How to carry out retrospective studies in metastatic renal cell cancer: two caveats that should be avoided

The results achieved with targeted therapy have changed the natural course of kidney cancer not amenable to local therapy. Sunitinib, bevacizumab and pazopanib are approved in the first-line setting for patients at good/intermediate prognosis, while temsirolimus should be the first-line agent to be used in patients at poor prognosis. The oncology community has been eagerly awaiting results as far as second-line treatment is concerned. The RECORD-1 and AXIS trials provided evidence in favor of everolimus and axitinib, respectively, in patients pretreated with VEGF-directed agents. As the number of available agents grows, so does the possibility of using multiple lines of therapy with a potential benefit in overall survival. The third-line setting has been poorly investigated, and no comparative prospective trials are presently available. Retreatment with VEGF-directed therapy may be an option in everolimus-pretreated patients, with the possibility that mTOR inhibitors may reverse resistance to VEGF-directed therapy. Grunwald et al. presented retrospective data showing that retreatment with VEGF-directed targeted agents, including sunitinib, bevacizumab/interferon, dovitinib and sorafenib, was associated with a progression-free survival time of approximately 5 months. Although the evidence provided by retrospective studies is weak, their role in highlighting matters of clinical relevance deserving investigation is undoubtful, as demonstrated by the retrospective study discussed in this paper.     

Video-assisted thoracoscopic pneumonectomy: a minimally invasive approach for a rare inidication

Minimally invasive video-assisted thoracoscopic surgery (VATS) is considered as an alternative to thoracotomy for early stage lung cancer. Since 2009, we use a VATS approach for all early stage lung tumors as well as benign indications for lung lobectomy. As experience with the technique is growing, indications are expanded. Here, we report our first minimally invasive pneumonectomies of two patients with non-small cell lung cancer (NSCLC). Case 1: A 60-year-old man was diagnosed with a centrally located tumor of the right lung invading all three lobes without any obvious lymph node metastasis in the preoperative work-up. The patient was scheduled for a right-sided VATS pneumonectomy. Case 2: A 62-year-old woman was diagnosed with a centrally located tumor of the left lung with an ipsilateral positron emission tomography (PET) positive lymph node (aortopulmonary window). After neoadjuvant treatment, the patient was scheduled for a left-sided pneumonectomy. Written informed consent was given in both cases. The procedures were completed using three incisions. A complete mediastinal lymph node dissection was performed. The postoperative courses were uneventful. VATS pneumonectomy is feasible in highly selected cases. It offers all advantages known from minimally invasive lung lobectomy with less pain and faster rehabilitation, which might facilitate the delivery of adjuvant treatment.     

Extra-abdominal primary fibromatosis: Aggressive management could be avoided in a subgroup of patients

Objective

To evaluate the impact of surgery as first-line treatment on event-free survival (EFS) of primary aggressive fibromatosis.

Patients and methods

Treatments were categorized into: surgery with or without radiotherapy and nonsurgical strategies with systemic treatment alone or wait and see policy. Eighty-nine patients had initial resection of their primary tumour followed by postoperative radiotherapy in 13 cases. Twenty-three did not undergo surgery but received systemic treatment or watch and wait policy.

Results

Median follow-up was 76 months. Overall 3 years EFS was 49%. In the univariate analysis, patients with microscopically complete surgery had a similar outcome to patients in the no-surgery group (3 years EFS of 65% and 68%, respectively). Gender, age, tumour size, treatment period and strategy (surgery versus no-surgery) were not statistically significant. Quality of resection according to margins and the tumour site were the only prognostic factors. There was a significant correlation between tumour site and quality of surgery (p = 0.0002).

Conclusions

A subset of patients with extra-abdominal fibromatosis could be managed with a nonaggressive policy, as growth arrest concerned 2/3 of nonoperated patients. When surgery is finally necessary, it should be performed with the aim of achieving negative margins.     

A comparison of autofluorescence bronchoscopy and white light bronchoscopy in detection of lung cancer and preneoplastic lesions: a meta-analysis

Introduction

It is known that autofluorescence bronchoscopy (AFB) has limited value in detection of lung cancer and preneoplastic lesions. Though a substantial number of studies have evaluated the diagnostic yield of AFB, the variable estimates limited the ability to accurately assess its test performance and future role in clinical practice. The clinical utility of AFB has never been supported by a meta-analysis due to the inconsistent characteristics in some of studies. A meta-analysis was performed to re-examine the diagnostic efficiency of AFB compared with white light bronchoscopy (WLB).

Methods

Search of both MEDLINE and EMBASE database up to June 2009 was conducted and hand search was performed against the extracted reference list for relevancy. Included studies had to have a conclusive histology as diagnostic standard, and provided sufficient data to construct a 2X2 table for assessing the diagnostic yield of AFB for detection of lung cancer and preneoplastic lesions. After examining the source of variation, pooled sensitivity and specificity of AFB were estimated using a bivariate random-effects regressing model and compared with that of WLB.

Results

Of 439 publications, 14 studies, providing 15 sets of data, were suitable for analysis. The pooled sensitivity and specificity of AFB and WLB were 0.90 (95% CI 0.84-0.93) and 0.56 (95% CI 0.45-0.66), 0.66 (95% CI 0.58-0.73) and 0.69 (95% CI 0.57-0.79). The contribution of differences in excitation light source, histological criteria and biopsy strategy was not counted as a covariate.

Conclusions

The result indicated that AFB was superior to conventional WLB in detecting lung cancer and preneoplastic lesions.     

Extrapleural pneumonectomy for early stage malignant pleural mesothelioma: a harmful procedure

The effects on long-term post-operative quality of life (QoL) and disease-control in malignant pleural mesothelioma (MPM) of extrapleural pneumonectomy (EPP) and pleurectomy/decortication (P/D) are compared. Seventy-seven patients affected by early-stage MPM received EPP (40) or P/D (37) associated with multimodal treatment between 1998 and 2009 at our institution. The last consecutive 39 (19 EPP and 20 P/D) were asked to answer the EORTC-QLQ-C30 questionnaire at baseline and at 6- and 12-months after treatment completion to evaluate the impact on QoL of both procedures. QoL evaluation was stopped at recurrence demonstration. Twenty-five (62%) EPP vs 9 (24%) P/D patients (p = 0.002) had in-hospital major complications, and 2/40 (5%) EPP vs no one P/D patients died after surgery. Both procedures caused a significant impairment of all the considered variables of the EORTC-QLQ-C30 questionnaire after treatment completion; only P/D patients returned at baseline levels after 12 months. EPP patients had a worse long-term post-operative QoL when compared with P/D. Median post-operative disease-free period was longer for EPP patients (14 vs 11 months) whereas the residual life to death period after recurrence detection was significantly longer for P/D patients (13 vs 9 months) (p = 0.01). Median long-term survival was longer, even not significant, for P/D patients (25 vs 20 months). MPM patients submitted to EPP had a higher post-operative complication rate, a worse long-term QoL, a shorter residual life time after recurrent disease, despite a similar long-term survival when compared to P/D.     

EUS-guided FNA of centrally located lung tumours following a non-diagnostic bronchoscopy

OBJECTIVE: To assess the feasibility and yield of endoscopic ultrasound (EUS) guided fine needle aspiration (FNA) in diagnosing centrally located lung tumours after a previously non-diagnostic bronchoscopy. BACKGROUND AND HYPOTHESIS: Bronchoscopy fails to establish a diagnosis in up to 30% of patients with suspected lung cancer. Intrapulmonary tumours located near or adjacent to the esophagus might be visualized and biopsied under real-time ultrasound guidance by EUS-FNA. DESIGN: Patients with suspected lung cancer and an intrapulmonary tumour located near or adjacent to the esophagus who had undergone a non-diagnostic bronchoscopy, underwent EUS-FNA for diagnostic purposes. Surgical-pathological verification occurred when EUS-FNA was non-diagnostic and in those patients diagnosed with non-small-cell lung cancer by EUS-FNA who were surgical candidates. RESULTS: EUS-FNA diagnosed lung cancer in 31 of 32 patients (97%). No complications occurred. The diagnosis obtained by EUS-FNA was confirmed in all 11 patients who were operated. In one case, in which EUS-FNA was non-diagnostic, a lymphoma was diagnosed after pneumonectomy. CONCLUSIONS AND SIGNIFICANCE: EUS-FNA qualifies as the next diagnostic step in patients with suspected lung cancer and a non-diagnostic bronchoscopy if the intrapulmonary mass is located adjacent or near the esophagus. In these cases, EUS-FNA may replace computed tomography of the chest (CT)-guided biopsies and reduce the number of exploratory thoracotomies.     

Adjuvant radiotherapy after extrapleural pneumonectomy for mesothelioma. Prospective analysis of a multi-institutional series

Background and purpose

To evaluate survival, locoregional control and toxicity in a series of 56 mesothelioma patients treated from May 2005 to May 2010 with post-operative radiotherapy after extrapleural pneumonectomy (EPP) in three Italian Institutions (Brescia, Florence, and Modena).

Material and methods

Fifty-six patients treated with adjuvant radiotherapy (RT) after EPP were analyzed. Four patients were treated with 3DCRT, 50 with IMRT and two with helical tomotherapy. Forty-five to 50 Gy in 25 fractions were given to the affected hemithorax and to ipsilateral mediastinum, with a simultaneous integrated boost to the sites of microscopically involved margins up to 60 Gy in 20/56 cases.

Results

Three year locoregional control (LRC), distant metastasis free (DMF), disease free (DF), disease specific (DSS) and overall survival (OS) rates are 90%, 66%, 57%, 62%, and 60%, respectively.

Conclusion

Postoperative RT with modern techniques is an effective method to obtain excellent local control and cure rates in mesothelioma patients submitted to EPP.     

Fluorescence versus white-light bronchoscopy for detection of preneoplastic lesions: a randomized study

BACKGROUND: There are no currently approved methods for the screening and early detection of lung cancer. We compared the ability of conventional white-light bronchoscopy (WLB) and laser-induced fluorescence endoscopy (LIFE) to detect preneoplastic lung lesions in a randomized trial in which both the order of the procedures and the bronchoscopists were randomly assigned. METHODS: The study included high-risk subjects enrolled because of a cigarette smoking history of at least 30 pack-years, an air-flow obstruction, and either an abnormal sputum cytology (n = 48) or a previous or suspected lung cancer (n = 7). LIFE and WLB were performed on all patients. Biopsy specimens were assessed for histologic abnormalities, including the presence of angiogenic squamous dysplasia. All statistical tests were two-sided. RESULTS: A total of 391 biopsy specimens were taken from the 55 patients. Thirty-two patients (58%; 95% confidence interval [CI] = 44% to 71%) had at least one biopsy with moderate or severe dysplasia, and 19 (59%; 95% CI = 41% to 76%) of these patients could be diagnosed based solely on the results of LIFE. LIFE was statistically significantly more sensitive than WLB for detecting moderate dysplasia or worse (68.8% versus 21.9%, respectively) (difference = 46.9%; 95% CI = 25% to 68%; P< .001). The relative sensitivities (WLB = 1.0) were 3.1 (95% CI = 1.6 to 6.3) for LIFE and 3.7 (95% CI = 1.9 to 7.3) for LIFE and WLB combined. LIFE was less specific than WLB (69.6% versus 78.3%, respectively; P = .45), but the difference was not statistically significant. The relative specificities (WLB = 1.0) were 0.9 for LIFE (95% CI = 0.6 to 1.3) and 0.6 (95% CI = 0.4 to 1.0) for LIFE and WLB combined. The results were similar regardless of the order of the procedures or the order of the bronchoscopists. Also, LIFE was better at identifying angiogenic squamous dysplasia lesions than WLB (detection ratio [DR], which indicates the relative likelihood of getting a positive result in a sample with dysplasia compared with one without, for LIFE = 1.39 [95% CI = 1.17 to 1.65] versus DR for WLB = 0.67 [95% CI = 0.38 to 1.21]). CONCLUSION: LIFE was more sensitive than WLB in detecting preneoplastic bronchial changes in high-risk subjects. The prognostic implication of this finding is not yet clear.     

Fluorescence bronchoscopy for early detection of lung cancer: a clinical perspective.

The conventional method of bronchoscopy has only a 30% sensitivity to detect early stage cancer in the central airways. For patients with positive sputum cytology who clearly harbor early cancers, repeat and lengthy sessions of bronchoscopies are required for accurate localization of these lesions. This leads to a significant delay in obtaining the diagnosis, postponing an appropriate treatment and reduces the chance for cure. There are valid reasons for improving the detection rate of early stage lung cancers. The number of individuals at risk forms a large population, the outcome of patients treated with early stage cancer has been shown to be better and bronchoscopic treatments, e.g. photodynamic therapy and electrocautery, are currently alternatives for surgical resection. Finding more early stage cancers by screening the population at risk and accurate staging to enable treatment at the earliest stage feasible, may improve the dismal prognosis of many patients. This article deals with the clinical background and current problems in early detection of lung cancer and discusses our expectations regarding new developments in bronchoscopy for early detection, accurate staging and treatment of lung cancer.     

Imaging of a pediatric abdominal mass

The approach to the child with an abdominal mass will be aided by careful consideration of the radiographic imaging modalities available at an institution. The relative advantages, disadvantages, costs, and radiation of each modality are presented. The recommended workup of a pediatric abdominal mass, as well as the most common masses and their differential diagnosis, are outlined.     

Deep-neck space infections — a diagnostic dilemma!

Deep Neck Space Infections (DNI) are a potentially life threatening condition. This paper highlights the importance of their early diagnosis and early intervention. The deep-neck space infections may be odontogenic in origin. The severe airway compromise caused by them may make diagnosis difficult. Suspicion of simultaneous occurrence of tetanus and retropharyngeal space infection in a child can further increase the dilemma.     

Acute leukemia: a pediatric perspective

The spectrum of hematological malignancies differs markedly between children and adults. Moreover, diseases such as acute lymphoblastic leukemia, acute myeloid leukemia, and myelodysplastic syndrome also demonstrate distinct biologic features and responses to treatment between these populations. In this review, we summarize our current understanding of the molecular pathology of acute leukemia and myelodysplastic syndrome, emphasizing areas in which studies in pediatric patients are providing unique insights into the hematopoietic malignancies of adults.