Pneumonectomy for Unilateral Proximal Interruption of Pulmonary Artery: A Case Series from the Literature.

BACKGROUND: Unilateral proximal interruption of the pulmonary artery (UPIPA) is a rare congenital disease, and its optimal management remains undefined in the existing literature. The occasional necessity for pneumonectomy is still supported by limited evidence. METHODS: A systematic review of the literature was conducted using the PubMed search engine, focusing on UPIPA cases that received pneumonectomy. Thirty-one pertinent articles were selected and included in the analysis. A case reported from our institution was included in the analysis. RESULTS: We found 25 adults and seven children affected by UPIPA who received an indication for pneumonectomy, plus an additional case that was reported by our institution. Among adult patients, the predominant indication was hemoptysis (57%), followed by suspected or confirmed lung cancer (23%). Approximately 46% of surgical procedures were classified as urgent or emergent. Postoperative complications were observed in 36% of cases, with no recorded mortality. In pediatric cases, pneumonectomy was primarily a life-saving intervention, performed urgently or emergently in 75% of instances. A possible late complication in pediatric patients involves a mediastinal shift leading to respiratory distress, which may be mitigated using an inflatable prosthesis. CONCLUSIONS: Pneumonectomy achieves complete resolution of UPIPA symptoms. In the adult population, its primary indication is hemoptysis, with procedures conducted in both elective and urgent/emergent settings. Despite a mortality rate of zero, a notable proportion of patients may experience postoperative complications. In pediatric cases, the clinical presentation varies more extensively, and pneumonectomy is typically reserved for life-threatening situations, emphasizing the need for careful patient selection.

Pulmonary Lobectomy for Early-Stage Lung Cancer with Uniportal versus Three-Portal Video-Assisted Thoracic Surgery: Results from a Single-Centre Randomized Clinical Trial.

Video-assisted thoracic surgery (VATS) is a consolidated approach; however, there is no consensus on the number of ports leading to less postoperative pain. We compared early postoperative pain after uniportal and three-portal VATS lobectomy for early-stage NSCLC. In this randomized clinical trial, patients undergoing VATS lobectomy were randomly assigned to receive uniportal (U-VATS Group) or three-portal (T-VATS Group) VATS. The inclusion criteria were age ≤ 80 years and ASA < 4. The exclusion criteria were clinical T3, previous thoracic surgery, induction therapy, chest radiotherapy, connective tissue or vascular diseases, major organ failure, and analgesics or corticosteroids use. The postoperative analgesia protocol was based on NRS. Pain was measured as analgesic consumption; the secondary endpoints were intra- and postoperative complications, conversion rate, surgical time, dissected lymph nodes, hospital stay, and respiratory function. Out of 302 eligible patients, 120 were included; demographics were distributed homogeneously. The mean cumulative morphine consumption (CMC) in the U-VATS Group after 7 days was lower than in the T-VATS Group (77.4 mg vs. 90.1 mg, p = 0.003). Intraoperative variables and postoperative complications were comparable. The 30-day intercostal neuralgia rate was lower in the U-VATS Group, without reaching statistical significance. Patients undergoing U-VATS showed a lower analgesic consumption compared with the T-VATS Group; analgesic consumption was moderate in both groups.

Oncological Outcomes of Segmentectomy versus Lobectomy in Clinical Stage I Non-Small Cell Lung Cancer up to Two Centimeters: Systematic Review and Meta-Analysis.

OBJECTIVE: In recent years, pulmonary segmentectomy has emerged as an alternative to lobectomy for the treatment of patients with clinical stage I non-small cell lung cancer. Considering the conflicting results reported in the literature, the oncological effectiveness of segmentectomy remains controversial. To provide new insight into oncological results, we reviewed the literature, including recent randomized trials. METHODS: We performed a systematic review for surgical treatment of stage I NSCLC up to 2 cm using MEDLINE and the Cochrane Database from 1990 to December 2022. Primary outcomes for pooled analysis were overall and disease-free survival; secondary outcomes were postoperative complications and 30-day mortality. RESULTS: Eleven studies were considered for the meta-analysis. The pooled analysis included 3074 and 2278 patients who received lobectomy and segmentectomy, respectively. The estimated pooled hazard ratio showed a similar hazard for segmentectomy compared to lobectomy in terms of overall and disease-free survival. The restricted mean survival time difference between the two procedures was statistically and clinically not significant for overall and disease-free survival. Nevertheless, the overall survival hazard ratio was time-dependent: segmentectomy was at a disadvantage starting from 40 months after surgery. Six papers reported 30-day mortality: there were no events on 1766 procedures. The overall relative risk showed that the postoperative complication rate was higher in segmentectomy compared to lobectomy, without statistical significance. CONCLUSIONS: Our results suggest that segmentectomy might be a useful alternative to lobectomy for stage I NSCLC up to 2 cm. However, this appears to be time-dependent; in fact, the risk ratio for overall mortality becomes unfavorable for segmentectomy starting at 40 months after surgery. This last observation, together with some still undefined questions (solid/non-solid ratio, depth of the lesion, modest functional savings, etc.), leave room for further investigations on the real oncological effectiveness of segmentectomy.

A real-world experience of transition to robotic-assisted thoracic surgery (RATS) for lung resections.

Objective: We report our experience of transition to robotic-assisted thoracic surgery (RATS) for lung resections with the da Vinci Xi surgical system, exposing short-term results. Materials and methods: This is a single-center, retrospective analysis of RATS lung resections performed between April 2021 and September 2022 during our new robotic program. The surgical approach evolved over time, starting from a four-arm approach with four incisions. Alternative RATS approaches were subsequently evaluated, such as uniportal and biportal. Results: During a 17-month period, 29 lung resections were performed. Of them, 16 were lobectomies, 7 were segmentectomies, and 6 were wedge resections. The most common indication for anatomical lung resection was non-small cell lung cancer. A uniportal approach was used for two simple segmentectomies and a biportal RATS was performed in five lobectomies and two segmentectomies. A mean number of 8.1 lymph nodes and a mean of 2.6 N2 and 1.9 N1 stations were resected during surgery, and no nodal upstaging was observed. Negative resection margins were 100%. There were two (7%) conversions, one to open surgery and one to video-assisted thoracic surgery (VATS). Eight (28%) patients experienced complications with no 30-day mortality. Discussion: High-ergonomic and high-quality views were immediately observed. After some procedures, we abandoned uniportal RATS because of the possibility of arm collisions and the necessity of a VATS-skilled surgeon at the operating table. Conclusion: RATS for lung resections was safe and effective, and from the surgeon's standpoint, several practical advantages over VATS were observed. Further analysis on outcomes will help better understand the value of this technology.

Comparison Between Electronic and Traditional Chest Drainage Systems: A Multicenter Randomized Study.

BACKGROUND: Air leak is the major factor that influences the permanence of the chest tube and the in-hospital length of stay (LOS) among patients undergoing lung resections. The aim of this study was to determine whether the use of digital chest drain systems, compared with traditional ones, reduced the duration of chest drainage and postoperative in-hospital LOS in patients undergoing video-assisted thoracoscopic (VATS) lobectomy. METHODS: The study was a prospective, randomized, multicenter trial. Patients undergoing VATS lobectomy were randomized in 2 groups, receiving a digital drain system or a traditional one and managed accordingly to the protocol. RESULTS: Among 503 patients who fulfilled inclusion criteria and were randomized, 38 dropped out after randomization. Finally, 465 patients were analyzed, of whom 204 used the digital device and 261 the traditional one. In the digital group, there was a significantly shorter median chest tube duration of 3 postoperative days (interquartile range [IQR], 2-4 days) vs 4 postoperative days (IQR, 3-4 days; P = .001) and postoperative in-hospital LOS of 4 days (IQR, 3-6 days) vs 5 days (IQR, 4-6 days; P = .035). Analysis of predictors for increased duration of air leaks showed a relationship with male sex (P = .039), forced expiratory volume in 1 second percentage (P = .004), forced vital capacity percentage (P = .03), and presence of air leaks at the end of surgery (P = .001). CONCLUSIONS: In patients undergoing VATS lobectomy, the use of a digital drainage system allows an earlier removal of the chest drain compared with the traditional system, leading to a shorter in-hospital LOS.

Thymic Epithelial Tumors: An Evolving Field.

Despite their rarity, thymic epithelial tumors (TETs) have attracted much interest over the years, leading to an impressive number of histological and staging classifications. At present, TETs are divided by the WHO classification into four main subtypes: type A, type AB, and type B thymomas (subdivided into B1, B2, and B3), and thymic carcinomas, going from the more indolent to the most aggressive ones. Among many debated staging proposals, the TNM and the Masaoka-Koga staging systems have been widely accepted and used in routine practice. The four-tiered histological classification is symmetrically mirrored by the molecular subgrouping of TETs, which identifies an A-like and an AB-like cluster, with frequent GTF2I and HRAS mutations; an intermediate B-like cluster, with a T-cell signaling profile; and a carcinoma-like cluster comprising thymic carcinomas with frequent CDKN2A and TP53 alterations and a high tumor molecular burden. Molecular investigations have opened the way to tailored therapies, such as tyrosine kinase inhibitors targeting KIT, mTOR, and VEGFR, and immune-checkpoints that have been adopted as second-line systemic treatments. In this review, we discuss the crucial events that led to the current understanding of TETs, while disclosing the next steps in this intriguing field.

Approaches and outcomes of Robotic-Assisted Thoracic Surgery (RATS) for lung cancer: a narrative review.

Robotic-Assisted Thoracic Surgery (RATS) is considered one of the main issues of present thoracic surgery. RATS is a minimally invasive surgical technique allowing enhanced view, accurate and complex movements, and high ergonomics for the surgeon. Despite these advantages, its application in lung procedures has been limited, mainly by its costs. Since now many different approaches have been proposed and the experience in RATS for lungs ranges from wedge resection to pneumonectomy and is mainly related to lung cancer. The present narrative review explores main approaches and outcomes of RATS lobectomy for lung cancer. A non-systematic review of literature was conducted using the PubMed search engine. An overview of lung robotic surgery is given, and main approaches of robotic lobectomy for lung cancer are exposed. Initial experiences of biportal and uniportal RATS are also described. So far, retrospective analysis reported satisfactory robotic operative outcomes, and comparison with VATS might suggest a more accurate lymphadenectomy. Some Authors might even suggest better perioperative outcomes too. From an oncological standpoint, no definitive prospective study has yet been published but several retrospective analyses report oncological outcomes comparable to those of VATS and open surgery. Literature suggests that RATS for lung procedures is safe and effective and should be considered as a valid additional surgical option.

Improving the efficiency of identifying malignant pulmonary nodules before surgery via a combination of artificial intelligence CT image recognition and serum autoantibodies.

OBJECTIVE: To construct a new pulmonary nodule diagnostic model with high diagnostic efficiency, non-invasive and simple to measure. METHODS: This study included 424 patients with radioactive pulmonary nodules who underwent preoperative 7-autoantibody (7-AAB) panel testing, CT-based AI diagnosis, and pathological diagnosis by surgical resection. The patients were randomly divided into a training set (n = 212) and a validation set (n = 212). The nomogram was developed through forward stepwise logistic regression based on the predictive factors identified by univariate and multivariate analyses in the training set and was verified internally in the verification set. RESULTS: A diagnostic nomogram was constructed based on the statistically significant variables of age as well as CT-based AI diagnostic, 7-AAB panel, and CEA test results. In the validation set, the sensitivity, specificity, positive predictive value, and AUC were 82.29%, 90.48%, 97.24%, and 0.899 (95%[CI], 0.851-0.936), respectively. The nomogram showed significantly higher sensitivity than the 7-AAB panel test result (82.29% vs. 35.88%, p < 0.001) and CEA (82.29% vs. 18.82%, p < 0.001); it also had a significantly higher specificity than AI diagnosis (90.48% vs. 69.04%, p = 0.022). For lesions with a diameter of ≤ 2 cm, the specificity of the Nomogram was higher than that of the AI diagnostic system (90.00% vs. 67.50%, p = 0.022). CONCLUSIONS: Based on the combination of a 7-AAB panel, an AI diagnostic system, and other clinical features, our Nomogram demonstrated good diagnostic performance in distinguishing lung nodules, especially those with ≤ 2 cm diameters. KEY POINTS: • A novel diagnostic model of lung nodules was constructed by combining high-specific tumor markers with a high-sensitivity artificial intelligence diagnostic system. • The diagnostic model has good diagnostic performance in distinguishing malignant and benign pulmonary nodules, especially for nodules smaller than 2 cm. • The diagnostic model can assist the clinical decision-making of pulmonary nodules, with the advantages of high diagnostic efficiency, noninvasive, and simple measurement.

Isolation and characterization of two newly established thymoma PDXs from two relapses of the same patient: a new tool to investigate thymic malignancies.

BACKGROUND: Thymic malignancies are a heterogeneous group of rare cancers for which systemic chemotherapy is the standard treatment in the setting of advanced, recurrent or refractory diseases. Both environmental and genetic risk factors have not been fully clarified and few target-specific drugs have been developed for thymic epithelial tumors. A major challenge in studying thymic epithelial tumors is the lack of preclinical models for translational studies. MAIN BODY: Starting from bioptic material of two consecutive recurrences of the same patient, we generated two patient-derived xenografts. The patient-derived xenografts models were characterized for histology by immunohistochemistry and mutations using next-generation sequencing. When compared to the original tumors resected from the patient, the two patient-derived xenografts had preserved morphology after the stain with hematoxylin and eosin, although there was a moderate degree of de-differentiation. From a molecular point of view, the two patient-derived xenografts maintained 74.3 and 61.8% of the mutations present in the human tumor of origin. SHORT CONCLUSION: The newly generated patient-derived xenografts recapitulate both the molecular characteristics and the evolution of the thymoma it derives from well, allowing to address open questions for this rare cancer.

Prediction of Ablation Volume in Percutaneous Lung Microwave Ablation: A Single Centre Retrospective Study.

BACKGROUND: Percutaneous Microwave Ablation (MWA) of lung malignancies is a procedure with many technical challenges, among them the risk of residual disease. Recently, dedicated software able to predict the volume of the ablated area was introduced. Cone-beam computed tomography (CBCT) is the imaging guidance of choice for pulmonary ablation in our institution. The volumetric prediction software (VPS) has been installed and used in combination with CBCT to check the correct position of the device. Our study aimed to compare the results of MWA of pulmonary tumours performed using CBCT with and without VPS. METHODS: We retrospectively reviewed 1-month follow-up enhanced contrast-enhanced computed tomography (CECT) scans of 10 patients who underwent ablation with the assistance of VPS (group 1) and of 10 patients who were treated without the assistance of VPS (group 2). All patients were treated for curative purposes, the maximum axial diameter of lesions ranged between 5 and 22 mm in group 1 and between 5 and 25 mm in group 2. We compared the presence of residual disease between the two groups. RESULTS: In group 1 residual disease was seen in only 1 patient (10%) in which VPS had ensured complete coverage of the tumour. In group 2 residual disease was found in 3 patients (30%). CONCLUSIONS: Using this software during MWA of lung malignancies could improve the efficacy of the treatment compared to the conventional only CBCT guidance.

LKB1: Can We Target an Hidden Target? Focus on NSCLC.

LKB1 (liver kinase B1) is a master regulator of several processes such as metabolism, proliferation, cell polarity and immunity. About one third of non-small cell lung cancers (NSCLCs) present LKB1 alterations, which almost invariably lead to protein loss, resulting in the absence of a potential druggable target. In addition, LKB1-null tumors are very aggressive and resistant to chemotherapy, targeted therapies and immune checkpoint inhibitors (ICIs). In this review, we report and comment strategies that exploit peculiar co-vulnerabilities to effectively treat this subgroup of NSCLCs. LKB1 loss leads to an enhanced metabolic avidity, and treatments inducing metabolic stress were successful in inhibiting tumor growth in several preclinical models. Biguanides, by compromising mitochondria and reducing systemic glucose availability, and the glutaminase inhibitor telaglenastat (CB-839), inhibiting glutamate production and reducing carbon intermediates essential for TCA cycle progression, have provided the most interesting results and entered different clinical trials enrolling also LKB1-null NSCLC patients. Nutrient deprivation has been investigated as an alternative therapeutic intervention, giving rise to interesting results exploitable to design specific dietetic regimens able to counteract cancer progression. Other strategies aimed at targeting LKB1-null NSCLCs exploit its pivotal role in modulating cell proliferation and cell invasion. Several inhibitors of LKB1 downstream proteins, such as mTOR, MEK, ERK and SRK/FAK, resulted specifically active on LKB1-mutated preclinical models and, being molecules already in clinical experimentation, could be soon proposed as a specific therapy for these patients. In particular, the rational use in combination of these inhibitors represents a very promising strategy to prevent the activation of collateral pathways and possibly avoid the potential emergence of resistance to these drugs. LKB1-null phenotype has been correlated to ICIs resistance but several studies have already proposed the mechanisms involved and potential interventions. Interestingly, emerging data highlighted that LKB1 alterations represent positive determinants to the new KRAS specific inhibitors response in KRAS co-mutated NSCLCs. In conclusion, the absence of the target did not block the development of treatments able to hit LKB1-mutated NSCLCs acting on several fronts. This will give patients a concrete chance to finally benefit from an effective therapy.

Outcomes of extended surgical resections for locally advanced thymic malignancies: a narrative review.

Background and Objective: Thymic malignancies represent the most common anterior mediastinal neoplasms, as well as rare and challenging tumors. Surgery is the cornerstone in the treatment of thymic malignancies, although a multidisciplinary approach is mandatory, for both, locally advanced or metastatic disease. In our narrative review, we explored the recent literature to investigate clinical and radiological assessment, multimodality approach and outcomes of locally advanced thymic tumors. More than one-third of patients affected by an anterior mediastinal mass are asymptomatic at diagnosis. In case of locally advanced thymoma, symptoms are related to compression or invasion of adjacent structures, such as the superior vena cava (SVC), innominate veins and pericardium. Paraneoplastic syndromes, such as myasthenia gravis (MG), are related to release of antibodies, hormones and cytokines. Methods: Diagnostic methods must be chosen accurately to avoid unnecessary surgical resections, to define the best strategy of care, and to plan the surgical strategy. Therefore, each case must be evaluated in a multidisciplinary context, where surgery plays an essential role. Key Content and Findings: In this narrative review, we describe indications and surgical techniques for the treatment of locally advanced thymoma; focusing on oncological outcomes after different approaches. Conclusions: In conclusion, aggressive surgery is always indicated, when possible, and when a complete resection can be planned, yet, the multidisciplinary approach is mandatory, in case of both locally or metastatic advanced disease.

CT after Lung Microwave Ablation: Normal Findings and Evolution Patterns of Treated Lesions.

Imaging-guided percutaneous ablative treatments, such as radiofrequency ablation (RFA), cryoablation and microwave ablation (MWA), have been developed for the treatment of unresectable primary and secondary lung tumors in patients with advanced-stage disease or comorbidities contraindicating surgery. Among these therapies, MWA has recently shown promising results in the treatment of pulmonary neoplasms. The potential advantages of MWA over RFA include faster ablation times, higher intra-tumoral temperatures, larger ablation zones and lower susceptibility to the heat sink effect, resulting in greater efficacy in proximity to vascular structures. Despite encouraging results supporting its efficacy, there is a relative paucity of data in the literature regarding the role of computer tomography (CT) to monitor MWA-treated lesions, and the CT appearance of their morphologic evolution and complications. For both interventional and non-interventional radiologists, it is crucial to be familiar with the CT features of such treated lesions in order to detect incomplete therapy or recurrent disease at early stage, as well as to recognize initial signs of complications. The aim of this pictorial essay is to describe the typical CT features during follow-up of lung lesions treated with percutaneous MWA and how to interpret and differentiate them from other radiological findings, such as recurrence and complications, that are commonly encountered in this setting.

Surgical resection of Masaoka stage III thymic epithelial tumours with great vessels involvement: a retrospective multicentric analysis from the European Society of Thoracic Surgeons thymic database.

OBJECTIVES: The aim of this study was to analyse the outcomes of an international cohort of patients affected by Masaoka stage III thymic epithelial tumours with vascular involvement and treated by surgery. METHODS: Study design was the observational multicentre retrospective cohort study. Data were extracted from the European Society of Thoracic Surgeons thymic database; additional variables were collected. Inclusion criteria were as follows: stage III (Masaoka-Koga) thymic epithelial tumours; surgery with radical intention; clinical or pathological great vessels involvement; and radiologically suspected or diagnosed intraoperatively. Outcome items were analysed. RESULTS: Sixty-five patients submitted to surgery from 2001 to 2017 fulfilled inclusion criteria. Thymoma and thymic carcinoma patients did not differ for demographics and clinical characteristics. The majority of great vessel treated were superior vena cava or innominate veins (72.3%). Eleven patients (16.9%) had postoperative cardiopulmonary complications; vascular stenosis was observed in 3 patients (4.6%). The multivariable Cox analysis for disease-free survival showed an increased hazard of recurrence for thymic carcinoma (hazard ratio = 3.59; 95% confidence interval: 1.66-7.78, P = 0.001). The 1-, 3-, 5- and 10-year overall survival rates were 0.86, 0.84, 0.81, and 0.53, respectively. There was no significant difference in overall survival according to resection status or between thymoma and thimic carcinoma. The univariable Cox regression model did not show an increased hazard of death for myasthenic patients considering all resection status and for patients who received neoadjuvant therapy. CONCLUSIONS: We observed that clinical outcomes of patients treated for stage III thymic epithelial tumours with vascular involvement are satisfactory suggesting to increase the confidence in dealing with these complex surgeries. Complete resection should be achieved, even though extensive vascular reconstructions are required.

Lobar size reduction in lung transplantation: A propensity score study.

OBJECTIVE: For small-sized recipients of lung transplantation, the time span for organ reception from standard donors is generally longer than for normal-sized patients. Despite its underuse, lobar reduction may be a concrete option for these patients. This study aims to assess early and long-term outcomes associated with lobar reduction in lung transplantation. METHODS: A retrospective study was performed on 608 consecutive lung transplantations at 2 centers between January 2005 and August 2019 (559 standard lung transplantations [standard transplantation] and 49 with lobar reduction [lung transplantation group]). A propensity-score weighting approach was used to account for potential confounding related to patients' nonrandom allocation to the 2 intervention groups. The effects of the intervention on postoperative outcomes were assessed with a weighted regression approach. RESULTS: The propensity score was estimated on 571 patients (522 in standard transplantation group and 49 in lung transplantation group). In terms of early outcomes, the lung transplantation group showed a higher percentage of severe primary graft dysfunction at 0 hours and reported longer intensive care unit stay than the standard transplantation group. No other differences in terms of morbidity, mortality, mechanical ventilation time, hospital stay, and anastomotic complications were observed. Although the lung transplantation group showed worse long-term pulmonary function, the 2 populations had comparable survival outcomes. CONCLUSIONS: The use of lobar reduction showed early and long-term results comparable to those after standard lung transplantation. Although a higher rate of early severe primary graft dysfunction and slightly reduced respiratory function were detected in the lobar group, these did not affect patients' morbidity and survival.

Is PET/CT Able to Predict Histology in Thymic Epithelial Tumours? A Narrative Review.

BACKGROUND: The usefulness of 18FDG PET/CT scan in the evaluation of thymic epithelial tumours (TETs) has been reported by several authors, but data are still limited and its application in clinical practice is far from being defined. METHODS: We performed a narrative review of pertinent literature in order to clarify the role of 18FDG PET/CT in the prediction of TET histology and to discuss clinical implications and future perspectives. RESULTS: There is only little evidence that 18FDG PET/CT scan may distinguish thymic hyperplasia from thymic epithelial tumours. On the other hand, it seems to discriminate well thymomas from carcinomas and, even more, to predict the grade of malignancy (WHO classes). To this end, SUVmax and other PET variables (i.e., the ratio between SUVmax and tumour dimensions) have been adopted, with good results. Finally, however promising, the future of PET/CT and theranostics in TETs is far from being defined; more robust analysis of imaging texture on thymic neoplasms, as well as new exploratory studies with "stromal PET tracers," are ongoing. CONCLUSIONS: PET may play a role in predicting histology in TETs and help physicians in the management of these insidious malignancies.

Management of Pleural Effusion Secondary to Malignant Mesothelioma.

Malignant pleural mesothelioma (MPM) is a highly aggressive pleural tumour which has been epidemiologically linked to occupational exposure to asbestos. MPM is often associated with pleural effusion, which is a common cause of morbidity and whose management remains a clinical challenge. In this review, we analysed the literature regarding the diagnosis and therapeutic options of pleural effusion secondary to mesothelioma. Our aim was to provide a comprehensive view on this subject, and a new algorithm was proposed as a practical aid to clinicians dealing with patients suffering from pleural effusion.

Case Report: A Challenging Localization of a Pulmonary Ectopic ACTH-Secreting Tumor in a Patient With Severe Cushing's Syndrome.

Background: Ectopic adrenocorticotropic syndrome (EAS) is a rare cause of endogenous ACTH-dependent Cushing's syndrome, usually associated with severe hypercortisolism as well as comorbidities. Tumor detection is still a challenge and often requires several imaging procedures. In this report, we describe a case of an ectopic ACTH secretion with a misleading localization of the responsible tumor due to a concomitant rectal carcinoma. Case presentation: A 49-year-old man was referred to our Endocrinology Unit due to suspicion of Cushing's syndrome. His medical history included metastatic rectal adenocarcinoma, diagnosed 5 years ago and treated with adjuvant chemotherapy, radiotherapy and surgical resection. During follow-up, a thoracic computed tomography scan revealed two pulmonary nodules located in the superior and middle lobes of the right lung with a diameter of 5 and 10 mm, respectively. However, these nodules remained radiologically stable thereafter and were not considered relevant. All biochemical tests were suggestive of EAS (basal ACTH levels: 88.2 ng/L, nv 0-46; basal cortisol levels: 44.2 µg/dl, nv 4.8-19.5; negative response to CRH test and high dose dexamethasone suppression test) and radiological localization of the ectopic ACTH-secreting tumor was scheduled. The CT scan revealed a dimensional increase of the right superior lung nodule (from 5 to 12 mm). [68Ga]-DOTA-TOC PET/CT scan was negative, while [18F]-FDG-PET/CT showed a tracer accumulation in the superior nodule. After a multidisciplinary consultation, the patient underwent thoracic surgery that started with two atypical wedge resections of nodules. Frozen section analyses showed a neuroendocrine tumor on the right middle lobe nodule and a metastatic colorectal adenocarcinoma on the superior lesion. Then, a right superior nodulectomy and a right middle lobectomy with mediastinal lymphadenectomy were performed. The final histopathological examination confirmed a typical carcinoid tumor, strongly positive for ACTH. A post-surgical follow-up showed a persistent remission of Cushing's syndrome. Conclusions: The present report describes a case of severe hypercortisolism due to EAS not detected by functional imaging methods, in which the localization of ACTH ectopic origin was puzzled by a concomitant metastatic rectal carcinoma. The multidisciplinary approach was crucial for the management of this rare disease.