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1.
J Surg Oncol ; 120(4): 736-739, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31309554

ABSTRACT

BACKGROUND: The misdiagnosis of appendiceal cancer as inflammatory appendicitis is becoming of greater clinical concern because of the rise of nonoperative management especially in the elder population. To quantify this rate of misdiagnosis, we retrospectively reviewed SEER-Medicare data. METHODS: The SEER-Medicare database was reviewed from 2000 to 2014. We identified patients older than 65 years old who were diagnosed with appendiceal cancer and then cross-referenced them for a diagnosis of inflammatory appendicitis. Demographic data and oncologic stage were collected. RESULTS: Our results showed that 28.6% of appendiceal cancer patients received an incorrect initial diagnosis of inflammatory appendicitis. Patients older than 75 years of age were more likely to be misdiagnosed than those between ages 65 and 75 (risk ratio [RR]: 0.81; 95% confidence interval: 0.70-0.93; P = .003). We found that 42% of patients within the misdiagnosis group presented with an earlier stage of disease (stage 1 or 2) compared to 26% of those primarily diagnosed with appendiceal cancer (P < .001). CONCLUSION: A significant proportion of patients older than 65 years old with appendiceal cancer were initially misdiagnosed with acute appendicitis. We suggest caution when considering a nonoperative approach for appendicitis in the elderly and follow-up imaging or an interval appendectomy should be part of the treatment plan.


Subject(s)
Appendiceal Neoplasms/diagnosis , Appendicitis/diagnosis , Aged , Appendectomy , Appendiceal Neoplasms/epidemiology , Appendiceal Neoplasms/surgery , Appendicitis/epidemiology , Appendicitis/surgery , Databases, Factual , Diagnosis, Differential , Female , Follow-Up Studies , Humans , Male , Medicare , Prognosis , Retrospective Studies , United States/epidemiology
2.
Ann Surg ; 266(4): 610-616, 2017 10.
Article in English | MEDLINE | ID: mdl-28742699

ABSTRACT

OBJECTIVE: The aim of the study was to explore specific microRNAs (miRs) in rectal cancer that would predict response to radiation and identify target pathways that may be exploited for neoadjuvant therapies. SUMMARY BACKGROUND DATA: Chemoradiotherapy (CRT) response is a predictor of survival in rectal cancer. Studies have demonstrated changes in RNA expression correlate with chemoradiation sensitivity across cancers. METHODS: Forty-five rectal cancer patients, partial responders (PR = 18), nonresponders (NR = 13), and complete responders (CR = 14) to CRT, as defined by a tumor regression score, were examined. miRs differentially expressed, using NanoString microArray profiling, were validated with qPCR. We quantified 1 miR and its downstream targets in patient samples. Chemosensitivity was measured in HCT-116, a human colorectal carcinoma cell line, using inhibitors of SHP2 and RAF. RESULTS: miR-451a, 502-5p, 223-3p, and 1246 were the most upregulated miRs (>1.5-fold change) in a NanoString profiling miR panel. qPCR revealed a decrease in expression of miR-451a in NRs. EMSY and CAB39, both downstream targets of miR-451a and involved in carcinogenesis (shown in TCGA) were increased in NRs (qPCR). Both targets are associated with worse survival in colorectal cancer. Inhibition of miR-451a in HCT-116 cells significantly decreased cell proliferation with treatment of SHP2 and RAF inhibitors. CONCLUSIONS: An integrated analysis of rectal cancer miRs may yield biomarkers of radioresistance and offer treatment targets for resensitization.


Subject(s)
Chemoradiotherapy , Gene Expression Regulation, Neoplastic , MicroRNAs/genetics , Radiation Tolerance , Rectal Neoplasms/genetics , Rectal Neoplasms/therapy , Female , Gene Expression Profiling , HCT116 Cells , Humans , Male , Middle Aged , Neoadjuvant Therapy , Retrospective Studies
3.
Dis Colon Rectum ; 60(5): 537-543, 2017 May.
Article in English | MEDLINE | ID: mdl-28383454

ABSTRACT

BACKGROUND: Underrepresentation of highly ranked women in academic surgery is recognized. OBJECTIVE: Our objective was to examine whether sex differences exist in faculty representation, academic rank, and publication productivity among colorectal faculty in fellowship programs. DESIGN: American Society of Colon and Rectal Surgeons fellowship program faculty were identified. Bibliometric data were obtained for each faculty member, including Hirsch index, the Hirsch index divided by research career duration, and number of publications. Linear mixed-effect regression models were constructed to determine the association between the Hirsch index and the Hirsch index divided by research career duration and sex, when controlling for institutional measures. A subset analysis of academic faculty examined the association between academic rank, sex, and Hirsch index and the Hirsch index divided by research career duration. SETTINGS: Colorectal fellowship programs, defined as academic, satellite-academic, and nonacademic, were evaluated. RESULTS: Three hundred fifty-eight faculty members were examined across 55 training programs; 22% (n = 77) were women and 78% (n = 281) were men. Sixty-one percent (n = 220) practiced in an academic setting, 23% (n = 84) in a satellite-academic setting, and 15% (n = 54) in a nonacademic setting. There was no difference in median number of publications between sexes (15 vs 10, p = 0.33); men, however, had longer careers (18 vs 11 years, p < 0.001). When controlling for confounders, there was no difference in the Hirsch index (p = 0.42) or the Hirsch index divided by research career duration (p = 0.73) between sexes. Academic rank was significantly associated with Hirsch index and the Hirsch index divided by research career duration (p < 0.001) after controlling for sex. LIMITATIONS: Our assessment of association between publication productivity and academic rank was only possible in the subset of academic faculty. In addition, this study is limited by its retrospective nature. CONCLUSIONS: We found no difference in median number of publications between men and women. When controlling for possible confounders, sex was not a significant predictor of a faculty member's publication productivity, as measured by the Hirsch index or the Hirsch index divided by research career duration; academic rank, however, was.


Subject(s)
Colorectal Surgery , Education , Faculty, Medical , Physicians, Women , Bibliometrics , Career Choice , Colorectal Surgery/education , Colorectal Surgery/organization & administration , Colorectal Surgery/statistics & numerical data , Education/methods , Education/organization & administration , Faculty, Medical/organization & administration , Faculty, Medical/statistics & numerical data , Fellowships and Scholarships/statistics & numerical data , Female , Humans , Male , Physicians, Women/psychology , Physicians, Women/statistics & numerical data , Sex Factors , United States
4.
Clin Exp Gastroenterol ; 10: 39-46, 2017.
Article in English | MEDLINE | ID: mdl-28223835

ABSTRACT

Perianal Crohn's disease affects a significant number of patients with Crohn's disease and is associated with poor quality of life. The nature of the disease, compounded by presentation of various disease severities, has made the treatment of perianal Crohn's disease difficult. The field continues to evolve with the use of both historical and contemporary solutions to address the challenges associated with it. The goal of this article is to review current literature regarding medical and surgical treatment, as well as the future directions of therapy.

5.
Cancer Prev Res (Phila) ; 9(12): 942-949, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27658891

ABSTRACT

Colorectal cancer and adenoma adjacent to cancer exhibit distinct microRNA (miRNA) alterations in an apparent mucosa-to-adenocarcinoma sequence. The pattern of microRNAs in screen-detected polyps in relation to histologic features and cancer risk has not been investigated. miRNA expression analysis was performed on normal mucosa (NM), hyperplastic polyps (HP), tubular adenomas (TA), tubulovillous adenomas or high-grade dysplasia (TVHG), and serrated polyps [sessile serrated adenoma/polyps (SSA/P) and traditional serrated adenomas (TSA)] in biopsy specimens from 109 patients undergoing screening/surveillance colonoscopy. Generalized linear models were used to identify differentially expressed miRNAs by histologic type and logistic regression to identify miRNA predictors of histopathology. False discovery rate (FDR) was used to control for multiple comparisons. We identified 99 miRNAs differing in at least one of five histopathologic groups (FDR ≤0.05). In a comparison of HPNM versus TVHG, the top most upregulated and downregulated miRNAs in HPNM included miR-145, -143, -107, -194, and -26a (upregulated), and miR-663, -1268, -320b, -1275, and -320b (downregulated; FDR P < 0.05). miR-145 and -619 showed high accuracy to discriminate low- from high-risk polyps without serrated histology (TVHG vs. HPNM + TA; CI, 95.6%), whereas miR-124, -143, and -30a showed high accuracy of separating high-risk polyps (TVHG + TSA) from low-risk polyps (HPNM + TA + SSA/P; CI, 96.0%). For TSAs, miR-125b and -199a were uniquely downregulated relative to HPNMs, and miR-335, -222, and -214 discriminated between non-serrated and serrated histology. Our data support the presence of colorectal cancer-associated miRNA alterations in screen-detected adenomas that may be useful for risk stratification for surveillance interval planning. Cancer Prev Res; 9(12); 942-9. ©2016 AACR.


Subject(s)
Adenoma/genetics , Adenoma/pathology , Colonic Polyps/genetics , Colonic Polyps/pathology , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , MicroRNAs/genetics , Adenoma/diagnosis , Aged , Colonic Polyps/diagnosis , Colonoscopy , Colorectal Neoplasms/diagnosis , Early Detection of Cancer/methods , Female , Gene Expression Profiling/methods , Humans , Logistic Models , Male , Middle Aged , Neoplasm Grading , Risk
6.
Ann Surg Oncol ; 23(12): 3934-3940, 2016 11.
Article in English | MEDLINE | ID: mdl-27444107

ABSTRACT

BACKGROUND: Treatment for anal canal cancer has evolved from radical operations to definitive chemoradiotherapy (CRT), which allows for sphincter preservation in most patients. OBJECTIVE: The aim of this study was to examine the use of CRT for patients with stage II and III anal cancer, among different patient demographics, geographic regions, and facility types. METHODS: Utilizing the National Cancer Data Base, we examined patients with stage II and III anal canal squamous cell carcinoma from 2003 to 2010. Via univariate analysis, we examined patterns of treatment by patient demographics, tumor characteristics, geographic region, and facility type (academic vs. community). A multivariable logistic regression model was built to evaluate differences in treatment patterns when adjusting by age, sex, race, comorbidities, and stage. RESULTS: A total of 12,801 patients were analyzed, of which 11,312 (88 %) received CRT. After adjusting for confounders, CRT was less likely to be administered to males [odds ratio (OR) 0.61, 95 % confidence interval (CI) 0.54-0.69], Black patients (OR 0.70, 95 % CI 0.59-0.83), and those with multiple comorbidities (OR 0.60, 95 % CI 0.51-0.72). CRT was not as widely utilized in the West (OR 0.74, 95 % CI 0.59-0.93), and patients treated in academic-based centers were less likely to receive CRT (OR 0.81, 95 % CI 0.72-0.92). Improved median overall survival was observed when CRT was utilized (p = 0.008). CONCLUSION: When controlling for age, sex, race, comorbidities, and stage, discrepancies in the use of CRT for anal cancer treatment exist between demographic subtypes, geographical regions, and facility types.


Subject(s)
Anus Neoplasms/epidemiology , Anus Neoplasms/therapy , Carcinoma, Squamous Cell/epidemiology , Carcinoma, Squamous Cell/therapy , Chemoradiotherapy/statistics & numerical data , Academic Medical Centers/statistics & numerical data , Black or African American/statistics & numerical data , Aged , Anus Neoplasms/pathology , Carcinoma, Squamous Cell/pathology , Comorbidity , Databases, Factual , Female , Humans , Male , Middle Aged , Neoplasm Staging , Sex Factors , Survival Rate , United States , White People/statistics & numerical data
7.
Dis Colon Rectum ; 59(1): 1-7, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26651105

ABSTRACT

BACKGROUND: Anal cancer treatment has evolved from abdominoperineal resection to chemoradiotherapy, which allows for sphincter preservation. OBJECTIVE: The aim of this study was to develop an accurate model and nomogram to predict overall survival and the probability of salvage abdominoperineal resection for anal cancer patients. DESIGN: This is a retrospective cohort study. SETTINGS: Data were gathered from National Cancer Database entries from 1998 to 2010. PATIENTS: Patients with de novo anal cancer were selected from the National Cancer Database in the years 1998 through 2010; 1778 patients were included, and their data were analyzed. MAIN OUTCOME MEASURES: Variables included time to death, censoring indicator, age, race, sex, tumor size, year of diagnosis, surgery status, nodal status, TNM stage, and chemoradiation therapy. A stratified Cox proportional hazards model for overall survival and a logistic regression model for salvage abdominoperineal resection were developed. Our final models were internally validated for discrimination and validation. RESULTS: Statistically significant variables in the salvage surgery model were tumor size and nodal status (p ≤ 0.001). For overall survival model, statistically significant variables (all with p ≤ 0.005), fitted across the strata of TNM clinical stage included age, sex, tumor size, nodal status, chemoradiotherapy treatment, and combination salvage surgery and chemoradiotherapy. Nomograms that predict events are based on our final models. LIMITATIONS: Limitations included clerical database errors and nonmeasured variables, such as HIV status. CONCLUSIONS: A nomogram can predict overall survival and salvage surgery for an individual with anal cancer. Such tools may be used as decision support aids to guide therapy and predict whether or not patients may need salvage surgery.

9.
J Gastrointest Surg ; 19(10): 1862-8, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26286366

ABSTRACT

INTRODUCTION: Although medical management of Crohn's disease has changed in recent years, it is unclear whether surgical management has altered. We examined rate changes of surgical interventions, stoma constructions, and subset of ileostomy and colostomy constructions. MATERIALS AND METHODS: We reviewed the Nationwide Inpatient Sample database from 1988 to 2011. We examined the number of Crohn's-related operations and stoma constructions, including ileostomies and colostomies; a multivariable logistic regression model was developed. RESULTS: A total of 355,239 Crohn's-related operations were analyzed. Operations increased from 13,955 in 1988 to 17,577 in 2011, p < 0.001. Stoma construction increased from 2493 to 4283, p < 0.001. The subset of ileostomies increased from 1201 to 3169, p < 0.001 while colostomies decreased from 1351 to 1201, p = 0.05. Operation percentages resulting in stoma construction increased from 18 to 24 %, p < 0.001. Weight loss (OR 2.25, 95 % CI 1.88, 2.69) and presence of perianal fistulizing disease (OR 2.91, 95 % CI 2.31, 3.67) were most predictive for requiring stoma construction. CONCLUSIONS: Crohn's-related surgical interventions and stoma constructions have increased. The largest predictors for stoma construction are weight loss and perianal fistulizing disease. As a result, nutrition should be optimized and the early involvement of a multidisciplinary team should be considered.


Subject(s)
Colostomy/trends , Crohn Disease/surgery , Ileostomy/trends , Intestinal Fistula/surgery , Adult , Colostomy/statistics & numerical data , Crohn Disease/complications , Databases, Factual , Female , Humans , Ileostomy/statistics & numerical data , Intestinal Fistula/etiology , Male , Middle Aged , United States , Weight Loss
10.
Ann Gastroenterol ; 28(1): 25-30, 2015.
Article in English | MEDLINE | ID: mdl-25608492

ABSTRACT

Sigmoid diverticulitis is an increasingly common Western disease associated with a high morbidity and cost of treatment. Improvement in the understanding of the disease process, along with advances in the diagnosis and medical management has led to recent changes in treatment recommendations. The natural history of diverticulitis is more benign than previously thought, and current trends favor more conservative, less invasive management. Despite current recommendations of more restrictive indications for surgery, practice trends indicate an increase in elective operations being performed for the treatment of diverticulitis. Due to diversity in disease presentation, in many cases, optimal surgical treatment of acute diverticulitis remains unclear with regard to patient selection, timing, and technical approach in both elective and urgent settings. As a result, data is limited to mostly retrospective and non-randomized studies. This review addresses the current treatment recommendations for surgical management of diverticulitis, highlighting technical aspects and patterns of care.

11.
J Surg Oncol ; 111(1): 96-102, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25297801

ABSTRACT

Colorectal adenocarcinoma (CRC), the second leading cancer-related death in the United States, remains a global public health issue. Sporadic CRC is considered the result of sequential mucosal changes from normal colonic mucosa to adenocarcinoma. Efforts in understanding the molecular pathways leading to CRC tumorigenesis may lead to identifying novel, individually tailored therapeutic targets for patients. In this review, we focus on well-published prognostic and predictive markers in CRC and examine their role in clinical practice.


Subject(s)
Antineoplastic Agents/therapeutic use , Biomarkers, Tumor/genetics , Colonic Neoplasms/genetics , Gene Expression Regulation, Neoplastic/drug effects , Molecular Targeted Therapy , Colonic Neoplasms/diagnosis , Colonic Neoplasms/therapy , Humans , Prognosis
12.
Dis Colon Rectum ; 57(12): 1358-63, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25380000

ABSTRACT

BACKGROUND: The initial minimum operation for ulcerative colitis is a total abdominal colectomy. Healthy patients may undergo proctectomy at the same time; however, for ill patients, proctectomy is delayed. Since the introduction of biologic medications in 2005, ulcerative colitis medical management has changed dramatically. OBJECTIVE: We examined how operative management for ulcerative colitis has changed from the prebiologic to biologic eras. DESIGN: We conducted a retrospective review of data on patients with ulcerative colitis who were included in the Nationwide Inpatient Sample database. SETTINGS: This study was conducted at a single university. PATIENTS: A total of 1,547,852 patients with ulcerative colitis who were admitted to a US hospital from 1991 to 2011 were included in the study. MAIN OUTCOME MEASURES: We examined patients whose initial operation consisted of total abdominal colectomy without proctectomy versus a total proctocolectomy with or without a pouch. We also examined which operation was done at the time of the construction of an ileoanal pouch. Patients who underwent colectomy and pouch construction in the same hospitalization were compared with those who received pouch formation at a subsequent hospitalization. RESULTS: Ulcerative colitis-related admissions rose by 170% during the years examined, and the number of patients who required total abdominal colectomy increased by 44%. Total abdominal colectomy increased by 15%, as opposed to total proctocolectomy (p < 0.001). Pouch construction at a subsequent operation increased by 16% (p = 0.002). Since 2008, total abdominal colectomy has surpassed total proctocolectomy as the most common initial surgical intervention for ulcerative colitis. LIMITATIONS: The Nationwide Inpatient Sample is a retrospective database, and we were limited to examining the variables within it. CONCLUSIONS: Total abdominal colectomy is currently the most common initial operation for patients with ulcerative colitis, and an ileoanal pouch is more frequently constructed at a subsequent hospitalization. These trends coincide with the initiation of biologic treatments and may imply that patients are acutely ill at the time of initial operation. Alternately, there may be surgeon-perceived bias of increased surgical risk or a shift in care to specialized surgeons for pouch construction.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Colectomy , Colitis, Ulcerative , Colonic Pouches , Proctocolectomy, Restorative , Adult , Colectomy/methods , Colectomy/statistics & numerical data , Colectomy/trends , Colitis, Ulcerative/diagnosis , Colitis, Ulcerative/epidemiology , Colitis, Ulcerative/physiopathology , Colitis, Ulcerative/surgery , Colonic Pouches/statistics & numerical data , Disease Management , Female , Humans , Immunologic Factors/therapeutic use , Infliximab , Male , Middle Aged , Outcome Assessment, Health Care , Patient Acuity , Patient Readmission/statistics & numerical data , Patient Readmission/trends , Proctocolectomy, Restorative/instrumentation , Proctocolectomy, Restorative/methods , Proctocolectomy, Restorative/statistics & numerical data , Reoperation/methods , Reoperation/statistics & numerical data , Reoperation/trends , Retrospective Studies , United States/epidemiology
13.
Ann Gastroenterol ; 27(4): 320-330, 2014.
Article in English | MEDLINE | ID: mdl-25331917

ABSTRACT

Perianal manifestations of Crohn's disease (CD) are common and, of them, fistulas are the most common. Perianal fistulas can be extremely debilitating for patients and are often very challenging for clinicians to treat. CD perianal fistulas usually require multidisciplinary and multimodality treatment, including both medical and surgical approaches. The majority of patients require multiple surgical interventions. CD patients with perianal fistulas have a high rate of primary non-healing, surgical morbidity, and high recurrence rates. This has led to constant efforts to improve surgical management of this disease process.

14.
BMC Cancer ; 14: 336, 2014 May 16.
Article in English | MEDLINE | ID: mdl-24886281

ABSTRACT

BACKGROUND: The aim of this study was to evaluate clinico-pathologic specific predictors of recurrence for stage II/III disease. Improving recurrence prediction for resected stage II/III colon cancer patients could alter surveillance strategies, providing opportunities for more informed use of chemotherapy for high risk individuals. METHODS: 871 stage II and 265 stage III patients with colon cancers were included. Features studied included surgery date, age, gender, chemotherapy, tumor location, number of positive lymph nodes, tumor differentiation, and lymphovascular and perineural invasion. Time to recurrence was evaluated, using Cox's proportional hazards models. The predictive ability of the multivariable models was evaluated using the concordance (c) index. RESULTS: For stage II cancer patients, estimated recurrence-free survival rates at one, three, five, and seven years following surgery were 98%, 92%, 90%, and 89%. Only T stage was significantly associated with recurrence. Estimated recurrence-free survival rates for stage III patients at one, three, five, and seven years following surgery were 94%, 78%, 70%, and 66%. Higher recurrence rates were seen in patients who didn't receive chemotherapy (p = 0.023), with a higher number of positive nodes (p < 0.001). The c-index for the stage II model was 0.55 and 0.68 for stage III. CONCLUSIONS: Current clinic-pathologic information is inadequate for prediction of colon cancer recurrence after resection for stage II and IIII patients. Identification and clinical use of molecular markers to identify the earlier stage II and III colon cancer patients at elevated risk of recurrence are needed to improve prognostication of early stage colon cancers.


Subject(s)
Colectomy , Colonic Neoplasms/pathology , Colonic Neoplasms/therapy , Neoplasm Recurrence, Local , Aged , Aged, 80 and over , Chemotherapy, Adjuvant , Colectomy/adverse effects , Colectomy/mortality , Colonic Neoplasms/mortality , Disease Progression , Disease-Free Survival , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Multivariate Analysis , Neoplasm Staging , Proportional Hazards Models , Risk Factors , Time Factors , Treatment Outcome
15.
Ann Surg Oncol ; 21(11): 3616-20, 2014 Oct.
Article in English | MEDLINE | ID: mdl-24943237

ABSTRACT

BACKGROUND: Chemoradiotherapy (CRT), the primary treatment for anal cancer, achieves complete tumor regression in most patients. Abdominoperineal resection (APR) is reserved for persistent or recurrent disease. An additional boost dose of radiation after CRT often is used to improve the response rate for advanced local disease (T3, 4, and N+). This study examines the need for salvage APR after radiation boost. METHODS: Patients with de novo anal cancer in the National Cancer Data Base from the years 2004-2010 were analyzed. Patients with missing data points or who did not receive standard CRT were excluded. Variables included age, gender, race, primary tumor size, clinical nodal status, TNM stage, radiation boost, and APR. A logistic regression model assessing the relationship between boost radiation and APR was developed. RESULTS: Of 1,025 patients meeting inclusion criteria, 450 patients received CRT without a radiation boost and 575 patients received CRT with a radiation boost. The two groups were similar in age, gender, race, tumor size, nodal status, and TNM stage (p values all >0.05). Significant multivariate predictors of salvage APR were tumor size, negative nodal status, and boost RT (all p < 0.05), whereas gender, age, race, and TNM stage were not significant (all p > 0.05). When controlling for age, tumor size, and nodal status, salvage APR is less likely to occur after boost RT (odds ratio 0.63; 95 % confidence interval 0.47, 0.85; p = 0.003). CONCLUSIONS: When controlling for age, tumor size, and nodal status, those who received boost radiation for anal cancer were less likely to require salvage APR.


Subject(s)
Abdomen/surgery , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Anus Neoplasms/radiotherapy , Carcinoma, Squamous Cell/radiotherapy , Chemoradiotherapy , Perineum/surgery , Salvage Therapy , Aged , Anus Neoplasms/drug therapy , Anus Neoplasms/surgery , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/surgery , Combined Modality Therapy , Databases, Factual , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Staging , Prognosis , Radiotherapy Dosage , Risk Factors
16.
Am J Surg ; 207(5): 717-22; discussion 722, 2014 May.
Article in English | MEDLINE | ID: mdl-24791633

ABSTRACT

BACKGROUND: MicroRNA (miR)-320a, miR-145, and miR-192 have been shown to play a role in colorectal carcinogenesis and metastasis. We examined if there is a difference in expression during the histologic progression from normal mucosa (NM) to high-grade dysplastic adenomas (HG). METHODS: Genome-wide miRNA expression profiling was performed on 113 colon adenomas. Information included histologic type, tumor grade, location, sex, age, family, and smoking history. A 2-way ANOVA was performed to evaluate the effect of the following factors adjusted for scan dates: location, sex, age, family history, smoking, and histology. RESULTS: The expression of miR-320a increased; miR-145 and miR-192 expression decreased (P < .0001), with higher histologic grade, and were independent of age, sex, family history, and smoking status. CONCLUSIONS: The miRs studied had statistically significant changes in expression with progression of histologic grade. These changes may signify progression of normal mucosa to HG and potentially serve as early markers for disease progression and differentiating high- from low-risk adenomas.


Subject(s)
Adenomatous Polyps/genetics , Biomarkers, Tumor/metabolism , Colorectal Neoplasms/genetics , Gene Expression Regulation, Neoplastic , Intestinal Mucosa/metabolism , MicroRNAs/metabolism , Adenomatous Polyps/metabolism , Adenomatous Polyps/pathology , Adult , Aged , Aged, 80 and over , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , Down-Regulation , Female , Gene Expression Profiling , Humans , Male , Middle Aged , Neoplasm Grading , Up-Regulation
17.
J Am Coll Surg ; 218(5): 1004-11, 2014 May.
Article in English | MEDLINE | ID: mdl-24661856

ABSTRACT

BACKGROUND: Current quality initiatives call for examination of at least 12 lymph nodes in curative colon cancer resections. The aim of this study was to determine if the number of nodes harvested has increased, and if the increased number nodes correlates with improved staging or overall survival. STUDY DESIGN: A review of the Surveillance, Epidemiology, and End Results program database from 2004-2010 was performed. All patients who underwent colon cancer resection during this date range were analyzed. Number of nodes retrieved, patient stage, overall survival, and overall survival by stage were examined. Multivariable analysis controlled for stage, cancer site, age, year of diagnosis, and number of nodes retrieved. Improved staging was defined as increased detection of stage III patients. RESULTS: A total of 147,076 patients met inclusion criteria. Median number of nodes analyzed increased sequentially with each year examined, from 12 in 2004 to 17 in 2010. Despite greater number of total nodes obtained and analyzed, there was no increase in the percentage of patients with positive nodes (stage III disease). On multivariable analysis, after controlling for stage, site of disease, age, and year of diagnosis, there was a slight overall survival benefit with increasing nodal retrieval (hazard ratio = 0.987 for each additional node removed; 95% CI, 0.986-0.988; p < 0.001). CONCLUSIONS: Since quality initiatives have been put in place, there has been an increase in the number of nodes examined in colon cancer resections, but no improvement in staging. The improved survival seen with higher node counts was independent of stage, site of disease, patient age, and year of diagnosis.


Subject(s)
Adenocarcinoma/secondary , Colectomy , Colonic Neoplasms/pathology , Lymph Nodes/pathology , Neoplasm Staging , SEER Program , Abdomen , Adenocarcinoma/diagnosis , Adenocarcinoma/surgery , Aged , Aged, 80 and over , Colonic Neoplasms/mortality , Colonic Neoplasms/surgery , Female , Follow-Up Studies , Humans , Lymphatic Metastasis , Male , Middle Aged , Postoperative Period , Prognosis , Retrospective Studies , Survival Rate/trends , United States/epidemiology
18.
Lasers Surg Med ; 45(9): 573-81, 2013 Nov.
Article in English | MEDLINE | ID: mdl-24114774

ABSTRACT

BACKGROUND AND OBJECTIVES: Colonoscopy is the preferred method for colon cancer screening, but can miss polyps and flat neoplasms with low color contrast. The objective was to develop a new autofluorescence method that improves image contrast of colonic neoplasms. STUDY DESIGN/MATERIALS AND METHODS: We selected the three strongest native fluorescence signals and developed a novel method where fluorescence images are processed in a ratiometric formula to represent the likely cellular and structural changes associated with neoplasia. Native fluorescence images of fresh surgical specimens of the colon containing normal mucosa, polypoid and flat adenomas as well as adenocarcinoma were recorded using a prototype multi-spectral imager. Sixteen patients, with a mean age of 62 years (range 28-81) undergoing elective resection for colonic neoplasms were enrolled. High contrast images were seen with fluorescence from tryptophan (Tryp), flavin adenine dinucleotide (FAD) and collagen. RESULTS: When the image intensity of Tryp was divided pixel by pixel, by the intensities of FAD and collagen, the resulting formulaic ratio (FR) images were of exceptionally high contrast. The FR images of adenomas and adenocarcinomas had increased Weber contrast. CONCLUSIONS: FR imaging is a novel imaging process that represents the likely metabolic and structural changes in colonic neoplasia that produces images with remarkably high contrast.


Subject(s)
Adenocarcinoma/diagnosis , Adenoma/diagnosis , Colonic Neoplasms/diagnosis , Colonoscopy/methods , Optical Imaging/methods , Adult , Aged , Aged, 80 and over , Colonoscopy/instrumentation , Female , Humans , Male , Middle Aged , Optical Imaging/instrumentation
19.
Am J Surg ; 205(5): 563-5; discussion 565, 2013 May.
Article in English | MEDLINE | ID: mdl-23592163

ABSTRACT

BACKGROUND: We hypothesized that surgeons can improve the collection of all necessary elements (tissue and clinical data) needed to build a complete, robust research biorepository. METHODS: All colorectal cancer patients treated at a university medical center and its affiliates were eligible for inclusion. Data were collected from an 18-page personal and family health questionnaire, a prospectively maintained clinical database, and molecular testing. Tissues included serum, plasma and peripheral blood mononuclear cells, and tumor and normal tissue. We compared 2 groups: the surgeon-referred group and the other clinician-referred group. The primary outcome was the complete collection of data (ie, preoperative/staging clinical data, blood samples, and tissue collection). Statistical analysis was performed using the Student t test. RESULTS: Since 2006, 452 patients were approached, and 430 (95%) have been enrolled. Of these, 124 were referred by their surgeon, and 306 were consented in a clinic or over the telephone. Of patients referred by their surgeon, tumor tissue, blood samples, and preoperative/staging clinical data were obtained in 119 patients; conversely, in patients referred by oncologists or other clinicians, only 133 patients had complete data (96% vs 43.5%, P < .05). A total of 257 tissue samples were obtained from all patients. Additional testing has been performed on 228 specimens including immunohistochemistry, microsatellite testing, and genotype mutational analysis. CONCLUSIONS: Surgeon-directed enrollment in a biorepository improves the ability to collect blood and tissue samples. Surgeons should take a leadership role in the development of tumor biorepositories.


Subject(s)
Biological Specimen Banks/organization & administration , Colorectal Neoplasms , Colorectal Surgery , Data Collection/methods , Physicians , Registries , Specimen Handling/methods , Biological Specimen Banks/statistics & numerical data , Biomedical Research , Colorectal Neoplasms/blood , Colorectal Neoplasms/pathology , Colorectal Neoplasms/surgery , Data Collection/statistics & numerical data , Humans , Medical Oncology , Oregon , Program Evaluation , Specimen Handling/statistics & numerical data
20.
Am J Surg ; 205(5): 608-12; discussion 612, 2013 May.
Article in English | MEDLINE | ID: mdl-23592171

ABSTRACT

BACKGROUND: Determining the molecular profile of colon and rectal cancers offers the possibility of personalized cancer treatment. The purpose of this study was to determine whether known genetic mutations associated with colorectal carcinogenesis differ between colon and rectal cancers and whether they are associated with survival. METHODS: The Oregon Colorectal Cancer Registry is a prospectively maintained, institutional review board-approved tissue repository with associated demographic and clinical information. The registry was queried for any patient with molecular analysis paired with clinical data. Patient demographics, tumor characteristics, microsatellite instability status, and mutational analysis for p53, AKT, BRAF, KRAS, MET, NRAS, and PIK3CA were analyzed. Categorical variables were compared using chi-square tests. Continuous variables between groups were analyzed using Mann-Whitney U tests. Kaplan-Meier analysis was used for survival studies. Comparisons of survival were made using log-rank tests. RESULTS: The registry included 370 patients: 69% with colon cancer and 31% with rectal cancer. Eighty percent of colon cancers and 68% of rectal cancers were stages III and IV. Mutational analysis found no significant differences in detected mutations between colon and rectal cancers, except that there were significantly more BRAF mutations in colon cancers compared with rectal cancers (10% vs 0%, P < .008). No differences were seen in 5-year survival rates of patients with colon versus rectal cancers when stratified by the presence of KRAS, PIK3CA, and BRAF mutations. CONCLUSIONS: Stage III and IV colon and rectal cancers share similar molecular profiles, except that there were significantly more BRAF mutations in colon cancers compared with rectal cancers.


Subject(s)
Biomarkers, Tumor/genetics , Colonic Neoplasms/genetics , Mutation , Rectal Neoplasms/genetics , Class I Phosphatidylinositol 3-Kinases , Colonic Neoplasms/mortality , Colonic Neoplasms/pathology , DNA Mutational Analysis , Female , GTP Phosphohydrolases/genetics , Genes, p53 , Genetic Markers , Humans , Kaplan-Meier Estimate , Male , Membrane Proteins/genetics , Neoplasm Staging , Oregon , Phosphatidylinositol 3-Kinases/genetics , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-met/genetics , Proto-Oncogene Proteins p21(ras) , Rectal Neoplasms/mortality , Rectal Neoplasms/pathology , Registries , ras Proteins/genetics
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