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Optical generation of microwave signals using photonic techniques offers benefits of frequency agility, ease of frequency scaling, and reduced hardware complexity. We demonstrate the generation and detection of QPSK modulated with symbol rates up to 5 GBaud at carrier frequencies of 8-12 GHz through optical heterodyning of two-phase-locked lasers. The received data is demodulated through appropriate post-processing to correct for the phase noise and IQ imbalance. The approach is scalable to mmWave and THz communication.
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The paper describes the synthesis and characterization of copper oxide nanoparticles (CuO NPs) using the mixture of plant rhizome extracts Ocimum sanctum and Saussurea lappa as a reducing agent. The prepared CuO nanoparticles are characterized and confirmed their formation based on data obtained from powder X-ray diffraction spectroscopy, Fourier Transmission Infrared, Ultraviolet-Visible spectra, Field Emission Scanning Electron Microscopy images, Energy Dispersive X-ray analysis and Dynamic light scattering techniques and data reveal that the average size of CuO Nps was 103.4 nm. The result of antibacterial and antifungal activities for concentrations 50, 100, and 170 ppm indicate that NPs may exhibit appreciable activity at higher (170 ppm) concentrations. The MTT cytotoxic assay studies of Chinese Hamster Ovary (CHO) cell lines showed a Half-maximal inhibitory concentration (IC50) value of 4.14 âµg/mL.
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Improving the chances of curing patients with cancer who have had surgery to remove metastatic sites of disease is a priority area for cancer research. Pexa-Vec (Pexastimogene Devacirepvec; JX-594, TG6006) is a principally immunotherapeutic oncolytic virus that has reached late-phase clinical trials. We report the results of a single-center, nonrandomized biological end point study (trial registration: EudraCT number 2012-000704-15), which builds on the success of the presurgical intravenous delivery of oncolytic viruses to tumors. Nine patients with either colorectal cancer liver metastases or metastatic melanoma were treated with a single intravenous infusion of Pexa-Vec ahead of planned surgical resection of the metastases. Grade 3 and 4 Pexa-Vec-associated side effects were lymphopaenia and neutropaenia. Pexa-Vec was peripherally carried in plasma and was not associated with peripheral blood mononuclear cells. Upon surgical resection, Pexa-Vec was found in the majority of analyzed tumors. Pexa-Vec therapy associated with IFNα secretion, chemokine induction, and resulted in transient innate and long-lived adaptive anticancer immunity. In the 2 patients with significant and complete tumor necrosis, a reduction in the peripheral T-cell receptor diversity was observed at the time of surgery. These results support the development of presurgical oncolytic vaccinia virus-based therapies to stimulate anticancer immunity and increase the chances to cure patients with cancer.
Subject(s)
Liver Neoplasms , Oncolytic Virotherapy , Oncolytic Viruses , Humans , Leukocytes, Mononuclear , Liver Neoplasms/therapy , Neoadjuvant Therapy , Oncolytic Virotherapy/methods , Oncolytic Viruses/genetics , Vaccinia virus/geneticsABSTRACT
The total synthesis of Benzannulated macrolide, (+)-Xestodecalactone A was accomplished starting from commercially available enantiomerically pure propylene oxide and 3,5-dihydroxyphenylacetic acid using Grignard reaction, alkylation of 1,3-dithiane and Yamaguchi macrolactonisation as key steps.
Subject(s)
Lactones , Macrolides , Stereoisomerism , AlkylationABSTRACT
The plant extracts are known for their anti-inflammatory, antifungal, antiviral and antibacterial properties. The use of plant extracts in the preparation of bio-materials increases their biological application. In this concern, herein reporting an eco-friendly procedure which is also a simple and cost effective, for the synthesis of Zinc Oxide nanoparticles (ZnONPs) using Saussurea lappa plant root (rhizome) extract as a fuel. The prepared nanoparticles were confirmed using various characterization techniques. The Dynamic light scattering data showed 123.5 nm particle size with -99.9 mv zeta potential which indicates excellent stability of the particles. The peak at 541 cm-1 in the IR spectrum is assigned to the stretching frequency of the zinc-binding to oxygen. The X-ray diffraction peaks confirm the close association with JCPDS Data Card No: 36-1451. The FESEM data revealed a hexagonal wurtzite structure with a hexagonal shape of synthesized ZnO nanoparticles. The antibacterial studies indicate the gram-negative strains showed better inhibition activity than gram-positive strains. Among Fungal strains, Aspergillus niger and flavus, Fusarium oxysporum, and Rhizopus oryzae showed good inhibition activity at higher concentrations. The cytotoxic data indicates the 5 µg/mL of the ZnO particles showed cytotoxicity on the CHO cell line and with IC50 value 3.164 ± 0.8956 µg/mL.
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In view of the recent global pandemic caused by COVID-19 intense efforts have been devoted worldwide towards the development of an effective treatment for this disease. Recently, PDE4 inhibitors have been suggested to attenuate the cytokine storm in COVID-19 especially tumour necrosis factor alpha (TNF-α). In our effort we have explored the 2-substituted pyrrolo[2,3-b]quinoxalines for this purpose because of their potential inhibitory properties of PDE-4 / TNF-α. Moreover, several of these compounds appeared to be promising in silico when assessed for their binding affinities via docking into the N-terminal RNA-binding domain (NTD) of N-protein of SARS-CoV-2. A rapid and one-pot synthesis of this class of molecules was achieved via the Cu-catalyzed coupling-cyclization-desulfinylation of 3-alkynyl-2-chloroquinoxalines with t-butyl sulfinamide as the ammonia surrogate under ultrasound irradiation. Most of these compounds showed good to significant inhibition of TNF-α in vitro establishing a SAR (Structure Activity Relationship) within the series. One compound e.g. 3i was identified as a promising hit for which the desirable ADME and acceptable toxicity profile was predicted in silico.
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AIM: There is uncertainty regarding the optimal sequence of surgery for patients with colorectal cancer (CRC) and synchronous liver metastases. This study was designed to describe temporal trends and inter-hospital variation in surgical strategy, and to compare long-term survival in a propensity score-matched analysis. METHOD: The National Bowel Cancer Audit dataset was used to identify patients diagnosed with primary CRC between 1 January 2010 and 31 December 2015 who underwent CRC resection in the English National Health Service. Hospital Episode Statistics data were used to identify those with synchronous liver-limited metastases who underwent liver resection. Survival outcomes of propensity score-matched groups were compared. RESULTS: Of 1830 patients, 270 (14.8%) underwent a liver-first approach, 259 (14.2%) a simultaneous approach and 1301 (71.1%) a bowel-first approach. The proportion of patients undergoing either a liver-first or simultaneous approach increased over the study period from 26.8% in 2010 to 35.6% in 2015 (P < 0.001). There was wide variation in surgical approach according to hospital trust of diagnosis. There was no evidence of a difference in 4-year survival between the propensity score-matched cohorts according to surgical strategy: bowel first vs simultaneous [hazard ratio (HR) 0.92 (95% CI: 0.80-1.06)] or bowel first vs liver first [HR 0.99 (95% CI: 0.82-1.19)]. CONCLUSION: There is evidence of wide variation in surgical strategy in dealing with CRC and synchronous liver metastases. In selected patients, the simultaneous and liver-first strategies have comparable long-term survival to the bowel-first approach.
Subject(s)
Colorectal Neoplasms/surgery , Digestive System Surgical Procedures/methods , Hepatectomy/methods , Hospitals , Liver Neoplasms/surgery , Metastasectomy/methods , Practice Patterns, Physicians' , Aged , Colorectal Neoplasms/pathology , Female , Humans , Kaplan-Meier Estimate , Liver Neoplasms/secondary , Male , Middle Aged , Propensity Score , Radiofrequency Ablation/methods , Survival Rate , Time Factors , United KingdomABSTRACT
OBJECTIVE AND IMPORTANCE: Transplantation-mediated alloimmune thrombocytopenia (TMAT) occurs when leukocytes transferred in a donor organ from a patient with immune thrombocytopenia (ITP), mount a response against recipient platelets. We present the first fatal case of TMAT following liver transplantation and review its aetiology and treatment. CLINICAL PRESENTATION: The liver donor had ITP and died from an intracranial haemorrhage. The recipient platelet count fell to 2 × 109/l on post-operative day 2. Treatment refractory thrombocytopenia resulted in pulmonary haemorrhage and death. TMAT did not occur in a kidney recipient from the same ITP donor. INTERVENTION: Extramedullary haematopoiesis was identified in the donor liver biopsy. Antibodies against platelet GPIb/IX were demonstrated in both donor and recipient. The thrombocytopenia was refractory to platelet transfusions, intravenous immunoglobulin, methylprednisolone, rituximab, romiplostim, plasmapheresis, vincristine and splenic artery embolization. On review of the literature, severe thrombocytopenia (<10 × 109/l) has started within 3 days of transplantation in all reported TMAT cases. Serious non-fatal bleeding was observed in 3/5 previously reported cases. The optimal treatment is unclear. TMAT should resolve as donor lymphocytes are eliminated but re-transplantation may be required in severe refractory cases. TMAT has been reported in recipients of a liver but not kidney or heart transplant from ITP donors, probably because of the greater burden of co-transplanted lymphoid tissue. CONCLUSION: Before using the liver of an ITP donor, the recipient's fully informed consent is required. However, the risk of TMAT from an ITP donor is currently unknown and systematic review of donor registries is needed.
Subject(s)
Liver Transplantation/adverse effects , Purpura, Thrombocytopenic, Idiopathic/etiology , Aged , Blood Coagulation , Blood Coagulation Tests , Blood Platelets/immunology , Fatal Outcome , Humans , Immunoglobulins, Intravenous/therapeutic use , Immunosuppressive Agents/therapeutic use , Isoantibodies/immunology , Liver/pathology , Male , Platelet Count , Purpura, Thrombocytopenic, Idiopathic/blood , Purpura, Thrombocytopenic, Idiopathic/diagnosis , Purpura, Thrombocytopenic, Idiopathic/therapy , ThrombelastographyABSTRACT
INTRODUCTION: Colorectal cancer (CRC) is the third commonest malignancy after lung and breast cancer. The most common cause of mortality from CRC is from distant metastases. Obesity is a known risk factor for primary CRC development. However, its role in metastatic disease progression is not fully understood. The article aims to provide an overview of the role of obesity in colorectal liver metastases (CRLM). Furthermore, possible strategies to minimise this effect are discussed. An electronic search of MedLine, EMBASE, CINAHL and google scholar was performed. Relevant articles were included in the article. Obesity causes localised inflammation within the liver microenvironment which may predispose to metastases development. Furthermore, obesity causes systemic inflammation leading to release of protumourigenic growth factors. Several studies demonstrated the effects of lifestyle modification, medications, bariatric surgery and omega-3 fatty acids on steatosis within the context of liver surgery. It is currently unclear whether obesity directly leads to metastatic disease via chronic systemic inflammation or whether obesity induced steatosis provides a fertile microenvironment for metastases deposition. With a global increase in obesity useful strategies to minimise the effects of obesity on the liver include life-style modification, pre-operative dietary regimes and omega-3 fatty acids intake. Pre-operative optimisation of the patient is a key concept. Further randomised control trials are needed to guide management strategies.
Subject(s)
Colorectal Neoplasms/therapy , Liver Neoplasms/therapy , Obesity/complications , Colorectal Neoplasms/etiology , Colorectal Neoplasms/pathology , Disease Management , Humans , Liver Neoplasms/etiology , Liver Neoplasms/secondary , Prognosis , Risk FactorsABSTRACT
BACKGROUND: Left hepatic trisectionectomy (LHT) is a challenging major anatomical hepatectomy with a high complication rate and a worldwide experience that remains limited. The aim of this study was to describe changes in surgical practice over time, to analyse the outcomes of patients undergoing LHT for hepatobiliary malignancy, and to identify factors associated with morbidity and mortality. METHODS: A cohort study was undertaken of patients who underwent LHT at a single tertiary hepatobiliary referral centre between January 1993 and March 2013. Univariable and multivariable analysis was used to identify factors associated with short- and long-term outcomes following LHT. RESULT: Some 113 patients underwent LHT for colorectal liver metastasis (57), hilar cholangiocarcinoma (22), intrahepatic cholangiocarcinoma (12) and hepatocellular carcinoma (11); 11 patients had various other indications. Overall morbidity and 90-day mortality rates were 46.0 and 9.7 per cent respectively. Overall 1- and 3-year survival rates were 71.3 and 44.4 per cent respectively. Total hepatic vascular exclusion and intraoperative blood transfusion were independent predictors of postoperative morbidity, whereas blood transfusion was the only factor predictive of in-hospital mortality. Time period analysis revealed a decreasing trend in blood transfusion, duration of hospital stay, and postoperative morbidity and mortality in the last 5 years. CONCLUSION: Morbidity, mortality and long-term survival after LHT support its use in selected patients with a significant tumour burden.
Subject(s)
Bile Duct Neoplasms/surgery , Carcinoma, Hepatocellular/surgery , Cholangiocarcinoma/surgery , Hepatectomy/methods , Liver Neoplasms/surgery , Postoperative Complications/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Child , Female , Follow-Up Studies , Humans , Incidence , Length of Stay/trends , Male , Middle Aged , Retrospective Studies , Survival Rate/trends , Treatment Outcome , United Kingdom/epidemiology , Young AdultABSTRACT
BACKGROUND: Colorectal cancer (CRC) is a major cause of mortality and morbidity. The impact of inflammatory biomarkers (C-reactive protein etc.) on CRC is increasingly studied including systemic neutrophil-to-lymphocyte ratio (NLR) as they seem to predict outcome. METHODS: All patients who underwent curative resection for CRC from 2000 to 2004 at Leeds Teaching Hospitals NHS Trust had pre-operative NLR calculated. Demographic, histopathological and survival data were collected. Tissue microarrays were created and stained to determine the mismatch repair (MMR) protein status of each tumour. Local lymphocytic response to the tumour was assessed and graded. RESULTS: About 358 patients were eligible. Of these 88 had an NLR ⩾5, which predicted lower overall survival and greater disease recurrence. A high NLR is associated with higher pT- and pN-stage and a greater incidence of extramural venous invasion. MMR protein status was not associated with NLR. A pronounced lymphocytic reaction at the invasive margin (IM) indicated a better prognosis and was associated with a lower NLR. CONCLUSION: Neutrophil-to-lymphocyte ratio predicts disease-free and overall survival and is associated with a more aggressive tumour phenotype. The lymphocytic response to tumour at the IM is associated with NLR however dMMR is not. Neutrophil-to-lymphocyte ratio is a cheap, easy-to-access test that predicts outcome in CRC.
Subject(s)
Colorectal Neoplasms/immunology , Lymphocytes/immunology , Neutrophils/immunology , Adult , Aged , Aged, 80 and over , Colorectal Neoplasms/mortality , Colorectal Neoplasms/pathology , DNA Mismatch Repair , Female , Humans , Male , Middle AgedABSTRACT
BACKGROUND: Surgical resection of colorectal liver metastases (CRLMs) is the standard of care when possible, although this strategy has not been compared with non-operative interventions in controlled trials. Although survival outcomes are clear, the cost-effectiveness of surgery is not. This study aimed to estimate the cost-effectiveness of resection for CRLMs compared with non-operative treatment (palliative care including chemotherapy). METHODS: Operative and non-operative cohorts were identified from a prospectively maintained database. Patients in the operative cohort had a minimum of 10 years of follow-up. A model-based cost-utility analysis was conducted to quantify the mean cost and quality-adjusted life-years (QALYs) over a lifetime time horizon. The analysis was conducted from a healthcare provider perspective (UK National Health Service) in a secondary care (hospital) setting. RESULTS: Median survival was 41 and 21 months in the operative and non-operative cohorts respectively (P < 0·001). The operative strategy dominated non-operative treatments, being less costly (22,200 versus 32,800) and more effective (4·017 versus 1·111 QALYs gained). The results of extensive sensitivity analysis showed that the operative strategy dominated non-operative treatment in every scenario. CONCLUSION: Operative treatment of CRLMs yields greater survival than non-operative treatment, and is both more effective and less costly.
Subject(s)
Colorectal Neoplasms , Liver Neoplasms/economics , Aged , Antineoplastic Combined Chemotherapy Protocols/economics , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Female , Humans , Liver Neoplasms/secondary , Liver Neoplasms/therapy , Male , Markov Chains , Metastasectomy/economics , Middle Aged , Palliative Care/economics , Prospective Studies , Quality-Adjusted Life Years , Survival Analysis , Treatment OutcomeABSTRACT
BACKGROUND: The most common sites of metastasis from colorectal cancer (CRC) are hepatic and pulmonary; they can present simultaneously (hepatic and pulmonary metastases) or sequentially (hepatic then pulmonary metastases, or vice versa). Simultaneous disease may be aggressive, and thus may be approached with caution by the clinician. The aim of this study was to determine the outcomes following hepatic and pulmonary resection for simultaneously presenting metastatic CRC. METHODS: A retrospective review was undertaken of a prospectively maintained database to identify patients presenting with simultaneous hepatopulmonary disease who underwent hepatic resection. Patients' electronic records were used to identify clinicopathological variables. The log rank test was used to determine survival, and χ(2) analysis to determine predictors of failure of intended treatment. RESULTS: Fifty-nine patients were identified and underwent hepatic resection; median survival was 45·4 months and the 5-year survival rate 38 per cent. Twenty-two patients (37 per cent) did not have the intended pulmonary intervention owing to progression or recurrence of disease. Thirty-seven patients who progressed to hepatopulmonary resection had a median survival of 54·2 months (5-year survival rate 43 per cent). Those who had hepatic resection alone had a median survival of 24·0 months (5-year survival rate 30 per cent). Failure to progress to pulmonary resection was predicted by heavy nodal burden of primary colorectal disease and bilobar hepatic metastases. Redo pulmonary surgery following pulmonary recurrence did not confer a survival benefit. CONCLUSION: Selected patients with simultaneous hepatopulmonary CRC metastases should be considered for attempted curative resection, but some patients may not receive the intended treatment owing to progression of pulmonary disease after hepatic resection.
Subject(s)
Colorectal Neoplasms , Liver Neoplasms/secondary , Lung Neoplasms/secondary , Chemotherapy, Adjuvant/mortality , Female , Humans , Kaplan-Meier Estimate , Liver Neoplasms/mortality , Liver Neoplasms/surgery , Lung Neoplasms/mortality , Lung Neoplasms/surgery , Male , Metastasectomy/methods , Metastasectomy/mortality , Middle Aged , Retrospective Studies , Treatment OutcomeABSTRACT
BACKGROUND: This study was designed to determine the impact of positive margin and neoadjuvant chemotherapy (NAC) on recurrence and survival after resection of colorectal liver metastasis (CRLM). METHODS: Prospective analysis of 1,255 patients undergoing resection of CLRM was undertaken. The impact of NAC, site of recurrence, and survival between R0 and R1 groups was analysed. RESULTS: The R0 and R1 resection rates were 68.9 % (n = 865) and 31.1 % (390). The median OS for R0 group was 2.7 years (95 % CI 2.56-2.85) and R1 group 2.28 years (CI 2.06-2.52; P < 0.001). The median DFS for R0 group was 1.52 years (CI 1.38-1.66) and R1 group 1.04 years (CI 0.94-1.19; P < 0.001). The intrahepatic recurrence was higher in R1 group 132 (33.8 %) versus 142 (16.4 %) [P = 0.0001]. A total of 103 (11.9 %) patients in R0 group underwent redo liver resection for recurrence compared with 66 (16.9 %) patients in R1 group (P = 0.016). NAC did not impact recurrence rate (57.8 % vs. 61.5 %, P = 0.187) and redo liver surgery between R0 and R1 groups (13 % vs. 17 %, P = 0.092). Within the R1 group, the intrahepatic recurrence rates were similar with and without NAC (33.9 % vs. 33.7 %, P = 0.669). However, DFS was longer in the no chemotherapy group than the chemotherapy group. CONCLUSIONS: R1 resections increase the likelihood of recurrence in the liver and redo liver surgery. NAC does not seem to improve survival in margin positive patients or have an impact on recurrence or reduce need for redo liver surgery for recurrence. In patients with R1 resection, neoadjuvant chemotherapy may have adverse outcome on disease free survival.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/mortality , Hepatectomy/mortality , Liver Neoplasms/mortality , Neoadjuvant Therapy/mortality , Neoplasm Recurrence, Local/mortality , Adult , Aged , Aged, 80 and over , Colorectal Neoplasms/pathology , Colorectal Neoplasms/therapy , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Liver Neoplasms/secondary , Liver Neoplasms/therapy , Male , Middle Aged , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/therapy , Neoplasm Staging , Prognosis , Prospective Studies , Survival Rate , Young AdultABSTRACT
BACKGROUND: Lymph node (LN) status is an important predictor of survival following resection of perihilar cholangiocarcinoma (PHCCA). Controversies still exist with regard to the prognostic value of optimum extent of lymphadenectomy, total number of nodes removed, LN ratio (LNR) and neutrophil-lymphocyte ratio (NLR) on overall survival (OS) and disease-free survival (DFS) following PHCCA resection. METHODS: From 1994 to 2010, 84 PHCCAs were resected; 78 are included in this analysis. Kaplan-Meier survival curves were studied using log-rank statistics to assess which variables affected OS and DFS. The variables that showed statistical significance (P<0.05) on Kaplan-Meier univariate analysis were subjected to multivariate analysis using Cox proportional hazards model. RESULTS: Five-year OS for node-positive status (n=45) was 10%, whereas node-negative (n=33) OS was 41% (P<0.001). Similarly, 5-year DFS was worse in the node-positive group (8%) than in the node-negative group (36%, P=0.001). There was no difference in 5-year OS (31 vs. 12%, P=0.135) and DFS (22 vs. 16%, P=0.518) between those with regional lymphadenectomy and those who underwent regional plus para-aortic lymphadenectomy, respectively. On univariate analysis, patients with 20 or more LNs removed had worse 5-year OS (0%) when compared with those with less than 20 LNs removed (29%, P=0.047). Moderate/poor tumour differentiation, distant metastasis and LN involvement were independent predictors of OS. Positive LNR had no effect on OS. Vascular invasion and an LNR of at least 0.37 were independent predictors of DFS. NLR had no effect on OS and DFS. CONCLUSION: Extended lymphadenectomy patients (≥20 LNs) had worse OS when compared with those with more limited (<20 LNs) resection. An LNR of at least 0.37 is an independent predictor of DFS.
Subject(s)
Bile Duct Neoplasms/surgery , Bile Ducts, Intrahepatic , Cholangiocarcinoma/secondary , Cholangiocarcinoma/surgery , Lymph Node Excision/methods , Adult , Aged , Aged, 80 and over , Bile Duct Neoplasms/immunology , Bile Duct Neoplasms/pathology , Cholangiocarcinoma/immunology , Cholangiocarcinoma/pathology , Female , Humans , Kaplan-Meier Estimate , Leukocyte Count , Lymphatic Metastasis , Lymphocytes/pathology , Male , Middle Aged , Neoplasm Invasiveness , Neoplasm Staging , Neutrophils/pathology , Prognosis , Treatment OutcomeABSTRACT
INTRODUCTION: Sinusoidal obstructive syndrome (SOS) is well associated with the use oxaliplatin-based chemotherapy, and represents a spectrum of hepatotoxicity, with nodular regenerative hyperplasia (NRH) representing the most significant degree of injury. The aim of this study was to determine the prevalence of NRH in patients undergoing resection of colorectal liver metastases (CRLM) and to determine its impact on outcome. METHODS: From January 2000 to December 2010, some 978 first primary liver resections were performed for CRLM. A prospectively maintained database was analysed to identify all patients with evidence of NRH in the non-tumour portion of their histopathology specimens. Clinical data of these patients was reviewed and outcomes assessed. RESULTS: Five patients exhibited NRH (four males, one female) with a median age of 69 years (range: 35-74). Three patients presented with synchronous hepatic metastases, and two with metachronous lesions. All received at least 6 cycles of oxaliplatin as either adjuvant or neo-adjuvant chemotherapy. Only one patient developed a post-operative complication namely transient hepatic failure that required a 4-day stay in the intensive care unit. The median hospital stay was 6 days (range: 6-14 days). There were no 90-day mortalities. One patient is alive and disease free at 55 months, the remaining 4 died of recurrent disease between 37 and 70 months following diagnosis of their primary tumours. CONCLUSIONS: NRH is not an uncommon finding amongst patients with SOS with all patients having received oxaliplatin-based chemotherapy. Data on outcome would suggest no increased morbidity and mortality associated with the presence of NRH.
Subject(s)
Antineoplastic Agents/adverse effects , Colorectal Neoplasms/pathology , Focal Nodular Hyperplasia/chemically induced , Hepatectomy , Liver Neoplasms/secondary , Liver Neoplasms/therapy , Liver/pathology , Neoadjuvant Therapy/methods , Organoplatinum Compounds/adverse effects , Adult , Aged , Antineoplastic Agents/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemotherapy, Adjuvant , Databases, Factual , Drug Administration Schedule , Female , Hepatic Veno-Occlusive Disease/chemically induced , Humans , Liver/drug effects , Liver Neoplasms/drug therapy , Liver Neoplasms/surgery , Liver Regeneration , Magnetic Resonance Imaging , Male , Middle Aged , Organoplatinum Compounds/administration & dosage , Oxaliplatin , Prospective Studies , Retrospective StudiesABSTRACT
BACKGROUND: Half of patients with colorectal cancer develop liver metastases. There remains great variability between hospitals in rates of liver resection for colorectal cancer liver metastases (CLM). This study aimed to determine how many patients with potentially resectable CLM are not seen by specialist liver surgeons. METHODS: Patients presenting with new CLM in a cancer network consisting of a tertiary centre and seven attached hospitals were studied prospectively over 12 months. Data were collected retrospectively for patients who did not have a complete data set. Outcomes for patients referred to the liver tertiary centre were collated. The radiology of tumours deemed inoperable by the local colorectal specialist teams was reviewed by specialist liver surgeons and radiologists. RESULTS: In total, 631 patients with CLM were assessed. Prospective data were complete for 241 patients, and 64 (26.6 per cent) of these were referred to the specialist liver team for consideration of resection. No decision was documented for 16 patients (6.6 per cent). Of those not referred, 30 (18.6 per cent) were deemed unfit or refused and 131 (81.4 per cent) were thought inoperable. Referral rates varied between hospitals (13-43.6 per cent). Of 131 patients deemed fit but inoperable by the colorectal specialist teams, 38 (29.0 per cent) were deemed operable and 20 (15.3 per cent) had equivocal imaging when assessed retrospectively by liver specialists. In total, 142 of the 631 patients were referred to liver specialists for consideration of treatments, and 107 (75.4 per cent) treated with curative intent. CONCLUSION: A considerable number of patients with potentially resectable CLM are not assessed by specialist liver teams. Improved referral rates could greatly improve resection rates for CLM, which may improve outcomes for patients with colorectal cancer.
Subject(s)
Colorectal Neoplasms , Liver Neoplasms/surgery , Referral and Consultation/statistics & numerical data , Adult , Aged , Aged, 80 and over , England , Female , Humans , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/secondary , Male , Middle Aged , Patient Care Team , Prospective Studies , Radiography , Referral and Consultation/standards , Retrospective StudiesABSTRACT
AIM: The best method to teach anatomy is widely debated. A shift away from cadaveric dissection in UK medical schools towards newer approaches has taken place without adequate evaluation of their suitability. The impact of this on future anatomical and surgical competencies is unclear. We assessed student perceptions to different methods of anatomy teaching. METHODS: All 2nd year students at Leeds School of Medicine were invited to complete a matrix-grid questionnaire. Participants were asked to score six methods of anatomy teaching (dissection; prosection; lectures; models; PC software packages; living & radiological anatomy) using a 5-point Likert-type scale on the ability to achieve nine learning objectives. Kruskal-Wallis and Mann-Whitney analyses suitable for non-parametric data were used to evaluate differences in scores between teaching methods. RESULTS: 170 students (71%) responded to the survey. Overall, dissection was the single highest scored method, followed by prosection. Newer approaches such as models, computer software packages and living & radiological anatomy scored comparatively worse. The most suitable method for achieving individual learning objectives was variable with dissection perceived as most suitable for four out of nine objectives. CONCLUSIONS: Cadaveric dissection is a favourable approach for achieving important learning objectives in the field of anatomy. Further evaluation of teaching methods is required prior to changes being made in the curricula of UK medical schools.
Subject(s)
Anatomy/education , Education, Medical/trends , Students, Medical , Adolescent , Attitude of Health Personnel , Curriculum , Data Interpretation, Statistical , Female , Humans , Learning , Male , Surveys and Questionnaires , Young AdultABSTRACT
BACKGROUND: Obesity and tissue adiposity constitute a risk factor for several cancers. Whether tissue adiposity increases the risk of cancer recurrence after curative resection is not clear. The present study analysed the influence of hepatic steatosis on recurrence following resection of colorectal liver metastases. METHODS: A prospective cohort of patients who had primary resection of colorectal liver metastases in two major hepatobiliary units between 1987 and 2010 was studied. Hepatic steatosis was assessed in non-cancerous resected liver tissue. Patients were divided into two groups based on the presence of hepatic steatosis. The association between hepatic steatosis and local recurrence was analysed, adjusting for relevant patient, pathological and surgical factors using Cox regression and propensity score case-match analysis. RESULTS: A total of 2715 patients were included. The cumulative local (liver) disease-free survival rate was significantly better in the group without steatosis (hazard ratio (HR) 1·32, 95 per cent confidence interval 1·16 to 1·51; P < 0·001). On multivariable analysis, hepatic steatosis was an independent risk factor for local liver recurrence (HR 1·28, 1·11 to 1·47; P = 0·005). After one-to-one matching of cases (steatotic, 902) with controls (non-steatotic, 902), local (liver) disease-free survival remained significantly better in the group without steatosis (HR 1·27, 1·09 to 1·48; P = 0·002). Patients with steatosis had a greater risk of developing postoperative liver failure (P = 0·001). CONCLUSION: Hepatic steatosis was an independent predictor of local hepatic recurrence following resection with curative intent of colorectal liver metastases.