Reoperative Experience with Papillary Thyroid Cancer

Background

Intense postoperative monitoring has resulted in increasing detection of patients with recurrent papillary thyroid cancer (PTC). Our goals included quantifying successful reoperation, and analyzing surgical complications and reasons for relapse.

Methods

From 1999 to 2008, a total of 410 patients underwent reoperation for PTC relapse. We analyzed post-reoperative disease outcomes, reasons for relapse, and complications.

Results

Bilateral reoperative thyroidectomy was performed in 13 (3 %) patients; lobectomy, 34 (8 %); central neck (VI) soft tissue local recurrence excision, 47 (11.5 %); bilateral VI node dissection, 107 (26 %); unilateral VI dissection, 112 (27 %); levels II–V dissection, 93 (23 %); levels III–V, 86 (21 %); lateral single- or two-compartment dissection, 51 (12 %); and node picking, 20 (5 %) of level VI and 53 (13 %) lateral neck. Complications occurred in 6 %; including hypoparathyroidism, 3 %; unintentional recurrent laryngeal nerve (RLN) paralysis, 3 %; phrenic nerve injury, 0.5 %; spinal accessory nerve injury, 0.5 %; and chyle leak in 1.6 %. Of 380 (93 %) patients with follow-up (mean 5.2 years); 274 (72 %) patients are alive with no structural evidence of disease, 38 % developed disease relapse (mean 2.1 years), 42 (11 %) died from PTC, and 55 (14 %) are alive with disease. The reason for relapse was a false negative pre-reoperative ultrasound (US) in 18 (5 %), nodal recurrence in the operative field in 37 (10 %), a combination of these two reasons in 10 (3 %), and disease virulence (local or systemic recurrence) in 81 (21 %).

Conclusions

Although 72 % of patients were rendered structurally disease free after reoperation, nearly 40 % suffered additional relapse. Improved surgical technique or preoperative localization might positively affect 15–20 %; at least 20 % reflect the biologic aggressiveness of the disease.     

Acquired Glanzmann's thrombasthenia without thrombocytopenia: a severe acquired autoimmune bleeding disorder

Acquired Glanzmann's thrombasthenia (GT) is an uncommon accompaniment to immune thrombocytopenic purpura. Rarely, GT may present as an acquired autoimmune disorder of platelet function, with rapid onset of a moderate-to-severe bleeding tendency, a prolonged bleeding time, but with a normal platelet count and normal platelet glycoprotein (GP) expression. This is caused by an autoantibody with specificity for platelet GP IIb/IIIa or an epitope close to that of the GP, resulting in partial or complete refractoriness of the patient's platelets to ADP, collagen and arachidonic acid. We describe two patients with acquired GT and a normal platelet count, who presented with severe bleeding. The first patient responded gradually to immunosuppressive treatment but eventually developed non-Hodgkin's lymphoma. The second patient had no other underlying conditions and remitted spontaneously within 2 years.     

Covalent structure of human haptoglobin: a serine protease homolog.

The complete amino acid sequences and the disulfide arrangements of the two chains of human haptoglobin 1-1 were established. The alpha 1 and beta chains of haptoglobin contain 83 and 245 residues, respectively. Comparison of the primary structure of haptoglobin with that of the chymotrypsinogen family of serine proteases revealed a significant degree of chemical similarity. The probability was less than 10(-5) that the chemical similarity of the beta chain of haptoglobin to the proteases was due to chance. The amino acid sequence of the beta chain of haptoglobin is 29--33% identical to bovine trypsin, bovine chymotrypsin, porcine elastase, human thrombin, or human plasmin. Comparison of haptoglobin alpha 1 chain to activation peptide regions of the zymogens revealed an identity of 25% to the fifth "kringle" region of the activation peptide of plasminogen. The probability was less than 0.014 that this similarity was due to chance. These results strongly indicate haptoglobin to be a homolog of the chymotrypsinogen family of serine proteases. Alignment of the beta-chain sequence of haptoglobin to the serine proteases is remarkably consistent except for an insertion of 16 residues in the region corresponding to the methionyl loop of the serine proteases. The active-site residues typical of the serine proteases, histidine-57 and serine-195, are replaced in haptoglobin by lysine and alanine, respectively; however, aspartic acid-102 and the trypsin specificity, residue, aspartic acid-189, do occur in haptoglobin. Haptoglobin and the serine proteases represent a striking example of homologous proteins with different biological functions.     

Coagulation abnormalities and ivermectin.

Prothrombin ratios were measured 13-16 days after treatment in 148 subjects from Sierra Leone taking part in a double-blind placebo-controlled trial of ivermectin. Prolonged prothrombin ratios were observed more frequently in the ivermectin group, although this difference was not significant and no patients suffered bleeding complications. Further investigation of these patients failed to reveal any abnormality of liver function, although factor VII and II levels were reduced in most affected individuals, suggesting interference with vitamin K metabolism. Ivermectin has a minimal effect on coagulation and concern about mass treatment for this reason appears to be unjustified.     

Mechanism of antithrombin III inhibition of factor VIIa/tissue factor activity on cell surfaces. Comparison with tissue factor pathway inhibitor/factor Xa-induced inhibition of factor VIIa/tissue factor activity

Recent studies have shown that antithrombin III (AT III)/heparin is capable of inhibiting the catalytic activity of factor VIIa bound either to relipidated tissue factor (TF) in suspension or to TF expressed on cell surfaces. We report studies of the mechanism of which by AT III inhibits factor VIIa bound to cell surface TF and compare this inhibitory mechanism with that of tissue factor pathway inhibitor (TFPI)-induced inhibition of factor VIIa/TF. AT III alone and AT III/heparin to a greater extent reduced factor VIIa bound to cell surface TF. Our data show that the decrease in the amount of factor VIIa associated with cell surface TF in the presence of AT III was the result of (1) accelerated dissociation of factor VIIa from cell surface TF after the binding of AT III to factor VIIa/TF complexes and (2) the inability of the resultant free factor VIIa-AT III complexes to bind effectively to a new cell surface TF site. Binding of TFPI/factor Xa to cell surface factor VIIa/TF complexes markedly decreased the dissociation of factor VIIa from the resultant quaternary complex of factor VIIa/TF/TFPI/factor Xa. Addition of high concentrations of factor VIIa could reverse the AT III-induced inhibition of cell surface factor VIIa/TF activity but not TFPI/factor Xa-induced inhibition of factor VIIa/TF activity.     

Chronic shoulder pain in the community: a syndrome of disability or distress?

Objectives: To investigate two questions in a community based population of people with chronic shoulder pain. Firstly, does chronic pain lead to impaired psychological health over time? Secondly, how does restriction of daily activity influence pain perception and psychological health? Methods: Two postal surveys, two years apart, were carried out to identify a group of subjects with chronic shoulder pain. The first survey was sent to a random sample of adults (n=40026) registered with a primary care practice, and included a pain manikin, demographic information, and the Hospital Anxiety and Depression scale (HAD). The second survey was sent to those subjects who reported unilateral shoulder region pain in the first survey and it included a shoulder-specific disability scale, pain severity score, and the HAD. Results: 2606 (65.1%) people responded to the initial survey. Of these, 304 (11.7%) reported unilateral shoulder region pain at baseline. In the subsequent survey, there were 234 responders (83.3% adjusted response): 142 of these reported shoulder pain and formed our study group of "subjects with chronic shoulder pain". Within this group there was no significant change in psychological distress scores between baseline and follow up. Both the disability score and psychological distress scores correlated significantly with pain severity (disability v pain r=0.536, p<0.001; psychological distress v pain r=0.269, p=0.002). When the correlation between disability and pain severity was corrected for possible confounders, it remained significant (r=0.490, p<0.001). This was not the case for the correlation between psychological distress and pain (p>0.05). Disability was significantly correlated with psychological distress on univariate (r=0.445, p<0.001) and multivariate analysis (r=0.341, p=0.002). Conclusion: In those with chronic shoulder pain the relation between pain and psychological health seems to be linked to disability. Psychological distress was not explained by persistent pain itself.     

Synthesis of two collagen types by embryonic chick corneal epithelium in vitro.

To better understand the mechanisms involved in matrix development, we have analyzed the collagen synthesized by embryonic corneal epithelium, the tissue known to produce the collagenous component of the primary corneal stroma. Isolated epithelia were cultured in vitro in medium containing [oH]proline and the newly synthesized, labeled collagen was extracted, fractionally salt precipitated, and analyzed by carboxymethyl-cellulose chromatography and peptide mapping after cleavage with cyanogen bromide. The data show that the cornela epithelium produces at least two different types of collagen, one similar, if not identical, to the type I molecule of skin, and a second similar, if not identical, to the type II molecule of cartilage. Type II, heretofore, had been thought to be characteristic of cartilage extracellular matrix.     

Natural history of aberrant crypt foci

BACKGROUND: The aberrant crypt focus (ACF) appears to be an important early step in colorectal carcinogenesis. Our objectives were to determine the natural history of ACF in a surgical model. METHODS: The natural history of ACF was followed by marking the lesions in vivo with tattoos. Rats were given four weekly injections of azoxymethane (AOM; 20 mg/kg). One hundred days after the first injection of AOM, rats were anesthetized, and individual aberrant crypt focus was identified by staining with methylene blue. A 3× 3 mm area, identifying one large (4–8 crypts) ACF was marked with a tattoo dye in each colon. Control animals received saline or AOM injections and were tattooed in areas without ACF. At 200 days, colons were examined for the presence of macroscopic lesions. RESULTS: A total of 54 tumors were found in the study group of 38 animals, and 21 of these were in the transverse and proximal descending colon. The marked areas (all in transverse and proximal descending colon) yielded 6 tumors and 2 ACF, but in 30 instances no abnormality was noted. Probability of observing a tumor in the 3×3 mm area of the colon that was identified as containing ACFs was 17 times greater than expected from the observed tumor rate in approximately the same zone (16 vs. 1.7 percent; 95 confidence interval, 10 to 22 and 0.5 to 1.3 percent). Twenty control animals receiving saline had no tumors of epithelial origin. Nine control animals that were carcinogen-treated and tattooed in areas without ACF had no tumors in the marked areas. CONCLUSION: Results thus show regression of many ACF identified early in the carcinogenesis process. Results also support the hypothesis that some ACF are precursor lesions for adenomas and cancers.Supported by S. Lederman Fellowship Foundation, American Physician Fellowship, and, in part, by National Cancer Institute of Canada.