Temozolomide based treatment in glioblastoma: 6 vs. 12 months.

The Stupp regimen remains the standard treatment for newly diagnosed glioblastomas, although the prognosis remains poor. Several temozolomide alternative schedules have been studied, with extended adjuvant treatment (>6 cycles of temozolomide) frequently used, although different trials have indicated contrasting results. Survival data of 87 patients who received 6 ('6C' group) or 12 ('12C' group) cycles of temozolomide were collected between 2012 and 2022. A total of 45 patients were included in the 6C group and 42 patients were included in the 12C group. Data on isocitrate dehydrogenase mutation and methylguanine-DNA-methyltransferase (MGMT) promoter methylation status were also collected. The 12C group exhibited statistically significantly improved overall survival [OS; 22.8 vs. 17.5 months; hazard ratio (HR), 0.47; 95% CI, 0.30-0.73; P=0.001] and progression-free survival (15.3 vs. 9 months; HR, 0.39; 95% CI, 0.25-0.62; P=0.001). However, in the subgroup analysis according to MGMT status, OS in the 12C group was significantly superior to OS in the 6C group only in the MGMT unmethylated tumors. The present data suggested that extended adjuvant temozolomide appeared to be more effective than the conventional six cycles.

TGF-ß Modulated Pathways in Colorectal Cancer: New Potential Therapeutic Opportunities.

Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide, with 20% of patients presenting with metastatic disease at diagnosis. TGF-ß signaling plays a crucial role in various cellular processes, including growth, differentiation, apoptosis, epithelial-mesenchymal transition (EMT), regulation of the extracellular matrix, angiogenesis, and immune responses. TGF-ß signals through SMAD proteins, which are intracellular molecules that transmit TGF-ß signals from the cell membrane to the nucleus. Alterations in the TGF-ß pathway and mutations in SMAD proteins are common in metastatic CRC (mCRC), making them critical factors in CRC tumorigenesis. This review first analyzes normal TGF-ß signaling and then investigates its role in CRC pathogenesis, highlighting the mechanisms through which TGF-ß influences metastasis development. TGF-ß promotes neoangiogenesis via VEGF overexpression, pericyte differentiation, and other mechanisms. Additionally, TGF-ß affects various elements of the tumor microenvironment, including T cells, fibroblasts, and macrophages, promoting immunosuppression and metastasis. Given its strategic role in multiple processes, we explored different strategies to target TGF-ß in mCRC patients, aiming to identify new therapeutic options.

Modified blade: an interventional option in rigid bronchoscopy for non-resectable benign tracheal stenosis.

INTRODUCTION: Benign tracheobronchial stenosis is a abnormal tracheal lumen narrowing that may incur progressive dyspnea and life-threatening hypoxemia. There is no consensus on which patients should be treated with endoscopic or surgical method. This study investigates the outcomes of bronchoscopic dilatation in the treatment of benign tracheal stenosis using a device equipped with a blade to cut the stenotic lesions with dense fibrosis. MATERIALS AND METHODS: The procedure was carried out in an operating room under general anesthesia. All patients were intubated with a Rigid Bronchoscope (RB) placed just above the stenosis. Through Rigid Bronchoscopy combined modalities were used as needed: radial incisions of the mucosal stenosis with blade at the levels of 4, 8 and 12 o'clock, with back and forth movements, then the stenotic area was dilated more easily with a rigid bronchoscope. Dilatation was performed by passing the RB of increasing diameter through stenotic areas and then Balloon dilatation of increasing diameter. There were no complications during the procedure. RESULT: We conducted an observational, retrospective, single-centre study in the Thoracic Surgery Unit of the University of 'Luigi Vanvitelli' of Naples from November 2011 to September 2021. We included all consecutive patients with benign tracheal stenosis inoperable. During the study period, 113 patients were referred to our department with benign tracheal stenosis inoperable. 61 patients were treated with the blade. During the follow-up, a recurrence of the stenosis was observed in 8 patients in the first month and in 4 patients in the third month. Instead in the patients treated with the use of laser (52 patients), during the follow-up a recurrence was observed in 16 patients in the first month and in 6 patients in the third month; no patient relapsed after 6 months and after 1 year. Long term successful bronchoscopic management with blade was attained by 99% in simple and 93% in mixed stenosis and in complex type stenosis. CONCLUSION: Our study underlines the importance of the use of the blade in bronchoscopic treatment as a valid conservative approach in the management of patients with inoperable benign tracheal stenosis as an alternative to the use of the laser, reducing the abnormal inflammatory reaction in order to limit recurrences.

Prediction of classical versus non classical papillary thyroid carcinoma subtypes from cytology of nodules classified according to TIRADS.

PURPOSE: Our purposes were: 1) to estimate the prediction performance (PP) of cytology in identifying papillary thyroid carcinoma (PTC) subtypes; 2) to explore how the PTC subtypes distribute among the American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) categories. METHODS: Nodules were included if both the histology with the PTC subtype report and the cytology report with the possible PTC subtype were available. The PP was calculated by making the proportion of True positives/False positives+false negatives. RESULTS: 309 cytologically "suspicious for malignancy" and "malignant" thyroid nodules with PTC histology were evaluated. ACR TI-RADS categorization for classical PTC was significantly different from non-classical PTC (p-value 0.02). For the whole cohort the PP of cytologically classical cases was 0.74, while that of cytologically non classical cases was 0.41. ACR TI-RADS categorization was not significantly different for aggressive vs non-aggressive PTC subtypes (p-value 0.1). When considering only aggressive or non-aggressive PTC subtypes, the PP of cytologically classical cases was respectively 0.86 and 0.87, while that of cytologically non classical cases was respectively 0.27 and 0.22. The PP of cytologically classical cases was 0.73 and 0.79, respectively for macroPTCs and microPTCs, while that of cytologically non classical cases was 0.55 and 0.33, respectively for macroPTCs and microPTCs. CONCLUSION: Cytology examination reliably performed in predicting classical PTC versus non classical PTC subtypes. ACR TI-RADS categorization was significantly different among classical PTC versus non classical PTC subtypes.

Intraoperative lung ultrasound improves subcentimetric pulmonary nodule localization during VATS: Results of a retrospective analysis.

BACKGROUND: Video-assisted thoracoscopic surgery (VATS) resection of deep-seated lung nodules smaller than 1 cm is extremely challenging. Several methods have been proposed to overcome this limitation but with not neglectable complications. Intraoperative lung ultrasound (ILU) is the latest minimally invasive proposed technique. The aim of the current study was to analyze the accuracy and efficacy of ILU associated with VATS to visualize solitary and deep-seated pulmonary nodules smaller than 1 cm. METHODS: Patients with subcentimetric solitary and deep-seated pulmonary nodules were included in this retrospective study from November 2020 to December 2022. Patients who received VATS aided with ILU were considered as group A and patients who received conventional VATS as group B (control group). The rate of nodule identification and the time for localization with VATS alone and with VATS aided with ILU in each group were analyzed. RESULTS: A total of 43 patients received VATS aided with ILU (group A) and 31 patients received conventional VATS (group B). Mean operative time was lower in group A (p < 0.05). In group A all the nodules were correctly identified, while in group B in one case the localization failed. The time to identify the lesion was lower in group A (7.1 ± 2.2 vs. 13.8 ± 4.6; p < 0.05). During hospitalization three patients (6.5%; p < 0.05) in group B presented air leaks that were conservatively managed. CONCLUSION: Intracavitary VATS-US is a reliable, feasible, real-time and effective method of localization of parenchymal lung nodules during selected wedge resection procedures.

Endoscopic treatment of solitary fibrous tumor of the trachea: a case report.

Background: Solitary fibrous tumor (SFT) is a rare mesenchymal neoplasm, generally arising in the visceral pleura. It rarely originates from other sites such as trachea, orbital cavities, nasal cavities, peritoneum, paranasal sinuses, meninges, salivary glands, thyroid gland, diaphragm, liver, pancreas, lung kidney, adrenal gland, mediastinum, spermatid cord, pericardium, urinary bladder, prostate, uterine cervix, testis, spinal cord, periosteum, skin, soft tissue and bone. Case Description: We present a surgical case of a rare primary tracheal tumor. High resolution computed tomography (HRCT) scan of the chest showed a 5 mm hypodense lesion, located on the right lateral wall of the proximal third of trachea; however the tracheal lumen was normal. We performed a rigid bronchoscopy in order to remove the endotracheal tumor with palliative purposes only. For this reason, we did not perform a prior histologic examination. The lesion was easily removed with common biopsy forceps and with standard aspirator. The debulking of the tumor was achieved with the use of laser Nd-YAP, electrocautery was used also for hemostasis to prevent bleeding during the operation. Without complications during the endoscopic treatment, the procedure was well tolerated by the patient. The pathological diagnosis was SFT. Conclusions: SFT located in the trachea can be endoscopically resceted. Endoscolical treatment is indicated for patients with poor clinical conditions (heart disease, respiratory failure) that are not elegible for surgical resection.

Clinical activity of regorafenib in elderly patients with recurrent glioblastoma.

Glioblastoma multiforme is one of the most frequent and aggressive primary tumors in the central nervous system, representing >60% of all brain tumors in adults. Despite treatment, prognosis remains poor with most if not all patients experiencing disease recurrence and a 2-year survival rate of 27%. At present, no confirmed standard treatment exists for recurrent glioblastoma. Regorafenib is one of the few options available, based on results from the REGOMA trial. In the present study, a real-life retrospective investigation on the role of regorafenib in patients with recurrent glioblastoma (>60 years old) from two main Oncological Units in South Italy (Azienda Ospedaliera Universitaria Luigi Vanvitelli, Naples, Italy and Ospedale Civile San Giovanni di Dio, Frattamaggiore, Naples, Italy), was performed. The primary endpoint was overall survival (OS), whereas progression-free survival (PFS), objective response rate and disease control were secondary endpoints. Survival was then analyzed according to age, isocitrate dehydrogenase (IDH) and methylated methylguanine-DNA-methyltransferase (MGMT) status. A total of 56 patients met the eligibility criteria. The intention to treat population median PFS (mPFS) was 4.1 months and median OS (mOS) was 6.8 months. Age did not appear to have a significant influence on mPFS. mOS in MGMT-methylated patients was improved compared with that of the unmethylated group (7.7 months vs. 5.6 months). Both mOS and mPFS were longer in IDH-mutant patients. The present study was one of the first real life analyses of regorafenib in recurrent glioblastoma. The results were in line with the REGOMA trial. Age did not appear to be a prognostic factor, thus suggesting that treatment choice should not be different in elderly. MGMT methylation appeared to influence OS. To the best of our knowledge, this was the first report of regorafenib activity in older patients and, while the results were statistically significant, these should be confirmed in further studies.

Diagnosis of malignant pleural disease: Ultrasound as "a detective probe".

BACKGROUND: Malignant pleural mesothelioma (MPM) is an invasive, aggressive pleural tumor with a predominantly local spread. The objective of this study was to assess thoracic ultrasound (TUS) as an imaging modality with high sensitivity for the identification of malignant pleural involvement and in order to guide pleural biopsies. METHODS: In this retrospective single-center study between January 2018 and June 2022, 51 consecutive patients with impassable circumferential pleural thickening underwent TUS at the Thoracic Surgery Unit of the Vanvitelli University of Naples. Pleural biopsies were performed, and then large and multiple samples were sent to the pathological anatomy for histological examination. RESULTS: In all patients who underwent ultrasound examination, we chose the optimal point of entry to perform pleural biopsies and selected the areas of greater thickening without pleural effusion. No patient had any complications. No drainage tubes were placed after the pleural biopsies and no pneumothorax was present during the following days of hospitalization. The patients were discharged on the second postoperative day. CONCLUSION: With TUS the precise pleural thickening localization, local infiltration, mass extent, its nature (solid, cystic or complex) and ultrasound features can be easily defined. Furthermore, ultrasound is more economical than computed tomography and avoids the risks associated with radiation. Thoracic ultrasound is an important component of the diagnostic procedure in detecting a safe entry site for biopsies of MPMs.

Ventilation challenge in rigid bronchoscopy: Laser tube as an alternative management in patients with lung cancer and central airway obstruction.

INTRODUCTION: Central airway tumors involving the trachea and main-stem bronchi are a common cause of airway obstruction and a significant cause of mortality among the patients of thoracic diseases with respiratory failure. Debulking in rigid bronchoscopy is quick, safe, and effective. It can be complex and hard in patients with severe bronchial or tracheal obstruction and/or with intraluminal bleeding tumors because of inadequate distal airway control. We have used laser tube as a new technique of ventilation for severe central airway obstruction. MATERIALS AND METHODS: Forty-six patients with severe airway obstruction undergoing rigid bronchoscopy from September 2020 to June 2022 at the Thoracic Surgery Department of the University L. Vanvitelli of Naples underwent placement of laser tube. RESULTS: In all patients who underwent rigid bronchoscopy with the use of the laser tube, a reduction of obstruction of more than 50% was obtained and in all patients no hypoxia (saturation < 88%), nor hypercapnia, nor significant bleeding were reported. DISCUSSION: The results of this study suggest that rigid bronchoscopic debulking with the use of laser tube is a safe and effective technique in the management of central airway obstruction. CONCLUSIONS: The use of the laser tube allows the monitoring of gas exchange, which controls hypoxemia. Thanks to the double cuff put distally to the tracheal obstruction or in the contralateral bronchus to the obstructed one, the laser tube prevents the flooding of blood from debulking below the stenosis. Rigid bronchoscopy with laser tube will expand its use in the future.

Intraoperative ultrasound: "Alternative eye" in lymph nodal dissection in non-small cell lung cancer.

INTRODUCTION: Staging of the mediastinum lymph nodes involvement in patients with non-small cell lung cancer (NSCLC) is an important prognostic factor determining the most appropriate multimodality treatment plan. The objective of this study is to assess ultrasound characteristics of mediastinal lymph nodes metastasis and effectiveness of intraoperative ultrasound-guided mediastinal nodal dissection in patients with resected NSCLC. MATERIALS AND METHODS: All patients undergoing video-assisted thoracoscopic surgery lobectomy and pulmonary lymphadenectomy from November 2020 to March 2022 at the thoracic surgery department of the Vanvitelli University of Naples underwent intraoperative ultrasound-guided mediastinal lymph nodal dissection. RESULTS: This study evaluates whether individual B-mode features and a compounding thereof can be used to accurately and reproducibly predict lymph node malignancy. DISCUSSION: Intraoperative ultrasound, during systematic mediastinal lymph node dissection, is helpful in preventing lesion to mediastinal structures. Pathological nodal sonographic characteristics are round shape, short-axis diameter, echogenicity, margin, the absence or presence of coagulation necrosis sign, and the absence or presence of central hilar structure, increased color Doppler flow, the absence or presence of calcification, and nodal conglomeration. Operating time was not substantially prolonged. The procedure is simple, safe and highly accurate. CONCLUSIONS: Ultrasonic techniques allow surgeons to detect the relationship between lymph nodes and surrounding large blood vessels during biopsy, improving the safety and simplicity of the operation, increasing the number of harvested lymph nodes, and reducing the risk of intraoperative injury; it is a fast, easily reproducible, and inexpensive method.

Beyond N staging in colorectal cancer: Current approaches and future perspectives.

Traditionally, lymph node metastases (LNM) evaluation is essential to the staging of colon cancer patients according to the TNM (tumor-node-metastasis) system. However, in recent years evidence has accumulated regarding the role of emerging pathological features, which could significantly impact the prognosis of colorectal cancer patients. Lymph Node Ratio (LNR) and Log Odds of Positive Lymph Nodes (LODDS) have been shown to predict patients' prognosis more accurately than traditional nodal staging and it has been suggested that their implementation in existing classification could help stratify further patients with overlapping TNM stage. Tumor deposits (TD) are currently factored within the N1c category of the TNM classification in the absence of lymph node metastases. However, studies have shown that presence of TDs can affect patients' survival regardless of LNM. Moreover, evidence suggest that presence of TDs should not be evaluated as dichotomic but rather as a quantitative variable. Extranodal extension (ENE) has been shown to correlate with presence of other adverse prognostic features and to impact survival of colorectal cancer patients. In this review we will describe current staging systems and prognostic/predictive factors in colorectal cancer and elaborate on available evidence supporting the implementation of LNR/LODDS, TDs and ENE evaluation in existing classification to improve prognosis estimation and patient selection for adjuvant treatment.

Regorafenib beyond the Second Line in Relapsed Glioblastoma: A Case Report and Literature Review.

Glioblastoma multiforme (GBM) is one of the most frequent and aggressive primary tumors in the central nervous system, representing more than 60% of all brain tumors in adults. Primary GBM remains incurable with a poor prognosis both for limited therapeutic alternatives and for a high risk of progression or recurrence. In fact, at recurrence, the few treatment options available, and often characterized by limited effectiveness, have always been an Achilles' heel. The recent approval of second line of regorafenib, a multikinase inhibitor, has given hope after several years of darkness for new therapies in the treatment of GBM. Indeed, in the REGOMA trial, a phase 2 study, regorafenib was the first drug to show a statistically significant improvement in median overall survival compared with lomustine group, usually used in the second-line treatment after temozolomide failure. We report a case of a 43-year-old patient affected by GBM in treatment with regorafenib in third line of therapy with good disease control and long PFS.

Sorafenib in Metastatic Papillary Thyroid Carcinoma with BRAF K601E Mutation on Liquid Biopsy: A Case Report and Literature Review.

Differentiated thyroid cancer (DTC) includes papillary and follicular carcinomas and is the most common type of thyroid cancer. The incidence of this cancer has increased in the last few years, and even if its prognosis is generally good for a subset of patients that does not respond to radioactive iodine (RAI) therapy, the prognosis is much worse: the median overall survival (OS) from discovery of metastasis is 3-5 years and the 10-year survival rate is only 10%. Several mutations, including RAS or RET, as well as BRAF signaling, are associated with thyroid cancer. Liquid biopsy may be useful in selected patient to identify genomic alterations and thus allowing for a precision medicine approach with target therapy. Sorafenib, an oral multi-kinase inhibitor, can be used in the treatment of DTC. Case presentation: A 77 years old. man with diagnosis of metastatic DTC and evidence of presence of mutation of BRAF K601E on liquid biopsy was treated with sorafenib, showing a good response to the treatment and an improvement in the quality of life (QoL). Currently, this patient is still on treatment with sorafenib, gaining control of a multi-metastatic disease, generally characterized by a very poor prognosis. In conclusion, sorafenib has an active role in the treatment of DTC. It also has been considered the standard of care for patients with advanced unresectable hepatocellular carcinoma (HCC) and renal cell carcinoma (RCC). In our case we observe the efficacy of using sorafenib in Papillary thyroid carcinoma (PTC) such as confirming both stable disease (SD) in the CT scan as clinical benefit with an increase in QoL. Therefore, use of sorafenib remains an important treatment option, even in case of BRAF mutation, despite a rapidly evolving treatment landscape. It also seems important to perform liquid biopsies, especially in patients in whom it is not possible to repeat a new tissue biopsy. Ongoing clinical trials continue to evaluate sorafenib in different settings, and in combination with other therapies in DTC and HCC.

Prediction of preoperative intrathoracic adhesions for ipsilateral reoperations: sliding lung sign.

INTRODUCTION: Video-assisted thoracic surgery (VATS) for ipsilateral reoperations is controversial, because after the first surgical intervention, pleural adhesions occur frequently in the thoracic cavity and/or chest wall. This study assessed the usefulness of preoperative ultrasonography to reduce the incidence of lung injury at the time of the initial port insertion during secondary ipsilateral VATS. MATERIALS AND METHODS: This was a retrospective, single-center study. Nine patients who underwent thoracic surgery at Vanvitelli Hospitalfrom September 2019 to February 2022, were scheduled for a second VATS surgeryon ipsilateral lung, because of inconclusive intraoperative histologic examination. All nine patients underwent preoperative ultrasonography to assess the possible presence of pleural adhesions. We evaluated the lung sliding, since the presence of pleural adhesions does not permit to appreciate it. STATISTICAL ANALYSIS: Hard severe adhesions were observed in all nine patients without sliding lung sign (specificity 100%). In this series, the sensitivity, PPV, and NPV of the sliding lung sign were 93%, 100% and 94% respectively. RESULTS: The presence of the lung respiratory changes can be evaluated as the "sliding lung sign" by chest ultrasonography; we believe that the sliding lung sign might also predict intrathoracic adhesion. CONCLUSIONS: Preoperative detection of pleural adhesions using transthoracic ultrasonography was useful for ipsilateral secondary pulmonary resection patients undergoing VATS. Using preoperative ultrasonography can improve the safety and feasibility of placing the initial port in VATS.

Head and Neck Squamous Cell Carcinoma in Elderly Patients: Role of Radiotherapy and Chemotherapy.

Head and neck squamous cell carcinomas (HNSCC) constitute the sixth most common malignancy worldwide, with approximately 25-40% of the diagnosed patients older than 70 years. HNSCC patients are often frail and frequently have multiple comorbidities due to their unhealthy lifestyle, and evidence suggests that older patients may receive less aggressive and suboptimal treatment than younger patients with the same disease status. The aim of this review is to depict and summarize the evidence regarding the different strategies that can be used in the clinical management of elderly HNSCC patients. Key references were derived from a PubMed query. Hand searching and clinicaltrials.gov were also used. This paper contains a narrative report and a critical discussion of clinical approaches in the context of elderly HNSCC.

Dramatic Therapeutic Response to Dabrafenib Plus Trametinib in BRAF V600E Mutated Papillary Craniopharyngiomas: A Case Report and Literature Review.

BACKGROUND: Craniopharyngioma is a rare intracranial tumor, with a high morbidity rate due to its common refractiveness to conventional treatments. BRAF V600E mutation has recently been identified as the principal oncogenic molecular driver of papillary craniopharyngiomas (PCP), one of the two main variants of craniopharyngioma. CASE PRESENTATION: A 49-year-old man with recurrent craniopharyngioma, harboring BRAF V600E mutation, has been treated with targeted therapy based on a combination of a BRAF-inhibitor, dabrafenib (150 mg, orally two times daily), and a MEK-inhibitor, trametinib (2 mg, orally two times daily). Before starting treatment, the patient was symptomatic: he lamented confusion, dysphasia, and intense fatigue, that did not allow him to work normally. After just one cycle of treatment, the patient showed an important clinical improvement, reporting a progressive regression of the basal symptoms, hinting at a rapid and dramatic response, which was confirmed at the first radiological assessment. Thus, treatment was continued and at the time of writing, the treatment is still ongoing (total duration of treatment: 14 months) and it is well tolerated, with very good quality of life: the patient has no limitations in daily activities and he has even been able to restart to work. CONCLUSION: The use of targeted therapies-as a clinical practice or in clinical trials-represents an important therapeutic alternative and a great evolution for patients' prognosis vs. the standard of care, historically represented by unselected chemotherapies. The discovery of the BRAF V600E mutation in patients with PCP is very rare, resulting in a lack of data on the efficacy of the combination of dabrafenib and trametinib.