EGFR mutation analysis on circulating free DNA in NSCLC: a single-center experience.

PURPOSE: Monitoring mutation status in circulating free DNA (cfDNA) during target therapy could hold significant clinical importance in non-small cell lung cancer (NSCLC). Our aim is to establish if EGFR mutational status change on cfDNA has predictive value that can impact clinical management of NSCLC patients care. METHODS: This study included 30 patients with EGFR-mutated NSCLC. Blood samples were collected at diagnosis (T0) and in 19 patients during therapy (T1). RESULTS: Concordance between T0 and T1 EGFR mutation status for patients evaluable for both samples (n = 19) was 79%, with a sensitivity of 100% (95% CI: 55.5-100.0) and specificity of 60.0% (95% CI: 26.2-86.8). For the patients in oncological therapy with targeted drug and with T1 sample available (n = 18), survival outcomes were evaluated. For both mutation-negative T0 and T1 patients, 12-month progression-free survival (PFS) was 66.7% (95% CI: 27.2-100.0) and 12-month overall survival (OS) was 100% (95% CI: 1.00-1.00); for patients mutated both at T0 and T1, PFS was 22.2% (95% CI: 6.5-75.4%) and OS was 55.6% (95% CI: 20.4-96.1%). CONCLUSION: EGFR mutation status can be assessed using cfDNA for routine purposes and longitudinal assessment of plasma mutation is an easy approach to monitor the therapeutic response or resistance onset.

Contour prognostic model for predicting survival after resection of colorectal liver metastases: development and multicentre validation study using largest diameter and number of metastases with RAS mutation status.

BACKGROUND: Most current models for predicting survival after resection of colorectal liver metastasis include largest diameter and number of colorectal liver metastases as dichotomous variables, resulting in underestimation of the extent of risk variation and substantial loss of statistical power. The aim of this study was to develop and validate a new prognostic model for patients undergoing liver resection including largest diameter and number of colorectal liver metastases as continuous variables. METHODS: A prognostic model was developed using data from patients who underwent liver resection for colorectal liver metastases at MD Anderson Cancer Center and had RAS mutational data. A Cox proportional hazards model analysis was used to develop a model based on largest colorectal liver metastasis diameter and number of metastases as continuous variables. The model results were shown using contour plots, and validated externally in an international multi-institutional cohort. RESULTS: A total of 810 patients met the inclusion criteria. Largest colorectal liver metastasis diameter (hazard ratio (HR) 1.11, 95 per cent confidence interval 1.06 to 1.16; P < 0.001), number of colorectal liver metastases (HR 1.06, 1.03 to 1.09; P < 0.001), and RAS mutation status (HR 1.76, 1.42 to 2.18; P < 0.001) were significantly associated with overall survival, together with age, primary lymph node metastasis, and prehepatectomy chemotherapy. The model performed well in the external validation cohort, with predicted overall survival values almost lying within 10 per cent of observed values. Wild-type RAS was associated with better overall survival than RAS mutation even when liver resection was performed for larger and/or multiple colorectal liver metastases. CONCLUSION: The contour prognostic model, based on diameter and number of lesions considered as continuous variables along with RAS mutation, predicts overall survival after resection of colorectal liver metastasis.

Is Laparoscopic CME Right Hemicolectomy an Optimal Indication for NET of the Right Colon and Terminal Ileum?

PURPOSE: Since lymphadenectomy is crucial in midgut neuroendocrine tumor (NET) surgery, we adopted laparoscopic CME right hemicolectomy (LRH-CME) for the treatment of right colon and terminal ileum NETs. In this report, we present a series of nine cases of terminal midgut NETs (TM-NETs) treated by LRH-CME with a video demonstrating oncological principles and the surgical technique. METHODS: From September 2014 to November 2019, nine patients affected by TM-NETs underwent LRH-CME at the Unit of General and Hepatobiliary Surgery, University of Verona Hospital Trust, ENETS Center of Excellence. Clinicopathological data, post-operative and oncological outcomes were prospectively collected and analyzed. RESULTS: Tumors were in ileocecal valve or terminal ileum (5 cases), right colon (3 cases), and appendix (one case). Surgery had a curative intent (R0 resection) in 7 cases. Surgical debulking was required in 2 metastatic cases. Mean surgical time was 212 + 41 min and blood loss 47 + 24 mL. No postoperative mortality was observed. Post-operative course was uneventful in all except one case (Clavien-Dindo III). Median number of harvested lymph nodes was 21 (range, 11-31) and eight out of 9 patients were node positive (median 3, range 0-6). At a median follow-up of 18 months (range, 6-50), none of the patients suffered from mesenteric locoregional recurrence and all R0 resected patients were disease-free. CONCLUSIONS: Terminal midgut NETs represent an optimal indication for LRH-CME which increases the chance of complete resection and allows optimal lymphadenectomy. In expert hands, laparoscopic approach should be favored in consideration of good short-term outcomes.

Impact of visceral obesity and sarcobesity on surgical outcomes and recovery after laparoscopic resection for colorectal cancer.

BACKGROUND & AIMS: Studies analyzing the impact of visceral fat excess on surgical outcomes after resection for colorectal cancer (CRC) have yielded conflicting results. Visceral obesity (VO) and sarcobesity (SO) have been recently addressed as risk factors for poor short-term results while no data are available for recovery goals after surgery. No data are available on the protective effect of ERAS in VO and SO patients. The aim of this study was to assess clinical implications of computed tomography (CT) assessed VO and SO on surgical and recovery outcomes after minimally invasive resection for CRC before and after ERAS protocol implementation. METHODS: Visceral adipose tissue (VAT) and skeletal muscle area (SMA) were retrospectively assessed using pre-operative CT studies of 261 patients who underwent laparoscopic resection for CRC between January 2012 and April 2019; ERAS protocol was adopted in 160 patients operated on after March 2014. Patients' surgical and recovery outcomes were compared according to BMI categories, VO and SO which was defined using the VAT/SMA ratio (Sarcobesity Index). Predictive factors for poor surgical and recovery outcomes were evaluated by univariate and multivariate analyses. RESULTS: Of the 261 patients, 12.6% were BMI obese while 68.6% presented visceral obesity. BMI was not associated to any of the outcomes considered. No differences in intra-operative results were found except for a lower number of retrieved lymph nodes both in VO and SO patients. While VO showed no impact on post-operative course, SO resulted an independent risk factor for cardiac complications and prolonged post-operative ileus (PPOI) at logistic regression analysis. Furthermore, sarcobese patients showed delayed recovery after surgery. Patients enrolled in the ERAS protocol showed improved recovery outcomes for both VO and SO groups, although ERAS did not result to be a protective factor for cardiac complications and PPOI. CONCLUSIONS: A high Sarcobesity Index is a risk factor for developing cardiac complications and PPOI after laparoscopic resection for CRC. A reduced number of lymph nodes retrieved is associated to VO and SO. These conditions should then be considered in clinical practice for the risk of down staging the N stage. Effect of VO and SO on recovery items after surgery should be further investigated. ERAS protocol application should be implemented to improve recovery outcomes in VO and SO patients undergoing laparoscopic colorectal resection.

Multicentre evaluation of case volume in minimally invasive hepatectomy.

BACKGROUND: Surgical outcomes may be associated with hospital volume and the influence of volume on minimally invasive liver surgery (MILS) is not known. METHODS: Patients entered into the prospective registry of the Italian Group of MILS from 2014 to 2018 were considered. Only centres with an accrual period of at least 12 months and stable MILS activity during the enrolment period were included. Case volume was defined by the mean number of minimally invasive liver resections performed per month (MILS/month). RESULTS: A total of 2225 MILS operations were undertaken by 46 centres; nine centres performed more than two MILS/month (1376 patients) and 37 centres carried out two or fewer MILS/month (849 patients). The proportion of resections of anterolateral segments decreased with case volume, whereas that of major hepatectomies increased. Left lateral sectionectomies and resections of anterolateral segments had similar outcome in the two groups. Resections of posterosuperior segments and major hepatectomies had higher overall and severe morbidity rates in centres performing two or fewer MILS/month than in those undertaking a larger number (posterosuperior segments resections: overall morbidity 30·4 versus 18·7 per cent respectively, and severe morbidity 9·9 versus 4·0 per cent; left hepatectomy: 46 versus 22 per cent, and 19 versus 5 per cent; right hepatectomy: 42 versus 34 per cent, and 25 versus 15 per cent). CONCLUSION: A volume-outcome association existed for minimally invasive hepatectomy. Complex and major resections may be best managed in high-volume centres.

ANTECEDENTES: Los resultados quirúrgicos pueden estar relacionados con el volumen de casos del hospital, pero no se conoce la influencia en la cirugía mínimamente invasiva del hígado (minimally­invasive liver surgery, MILS). MÉTODOS: Se incluyeron los pacientes registrados en el registro prospectivo del grupo italiano de MILS desde 2014 a 2018. Solo se consideraron centros con extensión de ≥ 12 meses y actividad estable de MILS durante el periodo de reclutamiento. El volumen de casos se definió como el número de MILS efectuado por mes. RESULTADOS: Se llevaron a cabo un total de 2.225 MILS en 46 centros, 9 de ellos con > 2 MILS/mes (n = 1.376 pacientes) y 37 centros con ≤ 2 MILS/mes (n = 849). La proporción de resecciones de segmentos anterolaterales disminuyó con el volumen de casos, mientras que la proporción de hepatectomías mayores aumentó. Los resultados para ambos grupos fueron similares en las seccionectomías lateral izquierda y en las resecciones del segmento anterolateral. Las resecciones del segmento posterosuperior y las hepatectomías mayores presentaron tasas más altas de morbilidad global y morbilidad grave en centros que realizaban ≤ 2 MILS/mes que en los que realizaban > 2 MILS/mes (resecciones del segmento posterosuperior, morbilidad global 30,4 versus 18,7%, morbilidad grave 9,9 versus 4,0%; hepatectomía izquierda, 46,2 versus 22,0%, 19,2 versus 5,5%; hepatectomía derecha, 41,7 versus 33,8%, 25,0 versus 14.9%). CONCLUSIÓN: Se observó una asociación volumen­resultado para la resección hepática mínimamente invasiva. Las resecciones complejas y mayores se pueden manejar mejor en centros de gran volumen.

Hepatocellular carcinoma tumour burden score to stratify prognosis after resection.

BACKGROUND: Although the Barcelona Clinic Liver Cancer (BCLC) staging system has been largely adopted in clinical practice, recent studies have emphasized the need for further refinement and subclassification of this system. METHODS: Patients who underwent hepatectomy with curative intent for BCLC-0, -A or -B hepatocellular carcinoma (HCC) between 2000 and 2017 were identified using a multi-institutional database. The tumour burden score (TBS) was calculated, and overall survival (OS) was examined in relation to TBS and BCLC stage. RESULTS: Among 1053 patients, 63 (6·0 per cent) had BCLC-0, 826 (78·4 per cent) BCLC-A and 164 (15·6 per cent) had BCLC-B HCC. OS worsened incrementally with higher TBS (5-year OS 77·9, 61 and 39 per cent for low, medium and high TBS respectively; P < 0·001). No differences in OS were noted among patients with similar TBS, irrespective of BCLC stage (61·6 versus 58·9 per cent for BCLC-A/medium TBS versus BCLC-B/medium TBS, P = 0·930; 45 versus 13 per cent for BCLC-A/high TBS versus BCLC-B/high TBS, P = 0·175). Patients with BCLC-B HCC and a medium TBS had better OS than those with BCLC-A disease and a high TBS (58·9 versus 45 per cent; P = 0·005). On multivariable analysis, TBS remained associated with OS among patients with BCLC-A (medium TBS: hazard ratio (HR) 2·07, 95 per cent c.i. 1·42 to 3·02, P < 0·001; high TBS: HR 4·05, 2·40 to 6·82, P < 0·001) and BCLC-B (high TBS: HR 3·85, 2·03 to 7·30; P < 0·001) HCC. TBS could also stratify prognosis among patients in an external validation cohort (5-year OS 79, 51·2 and 28 per cent for low, medium and high TBS respectively; P = 0·010). CONCLUSION: The prognosis of patients with HCC varied according to the BCLC stage but was largely dependent on the TBS.

ANTECEDENTES: Aunque el sistema de estadificación del Barcelona Clinic Liver Cancer (BCLC) ha sido adoptado en gran medida en la práctica clínica, estudios recientes han enfatizado la necesidad de un mayor refinamiento y subclasificación del sistema BCLC. MÉTODOS: Los pacientes con carcinoma hepatocelular (hepatocellular cancer, HCC) BCLC-0, A y B que se sometieron a una hepatectomía con intención curativa entre 2000 y 2017 fueron identificados utilizando una base de datos multi-institucional. Se calculó la puntuación de carga tumoral (tumour burden score, TBS) y se examinó la supervivencia global (overall survival, OS) en relación con la TBS y los estadios BCLC. RESULTADOS: En la serie de 1.053 pacientes, 63 (6%) tenían HCC BCLC-0, 826 (78,4%) HCC BCLC-A y 164 (15,6%) HCC BCLC-B. La OS disminuyó de forma incremental en función de la mayor TBS (OS a 5 años; TBS baja: 77,9% versus TBS media: 61% versus TBS alta: 39%, P < 0,001). No se observaron diferencias en la OS entre pacientes con una puntuación TBS similar, independientemente del estadio BCLC (BCLC-A/TBS media: 61,6% versus BCLC-B/TBS media: 58,9%, P = 0,93; BCLC-A/TBS alta: 45,1% versus BCLC-B/TBS alta: 12,8%, P = 0,175). Los pacientes con BCLC-B/TBS media tuvieron una mejor OS que los pacientes con BCLC-A/TBS alta (58,9% versus 45,1%, P = 0,005). En el análisis multivariable, la TBS se mantuvo asociada a la OS en el caso de BCLC-A (TBS media: cociente de riesgos instantáneos, hazard ratio, HR = 2,07, i.c. del 95%: 1,42-3,02, P < 0,001; TBS alta: HR = 4,05, i.c. del 95%: 2,40-6,82, P < 0,001) y BCLC-B pacientes (TBS alta: HR = 3,85, i.c. del 95%: 2,03-7,30, P < 0,001). La TBS también pudo estratificar el pronóstico entre pacientes en una cohorte de validación externa (OS a 5 años; TBS baja: 78,7% versus TBS media: 51,2% versus TBS alta: 27,6%, P = 0,01). CONCLUSIÓN: El pronóstico de los pacientes con HCC varió según el estadio BCLC, pero dependió en gran medida de la TBS.

Risk-adjusted benchmarks in laparoscopic liver surgery in a national cohort.

BACKGROUND: This study aimed to assess the best achievable outcomes in laparoscopic liver resection (LLR) after risk adjustment based on surgical technical difficulty using a national registry. METHODS: LLRs registered in the Italian Group of Minimally Invasive Liver Surgery registry from November 2014 to March 2018 were considered. Benchmarks were calculated according to the Achievable Benchmark of Care (ABC™). LLRs at each centre were divided into three clusters (groups I, II and III) based on the Kawaguchi classification. ABCs for overall and major morbidity were calculated in each cluster. Multivariable analysis was used to identify independent risk factors for overall and major morbidity. Significant variables were used in further risk adjustment. RESULTS: A total of 1752 of 2263 patients fulfilled the inclusion criteria: 1096 (62·6 per cent) in group I, 435 (24·8 per cent) in group II and 221 (12·6 per cent) in group III. The ABCs for overall morbidity (7·8, 14·2 and 26·4 per cent for grades I, II and II respectively) and major morbidity (1·4, 2·2 and 5·7 per cent) increased with the difficulty of LLR. Multivariable analysis showed an increased risk of overall morbidity associated with multiple LLRs (odds ratio (OR) 1·35), simultaneous intestinal resection (OR 3·76) and cirrhosis (OR 1·83), and an increased risk of major morbidity with intestinal resection (OR 4·61). ABCs for overall and major morbidity were 14·4 and 3·2 per cent respectively for multiple LLRs, 30 and 11·1 per cent for intestinal resection, and 14·9 and 4·8 per cent for cirrhosis. CONCLUSION: Overall morbidity benchmarks for LLR ranged from 7·8 to 26·4 per cent, and those for major morbidity from 1·4 to 5·7 per cent, depending on complexity. Benchmark values should be adjusted according to multiple LLRs or simultaneous intestinal resection and cirrhosis.

ANTECEDENTES: Este estudio tuvo como objetivo evaluar los mejores resultados que se pueden conseguir en la resección hepática laparoscópica (laparoscopic liver resection, LLR) después del ajuste por riesgos basado en la dificultad de la técnica quirúrgica utilizando un registro nacional. MÉTODOS: Se consideraron las LLRs incluidas en el Registro del Grupo Italiano de Cirugía Hepática Mínimamente Invasiva desde 11/2014 a 03/2018. Los resultados de referencia (benchmarks) se calcularon de acuerdo con el Achievable Benchmark of Care (ABC™). Las LLRs de cada uno de los centros se dividieron en 3 grupos (Grupo I, II y III) en base a la clasificación de Kawaguchi. Se calculó el ABC de la morbilidad global y de la morbilidad mayor para cada grupo. Se realizó un análisis multivariable para identificar los factores independientes de riesgos para la morbilidad global y morbilidad mayor. Se utilizaron variables significativas para realizar ajustes de riesgo adicionales. RESULTADOS: Un total de 1.752 pacientes de los 2.263 cumplían los criterios de inclusión, de los cuales 1.096 (62,6%) se incluyeron en el Grupo I, 435 (24,8%) en el Grupo II y 221 (12,6%) en el Grupo III. El ABC de la morbilidad global (7,8%, 14,2%, 26,4%) y de la morbilidad mayor (1,4%, 2,2%, 5,7%) aumentó del Grupo I al Grupo III. El análisis multivariable mostró un incremento del riesgo para la morbilidad global asociada con múltiples LLRs (razón de oportunidades, odds ratio, OR 1,349), resección intestinal simultánea (OR 3,760) y cirrosis (OR 1,825), y para la morbilidad mayor con la resección intestinal (OR 4,606). Los ABC de la morbilidad global y morbilidad mayor fueron 14,4% y 3,2% para las LLR múltiples, 30% y 11% para la resección intestinal, y 14,9% y 4,8% para la cirrosis, respectivamente. CONCLUSIÓN: Los resultados de referencia (benchmark) para la morbilidad global y morbilidad mayor en la LLR variaron entre un 8% y un 26% y entre un 1,4% y un 5,7%, dependiendo de la complejidad. Los valores de referencia deberían ajustarse de acuerdo con la práctica de LLRs múltiples o resección intestinal simultánea y cirrosis.

Prognostic value of thrombocytosis in patients undergoing surgery for colorectal cancer with synchronous liver metastases.

PURPOSE: The purpose of this study was to evaluate the prognostic role of thrombocytosis in patients with synchronous colorectal liver metastases (CRLM). METHODS: Retrospective analysis of patients who underwent surgery for colorectal cancer with synchronous CRLM at the Division of General and Hepatobiliary Surgery, University of Verona Hospital Trust between 2005 and 2016. RESULTS: One hundred and ninety-six patients met the inclusion criteria. High platelet count (H-PC) was found in 32%, and it was associated with a higher rate of palliative surgery (p < 0.001), extra-hepatic metastases (p < 0.001), bilobar liver disease (p = 0.007), presence of more than three metastases (p = 0.005), biggest metastasis larger than 5 cm (p < 0.001), and CEA level higher than 200 ng/mL (p = 0.035). H-PC was significantly associated with poorer 5-year overall survival (14.3% vs. 34.3%; p = 0.001). At the multivariate analysis on R0-1 cases, platelet count resulted the only independent predictor of survival (HR 2.07, p = 0.036). CONCLUSION: H-PC correlates with the main negative clinical-pathological factors in patients with synchronous CRLM, as well as with overall survival. Moreover, it was the only independent prognostic factor in those who underwent curative surgery.

Tumour infiltrating lymphocytes and PD-L1 expression as potential predictors of outcome in patients with malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is a rare and aggressive form of tumour. Some mesotheliomas have been proven to be highly immunogenic. Here, we investigated the correlation between tumour infiltrating lymphocytes (TILs) or programmed cell death ligand 1 (PD-L1) expression with overall survival (OS) in patients with MPM. 62 Paraffin-embedded formalin fixed (PEFF) samples were analysed for TILs and PD-L1 expression. Patients were divided in 4 groups according to a cut-off of the percentage of TILs found per sample as measured by immunohistichemistry: "0" or absent (between 0 and 5%), "1" or low (between 6 and 25%), "2" or moderate (between 26 and 50%) and "3" or high (between 51 and 75%). OS was then correlated with different TILs' expression patterns. Moreover, PD-L1 expression was assessed within the tumour as well as in the adjacent stroma on the same samples. Higher expression of peritumoral TILs (Group 2 + 3) versus Group 0 and 1 correlated with improved OS (p-value = 0.02). On the contrary PD-L1 expression seemed to be inversely correlated with clinical outcomes, even in the absence of statistical significance (HR 1.76; p = 0.083 95% IC 0.92-3.36 in areas within the tumour; HR 1.60; p = 0.176 95%; IC 0.80-3.19 in areas within the stroma). No relationship between TILs and PD-L1 expression was identified. Our research supports the use of TILs and PD-L1 expression as potential outcome predictors in patients with MPM. The use of TILs and PD-L1 as biomarkers for checkpoint inhibitors' efficacy warrants future investigation.

Small bowel adenocarcinoma in a patient with a 5-year history of untreated Crohn's disease: a case report.

AIM: Complication of Crohn's disease (CD) of the small intestine is small bowel adenocarcinoma (SBA). A lot of studies on Crohn's disease have estimated the increased relative risk of small bowel carcinoma compared to the general population. In clinical settings, it is difficult to detect SBA in CD, therefore most of cases are diagnosed after surgery for strictures without suspicion of malignancy. CASE REPORT: The present case concerns a 48-year-old man with a suspicious 5-year history of untreated chronic inflammatory bowel disease. The patient was admitted to our unit with persistent abdominal pain, 20 kg weight loss and intestinal obstruction, confirmed at CT scans. It was performed an emergency laparotomy, terminal ileus was resected and intestinal continuity was restored. Histological examination revealed a poorly differentiated adenocarcinoma. DISCUSSION: The risk factors of SBA include long-standing and extensive Crohn's disease, young age, male sex, smoke, early onset, complications such as strictures and fistulas The most common clinical presentation of small bowel carcinoma in Crohn's disease is intestinal obstruction accompanied by wheight loss. The diagnosis is very difficult because imaging techniques may not be able to differentiate areas of small bowel carcinomas from benign fibrotic or acute inflammatory strictures. CONCLUSION: Small bowel adenocarcinoma is a rare disease but this evenience must be considered in patients with strictures for Crohn's disease. Preoperative diagnosis is still highly challenging despite significant radiological and endoscopic progress.

Trends in use of lymphadenectomy in surgery with curative intent for intrahepatic cholangiocarcinoma.

BACKGROUND: The role of routine lymph node dissection (LND) in the surgical treatment of intrahepatic cholangiocarcinoma (ICC) remains controversial. The objective of this study was to investigate the trends of LND use in the surgical treatment of ICC. METHODS: Patients undergoing curative intent resection for ICC in 2000-2015 were identified from an international multi-institutional database. Use of lymphadenectomy was evaluated over time and by geographical region (West versus East); LND use and final nodal status were analysed relative to AJCC T categories. RESULTS: Among the 1084 patients identified, half (535, 49·4 per cent) underwent concomitant hepatic resection and LND. Between 2000 and 2015, the proportion of patients undergoing LND for ICC nearly doubled: 44·4 per cent in 2000 versus 81·5 per cent in 2015 (P < 0·001). Use of LND increased over time among both Eastern and Western centres. The odds of LND was associated with the time period of surgery and the extent of the tumour/T status (referent T1a: OR 2·43 for T2, P = 0·001; OR 2·13 for T3, P = 0·016). Among the 535 patients who had LND, lymph node metastasis (LNM) was noted in 209 (39·1 per cent). Specifically, the incidence of LNM was 24 per cent in T1a disease, 22 per cent in T1b, 42·9 per cent in T2, 48 per cent in T3 and 66 per cent in T4 (P < 0·001). AJCC T3 and T4 categories, harvesting of six or more lymph nodes, and presence of satellite lesions were independently associated with LNM. CONCLUSION: The rate of LNM was high across all T categories, with one in five patients with T1 disease having nodal metastasis. The trend in increased use of LND suggests a growing adoption of AJCC recommendations in the treatment of ICC.

What is the most accurate lymph node staging method for perihilar cholangiocarcinoma? Comparison of UICC/AJCC pN stage, number of metastatic lymph nodes, lymph node ratio, and log odds of metastatic lymph nodes.

BACKGROUND: We compared the prognostic performance of the International Union Against Cancer/American Joint Committee on Cancer (UICC/AJCC) 7th edition pN stage, number of metastatic LNs (MLNs), LN ratio (LNR), and log odds of MLNs (LODDS) in patients with perihilar cholangiocarcinoma (PCC) undergoing curative surgery in order to identify the best LN staging method. METHODS: Ninety-nine patients who underwent surgery with curative intent for PCC in a single tertiary hepatobiliary referral center were included in the study. Two approaches were used to evaluate and compare the predictive power of the different LN staging methods: one based on the estimation of variable importance with prediction error rate and the other based on the calculation of the receiver operating characteristic (ROC) curve. RESULTS: LN dissection was performed in 92 (92.9%) patients; 49 were UICC/AJCC pN0 (49.5%), 33 pN1 (33.3%), and 10 pN2 (10.1%). The median number of LNs retrieved was 8. The prediction error rate ranged from 42.7% for LODDS to 47.1% for UICC/AJCC pN stage. Moreover, LODDS was the variable with the highest area under the ROC curve (AUC) for prediction of 3-year survival (AUC = 0.71), followed by LNR (AUC = 0.60), number of MLNs (AUC = 0.59), and UICC/AJCC pN stage (AUC = 0.54). CONCLUSIONS: The number of MLNs, LNR, and LODDS appear to better predict survival than the UICC/AJCC pN stage in patients undergoing curative surgery for PCC. Moreover, LODDS seems to be the most accurate and predictive LN staging method.

Groin Pain Syndrome Italian Consensus Conference on terminology, clinical evaluation and imaging assessment in groin pain in athlete.

The nomenclature and the lack of consensus of clinical evaluation and imaging assessment in groin pain generate significant confusion in this field. The Groin Pain Syndrome Italian Consensus Conference has been organised in order to prepare a consensus document regarding taxonomy, clinical evaluation and imaging assessment for groin pain. A 1-day Consensus Conference was organised on 5 February 2016, in Milan (Italy). 41 Italian experts with different backgrounds participated in the discussion. A consensus document previously drafted was discussed, eventually modified, and finally approved by all members of the Consensus Conference. Unanimous consensus was reached concerning: (1) taxonomy (2) clinical evaluation and (3) imaging assessment. The synthesis of these 3 points is included in this paper. The Groin Pain Syndrome Italian Consensus Conference reached a consensus on three main points concerning the groin pain syndrome assessment, in an attempt to clarify this challenging medical problem.

Role of surgery in the treatment of intrahepatic cholangiocarcinoma.

Intrahepatic Cholangiocarcinoma (ICC) is the second most common primary liver cancer, accounting for 10% to 15% of primary hepatic malignancy, and its incidence is increasing in Western Countries. Surgery with curative intent is the only treatment that offers a chance of long-term survival, with a reported 5-year overall survival rate ranging from 17% to 48%. In the most of recent series postoperative mortality is lower than 5% and morbidity varied from 6% to 66%. The macroscopic classification of ICC, proposed by Liver Cancer Study Group of Japan (LCSGJ), reflects different biologic behaviours, pattern of tumor growth and clinicopathological findings. The most important prognostic factors after resection are positive resection margins, lymph-node metastases, tumor size, presence of macrovascular invasion and intrahepatic metastases. Unfortunately, recurrence is still frequent and it is the leading cause of death. The treatment of the recurrence varied according to the location and extension of the disease. Recently, expression of several genes found to be related with the carcinogenesis of ICC. These molecular findings are helpful to differentiate the biological behaviour and will provide evidence for the development of new target therapies.

Intrahepatic, peri-hilar and distal cholangiocarcinoma: Three different locations of the same tumor or three different tumors?

BACKGROUND: Few papers deal with pathologic characteristics and outcome of the 3 different cholangiocarcinomas based on location (intrahepatic, peri-hilar, distal). There is little evidence regarding similarity and differences. PATIENTS AND METHODS: From two tertiary referral Italian Centers (in Bologna and Verona), 479 patients with cholangiocarcinoma were evaluated between 1980 and 2011. Several pathologic characteristics and their impact on survival were analyzed among resected patients for cholangiocarcinomas depending on the site of origin. RESULTS: Tumour location was intrahepatic in 172 cases (36%), peri-hilar in 243 (51) and distal in 64(13%). Curative resection was performed in 339 (70%) patients. Intrahepatic cholangiocarcinoma showed higher probability to achieve R0 resection (81%), but was more frequently associated with presence of microvascular invasion (71%). Distal cholangiocarcinoma presented less R0 resections (58%), higher lymphnode involvement (60%) and lower microvascular invasion (49%). Hilar cholangiocarcinoma had intermediate characteristics (R0: 65% of cases). Median follow up was 30.2 ± 38 months; the 5 years overall survival was 31% in the resected population. Overall survival curves were similar among the three groups. At univariate analysis surgical margins, lymphnode status, perineural invasion, T category, TNM stage, microvascular invasion, tumour grading had significant impact on survival. At multivariate analysis, only microvascular invasion was significantly related to long term results (HR = 1,7; 95% CI = 1,0-2,5)". CONCLUSION: Micro-vascular invasion has the strongest impact on survival in all three types of cholangiocarcinoma. In case of comparable pathologic characteristics and stage, the three tumors show similar outcome; depending on location, it shows a different tendency to invade bordering structures which affect the outcome.

Hepatolithiasis-associated cholangiocarcinoma: results from a multi-institutional national database on a case series of 23 patients.

AIMS: Few papers focused on association between hepatolithiasis (HL) and cholangiocarcinoma (CCC) in Western countries. The aims of this paper are to describe the clinical presentation, treatment, and postoperative outcomes of CCC with HL in a cohort of Western patients and to compare the surgical outcomes of these patients with patients with CCC without HL. MATERIALS AND METHODS: Among 161 patients with HL from five Italian tertiary hepato-biliary centers, 23 (14.3%) patients with concomitant CCC were analyzed. The results of surgery in these patients were compared with patients with CCC without HL. RESULTS: The 60.9% of patients with HL received the diagnosis of CCC intra- or postoperatively, with a resectability rate of 91.3%. The postoperative morbidity was 61.6%. The 1- and 3-year survival rates were 78.6% and 21.0%, respectively. The recurrence rate was 44.4% and the 3-year disease-free survival rates were 18.8%. The comparison with patients with CCC without HL showed a higher resectability rate (p = 0.02) and a higher frequency of earlier stage (p = 0.04) in CCC with HL. Biliary leakage was more frequent in CCC with HL group (p = 0.01) compared to CCC without HL group. We found no differences in overall and disease-free survival between the two groups. CONCLUSIONS: Patients with HL and CCC showed a high resectability rate but a higher morbidity. Nevertheless, overall and disease-free survival of patients with CCC and HL showed no differences compared to those of patients with CCC without HL. Also in Western countries, HL needs a careful management for the possible presence of CCC.

Patients attitudes towards sleep disturbances during chemotherapy.

Sleep disturbances are among the most distressing symptoms in cancer: they often co-occur with fatigue, pain and psychological distress. Despite the negative impact on quality of life, patients rarely seek help for managing their sleep disturbances. This paper presents the results of a multicentre observational study on patients' attitudes towards their sleep problems. The study also investigates symptom correlates. Patients responded to a semi-structured interview and completed the following questionnaires: Pittsburgh Sleep Quality Index; Brief Fatigue Inventory; Hospital Anxiety and Depression Scale; and European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life QLQ-C30 Questionnaire (QLQ-C30). Four hundred and three cancer patients were enrolled in the study. Bad sleepers constituted 66% of the sample. Thirty-eight per cent of them had not turned to any professional to solve their sleep disturbances because they had various beliefs about the importance of the problem and the possibility to be treated. The main correlates of sleep disturbances were psychological distress, reduced physical functioning and reduced overall quality of life. In conclusion, there is a need to sensitise patients to actively search for a solution to their sleep disturbances so they can be solved along with other co-occurring symptoms. Doctors could also be encouraged to dedicate more attention to routinely asking cancer patients about eventual sleep disturbances.

Effect of sodium hyaluronate on mucociliary clearance after functional endoscopic sinus surgery.

BACKGROUND: To determine the effect of intranasal sodium hyaluronate on mucociliary clearance time following functional endoscopic sinus surgery in patients with nasal polyposis. STUDY DESIGN: Randomized, controlled, blinded study. METHODS: Thirty-six patients with grade II nasal polyposis undergoing functional endoscopic sinus surgery received intranasal sodium hyaluronate 9 mg twice daily or saline for 30 days commencing on the second day after surgery. Ciliary mucous transport time was assessed using charcoal powder and saccharin administered during rhinoscopy. Other outcomes included changes in symptoms, endoscopic appearance of the nasal mucosa, and tolerability. RESULTS: Patients receiving sodium hyaluronate had a significantly faster mucociliary clearance time at 1 month compared with controls (14.3 +/- 2.5 vs. 23.6 +/- 3.3 minutes; p = 0.000). Furthermore, sodium hyaluronate recipients experienced a lower incidence of rhinorrhea, less nasal obstruction and a lower incidence of exudate on endoscopy than control subjects at 1 month (all p < 0.05). Sodium hyaluronate was well tolerated in patients following functional endoscopic sinus surgery. CONCLUSION: The use of intranasal sodium hyaluronate in patients undergoing functional endoscopic sinus surgery for nasal polyposis augmented the improvement in mucociliary clearance observed following this procedure and improved several clinical and endoscopic parameters. These data provide encouraging evidence of the beneficial effects of sodium hyaluronate in the care of patients undergoing functional endoscopic sinus surgery with which to continue the development of the product for this indication.