An Overview of the Use of Anti-Angiogenic Agents in the Treatment of Thymic Epithelial Tumors.

Angiogenesis significantly influences the carcinogenesis of thymic epithelial tumors (TET). Both thymomas and thymic carcinoma (TC) overexpress VEGF-A and VEGFR-1 and -2. This review aims to provide an appraisal of the use of anti-angiogenics in the treatment of TET. The literature research identified 16 studies that were deemed eligible for further analysis. Seven studies assessed the clinical efficacy of sunitinib and five studies the use of apatinib and/or anlotinib. The multicenter Japanese phase II REMORA trial investigated the efficacy of lenvatinib, which is a multi-targeted inhibitor of VEGFR, FGFR, RET, c-Kit, and other kinases. The objective response rate was 38% (25.6-52%), which is the highest documented in TET that progressed after first-line chemotherapy. Anti-angiogenic agents may be useful in the treatment of TET, which are not amenable to curative treatment. Their toxicity profile seems to be acceptable. However, angiogenesis inhibitors do not appear to have a major influence on either thymomas or TC, although multikinase inhibitors may have some effect on TC. The current evidence suggests that the most active agent is lenvatinib, whereas sunitinib could be proposed as an acceptable second-line therapy for TC. Further research concerning the combination of immune checkpoint inhibitors with anti-angiogenic drugs is warranted.

Minimally Invasive Surgery in Non-Small Cell Lung Cancer: Where Do We Stand?

In the last two decades, robotic-assisted thoracoscopic surgery (RATS) has gained popularity as a minimally invasive surgical (MIS) alternative to multi- and uniportal video-assisted thoracoscopic surgery (VATS). With this approach, the surgeon obviates the known drawbacks of conventional MIS, such as the reduced in-depth perception, hand-eye coordination, and freedom of motion of the instruments. Previous studies have shown that a robotic approach for operable lung cancer has treatment outcomes comparable to other MIS techniques such as multi-and uniportal VATS, but with less blood loss, a lower conversion rate to open surgery, better lymph node dissection rates, and improved ergonomics for the surgeon. The thoracic surgeon of the future is expected to perform more complex procedures. More patients will enter a multimodal treatment scheme making surgery more difficult due to severe inflammation. Furthermore, due to lung cancer screening programs, the number of patients presenting with operable smaller lung nodules in the periphery of the lung will increase. This, combined with the fact that segmentectomy is becoming an increasingly popular treatment for small peripheral lung lesions, indicates that the future thoracic surgeons need to have profound knowledge of segmental resections. New imaging techniques will help them to locate these lesions and to achieve a complete oncologic resection. Current robotic techniques exist to help the thoracic surgeon overcome these challenges. In this review, an update of the latest MIS approaches and nodule detection techniques will be given.

Good's syndrome and COVID-19: case report and literature review.

Background: Good's syndrome (GS) is an adult-onset acquired immunodeficiency, in which patients present with thymoma and hypogammaglobulinemia (HGG). GS is characterized by low to absent peripheral B cells and impaired T-cell mediated immunity, often resulting in various (opportunistic) infections and concurrent autoimmune disorders. In this case report, we present a case of a patient with GS and coronavirus disease 2019 (COVID-19) infection after surgical removal of a thymoma. The simultaneous occurence of these two entities is extremely rare. Case Description: A 55-year-old man presented with oral lichen planus and cutaneous lesions. Additional symptoms included a weight loss of 5 kilograms in the last six months. Computed tomography (CT) and positron emission tomography (PET) of the chest showed a large anterior mediastinal mass with a maximum diameter of 10 centimetres. A core needle biopsy was performed, which led to a pathological diagnosis of thymoma type AB. In addition to these earlier findings, laboratory analysis revealed HGG. The combination of a thymoma and HGG led to a diagnosis of GS. Induction chemotherapy with cisplatin-etoposide was started, however, the patient developed COVID-19 after 2 cycles. Treatment with remdesivir was initiated and, subsequently, a thymectomy via sternotomy was performed. Final pathology confirmed a thymoma type AB of 14 centimetres, fully encapsulated, and without invasion. Resection margins were negative and the tumour was classified as pT1aN0, R0 resection. The patient has received immunoglobulin treatments every 4 weeks for his GS and has not developed any new infections since the start of this therapy. Conclusions: Patients with GS are prone to developing (pulmonary) infections. Clinicians should be aware of the possible clinical effects of COVID-19 infections in this patient population.

Multimodality Treatment including Surgery Related to the Type of N2 Involvement in Locally Advanced Non-Small Cell Lung Cancer.

For patients with locally advanced non-small cell lung cancer (NSCLC) or positive N1 nodes, multimodality treatment is indicated. However, the optimal management of patients presenting with ipsilateral positive mediastinal nodes (N2 disease) has not been determined yet. Different treatment regimens consisting of chemotherapy, radiation therapy, and surgery have been proposed and implemented previously. In more recent years, immunotherapy and targeted therapies have been added as therapeutic options. The role of surgery is currently redefined. Recent studies have shown that surgical resection after induction immunotherapy or targeted therapy is feasible and yields good short-term results. In this review, we summarize the latest data on multimodality treatment options for stage IIIA-N2 locally advanced NSCLC, depending on the extent of nodal involvement.

Safety and Feasibility of Lung Cancer Surgery under the COVID-19 Circumstance.

The current coronavirus disease 2019 (COVID-19) pandemic has forced healthcare providers worldwide to adapt their practices. Our understanding of the effects of COVID-19 has increased exponentially since the beginning of the pandemic. Data from large-scale, international registries has provided more insight regarding risk factors for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and has allowed us to delineate specific subgroups of patients that have higher risks for severe complications. One particular subset of patients that have significantly higher risks of SARS-CoV-2 infection with higher morbidity and mortality rates are those that require surgical treatment for lung cancer. Earlier studies have shown that COVID-19 infections in patients that underwent lung cancer surgery is associated with higher rates of respiratory failure and mortality. However, deferral of cancer treatments is associated with increased mortality as well. This creates difficult situations in which healthcare providers are forced to weigh the benefits of surgical treatment against the possibility of SARS-CoV-2 infections. A number of oncological and surgical organizations have proposed treatment guidelines and recommendations for patients planned for lung cancer surgery. In this review, we summarize the latest data and recommendations for patients undergoing lung cancer surgery in the COVID-19 circumstance.

Conservative Treatment of a Floating Mural Thrombus in the Descending Aorta.

A 70-year-old woman was referred to the department of thoracic and vascular surgery after a floating mural thrombus was found in the distal aortic arch with extension into the proximal descending aorta. Imaging and clinical examination did not show signs of embolization and treatment with aspirin and low-molecular weight heparin was started. Follow-up after 2 weeks and 6 months showed a complete resolution of the aortic mural thrombus.

Update on Pulmonary Ossifications in the Differential Diagnosis of Solitary Pulmonary Nodules.

Pulmonary ossifications have often been regarded as rare, post-mortem findings without any clinical significance. We have investigated the occurrence of pulmonary ossifications in patients undergoing thoracic procedures, and how this may affect the differential diagnosis of solitary pulmonary nodules. In addition, we have performed a literature search on the occurrence and possible pathogenesis of these ossifications. From January 2008 until August 2019, we identified pulmonary ossifications in 34 patients who underwent elective pulmonary surgery. Pre-operative imaging was unable to differentiate these ossifications from solid tumors. A definitive diagnosis was made by an experienced pathologist (VS, ML). The PubMed database was researched in December 2019 with the search terms "pulmonary ossifications"; "heterotopic ossifications"; and "solitary pulmonary nodule". In total, 27 patients were male, with a mean age of 63 ± 12 years (age 41 to 82 on diagnosis). All lesions were identified on thoracic CT and marked for resection by a multidisciplinary team. A total of 17 patients were diagnosed with malignancy concurrent with ossifications. There was a clear predilection for the right lower lobe (12 cases, 35.3%) and most ossifications had a nodular form (70.6%). We could not identify a clear association with any other pathology, either cancerous or non-cancerous in origin. Oncologic or pulmonary comorbidities did not influence patient survival. Pulmonary ossifications are not as seldom as thought and are not just a curiosity finding by pathologists. These formations may be mistaken for a malignant space-occupying lesion, both pre-and perioperatively, as they are indistinguishable in imaging. We propose these ossifications as an underestimated addition to the differential diagnosis of a solitary pulmonary nodule.

The role of the surgeon in the management of oligometastatic non-small cell lung cancer: a literature review.

OBJECTIVE: In this review, we aim to summarize the most recent data on the surgical management of oligometastatic non-small cell lung cancer (NSCLC). BACKGROUND: Approximately 60-70% of all patients with NSCLC initially present with advanced stages of cancer at time of diagnosis. These patients are generally treated with chemotherapy, radiation therapy, or a combination of these modalities. Patients with late-stage disease are usually not considered to be amenable for curative-intent treatments due to poor prognoses. Despite advances in systemic therapies, 5-year overall survival rates in these patients remain poor. However, technological advances in imaging modalities and new imaging strategies have substantially increased tumor detection rates and have resulted in a shift towards earlier diagnosis of NSCLC, possibly in stages in which metastatic disease is limited and still treatable. Studies in recent years have shown that there is a distinct group of patients with metastatic lesions at one or a few sites, often referred to as oligometastatic disease, that may have better survival outcomes compared to patients with more disseminated diseases. Furthermore, it is suggested that these patients may benefit from a combination of systemic treatment and local treatment aimed at the metastatic site(s). However, the role of surgery in this setting remains a controversial subject, with many unanswered questions. METHODS: The PubMed/MEDLINE database and the Cochrane database were searched to find relevant articles regarding oligometastatic NSCLC. Specifically, articles regarding definitions of oligometastatic disease, oligometastatic tumor biology, diagnosis, and the treatment of oligometastatic disease were identified. CONCLUSIONS: Oligometastatic NSCLC represents a wide spectrum of diseases and encompasses a heterogeneous patient population. Current data suggests that local ablative treatment of oligometastatic lesions with surgery or stereotactic body radiation therapy may result in improved overall survival and progression-free survival rates. However, more data from multi-center prospective trials are necessary to shed light on which therapeutic modalities are most suitable for the treatment of oligometastatic NSCLC. Integration of clinical and molecular staging data is necessary to allow for more personalized treatment approaches.

Surgery after Induction Targeted Therapy and Immunotherapy for Lung Cancer.

Multimodality therapy for locally advanced non-small cell lung cancer (NSCLC) is a complex and controversial issue, especially regarding optimal treatment regimens for patients with ipsilateral positive mediastinal nodes (N2 disease). Many trials investigating neoadjuvant immunotherapy and targeted therapy in this subpopulation have shown promising results, although concerns have risen regarding surgical feasibility. A thorough literature review was performed, analyzing all recent studies regarding surgical morbidity and mortality. Despite the fact that two major trials investigating this subject were terminated early, the overall consensus is that surgical management seems feasible. However, dissection of hilar vessels may be challenging due to hilar fibrosis. Further research is necessary to identify the role of surgery in these multimodality treatment regimens, and to define matters such as the optimal treatment regimen, the dosage of the different agents used, the interval between induction therapy and surgery, and the role of adjuvant therapy.

Pulmonary metastasectomy in colorectal carcinoma.

Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. It is estimated that 50% of all patients with CRC develop metastases, most commonly in the liver and the lung. Lung metastases are seen in approximately 10-15% of all patients with CRC. A large number of these patients with metastatic CRC can only receive palliative treatment due to invasion of other organs and disseminated disease. However, a subset of these patients present with potentially resectable metastases. Pulmonary metastasectomy is considered to be a potentially curative treatment for selected patients with resectable metastatic CRC. Current data suggest that patients that undergo pulmonary metastasectomy have 5-year survival rates of approximately 40%. However, the majority of data published regarding lung metastasectomy is based on small, retrospective case series. Due to this lack of prospective data, it is still unclear which subset of patients will benefit most from curative-intent surgery. Furthermore, there is also controversy regarding which prognostic and genetic factors are related to survival outcomes and whether there is a difference between open and thoracoscopic approaches in terms of overall and disease-free survival. In this review, we aim to summarize the latest data on prognostic factors and survival outcomes after pulmonary metastasectomy in patients with metastatic CRC.

Use of Robotics in Surgical Treatment of Non-small Cell Lung Cancer.

OPINION STATEMENT: Robotic-assisted videothoracoscopic surgery (R-VATS) has become increasingly popular and widely used since its introduction and is nowadays considered a standard treatment approach in many centres for the treatment of non-small cell lung cancer. R-VATS was initially developed to overcome the drawbacks of VATS by offering surgeons more flexibility and three-dimensional optics during thoracoscopic surgery. The effectiveness of R-VATS lobectomy regarding oncological outcomes, morbidity, mortality, and postoperative quality of life (QoL) has been shown in an increasing number of studies. More recently, these results have also been corroborated for sublobar resections, more specifically for segmentectomy. However, no well-powered, multicentre randomized trials have been performed to demonstrate the superiority of R-VATS compared with open surgery or conventional types of VATS (total VATS, uniportal VATS, etc.). The majority of the evidence currently available is based on non-randomized studies, and many studies report conflicting results when comparing R-VATS and conventional VATS. Moreover, there is a lack of data regarding the cost and the cost-efficiency of robotic surgery compared with VATS and open surgery. Current evidence suggests that R-VATS costs are higher than VATS and that a deficit can only be prevented when up to 150-300 thoracic surgery procedures are performed annually. Finally, robotic-assisted laparoscopic surgery showed better ergonomics and reduced musculoskeletal disorders compared with non-robotic laparoscopic surgery.

Dynamic Infrared Thermography (DIRT) in DIEP flap breast reconstruction: A clinical study with a standardized measurement setup.

OBJECTIVE: Breast reconstructions with perforator flaps from the lower abdomen, commonly known as Deep Inferior Epigastric artery Perforator flap (DIEP-flap), have become the golden standard for autologous breast reconstruction after breast amputation. During this surgical procedure multiple challenging steps are encountered such as the selection of a suitable perforator that provides sufficient blood supply for the flap, surgical dissection of the chosen perforator, determination of perfusion area of the chosen perforator, microsurgical anastomosis, flap inset and shaping the flap into a breast. The current gold standard for perforator mapping is Computed Tomography Angiography (CTA). However, this is a relatively expensive imaging modality that requires intravenous contrast injection and exposes patients to ionizing radiation. More recently, Dynamic Infrared Thermography (DIRT) has been proposed as an alternative imaging modality for perforator identification. DIRT appears to be an ideal alternative technique not only for the identification of the dominant perforators, but also for the mapping of the individual influence of each perforator on the flap perfusion, to monitor integrity of the perforator after dissection and to monitor the patency of the pedicle of the free flap after the anastomosis, during flap inset and flap shaping. STUDY DESIGN: In this clinical study we present the results of the use of DIRT in 33 DIEP-flaps in 21 patients after mastectomy. The same standardized measurement set-up was used for all the flaps in the pre-, intra- and postoperative period. RESULTS: In the pre-operative period DIRT confirmed the location of the 69 perforators shown on the CTA. In the intra-operative period the rate and pattern of rewarming was successfully observed. One perforator was severely damaged during dissection and the DIEP flap was converted to a Muscle Sparing free Transverse Rectus Abdominis Muscle (TRAM) flap, after viability check of the flap by DIRT. DIRT diagnosed one kinking of the pedicle after microsurgical anastomosis. Two flaps were monitored successfully post-operatively. All 33 breast reconstructions were with good outcome. CONCLUSION: The use of DIRT with our standardized measurement setup is a useful, non-invasive tool during breast reconstructions with free DIEP-flaps in all the phases of the reconstruction (pre-, intra- and post-operative). This study confirms that DIRT with the standardized measurement setup provides information on perforator location, blood supply and patency of the anastomosis without interference with the operating surgeon.

Robotic-assisted thoracoscopic lobectomy of the right middle lobe.

Robotic-assisted thoracoscopic surgery has increased in popularity during the past two decades because it offers 3-dimensional optics, increased instrument and wrist flexibility compared to classical video-assisted thoracoscopic surgery, and, for patients, improved quality of life and shorter hospital stays compared to open surgery.  In this video tutorial, we demonstrate a robotic-assisted thoracoscopic surgery lobectomy in a patient with a tumor in the right middle lobe. The patient had an excellent recovery with no perioperative or postoperative complications.

Thymoma mimicking an aortic aneurysm: always expect the unexpected.

Thymic epithelial tumours (TETs) are rare lesions that represent less than 1% of all malignancies in adults. Presentation occurs in three ways: asymptomatic, with local thoracic symptoms or with paraneoplastic symptoms. Heterotopic ossifications are rare histological features in neoplasms and non-neoplastic lesions. Here, we present a 49-year-old male patient with a thymoma type B2 mimicking an aortic aneurysm. Alongside the thymoma, a cholesterol granuloma with unusual ossification features was found as well. This clinical presentation and pathological diagnosis are unusual findings.