The enzyme indoleamine 2,3-dioxygenase 1 (IDO1) degrade tryptophan (Trp) into kynurenine (Kyn) at the initial step of an enzymatic pathway affecting T cell proliferation. IDO1 is highly expressed in various cancer types and associated with poor prognosis. Nevertheless, the serum Kyn/Trp concentration ratio has been suggested as a marker of cancer-associated immune suppression. We measured Kyn and Trp in blood samples of a wide cohort of non-small-cell lung cancer (NSCLC) patients, before they underwent surgery, and analyzed possible correlations of the Kyn/Trp ratio with either IDO1 expression or clinical–pathological parameters. Low Kyn/Trp significantly correlated with low IDO1 expression and never-smoker patients; while high Kyn/Trp was significantly associated with older (≥68 years) patients, advanced tumor stage, and squamous cell carcinoma (Sqcc), rather than the adenocarcinoma (Adc) histotype. Moreover, high Kyn/Trp was associated, among the Adc group, with higher tumor stages (II and III), and, among the Sqcc group, with a high density of tumor-infiltrating lymphocytes. A trend correlating the high Kyn/Trp ratio with the probability of recurrences from NSCLC was also found. In conclusion, high serum Kyn/Trp ratio, associated with clinical and histopathological parameters, may serve as a serum biomarker to optimize risk stratification and therapy of NSCLC patients.

Programmed death ligand 1 (PD-L1) expression is a predictive biomarker of the success of PD-1/PD-L1 inhibitor therapy for patients with advanced non-small cell lung cancer (NSCLC) but its role as a prognostic marker for early-stage resectable NSCLC remains unclear. We studied gene expression levels of immune-related genes PD-1, PD-L1, PD-L2, IDO-1, IDO-2 and INFγ in tumor tissue of surgically resected NSCLC and correlated the finding with clinicopathological features and patient outcomes. A total of 191 consecutive early-stage NSCLC patients who underwent curative pulmonary resection were studied. The mRNA expression levels of immune-related genes were evaluated by quantitative reverse transcription polymerase chain reaction (qRT-PCR) using RT² Profiler PCR Arrays (Qiagen). PD-1, PD-L2 and IDO-2 gene expression levels were significantly higher in patients with squamous histology (p = 0.001, p = 0.021 and p < 0.001; respectively). PD-1, PD-L1 and IDO-2 gene expression levels were significantly higher in patients with higher stage (p = 0.005, p = 0.048 and p = 0.002, respectively). The univariate analysis for recurrence-free survival (RFS) and overall survival (OS) showed that patients with higher levels of three-genes (PD-L1/PD-L2/INFγ) (hazard ratio (HR)) 1.90 (95% confidence interval (CI), 1.13–3.21), p = 0.015) were associated with a worse RFS, while patients with higher levels of both genes (PD-L1/IDO-2) or (PD-L2/IDO-1) were associated with a worse OS (HR 1.63 95% CI, 1.06–2.51, p = 0.024; HR 1.54 95% CI, 1.02–2.33, p = 0.04; respectively). The multivariate interaction model adjusted for histology and stage confirmed that higher levels of three genes (PD-L1/PD-L2/INFγ) were significantly associated with worse RFS (HR 1.98, p = 0.031) and higher levels of both genes (PD-L1/IDO-2) and (PD-L2/IDO-1) with worse OS (HR 1.98, p = 0.042, HR 1.92, p = 0.022). PD-L1/IDO-2 and PD-L2/IDO-1 co-expression high levels are independent negative prognostic factors for survival in early NSCLC. These features may have important implications for future immune-checkpoint therapeutic approaches.

Background: Post-intubation tracheoesophageal fistula (PITEF) is an often mistreated, severe condition. This case series reviewed for both the choice and timing of surgical technique and outcome PITEF patients. Methods: This case series reviewed ten consecutive patients who had undergone esophageal defect repair and airway resection/reconstruction between 2000 and 2014. All cases were examined for patients: general condition, medical history, preparation to surgery, diagnostic work-up, timing of surgery and procedure, fistula size and site, ventilation type, nutrition, post-operative course and complications. Results: All patients were treated according to Grillo’s technique. Overall, 6/10 patients had undergone a preliminary period of medical preparation. Additionally, 3 patients had already had a tracheostomy, one had had a gastrostomy and 4 had both. One patient had a Dumon stent with enlargement of the fistula. Concomitant tracheal stenosis had been found in 7 patients. The mean length of the fistulas was 20.5 mm (median 17.5 mm; range, 8–45 mm), at a median distance from the glottis of 43 mm (range, 20–68 mm). Tracheal resection was performed in all ten cases. The fistula was included in the resection in 6 patients, while it was excluded in the remaining 4 due to their distance. Post-repair tracheotomy was performed in 3 patients. The procedure was performed in 2 ventilated patients. Morbidity related to fistula and anastomosis was recorded in 3 patients (30%), with one postoperative death (10%); T-Tube placement was necessary in 3 patients, with 2/3 decannulations after long-stenting. Definitive PITEF closure was obtained for all patients. At 5-year follow-up, the 9 surviving patients had no fistula-related morbidity. Conclusions: Primary esophageal closure with tracheal resection/reconstruction seemed to be effective treatment both short and long-term. Systemic conditions, mechanical ventilation, detailed preoperative assessment and appropriate preparation were associated with outcome. Indeed, the 3 patients who had received T-Tube recovered from anastomotic complications.

Lateral neck dissection (LND) leads to a significant morbidity involving accessory nerve injury. Modified radical neck dissection (MRND) aims at preservation of the accessory nerve, but patients often present with negative functional outcomes after surgery. The role of neuromonitoring (IONM) in the prevention of shoulder syndrome has not yet been defined in comparison to nerve visualization only. We retrospectively analyzed 56 thyroid cancer patients who underwent MRND over a period of six years (2015–2020) in a high-volume institution. Demographic variables, type of surgical procedure, removed lymph nodes and the metastatic node ratio, pathology, adoption of IONM and shoulder functional outcome were investigated. The mean number of lymph nodes removed was 15.61, with a metastatic node ratio of 0.2745. IONM was used in 41.07% of patients, with a prevalence of 68% in the period 2017–2020. IONM adoption showed an effect on post-operative shoulder function. There were no effects in 89.29% of cases, and temporary and permanent effects in 8.93% and 1.79%, respectively. Confidence intervals and two-sample tests for equality of proportions were used when applicable. Expertise in high-volume centres and IONM during MRND seem to be correlated with a reduced prevalence of accessory nerve lesions and limited functional impairments. These results need to be confirmed by larger prospective randomized controlled trials.