Active thymus in adult with lung cancer: preliminary results from the Adult Thymic Project.

Thymus is considered a non-functional remnant in adults, but some evidence suggest that it may harbor residual activity. Lung cancer patients represent the ideal model to study thymic residual activity, as their thymus can be easily harvested during surgery. This study was designed to confirm the presence of residual thymic activity both in adult mice (step 1) and in humans (step 2). In step 1, lung cancer was induced by activating k-ras mutation in a cohort of 20 young and adult mice. After killing, thymus and lungs were analyzed. Thymus was considered active when medullary was evident, cortico-medullary ratio was 50:50 or higher and adipose involution was present. In step 2, a cohort of 20 patients, undergoing surgery for lung cancer, had biopsy of pericardial fat pad, site of ectopic thymus. Thymus was considered present if Hassall's bodies were detected. In mice, active thymus was detected in a high proportion of cases, without significant difference between adult and young (70% vs 44.4% respectively). Two cases without evidence of lung tumor had a fully functional thymus. In humans, ectopic thymus was detected in the pericardial fat pad in 2 cases (10.5%), confirmed by immunohistochemistry. Signs of previous thymic activity were detected in 8 additional patients. Results confirmed thymus activity in animal models and humans with lung cancer, providing the rationale for future systematic mediastinal thymic biopsy. The comprehension of interactions between thymus, lymphocytes and tumor may open a new potentially targetable perspective in lung cancer.

Pulmonary Low Malignant Potential Adenocarcinoma: A Validation of the Proposed Criteria for This Novel Subtype.

Adenocarcinoma (ADC) is the most common histologic type of lung cancer, including in situ (lepidic), minimally invasive, and invasive forms. While the former 2 types are associated with a favorable outcome, the latter includes tumors with variable behavior, often tumor stage-related. A recent study proposed strict morphologic criteria defining a new subgroup of resected stage I invasive ADC (16% of cases) with favorable outcomes (100% disease-specific survival), named "ADC of low malignant potential (LMP-ADC)." The following criteria were met: ≤3 cm size, nonmucinous histotype, ≥15% lepidic growth, and the absence of the following: high-grade patterns, >1 mitosis/2 mm 2 , necrosis, and vascular/pleural invasion. The aim of the present study was to validate the performance of such criteria to identify LMP-ADC in a series of 274 stage IA resected lung ADCs from a single institution. Thirty-four tumors (12.4%) met the proposed criteria for LMP-ADC, as confirmed by additional stains for mitotic figures, Ki67 index, and elastic fibers (helpful to assess alveolar wall invasion). Minor differences between the lepidic and invasive components were observed regarding cell atypia and proliferation. p53 was normally expressed by invasive tumor cells. Mutations occurred in known lung cancer genes (mostly KRAS and EGFR). Five patients (14.7%) developed disease progression and 2 of them (5.9%) died of the disease. In our series, the disease-specific survival was 94.1%. In conclusion, in resected invasive lung ADC, a subgroup presenting low-grade morphologic features and associated with favorable prognosis does exist. Morphologic criteria for LMP-ADC supported by ancillary techniques represent a valid tool to better define this novel subgroup and to refine the stratification of invasive lung ADC, possibly suggesting modified follow-up protocols, based on the observed indolent behavior in most cases.

Diagnostic and Therapeutic Challenges of Malignant Pleural Mesothelioma.

Malignant pleural mesothelioma is a rare cancer characterized by a very poor prognosis. Exposure to asbestos is the leading cause of malignant pleural mesothelioma. The preinvasive lesions, the mesothelial hyperplasia and its possible evolution are the focus of the majority of the studies aiming to identify the treatable phase of the disease. The role of BAP-1 and MTAP in the diagnosis of mesothelioma in situ and in the prognosis of malignant pleural mesothelioma is the main topic of recent studies. The management of preinvasive lesions in mesothelioma is still unclear and many aspects are the subject of debate. The diagnosis, the disease staging and the accurate, comprehensive assessment of patients are three key instants for an appropriate management of patients/the disease.

Pulmonary Hamartoma Associated With Lung Cancer (PHALC Study): Results of a Multicenter Study.

PURPOSE: Pulmonary hamartoma is the most common benign tumor of the lung. We analyzed a 20-year historical series of patients with pulmonary hamartoma undergoing surgical resection, aiming to evaluate the characteristics, the outcomes, and the association between hamartoma and lung cancer. METHODS: It was a retrospective multicenter study including the data of all consecutive patients with pulmonary hamartoma undergoing surgical resection. The end-points were to evaluate: (i) the characteristics of hamartoma, (ii) outcomes, and (iii) whether hamartoma was a predictive factor for lung cancer development RESULTS: Our study population included 540 patients. Upfront surgical or endoscopic resection was performed in 385 (71%) cases while in the remaining 155 (29%) cases, the lesions were resected 20 ± 3.5 months later due to increase in size. In most cases, lung sparing resection was carried out including enucleation (n = 259; 48%) and wedge resection (n = 230; 43%) while 5 (1%) patients underwent endoscopic resection. Only two patients (0, 2%) had major complications. One patient (0.23%) had recurrence after endoscopic resection, while no cases of malignant degeneration were seen (mean follow-up:103.3 ± 93 months). Seventy-six patients (14%) had associated lung cancer, synchronous in 9 (12%) and metachronous in 67 (88%). Only age > 70-year-old (p = 0.0059) and smokers > 20 cigarettes/day (p < 0.0001) were the significant risk factors for lung cancer. CONCLUSION: PH was a benign tumor, with no evidence of recurrence and/or of malignant degeneration after resection. The association between hamartoma and lung cancer was a spurious phenomenon due to common risk factors.

Is Ovarian Cancer Being Managed According to Clinical Guidelines? Evidence From a Population-Based Clinical Audit.

BACKGROUND: In the northwestern Italian region of Piedmont, current statistics on hospitalizations show that surgical treatment for ovarian cancer (OC) is taking place in many small hospitals, as opposed to a more centralized approach. A population-based clinical audit was promoted to investigate whether OC is being managed according to clinical guidelines, identify determinants of lack of adherence to guidelines, and evaluate the association between adherence to guidelines and survival. PATIENTS AND METHODS: Residents diagnosed with OC in 2009 were identified in the regional hospital discharge records database. All hospitalizations within 2 years from diagnosis were reviewed. Patients were classified according to their initial pattern of care, defined as "with curative intent" (CIPC) if including debulking surgery aimed at maximal cytoreduction. Adherence to guidelines for surgery and chemotherapy and the effects of this adherence on OC survival were investigated with logistic regression and Cox models. RESULTS: The final study sample consisted of 344 patients with OC, 215 (62.5%) of whom received CIPC. Increasing age, comorbidities, and metastases were negatively associated with receiving CIPC. In the CIPC group, surgical treatment was adherent to guidelines in 35.2%, whereas chemotherapy was adherent in 87.8%. Surgical treatment that was adherent to guidelines [hazard ratio (HR), 0.72; 95% confidence interval (CI), 0.45-1.15] and absence of residual tumor (HR, 0.55; 95% CI, 0.32-0.94) were associated with better survival in the CIPC group, and chemotherapy that was adherent to guidelines was associated with a significant reduction in the risk of death (HR, 0.49; 95% CI, 0.28-0.87). CONCLUSIONS: Results support the need to reorganize the clinical pathway of patients with OC in the Piedmont Region and the need for better adherence to current guidelines.

Economic Considerations on the Follow-Up Practice in Gynecologic Cancers: Few Lights and Many Shadows From a Literature Review.

OBJECTIVE: The aim of this review was to analyze the existing literature on the cost of follow-up in gynecology oncology. METHODS/MATERIALS: We performed a literature search in Medline and NHS CRD (University of Oxford) databases. Research strings were mainly based on MESH terms referring to economic studies and to neoplasms follow-up/aftercare and cancer recurrences. Two independent searches were performed for ovarian neoplasm and uterine neoplasm. Some studies were also identified among the references of the selected articles. Potentially relevant studies were identified based on the title and abstract by 2 independent readers. RESULTS: Finally, the reviewing process selected 2 studies on gynecologic cancers in general, including uterine and ovarian cancers, 3 specific on ovarian cancer, 7 on endometrium, and 9 on cervix. The identified economic literature on economic evaluation of gynecologic cancer follow-up procedures showed to be based on weak evidence of effectiveness and to lack formal methodological approaches. In general, such literature is quite recent, relies on small sample observational studies, and suffers from a lack of financial support. CONCLUSIONS: There are few available lights in economic considerations on gynecologic cancer follow-up, represented by all the published studies, and many shadows that require to be clarified by properly designed randomized trials including cost-effectiveness analysis.