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1.
HPB (Oxford) ; 26(5): 703-710, 2024 May.
Article in English | MEDLINE | ID: mdl-38443235

ABSTRACT

BACKGROUND: This study assessed the long-term quality of life (QOL) and priorities of pancreaticoduodenectomy (PD) survivors. METHODS: Survivors were surveyed via internet-based support groups. The relative importance of longevity, experience, costs, and QOL were assessed. RESULTS: The PD cohort (n = 247, 35%) was 60 ± 12 years, 71% female, and 93% white. With moderate agreement, patients ranked survival most important, followed by functional and emotional well-being; costs and experience were least important (W = 35.7%, p < 0.001). Well-being improved throughout survivorship (P-QOL: 39 ± 12 at ≤3 mo vs 43 ± 12 at >10 y, p = 0.170; M-QOL: 38 ± 13 at ≤3 mo vs 44 ± 16 at >10 y; p = 0.015) but remained below the general population (p < 0.001). PD patients with benign diagnoses ranked functional independence as most important (2.00 ± 1.13 vs 2.63 ± 1.19, p < 0.001, W = 41.1%); PD patients with malignant diagnoses regarded overall survival most important (2.10 ± 1.20 vs 1.82 ± 1.22, p < 0.16, W = 35.1%). The mean rank order of priorities remained concordant between short-term (<1 year) and long-term (>5 years) survivors. CONCLUSION: PD survivors experience long-term mental and physical health impairments, underscoring the importance of functional and emotional support. Survivors place paramount importance on overall survival, functional independence, and emotional well-being. Cancer survivors prioritize longevity, while survivors of chronic benign conditions prioritize functional independence.


Subject(s)
Pancreaticoduodenectomy , Quality of Life , Humans , Pancreaticoduodenectomy/adverse effects , Female , Male , Middle Aged , Aged , Time Factors , Surveys and Questionnaires , Survivors/psychology , Emotions , Mental Health , Functional Status , Treatment Outcome , Longevity
2.
Ann Surg Oncol ; 31(3): 2069-2077, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37996643

ABSTRACT

BACKGROUND OR PURPOSE: Carcinomatosis, a distinct pattern of metastatic cancer in the peritoneal cavity, poses challenges for treatment and has limited therapeutic options. Understanding the immune environment of peritoneal surface malignancies is crucial for developing effective immunotherapeutic approaches. This study characterizes soluble immune mediators in the peritoneal fluid of patients with and without carcinomatosis to identify targets for novel treatment strategies. PATIENTS AND METHODS: Serum and peritoneal fluid samples were collected from surgical patients, and a multianalyte analysis was performed using the Luminex platform. Patient characteristics, tumor sites, and sample collection details were recorded. Soluble immune mediator levels were measured and compared between peritoneal fluid and serum samples and among clinical subgroups. Statistical analysis was conducted to assess differences in analyte concentrations and correlations between samples. RESULTS: There were 39 patients included in the study, with varying surgical indications. Significant differences were observed in soluble immune mediator levels between peritoneal fluid and serum, with peritoneal fluid exhibiting lower concentrations. Carcinomatosis was associated with elevated levels of proinflammatory mediators, including IL-6 and IL-8, while adaptive immune response markers were low in peritoneal fluid. CONCLUSIONS: The peritoneal immune microenvironment in carcinomatosis favors innate immunity, presenting a challenging environment for effective antitumor response. High levels of proinflammatory mediators suggest potential targets for intervention, such as the IL-6 axis, FGF2, IL-8, and CCL2; these could be explored as potential mitigators of malignant ascites and enhance anti-tumor immune responses. These findings provide valuable insights for developing immunotherapy strategies and improving outcomes in patients with peritoneal carcinomatosis.


Subject(s)
Carcinoma , Peritoneal Neoplasms , Humans , Peritoneal Neoplasms/secondary , Interleukin-8 , Interleukin-6 , Ascitic Fluid , Carcinoma/pathology , Immunotherapy , Tumor Microenvironment
3.
Am Surg ; 90(1): 85-91, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37578387

ABSTRACT

BACKGROUND: Complex, minimally invasive hepatopancreatobiliary surgery (MIS HPB) is safe at high-volume centers, yet outcomes during early implementation are unknown. We describe our experience during period of rapid growth in an MIS HPB program at a large regional health system. METHODS: During an increase in MIS HPB (60% greater from preceding year), hospital records of patients who underwent HPB surgery between 1/1/2019 and 12/31/2020 were reviewed. Operative time, estimated blood loss (EBL), conversion rates, length of stay (LOS), and perioperative outcomes were assessed. RESULTS: 267 patients' cases were reviewed. The population was 62 ± 13 years, 50% female, 90% white. MIS was more frequently performed for hepatic than pancreatic resections (59% vs 21%, P < .001). Open cases were more frequently performed for invasive malignancy in both pancreatic (70% vs 40%, P < .018) and hepatic (87% vs 70%, P = .046) resections. There was no difference in operative time between MIS and open surgery (293[218-355]min vs 296[199-399]min, P = .893). When compared to open, there was a shorter LOS (4[2-6]d vs 7[6-10]d, P < .001) and lower readmission rate (21% vs 37%, P = .005) following MIS. Estimated blood loss was lower in MIS liver resections, particularly when performed for benign disease (200[63-500]mL vs 600[200-1200]mL, P = .041). Overall 30-day mortality was similar between MIS and open surgery (1.0% vs 1.8%, P = 1.000). DISCUSSION: During a surgical expansion phase within our regional health system, MIS HPB offered improved perioperative outcomes when compared to open surgery. These data support the safety of implementation even during intervals of rapid programmatic growth.


Subject(s)
Hepatectomy , Liver , Humans , Female , Male , Liver/surgery , Pancreatectomy , Length of Stay , Pancreas/surgery , Minimally Invasive Surgical Procedures , Retrospective Studies
4.
J Gastrointest Cancer ; 51(3): 836-843, 2020 Sep.
Article in English | MEDLINE | ID: mdl-31605289

ABSTRACT

PURPOSE: Despite advances in various treatment modalities, surgical resection for pancreatic ductal adenocarcinoma (PDA) remains the only curative treatment. Data remains limited regarding survival rates for resectable PDA when managed by a multidisciplinary pancreas conference (MDPC). The aim of this study is to assess survival rates, identify significant predictors of mortality, and assess the benefits of adjuvant chemotherapy for resectable PDA following presentation at a MDPC. METHODS: All patients presented from April 2013 to August 2016 with resectable PDA were discussed at a MDPC at a tertiary care center and were followed prospectively until November 2017. Survival analysis was performed using Kaplan-Meier for age, tumor size, tumor differentiation, T-stage, lymph node status, and completion of adjuvant chemotherapy cycles. Independent predictors of survival were determined using multivariate Cox regression modeling. RESULTS: After MDPC consensus and exclusions, total of 64 patients underwent successful surgery. Amongst this cohort, 1-, 2-, and 3-year survival was 78.13%, 46.30%, and 27.27%, respectively. A total of 37 patients (58%) initiated and 16 patients (25%) finished chemotherapy following surgery. Log-rank analysis revealed that tumor size, age, surgical margins, lymph node status, and number of adjuvant chemotherapy cycles received significantly influenced post-operative survival. Tumor size (p < 0.001), lymph node status (p = 0.035), and number of adjuvant chemotherapy cycles (p = 0.041) remained significant after multivariate Cox regression model. CONCLUSIONS: Our results suggest that patients with PDA with tumor size > 50 mm and/or lymph node involvement have poor outcomes despite being surgically resectable. Successful completion of adjuvant chemotherapy has better survival outcomes as compared with incomplete or no adjuvant chemotherapy. The role of alternative management such as down-staging with neoadjuvant therapy should be considered.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Pancreatic Ductal/therapy , Pancreatectomy , Pancreatic Neoplasms/therapy , Patient Care Team/organization & administration , Age Factors , Aged , Carcinoma, Pancreatic Ductal/diagnosis , Carcinoma, Pancreatic Ductal/mortality , Carcinoma, Pancreatic Ductal/pathology , Chemotherapy, Adjuvant/standards , Female , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Lymphatic Metastasis/diagnosis , Lymphatic Metastasis/pathology , Lymphatic Metastasis/therapy , Male , Middle Aged , Pancreas/diagnostic imaging , Pancreas/pathology , Pancreas/surgery , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/mortality , Pancreatic Neoplasms/pathology , Patient Care Team/standards , Prognosis , Prospective Studies , Survival Rate , Tertiary Care Centers/organization & administration , Tertiary Care Centers/standards , Treatment Outcome , Tumor Burden
5.
Pancreas ; 48(8): 1086-1091, 2019 09.
Article in English | MEDLINE | ID: mdl-31404024

ABSTRACT

OBJECTIVES: The appropriate timing of chemotherapy following surgery for resectable pancreatic adenocarcinoma is controversial. Using the National Cancer Database we evaluated time to initiation of chemotherapy postresection and correlated with outcome. METHODS: We identified stage I-III pancreatic adenocarcinoma treated surgically with adjuvant chemoradiotherapy. Receiver operator curve analysis identified an interval of 66 days as the a priori value for largest discrepancy in outcome. Multivariable logistic regression analysis identified variables associated with increased time to chemotherapy postoperatively (>66 days). Propensity matching was performed to account for indication bias. RESULTS: In total, 6873 and 3348 patients received chemotherapy before and after the 66-day cutoff, respectively. Predictors of expedited chemotherapy included lower comorbidity, treatment outside a community program in an urban location, having insurance, white race, and treatment after 2009. Propensity-matched median survival was 21.8 months for all patients, and of these, 6462 were stage 1. Five-year survival was 20% in patients receiving chemotherapy within 66 days and 18% in those not (P = 0.0266). In stage 1 patients, 5-year survival was 23% versus 21% (P = 0.0116) in favor of expedited chemotherapy. CONCLUSIONS: The present propensity-matched analysis showed a significant association with survival for earlier delivery of chemotherapy in the adjuvant setting.


Subject(s)
Adenocarcinoma/therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Pancreatectomy/methods , Pancreatic Neoplasms/therapy , Adenocarcinoma/pathology , Adult , Aged , Chemotherapy, Adjuvant/methods , Cohort Studies , Combined Modality Therapy , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Staging , Pancreatic Neoplasms/pathology , Propensity Score , Time Factors
6.
J Gastrointest Oncol ; 10(6): 1080-1093, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31949925

ABSTRACT

BACKGROUND: The only potentially curative approach for pancreatic cancer is surgical resection, but this technically challenging procedure carries risks for postoperative morbidities and mortality. This study of a large, contemporary national database illustrates incidences of, and risk factors for, post-procedural mortality, prolonged hospital stay, and 30-day readmission. METHODS: From the National Cancer Database (NCDB), stage I-III pancreatic adenocarcinomas were identified [2004-2015]. Surgical techniques included pancreaticoduodenectomy, partial pancreatectomy (selective removal of the pancreatic body/tail), total pancreatectomy (removal of the entire pancreas) with or without subtotal resection of the duodenum and/or stomach, and extended pancreatectomy. Predictors of 30/90-day post-operative mortality, 30-day readmission rates, and prolonged hospital stay (>17 days per receiver operating curve analysis) were identified via multivariable logistic regression. RESULTS: Overall, 24,798 patients were analyzed (median age of 66). The majority of cases were T3 (47%), N0 (65%), pancreatic head lesions (83%), and treated with pancreaticoduodenectomy (57%). Only 16% received neoadjuvant therapy. Overall unadjusted risk of 30- and 90-day mortality ranged from 1.3-2.5% and 4.1-7.1%, respectively, depending on extent of surgery. Independent predictors of 30-/90-day mortality included preoperative therapy, increasing age, higher comorbidity score, lower income, case volume, and more extensive surgery. Similar findings were demonstrated regarding prolonged hospital stay and 30-day readmission. Age ≥70 was most associated with 30-day mortality, whereas age ≥60 was most associated with 90-day mortality and prolonged hospital stay. CONCLUSIONS: Quantitation of incidences and risk factors for postoperative outcomes following resection for pancreatic cancer is essential for judicious patient selection and shared decision-making between providers and patients.

7.
Pancreas ; 48(1): 80-84, 2019 01.
Article in English | MEDLINE | ID: mdl-30451791

ABSTRACT

OBJECTIVES: Surgery is the curative treatment for pancreatic ductal adenocarcinoma (PDA). Guidelines recommend utilizing a multidisciplinary pancreatic cancer conference (MDPC) in treatment; however, data are limited. The objective of this study was to assess the accuracy of an MDPC. METHODS: Patients with PDA presented at an MDPC were prospectively collected from April 2013 to August 2016. Patients were included if the MDPC predicted them to have resectable PDA and underwent upfront surgery. Secondary aims were to compare differences in tumor characteristics, time to surgery, and resection rates with patients prior to MDPC implementation (pre-MDPC). RESULTS: A total of 278 patients were presented at the MDPC. After excluding borderline and nonresectable cases, 91 patients were predicted as resectable on evaluation, and 70 were fit for surgery. The MDPC predicted resection in 91.4%. The MDPC had larger tumor size (32.6 vs 24.0 mm), greater proportion of stage II tumor, and a shorter time from diagnosis to resection (27.3 vs 35.5 days) compared with the pre-MDPC. Microscopically negative resections were similar between MDPC and pre-MDPC (85.9% vs 88.0%) despite advanced tumor size and stage. CONCLUSIONS: The MDPC demonstrates a high resection rate. Compared with a pre-MDPC, MDPC provides shorter time to surgery and selects for advanced tumors.


Subject(s)
Carcinoma, Pancreatic Ductal/surgery , Consensus Development Conferences as Topic , Pancreatectomy/methods , Pancreatic Neoplasms/surgery , Aged , Carcinoma, Pancreatic Ductal/diagnosis , Female , Humans , Male , Middle Aged , Outcome Assessment, Health Care/methods , Outcome Assessment, Health Care/statistics & numerical data , Pancreatectomy/statistics & numerical data , Pancreatic Neoplasms/diagnosis , Prognosis , Prospective Studies
9.
Curr Probl Diagn Radiol ; 47(5): 353-356, 2018 Sep.
Article in English | MEDLINE | ID: mdl-28684057

ABSTRACT

Richter transformation is the development of a high-grade lymphoma from chronic lymphocytic leukemia. This rare disease manifestation is difficult to predict and carries a poor prognosis. We describe the case of a 75-year-old man with refractory chronic lymphocytic leukemia who presented with multiple growing fatty abdominal masses on computed tomography and vague abdominal distension. The patient underwent exploratory laparotomy with mass resection due to the nonspecific imaging findings. A mesenteric mass was found to contain nodules of diffuse large B-cell lymphoma. This case highlights the importance of radiologists to consider the prospect tumor transformation in the differential diagnosis of enlarging abdominal masses.


Subject(s)
Leukemia, Lymphocytic, Chronic, B-Cell/diagnostic imaging , Leukemia, Lymphocytic, Chronic, B-Cell/pathology , Lymphoma, Large B-Cell, Diffuse/diagnostic imaging , Lymphoma, Large B-Cell, Diffuse/pathology , Mesentery/diagnostic imaging , Mesentery/pathology , Tomography, X-Ray Computed , Aged , Cell Transformation, Neoplastic , Diagnosis, Differential , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/surgery , Lymphoma, Large B-Cell, Diffuse/surgery , Male , Mesentery/surgery , Neoplasm Grading , Radiography, Abdominal
10.
J Surg Res ; 202(2): 246-52, 2016 05 15.
Article in English | MEDLINE | ID: mdl-27229097

ABSTRACT

BACKGROUND: The purpose of this study was to evaluate the impact of a multidisciplinary clinic (MDC) on the treatment of pancreatic ductal adenocarcinoma. We hypothesized that an MDC would improve trial participation, multimodality therapy, neoadjuvant therapy, time to treatment, and survival. MATERIALS AND METHODS: Pancreatic ductal adenocarcinoma cancer registry patients from 2008-2012 were analyzed. Outcomes of patients evaluated at the MDC were compared with patients not evaluated at the MDC (non-MDC). RESULTS: A total of 1408 patients were identified, 557 (40%) MDC and 851 (60%) non-MDC. MDC were more likely to be an earlier stage than non-MDC (P = 0.0005): I - 4% versus 4%, II - 54% versus 43%, III - 11% versus 9%, and IV - 32% versus 44%. MDC were younger than non-MDC (68 versus 70; P = 0.005); however, younger (<75) and older (≥75) patients were more likely to receive treatment in MDC than non-MDC. MDC were more likely to participate in trials than non-MDC (28% versus 14%; P < 0.0001). MDC were more likely to receive treatment than non-MDC (90% versus 71%; P < 0.0001). MDC were more likely to receive two (38% versus 24%; P < 0.0001) or three (12% versus 9%; P = 0.02) therapies than non-MDC. No difference in time to first treatment in MDC than non-MDC (0.95 versus 0.92 mo; P = 0.69). After adjusting for age, stage, and therapy, there was a trend; however, no statistical difference in disease-free survival (hazard ratio [HR] of non-MDC versus MDC 0.80; 95% confidence interval [95% CI] 0.61-1.05; P = 0.11), time to recurrence (HR of non-MDC versus MDC 0.69; 95% CI 0.45-1.04; P = 0.07), or overall survival (HR of non-MDC versus MDC 0.81; 95% CI, 0.62-1.07; P = 0.13). CONCLUSIONS: Patients evaluated in an MDC were more likely to receive any treatment, receive multimodality therapy, neoadjuvant therapy, and participate in a clinical trial.


Subject(s)
Cancer Care Facilities/organization & administration , Carcinoma, Pancreatic Ductal/therapy , Interdisciplinary Communication , Pancreatic Neoplasms/therapy , Adult , Aged , Aged, 80 and over , Carcinoma, Pancreatic Ductal/diagnosis , Carcinoma, Pancreatic Ductal/mortality , Clinical Trials as Topic , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Staging , Outcome and Process Assessment, Health Care , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/mortality , Pennsylvania , Prognosis , Quality Improvement , Registries , Retrospective Studies , Survival Analysis
11.
Surgery ; 157(2): 211-22, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25282529

ABSTRACT

BACKGROUND: Laparoscopic liver resection (LLR) for metastatic colorectal cancer (mCRC) remains controversial. The objective of this manuscript was to perform a metaanalysis comparing outcomes of LLR with open liver resection (OLR) in patients with hepatic mCRC, and to identify which patients were suitable candidates for LLR. STUDY DESIGN: A PubMed search identified 2,122 articles. When filtered for case-matched articles comparing LLR with OLR for mCRC, 8 articles were identified consisting of 610 patients (242 LLR, 368 OLR). A random effects metaanalysis was performed. RESULTS: The 2 groups were well-matched for age, sex, American Society of Anesthesiologists score, tumor size, number of metastases, extent of major hepatectomy, and use of neoadjuvant/adjuvant chemotherapy. The mean number of metastases in the LLR and OLR groups were 1.4 and 1.5, respectively (P = .14). Estimated blood loss was less in LLR group (262 vs 385 mL; P = .049). Transfusion rate was significantly less in LLR group (9.9 vs 19.8%; P = .004). There was no difference in operative time (248.7 vs 262.8 min; P = .85). Length of stay (LOS) was less in the LLR group (6.5 vs 8.8 days; P = .007). The overall complication rate was less in LLR group (20.3% vs 33.2%; P = .03). Importantly, there was no difference in the 1-, 3-, and 5-year disease-free survival (DFS) or overall survival (OS) rates. CONCLUSION: In carefully selected patients with limited mCRC (1 or 2 tumors), LLR provides marked perioperative benefits without compromising oncologic outcomes or long-term survival. Specifically, LLR offers decreased blood loss, LOS, and overall complication rates with comparable 5-year OS and DFS.


Subject(s)
Colorectal Neoplasms , Hepatectomy/methods , Liver Neoplasms/secondary , Liver Neoplasms/surgery , Disease-Free Survival , Female , Hepatectomy/adverse effects , Humans , Laparoscopy/adverse effects , Laparoscopy/methods , Length of Stay , Male , Patient Selection , Postoperative Complications/prevention & control
12.
J Surg Oncol ; 109(2): 98-103, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24122302

ABSTRACT

BACKGROUND: This study sought to determine clinical and molecular factors related to recurrence and survival in patients with ICC following hepatectomy. METHODS: Database review identified 34 patients. Molecular markers (Ki67, p53, beta-catenin) and standard pathological evaluations were performed. RESULTS: The most common resections were right (n = 11), extended right (n = 8), and left hepatectomy (n = 7). The 30- and 90 -day mortality rates were 5.9% and 11.8%. The median tumor size was 7.8 cm. Nine patients (26.5%) had positive lymph nodes and ten patients (29.4%) received adjuvant therapy. Median follow up was 33.5 months. The median disease-free interval was 6 months. The median overall survival was 37.9 months. Univariate predictors of recurrence were tumor size (P = 0.02) and differentiation (P = 0.05). On multivariate analysis, differentiation (P = 0.03; OR = 0.38; 95% CI: 0.17-0.89) remained significant. Univariate predictors of survival were tumor size (P = 0.02), lymphovascular invasion (P = 0.02), satellite nodules (P = 0.006), beta-catenin expression (P = 0.008), and recurrence (P = 0.026). On multivariate analyses, satellite lesions (P = 0.05, OR = 3.15, 95% CI: 0.96-10.4) and beta-catenin (P = 0.04, OR = 3.23; 95% CI: 1.1-9.7) remained significant and differentiation (P = 0.045; OR = 0.42; 95% CI: 0.18-0.98) was an additional predictor. CONCLUSION: Future clinical trials could include certain molecular and pathologic factors to assist in determining the necessity and type of adjuvant therapy.


Subject(s)
Bile Duct Neoplasms/mortality , Bile Duct Neoplasms/pathology , Bile Ducts, Intrahepatic/pathology , Cholangiocarcinoma/mortality , Cholangiocarcinoma/pathology , Hepatectomy , Adult , Aged , Aged, 80 and over , Bile Duct Neoplasms/metabolism , Bile Duct Neoplasms/therapy , Chemotherapy, Adjuvant , Cholangiocarcinoma/metabolism , Cholangiocarcinoma/therapy , Female , Follow-Up Studies , Genes, p53 , Humans , Ki-67 Antigen/metabolism , Male , Middle Aged , Multivariate Analysis , Neoplasm Recurrence, Local , Registries , beta Catenin/metabolism
14.
J Surg Res ; 176(2): 535-41, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22316666

ABSTRACT

BACKGROUND: The aim of this study was to investigate the relationship between reflux induced bile insult and MnSOD expression, as well as to examine therapies to preserve MnSOD expression. Additionally, we sought to examine the relationship between MnSOD protein expression and MnSOD enzymatic activity. METHODS: MnSOD protein expression was determined by Western blot assay and enzymatic activity was determined by SOD assay. The enzymatic activity of the Het-1A and Bar-T cells were compared both before and after treatments. RESULTS: MnSOD expression in Het-1A cells was decreased after bile salt exposure. The cells that received MnTBAP or curcumin oil pretreatment showed increased MnSOD expression compared with control untreated cells. The Bar-T cells showed an increase in MnSOD expression after treatment with bile salts. The cells that were pretreated with MnTBAP displayed a larger increase in MnSOD expression compared with the cells that were not pretreated prior to bile salt exposure. The MnSOD activity was significantly different between the untreated cell lines (P = 0.01) and after treatment with bile salt (P = 0.03). Additionally, Bar-T cells had significantly less MnSOD activity than Het-1A cells after each of the pretreatments. CONCLUSIONS: We demonstrated preservation of MnSOD expression in Het-1A cells that were pretreated with antioxidants including MnTBAP, curcumin oil, and certain berry extracts. Additionally, we demonstrated that Bar-T cells have significantly less MnSOD activity than Het-1A cells. These finding have important implications for future studies regarding chemoprevention and the treatment of esophageal cancer.


Subject(s)
Barrett Esophagus/drug therapy , Barrett Esophagus/metabolism , Curcumin/pharmacology , Esophageal Neoplasms/prevention & control , Metalloporphyrins/pharmacology , Superoxide Dismutase/metabolism , Barrett Esophagus/complications , Bile Acids and Salts/pharmacology , Cell Line, Transformed , Disease Progression , Enzyme Activation/drug effects , Enzyme Inhibitors/pharmacology , Esophageal Neoplasms/etiology , Esophageal Neoplasms/metabolism , Esophagus/cytology , Esophagus/enzymology , Free Radical Scavengers/pharmacology , Fruit/chemistry , Gastroesophageal Reflux/complications , Humans , Plant Extracts/pharmacology , Respiratory Mucosa/cytology
15.
J Surg Oncol ; 105(1): 91-6, 2012 Jan.
Article in English | MEDLINE | ID: mdl-21815152

ABSTRACT

BACKGROUND AND OBJECTIVES: Patients with peri-hilar cholangiocarcinoma who undergo R1 resection with curative intent will have an improved survival compared to patients who were not resected. METHODS: Review of a prospective hepatobiliary database identified 130 patients. Survival was compared using the log-rank test. RESULTS: Seventy-nine patients (61%) were resected while 51 (49%) patients were not. Forty-two patients (54%) had an R0 resection. There was no difference in mean age (69 vs. 67; P = 0.8), BMI (27.8 vs. 27.9; P = 1.0), gender (73% vs. 43% male; P = 0.1), presence of jaundice (77% vs. 64%; P = 0.5), vascular involvement on pre operative imaging (77% vs. 64%; P = 0.5), stent (73.1% vs. 64.3%; P = 0.72), and lobar atrophy (27% vs. 7%, P = 0.2) in the resected versus non-resected patients. All patients underwent chemotherapy and/or radiation therapy. After a median follow up of 35.6 months the median OSl for all peri-hilar patients was 16.2 months (95% CI = 11.2-23.4). The median OS for resected patients was 18.9 months (95% CI = 12.5-24.7) versus 5.0 months (95% CI = 0-6.9) for patients not resected (P < 0.001). The only pre-operative predictor of OS was resection (P = 0.041). Vascular invasion, lobar atrophy, and stent placement were not statistically significant predictors. CONCLUSION: Overall survival is improved in patients undergoing R1 resection and multi-modality therapy compared to patients not resected.


Subject(s)
Bile Duct Neoplasms/mortality , Bile Duct Neoplasms/surgery , Bile Ducts, Intrahepatic/surgery , Cholangiocarcinoma/mortality , Cholangiocarcinoma/surgery , Endoscopy , Adolescent , Adult , Aged , Aged, 80 and over , Bile Duct Neoplasms/pathology , Bile Ducts, Intrahepatic/pathology , Cholangiocarcinoma/pathology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prognosis , Prospective Studies , Retrospective Studies , Young Adult
16.
Nutr Cancer ; 63(8): 1256-62, 2011 Nov.
Article in English | MEDLINE | ID: mdl-22043833

ABSTRACT

The incidence of esophageal adenocarcinoma in humans is increasing more rapidly than any other malignancy in the United States. Animal studies have demonstrated the efficacy of freeze-dried berry supplementation on carcinogen-induced esophageal squamous cell carcinoma in rats; however, no such studies have been done in esophagoduodenal anastomosis (EDA), an animal model for reflux-induced esophageal adenocarcinoma (EAC) development. Eight-week-old male Sprague-Dawley rats were randomized into 3 groups: EDA + control diet (EDA-CD; n = 10); EDA + 2.5% black raspberry diet (EDA-BRB; n = 11) and EDA + 2.5% blueberry diet (EDA-BB; n = 12). After 2 wk of feeding the respective diets, the rats underwent EDA surgery to induce gastroesophageal reflux and then continued the diet. Measurement of feed intake suggested that all EDA-operated animals had lower feed intake starting at 10 wk after surgery and this was significant close to termination at 24 wk. There were no significant differences in either reflux esophagitis (RE), intestinal metaplasia (IM) (70% in CD, 64% in BRB, and 66% in BB; P = 0.1) or EAC incidence (30% for CD, 34% for BRB, and 25% for BB; P = 0.2) with supplementation. Berry diets did not alter COX-2 levels, but BB diet significantly reduced MnSOD levels (1.23 ± 0.2) compared to control diet (2.05 ± 0.14; P < 0.05). We conclude that a dietary supplementation of freeze-dried BRB and BB at 2.5% (w/w) was not effective in the prevention of reflux-induced esophageal adenocarcinoma in this EDA animal model.


Subject(s)
Dietary Supplements , Esophageal Neoplasms/drug therapy , Esophagitis, Peptic/pathology , Esophagus/drug effects , Fruit/chemistry , Plant Preparations/pharmacology , Adenocarcinoma/drug therapy , Adenocarcinoma/prevention & control , Anastomosis, Surgical , Animals , Anthocyanins/analysis , Ascorbic Acid/analysis , Biomarkers/analysis , Blueberry Plants/chemistry , Cyclooxygenase 2/drug effects , Cyclooxygenase 2/genetics , Cyclooxygenase 2/metabolism , Disease Models, Animal , Disease Progression , Esophageal Neoplasms/prevention & control , Esophagitis, Peptic/drug therapy , Esophagitis, Peptic/prevention & control , Esophagus/pathology , Food Handling/methods , Freeze Drying/methods , Linear Models , Male , Rats , Rats, Sprague-Dawley , Selenium/analysis , Superoxide Dismutase/drug effects , Superoxide Dismutase/genetics , Superoxide Dismutase/metabolism , Weight Gain/drug effects
17.
J Am Coll Surg ; 213(1): 45-52; discussion 52-3, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21601490

ABSTRACT

BACKGROUND: The optimal method for classifying lymph node (LN) status in breast cancer patients is unknown. We sought to determine if LN ratio (LNR) improves axillary staging. STUDY DESIGN: Kentucky Cancer Registry data (1996 to 2007) were used to compare LN categorization schemas. Overall survival (OS) was evaluated using the Kaplan-Meier method and log rank tests. Schemas included: LN positive (+) vs negative (-) disease, current American Joint Committee on Cancer (AJCC) staging (0 vs 1 to 3 vs 4 to 9 vs ≥10 LN+), and LNR 0 vs 0.01 to 0.20 vs 0.21 to 0.65 vs >0.65 (LN- vs low, intermediate, and high risk LN+ groups). RESULTS: There were 1,436 patients who had complete LN evaluation data: 880 (61.3%) were LN- and 556 (39.6%) were LN+; 309 (21.5%) had 1 to 3 positive LNs, 138 (9.6%) had 4 to 9 positive LNs, and 109 (7.6%) had 10 or more positive LNs. For LN+ patients, the median number of positive LNs was 3; median LNR was 0.23. The median follow-up was 65 months. LN status was associated with 5-year OS (91.3% and 73.3% for LN- and LN+ groups, respectively, p < 0.001). Increasing AJCC pN stage was associated with worse OS (5-year OS 80.5%, 75.3%, and 49.8% for pN1 to N3, respectively, p < 0.001). LNR was also associated with OS (5-year OS of 83.1%, 72.7%, and 52.7% for the low, intermediate, and high risk LN+ groups, respectively, p < 0.001). In subgroup analyses of patients in the 1 to 3 and 4 to 9 LN+ groups, OS was statistically associated with LNR (p = 0.021 and p = 0.016, respectively). On multivariable survival analysis, LNR was associated with OS, independent of AJCC categorization, p = 0.003. CONCLUSIONS: LNR was associated with OS, regardless of AJCC LN categories.


Subject(s)
Breast Neoplasms/mortality , Breast Neoplasms/pathology , Lymph Nodes , Neoplasm Staging , Adult , Aged , Aged, 80 and over , Axilla , Breast Neoplasms/therapy , Female , Humans , Kentucky , Lymph Node Excision , Middle Aged , Predictive Value of Tests , Registries , Retrospective Studies , Survival Analysis , Survival Rate , Young Adult
18.
Ann Surg Oncol ; 18(2): 431-8, 2011 Feb.
Article in English | MEDLINE | ID: mdl-20862554

ABSTRACT

BACKGROUND: Unresectable intrahepatic cholangiocellular carcinoma (ICC) carries a poor prognosis, and there are few chemotherapeutic treatments to prolong survival. The purpose of this study was to assess the efficacy of drug-eluting bead (DEB) therapy by transarterial infusion for unresectable ICC. METHODS: A prospective multicenter study of ICC patients who received hepatic arterial DEB therapy. RESULTS: Twenty-four patients with unresectable ICC were treated with DEB. Ten patients (41.6%) had recurrent ICC after prior radiofrequency ablation (n = 3) or hepatectomy (n = 7). Twenty patients (80%) had received prior chemotherapy, mostly of gemcitabine (n = 8) or Eloxatin (n = 6). The percent of overall liver involvement was < 25% (n = 8), 26% to 50% (n = 11), and > 50% (n = 4). Ten patients (40%) had sites of extrahepatic disease located at lymph nodes (n = 5), bone (n = 2), peritoneum (n = 1), lung (n = 1), and mouth (n = 1). A total of 42 DEB treatments were administered. Eight were administered in combination with systemic chemotherapy of FOLFOX (n = 4) or Gemzar (n = 4). Twelve patients (48%) received a second treatment, and 4 patients (16%) received a third treatment. The median length of stay was 23 h (23-72 h). Eleven adverse reactions (26.2%) were reported. Of these, 7 (63.6%) were minor (less than grade 3). One patient died from hepatorenal syndrome. The disease of one patient was downstaged to resection. After a median follow-up of 13.6 months, the median overall survival of a multitherapeutic regimen with DEB therapy was significantly greater than chemotherapy alone (17.5 vs. 7.4 months; P = 0.02). CONCLUSIONS: Bead therapy is safe and effective in patients with unresectable ICC. There is a marked survival benefit when DEB therapy is used as adjunctive therapy.


Subject(s)
Antineoplastic Agents, Phytogenic/administration & dosage , Bile Duct Neoplasms/drug therapy , Bile Ducts, Intrahepatic/drug effects , Camptothecin/analogs & derivatives , Cholangiocarcinoma/drug therapy , Hepatic Artery , Salvage Therapy , Adult , Aged , Aged, 80 and over , Bile Duct Neoplasms/mortality , Bile Duct Neoplasms/surgery , Bile Ducts, Intrahepatic/surgery , Camptothecin/administration & dosage , Cholangiocarcinoma/mortality , Cholangiocarcinoma/surgery , Female , Follow-Up Studies , Humans , Irinotecan , Male , Middle Aged , Prodrugs , Prospective Studies , Survival Rate , Treatment Outcome
19.
Am J Surg ; 201(4): 519-24, 2011 Apr.
Article in English | MEDLINE | ID: mdl-20864079

ABSTRACT

BACKGROUND: Patients with pancreatic cancer who present with biliary symptoms may undergo cholecystectomy and thus delay cancer diagnosis. We hypothesized that prior cholecystectomy leads to decreased overall survival in patients with pancreatic adenocarcinoma. METHODS: Retrospective study of hepatobiliary database. RESULTS: Three hundred sixty-five patients with a diagnosis of resectable periampullary pancreatic adenocarcinoma were identified. Eighty-seven patients underwent prior cholecystectomy. Median age (P = .48), body mass index (BMI) (P = .8), diabetes status (P = .06), American Society of Anesthesiologists (ASA) class (P = .22), stent placement (P = .13), operative time (P = .76), estimated blood loss (EBL) (P = .24), intraoperative transfusion (P = .91), portal vein resection (P = .25), LOS (P = .09) adjuvant therapy (P = .2), tumor size (P = .89), differentiation (P = .67), angiolymphatic invasion (P = .69), perineural invasion (P = 54), nodal metastasis (P = .43), complication rate (P = .75), and 30-day mortality (P = .58) were not statistically different between patients with previous cholecystectomy and those without. Median survival was 14 months for patients with a history of cholecystectomy and 16 months for those without (P = .25). Previous cholecystectomy was not a predictor of survival on Cox regression analysis. CONCLUSION: There was no difference in overall survival in patients with pancreatic cancer with prior cholecystectomy versus those without.


Subject(s)
Adenocarcinoma/surgery , Cholecystectomy/adverse effects , Pancreatic Neoplasms/surgery , Pancreaticoduodenectomy , Adenocarcinoma/mortality , Aged , Cholecystectomy/mortality , Female , Humans , Male , Pancreatic Neoplasms/mortality , Retrospective Studies , Survival Analysis , Treatment Outcome
20.
J Surg Res ; 171(2): 623-30, 2011 Dec.
Article in English | MEDLINE | ID: mdl-20638682

ABSTRACT

BACKGROUND: Bile acids are implicated as etiologic agents in esophageal cancer. We sought to analyze the impact of bile acid exposure on esophageal epithelial cells, Barrett's metaplastic cells (BE), esophageal adenocarcinoma cells (EAC), and esophageal squamous carcinoma cell (ESC). We sought to determine if cellular resistance is related to manganese superoxide dismutase expression. METHODS: Cells were exposed to sodium choleate (CA), sodium deoxycholate (DCA), sodium glycocholate (GCA), sodium taurocholate (TCA), or a 1:1 mixture (MIX) of reagents at concentrations in the range 0.2-0.8 mM. Cell viability was evaluated by MTT assay. Manganese superoxide dismutase (MnSOD) expression was analyzed by Western blot. Statistical analysis was performed using SPSS ver. 17.0, SPSS Inc., Chicago, IL. RESULTS: Bile salt exposure inhibited cell viability in esophageal squamous cells in time- and growth-dependent manner. There was a 50% decrease in cell viability from 4 to 24 h. BE, EAC, and ESC cell lines were more resistant to bile insult. In untreated cell lines, MnSOD expression was significantly decreased in EAC and ESC cell lines compared with esophageal squamous epithelial cells and BE cells (P=0.002). Exposure of ESC cells to bile salt increased MnSOD expression. CONCLUSION: The confirmation of the role of reactive oxygen species (ROS) and bile acids in esophageal carcinogenesis has interesting implications for chemoprevention in patients with reflux esophagitis and Barrett's esophagus. Further studies are necessary to assess the preventative role of antioxidant supplementation.


Subject(s)
Adenocarcinoma/metabolism , Adenocarcinoma/pathology , Bile Acids and Salts/metabolism , Esophageal Neoplasms/metabolism , Esophageal Neoplasms/pathology , Superoxide Dismutase/metabolism , Antioxidants/metabolism , Barrett Esophagus/metabolism , Barrett Esophagus/pathology , Bile Acids and Salts/toxicity , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/pathology , Cell Line, Transformed , Cell Line, Tumor , Cell Survival/drug effects , Cell Survival/physiology , Humans , Oxidative Stress/drug effects , Oxidative Stress/physiology , Reactive Oxygen Species/metabolism
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