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.     

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.     

Fish navigation of large dams emerges from their modulation of flow field experience

Navigating obstacles is innate to fish in rivers, but fragmentation of the world’s rivers by more than 50,000 large dams threatens many of the fish migrations these waterways support. One limitation to mitigating the impacts of dams on fish is that we have a poor understanding of why some fish enter routes engineered for their safe travel around the dam but others pass through more dangerous routes. To understand fish movement through hydropower dam environments, we combine a computational fluid dynamics model of the flow field at a dam and a behavioral model in which simulated fish adjust swim orientation and speed to modulate their experience to water acceleration and pressure (depth). We fit the model to data on the passage of juvenile Pacific salmonids (Oncorhynchus spp.) at seven dams in the Columbia/Snake River system. Our findings from reproducing observed fish movement and passage patterns across 47 flow field conditions sampled over 14 y emphasize the role of experience and perception in the decision making of animals that can inform opportunities and limitations in living resources management and engineering design.Understanding how the design and management of civil infrastructure modifies the outcome of naturally evolved behavior in animals is critical for sustainably using limited environmental resources to spur economic development and maintain native species. The issue is particularly relevant for rivers, which make up only 0.0002% of water on Earth (1) but support more than 40% of the world’s human population (2, 3). River regulation to meet society’s needs has accelerated in the past two centuries (4), leaving over half of the world’s major rivers now fragmented by >50,000 large dams providing water, energy, flood control, and transportation (3, 5, 6). The demand for large hydropower continues, spurred by the need for economic development while limiting carbon use (7). However, dams impede the dispersal and migration of fish, a problem that, along with other factors, has contributed to the loss of populations and entire species (5). These losses have cultural, economic, and geopolitical repercussions (3, 8), because more than 40% of the world’s human population lives in internationally shared river basins (9) and declines in fish populations jeopardize the food security of hundreds of millions worldwide (10–12).In North America, the tension between economic development and living resource conservation is evident in the Columbia River basin. Flowing from Canada to the United States, the river once supported one of the world’s largest salmon runs, with annual returns of 10–16 million fish (13) sustaining tribal nations and ecosystems far from the ocean (14). However, years of overharvesting, land-use changes, ocean conditions, and dams have contributed to a decline in the annual return of salmon (15). To reverse the decline, millions of dollars are spent each year seeking a durable hydroelectric strategy to improve annual returns (1–2 million fish). A major emphasis in restoration is ensuring that millions of downstream migrating juvenile salmon reach the ocean where they grow before returning to the river as adults.Hydropower dams on the river provide three general routes of passage for downstream migrating fish: powerhouse turbines, a spillway, and often a bypass specifically designed for fish. These routes differ in their mortality effects on fish, so an understanding of how fish behavior determines route selection is important for mitigating the impacts of dams on the populations. However, route selection behavior is poorly understood. Not only has it been difficult to explain route passage patterns at one dam, but it has been even more difficult to explain why the pattern may be different at another dam with similar routes.