue (either insulin lispro 25/75 or biphasic insulin aspart 30/70, twice daily) after suboptimal glycaemic control on oral antidiabetic agents. Treatment decisions were made solely in the course of usual practice. RESULTS: Study follow-up was completed by 991 (85.5%) of the 1150 patients enrolled. At baseline, mean (SD) age was 57.9 (10.1) years; mean diabetes duration was 9.2 (5.9) years; mean haemoglobin A(1c) (HbA(1c)) was 9.9 (1.8) % and the rate of severe hypoglycaemia was 0.03 episode/patient-year. At 12 months, the rate of severe hypoglycaemia was 0.04 episode/patient-year (95% CI 0.023, 0.055 episode/patient-year) and mean insulin dose was 41.5 (19.4) units. Changes from baseline to 12 months for mean fasting plasma glucose and HbA(1c) were -5.1 mmol/l and -2.5%, respectively. CONCLUSIONS: After initiation of premixed insulin analogues in patients with type 2 diabetes in real-world settings, the incidence of severe hypoglycaemia was lower than expected from previously reported studies.
Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Hypoglycemia/chemically induced , Hypoglycemic Agents/adverse effects , Insulin/analogs & derivatives , Ambulatory Care , Blood Glucose/metabolism , Body Mass Index , Body Weight , Diabetes Mellitus, Type 2/blood , Fasting/blood , Female , Glycated Hemoglobin/metabolism , Humans , Insulin/adverse effects , Male , Middle Aged , Prospective StudiesABSTRACT
BACKGROUND: While it is suggested that more than 15 lymph nodes (LNs) should be evaluated for accurate staging of gastric cancer, LN yield in western countries is generally low. The effect of preoperative chemotherapy on LN yield in gastric cancer is unknown. The aim of the present study is to determine whether preoperative chemotherapy is associated with any difference in the number of LNs obtained from specimens of patients who underwent curative surgery for gastric adenocarcinoma. PATIENTS AND METHODS: In 1205 patients from Memorial Sloan-Kettering Cancer Center (MSKCC) and 1220 patients from the Netherlands Cancer Registry (NCR) who underwent a gastrectomy with curative intent for gastric adenocarcinoma without receiving preoperative radiotherapy, LN yield was analyzed, comparing patients who received preoperative chemotherapy and patients who received no preoperative therapy. RESULTS: Of the 2425 patients who underwent a gastrectomy, 14% received preoperative chemotherapy. Median LN yields were 23 at MSKCC and 10 in the NCR. Despite this twofold difference in LN yield between the two populations, with multivariate Poisson regression, chemotherapy was not associated with LN yield of either population. Variables associated with increased LN yield were institution, female sex, lower age, total (versus distal) gastrectomy and increasing T-stage. CONCLUSIONS: In this patient series, treatment at MSKCC, female sex, lower age, total gastrectomy and increasing primary tumor stage were associated with a higher number of evaluated LNs. Preoperative chemotherapy was not associated with a decrease in LN yield. Evaluating more than 15 LNs after gastrectomy is feasible, with or without preoperative chemotherapy.