Vassiliki L. Tsikitis

Trends of Incidence and Survival of Gastrointestinal Neuroendocrine Tumors in the United States: A Seer Analysis

OBJECTIVES: To examine trends in detection and survival of hollow viscus gastrointestinal neuroendocrine tumors (NETs) across time and geographic regions of the U.S. METHODS: We used the Surveillance, Epidemiology and End Results (SEER) database to investigate 19,669 individuals with newly diagnosed gastrointestinal NETs. Trends in incidence were tested using Poisson regression. Cox proportional hazards regression was used to examine survival. RESULTS: Incidence increased over time for NETs of all gastrointestinal sites (all P < 0.001), except appendix. Rates have risen faster for NETs of the small intestine and rectum than stomach and colon. Rectal NETs were detected at a faster pace among blacks than whites (P < 0.001) and slower in the East than other regions (P < 0.001). We observed that appendiceal and rectal NETs carry the best prognosis and survival of small intestinal and colon NETs has improved for both men and women. Colon NETs showed different temporal trends in survival according to geographic region (Pinteraction = 0.028). Improved prognosis was more consistent across the country for small intestinal NETs. CONCLUSIONS: Incidence of gastrointestinal NETs has increased, accompanied by inconsistently improved survival for different anatomic sites among certain groups defined by race and geographic region.

Postoperative surveillance recommendations for early stage colon cancer based on results from the clinical outcomes of surgical therapy trial

4013 Background: Intensive postoperative surveillance is associated with improved survival and recommended for patients with late stage (stage IIB & III) colon cancer. We hypothesized that stage I & IIA colon cancer patients would experience similar benefits. METHODS Secondary analysis of data from the Clinical Outcomes of Surgical Therapy trial was performed by analyzing results according to TNM stage; early (stage I & IIA; 537 patients) and late (stage IIB & III; 254 patients) stage disease. Five-year recurrence rates were higher in patients with late (35.7%) versus early stage disease (9.5%). Early and late stage salvage rates, recurrence patterns and methods of first detection were compared by χ2 test. RESULTS Salvage rates for early and late stage disease patients with recurrence were the same (35.9% versus 37%, p=0.9 respectively). Median survival following second surgery after recurrence was 35.8 months late stage and 51.2 months for early stage patients respectively. Sites of first recurrence did not significantly differ between late and early stage disease: liver (37.4% vs. 27.2%); lung (29.7% vs.23.6%); intraabdominal (24.2% vs.10.9%); and locoregional (12.1% vs.10.9%). Methods of first detection of recurrence were also not significantly different: CEA (37.4% vs. 29.1%); CT scan (26.4% vs. 23.6%); chest X-ray (12.1% vs. 7.3%); and colonoscopy (8.8% vs. 12.7%), for late versus early stage disease, respectively. CONCLUSIONS Patients with early stage colon cancer have similar sites of recurrence, and receive similar benefit from post-recurrence therapy as later stage patients; implementation of existing surveillance guidelines for early stage patients is appropriate. No significant financial relationships to disclose.PURPOSE Intensive postoperative surveillance is associated with improved survival and recommended for patients with late stage (stage IIB and III) colon cancer. We hypothesized that stage I and IIA colon cancer patients would experience similar benefits. PATIENTS AND METHODS Secondary analysis of data from the Clinical Outcomes of Surgical Therapy trial was performed by analyzing results according to TNM stage; early (stage I and IIA, 537 patients) and late (stage IIB and III, 254 patients) stage disease. Five-year recurrence rates were higher in patients with late (35.7%) versus early stage disease (9.5%). Early and late stage salvage rates, recurrence patterns and methods of first detection were compared by chi(2) test. RESULTS Salvage rates for early- and late-stage disease patients with recurrence were the same (35.9% v 37%; P = .9, respectively). Median survival after second surgery after recurrence was 51.2 and 35.8 months for early- and late-stage patients, respectively. Single sites of first recurrence did not significantly differ between early and late stage, but multiple sites of recurrence occurred less often in early-stage patients (3.6% v 28.6%, for early v late, respectively; P < .001). METHODS of first detection of recurrence were not significantly different: carcinoembryonic antigen (29.1% v 37.4%), computed tomography scan (23.6% v 26.4%), chest x-ray (7.3% v 12.1%), and colonoscopy (12.7% v 8.8%), for early versus late stage disease, respectively. CONCLUSION Patients with early-stage colon cancer have similar sites of recurrence, and receive similar benefit from postrecurrence therapy as late-stage patients; implementation of surveillance guidelines for early-stage patients is appropriate.

Survival in Stage III Colon Cancer Is Independent of the Total Number of Lymph Nodes Retrieved

BACKGROUND Retrieval of >/= 12 lymph nodes has been set as a marker of quality for surgical resection for colon cancer. The aim of our study was to determine if increasing the number of lymph nodes recovered in stage III colon cancer results in improved survival and if it does represent a reasonable quality metric. STUDY DESIGN Data from patients with stage III colon cancer from 1996 to 2001 were analyzed. Outcomes after operation (cancer-specific survival, disease-free survival, and overall survival) with or without adjuvant therapy were evaluated in 3 categories: the entire cohort, patients with N1, and patients with N2 disease. These categories were then classified into subgroups by the number of nodes (</= 12 versus >12) retrieved per specimen and whether they had 5-FU-based chemotherapy or not. RESULTS Three hundred twenty-nine patients, with a median followup of 5 years with stage III colon cancer, were identified. Five-year cancer-specific and disease-free survival was 67.2% and 59.7%, respectively. A positive correlation between number of positive lymph nodes and overall survival was found (p < 0.05). No significant association was observed between the total number (> 12 versus </= 12) of lymph nodes removed either in the entire cohort or in patients with N1 (249 patients) and N2 (80 patients) disease. CONCLUSION Accurate staging requires an appropriate operation and a concerted pathologic effort to identify lymph nodes in the colon specimen. The total number of lymph nodes analyzed for stage III colon cancer is not a prognostic indicator of cancer-specific and disease-free survival.

Postoperative Morbidity with Diversion after Low Anterior Resection in the Era of Neoadjuvant Therapy: A Single Institution Experience

BACKGROUND The use of defunctioning stomas has been advocated to mitigate the adverse sequela from anastomotic dehiscence after rectal cancer resection. The aim of this study was to report our experience with anastomotic dehiscence and overall morbidity of low anterior resections in the era of neoadjuvant therapy, where the use of fecal diversion is part of the standard operative strategy for low (< 5 cm) rectal anastomoses. STUDY DESIGN This retrospective case series included patients who were treated with neoadjuvant therapy and had rectal cancer resection with curative intent, from 1996 to 2007. RESULTS Two hundred thirty-seven patients (159 men, 78 women) with mean age of 59 years (SD+/-12.7 years), received 5-flurouracil-based infusional chemotherapy and external-beam radiation in the range of 45 to 54 Gy. Fifty-seven percent of patients underwent anterior resection and 43% had coloanal anastomosis. Anastomotic dehiscence occurred in 9 patients (3.8%). Seven of the anastomotic leaks were diagnosed as pelvic abscesses (2.1%) and 2 patients needed reexploration (0.8%). Early overall postoperative morbidity was 26%, and there was no postoperative mortality. One hundred ninety-one of 193 patients had their ileostomy reversed, with minimal morbidity (0.5% leak rate). CONCLUSIONS Low postoperative morbidity after colorectal and coloanal anastomosis for adenocarcinoma is possible in patients who have received neoadjuvant therapy. Defunctioning stomas are safe and may mitigate the serious sequela of anastomotic dehiscence after low rectal anastomoses.

Predictors of recurrence free survival for patients with stage II and III colon cancer

BackgroundThe 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.Methods871 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.ResultsFor 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.ConclusionsCurrent 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.

Ratio images and ultraviolet C excitation in autofluorescence imaging of neoplasms of the human colon

Abstract. The accepted screening technique for colon cancer is white light endoscopy. While most abnormal growths (lesions) are detected by this method, a significant number are missed during colonoscopy, potentially resulting in advanced disease. Missed lesions are often flat and inconspicuous in color. A prototype ultraviolet spectral imager measuring autofluorescence (AF) and reflectance has been developed and applied in a study of 21 fresh human colon surgical specimens. Six excitation wavelengths from 280 to 440 nm and formulaic ratio imaging were utilized to increase lesion contrast and cause neoplasms to appear bright compared to normal tissue. It was found that in the subset of lesions which were most difficult to visualize in standard color photographs [low contrast lesions, (LCLs)] a ratio image (F340/F440) of AF images excited at 340 and 440 nm produced extraordinary images and was effective in about 70% of these difficult cases. Contrast may be due to increased levels of reduced nicotinamide adenine dinucleotide, increased hemoglobin absorption, and reduced signal from submucosal collagen. A second successful ratio image (R480/R555) combined two reflectance images to produce exceptional images especially in particular LCLs where F340/F440 was ineffective. The newly discovered ratio images can potentially improve detection rate in screening with a novel AF colonoscope.

Disparities in Treatment and Survival of White and Native American Patients with Colorectal Cancer: A SEER Analysis

BACKGROUND Minority groups with colorectal cancer have not experienced the decline in incidence and mortality that has been reported in whites. We sought to determine whether differences exist in treatment and survival between white and Native American patients with colorectal cancer because little has been written about this specific minority group. STUDY DESIGN The Surveillance Epidemiology and End Results (SEER) database for colorectal cancer was used to compare treatment and survival in whites (colon, n = 137,949; rectum, n = 46,843) and Native Americans (colon, n = 872; rectum, n = 316). Cox proportional hazards models were used to compare cancer-specific survival in Native Americans with whites, adjusted for stage, sex, age and year of diagnosis, socioeconomic status, and treatment. RESULTS Native Americans presented at younger ages than whites for both colon and rectal cancer (p < 0.001). They were diagnosed at more advanced stages of disease than whites for only colon cancer. No significant differences were detected in the proportion of patients recommended for surgery between the two groups, for either cancer at any stage (all p > 0.05). Native Americans with rectal cancer were more likely to receive radiation than whites (p < 0.001), but they received less sphincter-preserving surgery (60.0% vs 65.4%; p = 0.045). Native Americans with colon cancer fared significantly worse than whites (hazard ratio = 1.20; 95% CI = 1.08 to 1.34), but there is no difference in cancer-free survival between races for rectal cancer. CONCLUSIONS Compared with whites, Native Americans with colon cancer have worse cancer-specific survival.

Molecular markers for colon diagnosis, prognosis and targeted therapy

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. J. Surg. Oncol. 2015 111:96–102.

Perceived Impact of the 80-Hour Workweek: Five Years Later1

BACKGROUND We aimed to assess perceptions of the effects of the 80-hour workweek (80hWW) restriction on patient care, education, and resident quality of life. MATERIALS AND METHODS In April 2007, attending surgeons and residents in nine surgical specialties at our institution were surveyed. Respondents were categorized into three groups: (1) attending surgeons; (2) residents beginning their training before the 80hWW implementation (ResBefore); and (3) residents beginning training after the 80hWW implementation (ResAfter). Differences between groups were assessed with univariate analysis. RESULTS The overall response rate was 57%. A minority in all three groups (< or =33%) believed the 80hWW improved patient care. Fifteen percent of attending surgeons, 30% of ResBefore, and 67% of ResAfter believed patients were safer (P < 0.001). Eighty-three percent of attending surgeons, 74% of ResBefore, and 41% of ResAfter (P < 0.001) believed continuity of care was compromised. All groups (> or =84%) agreed that midlevel providers were now critical to successfully deliver health care (P = 0.40). Fewer attending surgeons (21%) and ResBefore (29%) perceived improvements in education compared with ResAfter (68%; P <0.001). A majority perceived improved work-life balance for residents (attending surgeons [85%], ResBefore [71%], and ResAfter [92%]; P = 0.008), but 76% of attending surgeons reported decreased job satisfaction. CONCLUSION We showed a discrepancy between perceptions of attending surgeons and residents regarding the effect of the 80hWW on patient care and surgical education. Quality of life was improved for residents but not for attending surgeons. The impact of the 80hWW on patient care and surgical education needs to be quantified.

Initial surgical management of ulcerative colitis in the biologic era

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.