Michele Camandona

Secondary and Tertiary Hyperparathyroidism: Causes of Recurrent Disease After 446 Parathyroidectomies

ObjectiveTo determine, in a series of patients with secondary and tertiary parathyroid hyperplasia, whether the type of parathyroidectomy (subtotal, total with autotransplantation, or total), the histologic pattern of the parathyroid tissue, or the proliferative index, as determined by Ki-67 analysis, could predispose patients to recurrent hyperparathyroidism. Summary Background DataRecurrent hyperparathyroidism appears in 10–70% of the patients undergoing surgery for secondary or tertiary hyperparathyroidism. The incidence could be related to the type of operation (Rothmund) but also depends on the histologic pattern of the glands removed (Niederle). MethodsThe retrospective investigation was performed on 446 patients undergoing parathyroid surgery. They were also studied in relation to the possibility of renal transplantation. In this population, two homogeneous groups were subsequently identified (23 patients with clear signs of recurrence and 27 patients apparently cured); they were studied from the histologic and immunohistochemical point of view using antibody to Ki-67 antigen. ResultsSubtotal parathyroidectomy, total parathyroidectomy with autotransplantation, and total parathyroidectomy produced similar results when considering the regression of osteodystrophy, pruritus, and ectopic calcification. As one could anticipate, tota1parathyroidectomy increased the incidence of hypoparathyroidism. The percentage of recurrence was 5% to 8% after subtotal parathyroidectomy, total parathyroidectomy with autotransplantation, and total parathyroidectomy, and only after incomplete parathyroidectomy did this percentage climb to 34.7%. In the recurrence group, the nodular form was more common and the proliferative fraction detected by Ki-67 was 1.9%; it was 0.81% in the control group. ConclusionsBecause more radical procedures were not more effective, the authors favor a less radical procedure such as subtotal parathyroidectomy. Histologic patterns and proliferative fraction could be useful indices of a recurrence, and these patients should be watched closely after surgery.

Endoscopic insertion of 248 prostheses in inoperable carcinoma of the esophagus and cardia: short-term and long-term results

We present our findings after 248 endoscopic intubations with the Nottingham introducer and more recently with the Dumon-Gilliard system for inoperable carcinoma of the esophagus and cardia. Mortality within the first week was 7.6% decreasing to 4.3% with the Dumon-Gilliard method. Survival after 3 months was 61.5%, after 6 months 32.3%, after 1 year 4.8%. The quality of swallowing was very good in 51.5% of the cases, while 36.7% of the patients suffered from dysphagia for semisolids and 10.1% for semiliquids. Obstruction occurred in 36 cases; proximal and distal dislocations were found in four cases each. In 20 patients with esophagorespiratory fistula we had an operative mortality of 15%, but 6-month survival was 35.7% and 1 year survival was 7.1%.

Differential expression of transforming growth factors-β1, -β2 and -β3 in human colon carcinoma

Transforming growth factor (TGF)-beta is a protein family which affects multiple cellular functions including survival, proliferation, differentiation and adhesion. Among the three known isoforms, TGF-beta1 is commonly overexpressed in solid malignancies. Recent studies in knock-out mice demonstrated non-redundant roles of different TGF-beta isoforms in development. The present study was performed to assess tumour-associated expression of the three TGF-beta isoforms in colon carcinoma. We report that colon carcinoma progression is associated with gradual and significant increases in expression of TGF-beta1 and TGF-beta2 mRNA and proteins. By contrast, TGF-beta3 expression was detected in normal colonic mucosa and, at slightly higher levels, in tumour tissues. In addition, plasma levels of both TGF-beta1 and TGF-beta2 were significantly higher in cancer patients when compared with unaffected individuals. Taken together, our results indicate distinct expression patterns of the three TGF-beta isoforms in colon carcinoma cells and possible systemic effects of TGF-beta1 and TGF-beta2 in tumour patients.

The usefulness of preoperative dual-phase 99mTc MIBI-scintigraphy and IO-PTH assay in the treatment of secondary and tertiary hyperparathyroidism.

Background:Persistent secondary or tertiary hyperparathyroidism (HPT) results from failure to remove enough hyperfunctioning parathyroid tissue. Ectopically situated parathyroid glands and supernumerary glands make failure more likely. Recurrent HPT after subtotal Ptx is usually due to regrowth of the remaining parathyroid tissue. Recurrence may also develop from a hyperplastic supernumerary gland or rarely from parathyromatosis. Recurrent HPT after total Ptx with autotransplantation is usually due to overgrowth of the autograft or for the previously mentioned reasons. Methods:Since 1995, 464 patients with SHPT or THPT were treated surgically; intraoperative parathormone (PTH) was measured in 277 patients. Sixty-eight patients also had a preoperative MIBI scan. We compared the preoperative MIBI scan results with intraoperative findings, parathyroid gland weight and histology. We questioned whether MIBI uptake corresponded to parathyroid gland size and weight. We also correlated the number of Ki67 nuclear positive cells with MIBI uptake. For SHPT in group I with 145 patients, neither intraoperative PTH (IO-PTH) assay nor MIBI scanning was done. In group II with 163 patients IO-PTH was used and in group III with 48 patients both IO-PTH and MIBI scanning was used. For THPT in group I with 42 patients, neither IO-PTH assay nor MIBI scanning was done. In group II with 46 patients IO-PTH was used and in group III with 20 patients both IO-PTH and MIBI scanning was used. Results:Parathyroid weight correlated directly with MIBI uptake. No correlation, however, occurred between MIBI uptake and parathyroid histology or between Ki67 staining and MIBI scanning. For SHPT in group I the persistence rate was 6.2% and recurrence rate 11%; in group II the persistence rate was 4.9% and recurrence rate 4.9%; in group III the persistence rate was 2%, and recurrence 4.2% (P < 0.05 between group I and III for persistence and recurrence). We obtained similar results in THPT, but recurrence was 0 in groups II and III, also when only 3 glands were removed, probably due to asymmetric hyperplasia commonly seen in this particular population (P < 0.05 regarding recurrence between group I and II–III, no difference between group II and III). Conclusion:In conclusion our findings support that the surgeon experience is a very important factor for good results in patients with SHPT and THPT. Preoperative MIBI scanning and IO-PTH are helpful but not essential except in reoperations.

Comparative evaluation of cancer stem cell markers in normal pancreas and pancreatic ductal adenocarcinoma

Chemoresistance and self-renewal of cancer stem cells (CSC), found in many tumors including pancreatic ductal adenocarcinoma (PDAC), are believed to underlie tumor mass regrowth. The distribution of cells carrying the putative stem-cell markers CD133, Nestin, Notch1-4, Jagged1 and 2, ABCG2 and aldehyde dehydrogenase (ALDH1) was assessed immunohistochemically using PDAC and normal pancreas tissue microarrays. The immunoreactivity was semi-quantitatively graded against the normal pancreas and was correlated with the differentiation grade and disease stage. No statistical significant differences were found between normal pancreas and PDAC in the expression of Nestin, Notch1, 3 and 4, ABCG2 or ALDH1. Notch2 and Jagged1 and 2 expression were increased in PDAC. CD133-positive cells were above-normal in PDAC, but the difference was not statistically significant. Nestin, Notch1-4, Jagged1, ABCG2 and ALDH1 immunostaining scores were not correlated with tumor grade or disease stage. CD133 and Notch2 expression was significantly inversely correlated with tumor grade, but not disease stage. Notch3 immunostaining positively correlated with tumor stage, but not with differentiation grade. Jagged2 protein expression correlated inversely with disease stage, but not with tumor grade. From the clinical standpoint, improved delineation of the tumor CSC signature, putatively responsible for tumor initiation and recurrence after initial response to chemotherapy, may offer novel therapeutic targets for this highly lethal cancer.

The diagnostic accuracy of the immunocytochemical markers in the pre-operative evaluation of follicular thyroid lesions

Aim of the study was to consider the diagnostic accuracy of galectine-3 (GAL3) in the pre-operative cytological evaluation of follicular lesions. Materials and methods: We retrospectively evaluated 100 patients suffering from thyroid nodular disease submitted to thyroidectomy from 2006 to 2007 in our Institution. Before surgery all patients underwent fine needle aspiration biopsy. The immunocytochemical analysis was performed on fine needle aspiration specimens using species-specific monoclonal antibodies and a biotin-free detection system. Based on preoperative cytological reports, 40 patients had pre-operative malignant results, and 60 patients (46 females and 14 males) showed follicular lesions. The sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy of GAL3 was evaluated. Statistical analysis: Chisquare test was used to compare frequencies of GAL3 expression between the different hystopathological groups. Results: GAL3 proved to have 55% sensitivity, 100% specificity, 70% negative predictive value, and 78% diagnostic accuracy. The GAL3 expression in neoplastic and benign lesions was significantly different (GAL3+ in 16 out of 29 neoplastic lesions, GAL3+ 0 out of 31 benign lesions, p<0.01). Even comparing the GAL3 positivity between the follicular adenomas (0 GAL3+ out of 20) and the group of follicular carcinomas (5 GAL3+ out of 6), we found a statistically significant difference (p<0.01). Conclusions: Based on the data from our experience, the patients with a cytological diagnosis of GAL3 positive follicular neoformation should be referred for surgery without any further immunocytological testing.

Transforming Growth Factor-β Binding Receptor Endoglin (CD105) Expression in Esophageal Cancer and in Adjacent Nontumorous Esophagus as Prognostic Predictor of Recurrence

BackgroundWe hypothesized that the potent neovascularization marker endoglin (CD105), by differentially highlighting a subset of microvessels (MV) in esophageal cancer (EC), could provide better prognostic/therapeutic information than the panendothelial marker CD34, which also highlights MV.MethodsEndoglin messenger ribonucleic acid (mRNA) expression in normal, malignant, and adjacent nontumorous esophagus tissue was quantified by real-time reverse-transcription polymerase chain reaction (RT-PCR). Sections of formalin-fixed, paraffin-embedded tissues were analyzed immunohistochemically for CD105 and CD34. MV density was counted following a standard protocol. Circulating soluble endoglin levels were determined in patient and control sera, and compared with clinical outcome.ResultsCD105 mRNA was upregulated by a median factor of 2.89 in ECs versus controls. In 28% of patients, CD105 mRNA was upregulated by a median factor of 2.65 in adjacent non-tumorous versus normal tissue. In tumor tissues, CD105 was stained negatively or positively only in a subset of MV. CD34 always showed positive extensive MV staining. In adjacent nontumorous esophagus, CD105 rarely showed diffuse MV staining, while CD34 stained blood-vessel endothelial cells in all non-neoplastic tissue. CD105 expression was high in residual highly dysplastic Barrett’s-type mucosa associated with some adenocarcinomas. No statistically significant difference in endoglin serum levels appeared between patients and normal subjects. Correlation with clinicopathological data showed higher intra-tumor MV-CD105+ scores at more-advanced clinical stages. High-scoring MV-CD105+ patients had significantly shorter disease-free and overall survival; MV-CD34+ density was not survival related. Diffuse CD105 expression in adjacent nontumorous esophagus predicted poorer disease-free and overall survival.ConclusionsOur findings could help identify EC patients who may benefit from targeted anti-angiogenic therapies.

Problems in reconstructive surgery in the treatment of carcinoma of the hypopharyngoesophageal junction

Thirty percent of carcinomas of the pyriform sinus manifest generally with infiltrations in the cervical esophagus. In recent years, progress in reconstructive surgery has broadened surgical indications to include tumors previously managed with palliative measures alone. In some cases, radical surgery has been extended to creating safer resection margins, with more and more indications for circular pharyngectomy. Lesions involving the hypopharyngoesophageal junction pose particular problems; furthermore, the high rate of synchronous or metachronous tumors warrants the indication for total esophagectomy, which requires complex reconstructive techniques.

Sliding Hiatal Hernia in the Elderly: A Clinical Entity

ABSTRACT: Sliding hiatal hernia occurs in the elderly with a symptom complex which differs from that seen in younger persons. A comparison of the symptoms of this disease in 66 older patients with the symptoms in 154 younger patients revealed four categories in the elderly: digestive, anemic, anginal, and pseudoneoplastic. Of these, the digestive‐tract abnormality, even though the most common, was the least characteristic and was caused by the associated pathologic lesions rather than by the hiatal hernia itself.

Carcinosarcoma of the esophagogastric junction.

Carcinosarcoma of the esophagus and the stomach are rare neoplasms characterized by the simultaneous presence of carcinomatous and sarcomatous elements. There is no report in the literature of carcinosarcoma of the esophagogastric junction. We present a case of carcinosarcoma of the esophagogastric junction whose unique clinical presentation, surgical issues, morphological and immunohistochemical features makes it quite distinctive from similar cases observed in the esophagus or in the stomach.