Can IDO activity predict primary resistance to anti-PD-1 treatment in NSCLC?

BACKGROUND: Immune checkpoint inhibitors have revolutionized the treatment paradigm of highly lethal malignancies like advanced non-small cell lung cancer (NSCLC), demonstrating long-term tumour control and extended patient survival. Unfortunately, only 25-30% of patients experience a durable benefit, while the vast majority demonstrate primary or acquired resistance. Recently, indoleamine 2,3-dioxygenase (IDO) activity has been proposed as a possible mechanism of resistance to anti-PD-1 treatment leading to an immunosuppressive microenvironment. METHODS: Pre-treatment serum concentrations of tryptophan (trp) and kynurenine (kyn) were measured by high-performance liquid chromatography tandem mass spectrometry in NSCLC patients treated with second-line nivolumab. The IDO activity was expressed with kyn/trp ratio. The associations between kyn/trp ratio and early progression, performance status (PS), age, sex, brain metastases, pleural effusion, progression free survival (PFS) and overall survival (OS) were analyzed using Spearman test and Mann-Whitney test. RESULTS: Twenty-six NSCLC patients were included in our study; 14 of them (54%) presented early progression (< 3 months) to nivolumab treatment. The median value of kyn/trp ratio was 0.06 µg/ml and the median value of quinolinic acid was 68.45 ng/ml. A significant correlation between early progression and higher kyn/trp ratio and quinolinic acid concentration was observed (p = 0.017 and p = 0.005, respectively). Patients presenting lower values of kyn/trp ratio and quinolinic acid levels showed longer PFS (median PFS not reached versus 3 months; HR: 0.3; p = 0.018) and OS (median OS not reached vs 3 months; HR: 0.18; p = 0.0005). CONCLUSION: IDO activity, expressed as kyn/trp ratio, is associated with response to immunotherapy; in particular, higher kyn/trp ratio could predict resistance to anti-PD-1 treatment. These preliminary results suggest the possibility of using anti-PD-1 plus IDO inhibitor in those patients with high level of kyn/trp ratio

Rectal tumor recurrence: What more may we learn?

Background: Notwithstanding real progress in the treatment of rectal cancers, local recurrence remains a challenging problem. We performed a retrospective observational study focusing on anatomo-surgical data. Methods: In our retrospective study, we adopted new morphological classifications of primary tumor downstaging, after neoadjuvant treatment, and of local recurrence of rectal cancers, mainly based on CT and MRI images. Results: Different risk factors of rectal cancer recurrence were identified: its initial advanced stage, its high histological grading, and its non-responsiveness to neoadjuvant treatment. In addition, particular anatomo-surgical points have been underlined, mainly focused on the total mesorectal excision. Conclusions: We reaffirmed the value of a correct surgical technique, although other aspects of this disease demand further research. [Arch Clin Exp Surg 2017; 6(3.000): 132-137

Rectal cancer restaging after neoadjuvant chemoradiation: towards a down-staging system

It is our policy to submit the patients affected by rectal cancer, T3 and T4, independently from N, to a neoadjuvant treatment with 50 Grays and FOLFOX chemotherapy. Surgery follows after 4–5 weeks, and it is preceded by a restaging procedure. In order to classify the down-staging of rectal tumors, we have adopted a score system (Table 1), inspired to the current TNM classification and based on imaging criteria

Acute massive pulmonary embolism during patient repositioning following excision of a thymic carcinoma in a patient affected by cryoglobulinemia

Acute pulmonary embolism (APE) is a well-described complication following surgical procedures. The incidence of such a complication can be related to the presence of a peculiar patient's condition. Cryoglobulinemia, which consists in the presence of one or more immunoglobulins in the serum that precipitate at temperatures below 37°C and redissolve on warming, seems to increase the risk of thrombotic events. Treatment options of APE, according to clinical severity, include systemic thrombolysis, surgical embolectomy, and systemic anticoagulation. Thrombolysis is considered the first-line treatment, whereas surgery is reserved in case of extremely-compromised hemodynamic conditions related to massive central embolism, and in case of contraindication to thrombolysis. Here, we report a case of acute massive pulmonary embolism occurring at the end of a surgical procedure for a thymic carcinoma resection, in a patient with cryoglobulinemia, which required an emergent surgical pulmonary embolectom

Neuropsychological outcomes after pulmonary endarterectomy using moderate hypothermia and periodic circulatory arrest

BACKGROUND: In this prospective, single-center, observational study, we investigated the association between repeated short periods of circulatory arrest with moderate hypothermia during pulmonary endarterectomy (PEA) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) and different neuropsychological dimensions. METHODS: We examined 70 patients with CTEPH, >18 to 80 years of age, who had been treated with PEA. Neuropsychological testing was performed. RESULTS: Learning ability and delayed memory remained well within the normal range for patients' age. We found a statistically significant post-surgical improvement in motor speed, which was accompanied by a better quality of life and reduced symptoms of depression and anxiety. CONCLUSION: PEA with repeated short periods of circulatory arrest in CTEPH did not result in any neuropsychological complications and may even lead to post-surgical psychological improvements