Predicting complete response to neoadjuvant CRT for distal rectal cancer using sequential PET/CT imaging.

BACKGROUND: Molecular imaging using positron emission tomography/computerized tomography (PET/CT) may add relevant incremental diagnostic information to standard structural cross-sectional imaging. Such information may allow identification of patients with rectal cancer that are more likely to develop complete tumor regression after neoadjuvant chemoradiation therapy (CRT). The objective of this report was to identify PET/CT features that are associated with a complete response after CRT. METHODS: 99 cT2-4N0-2M0 distal rectal cancer patients (≤7 cm from anal verge) were included in this prospective single center trial (NCT 00254683). Patients underwent baseline PET/CT followed by 54 Gy and 5-fluorouracil-based neoadjuvant CRT. After completion of therapy, patients underwent 6- and 12-week PET/CT. Clinical assessment of tumor response was performed at 12 weeks and was blinded to radiological information. Patients were treated according to clinical assessment. RESULTS: There were seven patients with a complete pathological response (pCR) and 16 with a complete clinical response (cCR) (23 complete responders). Comparison of pCR exclusively and non-pCR revealed that only baseline primary tumor standard uptake value (SUV) was a significant predictor of response. Comparison of complete responders (pCR or cCR) and non-complete responders showed that depth of rectal wall uptake at baseline PET/CT (p = 0.002) and variation between baseline and 12-week maximum standard uptake value (SUVmax) of primary tumor (p = 0.001) were independent predictors for complete response at multivariate analysis. A decrease >67 % between baseline and 6-week or 76 % between baseline and 12-week SUVmax were associated with complete response (pCR or cCR; p = 0.02 and p < 0.001, respectively). CONCLUSIONS: Positron emission tomography/computerized tomography at baseline, 6 and 12 weeks, may provide information regarding patients with a higher likelihood of developing complete tumor regression following neoadjuvant CRT.

Clinical relevance of positron emission tomography/computed tomography-positive inguinal nodes in rectal cancer after neoadjuvant chemoradiation.

AIM: Inguinal nodes may be a possible route for lymphatic spread in patients with distal rectal cancer. The outcome was examined for patients with distal rectal cancer undergoing neoadjuvant chemoradiation (CRT) and having 2-fluorine-18-fluoro-2-deoxy-d-glucose (FDG)-avid inguinal nodes using positron emission tomography/computed tomography (PET/CT) imaging. METHOD: Ninety-nine consecutive patients with cT2-4N0-2M0 distal rectal adenocarcinoma were enrolled in a clinical trial (NCT00254683) and underwent baseline PET/CT followed by 54 Gy and 5-fluorouracil-based CRT. After CRT, patients underwent 6- and 12-week PET/CT. Patients with positive inguinal node uptake were compared with patients with negative uptake. The inguinal region was not included in the field of radiation therapy. RESULTS: Seventeen (17%) patients had baseline positive inguinal node FDG uptake. They were more likely to have the tumour closer to the anal verge (2.0 vs 4.2 cm; P = 0.001). Of these, eight (47%) demonstrated a positive inguinal uptake at PET/CT after 12 weeks from CRT. Patients with inguinal node FDG uptake after CRT (positive PET at baseline and 12 weeks) had a significantly worse 3-year overall and disease-free survival (P = 0.02 and P = 0.03). After a median follow-up period of 22 months, none of these patients had developed inguinal recurrence. CONCLUSION: Uptake of inguinal nodes at PET/CT may be present in up to 17% of patients with distal rectal cancer, particularly with ultra-low tumours. Nearly half of these nodes no longer show uptake after CRT despite the groin area not being included in the radiation field. Persistence of inguinal node uptake 12 weeks after CRT completion may be a marker for worse oncological outcome.

Role of biopsies in patients with residual rectal cancer following neoadjuvant chemoradiation after downsizing: can they rule out persisting cancer?

AIM: The study aimed to determine the value of postchemoradiation biopsies, performed after significant tumour downsizing following neoadjuvant therapy, in predicting complete tumour regression in patients with distal rectal cancer. METHOD: A retrospective comparative study was performed in patients with rectal cancer who achieved an incomplete clinical response after neoadjuvant chemoradiotherapy. Patients with significant tumour downsizing (> 30% of the initial tumour size) were compared with controls (< 30% reduction of the initial tumour size). During flexible proctoscopy carried out postchemoradiation, biopsies were performed using 3-mm biopsy forceps. The biopsy results were compared with the histopathological findings of the resected specimen. UICC (Union for International Cancer Control) ypTNM classification, tumour differentiation and regression grade were evaluated. The main outcome measures were sensitivity and specificity, negative and positive predictive values, and accuracy of a simple forceps biopsy for predicting pathological response after neoadjuvant chemoradiotherapy. RESULTS: Of the 172 patients, 112 were considered to have had an incomplete clinical response and were included in the study. Thirty-nine patients achieved significant tumour downsizing and underwent postchemoradiation biopsies. Overall, 53 biopsies were carried out. Of the 39 patients who achieved significant tumour downsizing, the biopsy result was positive in 25 and negative in 14. Only three of the patients with a negative biopsy result were found to have had a complete pathological response (giving a negative predictive value of 21%). Considering all biopsies performed, only three of 28 negative biopsies were true negatives, giving a negative predictive value of 11%. CONCLUSION: In patients with distal rectal cancer undergoing neoadjuvant chemoradiation, post-treatment biopsies are of limited clinical value in ruling out persisting cancer. A negative biopsy result after a near-complete clinical response should not be considered sufficient for avoiding a radical resection.

Factors affecting management decisions in rectal cancer in clinical practice: results from a national survey.

BACKGROUND: Management of rectal cancer has become increasingly complex and a multidisciplinary approach is considered of key importance for improving outcomes. A national survey among specialists involved in this multidisciplinary setting was performed. METHODS: A web-based survey containing 11 questions regarding rectal cancer management was sent to surgeons and medical oncologists registered by their corresponding societies as members. Statistical analysis was performed using the chi-square and Fisher's exact tests for all categorical variables according to response to individual questions. Multivariate analysis was performed using Cox's logistic regression. RESULTS: Overall, 418 email recipients responded the survey. Local staging was performed without either magnetic resonance imaging or endorectal ultrasound by 64% of responders. Seventy-two percent considered that final management decision should be made after neoadjuvant chemoradiation therapy. Additionally, 46% considered that an alternative procedure (local excision or observation) was appropriate in a patient with a complete clinical response. Colorectal surgeons were more frequently in favor of longer intervals after completion of chemoradiation therapy (P = 0.001) and of alternative management procedures after a complete clinical response (P = 0.02). After multivariate analysis, the choice of a watch and wait approach after a complete clinical response following neoadjuvant chemoradiation therapy was significantly more frequent among surgeons (OR 3.5, 95% CI 1.8-7.1). CONCLUSIONS: Surgeons seem to be more in favor of tailoring management of rectal cancer according to tumor response after neoadjuvant chemoradiation therapy, with longer intervals after chemoradiation therapy, decisions about treatment strategy being made after chemoradiation therapy instead of before, and the use of alternative surgical procedures after a complete clinical response following neoadjuvant therapy.

Distribution of lymph nodes in the mesorectum: how deep is TME necessary?

BACKGROUND: Standardization of total mesorectal excision (TME) had a great impact on decreasing local recurrence rates for the treatment of rectal cancer. However, exact numbers and distribution of lymph nodes (LN) along the mesorectum remains controversial with some studies suggesting that few LNs are present in the distal third of the mesorectum. METHODS: Eighteen fresh cadavers without a history of rectal cancer were studied. The rectum was removed by TME and then was divided into right lateral, posterior and left lateral sides, which were further subdivided into 3 levels (upper, middle and lower). A pathologist determined the number and sizes of the LNs in each of the nine areas, b linded to their anatomical origin. RESULTS: Overall, the mesorectum had a mean of 5.7 LNs (SD=3.7) and on average each LN had a maximum diameter of 3.0 mm (SD=2.7). There was no association between the mean number or size of LNs with gender, BMI, or age. There was a significantly higher prevalence of LNs in the posterior location (2.8 per mesorectum) than in the two lateral locations (0.8 and 1.2 per mesorectum; p=0.02). The distribution of LNs in the three levels of the rectum was not significant. CONCLUSIONS: The distribution of LNs reinforces the fact that TME should always include the distal third of the mesorectum. Care must be taken to not violate the posterior aspect of the mesorectum.

Endoscopic management of postoperative stapled colorectal anastomosis hemorrhage.

Rectal bleeding following colorectal anastomosis is common but usually self-limited. Continuous hemorrhage is rare, and when it occurs, often requires further treatment. The most frequently used strategies for treatment of stapled anastomotic hemorrhage are clinical observation with or without blood transfusion, rectal packing, angiographic identification of the bleeding site with vasopressin infusion or embolization, and endoscopic eletrocoagulation. We report the case of a 49-year-old man with uncomplicated diverticular disease who was treated by laparoscopic sigmoidectomy, with double-stapled colorectal anastomosis. Six hours later, the patient presented intense rectal bleeding and was taken to the operation room for urgent colonoscopic examination. After complete removal of blood clots inside the rectum, a bleed localized at the anastomotic site was identified and submucosal peri-anastomotic injection of 10 ml adrenaline (1:200 000) in saline was performed with immediate bleeding control.