Optimal timing for assessment of tumor response to neoadjuvant chemoradiation in patients with rectal cancer: do all patients benefit from waiting longer than 6 weeks?

PURPOSE: To estimate the metabolic activity of rectal cancers at 6 and 12 weeks after completion of chemoradiation therapy (CRT) by 2-[fluorine-18] fluoro-2-deoxy-d-glucose-labeled positron emission tomography/computed tomography ([(18)FDG]PET/CT) imaging and correlate with response to CRT. METHODS AND MATERIALS: Patients with cT2-4N0-2M0 distal rectal adenocarcinoma treated with long-course neoadjuvant CRT (54 Gy, 5-fluouracil-based) were prospectively studied (ClinicalTrials.org identifier NCT00254683). All patients underwent 3 PET/CT studies (at baseline and 6 and 12 weeks from CRT completion). Clinical assessment was at 12 weeks. Maximal standard uptake value (SUVmax) of the primary tumor was measured and recorded at each PET/CT study after 1 h (early) and 3 h (late) from (18)FDG injection. Patients with an increase in early SUVmax between 6 and 12 weeks were considered "bad" responders and the others as "good" responders. RESULTS: Ninety-one patients were included; 46 patients (51%) were "bad" responders, whereas 45 (49%) patients were "good" responders. "Bad" responders were less likely to develop complete clinical response (6.5% vs. 37.8%, respectively; P=.001), less likely to develop significant histological tumor regression (complete or near-complete pathological response; 16% vs. 45%, respectively; P=.008) and exhibited greater final tumor dimension (4.3 cm vs. 3.3 cm; P=.03). Decrease between early (1 h) and late (3 h) SUVmax at 6-week PET/CT was a significant predictor of "good" response (accuracy of 67%). CONCLUSIONS: Patients who developed an increase in SUVmax after 6 weeks were less likely to develop significant tumor downstaging. Early-late SUVmax variation at 6-week PET/CT may help identify these patients and allow tailored selection of CRT-surgery intervals for individual patients.

Accuracy of positron emission tomography/computed tomography and clinical assessment in the detection of complete rectal tumor regression after neoadjuvant chemoradiation: long-term results of a prospective trial (National Clinical Trial 00254683).

BACKGROUND: Neoadjuvant chemoradiation (CRT) therapy may result in significant tumor regression in patients with rectal cancer. Patients who develop complete tumor regression have been managed by treatment strategies that are alternatives to standard total mesorectal excision. Therefore, assessment of tumor response with positron emission tomography/computed tomography (PET/CT) after neoadjuvant treatment may offer relevant information for the selection of patients to receive alternative treatment strategies. METHODS: Patients with clinical T2 (cT2) through cT4NxM0 rectal adenocarcinoma were included prospectively. Neoadjuvant therapy consisted of 54 grays of radiation and 5-fluorouracil-based chemotherapy. Baseline PET/CT studies were obtained before CRT followed by PET/CT studies at 6 weeks and 12 weeks after the completion of CRT. Clinical assessment was performed at 12 weeks after CRT completion. PET/CT results were compared with clinical and pathologic data. RESULTS: In total, 99 patients were included in the study. Twenty-three patients were complete responders (16 had a complete clinical response, and 7 had a complete pathologic response). The PET/CT response evaluation at 12 weeks indicated that 18 patients had a complete response, and 81 patients had an incomplete response. There were 5 false-negative and 10 false-positive PET/CT results. PET/CT for the detection of residual cancer had 93% sensitivity, 53% specificity, a 73% negative predictive value, an 87% positive predictive value, and 85% accuracy. Clinical assessment alone resulted in an accuracy of 91%. PET/CT information may have detected misdiagnoses made by clinical assessment alone, improving overall accuracy to 96%. CONCLUSIONS: Assessment of tumor response at 12 weeks after CRT completion with PET/CT imaging may provide a useful additional tool with good overall accuracy for the selection of patients who may avoid unnecessary radical resection after achieving a complete clinical response. Cancer 2012;3501-3511. © 2011 American Cancer Society.

Laparoscopic total mesorectal excision for rectal cancer after neoadjuvant treatment: targeting sphincter-preserving surgery.

BACKGROUND/AIMS: Laparoscopic total mesorectal excision for rectal cancer is under scrutiny. This study aimed at analyzing feasibility, adequacy of resection, impact on early outcomes after neoadjuvant chemoradiation therapy, and to investigate trend towards indication of laparoscopy for sphincter-preservation in a single university medical center. METHODOLOGY: Patients with distal rectal cancer submitted to neoadjuvant treatment followed by laparoscopic total mesorectal excision were prospectively enrolled. The studied parameters were: demographics, previous surgery, BMI, type of operation, rate of sphincter-preserving surgery, duration of surgery, conversion, specimen retrieval, lymphadenectomy, distal and radial margins, intra and postoperative morbidity, reoperations, hospital stay, and mortality. RESULTS: From January 2000 to July 2010, 68 patients were enrolled. Mean age was 60 (30-87) years. There were 27 anterior and 41 abdominoperineal resections. Six patients underwent a totally laparoscopic resection and coloanal anastomosis. There was a trend (p=0.003) towards more sphincter-preserving surgery. Conversion was 4.5%. Intraoperative complication was 7.4%. Postoperative complications occurred in 15%. Mortality was 3%. Lymph-node harvest was 11 (0-33). Mean distal margin was 2.5cm (1-4). Radial margins were positive in 3 (10%) cases. CONCLUSIONS: Laparoscopic total mesorectal excision after neoadjuvant treatment is feasible and safe. Sphincter-preserving laparoscopic oncologic rectal surgery has been accomplished more frequently.

Rectal and pouch recurrences after surgical treatment for familial adenomatous polyposis.

BACKGROUND: Familial adenomatous polyposis (FAP) is a genetic disease characterized by multiple adenomatous colorectal polyps and different extracolonic manifestations (ECM). The present work is aimed to analyze the outcome after surgical treatment regarding complications and cancer recurrence. METHODS: Charts from patients treated between 1977 and 2006 were retrospectively analyzed. Clinical and endoscopic data, results of treatment, pathological reports and information about recurrence were collected. RESULTS: Eighty-eight patients (41 men [46.6%] and 47 women [53.4%]) were assisted. At diagnosis, associated colorectal cancer (CRC) was detected in 53 patients (60.2%), whose average age was higher than those without CRC (40.0 vs. 29.5 years). At colonoscopy, polyposis was classified as attenuated in 12 patients (14.3%). Surgical treatment consisted in total proctocolectomy with ileostomy (PCI, 15 [17.4%]), restorative proctocolectomy (RPC, 27 [31.4%]), total colectomy with ileal-rectum anastomosis (IRA, 42 [48.8%]), palliative segmental resection (1 [1.2%]) and internal bypass (1 [1.2%]). Two patients were not operated on due to religious reasons and advanced disease. Complications occurred in 25 patients (29.0%), more commonly after RPC (48.1%). There was no operative mortality. Local or distant metastases were detected in six (11.3%) patients with CRC treated to cure. During the follow-up of 36 IRA, cancer developed in the rectal cuff in six patients (16.6%), whose average age was higher than in patients without rectal recurrence (45.8 vs. 36.6 years). Five of them have had colonic cancer in the resected specimen. Among the 26 patients followed after RPC, cancer in the ileal pouch developed in 1 (3.8%). CONCLUSIONS: (1) Within the present series, FAP patients presented a high incidence of associated CRC and diagnosis was generally established after the third decade of life; (2) operative complications occurred in about one third of the patients, being more frequent after the confection of an ileal reservoir; (3) rectal cancer after IRA was detected in 16.6% of patients and it was associated with greater age and previous colonic carcinoma; (4) both continuous and long-term surveillance of the rectal stump and ileal pouch are necessary during follow-up.

Absence of lymph nodes in the resected specimen after radical surgery for distal rectal cancer and neoadjuvant chemoradiation therapy: what does it mean?

PURPOSE: The number of retrieved lymph nodes during radical surgery has been considered of great importance to ensure adequate staging and radical resection. However, this finding may not be applicable after neoadjuvant therapy in which, not only is there a decrease in lymph nodes recovered, but also a subgroup of patients with absence of lymph nodes in the resected specimen. METHODS: Patients with absence of lymph nodes were compared with patients with ypN0 disease and patients with ypN+ disease. RESULTS: Thirty-two patients (11 percent) had absence of lymph nodes, 171 patients (61 percent) had ypN0 disease, and 78 patients (28 percent) had ypN+ disease. Patients with absence of lymph nodes had significantly lower ypT status (ypT0-1, 40 vs. 13 percent; P<0.001) and decreased risk of perineural invasion (6 vs. 21 percent; P=0.04) compared with ypN0 patients. Five-year disease-free survival (74 percent) was similar to patients with ypN0 (59 percent; P=0.2), and both were significantly better than patients with ypN+ disease (30 percent; P<0.001). CONCLUSIONS: Absence of lymph nodes retrieved from the resected specimen is associated with favorable pathologic features (ypT and perineural invasion status) and good disease-free survival rates. In this setting, absence of retrieved lymph nodes may reflect improved response to neoadjuvant chemoradiation therapy rather than inappropriate or suboptimal oncologic radicality.

Loop ileostomy morbidity: timing of closure matters.

PURPOSE: Diverting stomas are commonly performed during ileoanal and coloanal anastomoses. We studied a series of patients after loop ileostomy closure to determine risk factors and the impact of the interval from primary operation on morbidity. METHODS: Ninety-three consecutive patients undergoing loop ileostomy closure at a single institution after coloanal or ileoanal anastomosis were retrospectively reviewed. Complications were classified as medical or surgical according to its treatment requirements. Results were correlated to clinical and operative features. RESULTS: Of the 93 patients, 43 were male and 50 were female with mean age of 56 years. Overall, complication rate was 17.2 percent. The most common complication was small-bowel obstruction. Complications required operative management in 3.2 percent and medical management alone in 14 percent. There was no mortality. There was no correlation between complication occurrence and age, gender, type of suture (manual or mechanical), and operative time. Complications were significantly associated with primary disease and shorter interval between primary operation and ileostomy closure. Regarding the optimal interval between primary surgery and ileostomy closure, the cutoff value for increased risk of developing postoperative complications was 8.5 weeks, below which the risk of such occurrence was significantly higher with a sensitivity rate of 88 percent. CONCLUSIONS: Diverting loop ileostomy adds little cumulative morbidity to the primary operation and is a safe option for diversion to protect a low colorectal anastomosis. To further reduce morbidity, the interval between primary operation and ileostomy closure should be no shorter than 8.5 weeks.

Incidence and management of perineal hernia after laparoscopic proctectomy.

Perineal hernia (PH) is formed by the protrusion of intra-abdominal viscera through a defect in the pelvic floor. This is a rare complication after conventional abdominoperineal resection, pelvic exanteration, proctectomy, and other pelvic procedures. The purpose of the present paper is to report 4 cases of PH after laparoscopic abdominoperineal resection for rectal cancer and to review literature data about the incidence, predisposing factors, and treatment of this challenging problem. When added to other 3 cases previously reported in the Brazilian series of laparoscopic surgery, this group of 7 cases comprises a PH incidence of 3.5% after rectal resection procedures. Surgical treatment is indicated only in symptomatic patients with no signs of cancer recurrence. Proposed methods of surgical repair include abdominal, perineal, or combined approaches to the hernia in association with the use of autologous tissues or prosthetic meshes. Preventive measures are represented by closure of the pelvic peritoneum whenever possible, primary perineal suture and wound care to avoid infection.

Adenocarcinoma after ileoanal anastomosis for familial adenomatous polyposis: review of risk factors and current surveillance apropos of a case.

Restorative proctocolectomy has become the most common surgical option for familial adenomatous polyposis (FAP) patients, based on the premise that it provides good functional results and reduces colorectal cancer risk. But several adenomas may develop in the pouch mucosa over the years, and even cancer at the anastomosis or in the pouch mucosa has been reported rarely. This article aims to describe a case of pouch cancer after restorative proctocolectomy for FAP, reviewing the possible causes of this unfortunate outcome. A 40-year-old man started presenting with fecal blood loss 12 years after restorative proctocolectomy with mucosectomy and hand-sewn anastomosis for FAP. Proctologic examination revealed an elevated mass 3 cm from the anal margin, which biopsy determined to be a mucinous adenocarcinoma. The patient underwent pouch excision and terminal ileostomy. Histologic analysis showed a 2.2 cm mucinous adenocarcinoma between the ileal and anal mucosa (T2N0Mx) and multiple tubular microadenomas in the ileal pouch. The present case and the data presented here suggest that restorative proctocolectomy is not a "cancer-free" alternative to ileorectal anastomosis, because it does not remove the risk of metachronous intestinal neoplasia. Although the long-term risk of malignancy is not known, lifelong follow-up seems to be necessary after restorative proctocolectomy. Current recommendations for pouch surveillance are presented.

Long-term results of preoperative chemoradiation for distal rectal cancer correlation between final stage and survival.

Neoadjuvant chemoradiation treatment (CRT) has resulted in significant tumor downstaging and improved local disease control for distal rectal cancer. The purpose of the present study was to determine the correlation between final stage and survival in these patients regardless of initial disease stage. Two hundred sixty patients with distal (0-7 cm from anal verge) rectal adenocarcinoma considered resectable were treated by neoadjuvant CRT with 5-FU and leucovorin plus 5040 cGy. Patients with incomplete clinical response 8 weeks after CRT completion were treated by radical surgical resection. Patients with complete clinical response were managed by observation alone. Overall survival and disease-free survival were compared according to Kaplan-Meier curves and log-rank tests according to final stage. Seventy-one patients (28%) showed complete clinical response (clinical stage 0). One hundred sixty-nine patients showed incomplete clinical response and were treated with surgery. In 22 of these patients (9%), pathologic examination revealed pT0 N0 M0 (stage p0), 59 patients (22%) had stage I, 68 patients (26%) had stage II, and 40 patients (15%) had stage III disease. Overall survival rates were significantly higher in stage c0 (P=0.01) compared with stage p0. Disease-free survival rate showed better results in stage c0, but the results were not significant. Five-year overall and disease-free survival rates were 97.7% and 84% (stage 0); 94% and 74% (stage I); 83% and 50% (stage II); and 56% and 28% (stage III), respectively. Cancer-related overall and disease-free survival may be correlated to final pathologic staging following neoadjuvant CRT for distal rectal cancer. Also, stage 0 is significantly associated with improved outcome.

Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy: long-term results.

OBJECTIVE: Report overall long-term results of stage 0 rectal cancer following neoadjuvant chemoradiation and compare long-term results between operative and nonoperative treatment. METHODS: Two-hundred sixty-five patients with distal rectal adenocarcinoma considered resectable were treated by neoadjuvant chemoradiation (CRT) with 5-FU, Leucovorin and 5040 cGy. Patients with incomplete clinical response were referred to radical surgical resection. Patients with incomplete clinical response treated by surgery resulting in stage p0 were compared to patients with complete clinical response treated by nonoperative treatment. Statistical analysis was performed using chi2, Student t test and Kaplan-Meier curves. RESULTS: Overall and disease-free 10-year survival rates were 97.7% and 84%. In 71 patients (26.8%) complete clinical response was observed following CRT (Observation group). Twenty-two patients (8.3%) showed incomplete clinical response and pT0N0M0 resected specimens (Resection group). There were no differences between patient's demographics and tumor's characteristics between groups. In the Resection group, 9 definitive colostomies and 7 diverting temporary ileostomies were performed. Mean follow-up was 57.3 months in Observation Group and 48 months in Resection Group. There were 3 systemic recurrences in each group and 2 endorectal recurrences in Observation Group. Two patients in the Resection group died of the disease. Five-year overall and disease-free survival rates were 88% and 83%, respectively, in Resection Group and 100% and 92% in Observation Group. CONCLUSIONS: Stage 0 rectal cancer disease is associated with excellent long-term results irrespective of treatment strategy. Surgical resection may not lead to improved outcome in this situation and may be associated with high rates of temporary or definitive stoma construction and unnecessary morbidity and mortality rates.