Oral adverse events due to zinc deficiency after pancreaticoduodenectomy requiring continuous intravenous zinc supplementation: a case report and literature review.

BACKGROUND: Zinc is mainly absorbed in the duodenum and proximal jejunum, which are removed during pancreaticoduodenectomy (PD). Little is known about the adverse oral events and skin disorders caused by zinc deficiency after PD. Herein, we reviewed studies on the development of zinc deficiency after PD and reported about a patient with zinc deficiency after PD who required home intravenous zinc replacement. CASE PRESENTATION: A 73-year-old woman with glossitis, taste disorder, and acrodermatitis enteropathica-like eruption on her fingers presented to the Division of Dentistry and Oral Surgery 69 days after PD. Her serum zinc level markedly decreased to 30 µg/dL. Oral zinc administration was inadequate to treat hypozincemia after PD; therefore, multi-trace elements were injected intravenously during readmission. Her serum zinc levels recovered, and her lesions gradually improved. Furthermore, a central venous port was implanted to maintain normal serum zinc levels, and she continued self-injecting zinc at home. CONCLUSIONS: Zinc deficiency after PD rarely occurs. The clinical oncologist community, including dentists responsible for the oral care of cancer patients, should be aware of the oral adverse events, such as dysgeusia, glossitis, and oral pain, associated with zinc deficiency after cancer surgery and that induced by chemotherapy or head and neck radiation therapy.

An Adult Mouse Thyroid Side Population Cell Line that Exhibits Enriched Epithelial-Mesenchymal Transition.

BACKGROUND: Studies of thyroid stem/progenitor cells have been hampered due to the small organ size and lack of tissue, which limits the yield of these cells. A continuous source that allows the study and characterization of thyroid stem/progenitor cells is desired to push the field forward. METHOD: A cell line was established from Hoechst-resistant side population cells derived from mouse thyroid that were previously shown to contain stem/progenitor-like cells. Characterization of these cells were carried out by using in vitro two- and three-dimensional cultures and in vivo reconstitution of mice after orthotopic or intravenous injection, in conjunction with quantitative reverse transcription polymerase chain reaction, Western blotting, immunohisto(cyto)chemistry/immunofluorescence, and RNA seq analysis. RESULTS: These cells were named SPTL (side population cell-derived thyroid cell line). Under low serum culturing conditions, SPTL cells expressed the thyroid differentiation marker NKX2-1, a transcription factor critical for thyroid differentiation and function, while no expression of other thyroid differentiation marker genes were observed. SPTL cells formed follicle-like structures in Matrigel® cultures, which did not express thyroid differentiation marker genes. In mouse models of orthotopic and intravenous injection, the latter following partial thyroidectomy, a few SPTL cells were found in part of the follicles, most of which expressed NKX2-1. SPTL cells highly express genes involved in epithelial-mesenchymal transition, as demonstrated by RNA seq analysis, and exhibit a gene-expression pattern similar to anaplastic thyroid carcinoma. CONCLUSION: These results demonstrate that SPTL cells have the capacity to differentiate into thyroid to a limited degree. SPTL cells may provide an excellent tool to study stem cells, including cancer stem cells of the thyroid.

Expression of stanniocalcin 1 in thyroid side population cells and thyroid cancer cells.

BACKGROUND: Mouse thyroid side population (SP) cells consist of a minor population of mouse thyroid cells that may have multipotent thyroid stem cell characteristics. However the nature of thyroid SP cells remains elusive, particularly in relation to thyroid cancer. Stanniocalcin (STC) 1 and 2 are secreted glycoproteins known to regulate serum calcium and phosphate homeostasis. In recent years, the relationship of STC1/2 expression to cancer has been described in various tissues. METHOD: Microarray analysis was carried out to determine genes up- and down-regulated in thyroid SP cells as compared with non-SP cells. Among genes up-regulated, stanniocalcin 1 (STC1) was chosen for study because of its expression in various thyroid cells by Western blotting and immunohistochemistry. RESULTS: Gene expression analysis revealed that genes known to be highly expressed in cancer cells and/or involved in cancer invasion/metastasis were markedly up-regulated in SP cells from both intact as well as partial thyroidectomized thyroids. Among these genes, expression of STC1 was found in five human thyroid carcinoma-derived cell lines as revealed by analysis of mRNA and protein, and its expression was inversely correlated with the differentiation status of the cells. Immunohistochemical analysis demonstrated higher expression of STC1 in the thyroid tumor cell line and thyroid tumor tissues from humans and mice. CONCLUSION: These results suggest that SP cells contain a population of cells that express genes also highly expressed in cancer cells including Stc1, which warrants further study on the role of SP cells and/or STC1 expression in thyroid cancer.

Stem cell antigen 1-positive mesenchymal cells are the origin of follicular cells during thyroid regeneration.

Many tissues are thought to contain adult stem/progenitor cells that are responsible for repair of the tissue where they reside upon damage and/or carcinogenesis, conditions when cellular homeostasis becomes uncontrolled. While the presence of stem/progenitor cells of the thyroid has been suggested, how these cells contribute to thyroid regeneration remains unclear. Here we show the origin of thyroid follicular cells and the process of their maturation to become follicular cells during regeneration. By using ß-galactosidase (ß-gal) reporter mice in conjunction with partial thyroidectomy as a model for thyroid regeneration, and bromodeoxyuridine (BrdU) long label-retaining cell analysis, we demonstrated that stem cell antigen 1 (Sca1) and BrdU-positive, but ß-gal and NKX2-1 negative cells were found in the non-follicular mesenchymal area 7 days after partial thyroidectomy. They temporarily co-expressed cytokeratin 14, and were observed in part of follicles by day 35 post-partial thyroidectomy. Sca1, BrdU, ß-gal, and NKX2-1-positive cells were found 120 days post-partial thyroidectomy. These results suggested that Sca1 and BrdU positive cells may participate in the formation of new thyroid follicles after partial thyroidectomy. The process of thyroid follicular cell regeneration was recapitulated in ex vivo thyroid slice collagen gel culture studies. These studies will facilitate research on thyroid stem/progenitor cells and their roles in thyroid diseases, particularly thyroid carcinomas.

Thyroid regeneration: characterization of clear cells after partial thyroidectomy.

Although having the capacity to grow in response to a stimulus that perturbs the pituitary-thyroid axis, the thyroid gland is considered not a regenerative organ. In this study, partial thyroidectomy (PTx) was used to produce a condition for thyroid regeneration. In the intact thyroid gland, the central areas of both lobes served as the proliferative centers where microfollicles, and bromodeoxyuridine (BrdU)-positive and/or C cells, were localized. Two weeks after PTx, the number of BrdU-positive cells and cells with clear or faintly eosinophilic cytoplasm were markedly increased in the central area and continuous to the cut edge. Clear cells were scant in the cytoplasm, as determined by electron microscopy; some retained the characteristics of calcitonin-producing C cells by having neuroendocrine granules, whereas others retained follicular cell-specific features, such as the juxtaposition to a lumen with microvilli. Some cells were BrdU-positive and expressed Foxa2, the definitive endoderm lineage marker. Serum TSH levels drastically changed due to the thyroidectomy-induced acute reduction in T(4)-generating tissue, resulting in a goitrogenesis setting. Microarray followed by pathway analysis revealed that the expression of genes involved in embryonic development and cancer was affected by PTx. The results suggest that both C cells and follicular cells may be altered by PTx to become immature cells or immature cells that might be derived from stem/progenitor cells on their way to differentiation into C cells or follicular cells. These immature clear cells may participate in the repair and/or regeneration of the thyroid gland.

Oral health care reduces the risk of postoperative surgical site infection in inpatients with oral squamous cell carcinoma.

PURPOSE: Postoperative wound infection (WI) is a main complication after head and neck surgery. Poor oral health may be a risk factor for WI. We therefore assessed the contribution of oral health care in preventing postoperative WI in patients with oral squamous cell carcinoma (OSCC). METHODS: A total of 66 consecutive inpatients with OSCC (mean age, 68 years) was divided into two groups that did or did not receive oral health care. There were no significant between group differences in gender, age, or T-, N-, or clinical stage. Patients in the care group were given oral health care plans by doctors of oral medicine, whereas patients in the control group were not. Twenty-three variables were recorded for each patient. RESULTS: WI was observed in 14/66 patients (21%), three (3/33 = 9%) in the care group and 11 (11/33 = 33%) in the control group (p < 0.025). Univariate statistical analysis showed that 11 factors correlated with WI significantly: T-stage, clinical stage, wearing of dentures, tracheostomy, neck dissection, tissue transplantation, oral health care, preoperative radiation, blood transfusion, operation time, and blood loss. In multiple logistic regression analysis, only two factors were significant independent risk factors for WI: tissue transplantation (p = 0.01; odds ratio, 24.5) and lack of oral health care (p = 0.04; odds ratio, 6.0). CONCLUSION: Oral health care may reduce the risk of postoperative WI in patients with OSCC.

Changes in saliva interleukin-6 levels in patients with oral squamous cell carcinoma.

OBJECTIVE: The aim of this study was to elucidate changes in interleukin-6 (IL-6) levels in whole saliva during the treatment of patients with oral squamous cell carcinoma (OSCC). STUDY DESIGN: Twenty-nine consecutive inpatients with OSCC were enrolled. Stimulated saliva was collected just after hospitalization (period 1), just before main treatment (surgery in 26 cases; period 2), and at the time of discharge (period 3). The mean intervals were 11+/-8 days between periods 1 and 2 and 30+/-18 days between periods 2 and 3. Nineteen age-matched healthy control subjects were also recruited. Interleukin-6 concentrations were measured by a highly sensitive chemiluminescent enzyme immunoassay. RESULTS: Interleukin-6 was detected in 23 out of 29 samples in the OSCC group in period 1. The concentration of IL-6 was significantly higher in the OSCC group (mean 20.1+/-36.3 pg/mL) than in the control subjects (0.6+/-0.8 pg/mL; P=.003). The mean concentration of IL-6 at period 2 was 43.6+/-95.6 pg/mL, significantly higher than at period 1 (P=.002), and at period 3 was 17.1+/-27.6 pg/mL (P=.52 [compared with period 2]). CONCLUSIONS: Interleukin-6 was up-regulated in saliva in the OSCC patients. The IL-6 level tended to increase before treatment, and it returned to baseline levels after treatment.

Cystadenoma of the palate: immunohistochemistry of mucins.

Cystadenoma is a relatively rare benign epithelial tumor of the salivary glands, and described herein is an additional case. A 51-year-old Japanese man had noticed a mass of the left hard palate 25 years previously. Macroscopically, the resected specimen was a multicystic lesion. Histologically, the tumor was composed of bilayered columnar epithelium with cystic change and partial solid growth of glandular structures with clear cells. The tumor cells had mild cellular atypia, but the tumor lacked papillary growth and a fibrous capsule. Immunohistochemistry was positive for cytokeratins, epithelial membrane antigen, MUC1, MUC4 and MUC6, but negative for myoepithelial markers, MUC2, MUC5AC and MUC5B. Such MUC expression patterns suggested that cystadenoma occurs from excretory ducts.