Sandro Mattioli

68ga-dota-noc: a new Pet tracer for evaluating patients with bronchial carcinoid

BackgroundConventional imaging techniques [computed tomography (CT), ultrasound, magnetic resonance] and somatostatin receptor scintigraphy are often insufficient to make a conclusive diagnosis of bronchial carcinoid (BC). PET is commonly used for the assessment of lung cancer but 18F-fluorodeoxyglucose, the most frequently used PET tracer, presents a low sensitivity for the detection of neuroendocrine tumours (NETs). New PET radiopharmaceuticals such as 68Ga-DOTA peptides, which directly bind to somatostatin receptors and are usually expressed on NET cell surfaces, have been reported to be superior to both morphological and somatostatin receptor scintigraphy imaging for gastroenteropancreatic NETs. However, their role in BC has never been evaluated. Our aim is to evaluate the role of 68Ga-DOTA-NOC (68Ga-labelled [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]-1-Nal3-octreotide) PET for the assessment of BC patients. MethodsTen patients with pathologically proven well-differentiated BC and one patient with highly suggestive CT images for BC were studied by 68Ga-DOTA-NOC PET/CT. PET findings were compared with clinical follow-up, pathology and contrast-enhanced CT findings. Results68Ga-DOTA-NOC PET/CT detected at least one lesion in nine of 11 patients and was negative in two. PET/CT and contrast-enhanced CT were discordant in eight of 11 patients, whereas in only three patients both provided similar results. PET/CT detected a higher number of lesions in five patients and excluded malignancy at sites considered positive on CT in three of 11; follow-up confirmed PET/CT findings in all patients. In PET/CT-positive patients, the mean maximal standardized uptake value was 25.9 [4.4–60.5]. On a clinical basis, PET/CT provided additional information in nine of 11 patients leading to the changes in the clinical management of three of nine patients. ConclusionPET/CT with 68Ga-DOTA-NOC was useful in BC patients because it led to a better evaluation of the extent of the disease.

Long-term results of the Heller–Dor operation with intraoperative manometry for the treatment of esophageal achalasia

OBJECTIVEnQuality of outcome of the Heller-Dor operation is sometimes different between studies, likely because of technical reasons. We analyze the details of myotomy and fundoplication in relation to the results achieved over a 30-year single centers experience.nnnMETHODSnFrom 1979-2008, a long esophagogastric myotomy and a partial anterior fundoplication to protect the surface of the myotomy was routinely performed with intraoperative manometry in 202 patients (97 men; median age, 55.5 years; interquartile range, 43.7-71 years) through a laparotomy and in 60 patients (24 men; median age, 46 years; interquartile range, 36.2-63 years) through a laparoscopy. The follow-up consisted of periodical interview, endoscopy, and barium swallow, and a semiquantitative scale was used to grade results.nnnRESULTSnMortality was 1 of 202 in the laparotomy group and 0 of 60 in the laparoscopy group. Median follow-up was 96 months (interquartile range, 48-190.5 months) in the laparotomy group and 48 months (interquartile range, 27-69.5 months) in the laparoscopy group. At intraoperative manometry, complete abolition of the high-pressure zone was obtained in 100%. The Dor-related high-pressure zone length and mean pressure were 4.5xa0± 0.4 cm and 13.3xa0± 2.2 mm Hg in the laparotomy group and 4.5xa0± 0.5 cm and 13.2xa0± 2.2 mm Hg in the laparoscopy group (Pxa0=xa0.75). In the laparotomy group poor results (19/201 [9.5%]) were secondary to esophagitis in 15 (7.5%) of 201 patients (in 2 patients after 184 and 252 months, respectively) and to recurrent dysphagia in 4 (2%) of 201 patients, all with end-stage sigmoid achalasia. In the laparoscopy group 2 (3.3%) of 60 had esophagitis.nnnCONCLUSIONSnA long esophagogastric myotomy protected by means of Dor fundoplication cures or substantially reduces dysphagia in the great majority of patients affected by esophageal achalasia and effectively controls postoperative esophagitis. Intraoperative manometry is likely the key factor for achieving the reported results.

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

OBJECTIVESnTo 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.nnnMETHODSnWe 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.nnnRESULTSnTwo 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.nnnCONCLUSIONSnACs 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.

Prognostic Evaluation of Disease Outcome in Solid Tumors Investigated With 64Cu-ATSM PET/CT.

Purpose 64Cu-ATSM is a very promising PET radiopharmaceutical for tumor imaging of hypoxia. One of the advantages of this compound compared with other hypoxia-avid tracers is the high tumor-to-background signal offered, which guaranties facilitated tumor delineation. This study analyzes optimal semiquantitative and quantitative parameters obtained by 64Cu-ATSM PET/CT in the same cohort of patients with special focus on their correlation to disease outcome. Patients and Methods A prospective recruitment of 18 consecutive patients (M:F, 13:5; mean age, 60.7 years) with locally advanced non–small cell lung cancer (n = 7) or head and neck cancer (HNC) was performed. Each participant received 105 to 500 MBq of tracer according to body size and was scanned in a 3-dimensional mode PET/CT 60 minutes after tracer injection. PET images were reconstructed and visualized on a GE Advanced 4.6 workstation for the definition of semiquantitative and quantitative parameters: SUVmax, SUVratio-to-muscle, hypoxic tumor volume (HTV), and hypoxic burden (HB = HTV × SUVmean). These data were subsequently correlated to disease outcome, expressed in terms of progression-free survival calculated on a follow-up period with a median of 14.6 months. Results All patients showed a moderately to highly increased uptake of 64Cu-ATSM in tumor lesions, with a mean SUVmax of 5.2 (range, 1.9–8.3) and mean SUVratio of 4.4 (range, 1.6–6.8). In addition, a broad range of HTV and HB was defined as mean values of 99.3 cm3 (range, 2.5–453.7 cm3) and 301 (4.2–1134), respectively. Receiver operating characteristic analysis identified as reference cutoffs with respect to disease outcome with the following values: SUVmax >2.5 (AUC, 0.57; sensitivity, 88.9%; specificity, 50%), SUVratio ⩽4.4 (AUC, 0.60; sensitivity, 50; specificity, 83.3%), HTV >160.7 cm3 (AUC, 0.61; sensitivity, 55.6%; specificity, 75%), and HB >160.7 (AUC, 0.67; sensitivity, 58.3%; specificity, 83.3%). In our cohort, HB showed a statistically significant difference in terms of mean values on the analysis of variance test with respect to disease progression (P = 0.04). On univariate analysis, Cox regression confirmed these findings and showed a significant correlation to progression-free survival for HB (P = 0.05) and HTV (P = 0.02). Conclusions In our cohort, the definition of optimal semiquantitative and quantitative parameters on 64Cu-ATSM PET/CT seems feasible and in line with previously published data. However, when considering the prognostic role with respect to disease outcome, the more robust parameters are represented by HTV and HB.

Sublobar resection versus lobectomy for stage I non-small cell lung cancer: an appropriate choice in elderly patients?

PurposesThe aim of this study was to evaluate whether sublobar resection could achieve recurrence and survival rates equivalent to lobectomy in high-risk elderly patients.MethodsWe conducted a retrospective multicenter study that including all consecutive patients (agedxa0>75xa0years) who underwent operation for clinical stage I non-small cell lung cancer (NSCLC). The clinicopathological data, postoperative morbidity and mortality, recurrence rate and vital status were retrieved. The overall survival, cancer-specific survival and disease-free survival were also assessed.ResultsTwo hundred and thirty-nine patients (median age 78xa0years) were enrolled. Lobectomies were performed in 149 (62.3xa0%) patients and sublobar resections in 90 (39 segmentectomies, 51 wedge resections). There were no differences in the recurrence rates following lobar versus sublobar resections (19 versus 23xa0%, respectively; pxa0=xa00.5) or the overall survival (pxa0=xa00.1), cancer-specific survival (pxa0=xa00.3) or disease-free survival (pxa0=xa00.1). After adjusting for 1:1xa0propensity score matching and a matched pair analysis, the results remained unchanged. A tumor sizexa0>2xa0cm and pN2 disease were independent negative prognostic factors in unmatched (pxa0=xa00.01 and pxa0=xa00.0003, respectively) and matched (pxa0=xa00.02 and pxa0=xa00.005, respectively) analyses.ConclusionsHigh-risk elderly patients may benefit from sublobar resection, which provides an equivalent long-term survival compared to lobectomy.

The frequency of true short oesophagus in type II–IV hiatal hernia

OBJECTIVESnThe misdiagnosis of short oesophagus may occur on recurrence of the hernia after surgery for type II-IV hiatal hernia (HH). The frequency of short oesophagus in type II-IV hernia is undefined. The aim of this study was to assess the frequency of true short oesophagus in patients undergoing surgery for type II-IV hernia.nnnMETHODSnThirty-four patients with type II-IV hernia underwent minimally invasive surgery. After full isolation of the oesophago-gastric junction, the position of the gastric folds was localized endoscopically and two clips were applied in correspondence. The distance between the clips and the diaphragm (intra-abdominal oesophageal length) was measured. When the intra-abdominal oesophagus was <1.5 cm after oesophageal mobilization, the Collis procedure was performed. After surgery, patients underwent a follow-up, comprehensive of barium swallow and endoscopy.nnnRESULTSnAfter mediastinal mobilization (median 10 cm), the intra-abdominal oesophageal length was >1.5 cm in 17 patients (4 type II, 11 type III and 2 type IV) and ≤ 1.5 cm in 17 patients (13 type III and 4 type IV hernia). No statistically significant differences were found between patients with intra-abdominal oesophageal length > or ≤ 1.5 cm with respect to symptoms duration and severity. Global results (median follow-up 48 months) were excellent in 44% of patients, good in 50%, fair in 3% and poor in 3%. HH relapse occurred in 3%.nnnCONCLUSIONSnTrue short oesophagus is present in 57% of type III-IV and in none of type II HHs. The intraoperative measurement of the submerged intra-abdominal oesophagus is an objective method for recognizing these patients.

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

Early and delayed evaluation of solid tumours with 64Cu-ATSM PET/CT: a pilot study on semiquantitative and computer-aided fractal geometry analysis

Objective The aim of this study was to analyse early and delayed acquisition on copper-64 diacetyl-bisN4-methylthiosemicarbazone (64Cu-ATSM) PET/CT in a small cohort of patients by comparing semiquantitative and computer-aided fractal geometry analyses. Patients and methods Five cancer patients, including non-small-cell lung cancer and head and neck cancer, were investigated with 64Cu-ATSM PET/CT. Participants received an intravenous injection of 64Cu-ATSM according to body size and were imaged 60u2009min (early) and 16u2009h (delayed) later on hybrid PET/CT. Reconstructed images were visualized on advanced workstations for the definition of semiquantitative parameters: standardized uptake value (SUV)max, SUVratio-to-muscle, SUVmean, hypoxic volume (HV) and hypoxic burden (HB=HV×SUVmean). DICOM data retrieved from both scans were analysed using an ad-hoc computer program to determine the mean intensity value, SD, relative dispersion, three-dimensional histogram fractal dimension and three-dimensional fractal dimension. Results All tumour lesions showed increased uptake of 64Cu-ATSM at early evaluation, with a median SUVratio-to-muscle of 4.42 (range: 1.58–5.62), a median SUVmax of 5.3 (range: 1.9–7.3), a median SUVmean of 2.8 (range: 1.5–3.9), a median HV of 41.6u2009cm3 (range: 2.8–453.7) and a median HB of 161.5u2009cm3 (range: 4.4–1112.5). All semiquantitative data obtained at 1u2009h were consistent with the parameters obtained on delayed imaging (P>0.05). A borderline statistically significant difference was found only for SUVmax of the muscle (P=0.045). Fractal geometry analysis on DICOM images showed that all parameters at early imaging showed no statistically significant difference with late acquisition (P>0.05). Conclusion Our findings support the consistency of 64Cu-ATSM PET/CT images obtained at early and delayed acquisition for the assessment of tumour lesions.

Total Lymphadenectomy and Nodes-Based Prognostic Factors in Surgical Intervention for Esophageal Adenocarcinoma

BACKGROUNDnTo evaluate prognostic factors based on the number of resected lymph nodes, we considered 202 patients who underwent radical resection and total lymphadenectomy for esophageal adenocarcinoma according to a prospective protocol.nnnMETHODSnFifty-eight tumors surrounded by Barretts epithelium underwent esophagectomy and esophagogastrostomy, and 144 tumors without Barretts epithelium underwent esophageal resection at the azygos vein level, total gastrectomy, and Roux-en-Y esophagojejunostomy. All nodes and fat tissue were resected at the following stations: chest 4L and R3, R4, R7, R8, and R9 (TNM seventh edition) and abdomen 1-12 according to the Japanese Classification of Gastric Carcinoma (1998). The nodes were counted, excluding fragments. The correlations between the number of nodes yielded and the ratio of the metastatic lymph nodes/lymph nodes yielded with pT stage, grading measurements, and cancer-specific survival (CSS) were calculated.nnnRESULTSnA total of 6,270 nodes were yielded (interquartile range per patient, 22-38; minimum, 4 nodes; maximum, 61 nodes). In 3 of 21 (14%) stage pT1 cases, less than 10 nodes were counted, in 2 of 27 (8%) stage pT2 cases, less than 20 were counted, and in 73 of 154 (47%) stage pT3-4 cases, less than 30 nodes were counted. The lymph node yield (LNY) and T stage were not correlated (rxa0= 0 .048; pxa0= 0.5). The metastatic lymph nodes to lymph nodes yielded ratio was correlated withxa0pT stage (rxa0= 0.272; pxa0= 0.0001), and G (rxa0= 0.385; pxa0= 0.0001). CSSxa0positively correlated with pT stage (pxa0= 0.02), G (pxa0=xa00.001), and metastatic lymph nodes/lymph nodes yielded ratio (pxa0= 0.01) (multivariate analysis).nnnCONCLUSIONSnThe total number of lymph nodes to be removed in total and within each T stage indicated as thresholds could not be reached in up to 38.6% of patients. The metastatic lymph nodes/lymph nodes yield ratio not the total LNY, did correlate with cancer-specific survival.