Hepatic Arterial Infusion Chemotherapy With Folfirinox or Oxaliplatin Alone in Metastatic Colorectal Cancer.

Background: Hepatic arterial infusion (HAI) of chemotherapy is an option for the treatment of patients with liver metastases from colorectal cancer (LMCRC). Though HAI with oxaliplatin (HAI-Ox) is generally used, intravenous (IV) 5-fluoro-uracil (5FU)-oxaliplatin-irinotecan HAI (HAI-Folfirinox) is feasible and leads to curative-intent surgery in 30% of pretreated patients. We compared the efficacy and safety of HAI-Ox and HAI-Folfirinox. Methods: Patients who underwent HAI chemotherapy for LMCRC were retrospectively included from 2008 to 2019 from six French expert centers. Results: Data were collected from 273 previously treated patients with LMCRC. Patients received HAI-Folfirinox (n = 52) or HAI-Ox (n = 221) combined with IV chemotherapy. The objective response rate (ORR) was 43.2% in patients with HAI-Folfirinox and 45.9% (ns) in patients with HAI-Ox. Median overall survival (OS) was 17 months (95% CI: 15-32.3) with HAI-Folfirinox and 26.2 months (95% CI: 19.4-34.4; p = 0.1) with HAI-Ox. Median progression-free survival (PFS) was 7.9 months (95% CI: 4.9-10.3) with HAI-Folfirinox and 6.4 months (95% CI: 6.0-7.7; p = 0.6) with HAI-Ox. The secondary liver resection rate was 35.6% with HAI-Folfirinox and 16.7% with HAI-Ox (p = 0.007). Grade 2 and above toxicities were significantly more frequent with HAI-Folfirinox. In the global population, only 2 factors were prognostic for OS in multivariable analyses: liver-only disease [hazard ratio (HR): 0.4; 95% CI 0.20-0.83; p = 0.013] and local complications of the catheter (HR: 3.8; 95% CI 1.6-9.0; p = 0.002). Conclusion: Hepatic arterial infusion results in high response rates, secondary resections, and long survival in pretreated patients with LMCRC.

Predictive Factors of Chemotherapy Initiation after Biliary Drainage for Advanced Biliary Tract Cancer: A Retrospective Multicenter Study.

BACKGROUND AND AIMS: In unresectable biliary tract cancers, the management of biliary obstruction is often the first step before introduction of chemotherapy. Our aim was to study the predictive factors of chemotherapy initiation after biliary drainage in a series of patients presenting with advanced biliary tract cancer and obstructive jaundice. METHODS: Data of all patients treated for unresectable biliary tract cancer with initial biliary obstruction requiring a drainage in six institutions, from January 2009 to January 2019, were retrospectively collected. RESULTS: Among 82 patients included in this study (median age 68 years, men 61%), 48 (59%) received chemotherapy. Median overall survival was 4.9 months (0.2-38.7) in the group of patients who did not receive chemotherapy and 12.2 months (1.9-61.0) in chemotherapy group (HR=2.93; 95%CI: 1.6-5.3; p<0.0001). In univariate analysis, younger age, male gender, Eastern Cooperative Oncology Group (ECOG) score ≤2, high albumin level, low C-reactive protein level, and endoscopic drainage were significantly associated with introduction of chemotherapy. In multivariate analysis, only ECOG score ≤2 at diagnosis (HR=70.4; 95%CI: 4.6-1097.6; p=0.002) and male gender (HR=5; 95%CI: 1.5-16.5; p=0.009), were significant independent predictive factors of chemotherapy introduction. Age and bilirubin level at diagnosis were not significant factors in multivariate analysis. CONCLUSIONS: ECOG score ≤ 2 and male gender were the only independent predictive factors of chemotherapy introduction in unresectable biliary tract cancers. Age or initial bilirubin level were not predictors for chemotherapy introduction. These results might help defining the initial therapeutic strategy.

Hepatic Arterial Infusion Chemotherapy for Unresectable Liver Metastases of Colorectal Cancer: A Multicenter Retrospective Study.

INTRODUCTION: Hepatic arterial infusion chemotherapy (HAIC) is a treatment used for liver metastases (LM) of colorectal cancer (CRC). Because of its technical conditions, it has been used in only a few experienced centers in France. Our aim was to evaluate its feasibility, efficacy and tolerance in 4 centers. METHODS: Clinical, biological, and radiological data of patients treated with HAIC for unresectable LM from CRC in 4 institutions from October 2011 to January 2016 were retrospectively analyzed. RESULTS: Sixty-one patients with unresectable LM from CRC were included. Patients had previously received systemic chemotherapy in 95% of patients and 82.8% had previous oxaliplatin treatment. Oxaliplatin was administered using an intra-arterial route combined with intravenous (I.V.) Five-fluorouracil (5-FU) with leucovorin alone in 43.3% of patients, or combined with other I.V. chemotherapies or monoclonal antibodies in 56.7% of patients. Grade 3 to 4 clinical toxicities were reported in 16% of patients, including 9.8% of neurotoxicity, and Grade 3 to 4 biological toxicities were reported in 24.6% of patients including 22.2% with neutropenia. Catheter-related complications were observed in 31.1%. Tumor response rate in first- and second-line was 26.5% and third- and fourth-line was 11%. Median overall survival (OS) in first- and second-line was 13.5 months and third- and fourth-line was 8.3 months (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.39-1.12; P = .1729). Median progression-free survival (PFS) in first- and second-line was 9 months and third- and fourth-line were 6 months (HR, 0.53; 95% CI, 0.18-0.659; P = .0037). A secondary R0 resection was possible in 10 cases (16.4%) allowing a 2-year survival of 80%. CONCLUSION: These data confirm that in centers that recently developed HAIC using oxaliplatin, this treatment is feasible and has acceptable tolerance. The results, in terms of hepatic PFS, PFS, OS, and the rate of secondary resections of LM, are in the range of published data, and they confirm the interest of HAIC in patients in progression after multiple I.V.

Risk factors for exposure of glaucoma drainage devices: a retrospective observational study.

OBJECTIVES: The purpose of this study was to identify risk factors for exposure of glaucoma drainage devices (GDD). SETTING: This retrospective, observational study was conducted in the eye clinic of an academic medical centre. PARTICIPANTS: Participants included 1073 consecutive adults who underwent GDD surgery between 1 January 2005 and 1 January 2011. Participants were included if chart review indicated GDD surgery during the study period and excluded if at least 12 months of clinical follow-up was not available in the medical record. PRIMARY OUTCOME MEASURE: The primary outcome measure was exposure of the GDD occurring at least 1 month after implant surgery. The characteristics of participants who experienced exposure of the implant were compared to the characteristics of participants who did not experience exposure. RESULTS: Of the 1073 participants having undergone GDD surgery, 67 experienced exposure of the device. Neither the type of GDD, type of patch graft (eye bank sclera, Tutoplast sclera and Tutoplast pericardium), surgeon, location of GDD, number of GDD previously implanted into the eye, nor history of diabetes or uveitis were associated with likelihood of exposure. Women were more likely than men to experience exposure of the GDD (OR 2.004 (95% CI1.170 to 3.431)) in both univariable (p=0.011) and multivariable (p=0.013) analyses. In survival analysis, exposure of the GDD occurred earlier for women than for men (58 vs 61 months; p=0.024).White race (vs black) was also associated with increased risk of GDD exposure (OR 1.693 (95% CI 1.011 to 2.833)) in univariable (p=0.044) and multivariable (p=0.046) analyses. CONCLUSIONS: Women are two times more likely to experience GDD exposure than men, independent of age. White race is also a risk factor for exposure.

C-terminal substitution of MDM2 interacting peptides modulates binding affinity by distinctive mechanisms.

The complex between the proteins MDM2 and p53 is a promising drug target for cancer therapy. The residues 19-26 of p53 have been biochemically and structurally demonstrated to be a most critical region to maintain the association of MDM2 and p53. Variation of the amino acid sequence in this range obviously alters the binding affinity. Surprisingly, suitable substitutions contiguous to this region of the p53 peptides can yield tightly binding peptides. The peptide variants may differ by a single residue that vary little in their structural conformations and yet are characterized by large differences in their binding affinities. In this study a systematic analysis into the role of single C-terminal mutations of a 12 residue fragment of the p53 transactivation domain (TD) and an equivalent phage optimized peptide (12/1) were undertaken to elucidate their mechanistic and thermodynamic differences in interacting with the N-terminal of MDM2. The experimental results together with atomistically detailed dynamics simulations provide insight into the principles that govern peptide design protocols with regard to protein-protein interactions and peptidomimetic design.

Cyanoacrylate adhesive use in primary operation and reoperation in rabbit eye muscle surgery.

PURPOSE: To compare the performance of 2-octyl-cyanoacrylate to 6-0 polyglactin 910 suture in rabbit superior rectus muscle surgery after operation and reoperation procedures. METHODS: A prospective noninferiority trial was conducted in rabbits. Bilateral superior rectus muscle recessions were performed using cyanoacrylate in one eye and polyglactin suture in the other. At 5 weeks, reoperations to advance the superior rectus muscle were performed on 20 rabbits. Slippage, tensile strength, ease of reoperation, operative time, and inflammatory reaction were recorded. For the primary outcomes, the predetermined margin of noninferiority was 1 mm for slippage and 100 g for tensile strength. RESULTS: In both groups, the proportion of slippage > or =1 mm from the recession site was 1.9%. For the reoperation, it was 36.8% and 15.7% in the suture and cyanoacrylate groups, respectively, and the mean slippage was 0.60 mm and 0.42 mm. Mean tensile strength was 842.8 g for suture and 777.2 g for cyanoacrylate after the first operation and 877.73 g and 844.87 g after the reoperation. There was no difference between groups for surgical difficulty or inflammatory index. For the first operation, surgery using cyanoacrylate was on average 3.85 min faster than suture. CONCLUSIONS: Cyanoacrylate can achieve an adequate muscle-sclera bond in the immediate period after surgery to avoid major slippage and does not affect the long-term process of wound healing for both recession and advancement procedures. It is well tolerated and does not add technical difficulty even if used for reoperations. Because it eliminates the risk of globe perforation, cyanoacrylate may be a good alternative to sutures in strabismus surgery.