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INTRODUCTION In primary Crohn's disease (CD), laparoscopic ileocolic resection has been shown to be both feasible and safe, and is associated with improved outcomes in terms of postoperative morbidity and length of hospital stay. However, it is unclear whether the laparoscopic approach can be routinely proposed as a safe procedure for patients with complex enterovisceral fistulas.The aim of this study is to assess the feasibility and safety of laparoscopic surgery for complex enterovisceral fistulas, and compare it with CD patients who underwent primary laparoscopic ileocolic resection. PATIENTS AND METHODS All patients who underwent laparoscopic primary ileocolic resection (LICR) for complex enterovisceral fistulas between July 2006 and July 2017 were included. They were compared with all consecutive patients who underwent LICR for nonfistulizing CD in the same period of time. Patients with previous bowel resections or recurrent disease were excluded. RESULTS Nineteen patients with 20 enterovisceral fistulas (group I) were compared with 61 patients who underwent LICR for nonfistulizing disease (group II). There were no differences between the groups in age, sex, preoperative body mass index, nutritional status, and American Society of Anesthesiology score. There was no conversion to open surgery in both groups.There were no significant differences between groups in terms of operative time [120 (range: 65 to 232) vs. 117 (range: 62 to 217) min, P=0.7], hospital stay [6 (5 to 8) vs. 7 (5 to 65) days, P=0.56], overall morbidity 26.3% versus 16.4% (P=0.33), major morbidity (Clavien-Dindo >3) 15.7% versus 10% (P=0.66) and reoperation rates 5.3% versus 4.9% (P=0.9). There was no mortality in both groups. CONCLUSIONS Our experience shows that the laparoscopic approach for complex enterovisceral fistulas in selected CD patients is both feasible and safe in the hands of experienced inflammatory bowel disease surgeons with extensive expertise in laparoscopic surgery. Larger study cohorts are needed to confirm these findings.

Treatment of metastatic melanoma patients with adoptively transferred tumor infiltrating lymphocytes (TIL) has developed into an effective therapy. Various studies reported objective responses of 50% and more. The use of unselected, minimally cultured, bulk TIL (Young-TIL) has simplified the TIL production process and may therefore, allow the accessibility of this approach to cancer centers worldwide. This article describes the precise process leading to the large-scale production of Young-TIL for therapy. We have enrolled 55 melanoma patients and optimized their Young-TIL generation process. Young-TIL cultures were successfully established for 51 of 55 (93%) patients in 16.7 ± 5.5 days. In a large-scale expansion procedure Young-TIL of 32 patients were further expanded to treatment levels, resulting in a final number of 4.5 x 10¹⁰ ± 2.0 x 10¹⁰ TIL. Fifteen of 31 (48%) patients, who were evaluated, achieved a clinical response, including 4 complete and 11 partial responses. We confirmed the significant correlation between short culture duration, high number of infused cells, and tumor regression. A high percentage of CD8 T cells in the infusion product was beneficial to achieve an objective response. All responding patients were treated with Young-TIL cultures established in < 20 days. In summary, we describe here an efficient and reliable method to generate Young-TIL for adoptive transfer therapy, which may easily be adopted by other cancer centers and can lead to objective responses in 50% of refractory melanoma patients. In the future this approach may be used also in other types of malignancies.