Liver resection and ablation for squamous cell carcinoma liver metastases.

BACKGROUND: Limited evidence exists to guide the management of patients with liver metastases from squamous cell carcinoma (SCC). The aim of this retrospective multicentre cohort study was to describe patterns of disease recurrence after liver resection/ablation for SCC liver metastases and factors associated with recurrence-free survival (RFS) and overall survival (OS). METHOD: Members of the European-African Hepato-Pancreato-Biliary Association were invited to include all consecutive patients undergoing liver resection/ablation for SCC liver metastases between 2002 and 2019. Patient, tumour and perioperative characteristics were analysed with regard to RFS and OS. RESULTS: Among the 102 patients included from 24 European centres, 56 patients had anal cancer, and 46 patients had SCC from other origin. RFS in patients with anal cancer and non-anal cancer was 16 and 9 months, respectively (P = 0.134). A positive resection margin significantly influenced RFS for both anal cancer and non-anal cancer liver metastases (hazard ratio 6.82, 95 per cent c.i. 2.40 to 19.35, for the entire cohort). Median survival duration and 5-year OS rate among patients with anal cancer and non-anal cancer were 50 months and 45 per cent and 21 months and 25 per cent, respectively. For the entire cohort, only non-radical resection was associated with worse overall survival (hazard ratio 3.21, 95 per cent c.i. 1.24 to 8.30). CONCLUSION: Liver resection/ablation of liver metastases from SCC can result in long-term survival. Survival was superior in treated patients with liver metastases from anal versus non-anal cancer. A negative resection margin is paramount for acceptable outcome.

Outcome of microscopically non-radical oesophagectomy for oesophageal and oesophagogastric junctional cancer: nationwide cohort study.

BACKGROUND: Microscopically non-radical (R1) oesophageal cancer resection has been associated with worse survival. The aim of this study was to identify risk factors for R1 resection and to investigate how this affects long-term survival. METHODS: The Swedish National Register for Oesophageal and Gastric Cancer was used to identify all patients who underwent oesophageal cancer resection with curative intent between 2006 and 2017. Risk factors for R1 resection were assessed by multivariable logistic regression analysis, and factors predicting 5-year survival identified by multivariable Cox regression. RESULTS: The study included 1460 patients. Surgical margins were involved microscopically in 142 patients (9.7 per cent). The circumferential resection margin was involved in 114 (7.8 per cent), the proximal margin in 53 (3.6 per cent), and the distal margin in 29 (2.0 per cent). In 30 specimens (2.1 per cent), two or all three margins were involved. Independent risk factors for R1 resection were male sex, low BMI, absence of neoadjuvant treatments, and clinical T4 disease. The 5-year survival rate for the entire cohort was 42.2 per cent, but only 18.0 per cent for those who had an R1 resection. Independent risk factors for death within 5 years of resection were male sex, age above 60 years, normal BMI, ASA fitness grade III, intermediate-level education, R1 resection (hazard ratio 1.80, 95 per cent c.i. 1.40 to 2.32), clinical T3 disease, and clinical lymph node metastasis. CONCLUSION: R1 resection is common and predicts poor 5-year survival. Absence of neoadjuvant treatment is a risk factor for R1 resection.

Reinforced versus standard stapler transection on postoperative pancreatic fistula in distal pancreatectomy: multicentre randomized clinical trial.

BACKGROUND: Postoperative pancreatic fistula is the leading cause of morbidity after distal pancreatectomy. Strategies investigated to reduce the incidence have been disappointing. Recent data showed a reduction in postoperative pancreatic fistula with the use of synthetic mesh reinforcement of the staple line. METHODS: An RCT was conducted between May 2014 and February 2016 at four tertiary referral centres in Sweden. Patients scheduled for distal pancreatectomy were eligible. Enrolled patients were randomized during surgery to stapler transection with biological reinforcement or standard stapler transection. Patients were blinded to the allocation. The primary endpoint was the development of any postoperative pancreatic fistula. Secondary endpoints included morbidity, mortality, and duration of hospital stay. RESULTS: Some 107 patients were randomized and 106 included in an intention-to-treat analysis (56 in reinforced stapling group, 50 in standard stapling group). No difference was demonstrated in terms of clinically relevant fistulas (grade B and C): 6 of 56 (11 per cent) with reinforced stapling versus 8 of 50 (16 per cent) with standard stapling (P = 0.332). There was no difference between groups in overall postoperative complications: 45 (80 per cent) and 39 (78 per cent) in reinforced and standard stapling groups respectively (P = 0.765). Duration of hospital stay was comparable: median 8 (range 2-35) and 9 (2-114) days respectively (P = 0.541). CONCLUSION: Biodegradable stapler reinforcement at the transection line of the pancreas did not reduce postoperative pancreatic fistula compared with regular stapler transection in distal pancreatectomy. Registration number: NCT02149446 (http://www.clinicaltrials.gov).

Preoperative portal vein or portal and hepatic vein embolization: DRAGON collaborative group analysis.

BACKGROUND: The extent of liver resection for tumours is limited by the expected functional reserve of the future liver remnant (FRL), so hypertrophy may be induced by portal vein embolization (PVE), taking 6 weeks or longer for growth. This study assessed the hypothesis that simultaneous embolization of portal and hepatic veins (PVE/HVE) accelerates hypertrophy and improves resectability. METHODS: All centres of the international DRAGON trials study collaborative were asked to provide data on patients who had PVE/HVE or PVE on 2016-2019 (more than 5 PVE/HVE procedures was a requirement). Liver volumetry was performed using OsiriX MD software. Multivariable analysis was performed for the endpoints of resectability rate, FLR hypertrophy and major complications using receiver operating characteristic (ROC) statistics, regression, and Kaplan-Meier analysis. RESULTS: In total, 39 patients had undergone PVE/HVE and 160 had PVE alone. The PVE/HVE group had better hypertrophy than the PVE group (59 versus 48 per cent respectively; P = 0.020) and resectability (90 versus 68 per cent; P = 0.007). Major complications (26 versus 34 per cent; P = 0.550) and 90-day mortality (3 versus 16 per cent respectively, P = 0.065) were comparable. Multivariable analysis confirmed that these effects were independent of confounders. CONCLUSION: PVE/HVE achieved better FLR hypertrophy and resectability than PVE in this collaborative experience.

Cost-effectiveness of gallbladder histopathology after cholecystectomy for benign disease.

BACKGROUND: The prevalence of incidental gallbladder cancer is low when performing cholecystectomy for benign disease. The performance of routine or selective histological examination of the gallbladder is still a subject for discussion. The aim of this study was to assess the cost-effectiveness of these different approaches. METHODS: Four management strategies were evaluated using decision-analytical modelling: no histology, current selective histology as practised in Sweden, macroscopic selective histology, and routine histology. Healthcare costs and life-years were estimated for a lifetime perspective and combined into incremental cost-effectiveness ratios (ICERs) to assess the additional cost of achieving an additional life-year for each management strategy. RESULTS: In the analysis of the four strategies, current selective histology was ruled out due to a higher ICER compared with macroscopic selective histology, which showed better health outcomes (extended dominance). Comparison of routine histology with macroscopic selective histology resulted in a gain of 12 life-years and an incremental healthcare cost of approximately €1 000 000 in a cohort of 10 000 patients, yielding an estimated ICER of €76 508. When comparing a macroscopic selective strategy with no histological assessment, 50 life-years would be saved and the ICER was estimated to be €20 708 in a cohort of 10 000 patients undergoing cholecystectomy. CONCLUSION: A macroscopic selective strategy appears to be the most cost-effective approach.

The potential for quality assurance systems to save costs and lives: the case of early infant diagnosis of HIV.

OBJECTIVES: Scaling up of point-of-care testing (POCT) for early infant diagnosis of HIV (EID) could reduce the large gap in infant testing. However, suboptimal POCT EID could have limited impact and potentially high avoidable costs. This study models the cost-effectiveness of a quality assurance system to address testing performance and screening interruptions, due to, for example, supply stockouts, in Kenya, Senegal, South Africa, Uganda and Zimbabwe, with varying HIV epidemics and different health systems. METHODS: We modelled a quality assurance system-raised EID quality from suboptimal levels: that is, from misdiagnosis rates of 5%, 10% and 20% and EID testing interruptions in months, to uninterrupted optimal performance (98.5% sensitivity, 99.9% specificity). For each country, we estimated the 1-year impact and cost-effectiveness (US$/DALY averted) of improved scenarios in averting missed HIV infections and unneeded HIV treatment costs for false-positive diagnoses. RESULTS: The modelled 1-year costs of a national POCT quality assurance system range from US$ 69 359 in South Africa to US$ 334 341 in Zimbabwe. At the country level, quality assurance systems could potentially avert between 36 and 711 missed infections (i.e. false negatives) per year and unneeded treatment costs between US$ 5808 and US$ 739 030. CONCLUSIONS: The model estimates adding effective quality assurance systems are cost-saving in four of the five countries within the first year. Starting EQA requires an initial investment but will provide a positive return on investment within five years by averting the costs of misdiagnoses and would be even more efficient if implemented across multiple applications of POCT.

OBJECTIFS: L'intensification du dépistage au point des soins (DPS) pour le diagnostic précoce du VIH chez le nourrisson (DPVN) pourrait réduire le grand écart dans le dépistage des nourrissons. Cependant, un DPVN DPS sous-optimal pourrait avoir un impact limité et des coûts évitables potentiellement élevés. Cette étude modélise la rentabilité d'un système d'assurance qualité pour traiter les performances des tests et les interruptions de dépistage, dues par exemple à des ruptures de stock, au Kenya, au Sénégal, en Afrique du Sud, en Ouganda et au Zimbabwe, avec des épidémies variables du VIH et des systèmes de santé différents. MÉTHODES: Nous avons modélisé une qualité de DPVN soulevée par le système d'assurance qualité à partir de niveaux sous-optimaux: c'est-à-dire des taux d'erreurs de diagnostic de 5%, 10% et 20% et des interruptions des tests de DPVN en mois, à des performances optimales ininterrompues (sensibilité de 98,5%, spécificité de 99,9%). Pour chaque pays, nous avons estimé l'impact sur un an et la rentabilité (en USD/DALY évitée) de scénarios améliorés pour éviter les infections à VIH manquées et les coûts inutiles de traitement du VIH pour les diagnostics faux positifs. RÉSULTATS: Les coûts modélisés sur un an d'un système national d'assurance qualité DPS vont de 69.359 USD en Afrique du Sud à 334.341 USD au Zimbabwe. Au niveau des pays, les systèmes d'assurance de la qualité pourraient potentiellement éviter entre 36 et 711 infections manquées (c'est-à-dire des faux négatifs) par an et des coûts de traitement inutiles entre 5.808 et 739.030 USD. CONCLUSIONS: Le modèle estime que l'ajout de systèmes d'assurance qualité efficaces permet de réaliser des économies dans quatre des cinq pays au cours de la première année. Le lancement de l'assurance qualité nécessite un investissement initial, mais fournira un retour sur investissement positif dans les cinq ans en évitant les coûts des diagnostics erronés et serait encore plus efficace s'il était mis en œuvre dans plusieurs applications de DPS.

Comparison of the duration of hospital stay after laparoscopic or open distal pancreatectomy: randomized controlled trial.

BACKGROUND: Studies have suggested that laparoscopic distal pancreatectomy (LDP) is advantageous compared with open distal pancreatectomy (ODP) regarding hospital stay, blood loss and recovery. Only one randomized study is available, which showed enhanced functional recovery after LDP compared with ODP. METHODS: Consecutive patients evaluated at a multidisciplinary tumour board and planned for standard distal pancreatectomy were randomized prospectively to LDP or ODP in an unblinded, parallel-group, single-centre superiority trial. The primary outcome was postoperative hospital stay. RESULTS: Of 105 screened patients, 60 were randomized and 58 (24 women, 41 per cent) were included in the intention-to-treat analysis; there were 29 patients of mean age 68 years in the LDP group and 29 of mean age 63 years in the ODP group. The main indication was cystic pancreatic lesions, followed by neuroendocrine tumours. The median postoperative hospital stay was 5 (i.q.r. 4-5) days in the laparoscopic group versus 6 (5-7) days in the open group (P = 0·002). Functional recovery was attained after a median of 4 (i.q.r. 2-6) versus 6 (4-7) days respectively (P = 0·007), and duration of surgery was 120 min in both groups (P = 0·482). Blood loss was less with laparoscopic surgery: median 50 (i.q.r. 25-150) ml versus 100 (100-300) ml in the open group (P = 0·018). No difference was found in the complication rates (Clavien-Dindo grade III or above: 4 versus 8 patients respectively). The rate of delayed gastric emptying and clinically relevant postoperative pancreatic fistula did not differ between the groups. CONCLUSION: LDP is associated with shorter hospital stay than ODP, with shorter time to functional recovery and less bleeding. Registration number: ISRCTN26912858 ( www.isrctn.com).

ANTECEDENTES: Los estudios han sugerido que la pancreatectomía distal laparoscópica (laparoscopic dital pancreatectomy, LDP) resulta ventajosa en comparación con la pancreatectomía distal por vía abierta (open distal pancreatectomy, ODP) respecto a la estancia hospitalaria, pérdida sanguínea y recuperación. Solamente existe un estudio aleatorizado que muestra una mejor recuperación funcional después de la LDP en comparación con la ODP. MÉTODOS: En un ensayo de superioridad unicéntrico, abierto y de grupos paralelos, los pacientes consecutivos evaluados por el comité multidisciplinario de tumores y a los que se indicó una pancreatectomía distal estándar fueron asignados al azar de forma prospectiva a LDP o ODP. El resultado primario fue la estancia hospitalaria postoperatoria. RESULTADOS: De 105 pacientes evaluados, 60 fueron aleatorizados, de los cuales 58 pacientes (24 mujeres; 41%) fueron incluidos y asignados a LDP (n = 29; edad media 68 años) o ODP (n = 29; edad media 63 años) e incluidos en un análisis por intención de tratamiento. La principal indicación fueron las lesiones quísticas del páncreas seguida de los tumores neuroendocrinos. La estancia hospitalaria postoperatoria fue de 5 días (rango intercuartílico, interquartile range, IQR 4-5) en el grupo laparoscópico versus 6 (5-7) días en el grupo de cirugía abierta (P = 0,002). La recuperación funcional se alcanzó después de 4 (2-6) versus 6 (4-7) días (P = 0,007), y el tiempo operatorio fue de 120 minutos en ambos grupos (P = 0.48). Las pérdidas hemáticas fueron menores en la cirugía laparoscópica, 50 (25-150) versus 100 mL (100-300) (P = 0,018). No se hallaron diferencias en las tasas de complicaciones (grado Clavien-Dindo ≥ 3) con 4 versus 8 pacientes en el grupo laparoscópico y en el grupo abierto, respectivamente. La tasa de retraso en el vaciamiento gástrico y de fístula postoperatoria clínicamente relevante no difirió entre los grupos. CONCLUSIÓN: La pancreatectomía distal laparoscópica se asocia con una estancia hospitalaria más corta en comparación con la cirugía abierta, con un menor tiempo para la recuperación funcional y menos hemorragia.

Treatment patterns and survival in patients with hepatocellular carcinoma in the Swedish national registry SweLiv.

BACKGROUND: Consistent data on clinical features, treatment modalities and long-term survival in patients with hepatocellular carcinoma (HCC) using nationwide quality registers are lacking. This study aimed to describe treatment patterns and survival outcomes in patients diagnosed with HCC using a national maintained database. METHODS: Characteristics and treatment patterns in patients diagnosed with HCC and registered in the national register of liver and bile duct tumours (SweLiv) between 2009 and 2016 were reviewed. Overall survival (OS) was estimated using Kaplan-Meier analysis and the log rank test to compare subgroups for clinical features, treatment modalities and outcomes according to the year of treatment. RESULTS: A total of 3376 patients with HCC were registered over 8 years, 246 (7·3 per cent) of whom underwent transplantation. Some 501 (14·8 per cent) and 390 patients (11·6 per cent) had resection and ablation as primary treatment. Transarterial chemoembolization and systemic sorafenib treatment were intended in 476 (14·1 per cent) and 426 patients (12·6 per cent) respectively; the remaining 1337 (39·6 per cent) were registered but referred for best supportive care (BSC). The 5-year survival rate was approximately 75 per cent in the transplantation group. Median OS was 4·6 (i.q.r. 2·0 to not reached) years after resection and 3·1 (2·3-6·7) years following ablation. In patients referred for palliative treatment, median survival was 1·4 (0·8-2·9), 0·5 (0·3-1·2) and 0·3 (0·1-1·0) years for the TACE, sorafenib and BSC groups respectively (P < 0·001). Median survival was 0·9 years for the total HCC cohort in 2009-2012, before publication of the Swedish national treatment programme, increasing to 1·4 years in 2013-2016 (P < 0·001). CONCLUSION: The survival outcomes reported were in line with previous results from smaller cohorts. The introduction of national guidelines may have contributed to improved survival among patients with HCC in Sweden.

ANTECEDENTES: Se carece datos consistentes acerca de las características clínicas, modalidades terapéuticas y supervivencia a largo plazo en pacientes con carcinoma hepatocelular (hepatocellular carcinoma, HCC) basados en registros de calidad de ámbito nacional. El objetivo de este estudio fue describir los patrones de tratamiento y los resultados de supervivencia en pacientes diagnosticados de HCC usando una base de datos nacional. MÉTODOS: Se revisaron las características de los pacientes y los patrones de tratamiento en pacientes con un diagnóstico de HCC incluidos en el registro nacional de tumores de hígado y vías biliares (SweLiv) entre 2009 y 2016. La supervivencia global (overall sirvival, OS) se analizó mediante el método de Kaplan-Meier y test de log-rank para la comparación de subgrupos según las características clínicas de los pacientes, las modalidades de tratamiento y los resultados en función del año de tratamiento. RESULTADOS: Durante un periodo de 7 años, se incluyeron en el registro un total de 3.076 pacientes con HCC, 246 de los cuales recibieron un trasplante (7,2%). Se practicó resección y ablación como tratamiento primerio en 501 (14,8%) y 390 (11,6%) pacientes, respectivamente. La quimioembolización (TACE) y el tratamiento sistémico con sorafenib se efectuó en 476 (14,1%) y 426 (12,6%) pacientes, respectivamente; los 1.337 pacientes restantes (40,0%) fueron incluidos en la base de datos pero se derivaron para recibir el mejor tratamiento de soporte. La tasa de supervivencia a los 5 años fue del 75% en el grupo trasplantado. La mediana de OS fue de 4,6 años (rango intercuartílico, interquartile range, IQR 2,0-no alcanzado) tras la resección y de 3,1 años (IQR 2,3-6,7) tras la ablación. En los pacientes derivados para tratamiento paliativo, la mediana de supervivencia fue de 1,4 años (IQR 0,8-2,9), 0,5 años (IQR 0,2-1,2) y 0,3 años (IQR 0,1-1,0) para los grupos de TACE, sorafenib y mejor tratamiento de soporte, respectivamente (P < 0,001). La mediana de supervivencia para toda la cohorte de HCC en 2009-2012 fue de 0,9 años antes de la publicación del programa de nacional de tratamiento sueco, aumentando a 1,4 años en 2013-2016 (P <0,001). CONCLUSIÓN: Los resultados de supervivencia referidos eran consistentes con resultados previos obtenidos en cohortes más pequeñas; la introducción de guías nacionales puede haber contribuido a mejorar la supervivencia de los pacientes con HCC en Suecia.

Management of incidental gallbladder cancer in a national cohort.

BACKGROUND: Incidental gallbladder cancer is a rare event, and its prognosis is largely affected by the tumour stage and treatment. The aim of this study was to analyse the management, treatment and survival of patients with incidental gallbladder cancer in a national cohort over a decade. METHODS: Patients were identified through the Swedish Registry of Gallstone Surgery (GallRiks). Data were cross-linked to the national registry for liver surgery (SweLiv) and the Cancer Registry. Medical records were collected if registry data were missing. Survival was measured as disease-specific survival. The study was divided into two intervals (2007-2011 and 2012-2016) to evaluate changes over time. RESULTS: In total, 249 patients were identified with incidental gallbladder cancer, of whom 92 (36·9 per cent) underwent re-resection with curative intent. For patients with pT2 and pT3 disease, median disease-specific survival improved after re-resection (12·4 versus 44·1 months for pT2, and 9·7 versus 23·0 months for pT3). Residual disease was present in 53 per cent of patients with pT2 tumours who underwent re-resection; these patients had a median disease-specific survival of 32·2 months, whereas the median was not reached in patients without residual disease. Median survival increased by 11 months for all patients between the early and late periods (P = 0·030). CONCLUSION: Re-resection of pT2 and pT3 incidental gallbladder cancer was associated with improved survival, but survival was impaired when residual disease was present. A higher re-resection rate and more R0 resections in the later time period may have been associated with improved survival.

Characterization of early recurrences following liver resection by ALPPS and two stage hepatectomy in patients with colorectal liver-metastases and small future liver remnants; a translational substudy of the LIGRO-RCT.

BACKGROUND: Associated liver partition and portal vein ligation in staged hepatectomy (ALPPS) is an alternative resection method to portal vein embolization (PVE) in patients with small future liver remnants (FLR) but has been associated with early tumor recurrences. METHODS: Twenty-four patients with colorectal liver metastases (CRLM) patients from the randomized multicenter LIGRO trial comparing outcome of ALPPS (n = 13) vs PVE (n = 11) were included in the study. Mutational analyses of the KRAS, NRAS, BRAF, PIC3CA and TP53 genes of the metastases were performed in 21 patients and correlated to early tumor recurrence. RESULTS: Within 12 months, 13 patients experienced recurrences (6 in TSH group and 7 in ALPPS group). Nine of 13 patients with recurrences had mutations in the TP53 gene, while 3 of 8 patients without recurrence carried the same mutation. Only sporadic cases of the other mutations studied were identified. CONCLUSIONS: ALPPS did not appear to be associated with higher rate of rapid recurrences than PVE following radical resection of colorectal liver metastases. Mutations in genes associated with negative oncologic outcome after surgical resection most likely play a role for tumor recurrences in these patients.

Identification of Inequalities in the Selection of Liver Surgery for Colorectal Liver Metastases in Sweden.

BACKGROUND:: Liver resection for colorectal liver metastases offers a 5-year survival rate of 25%-58%. This study aimed to analyze whether patients with colorectal liver metastases undergo resection to an equal extent and whether selection factors play a role in the selection process. MATERIAL AND METHODS:: Data were retrieved from the Swedish Colorectal Cancer Registry (2007-2011) for colorectal cancer and colorectal liver metastases. The patients identified were linked to the Swedish Registry of Liver and Bile surgery and the National Patient Registry to identify whether liver surgery or ablative treatment was performed. Analyses for age, sex, type of primary tumor and treating hospital (university, county, or district), American Society of Anesthesiologists class, and radiology for detection of metastatic disease were performed. RESULTS:: Of 28,355 patients with colorectal cancer, 21.6% (6127/28,355) presented with liver metastases. Of the patients with liver metastases, 18.5% (1134/6127) underwent liver resection or ablation. The cumulative proportion of liver resection/ablation was 4% (1134/28,355) of all colorectal cancer. If "not bowel resected" were excluded, the proportion slightly increased to 4.7% (1134/24,262). Around 15% of the patients with metastases were registered as referrals for liver surgery. In a multivariable analysis patients treated at a university hospital for primary tumor were more frequently surgically treated for liver metastases (p < 0.0001). Patients with liver metastases from rectal cancer (p < 0.0001) and men more often underwent liver resection (p = 0.006). A difference was found between health-care regions for the frequency of liver surgery (p < 0.0001). Patients >70 years and those with American Society of Anesthesiologists class >2 underwent liver resection less frequently. Magnetic resonance imaging of the liver was more often used in diagnostic work-up in men. CONCLUSION:: Patients with colorectal liver metastases are unequally treated in Sweden, as indicated by the low referral rate. The proximity to a hepatobiliary unit seems important to enhance the patient's chances of being offered liver surgery.

Measurements of metastatic renal cell tumours as determined by diffusion weighted imaging or computed tomography are in close agreement, a pilot study.

BACKGROUND: Diffusion weighted magnetic resonance imaging (DWI) provides both functional and anatomical information regarding tumours but can also be used for tumour detection. Today, tumour treatment response in clinical trials is mainly assessed on Computed Tomography (CT) using established criteria. Despite availability of dedicated software, CT still requires significant manual work for selection and measurement in treatment response evaluation of solid tumours. PURPOSE: To compare the maximum diameter of tumour lesions on CT with the corresponding measurements on diffusion weighted images. MATERIALS AND METHODS: In this prospective cohort, metastatic lesions were identified on CT and on DWI in five patients with metastatic renal cell carcinoma before and after three months of treatment with pazopanib. Two radiologists independently measured the same lesions on axial CT images and separately also on axial DWI images. The measurements were compared between CT and DWI with respect to the number of target lesions measured, size of the lesions, size reduction due to treatment and the inter-observer variability. Wilcoxon signed rank test, linear regression and Bland-Altman plots were used for statistical analyses. RESULTS: In this pilot study, there was no significant inter-observer variability in terms of numbers of lesion selected between CT and DWI. A significant reduction of lesion size was observed both for CT and DWI when post-treatment scans were compared to pre-treatment scans. There was no significant difference in measurement of lesion size on both pre- and post treatment scans between CT and DWI (p = 0.099 and p = 0.388 respectively). CONCLUSION: Measurement of the size of metastatic lesions on the basis of axial DWI images are in close agreement with measurement based on conventional axial CT images, the most often employed approach in clinical trials today. The results in this pilot study can be used to estimate sufficient sample size in a larger trial with adequate power, were the results can be confirmed in a wider range of cancers other than renal cell carcinoma.

Ebola virus infection induces autoimmunity against dsDNA and HSP60.

Ebola virus (EBOV) survivors are affected by a variety of serious illnesses of unknown origin for years after viral clearance from the circulation. Identifying the causes of these persistent illnesses is paramount to develop appropriate therapeutic protocols. In this study, using mouse and non-human primates which survived EBOV challenge, ELISA, western blot, mass spectrometry and flow cytometry were used to screen for autoantibodies, identify their main targets, investigate the mechanism behind their induction and monitor autoantibodies accumulation in various tissues. In infected mice and NHP, polyclonal B cell activation and autoantigens secretion induced autoantibodies against dsDNA and heat shock protein 60 as well as antibody accumulation in tissues associated with long-term clinical manifestations in humans. Finally, the presence of these autoantibodies was confirmed in human EBOV survivors. Overall, this study supports the concept that autoimmunity is a causative parameter that contributes to the various illnesses observed in EBOV survivors.

Automation for clinical CD4 T-cell enumeration, a desirable tool in the hands of skilled operators.

BACKGROUND: Automation in HIV clinical flow cytometry when appropriately applied brings considerable standardisation benefits. The Canadian Immunology Quality Assessment Program (CIQAP) detected situations where operators did not manually override automated software in the event of improper output on the Epics XL and FC500 CD4 immunophenotyping platforms. The automated gating algorithm identifies lymphocytes using a double gate strategy based on CD45 × side scatter (SS) gating and a light scatter FS × SS gate known to fail with sub optimal specimens. METHOD: To generate correct interpretation and results CIQAP introduced a simple protocol modification, bypassing the light scatter gate to include all cells characterized by the CD45 gate. Seventeen problem cases were reanalysed for both absolute and relative T-cell subsets accuracy and compared to the CIQAP group mean values. Results were found to be associated with the percentage of lymphocytes excluded by the automated light scatter gate. RESULTS: The modified manual protocol resolved poor performance in 14 instances out of 17 problem cases. It was found to improve accuracy when the light scatter gate excluded greater than 5% of the cells. The remaining three cases had a lymphocyte recovery of greater than 94.6% in the original automated analysis. CONCLUSION: There is a risk in relying solely on automated gating procedures when using the Epics XL and FC500 CD4 immunophenotyping platforms. Laboratory managers have the responsibility to intervene when required. EQA providers are equally responsible to alert the clinical laboratories of the need to update operator training to deal with stressed specimens. © 2016 International Clinical Cytometry Society.

Multivisceral Resection in Patients with Advanced Abdominal Tumors.

BACKGROUND/AIM: Multivisceral resection for advanced tumors can result in prolonged survival but may also increase the risk of postoperative morbidity and mortality. The primary aim of this study was to investigate whether extensive resections increase the severity of postoperative complications. MATERIALS AND METHODS: A retrospective study was conducted between 2009 and 2014 at the Linköping University Hospital surgical department. All patients with a confirmed or presumed malignant disease who underwent a non-standardized surgical procedure requiring a multivisceral resection were included. The primary endpoint was 90-day complications according to the Clavien-Dindo score. RESULTS: Forty-eight patients were included, with an age range of 17-77 years. A median of three organs was resected. The most common diagnoses were neuroendocrine tumor (n = 8), gastric cancer (n = 7), and gastrointestinal stromal tumor (n = 6). One patient died during surgery. Complications ⩾ grade 3b according to Clavien-Dindo score occurred in 10 patients. R0 resection was achieved in 32 patients. No correlation was observed between the number of anastomoses, perioperative blood loss, operative time, and complications. Only postoperative blood transfusion was correlated with severe complications (p = 0.046); however, a tendency toward more complications with an increasing number of resected organs was observed (p = 0.06). CONCLUSION: Multivisceral resection can result in R0, potentially curing patients with advanced tumors. Here, no correlation between extensive resections and complications was observed. Only postoperative blood transfusion was correlated with severe complications.

Associating Liver Partition and Portal Vein Ligation for Primary Hepatobiliary Malignancies and Non-Colorectal Liver Metastases.

BACKGROUND AND AIMS: Associating liver partition and portal vein ligation for staged hepatectomy may increase the possibility of radical resection in the case of liver malignancy. Concerns have been raised about the high morbidity and mortality associated with the procedure, particularly when applied for diagnoses other than colorectal liver metastases. The aim of this study was to analyze the initial experience with associating liver partition and portal vein ligation for staged hepatectomy in cases of non-colorectal liver metastases and primary hepatobiliary malignancies in Scandinavia. MATERIALS AND METHODS: A retrospective analysis of all associating liver partition and portal vein ligation for staged hepatectomy procedures performed at two Swedish university hospitals for non-colorectal liver metastases and primary hepatobiliary malignancies was performed. The primary focus was on the safety of the procedure. RESULTS AND CONCLUSION: Ten patients were included: four had hepatocellular cancer, three had intrahepatic cholangiocarcinoma, one had a Klatskin tumor, one had ocular melanoma metastasis, and one had a metastasis from a Wilms' tumor. All patients completed both operations, and the highest grade of complication (according to the Clavien-Dindo classification) was 3A, which was observed in one patient. No 90-day mortality was observed. Radical resection (R0) was achieved in nine patients, while the resection was R2 in one patient. The low morbidity and mortality observed in this cohort compared with those of earlier reports on associating liver partition and portal vein ligation for staged hepatectomy for diagnoses other than colorectal liver metastases may be related to the selection of patients with limited comorbidity. In addition, procedures other than associating liver partition and portal vein ligation for staged hepatectomy had been avoided in most of the patients. In conclusion, associating liver partition and portal vein ligation for staged hepatectomy can be applied to primary hepatobiliary malignancies and non-colorectal liver metastases with acceptable rates of morbidity and mortality.

Associating liver partition and portal vein ligation for staged hepatectomy in patients with colorectal liver metastases--Intermediate oncological results.

BACKGROUND: Colorectal liver metastases (CRLM) not amenable for resection have grave prognosis. One limiting factor for surgery is a small future liver remnant (FLR). Early data suggests that associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) effectively increases the volume of the FLR allowing for resection in a larger fraction of patients than conventional two-stage hepatectomy (TSH) with portal vein occlusion (PVO). Oncological results of the treatment are lacking. The aim of this study was to assess the intermediate oncological outcomes after ALPPS in patients with CRLM. MATERIAL AND METHODS: Retrospective analysis of all patients with CRLM operated with ALPPS at the participating centres between December 2012 and May 2014. RESULTS: Twenty-three patients (16 male, 7 female), age 67 years (28-80) were operated for 6.5 (1-38) metastases of which the largest was 40 mm (14-130). Six (27.3%) patients had extra-hepatic metastases, 16 (72.7%) synchronous presentation. All patients received chemotherapy, 6 cycles (3-25) preoperatively and 16 (70%) postoperatively. Ten patients (43%) were rescue ALPPS after failed PVO. Severe complications occurred in 13.6% and one (4.5%) patient died within 90 days of surgery. After a median follow-up of 22.5 months from surgery and 33.5 months from diagnosis of liver metastases estimated 2 year overall survival was 59% (from surgery) and 73% (from diagnosis). Liver only recurrences (n = 8), were treated with reresection/ablation (n = 7) while lung recurrences were treated with chemotherapy. CONCLUSION: The overall survival, rate of severe complications and perioperative mortality associated with ALPPS for patients with CRLM is comparable to TSH.