Cytoreduction plus hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis in colorectal cancer patients: a single-center cohort study

BACKGROUND: In this study, we report our experience of cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) in patients with peritoneal carcinomatosis (PC) from colorectal cancer (CRC), focusing on the factors affecting survival. METHODS: All patients with surgically treated PC from colorectal cancer and with no involvement of other organs referred to our institute from March 2005 to December 2017 were included in the analysis. RESULTS: Thirty-eight patients underwent CRS-HIPEC, and all had a completeness of cytoreduction score of 0 (CC0). The median operating time was 645 min (interquartile range [IQR] 565-710). Five patients (13.1%) had Clavien-Dindo grade >\u20092 postoperative complications. Median overall survival (OS) was 60 months. In the Cox regression for OS, calculated on the CRS-HIPEC group, the peritoneal cancer index (PCI) >\u20096 (hazard ratio [HR] 4.48, IQR 1.68-11.9, P = 0.003) and significant nodal involvement (N2) (HR 3.89, IQR 1.50-10.1, P = 0.005) were independent prognostic factors. Median disease-free survival (DFS) was 16 months. Only N2 (HR 2.44, IQR 1.11-5.36, P = 0.027) was a significantly negative prognostic factor for DFS in multivariate analysis. CONCLUSIONS: CRS-HIPEC can substantially improve survival. However, patients with high PCI (PCI >\u20096) and significant nodal involvement (N2) may not benefit from the procedure

Preoperative Chemotherapy and Resection Margin Status in Colorectal Liver Metastasis Patients: A Propensity Score-Matched Analysis

In this article, we compared the early and long-term outcomes of patients with metastatic colorectal cancer treated with chemotherapy followed by resection with those of patients undergoing surgery first, focusing our analysis on resection margin status. Patients who underwent liver resection with curative intent for colorectal liver metastases from July 2001 to January 2018 were included in the analysis. Propensity score matching was used to reduce treatment allocation bias. The cohort comprised 164 patients; 117 (71.3%) underwent liver resection first, whereas the remaining 47 (28.7%) had preoperative chemotherapy. After a 1:1 ratio of propensity score matching, 47 patients per group were evaluated. A positive resection margin was found in 13 patients in the surgery-first group (25.5%) versus 4 (8.5%) in the preoperative chemotherapy group (P = 0.029). Postmatched logistic regression analysis showed that only preoperative chemotherapy was significantly associated with the rate of positive resection margin (odds ratio 0.24, 95% confidence interval 0.07-0.81; P = 0.022). Median follow-up was 41 months (interquartile range 8-69). Cox proportional hazard regression analysis revealed that only positive resection margin was a significant negative prognostic factor (hazard ratio 2.2, 95% CI 1.18-4.11; P = 0.014). Within the preoperative chemotherapy group, median overall survival was 40 months in R0 patients and 10 months in R1 patients (P = 0.016). Although preoperative chemotherapy in colorectal liver metastasis patients may affect the rate of positive resection margin, its impact on survival seems to be limited. In the present study, the most important prognostic factor was the resection margin status

Prolonged pemetrexed infusion plus gemcitabine in refractory metastatic colorectal cancer: Preclinical rationale and phase II study results

Background. We investigated the cytotoxic activity of pemetrexed in combination with several drugs (gemcitabine, carboplatin, vinorelbine, and mitomycin C) using different exposure schedules in three colon cancer cell lines. The best results were obtained with the following schedule: a prolonged pemetrexed exposure followed by a 48-hour wash-out and then gemcitabine. This combination was then advanced to a phase II clinical trial. Methods. Patients with metastatic colorectal cancer in progression after standard treatment were included in the study. Adequate bonemarrow reserve, normal hepatic and renal function, and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 were required. Treatment consisted of an 8-hour intravenous infusion of pemetrexed 150 mg/m 2 on day 1 and a 30-minute intravenous infusion of gemcitabine 1,000 mg/m 2 on day 3 of each cycle, repeated every 14 days. Results. Fourteen patients were enrolled onto the study (first step). No objective responses were seen, and evidence of stable disease was observed in only one of the 12 evaluable patients. The most important grade 3-4 side effects were hematological toxicity (neutropenia 64.2%, thrombocytopenia 71.4%, anemia 28.7%), fatigue (50.0%), and stomatitis (21.5%). Median overall survival and time to progression were 5.8 months (95% confidence interval [CI]: 3.9-7.1) and 2.1 months (95% CI: 1.7-2.8), respectively. Conclusion. The experimental pemetrexed-gemcitabine combination proved to be inactive and moderately toxic

Prognostic role of serum concentrations of high-sensitivity C-reactive protein in patients with metastatic colorectal cancer: Results from the ITACa trial

Serum levels of C-reactive protein are (CRP) higher in patients with neoplastic conditions and numerous studies have been performed to clarify the etiologic and prognostic role of the high-sensitivity CRP (hs-CRP) in cancer. Our study was conducted on patients enrolled in the prospective randomized "Italian Trial in Advanced Colorectal Cancer (ITACa)" to assess hs-CRP levels and their impact on overall survival (OS) and progression-free survival (PFS). Serum samples from 132 ITACa patients were collected at baseline and 2 months after starting first-line chemotherapy. The supernatant was immediately transferred to cryovials and stored at -80°C. After thawing, hs-CRP was measured with the Cobas c501 analyzer. High levels of hs-CRP (≥ 13.1 mg/L) were associated with poorer median PFS (p < 0.0001) and OS (p < 0.0001) than low hs-CRP levels (< 13.1 mg/L). hs-CRP values in 107 patients were evaluated again after 2 months of therapy, revealing that patients with low hs-CRP levels in both baseline and second serum samples had the best median PFS and OS. Our study confirms the prognostic value of hs-CRP in patients with metastatic colorectal carcinoma

Radiofrequency Ablation of hepatocellular carcinoma: a meta-analysis of overall survival and recurrence-free survival

Background and aims So far, no randomized trial or meta-analysis has been conducted on overall survival (OS) and recurrence-free survival (RFS) factors in patients treated with radiofrequency ablation (RFA) alone. The purpose of this meta-analysis was to evaluate prognostic factors of OS and RFS in patients treated with RFA. Methods A primary analysis was planned to evaluate the clinical prognostic factor of OS. RFS was the secondary aim. Thirty-four studies published from 2003 to 2017 were analyzed. They included 11,216 hepatocellular carcinoma patients. Results The results showed that Child\u2013Pugh B vs Child\u2013Pugh A (HR =2.32; 95% CI: 2.201\u20132.69; P<0.0001) and albumin\u2013bilirubin score 1 vs 0 (HR =2.69; 95% CI: 2.10\u20133.44; P<0.0001) were predictive of poor OS. Tumor size as a continuous variable was not predictive of OS, although it was predictive of OS when we considered the size as a cutoff value (.2 cm vs <2 cm: HR =1.41; 95% CI: 1.23\u20131.61; P<0.0001; >3 cm vs <3 cm: HR =1.43; 95% CI: 1.17\u20131.74; P<0.0001) and in presence of >1 nodule (HR =1.59; 95% CI: 1.46\u20131.74; P<0.0001). Alpha-fetoprotein >20 ng/mL (HR =1.46; 95% CI: 1.25\u20131.70; P<0.0001) was the only predictive factor of poor prognosis. Conclusion Our meta-analysis highlighted that the maximum benefit of RFA in terms of OS and RFS is reached in the presence of Child\u2013Pugh A, albumin\u2013bilirubin score 1, single-nodule tumor sized <2 cm, and alpha-fetoprotein <20 ng/mL

IL-8 and thrombospondin-1 as prognostic markers in patients with metastatic colorectal cancer receiving bevacizumab

Purpose: Bevacizumab (B) plus chemotherapy (CT) is a common choice for first-line treatment of metastatic colorectal cancer. Molecular predictors of B efficacy have still not been identified. We analyzed the role of 22 angiogenesis-associated proteins in patient outcome. Patients and methods: Serum samples collected at baseline and at the first clinical evaluation were available for 58 patients enrolled in the randomized multicenter ITACa trial and who received CT+ B. Serum protein levels were determined using multiplex ELISA. Results: Patients with baseline 65145 pg/mL IL-8 showed shorter median progression-free survival and overall survival (OS) than those with lower levels (6.5 vs 6. 12.6 months; HR 7.39, P<0.0001 and 8.7 vs 28.8 months, HR 7.68, P<0.001, respectively). Moreover, patients with baseline thrombospondin-1 levels 6512,000 ng/mL had a better median OS than those with lower levels (34.5 vs 13.1 months, HR 0.43, P=0.007). Patients with a 6520% reduction in IL-8 levels from baseline to first clinical evaluation showed a better progression-free survival and OS than the others (HR 0.41, P=0.005 and HR 0.43, P=0.007, respectively). Conclusion: Baseline IL-8 and thrombospondin-1 levels and reduced IL-8 during B treatment could represent potential prognostic markers in metastatic colorectal cancer

Serum angiogenesis associated proteins and clinical outcome in metastatic colorectal cancer patients receiving bevacizumab

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Hemangioblastoma of the gastrointestinal tract: A first case

We present the first documented case of hemangioblastoma located in the left colon. A 75-year-old woman undergoing adjuvant chemotherapy for breast cancer experienced rectal bleeding. Colonoscopy revealed a roundish mass covered with normal mucosa in the sigmoid colon. Endoscopic ultrasound showed an isoechoic lesion originating from the third layer of the intestinal wall; underlying layers were normal. Endoscopic ultrasound features were not suggestive of either cancer or malignant stromal tumor. Left hemicolectomy was subsequently performed due to repeated episodes of lower gastrointestinal bleeding. Grossly, a circumscribed submucosal yellowish nodule (13 mm) was observed, which was not attached to any peripheral nerve. Histologically, the lesion was composed of large, atypical cells traversed by a network of blood vessels. Immunohistochemically, the cells showed positivity for inhibin and NSE and weak positivity for S-100. A diagnosis of hemangioblastoma was made. This case highlights that hemangioblastoma of the gastrointestinal tract can also occur. © The Author(s) 2013

Genomic alterations in rectal tumors and response to neoadjuvant chemoradiotherapy: an exploratory study

<p>Abstract</p> <p>Background</p> <p>Neoadjuvant chemoradiotherapy is the treatment of choice in advanced rectal cancer, even though there are many patients who will not benefit from it. There are still no effective methods for predicting which patients will respond or not. The present study aimed to define the genomic profile of rectal tumors and to identify alterations that are predictive of response in order to optimize therapeutic strategies.</p> <p>Methods</p> <p>Forty-eight candidates for neoadjuvant chemoradiotherapy were recruited and their pretherapy biopsies analyzed by array Comparative Genomic Hybridization (aCGH). Pathologic response was evaluated by tumor regression grade.</p> <p>Results</p> <p>Both Hidden Markov Model and Smoothing approaches identified similar alterations, with a prevalence of DNA gains. Non responsive patients had a different alteration profile from responsive ones, with a higher number of genome changes mainly located on 2q21, 3q29, 7p22-21, 7q21, 7q36, 8q23-24, 10p14-13, 13q12, 13q31-34, 16p13, 17p13-12 and 18q23 chromosomal regions.</p> <p>Conclusions</p> <p>This exploratory study suggests that an in depth characterization of chromosomal alterations by aCGH would provide useful predictive information on response to neoadjuvant chemoradiotherapy and could help to optimize therapy in rectal cancer patients.</p> <p>The data discussed in this study are available on the NCBI Gene Expression Omnibus [GEO: GSE25885].</p

Dynamic contrast-enhanced ultrasonography (D-CEUS) for the early prediction of bevacizumab efficacy in patients with metastatic colorectal cancer

Objectives: To investigate early changes in tumour perfusion parameters by dynamic contrast-enhanced ultrasonography (D-CEUS) and to identify any correlation with survival and tumour response in patients with metastatic colorectal cancer (CRC) treated with bevacizumab (B). Methods: Thirty-seven patients randomized to either chemotherapy (C) plus B or C alone were considered for this study. D-CEUS was performed at baseline and after the first treatment cycle (day 15). Four D-CEUS perfusion parameters were considered: derived peak intensity (DPI), area under the curve (AUC), slope of wash-in (A) and time to peak intensity (TPI). Results: In patients treated with C plus B, a ≥22.5 % reduction in DPI, ≥20 % increase in TPI and ≥10 % reduction in AUC were correlated with higher progression-free survival in the C+B arm (p = 0.048, 0.024 and 0.010, respectively) but not in the C arm. None of the evaluated parameter modifications had a correlation with tumour response or overall survival. Conclusions: D-CEUS could be useful for detecting and quantifying dynamic changes in tumour vascularity as early as 15 days after the start of B-based therapy. Although these changes may be predictive of progression-free survival, no correlation with response or overall survival was found. Key Points: • D-CEUS showed early changes in liver metastasis perfusion in colorectal cancer. • A decrease in tumour perfusion was associated with longer progression-free survival. • The decrease in perfusion was not correlated with higher overall survival