Alberto Ruffato

Cutaneous granulomatous reaction to injectable hyaluronic acid gel: Another case

We report a case of a granulomatous reaction in the melolabial folds, occurring 10 days after treatment with Restylane®. The patient, who had previously been treated with the same product in the last 2 years without any adverse effect, developed an unusual early fibrotic reaction that we hypothesized related to hypersensitivity after repeated use. The lesions slowly disappeared with topical steroid therapy. An improved knowledge of the modality of these uncommon adverse effects is necessary to assess the long‐term safety and efficacy of this product.

Prognostic factors in a multicentre study of 247 atypical pulmonary carcinoids.

OBJECTIVES To analyse clinical and biomolecular prognostic factors associated with the surgical approach and the outcome of 247 patients affected by primary atypical carcinoids (ACs) of the lung in a multi-institutional experience. METHODS We retrospectively evaluated clinical data and pathological tissue samples collected from 247 patients of 10 Thoracic Surgery Units from different geographical areas of our country. All patients were divided into four groups according to surgical procedure: sub-lobar resections (SURG1), lobar resections (SURG2), tracheobronchoplastic procedures (SURG3) and pneumonectomies (SURG4). Overall survival analysis was performed using the Kaplan-Meier method and log-rank test. Survival was calculated from the date of surgery to the last date of follow-up or death. The parameters evaluated included age, gender, smoking habits, laterality, type of surgery, 7th edition of TNM staging, mitosis Ki-67 (MIB1), multifocal forms, tumourlets, type of lymphadenectomy and neo/adjuvant therapy. For multivariate analysis, a Cox regression model was used with a forward stepwise selection of covariates. RESULTS Two hundred and forty-seven patients (124 females and 123 males; range 10-84, median 60 years) underwent surgical resection for AC in the last 30 years as follows: n = 38 patients in SURG1, 181 in SURG2, 15 in SURG3 and 14 in SURG4. A smoking history was present in 136 of 247 (55%) patients. The median follow-up period was 98.7 (range 11.2-369.9) months. The overall survival probability analysis of the AC was 86.7% at 5 years, 72.4% at 10 years, 64.4% at 15 years and 58.1% at 20 years. Neuroendocrine multicentric forms were detected in 12 of 247 patients (4.8%; 1 of 12 pts) during the follow-up (range 11.2-200.4, median 98.7 months) and 33.4% had recurrence of disease. There were no significant differences between gender, tumour location and type of surgery at the multivariate analysis. Age [P < 0.001, hazard ratio (HR) 0.60; confidence interval (CI) 0.32-1.12], smoking habits (P = 0.002; HR 0.43, 95% CI 0.23-0.80) and lymph nodal metastatic involvement (P = 0.008; HR 0.46, 95% CI 0.26-0.82) were all significant at multivariate analysis. CONCLUSIONS ACs of the lung are malignant neuroendocrine tumours with a worst outcome in patients over 70 years and in smokers. With the exception of pneumonectomy, the extent of resection does not seem to affect survival and should be accompanied preferably by lymphadenectomy. Pathological staging, along with a mitotic index more than Ki-67 (MIB1), appears to be the most significant prognostic factor at the univariate analysis.

Do bone marrow isolated tumor cells influence long-term survival of non-small cell lung cancer?

INTRODUCTION Inconsistent information on the prognostic significance of non-small cell lung cancer (NSCLC) isolated tumor cells (ITC) has been reported to date. We sought to evaluate the survival for NSCLC in a group of patients in which the presence of bone marrow isolated tumor cells and their DNA ploidy was assessed. MATERIALS AND METHODS Seventy patients (58 males [83%]; median age 70 years, range 49-89) with T1-4, N0, M0 clinical staging entered the study; 68 who underwent complete resection, were included in the follow-up. Two patients with clinical stage T2 and T4, N0, M0 were excluded because of pleural carcinosis discovered at thoracotomy. Recruitment ended in 2002. None received neoadjuvant therapy. The rib bone marrow was extracted and assessed for ITC by hematoxylin and eosin (H&E) staining, immunohistochemistry and flow cytometry. The latter was regarded as positive when >10% of cells reacted to pan-cytokeratin antibody MNF116. DNA ploidy was studied by propidium iodide staining. Patient follow-up was with chest X-ray and abdominal US every 6 months, and CT-PET scan every 12 months for at least 5 years after surgery. Causes of death were assessed. RESULTS Rib bone marrow ITC were documented in 17 patients (25%), 6 with DNA euploidy (p stage: I 4; III 2), and 11 with DNA aneuploidy (p stage: I 5; II 4; III 2) while 51 (75%) patients were free of ITC (p stage: I 32; II 8; III 9; IV 2). The median follow-up was 61 months, 21 patients died from causes unrelated to NSCLC and 12 patients died from causes related to tumor relapse. Significant survival differences were observed according to stage, presence of ITC and DNA aneuploidy. In particular free from recurrence survival was significantly reduced in stage IA and IB patients presenting aneuploid ITC (Wilcoxon (Gehan) test p=0.031). CONCLUSIONS The prognostic role of bone marrow ITC seems to be corroborated by DNA ploidy studies. Patients with bone marrow ITC with abnormal DNA content showed a significantly reduced survival particularly in stage I NSCLC.

Does Anatomical Segmentectomy Allow an Adequate Lymph Node Staging for cT1a Non-small Cell Lung Cancer?

Introduction: Anatomical segmentectomy is again under evaluation for the cure of T1a N0 non-small cell lung cancer and carcinoid tumors. Whether anatomical segmentectomy does permit or not, an adequate resection of nodal stations for staging or cure is still pending. Methods: A case-matched study was ruled on patients with peripheral cT1a N0 M0 tumors that underwent anatomical segmentectomy or lobectomy. Dissection of lymph node stations 4, 5, 6, and 7 was identical in anatomical segmentectomy and lobectomy; stations 10, 11, 12, and 13 were also dissected carefully during anatomical segmentectomy. Results: We individually matched 46 (69% men) anatomical segmentectomy with 46 (71% men) lobectomy for age, anatomical segment, and size of the tumor. The median (interquartile range) size of the resected lesions was 1.7 cm (1.35–1.95 cm) in anatomical segmentectomy and 1.6 cm (1.3–1.9 cm) (p = 0.96) in lobectomy. The anatomical segmentectomy and lobectomy resection margins were free of cancer. The median number (interquartile range) of total dissected lymph nodes was 12 (8–5–14) in anatomical segmentectomy compared with 13 (12–14.5) in lobectomy (p = 0.68), with a number of N1 nodes being 6 (4–7.5) and 7 (4.5–9.5) (p = 0.43), respectively, and N2 nodes 5.5 (4–7.7) and 5 (4–6.5) (p = 0.88). Only 1 patient of 46 (2%) anatomical segmentectomy was N1, whereas in lobectomy, 4% had N1 (2 patients). Freedom from recurrence at 36 months was 100% for anatomical segmentectomy and 93.5% for lobectomy (p = 0.33). Conclusions: Anatomical segmentectomy for cT1a tumors compared with lobectomy procures an adequate number of N1 and N2 nodes for pathological examination. Cancer-specific survival was equivalent at 36 months.

Short-term onset of fatal pulmonary toxicity in a patient treated with intravenous amiodarone for post-operative atrial fibrillation

A 77 year-old man was admitted to our Institution with the diagnosis of adenocarcinoma of the cardia. The patient had no history of pulmonary or cardiac disease. In the past he had been a heavy smoker, he had undergone distal gastric resection for duodenal ulcer, but he did not complain of any pulmonary symptoms. The pre-operative work-up assessment of pulmonary function showed that FEV1 was 2.81 lt (111% of predicted); FEV1/FVC ratio was 76% (111% of the predicted value), PO2 was 107.3 mm Hg, PCO2 34.4 mm Hg and SATO

Esophagogastric metaplasia relates to nodal metastases in adenocarcinoma of esophagus and cardia.

BACKGROUND Immunohistochemical profiles of esophageal and cardia adenocarcinoma differ according to the presence or absence of Barretts epithelium (BIM) and gastric intestinal metaplasia (GIM) in the fundus and antrum. Different lymphatic spreading has been demonstrated in esophageal adenocarcinoma. We investigated the correlation among the presence or absence of intestinal metaplasia in the esophagus and stomach and lymphatic metastases in patients who underwent radical surgery for esophageal and cardia adenocarcinoma. METHODS The mucosa surrounding the adenocarcinoma and the gastric mucosa were analyzed. The BIM+ patients underwent subtotal esophagectomy and gastric pull up, and the BIM- patients underwent esophagectomy at the azygos vein, total gastrectomy, and esophagojejunostomy. The radical thoracic (station numbers 2, 3, 4R, 7, 8, and 9) and abdominal (station numbers 15 through 20) lymphadenectomy was identical in both procedures except for the greater curvature. RESULTS One hundred ninety-four consecutive patients were collected in three major groups: BIM+/GIM-, 52 patients (26.8%); BIM-/GIM-, 90 patients (46.4%); BIM-/GIM+, 50 patients (25.8%). Two patients (1%) were BIM+/GIM+. A total of 6,010 lymph nodes were resected: 1,515 were recovered in BIM+, 1,587 in BIM-/GIM+, and 2,908 in BIM-/GIM- patients. The percentage of patients with pN+ stations 8 and 9 was higher in BIM+ (p=0.001), and the percentage of patients with pN+ perigastric stations was higher in BIM- (p=0.001). The BIM-/GIM- patients had a number of abdominal metastatic lymph nodes higher than did the BIM-/GIM+ patients (p=0.0001). CONCLUSIONS According to the presence or absence of BIM and GIM in the esophagus and cardia, adenocarcinoma correspond to three different patterns of lymphatic metastasization, which may reflect different biologic and carcinogenetic pathways.