Prognostic impact of tumour-infiltrating lymphocytes and cancer-associated fibroblasts in patients with pancreatic adenocarcinoma of the body and tail undergoing resection.

BACKGROUND: The prognosis of patients with pancreatic cancer remains poor and novel therapeutic targets are required urgently. Treatment resistance could be due to the tumour microenvironment, a desmoplastic stroma consisting of cancer-associated fibroblasts and tumour-infiltrating lymphocytes (TILs). The aim of the study was to evaluate the prognostic value of TILs and cancer-associated fibroblasts (CAFs) in pancreatic cancer of the body and tail. METHODS: Using tissue microarray from resected left-sided pancreatic cancer specimens, the immunohistochemistry of TILs (cluster of differentiation (CD) 45, CD3, CD4, FoxP3 and CD8), CAFs (vimentin and α-smooth muscle actin (αSMA)) and functional markers (PD-L1 and Ki-67) was examined, and the association with disease-free (DFS) and overall (OS) survival investigated using a computer-assisted quantitative analysis. Patients were classified into two groups, with low or high levels or ratios, using the 75th percentile value as the cut-off. RESULTS: Forty-three patients were included in the study. Their median DFS and OS were 9 and 27 months respectively. A high CD4/CD3 lymphocyte ratio was associated with poorer DFS (8 months versus 11 months for a low ratio) (hazard ratio (HR) 2·23, 95 per cent c.i. 1·04 to 4·61; P = 0·041) and OS (13 versus 27 months respectively) (HR 2·62, 1·11 to 5·88; P = 0·028). A low αSMA/vimentin ratio together with a high CD4/CD3 ratio was correlated with poorer outcomes. No significant association was found between Ki-67, PD-L1 and survival. CONCLUSION: In patients with resected left-sided pancreatic cancer, a tumour microenvironment characterized by a high CD4/CD3 lymphocyte ratio along with a low αSMA/vimentin ratio is correlated with poorer survival.

ANTECEDENTES: El pronóstico del cáncer de páncreas sigue siendo malo y se requieren nuevas dianas terapéuticas de forma urgente. La resistencia al tratamiento podría ser atribuida al microambiente tumoral, un estroma desmoplásico compuesto por fibroblastos asociados al cáncer y linfocitos infiltrantes de tumor. El objetivo del estudio fue evaluar el valor pronóstico de los linfocitos infiltrantes de tumor y de los fibroblastos asociados al cáncer en el cáncer de cuerpo y cola de páncreas. MÉTODOS: Utilizando microarray para el análisis de muestras de tejido obtenidas tras la resección de cáncer de páncreas del lado izquierdo, se realizó inmunohistoquímica de linfocitos infiltrantes de tumor (CD45, CD3, CD4, FoxP3 y CD8), fibroblastos asociados al cáncer (vimentina y actina del músculo liso alfa (αSMA)) y marcadores funcionales (PD-L1 y Ki67), y se investigó la asociación con la supervivencia libre de enfermedad y la supervivencia global. Los resultados se obtuvieron tras un análisis cuantitativo asistido por ordenador. Los pacientes se clasificaron en dos grupos, de bajo y alto riesgo, utilizando el valor del percentil 75 como punto de corte. RESULTADOS: Se incluyeron 43 pacientes en el estudio. En esta población, la mediana de supervivencia libre de enfermedad y de supervivencia global fueron 9 meses y 27 meses, respectivamente. Una alta proporción de linfocitos CD4/CD3 se asoció a peor supervivencia libre de enfermedad (8 meses versus 11 meses; cociente de riesgos instantáneos, hazard ratio, HR 2,2; i.c. del 95% 1,0-4,6; P = 0,041) y supervivencia global (13 meses versus 27 meses; HR 2,6; i.c. del 95% 1,1-5,9; P = 0.028). Una baja proporción αSMA/vimentina junto con una alta proporción CD4/CD3 se correlacionó con peores resultados. No se encontró asociación significativa entre Ki67, PD-L1 y la supervivencia. CONCLUSIÓN: En pacientes con cáncer de páncreas izquierdo resecado, un microambiente tumoral caracterizado por una alta proporción de linfocitos CD4/CD3 junto con una baja proporción de αSMA/vimentina se correlaciona con una peor supervivencia.

Highlights, limitations and future challenges of laparoscopic resection for colorectal liver metastases.

The liver is the most common site for metastatic colorectal cancer (CRLM). Despite advances in oncologic treatment, resection of metastases is still the only curative option. Although laparoscopic surgery for primary colorectal cancer is well documented and widely used, laparoscopic surgery for liver metastases has developed more slowly. However, in spite of some difficulties, laparoscopic approach demonstrated strong advantages including minimal parietal damage, decreased morbidity (reduced blood loss and need for transfusion, fewer pulmonary complications), and simplification of subsequent iterative hepatectomy. Up to now, more than 9 000 laparoscopic procedures have been reported worldwide and long-term results in colorectal liver metastases seem comparable to the open approach. Only one recent randomized controlled trial has compared the laparoscopic and the open approach. The purpose of the present update was to identify the barriers limiting widespread acceptance of laparoscopic approach, the benefits and the limits of laparoscopic hepatectomies in CRLM.

Internal endoscopic drainage as first line or second line treatment in case of postsleeve gastrectomy fistulas.

BACKGROUND AND STUDY AIMS: Management of post-sleeve gastrectomy fistulas (PSGF) recently has evolved, resulting in prioritization of internal endoscopic drainage (IED). We report our experience with the technique in a tertiary center. PATIENTS AND METHODS: This was a single-center, retrospective study of 44 patients whose PSGF was managed with IED, comparing two periods: after 2013 (Group 1; n = 22) when IED was used in first line and before 2013 (Group 2; n = 22) when IED was applied in second line. Demographic data, pre-endoscopic management, characteristics of fistulas, therapeutic modalities and outcomes were recorded and compared between the two groups. The primary endpoint was IED efficacy; the secondary endpoint was a comparison of outcomes depending on the timing of IED in the management strategy. RESULTS: The groups were matched in gender (16 female, 16 male), mean age (43 years old), severity of fistula, delay before treatment, and exposure to previous endoscopic or surgical treatments. The overall efficacy rate was 84 % (37/44): 86 % in Group 1 and 82 % in Group 2 (NS). There was one death and one patient who underwent surgery. The median time to healing was 226 ±â€Š750 days (Group 1) vs. 305 ±â€Š300 days (Group 2) (NS), with a median number of endoscopies of 3 ±â€Š6 vs . 4.5 ±â€Š2.4 (NS). There were no differences in number of nasocavity drains and double pigtail stents (DPS), but significantly more metallic stents, complications, and secondary strictures were seen in Group 2. CONCLUSION: IED for management of PSGF is effective in more than 80 % of cases whenever it is used during the therapeutic strategy. This approach should be favored when possible.