Management of thyroid carcinoma showing thymus-like differentiation (CASTLE) invading the trachea

Purpose

To define the clinicopathological features and discuss the optimal management of carcinoma showing thymus-like differentiation (CASTLE).

Methods

We retrospectively analyzed six patients with CASTLE.

Results

The subjects comprised two men and four women (average age at initial diagnosis, 61 years, range 47–75 years). Preoperative biopsy yielded a correct diagnosis in two patients. Five patients underwent surgery and one was treated with radiation therapy alone. Four had extrathyroidal invasion and three had lymph node metastasis. During the clinical course, tracheal invasion was detected in five patients, the upper extent of the tumor being the lower half of the first tracheal ring. Two of these patients underwent tracheal sleeve resection. Two patients received postoperative radiotherapy for nodal metastasis, and one, after palliative surgery. The median follow-up period was 67 months (range 38–129). Recurrence was found 10 years post-therapy in the patient treated with radiation therapy only, resulting in death soon after. Although local recurrence was not found in the remaining five patients, new pulmonary metastases were diagnosed in the patient who underwent non-curative surgery.

Conclusions

CASTLE can be diagnosed preoperatively by core needle biopsy and CD5 staining. Curative resection with neck dissection followed by radiotherapy can yield a good outcome. Larynx-sparing complete resection may be more feasible for CASTLE, even though it has a higher incidence of tracheal invasion than differentiated thyroid carcinoma.     

Dose-Dependent Conjugation of Sulfobromophthalein and Hepatic Transit Time in Bile Fistula Rats

Sulfobromophthalein (BSP) is selectively taken up by the liver and secreted into the bile as unconjugated and conjugated forms. Our previous study demonstrated that unconjugated BSP, but not conjugated BSP, caused the dissociation of biliary lipid secretion from that of bile acids, suggesting that the hepatic BSP conjugation rate partly regulated biliary lipid secretion. To evaluate the mechanisms through which biliary lipid secretion is regulated by exogenous organic anions, we intravenously administered BSP to male Sprague–Dawley rats at various doses either continuously or as a bolus. Then the relationship of the dose of BSP to its conjugation rate, hepatic transit time, and biliary lipid secretion was determined. BSP decreased biliary secretion of cholesterol and phospholipids in a dose-dependent manner without affecting bile acid secretion. In contrast, the proportion of conjugated BSP in bile was associated with the dose. Although the serum clearance of BSP after bolus infusion was constant regardless of the dose administered (50 or 200 nmol/100 g), BSP secretion was delayed with increasing doses: unconjugated BSP was secreted predominantly in the early phase (0–15 min after bolus injection), and conjugated BSP was the predominant form in the late phase (15–30 min). Pretreatment with colchicine reduced the conjugation rate and hepatic transit time of BSP, suggesting that the microtubule-dependent vesicle pathway plays a role in biliary excretion and conjugation of BSP. We conclude that biliary lipid secretion is influenced by organic anions with an affinity for bile acids such as BSP and that this effect is dependent upon the hepatic metabolic rate, i.e., conjugation rate. The hepatic transit time also plays a key role in this process by influencing metabolism.     

Spontaneous resolution of multiple nodular pulmonary AA amyloidosis

A 62-year-old man presented with a two-week history of dry cough. A chest computed tomography (CT) showed three nodular masses of soft tissue density without calcification or cavitary formation in the right lung. F-18 fluorodeoxyglucose PET/CT scan revealed high FDG uptake in two out of three pulmonary nodules. Transbronchial lung biopsy specimens consisted of amorphous eosinophilic deposits that were demonstrated to be amyloid because they were positive for Congo Red staining. After oxidation with permanganate solution, the Congo Red staining disappeared, indicating that this amyloid was amyloid A protein-derived type. There was no evidence of any systemic diseases. We diagnosed the patient as having multiple nodular pulmonary AA amyloidosis. The patient was conservatively managed without treatment, and the pulmonary nodules disappeared spontaneously three months later.     

Hypereosinophilia in a Patient with Invasive Thymoma with Clonal T-Lymphocyte Expansion Expressing CD4, CD8, and CD25 Antigens

We report the case of a patient with hypereosinophilia and invasive thymoma harboring probable clonal proliferation of CD4+, CD8+, and CD25+ T-lymphocytes. A 64-year-old woman had eosinophilia (14.1 x 10(9)/L) and an anterior mediastinal tumor with elevated levels of serum immunoglobulin E (609.8 mg/dL) and interleukin 5 (239 pg/mL). Bone marrow aspirate showed marked infiltration by morphologically normal eosinophils with a normal karyotype but no FIP1L1-PDGFRA fusion gene. Flow cytometric analysis revealed an increasing number of CD3+/CD25+ lymphocytes in the peripheral blood, and the resected thymoma had infiltrated lymphocytes with CD4/CD8/CD25 antigens. Moreover, the thymoma had T-cell receptor rearrangements with a cytogenetically clonal nature, ie, t(2;4)(p22;q26). Although the number of patients with thymoma showing hypereosinophilia is small, this case suggests that a subset of patients with thymoma may have clonal expansion of T-lymphocytes with abnormal phenotypes that affect clinical manifestations, including hypereosinophilia.     

Adenovirus expressing mutant p27kip1 enhanced apoptosis against cholangiocarcinoma than adenovirus-p27kip1 wild type

BACKGROUND/AIMS: The prognosis of cholangiocarcinoma is extremely poor despite the aggressive multidisciplinary cancer therapies that have been used clinically. Thus, it is imperative to develop new and effective treatments, such as gene therapy in order to treat this disease. p53 is the most common target for cancer gene therapy treatment. However, cholangiocarcinoma has a low frequency of p53 mutation, which makes this protein a poor candidate for gene therapy in this disease and another suitable gene therapy target must be found. p27kip1 is a universal cyclin-dependent kinase (CDK) inhibitor that blocks cell cycle progression and inhibits proliferation. Our previous reports have demonstrated the role of p27kip1 in the induction of apoptosis using a recombinant adenoviral vector expressing p27kip1 (Adp27) in several different human cancer cells. p27kip1 is regulated by two mechanisms composed of a ubiquitin-proteasome system and proteolytic processing system that requires the phosphorylation of p27kip1 on Thr-187 by the cyclinE/Cdk2 complex followed by proteolytic degradation. METHODOLOGY: In this study, we focused our aim on the degradation of p27kip1 protein mediated by a recombinant adenoviral expressing a mutant p27kip1 (Adp27-mt), which has a mutation of Thr-187/Pro-188 (ACGCCC) to Met-187/Ile-188 (ATGATC). RESULTS: We observed that the mutated p27kip1 markedly inhibited ubiquitination and the subsequent degradation of p27kip1 when compared to wild type p27kip1. Consequently, we found that mutated p27kip1 induced a stronger induction of apoptosis and cell growth inhibition than wild type p27kip1 in cholangiocarcinoma cell lines TFK-1 and HuCCT-1. Furthermore, we demonstrated that Adp27-mt mainly caused G2/M arrest in the cell cycle progression and a decreased cyclinB1 and Cdc2 protein where as Adp27-wt mediated a G1/S arrest at 48 hours after infection. CONCLUSIONS: In this study, we showed that adenoviral vector expression of mutant p27kip1 protein inhibited degradation by the ubiquitin-proteasome system and strongly induced apoptosis and cell growth inhibition compared to wild type p27kip1. Thus recombinant adenovirus expressing mutant p27kip1 may be potentially useful for gene therapy against cholangiocarcinoma.     

Airway stenting for the treatment of laryngotracheal stenosis secondary to thyroid cancer

Background and objective:   Airway stenting can be a valuable therapeutic option for symptomatic airway stenosis, but its role in the palliation of advanced thyroid cancers invading the upper airway is unclear. This study examined the hypothesis that durable and replaceable silicone stents would give better results than self-expanding metallic stents.
Methods:   A retrospective analysis was conducted of consecutive patients stented for laryngotracheal obstruction due to thyroid cancer. Stenting was performed via a rigid bronchoscope when airway patency after dilatation was ≤50% of normal. Symptomatic improvement, Hugh-Jones (H-J) classification, Eastern Cooperative Oncology Group performance status (PS), and complications were analysed.
Results:   There were 37 stenotic lesions treated in 35 patients. The most common sites for these lesions were in the inclusive area extending from the cricoid cartilage to the first tracheal ring (26/37 lesions, 70%). Forty-five stents (12 silicone, 20 metallic, 13 T-tubes) were used in 43 interventions. All patients showed immediate symptomatic relief and significant improvement in both PS and H-J classifications. Critical complications were supraglottic stenosis (5/43 interventions, 12%) and, of those same five cases, stent migration was seen in all but one (4/45 implantations, 9%). As these complications occurred only in patients in whom the silicone stents had been placed in close proximity to the cricoid cartilage (5/10 patients, 50%), this emphasizes the unsuitability of silicone stents in such cases. The median survival time from stenting was 8 months. The 1-year survival rate was 40%.
Conclusions:   Airway stenting can achieve significant palliation in patients with thyroid cancer and airway obstruction. The study showed that for the most common lesions, the uncovered Ultraflex stent is associated with fewer critical complications than the silicone stents.     

Polymere Brenzcatechin-Derivate, 3. Darstellung und Eigenschaften von 3,4-Methylendioxybenzyl-methacrylat und seinen polymeren Derivaten

3,4-Methylenedioxybenzyl methacrylate ( 3 ) was synthesized from 3,4-methylenedioxybenzyl alcohol ( 2 ) and methacryloyl chloride. 3 was radically polymerized with tributylborane and copolymerized in cyclohexanone at room temperature under nitrogen. The following monomer reactivity ratios were determined M₁ = 3 : r₁ = 0,68 and r₂ = 0,40 for M₂ = styrene, r₁ = 0,78 and r₂ = 0,16 for M₂ = acrylonitril, and r₁ = 0,28 and r₂ = 1,47 for methyl methacrylate. Polymeric derivatives having 3,4-dihydroxybenzyl units in the side chains were prepared from homo- and copolymers of 3 . The thermal stability and redox behaviour of these polymers were investigated.     

Carbon Dioxide Water Bathing Enhances Myogenin but Not MyoD Protein Expression after Skeletal Muscle Injury

[Purpose] We reported that carbon dioxide (CO₂) water bathing acceleratesskeletal muscle regeneration; however, the underlying mechanism was unclear. MyoD andmyogenin play roles in muscle regeneration, and the purpose of this study was to determinechanges in MyoD and myogenin caused by CO₂ water bathing after injury.[Subjects] Sixteen female Wistar rats (n = 4 per group) were used. [Methods] The rats weredivided into four groups: no-injury (NI), injury (IC), injury + tap water bathing (ITW),and injury + CO₂ water bathing (ICO₂). Muscle injury was induced byinjection of bupivacaine hydrochloride into the left tibial anterior (TA) muscles. Tapwater and CO₂ (1,000 ppm) water bathing were performed at 37 °C for 30 minutesonce a day. The left TA muscles were removed 4 days after injury, and the expressions ofMyoD and myogenin were measured. [Results] MyoD and myogenin were increased in the IC,ITW, and ICO₂ groups compared with the NI group. Although the MyoD level wassimilar in the IC, ITW, and ICO₂ groups, myogenin increased more in theICO₂ group than in the IC and ITW groups. [Conclusion] CO₂ waterbathing after muscle injury appears to induce an increase in the expression ofmyogenin.     

The effect of eradicating helicobacter pylori on the development of gastric cancer in patients with peptic ulcer disease

OBJECTIVES: Infection with Helicobacter pylori is a risk factor for the development of gastric cancer. However, it is not known whether eradication therapy can prevent the development of gastric cancer in persons in whom the cancer is not yet established. In the present study, we investigated whether the eradication of H. pylori in patients with peptic ulcer disease reduces the likelihood of their developing gastric cancer. METHODS: Prospective posteradication evaluations were conducted in 1,342 consecutive patients (1,191 men and 151 women; mean age: 50 yr) with peptic ulcer diseases who had received H. pylori eradication therapy. After confirmation of eradication, endoscopy and a urea breath test were performed yearly. RESULTS: A total of 1,120 patients completed more than 1-yr follow-up and were followed for up to 8.6 yr (a mean of 3.4 yr). Gastric cancer developed in 8 of 944 patients cured of infection and 4 of 176 who had persistent infection (p= 0.04; log-rank test). All the gastric cancer developed in patients with gastric ulcer, but none in patients with duodenal ulcer (p= 0.005; Fisher's exact test). In patients with gastric ulcer, persistent infection was identified as a significant factor for the risk of developing gastric cancer (hazard ratio: 3.35; 95% confidence interval: 1.00-11.22; p= 0.04; Cox's proportional-hazards model). CONCLUSION: H. pylori eradication may reduce their risk of developing gastric cancer in patients with gastric ulcer. Large-scale studies in additional populations of this important international public-health issue are warranted.     

A randomized open trial for comparison of proton pump inhibitors, omeprazole versus rabeprazole, in dual therapy for Helicobacter pylori infection in relation to CYP2C19 genetic polymorphism

BACKGROUND AND AIM: The genetic polymorphism of cytochrome P450 (CYP) 2C19 has been shown to influence the efficacy of Helicobacter pylori eradication therapy with a proton pump inhibitor (PPI) and amoxicillin (so-called dual therapy). Omeprazole, a widely used PPI, and rabeprazole, a new PPI, are metabolized in different pathways in terms of CYP2C19 genetic polymorphisms. In this study, we compared the efficacy of omeprazole and rabeprazole in a 2-week dual therapy in relation to CYP2C19 polymorphism. METHODS: One hundred and ninety-nine patients with peptic ulcer disease were randomly assigned to receive one of the following regimens: 500 mg t.i.d. amoxicillin together with either 20 mg b.i.d. omeprazole or 10 mg b.i.d rabeprazole. The eradication of H. pylori was evaluated by using a bacterial culture and a [(13)C]-urea breath test at 1--2 months after completion of treatment. Cytochrome P4502C19 polymorphism was analyzed by using polymerase chain reaction-restriction fragment length polymorphism. RESULTS: Intention-to-treat-based cure rates for the omeprazole or rabeprazole regimens were 66.3% (95% CI, 56--75) and 62.4% (95% CI, 52--71), respectively, without significant difference. Cytochrome P4502C19 genetic polymorphism did not influence the cure rates in either of these regimens. We analyzed various factors associated with treatment failure (PPI, CYP2C19 genotype, and smoking habit) by using multiple logistic regression; smoking was the only significant independent factor for treatment failure. CONCLUSION: Omeprazole and rabeprazole were equally effective in combination with amoxicillin in eradicating H. pylori, irrespective of the PPI used (omeprazole or rabeprazole) and CYP2C19 genetic polymorphism. Smoking significantly decreased the cure rate of H. pylori infection in the dual therapy.