Effect of Paclitaxel-based Hyperthermic Intraperitoneal Chemotherapy (HIPEC) on colonic anastomosis in a rat model.

BACKGROUND: Paclitaxel has been used frequently for Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for ovarian carcinomatosis. Cytoreductive surgery and HIPEC are associated with high rates of morbidity being anastomotic dehiscence one of the most frequent. The objective of this study is to quantify the effect of Paclitaxel-based HIPEC on colonic anastomosis in an experimental rat model. METHODS: After left colon resection and anastomosis, animals were randomized into four groups: Controls (C); Hyperthermia (H); Normothermic Intraperitoneal Paclitaxel (CP) and Paclitaxel-based HIPEC (HP). On postoperative day four, animals' peritoneal cavities were examined macroscopically, colon anastomosis burst pressures measured and specimens analyzed histologically. RESULTS: Thirty-nine animals were randomized and 36 were included in the analysis. H group presented the highest burst pressure 105.11 ± 22.9 mmHg, which was 27% higher than C (77.89 ± 27.6 mmHg). On the other hand, HP presented the lowest burst pressure 64 ± 26 mmHg, 16% lower than C group and 39% lower than H, being this latter difference statistically significant (p = 0.004). There were no significant differences regarding weight loss, adhesion scores, perianastomotic abscesses and histological findings (inflammation, fibroblasts, neoangiogenesis, and collagen among groups). CONCLUSION: Strength of colonic anastomosis was improved by isolated hyperthermia and negatively affected by Paclitaxel-based HIPEC.

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.

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.