Steven J. Stryker

Laparoscopic colectomy for cancer is not inferior to open surgery based on 5-year data from the COST Study Group trial

Purpose:Oncologic concerns from high wound recurrence rates prompted a multi-institutional randomized trial to test the hypothesis that disease-free and overall survival are equivalent, regardless of whether patients receive laparoscopic-assisted or open colectomy. Methods:Eight hundred seventy-two patients with curable colon cancer were randomly assigned to undergo laparoscopic-assisted or open colectomy at 1 of 48 institutions by 1 of 66 credentialed surgeons. Patients were followed for 8 years, with 5-year data on 90% of patients. The primary end point was time to recurrence, tested using a noninferiority trial design. Secondary endpoints included overall survival and disease-free survival. (Kaplan–Meier) Results:As of March 1, 2007, 170 patients have recurred and 252 have died. Patients have been followed a median of 7 years (range 5–10 years). Disease-free 5-year survival (Open 68.4%, Laparoscopic 69.2%, P = 0.94) and overall 5-year survival (Open 74.6%, Laparoscopic 76.4%, P = 0.93) are similar for the 2 groups. Overall recurrence rates were similar for the 2 groups (Open 21.8%, Laparoscopic 19.4%, P = 0.25). These recurrences were distributed similarly between the 2 treatment groups. Sites of first recurrence were distributed similarly between the treatment arms (Open: wound 0.5%, liver 5.8%, lung 4.6%, other 8.4%; Laparoscopic: wound 0.9%, liver 5.5%, lung 4.6%, other 6.1%). Conclusion:Laparoscopic colectomy for curable colon cancer is not inferior to open surgery based on long-term oncologic endpoints from a prospective randomized trial.

Early results of laparoscopic surgery for colorectal cancer - Retrospective analysis of 372 patients treated by clinical outcomes of Surgical Therapy (Cost) Study Group

PURPOSE: This study was undertaken to determine the early experience of the embers of the COST Study Group with colorectal cancer treated by laparoscopic approaches. METHOD: A retrospective review was performed of all patients with colorectal cancer treated with laparoscopy by the COST Study Group before August 1994. Tumor site, stage, differentiation, procedure completion, presence of recurrence (local, distant, trocar site), and cause of death were analyzed. RESULTS: A total of 372 patients with adenocarcinoma of the colon and rectum were treated by laparoscopic approach between October 1991 and August 1994 (170 men and 192 women): right colectomy, 170; sigmoid colectomy, 55; low anterior resection, 56; abdominoperineal resection, 44; left colectomy, 22; colostomy, 8; total colectomy, 6; transverse colectomy, 7; exploration, 2. Conversion to an open procedure was required in 15.6 percent of cases. Operative mortality was 2 percent. Tumor characteristics were as follows: TNM state: I, 40 percent; II, 25 percent; III, 18 percent; IV, 17 percent; Differentiation: well-moderate, 88 percent; poor, 12 percent; carcinomatosis, 5 percent. Local (3.6 percent) and distant implantation occurred in four patients (1.1 percent). Only one of these patients died a cancer-related death (Stage III at 36 months). Cancer-related death rates increased with increasing stage of tumor: I, −4 percent; II, 17 percent; III, 31 percent; IV, 70 percent. CONCLUSION: A laparoscopic approach to colorectal cancer results in early outcome after treatment that is comparable with conventional therapy for colorectal cancer. A randomized trial is needed to compare long-term outcomes of open and laparoscopic approaches with colorectal cancer.

Accuracy of endoscopic ultrasound for restaging rectal cancer following neoadjuvant chemoradiation therapy.

OBJECTIVES:Endoscopic ultrasound (EUS) provides important information in the initial staging of patients with rectal cancer. Preoperative combined modality chemotherapy and radiation (neoadjuvant therapy) for patients with locally advanced rectal cancer may reduce local recurrence and improve survival. The accuracy of EUS restaging of rectal cancer after chemoradiation has not been extensively studied and its usefulness is unclear. The aim of this study was to verify the accuracy of EUS in staging rectal cancer after neoadjuvant chemoradiation in a large cohort of patients.METHODS:EUS staging was performed before and after concurrent 5-fluorouracil and hyperfractionated radiotherapy in 82 patients with recently diagnosed locally advanced rectal cancer. All patients underwent subsequent surgical resection and complete pathologic staging.RESULTS:After chemoradiation, 16 patients (20%) had no residual disease at pathologic staging. (T0N0). However, EUS correctly predicted complete response to chemoradiation in only 10 of 16 patients (63%). Overall accuracy of EUS post chemoradiation for pathologic T-stage was only 48%. Fourteen percent were understaged and 38% overstaged. EUS accuracy for N-stage was 77%. The T-category was correctly staged before surgery in 23 of the 56 responders (41%) and in 16 of 24 nonresponders (67%). EUS was unable to accurately distinguish postradiation changes from residual tumor.CONCLUSION:EUS staging of rectal cancer after chemoradiation is inaccurate, especially in the group of patients with visual and EUS evidence of response. Its routine use for staging purposes after neoadjuvant chemoradiation for rectal cancer should be discouraged.

Anal and Neorectal Function after Ileal Pouch-anal Anastomosis

Bowel function varies markedly among patients with colectomy and ileal pouch-anal anastomosis. Little is known of the mechanisms controlling fecal continence and frequency of defecation after operation. The aim of this study was to determine which features of the anal sphincter and neorectum accounted for the variation in clinical outcome. Twenty patients were studied 4 to 35 months after operation and compared to 12 healthy volunteers. Despite several patients exhibiting impaired fecal continence, anal sphincteric length and pressures and ileal pouch capacity and distensibility were similar in patients and controls. Patients with poor results, however, had rapid filling of their ileal pouch, which resulted in early onset of high amplitude propulsive pressure waves in the pouch. As these waves became more frequent, defecation resulted. Patients with poor results also were not able to empty adequately their pouch. The poorer the completeness of evacuation, the more frequent the defecation (r = 0.62, p less than 0.01). The authors conclude that rapid pouch filling and impaired pouch evacuation can lead to increased stool frequency in patients after ileal pouch-anal anastomosis.

Expression of RORγt Marks a Pathogenic Regulatory T Cell Subset in Human Colon Cancer

Tregs that expand in human colon cancer have proinflammatory properties and contribute to tumor progression. A Treg Melting Pot Some things are not what they seem. Like the allegorical wolf in sheep’s clothing, cell populations that may seem homogeneous may actually contain subsets with different functions. Indeed, such hidden subpopulations may result in contradictory findings in different systems. Blatner et al. now find a subset of regulatory T cells (Tregs) in human colon cancer that may explain disparate clinical outcomes between studies. The authors found preferential expansion in human colon cancer of Tregs that can suppress T cells but are not anti-inflammatory like more classic Tregs. They then looked in a mouse model of hereditary polyposis and found that these cells, which express Foxp3 and RORγt, express the proinflammatory cytokine IL-17 and are directly associated with inflammation and disease progression. The balance between anti-inflammatory Tregs and these “pathogenic” proinflammatory Tregs may play a role in regulating cancer inflammation. Targeting these RORγt+ Tregs may influence disease outcome in colon cancer. The role of regulatory T cells (Tregs) in human colon cancer (CC) remains controversial: high densities of tumor-infiltrating Tregs can correlate with better or worse clinical outcomes depending on the study. In mouse models of cancer, Tregs have been reported to suppress inflammation and protect the host, suppress T cells and protect the tumor, or even have direct cancer-promoting attributes. These different effects may result from the presence of different Treg subsets. We report the preferential expansion of a Treg subset in human CC with potent T cell–suppressive, but compromised anti-inflammatory, properties; these cells are distinguished from Tregs present in healthy donors by their coexpression of Foxp3 and RORγt. Tregs with similar attributes were found to be expanded in mouse models of hereditary polyposis. Indeed, ablation of the RORγt gene in Foxp3+ cells in polyp-prone mice stabilized Treg anti-inflammatory functions, suppressed inflammation, improved polyp-specific immune surveillance, and severely attenuated polyposis. Ablation of interleukin-6 (IL-6), IL-23, IL-17, or tumor necrosis factor–α in polyp-prone mice reduced polyp number but not to the same extent as loss of RORγt. Surprisingly, loss of IL-17A had a dual effect: IL-17A–deficient mice had fewer polyps but continued to have RORγt+ Tregs and developed invasive cancer. Thus, we conclude that RORγt has a central role in determining the balance between protective and pathogenic Tregs in CC and that Treg subtype regulates inflammation, potency of immune surveillance, and severity of disease outcome.

Use and Outcomes of Laparoscopic-Assisted Colectomy for Cancer in the United States

BACKGROUND Laparoscopic-assisted colectomy (LAC) has gained acceptance for the treatment of colon cancer. However, long-term outcomes of LAC have not been examined at the national level outside of experienced centers. OBJECTIVE To compare use and outcomes of LAC and open colectomy (OC). DESIGN Retrospective cohort study. SETTING National Cancer Data Base. PATIENTS Patients who underwent LAC (n = 11 038) and OC (n = 231 381) for nonmetastatic colon cancer (1998-2002). MAIN OUTCOME MEASURES Regression methods were used to assess use and outcomes of LAC compared with OC. RESULTS Laparoscopic-assisted colectomy use increased from 3.8% in 1998 to 5.2% in 2002 (P < .001). Patients were significantly more likely to undergo LAC if they were younger than 75 years, had private insurance, lived in higher-income areas, had stage I cancer, had descending and/or sigmoid cancers, or were treated at National Cancer Institute-designated hospitals. Compared with those undergoing OC, patents undergoing LAC had 12 or more nodes examined less frequently (P < .001), similar perioperative mortality and recurrence rates, and higher 5-year survival rates (64.1% vs 58.5%, P < .001). After adjusting for patient, tumor, treatment, and hospital factors, 5-year survival was significantly better after LAC compared with OC for stage I and II but not for stage III cancer. Highest-volume centers had comparable short- and long-term LAC outcomes compared with lowest-volume hospitals, except highest-volume centers had significantly higher lymph node counts (median, 12 vs 8 nodes; P < .001). CONCLUSIONS Laparoscopic-assisted colectomy and OC outcomes are generally comparable in the population. However, survival was better after an LAC than after an OC in select patients.

Use of Molecular Imaging to Predict Clinical Outcome in Patients With Rectal Cancer After Preoperative Chemotherapy and Radiation

PURPOSE To correlate changes in 2-deoxy-2-[18F]fluoro-d-glucose (18-FDG) positron emission tomography (PET) (18-FDG-PET) uptake with response and disease-free survival with combined modality neoadjuvant therapy in patients with locally advanced rectal cancer. METHODS AND MATERIALS Charts were reviewed for consecutive patients with ultrasound-staged T3x to T4Nx or TxN1 rectal adenocarcinoma who underwent preoperative chemoradiation therapy at Fox Chase Cancer Center (FCCC) or Robert H. Lurie Comprehensive Cancer Center of Northwestern University with 18-FDG-PET scanning before and after combined-modality neoadjuvant chemoradiation therapy . The maximum standardized uptake value (SUV) was measured from the tumor before and 3 to 4 weeks after completion of chemoradiation therapy preoperatively. Logistic regression was used to analyze the association of pretreatment SUV, posttreatment SUV, and % SUV decrease on pathologic complete response (pCR), and a Cox model was fitted to analyze disease-free survival. RESULTS A total of 53 patients (FCCC, n = 41, RLCCC, n = 12) underwent pre- and postchemoradiation PET scanning between September 2000 and June 2006. The pCR rate was 31%. Univariate analysis revealed that % SUV decrease showed a marginally trend in predicting pCR (p = 0.08). In the multivariable analysis, posttreatment SUV was shown a predictor of pCR (p = 0.07), but the test results did not reach statistical significance. None of the investigated variables were predictive of disease-free survival. CONCLUSIONS A trend was observed for % SUV decrease and posttreatment SUV predicting pCR in patients with rectal cancer treated with preoperative chemoradiation therapy. Further prospective study with a larger sample size is warranted to better characterize the role of 18-FDG-PET for response prediction in patients with rectal cancer.

Motility of the small intestine after proctocolectomy and ileal pouch-anal anastomosis.

Though the mechanisms of continence after proctocolectomy and ileal pouch-anal anastomosis have been studied, functions of the small intestine have received little attention. However, frequent stools and urgency plague some patients who are otherwise quite continent. Motility of the jejunum and ileum was assessed in eight patients with ulcerative colitis who were studied 4 to 24 months after proctocolectomy and ileal pouch-anal anastomosis; these findings were compared to those in six healthy volunteers. Continuous manometric recordings from the small bowel were obtained in both groups for 16 to 23 hours of fasting; postprandial recordings were made for 6 hours following a mixed meal (800 kcal, 20% protein, 40% fat, 40% carbohydrate) in the ileoanal patients. The duration, velocity of propagation, and periodicity of the migrating motor complex did not differ between the groups (P greater than 0.05). Discrete bursts of clustered contractions were recorded from all of the controls and in five of eight patients. Likewise, we recorded from all controls and five of eight patients large amplitude, prolonged waves of pressure which propagated distally. However, in controls these large amplitude waves were confined to the terminal ileum, but in patients these were detected in the jejunoileum, up to 125 cm proximal to the ileal pouch. We conclude that jejunoileal motility is not greatly altered by proctocolectomy with ileal pouch-anal anastomosis. However, the appearance of the large amplitude, rapidly propagating waves in the proximal jejunoileum after operation may be a response to increased storage within and distention of the distal bowel.

HIV and anal cancer outcomes: A single institution's experience

PURPOSE: The purpose of this study is to identify the effect of HIV status on outcome of treatment for squamous-cell carcinoma of the anal canal. METHODS: A retrospective review was performed on all patients with squamous-cell carcinoma of the anal canal treated at a single academic institution between January 1996 and December 2006. RESULTS: Our search identified 87 (21 HIV-positive) patients who had invasive squamous-cell cancer. The median follow-up was 38 months. Eighty-five percent of HIV-negative patients and 81 percent of HIV-positive were identified as complete responders at 6 weeks after completion of combined modality therapy. Eight percent of HIV-negative and 29 percent of HIV-positive patients developed recurrent disease after 6 months (P = 0.0009). Overall survival for HIV-negative and HIV-positive patients was 71 percent and 73 percent, respectively. CONCLUSIONS: HIV-positive patients respond equally to combined modality therapy but have recurrences more frequently than patients who are HIV negative. Overall survival in these two groups is equivalent.

Inflammatory pseudotumor of the pancreas

SummaryWe describe a rare example of inflammatory pseudotumor of the pancreas in a 42-yr-old woman, which developed following chemotherapy for lymphoma of the uterine cervix. The patient had developed fatigue, weight loss abdominal pain, and anemia; abdominal CT scan showed a large mass in the pancreas. Examination of the resected specimen revealed a fleshy, well-circumscribed, 7-cm mass., Histologically, there was a hypocellular to moderately hypercellular, bland spindle-cell proliferation admixed with a prominent infiltrate of lymphocytes, histiocytes, and plasma cells. The spindle cells were vimentin positive but negative for muscle markers; electron microscopy revealed only fibroblastic cells. DNA analysis revealed a diploid population with low S-phase fraction. The patient was well at 6-mo follow-up. It is important for the pathologist to be aware of the existence of this entity in unusual locations such as the pancreas so as to avoid a mistaken diagnosis of malignancy.