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Background: The FAST is a 2 × 2 factorial trial addressing two questions: (1) the role of replacing cisplatin (P) with a non-platinum agent, vinorelbine (N), and (2) the role of adding a third agent, ifosfamide (I), in a doublet based on gemcitabine (G).Methods: A total of 433 stage IIIB-IV non-small cell lung cancer (NSCLC) patients were randomised to one of four arms: gemcitabine-cisplatin (GP), gemcitabine-vinorelbine, gemcitabine-ifosfamide-cisplatin or gemcitabine-ifosfamide-vinorelbine. Two comparisons were performed: N- vs P-containing regimens and I-triplets vs non-I doublets.Results: For N- vs P-containing regimens, adjusted overall survival was 9.7 vs 11.3 months (P=0.044), progression-free survival was 4.9 vs 6.4 months (P=0.020) and response rate was 24% vs 31% (P=0.124), respectively. No statistically significant difference was observed between doublets and triplets. Grade 3-4 haematological toxicity was significantly more frequent in P-containing therapy; grade 3-4 leucopenia was significantly more common in triplets. Concerning non-haematological toxicity, grade 3-4 nausea-vomiting was significantly increased in P-containing regimens.Conclusions: This trial provides evidence of a slight survival superiority of GP-containing regimens over platinum-free N-containing chemotherapy. This trial also confirms that the addition of a third chemotherapy agent (I) to a standard G-based doublet does not improve treatment outcome. [ABSTRACT FROM AUTHOR]

Background: Hepatic arterial chemotherapy (HAC) is an effective treatment of liver metastases from colorectal cancer (CRC). Phase I and II studies have already shown the feasibility and efficacy of intra-arterial oxaliplatin (OXA)., Patients and Methods: Twenty-one pre-treated patients with liver metastases who received HAC with OXA/folinic acid (FA)/5-fluorouracil (5-FU) at our Division between March 2000 and November 2003, were clinically examined. Most patients were heavily pre-treated with two or more systemic chemotherapeutic regimes. All patients received a percutaneously implanted catheter into the hepatic artery through femoral or transaxillary access. Treatment was administered every 14 days: OXA 100 mg/m2 as a 12-hour infusion on day 1; FA 100 mg/m2 as a 2-hour infusion on days 2 and 3; 5-FU 2600 mg/m2 as a continuous infusion on days 2 and 3., Results: Grade 3-4 toxicities were: asthenia (2 out of 21), transaminase elevation (2 out of 21) and pain (2 out of 21), nausea and vomiting (1 out of 21), neutropenia (1 out of 21), thrombocytopenia (1 out of 21) and neurotoxicity (1 out of 21). Main dose limiting toxicity was right upper quadrant pain. Response rates were: 5% complete response, 19% partial response, 28% stable disease and 48% progressive disease. Two patients became operable and underwent complete resection of liver disease. The median overall survival was 36.1 months. Two-year and 3-year survival rates were 62% and 52%, respectively., Conclusion: This regimen is feasible with low toxicity and with an encouraging overall tumor growth control (52%) in a subset of heavily pre-treated patients. Intra-arterial OXA/FA/5-FU should be considered for the treatment of patients pre-treated with systemic chemotherapies with liver metastases from CRC.

Background: Patients with unresectable biliary tract carcinomas have a very poor prognosis. To improve the efficacy and tolerance of the ECF regimen (epirubicin at a dose of 50 mg/m2, cisplatin at a dose of 60 mg/m2, and 5-fluorouracil [5-FU] at a dose of 200 mg/m2 per day by continuous infusion), the authors designed a novel approach that combined locoregional and systemic chemotherapy with the same agents at the same dosages., Methods: Thirty consecutive patients with advanced or metastatic biliary tumors were treated with epirubicin at a dose of 50 mg/m2 and cisplatin at a dose of 60 mg/m2 administered as a bolus in the hepatic artery on Day 1, combined with systemic continuous infusion of 5-FU at a dose of 200 mg/m2 per day, from Day 1 to Day 14, every 3 weeks., Results: Tumor sites were the intrahepatic bile ducts in 25 patients and the gallbladder in 5 patients. The overall response rate was 40% (12 of 30 patients), including 1 complete response and 11 partial responses. Stable disease was observed in 12 of 30 patients (40%) and progressive disease in 6 of 30 patients (20%). The median progression-free and overall survival periods were 7.1 and 13.2 months, respectively, and the 1-year and 2-year survival rates were 54% and 20%, respectively. Performance status improved in 9 of 30 patients (30%) and a weight gain of > 7% was observed in 4 of 30 patients (13%). The treatment was well tolerated with minimal hematologic toxicity. The major clinical problem was the deep venous thrombosis related to the central venous catheter, which occurred in 5 patients (17%)., Conclusions: This novel combined locoregional and systemic chemotherapeutic regimen was found to be active and safe for patients with advanced biliary tract carcinoma., (Copyright 2005 American Cancer Society.)

Standard treatment for transitional cell carcinoma confined to the bladder is radical cystectomy that allow to obtain an overall 5-year disease-free survival rate only of 50-70%. It has been demonstrated that intra-arterial chemotherapy produces the same survival outcomes as radical cystectomy. This study aimed to evaluate the activity and toxicity of a bladder-sparing loco-regional treatment. Five patients with transitional cell carcinoma of the bladder (4 locally advanced and 1 pelvic relapse) were treated with doxorubycin 25 mg/m2, cisplatin 40 mg/m2 and methotrexate 50 mg/m2, all infused bolus via internal iliac arteries on day 1, every three weeks. We obtained 3 complete responses, 1 stable disease and 1 progression of disease. The treatment was well tolerated with a minimal hematological toxicity and no others major toxicity. Median disease free survival was 8 months (1-17), median overall survival was 22 months (2-55). This loco-regional regimen of chemotherapy is active and safe in locally advanced bladder cancer patients and permits a prolonged good quality of life regarding the maintenance of the physiological functions of the lower urinary tract.

Both CAV (Cyclophosphamide, Doxorubicin, Vincristine) and PE (Cisplatin, Etoposide) are effective and non cross-resistant regimens in the treatment of SCLC. We designed a chemotherapeutic scheme including CAV and PE given in an alternating fashion with the following schedule: Cyclophosphamide 1000 mg/sm, Doxorubicin 50 mg/sm, Vincristine 2 mg/sm I.V. on day 1, alternated every 21 days with Cisplatin 20 mg/sm and Etoposide 80 mg/sm I.V. days 1-5 for 6 cycles. Following chemotherapy (CT) chest radiotherapy in patients (pts) with limited disease (LD) in complete response (CR) or partial response (PR) and prophylactic cranial irradiation (PCI) in CRs were given, 32 pts entered the study and 27 were evaluable: 9/27 (33.3%) had CR (8/15 with LD had CR) and 15/27 (55.5%) PR. The overall median survival was 53.71 weeks: 79.85 weeks for LD pts and 32.86 for ED.4 pts with LD were alive after 2 years and 2 of them are still alive without disease at 44 and 46 months. Toxicity was acceptable in all patients. Alternating chemotherapy with CAV and PE followed by chest and brain RT in responding LD pts is an effective induction treatment for SCLC although long-term survival still remains disappointing.

Cholangiocarcinoma (CCA) is a hepatic malignancy that has a rapidly increasing incidence. CCA is anatomically classified into intrahepatic (iCCA) and extrahepatic (eCCA), which is further divided into perihilar (pCCA) and distal (dCCA) subtypes, with higher incidence rates in Asia. Despite its rarity, CCA has a low 5-year survival rate and remains the leading cause of primary liver tumor-related death over the past 10–20 years. The systemic therapy section discusses gemcitabine-based regimens as primary treatments, along with oxaliplatin-based options. Second-line therapy is limited but may include short-term infusional fluorouracil (FU) plus leucovorin (LV) and oxaliplatin. The adjuvant therapy section discusses approaches to improve overall survival (OS) post-surgery. However, only a minority of CCA patients qualify for surgical resection. In comparison to adjuvant therapies, neoadjuvant therapy for unresectable cases shows promise. Gemcitabine and cisplatin indicate potential benefits for patients awaiting liver transplantation. The addition of immunotherapies to chemotherapy in combination is discussed. Nivolumab and innovative approaches like CAR-T cells, TRBAs, and oncolytic viruses are explored. We aim in this review to provide a comprehensive report on the systemic and locoregional therapies for CCA. [ABSTRACT FROM AUTHOR]

Simple Summary: Due to the rarity of the entity of cholangiocarcinoma, there is a lack of randomized clinical trials which can compared modalities of treatment for unresectable intra-hepatic cholangiocarcinoma (iCC). In this review, we proposed to summarize current evidence regarding all the modalities of loco-regional treatment in iCC in order to help clinicians in their decision-making. For unresectable intrahepatic cholangiocarcinoma (iCC), different locoregional treatments (LRT) could be proposed to patients, including radiofrequency ablation (RFA) and microwave ablation (MWA), external beam radiotherapy (EBRT) or transarterial treatments, depending on patient and tumor characteristics and local expertise. These different techniques of LRT have not been compared in a randomized clinical trial; most of the relevant studies are retrospective and not comparative. The aim of this narrative review is to help clinicians in their everyday practice discuss the pros and cons of each LRT, depending on the individual characteristics of their patients. [ABSTRACT FROM AUTHOR]

A total of 375 Gram-negative bacterial strains were isolated from midstream urine specimens of the same number of patients affected by urinary tract infections. All bacteria were identified by standard bacteriological methods and their susceptibility to six quinoline derivatives (ciprofloxacin, cinoxacin, norfloxacin, oxolinic acid, pipemidic acid, nalidixic acid) was studied by determining the MICs and MBCs for each compound using a miniaturized dilution broth method in microtitre plates and twofold dilutions of each drug from 256 to 0.12 mcg/ml. Ciprofloxacin, a new quinoline carboxylic acid compound structurally related to nalidixic acid, showed a much higher antibacterial activity against all bacterial strains under examination, including Pseudomonas, than the other compounds, except for norfloxacin. The MIC90 and MBC90 of ciprofloxacin never exceeded 1 mcg/ml with any of the bacterial species; and MBC/MIC ratios were very low, which represents an important clinical advantage. Only norfloxacin showed comparable effectiveness. No bacterial strain showed resistance to the drug and the MIC90 and MBC90 never exceeded 8 mcg/ml.

A total of 127 Gram-negative bacteria resistant to nalidixic acid were isolated from as many patients affected by urinary tract infections and hospitalized in the first Clinic of Infectious Diseases, University of Naples. Enterobacteria were identified by Enterotube system (Roche) and API 20 system (Ayerst). Non-fermentative bacteria were identified by OXI/FERM system (Roche). The following bacteria were collected: Escherichia coli 50, Proteus spp. 35, Enterobacter agglomerans 12, Serratia sp. 5, Pseudomonas aeruginosa 25. The in vitro antibacterial activity of nalidixic acid and three other quinoline derivatives (pipemidic acid, oxolinic acid and ciprofloxacin) were studied by determining the MICs by a miniaturized dilution broth method. The MICs were compared to evaluate the eventual cross resistance to the drugs under examination within each bacterial species. The results showed that 23% of bacteria were resistant to nalidixic acid, pipemidic acid and oxolinic acid; 49.6% to nalidixic and pipemidic acid and 0.7% to nalidixic acid and oxolinic acid. On the other hand none of the bacteria were resistant to ciprofloxacin. The last showed very low MICs against all the bacteria under examination, including Pseudomonas and Serratia. The high antibacterial activity of ciprofloxacin even against bacteria highly resistant to the other quinolines could be due to a greater affinity of the target sites or to the better permeability of resistant strains to the newer drug or because it is unaffected until now by mutations of genes responsible for cross resistance.

A total of 343 Gram-negative bacteria were isolated and identified from urine specimens of patients with urinary tract infections. All the bacteria were investigated for their production of beta-lactamases by the nitrocefin test. beta-lactamase-producing strains were tested by the Datta method to detect any transfer of beta-lactamase production to a receiving E. coli K12 RN-strain. MICs of six beta-lactamase-stable compounds (ceftazidime, ceftriaxone, cefamandole, cefoxitin, cefotaxime, cefuroxime) were determined against all the beta-lactamase transferring bacteria and their respective transconjugants by a miniaturized dilution broth method. beta-lactamases produced by donors and transconjugants were purified and identified by determination of the isoelectric point by focusing; their hydrolytic activity was assessed by a spectrophotometric method using cytochrome c reduction. A total of 129 bacteria out of 343 produced beta-lactamases and 27 of these transferred the beta-lactamase production by conjugation. The beta-lactamases isolated from donors and transconjugants had the same pl and the same substrate profile. Ceftazidime was more stable to all the beta-lactamases isolated and more active against all the bacteria examined than the other compounds.

Three hundred seventy-five Gram-negative bacterial strains were isolated from urine specimens of as many patients affected by symptomatic or asymptomatic urinary tract infections. Susceptibility of bacteria to five chemotherapeutics (norfloxacin, oxolinic acid, pipemidic acid, nalidixic acid and nitrofurantoin) was studied determining minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of each compound by a miniaturized dilution broth method. Norfloxacin, a quinoline carboxylic acid compound structurally related to nalidixic acid, showed a much higher antibacterial activity against all bacterial strains under examination including Pseudomonas sp. The best activity of norfloxacin was expressed either by lower MICs and lower MBCs with respect to those of the other compounds, or by a low MBC/MIC ratio, which represents an important advantage in clinical practice.

The in vitro activity of ceftizoxime compared with other beta-lactamase stable compounds was assessed against recent urinary gram negative isolates. 343 bacterial strains were isolated from patients affected by UTI, identified by standard bacteriological methods and investigated for their production of beta-lactamases by Nitrocefin test. MICs and MBCs of ceftizoxime, ceftriaxone, cefamandole, cefoxitin and cefotaxime were determined by a miniaturized dilution broth method against all beta-lactamase producing bacteria (129 out of 343). Sensitivity of antibiotics to beta-lactamases isolated and semi-purified by ultrasonic disruption and high speed centrifugation was assessed by a spectrophotometric method. In vitro antibacterial activity of each antibiotics was correlated to their sensitivity to isolated beta-lactamases. Ceftizoxime showed lower MIC and MBC values and lower MBC/MIC ratio than the other compounds against all the bacteria including Pseudomonas. Ceftizoxime was not hydrolized by any isolated beta-lactamase.

beta-lactamase production was evaluated by chromogenic cephalosporin 87/312 in 116 E. coli isolated from clinical sources. Such test revealed beta-lactamase production in 54 strains out of 116 (46%): MICs of eight beta-lactam antibiotics (Ampicillin, Piperacillin, Cefazoline, Cephaloridine, Cephalexine, Cefuroxime, Cefotaxime, Cefotaxime) were determined using a miniaturized dilution broth method. Cefotaxime and Ceftriaxome and Ceftriaxone showed the highest antibacterial activity. All beta-lactamases produced by E. coli strains under examination were isolated and purified by ultrasonic disruption and high speed centrifugation. Sensitivity of the eight antibiotics to purified beta-lactamases was assessed by a spectrophotometric method that utilizes the velocity of cytochrome c reduction. The sensitivity to beta-lactamases was reflected in the in vitro activity of the antibiotics as assessed by the determination of the MICs.

Sixteen patients with previously untreated small-cell lung cancer, unsuitable for standard aggressive intravenous chemotherapy due to advanced age or poor performance status or very advanced disease including brain metastases or either extensive liver or marrow involvement with impaired organ function, were treated with combined oral chemotherapy including 4-demethoxydaunorubicin (IMI30, idarubicin) 30 mg/sm on day 1 and etoposide (VP16) 150 mg/sm on days 2,3,4 every 4 weeks. Out of 13 evaluable patients 1 had a complete response and 2 had a partial response with an overall objective response rate of 23% (95% confidence-limits 5-53.8%). Toxicity was generally very mild. Although the compliance of this regimen is excellent, its antitumor activity seems unsatisfactory even in this category of poor-risk small-cell lung cancer patients.

The in vitro activity of ceftazidime compared with other beta-lactamase stable compounds was assessed against recent Gram-negative isolates. Three hundred forty-three bacterial strains were isolated from patients affected with UTI, identified by standard bacteriological methods and investigated for their production of beta-lactamases by the Nitrocefin test. MICs and MBCs (minimum inhibitory concentrations and minimum bactericidal concentration) of ceftazidime, cefamandole, cefoxitin, cefotaxime and cefuroxime were determined by a miniaturized dilution broth method against all beta-lactamase producing bacteria (129 out of 343). Sensitivity of the antibiotics to beta-lactamases isolated and semipurified by ultrasonic disruption and high-speed centrifugation was assessed by a spectrophotometric method. The in vitro antibacterial activity of each antibiotic was correlated to its sensitivity to isolated beta-lactamases. Ceftazidime showed lower MIC and MBC values and lower MBC/MIC ratios than the other compounds against all the bacteria including Pseudomonas spp. In addition, ceftazidime was not hydrolyzed significantly by any isolated beta-lactamases.

326 gram negative bacteria have been isolated and quantitative bacteria counts performed from midstream urine of as many patients affected with symptomatic and non symptomatic urinary tract infections. Susceptibility of bacteria to four quinoline derivatives (Norfloxacin, Oxolinic acid, Pipemidic acid and Nalidixic acid) was studied determining the minimal inhibitory concentrations (MICs) of each drug by a miniaturized dilution broth method. The frequency of bacterial species isolated, the frequency of symptoms and the frequency of bacterial counts were studied to establish a possible relationship between these data. It has been observed that patients affected with pyuria without any other subjective symptoms demonstrate a colony count ranging between less than 10(4) and greater than 10(5) bacterial/ml of urine and these bacteriuria were determined by several different bacterial species. E. coli was much more frequently responsible for low or high count bacterial infections of the urinary tract than other species. In fact E. coli was detected in 64.4% of patients, P. mirabilis in 15.9%, E. agglomerans in 5.2%, P. aeruginosa in 4.9. Other species were detected in much lower percentages. Norfloxacin proved to be the most effective drug in vitro, out of those under examination. Its MIC50 never exceeded 8 mcg/ml even against Pseudomonas and Serratia strains, which were resistant to all the other antimicrobial agents.

Thirty-six specimens of feces were taken from as many chicken farms, from which 118 different strains of Enterobacteriaceae were isolated. The resistances of the single isolated bacteria were studied, performing plate sensitivity tests by the Kirby-Bauer method. The capacity of the bacteria under examination to transfer their antibiotic resistances in vitro to a sensitive E. coli strain (E. coli K 12 E 711 F--) was observed. A very high percentage of strains has shown resistance to one or more antibiotics (91%). However a much lesser number of strains were capable of transferring their antibiotic resistances (12.9%). It is suggestive, then, that the animals under examination do not represent an important source of antibiotic resistance diffusion to man.

Simple Summary: Due to the late onset of symptoms and aggressive growth, cholangiocellular carcinomas (CCA) are associated with poor outcome. In advanced stages, interventional therapies and systemic therapies are particularly used. The combination of locoregional therapeutic approaches with modern system therapies represents a promising approach to improve the outcome for cholangiocellular carcinoma patients. Locoregional therapy options for CCA are used, in particular, for non-resectable tumors and aim to reduce tumor viability or delay tumor growth and ultimately prolong overall survival. In addition to local ablative procedures such as radiofrequency- or microwave-ablation, transarterial procedures such as transarterial embolization (TAE), transarterial chemoembolization (TACE), or selective internal radiotherapy (SIRT) play a major role. In particular, in combination with advances in molecular medicine and immunotherapy, there has been a further development in the therapy of primary malignant liver tumors in recent years. In this review, we analyze data from recent studies and examine the implications for therapy of CCA, particularly with regard to the combination of locoregional therapies with modern systemic therapies. [ABSTRACT FROM AUTHOR]

The medical fraternity is currently burgeoned and stressed with a huge rush of patients who have inflammatory conditions, metabolite diseases, and cardiovascular diseases. In these circumstances, advanced sensing technologies could have a huge impact on the quality of life of patients. Given plasmonic resonance effects significantly improve the ability to rapidly and accurately detect biological markers, plasmonic technology is harnessed to develop a fast and accurate diagnosis that can provide timely intervention with the diseases and can also aid the recovery process by complementing the therapy stage. In this short review, we provide an overlook of how the field of plasmonic sensing has revolutionized the field of medical diagnostics. This article reviews the fundamentals and development of plasmonics. In addition, we highlight the sensitivity of various SPR and LSPR sensors. The chemistry for functionalizing plasmonic sensors is also discussed. This review also outlines some general suggestions for future directions that we feel might be useful to advance our understanding of the universe or speed up the development of plasmonic sensors in the future. [ABSTRACT FROM AUTHOR]

Background: Hepatic arterial infusion chemotherapy delivers the drug directly to the liver. We aim to explore the benefits and tolerability of Hepatic arterial infusion chemotherapy plus regorafenib in advanced colorectal liver metastasis refractory to standard systemic chemotherapy.Methods: This study analyzed 47 patients treated with hepatic arterial infusion chemotherapy plus regorafenib after standard systemic oxaliplatin and/or irinotecan in combination with bevacizumab or cetuximab between Jan 2017 and Jun 2020. Regorafenib was given for only 3 weeks in a 4-week cycle.Results: Among 47 patients, 32 (68%) were males. The median age was 61 (29-75). With a median follow-up of 22.2 months (3.7-50.7 months). Before Hepatic arterial infusion chemotherapy administration in combination with regorafenib, 34 (72.3%) patients previously received ≥ 2 prior lines of systemic therapy and 37 (78.7%)patients previously received targeted biological treatment (anti-VEGF or anti-EGFR, or both). The initial doses of regorafenib were 40 mg/d (n = 1, 2.13%), 80 mg/d (n = 11, 23.43%), 120 mg/d (n = 2, 4.26%), and 160 mg/d (n = 23, 48.94%), while for 24.6% (n = 14) dose was unknown. Median Overall Survival was 22.2 months. Median Progression-Free Survival was 10.8 (95% CI: 9.0-13.7) months. Common Adverse Events were hand-foot skin reaction (12.77%), fatigue (6.38%), vomiting (6.38%), and decreased appetite (6.38%). Only 2 patients discontinued regorafenib due to Adverse Events.Conclusions: Regorafenib combined with Hepatic arterial infusion was effective and tolerable in patients with liver predominant metastasis of colorectal cancer. Hence, this therapy can be considered as an alternative for second- or subsequent lines of therapy in patients refractory to standard systemic chemotherapy. [ABSTRACT FROM AUTHOR]

Objective: This study aims to evaluate the effectiveness and safety of hepatic arterial infusion chemotherapy (HAIC) following the simultaneous placement of self-expandable metallic stent (SEMS) and iodine-125 (125I) seed strands for the management of advanced cholangiocarcinoma (CCA) patients presenting with malignant obstructive jaundice (MOJ). Methods: Data from 74 patients with MOJ caused by advanced CCA treated with stent placement with 125I seed strands with or without HAIC between November 2015 and October 2020 were analysed retrospectively. Eighteen patients received 5 sessions of HAIC after SEMS placement with 125I seed strands (HAIC group), and 56 patients only underwent SEMS placement with 125I seed strands and served as controls (control group). HAIC consisted of infusions of gemcitabine (600–1000 mg/m2 given over 30 min) followed by oxaliplatin (60–100 mg/m2 given over 2 h), with an interval of 4 weeks. Propensity score matching (PSM) analysis was used to adjust for differences in the baseline characteristics of the groups (including age, total bilirubin, and serum alanine aminotransferase level). Overall survival (OS), stent patency, and adverse events were compared between the two groups. Results: OS and stent patency were significantly better in patients in the HAIC group than in those in the control group (median survival time: before PSM, 362 vs. 185 days, p = 0.005; after PSM, 357 vs. 183 days, p = 0.012; median duration of stent patency: before PSM, 294 vs. 156 days, p = 0.001; after PSM, 287 vs. 183 days, p = 0.039). All adverse reactions were controllable by temporary symptomatic treatment. Serious complications and treatment-related deaths were not observed. Conclusion: Our preliminary study showed that HAIC following SEMS placement with 125I seed strands is effective and safe for the management of advanced CCA patients presenting with MOJ and could improve stent patency and patient survival. [ABSTRACT FROM AUTHOR]

Background: In case of response to chemotherapy, unresectable liver metastases from colorectal cancer can be converted to resectable and thereby obtain a chance of cure. The primary aim of this trial was to evaluate the response rate with intrahepatic oxaliplatin in combination with systemic 5-FU +/– cetuximab. Secondary aims were to evaluate the conversion rate from unresectable to resectable liver metastases, median progression-free survival, median overall survival, and toxicity. Methods: Forty-five chemo-naïve patients with liver metastases from colorectal cancer were treated in a prospective phase II trial. Calcium folinate and 5-FU were delivered systemically while oxaliplatin was delivered alternating between systemic and intrahepatic administration. When oxaliplatin was delivered intrahepatic-ally, infusion time was reduced to 10 min followed by embolic material. In patients with KRAS wild-type tumors, cetuximab was added. Results: The treatment was well tolerated and only pain in the liver and a mild increase in liver enzymes were observed after intrahepatic oxaliplatin. The patients obtained a response rate of 82%. Further, 58% converted from having unresectable to resectable liver metastases. The median overall survival and progression-free survival were 38.7 months (95% confidence interval [CI] 33.0–44.3) and 12.9 months (95% CI 10.2–15.6), respectively. Conclusions: Intrahepatic infusion of oxaliplatin in 10 min with systemic 5-FU to patients with chemo-naïve colorectal cancer is feasible and with low toxicity. A high response rate and long median overall survival were obtained. [ABSTRACT FROM AUTHOR]

Purpose: S-1 and gemcitabine (GS) combination therapy is a promising treatment for advanced biliary tract cancer (BTC). However, systemic administration of GS is associated with a high rate of grade 3 and 4 neutropenia. Hepatic arterial infusion (HAI) of gemcitabine may overcome this problem. We conducted a prospective phase 1 trial to determine the maximum tolerated dose (MTD) of S-1 and rates of dose-limiting toxicities (DLTs) associated with HAI of gemcitabine in patients with unresectable BTC. Methods: BTC patients were treated with 21-day cycles of HAI of gemcitabine (1000 mg/m on days 1 and 8) and oral S-1 (60, 70, or 80 mg/m on days 1-14) until disease progression occurred. Results: Fifteen patients were enrolled in the study. Grade 3 and 4 neutropenia occurred in five of 15 (33 %) patients. Among six patients who were treated with 60 mg/m S-1, one developed grade 4 neutropenia. DLTs (grade 4 neutropenia and bladder infection) occurred in two of six patients who were treated with 70 mg/m S-1. Two of the three patients who were treated with 80 mg/m S-1 experienced DLTs (grade 4 leukopenia and neutropenia and grade 3 febrile neutropenia). Thus, 80 mg/m was defined as the MTD of S-1. Conclusion: The MTD of oral S-1 in GS therapy is 80 mg/m. Furthermore, HAI of gemcitabine may reduce the rate of grade 3 and 4 neutropenia in BTC patients receiving GS therapy. [ABSTRACT FROM AUTHOR]

Background: Hepatic arterial infusion (HAI) of chemotherapy requires the implantation of a transcatheter application system which is traditionally performed by surgery. This procedure, but particularly the adjacent drug application via pump or port is often hampered by specific complications and device failure. Interventionally implanted port catheter systems (IIPCS) facilitate the commencement of HAI without need for laparatomy, and are associated with favorable complication rates. We here present an evaluation of the most important technical endpoints associated with the use of IIPCS for HAI in patients with primary liver cancers.Methods: 70 patients (pts) with hepatocellular (HCC, n=33) and biliary tract cancer (BTC, n=37) were enrolled into a phase II -study. Of those, n=43 had recurrent disease and n=31 suffered from liver-predominant UICC-stage IVb. All pts were provided with IIPCSs before being treated with biweekly, intraarterial chemotherapy (oxaliplatin, 5-Flourouracil, folinic acid). The primary objective of the trial was defined as evaluation of device-related complications and port duration.Results: Implantation of port catheters was successful in all patients. Mean treatment duration was 5.8 months, and median duration of port patency was not reached. Disease-progression was the most common reason for treatment discontinuation (44 pts., 63%), followed by chemotherapy-related toxicity (12 pts., 17%), and irreversible device failure (5 pts., 7%). A total of 28 port complications occurred in 21 pts (30%). No unexpected complications were observed.Conclusions: HAI via interventionally implanted port catheters can be safely applied to patients with primary liver tumors far advanced or/and pretreated. [ABSTRACT FROM AUTHOR]

Past works on refractive index sensing using nanohole arrays in metal films typically achieved a resolution of around 10−4 to 10−5 refractive index units (RIU), up to 10−6 with complicated detection setups. This is an order of magnitude worse than commercial Kretschmann-based surface-plasmon resonance (SPR) sensors. Here, we demonstrate intensity-based bulk refractive index sensing in an aqueous environment with a resolution of 9.38 × 10−8 refractive index units (RIU), showing for the first time comparable performance for nanohole SPR with Kretschmann-based SPR. This is achieved by the combination of three advances in the materials properties: (a) template stripping to achieve ultra-flat Au surfaces of ∼0.2 nm roughness, (b) elliptical nanoholes to enhance transmission, and (c) a Cytop substrate to symmetrize the refractive index with the aqueous environment above the metal film. The simple optical microscope geometry and microfluidic integration used in this work is promising for multiplexed lab-on-chip analysis. [ABSTRACT FROM AUTHOR]

Background:The FAST was a factorial trial in first-line treatment of advanced non-small-cell lung cancer (NSCLC), addressing the role of replacing cisplatin with a non-platinum agent. The prognostic and predictive effect of ERCC1/BRCA1 expression and ERCC1/XPD/XRCC1-3 gene polymorphisms on outcomes of patients was examined.Methods:Patients were randomised to receive treatment with or without cisplatin. ERCC1/BRCA1 expression was determined by immunohistochemistry. ERCC1 (C8092A, C118T), XPD (Lys751Gln), XRCC1 (Arg399Gln) and XRCC3 (Thr241Met) gene polymorphisms were evaluated on tumour DNA by TaqMan allelic discrimination assay.Results:Tumour samples were available from 110 of 433 patients enrolled: 54.7% were ERCC1 positive and 51.4% were BRCA1 positive. Overall, ERCC1-negative patients had better response rate (P=0.004), progression-free survival (P=0.023) and overall survival (P=0.012) compared with positive ones, with no statistically significant treatment interaction. The BRCA1-positive patients showed numerically better outcomes, although not statistically significant, with no treatment interaction. Among DNA repair gene polymorphisms, only XRCC1 Gln/Gln genotype evidenced a potential prognostic role (P=0.036).Conclusion:This study confirms the prognostic role of ERCC1 expression and XRCC1 (Arg399Gln) polymorphism in advanced NSCLC treated with first-line chemotherapy. None of these biomarkers was shown to be a specific predictive factor of cisplatin efficacy. [ABSTRACT FROM AUTHOR]

Purpose: Systemic chemotherapy still represents the gold standard in the treatment of irresectable colorectal liver metastases. Modern anticancer agents like the monoclonal antibody cetuximab have improved the outcome of patients in clinical studies. As hepatic arterial infusion (HAI) is capable to potentially increase the anticancer effect of cytostatics, we herein studied whether HAI of cetuximab (CE) as a single agent or in combination with oxaliplatin (OX) exerts increased anticancer effects compared to the systemic application (SYS) of the drugs. Methods: WAG/Rij rats were randomized to eight groups and underwent 10 days after subcapsular hepatic tumor implantation either HAI or SYS of CE, OX, or the combination of both agents (CE + OX). Saline-treated animals served as controls. Tumor volume was measured at days 10 and 13 using three-dimensional ultrasound. On day 13, liver and tumor tissue was sampled for histological and immunohistochemical analysis. Results: In controls, the tumor volume significantly increased from day 10 to 13. Application of OX alone via HAI or SYS did not inhibit tumor growth compared to controls. SYS of CE or CE + OX did also not reduce tumor growth. In contrast, HAI of CE and CE + OX significantly inhibited tumor growth. HAI of CE significantly reduced tumor vascularization as measured by the number of platelet endothelial cell adhesion molecule-1-positive cells and significantly increased the number of apoptotic tumor cells as measured by the cellular caspase-3 expression. Conclusion: HAI of CE and CE + OX reduces tumor growth of colorectal rat liver metastases involving the inhibition of angiogenesis and induction of tumor cell apoptosis. [ABSTRACT FROM AUTHOR]