Jonathan A. Wilks

Perineural invasion in cancer: a review of the literature.

Perineural invasion (PNI) is the process of neoplastic invasion of nerves and is an under‐recognized route of metastatic spread. It is emerging as an important pathologic feature of many malignancies, including those of the pancreas, colon and rectum, prostate, head and neck, biliary tract, and stomach. For many of these malignancies, PNI is a marker of poor outcome and a harbinger of decreased survival. PNI is a distinct pathologic entity that can be observed in the absence of lymphatic or vascular invasion. It can be a source of distant tumor spread well beyond the extent of any local invasion; and, for some tumors, PNI may be the sole route of metastatic spread. Despite increasing recognition of this metastatic process, there has been little progress in the understanding of molecular mechanisms behind PNI and, to date, no targeted treatment modalities aimed at this pathologic entity. The objectives of this review were to lay out a clear definition of PNI to highlight its significance in those malignancies in which it has been studied best. The authors also summarized current theories on the molecular mediators and pathogenesis of PNI and introduced current research models that are leading to advancements in the understanding of this metastatic process. Cancer 2009.

Obesity increases wound complications in rectal cancer surgery

BACKGROUND Obesity increases the risk of wound infections following surgery for colon cancer. Considerably less data is available, however, regarding the impact of obesity on infections and wound complications after resection for rectal cancer. Additionally, the impact of minimally invasive surgery (MIS) on complications in rectal surgery remains unclear. We hypothesized that obesity is associated with prolonged operative time and more infectious complications in obese patients undergoing both MIS and open surgery for rectal cancer. MATERIALS AND METHODS Review of retrospective surgical database. RESULTS One hundred fifty patients underwent surgery for rectal cancer from 2002 to 2009. Open cases accounted for 72% (n = 108) and MIS for 28% (n = 42) of cases. BMI did not correlate with increased operative time in open rectal surgery, but in MIS patients, operative time increased from a median of 254 min in the lowest quartile of BMI to 333 min in the highest quartile (P < 0.004). Superficial wound infections in open rectal surgery increased from 17% to 52% with increasing BMI (P < 0.005). The increased rate of wound complications persisted in the MIS group. Rate of superficial wound infections and subsequent open packing in the MIS group increased from 0% in the lowest BMI quartile to 33% in the highest quartile (P < 0.029 and P < 0.007, respectively). CONCLUSIONS Elevated BMI is associated with increased wound complications in both minimally invasive and open rectal surgery. This trend may be related to prolonged operative time in obese patients, particularly in MIS. Our observations suggest that more aggressive techniques to prevent infection are warranted in obese patients undergoing rectal surgery.

Neurogenesis in colorectal cancer is a marker of aggressive tumor behavior and poor outcomes

Colorectal cancer staging criteria do not rely on examination of neuronal tissue. The authors previously demonstrated that perineural invasion is an independent prognostic factor of outcomes in colorectal cancer. For the current study, they hypothesized that neurogenesis occurs in colorectal cancer and portends an aggressive tumor phenotype.

Validating Quantitative Obesity Measurements in Colorectal Cancer Patients

BACKGROUND Over 70,000,000 American adults are overweight, and obesity accounts for

Minimally Invasive Surgery Improves Short Term Outcomes in Elderly Colorectal Cancer Patients

147 billion annually in medical expenses. Since measuring obesity by body mass index (BMI) fails to account for fat distribution and quantity, recent work has explored quantitative measures of visceral fat area (VFA) and subcutaneous fat area (SFA) obtained from CT imaging. However, use of CT to quantify adipose tissue has not been evaluated in colorectal cancer (CRC) patients and the optimal anatomic location for measuring VFA and SFA has yet to be determined. We measured VFA and SFA at three different anatomic locations to determine which location was optimal in CRC patients. METHODS A database of patients undergoing CRC surgery from 2002 to 2009 was reviewed to identify patients with preoperative CT imaging. Quantitative measurements of both VFA and SFA were calculated at the level of L4-L5, L2-L3, and mid-waist. RESULTS A total of 244 colorectal cancer patients had preoperative imaging available and 99% were men. VFA and SFA quantified by CT at the levels of L2-L3, L4-L5, and mid-waist were all significant independent predictors for medical complications of obesity including diabetes (HR 1.04 -1.06) and hypertension (HR 1.04-1.09) on multivariate analysis. The location used for imaging did not affect predictive power. Additionally, waist circumference was also a significant independent predictor of diabetes (HR 1.56) and hypertension (HR 1.70). CONCLUSIONS Quantitative measures of obesity from CT imaging in CRC patients correlated significantly with medical conditions known to be associated with obesity. This indicates that direct measurement of adiposity is valid in colorectal cancer patients.

Obese patients benefit from minimally invasive colorectal cancer surgery.

BACKGROUND Minimally invasive surgery (MIS) for colorectal resection has been shown to improve short-term outcomes compared with open surgery in patients with colorectal cancer. Currently, there is a paucity of data demonstrating similar efficacy between MIS and open colorectal resection in the elderly population. We hypothesized that minimally invasive surgery provides improved short-term outcomes in elderly patients with colorectal cancer. METHODS A review of 242 consecutive elderly (≥ 65 y of age) patients who underwent either open or MIS colorectal resection for adenocarcinoma at one institution was conducted. Short-term and oncologic outcomes were analyzed. Continuous variables were analyzed by the Mann-Whitney U test. Categorical variables were compared by χ(2) tests. Survival was compared by the Kaplan-Meier method using the log rank test for comparison. RESULTS Of the 242 elderly patients with colorectal cancer (median American Society of Anesthesiology score (ASA) scores of 3), 80% (n = 195) of patients underwent open and 20% (n = 47) had MIS colorectal cancer resections. Patients undergoing MIS had a faster return of bowel function, decreased days to nasogastric tube removal, decreased days to flatus and bowel movement, and quicker advancement to clear liquid and regular diets. The overall length of hospital stay in the MIS group was decreased by 40% as well as a trend towards a 50% decrease in SICU stay. Additionally, there was 66% decrease in cardiac complications in the MIS group. When evaluating for oncologic adequacy as measured by number of lymph nodes and surgical resection margins, MIS surgery offered equivalent results as open resection. Furthermore, there was no significant difference in overall survival for MIS versus open colorectal surgery. CONCLUSION Minimally invasive colorectal cancer resection leads to improved short-term outcomes as demonstrated by decreased length of hospital stay and faster return of bowel function. Additionally, there appears to be no difference in oncologic outcomes in the elderly. On the basis of our data, age alone should not be a contra-indication to laparoscopic colorectal cancer resection.

Rectal cancer patients benefit from implementation of a dedicated colorectal cancer center in a Veterans Affairs Medical Center.

BACKGROUND Minimally invasive surgery (MIS) for colorectal cancer offers improved short-term outcomes compared with open surgery. However, there is concern that MIS is more difficult in obese patients and may be associated with worse oncologic outcomes while failing to preserve short-term benefits. We hypothesized that obese patients undergoing surgery for colorectal cancer (CRC) would benefit from MIS. METHODS Retrospective database review. RESULTS Database review identified 155 obese patients undergoing resections for CRC from 2002-2009. Open cases accounted for 73% (N = 113) and MIS for 27% (N = 42). Conversion from MIS to open surgery occurred in 26% of cases. Obese patients had a nonsignificantly decreased rate of wound infection after MIS (21%) versus open surgery (28%, P < 0.645), while the incidence of other complications did not differ by surgical approach. The MIS cohort demonstrated faster return of bowel function and returned home a median of 2 days faster group than in the open surgery group (P < 0.003). From an oncologic standpoint, MIS was at least equivalent to open surgery as median number of lymph nodes extracted (20 versus 15, P < 0.073) and proportion of margin negative resections (97% versus 98%, P < 0.654) did not significantly differ between the two groups. CONCLUSIONS Minimally invasive surgery for CRC is safe and effective in obese patients since bowel function recovers rapidly, and hospital stay is significantly reduced while the quality of oncologic care is maintained.

A multidisciplinary cancer center maximizes surgeons' impact

BACKGROUND A dedicated colorectal cancer (CRC) center was created in a Veterans Affairs Medical Center with the intent of improving quality of patient care and multidisciplinary cooperation. METHODS Retrospective and prospective databases before and after creation of the CRC center, respectively, were created. Patients entered in each database included those requiring surgical intervention for CRC treatment. Statistical analyses included Fishers exact, chi-square, and unpaired Student t tests as well as analysis of variance. RESULTS The overall quality of care of CRC patients has improved as evidenced by a larger percentage of complete, margin-negative resections (P <.05) as well as an increase in the number of lymph nodes excised at surgery (P <.0001). Furthermore, a multidisciplinary approach is clearly beneficial as evidenced by the increased number of CRC patients receiving appropriate multidisciplinary therapy (P <.0001). CONCLUSIONS A dedicated CRC center has significantly improved quality of care for CRC patients.

The role of angiocidin in sarcomas

BACKGROUND Colorectal cancer patients require care across different disciplines. Integration of multidisciplinary care is critical to accomplish excellent oncologic results. We hypothesized that the establishment of a dedicated colorectal cancer center (CRCC) around specialty-trained surgeons will lead to increased multidisciplinary management and improved outcomes in colorectal cancer patients. METHODS We analyzed data from three periods: a baseline group, a period after the recruitment of specialty-trained surgeons, and a period after the creation of a dedicated multidisciplinary cancer center. Data analyzed included surrogate markers of surgical oncologic care, multidisciplinary integration, and oncologic outcomes. RESULTS Recruitment of specialized surgeons led to improvements in surgical oncologic care; the establishment of the CRCC resulted in further improvements in surgical oncologic care and multidisciplinary integration. CONCLUSION Our study suggests that although the recruitment of specialty-trained surgeons in a high volume center leads to improvement in surgical oncologic care, it is the establishment of a multidisciplinary center around the surgeons that leads to integrated care and improvements in oncologic outcomes.

431 Waist Circumference Predicts Complications in Rectal Cancer Surgery

Angiocidin, first identified as a tumor‐associated thrombospondin‐1 (TSP‐1) receptor, is a key mediator of tumor progression. TSP‐1, an extracellular protein produced by stromal cells, up‐regulates gelatinases and tumor cell invasion in epithelial malignancies. The authors recently developed 2 angiocidin‐inhibitory peptides that block angiocidin–TSP‐1 binding. They hypothesized that angiocidin mediates increased gelatinase expression and tumor cell invasion in sarcomas through its interaction with TSP‐1.