High resection rates of colorectal liver metastases after standardized follow-up and multimodal management: an outcome study within the COLOFOL trial.

BACKGROUND: Outcome after colorectal liver metastases (CRLM) resection has improved over time, despite increased resection rates. Hence, it's crucial to identify all patients possible to treat with curative intent. The objectives of this study were to map recurrence pattern, treatment strategy and survival depending on treatment and follow-up strategy. METHODS: In the COLOFOL-trial, patients with radically resected stage II-III colorectal cancer were randomized to high-frequency (6, 12, 18, 24 and 36 months; HF) or low-frequency (12 and 36 months; LF) follow-up. In this study, all CRLM within 5 years were identified and medical files scrutinized. Overall survival (OS) was analysed in uni- and multivariable analyses. Primary endpoint was 5-year OS. RESULTS: Of 2442 patients, 235 (9.6%) developed metachronous CRLM of which 123 (52.3%) underwent treatment with curative intent, resulting in 5-year OS of 58%. Five-year OS for patients with CRLM was 43% after HF versus 24% after LF. The survival benefit was confirmed for HF 8 years from resection of the primary tumour, HR 0.63 (CI 0.46-0.85). CONCLUSION: A high proportion of metachronous CRLM was possible to treat with curative intent, yielding high survival rates. More intense follow-up after colorectal cancer resection might be of value in high-risk patients.

In vivo positron emission tomography imaging of decreased parasympathetic innervation in the gut of vagotomized patients.

BACKGROUND: Parasympathetic neuropathy is a key feature in many common disorders, including diabetes, neurological disorders, and cancers, but few objective methods exist for assessing damage to the parasympathetic nervous system, particularly in the gastrointestinal system. This study aimed to validate the use of 11 C-donepezil positron emission tomography (PET) to assess parasympathetic integrity in a group of vagotomized patients. METHODS: Sixteen healthy controls and 12 patients, vagotomized due to esophagectomy, underwent 11 C-donepezil PET, measurement of colonic transit time, quantification of plasma pancreatic polypeptide (PP), and assessment of subjective long-term symptoms. KEY RESULTS: Vagotomized patients had significantly decreased PET signal in the small intestine and colon compared with healthy controls (5.7 [4.4-7.9] vs 7.4 [4.5-11.3], P = .01 and 1.4 [1.1-2.1] vs 1.6 [1.4-2.4], P < .01, respectively). Vagotomized patients also displayed a significantly increased colonic transit time (2.9 ± 0.9 h vs 1.9 ± 0.8 h), P < .01 and increased volumes of the small intestine and colon (715 ccm [544-1177] vs 443 ccm [307-613], P < .01 and 971 ccm [713-1389] vs 711 ccm [486-1394], P = .01, respectively). Patients and controls did not differ in PP ratio levels after sham feeding, but PP ratio at 10 minutes. after sham feeding and PET signal intensity in the small intestine was positively correlated (P = .03). CONCLUSIONS AND INFERENCES: We found significantly decreased 11 C-donepezil signal in the intestine of vagotomized patients, supporting that 11 C-donepezil PET is a valid measure of intestinal parasympathetic denervation.

The effect of postoperative gemcitabine on overall survival in patients with resected pancreatic cancer: A nationwide population-based Danish register study.

Background: Adjuvant chemotherapy following curative resection is the standard treatment for pancreatic adenocarcinoma (PC). Randomized clinical trials using gemcitabine have shown a median overall survival (mOS) of 2 years and a 5-year survival rate of 15-20%. However, the effect of gemcitabine outside these trials is less clear. We examined the effect of postoperative gemcitabine on survival in an unselected cohort of patients receiving curative resection for PC in Denmark during a five-year period. Material and methods: From 1 May 2011 to 30 April 2016, 731 patients treated with curative resection were identified in the Danish Pancreatic Cancer Database (DPCD). Thirty patients died within 10 weeks postoperatively; 78 received other regimens or preoperative chemotherapy and were excluded. Of the remaining 623 patients, the chemotherapy (CT) group (n = 409, 66%) received gemcitabine within 10 weeks after resection, whereas the non-chemotherapy (NCT) group (n = 214, 34%) did not receive CT within 10 weeks. Results: CT patients were slightly younger than NCT patients but did not otherwise differ in baseline characteristics. The CT group showed a mOS of 24 months (95% CI; 21-27) and a 5-year survival rate of 22% (95% CI; 17-27); the NCT group had a mOS of 22 months (95% CI; 16-26, p = .27) and a 5-year survival rate of 26% (95% CI; 19-34, p = .66). Most patients (415/623) had lymph node metastases. Of these patients, those in the CT group (n = 280) had significantly longer mOS [20 months (95% CI; 18-24)] than those in the NCT group (n = 135) [14 months (95% CI; 11-17)]. Conclusions: In this national Danish cohort of PC patients undergoing resection between 2011 and 2016, the survival after postoperative gemcitabine was similar to that reported in previous clinical trials. However, the survival advantage of postoperative gemcitabine was limited to patients with lymph node metastases.

Diagnostic accuracy of CE-CT, MRI and FDG PET/CT for detecting colorectal cancer liver metastases in patients considered eligible for hepatic resection and/or local ablation.

PURPOSE: To compare the diagnostic performance of contrast-enhanced computed tomography (CE-CT), magnetic resonance imaging (MRI) and combined fluorodeoxyglucose/positron emission tomography/computed tomography (FDG-PET/CT) for detection of colorectal liver metastases (CRLM) in patients eligible for local treatment. MATERIALS AND METHODS: This health-research ethics-committee-approved prospective consecutive diagnostic accuracy study, with written informed consent, included 80 cases (76 patients, four participating twice) between 29 June 2015 and 7 February 2017. Prior chemotherapy or local treatment did not exclude participation. Combined FDG-PET/CT including CE-CT and MRI was performed within 0-3 days shortly before local treatment. CE-CT and MRI images were read independently by two readers for each modality. The combined FDG-PET/CT images were read independently by two pairs of readers. A composite reference standard was used. Sensitivities, specificities and area under the receiver operating characteristic curves (AUCROC) were calculated and compared. RESULTS: In total, 260 CRLMs were confirmed. The MRI readers had significantly higher per-lesion sensitivity (85.9% and 83.8%) than both CE-CT readers (69.1% and 62.3%) and both PET/CT reader pairs (72.0% and 72.1%) (p<0.001). There were no significant differences in per-lesion specificity. MRI readers had significantly higher AUCROC (0.92 and 0.88) than both CE-CT readers (0.80 and 0.82) (p≤0.001). AUCROC for MR reader 1 was higher than that of both PET/CT reader pairs (0.83 and 0.84) (p≤0.0001). CONCLUSION: MRI performed significantly better than both CE-CT and combined FDG-PET/CT for detection of CRLM in consecutive patients eligible for local treatment irrespective of prior chemotherapy or local treatment. KEY POINTS: • Patients eligible for local treatment of colorectal liver-metastases require optimal imaging. • In 80 consecutive patients, MRI had superior per lesion diagnostic performance. • Findings were independent of prior treatment and type of planned local treatment. • Equally, MRI had superior diagnostic performance on per segment basis.