Survey of the attitudes of hepatopancreatobiliary surgeons in northern Europe to resection of choledochal cysts in asymptomatic Western adults.

Background: Todani type 1 and 4 choledochal cysts are associated with a risk of developing cholangiocarcinoma. Resection is usually recommended, but data for asymptomatic Western adults are sparse. The aim of this study was to investigate diagnostic interpretation and attitudes towards resection of bile ducts for choledochal cysts in this subgroup of patients across northern European centres. Methods: Thirty hepatopancreatobiliary centres were provided with magnetic resonance cholangiopancreatograms and asked to discuss the management of six cases: asymptomatic non-Asian women, aged 30 or 60 years, with variable common bile duct (CBD) dilatations and different risk factors in the setting of a multidisciplinary team (MDT). The Fleiss κ value was calculated to estimate overall inter-rater agreement. Results: For all case scenarios combined, 83·3 and 86·7 per cent recommended resection for a CBD of 20 and 26 mm respectively, compared with 19·4 per cent for a CBD of 13 mm (P < 0·001). For patients aged 30 and 60 years, resection was recommended in 68·5 and 57·8 per cent respectively (P = 0·010). There was a trend towards recommending resection in the presence of a common channel, most pronounced in the 60-year-old patient. High amylase levels in the CBD aspirate led to recommendations to resect, but only for the 13-mm CBD dilatation. There were no differences related to centre size or region. MDT discussion was associated with recommendations to resect. Inter-rater agreement was 73·3 per cent (κ = 0·43, 95 per cent c.i. 0·38 to 0·48). Conclusion: The inter-rater agreement to resect was intermediate, and the recommendation was dependent mainly on the diameter of the CBD dilatation.

Antecedentes: Los quistes de colédoco (choledochal cysts, CC) tipo 1 y tipo 4 de Todani se asocian con un riesgo de desarrollar colangiocarcinoma. Generalmente se recomienda la resección de los mismos, pero los datos para pacientes adultos occidentales son escasos. El objetivo del presente estudio fue investigar la interpretación diagnóstica y actitudes respecto a la resección de las vías biliares por CC en este subgrupo de pacientes atendidos en centros del norte de Europa. Métodos: Se proporcionaron imágenes de colangiopancreatografía por resonancia magnética (magnetic resonance cholangiopancreatography, MRCP) a un total de 30 centros especializados en patología hepatobiliar y se les solicitó que discutieran el tratamiento de seis casos: pacientes del sexo femenino no asiáticas asintomáticas, de edad entre 30 y 60 años con dilataciones variables del colédoco (common bile duct, CBD) y con diferentes factores de riesgo en el marco de un equipo multidisciplinario (multidisciplinary team, MDT). Se calculó el índice kappa de Fleiss para estimar el acuerdo global entre los evaluadores. Resultados: Para todos los escenarios de casos combinados, un 83,3% y un 86,7% recomendaron la resección para un CBD de 20 y 26 mm, respectivamente, en comparación con un 19,4% para un CBD de 13 mm (P < 0,001). En el caso de un paciente de 30 y de 60 años, la resección se recomendó en el 68,5% y 57,8%, respectivamente (P = 0,010). Se observaron tendencias hacia recomendar la resección en presencia de un canal pancreático­biliar común, más pronunciado en el paciente de 60 años. Los niveles elevados de amilasa en el aspirado del CBD condujeron a la recomendación de resecar, pero solo en la dilatación del CBD de 13 mm. No hubo diferencias relacionadas con el tamaño del centro o la región. La discusión en el MDT se asoció con recomendaciones para la resección. El acuerdo entre evaluadores fue 73,3% con un índice kappa de 0,43 (i.c. del 95% 0,38­0,48). Conclusión: El acuerdo entre evaluadores para indicar la resección fue intermedio y la recomendación dependió principalmente del diámetro de la dilatación del CBD.

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.

Factors associated with hernia recurrence after laparoscopic total extraperitoneal repair for inguinal hernia: a 2-year prospective cohort study.

BACKGROUND: Laparoscopic total extraperitoneal repair (TEP) of inguinal hernia has been associated with higher rates of recurrence compared to open methods. The aim of the present study was to determine independent risk factors for recurrence within 2 years after TEP. METHODS: This was a single-centre prospective cohort study with consecutive inclusion of patients undergoing inguinal hernia repair from 2010 to 2014. Systematic follow-up was conducted 6 months and 2 years postoperatively. Risk factors for recurrence after 2 years were analysed in univariate and multivariate analyses. RESULTS: A total of 1194 patients underwent TEP for inguinal or femoral hernia in the study period, of which 1047 were eligible for analyses. After 2 years, 56 (5.3%) patients had presented with recurrence. The following factors were associated with recurrence in univariate analyses: body mass index (BMI) >30 (HR 3.64; p = 0.011), medial vs. lateral hernia (HR 2.37; p = 0.004), repair of recurrent hernia vs. primary repair (HR 2.12; p = 0.049), and length of stay >1 day (HR 1.77; p = 0.043). In multivariate analyses, factors independently associated with recurrence after 2 years were BMI >30 (HR 3.74; p = 0.026) and medial vs. lateral hernia (HR 2.39; p = 0.004). CONCLUSION: The recurrence rate after TEP is higher than reported after open hernia repair. Attempts to decrease the rate should be persuaded. Good surgical technique with precise dissection and correct placement of the mesh, especially in medial hernias and obese patients, may be key points to improve outcomes after TEP.

Precision surgery for colorectal liver metastases: Opportunities and challenges of omics-based decision making.

Precision surgery involves improving patient selection to ensure that surgical intervention that is proven to benefit on a population level is the optimal treatment for each individual patient. For patients with colorectal liver metastases (CRLM), existing prognostic scoring systems rely on well-recognised histopathological features such as size and number of lesions. Advances in preoperative imaging algorithms mean that increasingly low volume disease can be detected, improving assessment of these factors. In addition, novel imaging modalities mean that underlying tumour biology and metabolic behaviour during therapy can be assessed. Molecular analysis of tumours can provide crucial prognostic information, with the critical role of RAS/RAF mutations in prognosis well recognised. The optimal source of tissue for this level of analysis is debated, with good concordance between primary and metastatic lesions for some recognised prognostic factors but marked discrepancies for a variety of other relevant mutations. As well as mutational heterogeneity between primary and metastatic lesions, heterogeneity within tumours and dynamic changes in tumour biology over time present a significant challenge in assessing tumour for prognostic biomarkers. Circulating tumour cells offer one potential method of longitudinal tumour analysis, but are limited by current technologies. This review article summarises some of the key advances in prognostication for patients with resectable colorectal liver metastases, as well as highlighting the potential limitations of such an approach.

Resection of synchronous liver metastases between radiotherapy and definitive surgery for locally advanced rectal cancer: short-term surgical outcomes, overall survival and recurrence-free survival.

AIM: There is debate as to the correct treatment algorithm sequence for patients with locally advanced rectal cancer with liver metastases. The aim of the study was to assess safety, resectability and survival after a modified 'liver-first' approach. METHOD: This was a retrospective study of patients undergoing preoperative radiotherapy for the primary rectal tumour, followed by liver resection and, finally, resection of the primary tumour. Short-term surgical outcome, overall survival and recurrence-free survival are reported. RESULTS: Between 2009 and 2013, 45 patients underwent liver resection after preoperative radiotherapy. Thirty-four patients (76%) received neoadjuvant chemotherapy, 24 (53%) concomitant chemotherapy during radiotherapy and 17 (43%) adjuvant chemotherapy. The median time interval from the last fraction of radiotherapy to liver resection and rectal surgery was 21 (range 7-116) and 60 (range 31-156) days, respectively. Rectal resection was performed in 42 patients but was not performed in one patient with complete response and two with progressive metastatic disease. After rectal surgery three patients did not proceed to a planned second stage liver (n = 2) or lung (n = 1) resection due to progressive disease. Clavien-Dindo ≥Grade III complications developed in 6.7% after liver resection and 19% after rectal resection. The median overall survival and recurrence-free survival in the patients who completed the treatment sequence (n = 40) were 49.7 and 13.0 months, respectively. Twenty of the 30 patients who developed recurrence underwent further treatment with curative intent. CONCLUSION: The modified liver-first approach is safe and efficient in patients with locally advanced rectal cancer and allows initial control of both the primary tumour and the liver metastases.

Meta-analysis of KRAS mutations and survival after resection of colorectal liver metastases.

BACKGROUND: In patients with advanced colorectal cancer, KRAS mutation status predicts response to treatment with monoclonal antibody targeting the epithelial growth factor receptor (EGFR). Recent reports have provided evidence that KRAS mutation status has prognostic value in patients with resectable colorectal liver metastases (CLM) irrespective of treatment with chemotherapy or anti-EGFR therapy. A meta-analysis was undertaken to clarify the impact of KRAS mutation on outcomes in patients with resectable CLM. METHODS: PubMed, Embase and Cochrane Library databases were searched systematically to identify full-text articles reporting KRAS-stratified overall (OS) or recurrence-free (RFS) survival after resection of CLM. Hazard ratios (HRs) and 95 per cent c.i. from multivariable analyses were pooled in meta-analyses, and a random-effects model was used to calculate weight and overall results. RESULTS: The search returned 355 articles, of which 14, including 1809 patients, met the inclusion criteria. Eight studies reported OS after resection of CLM in 1181 patients. The mutation rate was 27.6 per cent, and KRAS mutation was negatively associated with OS (HR 2.24, 95 per cent c.i. 1.76 to 2.85). Seven studies reported RFS after resection of CLM in 906 patients. The mutation rate was 28.0 per cent, and KRAS mutation was negatively associated with RFS (HR 1.89, 1.54 to 2.32). CONCLUSION: KRAS mutation status is a prognostic factor in patients undergoing resection of colorectal liver metastases and should be considered in the evaluation of patients having liver resection.