Expression of LGR5 in mammary myoepithelial cells and in triple-negative breast cancers.

Lineage tracing in mice indicates that LGR5 is an adult stem cell marker in multiple organs, such as the intestine, stomach, hair follicles, ovary, and mammary glands. Despite many studies exploring the presence of LGR5 cells in human tissues, little is known about its expression profile in either human mammary tissue or pathological lesions. In this study we aim to investigate LGR5 expression in normal, benign, and malignant lesions of the human breast using RNA in situ hybridization. LGR5 expression has not been observed in normal lactiferous ducts and terminal duct lobular units, whereas LGR5-positive cells have been specifically observed in the basal myoepithelium of ducts in the regenerative tissues, ductal carcinoma in situ, and in ducts surrounded by invasive cancer cells. These findings suggest LGR5 marks facultative stem cells that are involved in post injury regeneration instead of homeostatic stem cells. LGR5 positivity was found in 3% (9 of 278 cases) of invasive breast cancers (BC), and it showed positive associations with higher histologic grades (P = 0.001) and T stages (P < 0.001), while having negative correlations with estrogen receptor (P < 0.001) and progesterone receptor (P < 0.001) expression. Remarkably, all LGR5-positive BC, except one, belong to triple-negative BC (TNBC), representing 24% (9 of 38 cases) of all of them. LGR5 histoscores have no correlations with EGFR, CK5/6, Ki-67, or P53 expression. Additionally, no ß-catenin nuclear localization was observed in LGR5-positive BC, indicating that canonical Wnt pathway activation is less likely involved in LGR5 expression in BC. Our results demonstrate that LGR5 expression is induced in regenerative conditions in the myoepithelium of human mammary ducts and that its expression is only observed in TNBC subtype among all invasive BC. Further studies regarding the functional and prognostic impact of LGR5 in TNBC are warranted.

Inexpensive water soluble methyl methacrylate-functionalized hydroxyphthalimide: variations of the mycophenolic acid core for selective live cell imaging of free cysteine.

Evident from numerous studies, cysteine plays a crucial role in cellular function. Reactions with analyte also enables for molecular recognition to adhere to molecular therapeutic potential; integration between synthetic probes therefore allows for a potentially deep therapy-related interogation of biological systems (theranostics). The development of molecular cysteine probes with extremely accurate detection is still a key challenge for the field. The development of water-soluble organic molecular fluorescent probes able to efficiently distinguish common biothiols such as cysteine (Cys), homocysteine (Hcy) and glutathione (GSH) by chemical recognition means i.e. by (binding, cleavage) in biological systems is a greatly sought research challenge due to the similarity of the small sulfhydryl-containing species. Herein, we have developed a water-soluble and highly cell viable fluorescent organic molecule (log P = 0.82) for the selective detection of cysteine. The probe (Myco-Cys) shows a "turn-on" response with the cleavage ester linkage of the methacrylate as cysteine is encountered in solution. The probe shows strong fluorescence enhancement (16.5-fold) when treated with Cys (1 equiv., 10 µM) compared to closely related species such as amino acids, including HCy/GSH, and the limit of detection was determined as 45.0 nM. DFT calculations helped confirm the photomechanism of Myco-Cys. Furthermore, the sensing ability of the probe was demonstrated by living cell assays through the use of confocal fluorescence microscopy. Myco-Cys could selectively detect cysteine among biothiols. Myco-Cys was able to monitor the cysteine level, apart from the oxidative stress present in the form of H2O2 in A549 cells.

The clinical usefulness of chemokine C-X-C Motif Ligand 12 as a diagnostic marker for Papillary Thyroid Carcinoma.

BACKGROUND: Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer worldwide. It is essential to develop methods for the accurate diagnosis of PTC to avoid unnecessary surgery. The chemokine C-X-C motif ligand 12 (CXCL12) is associated with various cancers. We aimed to investigate the efficacy of CXCL12 in the diagnosis of PTC in fine-needle aspiration (FNA) specimens. METHODS: We prospectively collected samples from 58 patients who were scheduled for surgical treatment of PTC from 2013 to 2015. Tissue samples of 31 people with benign thyroid conditions were used as controls. Immunocytochemical and immunohistochemical staining for CXCL12 was performed on FNAs and corresponding tissue specimens. B-type Raf kinase (BRAF) V600E mutant protein expression and gene mutation were also analyzed to compare the clinical usefulness. RESULTS: : The mean age of the patients was 49.1 ± 1.4 years and 88.1% were women. Positive CXCL12 staining was observed in 6.5% of benign and in 98.3% of PTC samples; positive BRAF V600E mutant protein expression was found in 19.4% of benign and 93.1% of PTC samples. For the diagnosis of PTC for CXCL12 staining of FNA specimens, the calculated values were 93.1% sensitivity, 90.3% specificity, 94.7% positive predictive value, 87.5% negative predictive value, and 89.1% accuracy. CXCL12 had 100% sensitivity and specificity for the 12 cases of atypia of undetermined significance (AUS) diagnosed in FNA specimens. CONCLUSIONS: CXCL12 may be a useful diagnostic tool for PTC, especially when the FNA specimen is classified as AUS.

Surgical treatment of rhinophyma using an ordinary bur.

Rhinophyma is a painless benign tumor of the skin of the nose. It is the most severe form of rosacea. Rhinophyma is particularly rare among Asians. It can be treated with surgical resection using various methods, including scalpel excision, dermabrasion, cryosurgery, argon laser, carbon dioxide laser, and electrocautery. However, the gold standard treatment of rhinophyma remains unknown. In the present case, we debulked a giant rhinophyma with a scalpel and contoured it using a bur. Along with a relevant literature review, we present a case of rhinophyma in an Asian patient who was treated at no additional cost using a bur widely used in general plastic surgery.

Downregulation of SMOC2 expression in papillary thyroid carcinoma and its prognostic significance.

Secreted Protein Acidic and Rich in Cysteine (SPARC)-related modular calcium-binding protein-2 (SMOC2), a secreted matricellular protein, is reported to be involved in various processes related to cancer progression such as regulating the cell cycle, angiogenesis, and invasion. However, its expression and prognostic significance in papillary thyroid carcinomas (PTCs) remains unknown. Using immunohistochemistry, we evaluated the expression profile of SMOC2 and its prognostic value in a large cohort of PTCs. Real time-PCR analysis with fresh-frozen tissues showed that SMOC2 mRNA expression in PTCs was substantially lower than the expression in matched non-cancerous thyroid tissues, consistent with the results from thyroid cancer cell lines. Immunohistochemical analysis demonstrated that SMOC2 was normally present in thyroid follicular epithelial cells and the expression level was maintained in nodular hyperplasia. However, SMOC2 expression was significantly lower in lymphocytic thyroiditis and follicular tumors including follicular adenomas and carcinomas. In particular, 38% of PTCs exhibited a complete loss of SMOC2 expression, which was associated with the presence of BRAF (V600E) mutation. Moreover, SMOC2 further declined during lymph node metastasis in PTCs. DNA methylation chip analysis revealed one hypermethylated CpG site in the promoter region of SMOC2 gene, suggesting an epigenetic regulation of SMOC2 in PTCs. Remarkably SMOC2 positivity was associated with improved recurrence-free survival along with female sex, tumor size, and the N stage. However, SMOC2 was not identified as an independent prognostic marker in multivariate analyses. Taken together, SMOC2 expression is significantly down-regulated in PTCs and SMOC2 positivity is closely associated with better clinical outcomes, suggesting that SMOC2 can be a prognostic marker in PTC patients.

Detecting Synchronous Thyroid Adenoma and False-Positive Findings on Technetium-99m MIBI Single Photon-Emission Computed Tomography/Computed Tomography.

Technetium (Tc)-99m-methoxyisobutylisonitrile (MIBI) single photon-emission computed tomography/computed tomography (SPECT/CT) is now being used increasingly for preoperative localization of parathyroid adenomas. Tc-99m-MIBI scintigraphy in a 52-year-old man with a diagnosis of primary hyperparathyroidism revealed two focal areas with retention of radioactivity in the left lobe of the thyroid gland on the delayed phase of MIBI SPECT/CT but no significant focal radioactive uptake on MIBI planar images. The patient subsequently underwent left partial parathyroidectomy. Histological analysis identified one lesion to be thyroid hyperplasia and the other to be parathyroid adenoma. This case demonstrates the value of MIBI SPECT/CT for localization of a parathyroid lesion when compared with planar images and that false-positive findings can lead to misdiagnosis in a patient with coexisting thyroid disease. An appropriate diagnostic work-up that includes Tc-99m MIBI SPECT/CT in addition to ultrasonography is helpful for an accurate diagnosis in patients with concomitant thyroid disease.

Dual-Time-Point FDG Uptake Correlates with Prognostic Factors of Invasive Breast Cancer: Clinical Usefulness of Early Delayed Scanning.

This study investigated correlations between fluorodeoxyglucose (FDG) uptake in tumors as assessed by modified dual-time-point (mDTP) FDG positron emission tomography/computed tomography (PET/CT) in invasive breast cancer (iBC) and several prognostic parameters. Thirty-two women who underwent mastectomies for iBC were retrospectively evaluated. mDTP scanning was performed using standard FDG PET/CT (PET1), followed by early delayed acquisition (PET2) without repositioning and additional CT scanning. Using maximal standardized uptake values on PET1 (SUV1) and PET2 (SUV2) in the primary breast tumor, the percentage changes between SUV1 and SUV2 (retention index, (RI)) were calculated. Prognostic parameters (e.g., tumor size and stage; number of metastatic lymph nodes; histologic grade; expression of estrogen receptor (ER), progesterone, epidermal growth factor receptor (HER-2), and p53; and the Ki-67 labeling index (LI)) were evaluated from the surgical specimens. PET2 scans were conducted 17.7 ± 1.5 min after PET1. RI values gradually increased as the histologic grade increased (p = 0.016), and were significantly higher when ER expression was absent (p = 0.023) and Ki-67 LI was high (p < 0.001). RI values also showed a moderately positive correlation with Ki-67 LI (r = 0.629; p < 0.001). RI correlated with well-known biologic prognostic factors of iBC and mDTP scanning, which could be used as a substitute for conventional DTP PET.

The role of adjuvant external beam radiation therapy for papillary thyroid carcinoma invading the trachea.

PURPOSE: To evaluate the effect of adjuvant external beam radiation therapy (EBRT) on local failure-free survival rate (LFFS) for papillary thyroid cancer (PTC) invading the trachea. MATERIALS AND METHODS: Fifty-six patients with locally advanced PTC invading the trachea were treated with surgical resection. After surgery, 21 patients received adjuvant EBRT and radioactive iodine therapy (EBRT group) and 35 patients were treated with radioactive iodine therapy (control group). RESULTS: The age range was 26-87 years (median, 56 years). The median follow-up period was 43 months (range, 4 to 145 months). EBRT doses ranged from 50.4 to 66 Gy (median, 60 Gy). Esophagus invasion and gross residual disease was more frequent in the EBRT group. In the control group, local recurrence developed in 9 (9/35, 26%) and new distant metastasis in 2 (2/35, 6%) patients, occurring 4 to 68 months (median, 37 months) and 53 to 68 months (median, 60 months) after surgery, respectively. Two patients had simultaneous local recurrence and new distant metastasis. There was one local failure in the EBRT group at 18 months after surgery (1/21, 5%). The 5-year LFFS was 95% in the EBRT group and 63% in the control group (p = 0.103). In the EBRT group, one late grade 2 xerostomia was developed. CONCLUSION: Although, EBRT group had a higher incidence of esophagus invasion and gross residual disease, EBRT group showed a better 5-year LFFS. Adjuvant EBRT may have contributed to the better LFFS in these patients.

Agreement between MRI and pathologic breast tumor size after neoadjuvant chemotherapy, and comparison with alternative tests: individual patient data meta-analysis.

BACKGROUND: Magnetic resonance imaging (MRI) may guide breast cancer surgery by measuring residual tumor size post-neoadjuvant chemotherapy (NAC). Accurate measurement may avoid overly radical surgery or reduce the need for repeat surgery. This individual patient data (IPD) meta-analysis examines MRI's agreement with pathology in measuring the longest tumor diameter and compares MRI with alternative tests. METHODS: A systematic review of MEDLINE, EMBASE, PREMEDLINE, Database of Abstracts of Reviews of Effects, Heath Technology Assessment, and Cochrane databases identified eligible studies. Primary study authors supplied IPD in a template format constructed a priori. Mean differences (MDs) between tests and pathology (i.e. systematic bias) were calculated and pooled by the inverse variance method; limits of agreement (LOA) were estimated. Test measurements of 0.0 cm in the presence of pathologic residual tumor, and measurements >0.0 cm despite pathologic complete response (pCR) were described for MRI and alternative tests. RESULTS: Eight studies contributed IPD (N = 300). The pooled MD for MRI was 0.0 cm (LOA: +/-3.8 cm). Ultrasound underestimated pathologic size (MD: -0.3 cm) relative to MRI (MD: 0.1 cm), with comparable LOA. MDs were similar for MRI (0.1 cm) and mammography (0.0 cm), with wider LOA for mammography. Clinical examination underestimated size (MD: -0.8 cm) relative to MRI (MD: 0.0 cm), with wider LOA. Tumors "missed" by MRI typically measured 2.0 cm or less at pathology; tumors >2.0 cm were more commonly "missed" by clinical examination (9.3 %). MRI measurements >5.0 cm occurred in 5.3 % of patients with pCR, but were more frequent for mammography (46.2 %). CONCLUSIONS: There was no systematic bias in MRI tumor measurement, but LOA are large enough to be clinically important. MRI's performance was generally superior to ultrasound, mammography, and clinical examination, and it may be considered the most appropriate test in this setting. Test combinations should be explored in future studies.

Early radiographic and clinical results of Salto total ankle arthroplasty as a fixed-bearing device.

BACKGROUND: Total ankle replacement has increased in popularity in the management of severe tibiotalar arthritis. Most previous clinical reports focused on mobile-bearing designs. This study evaluates early radiographic and clinical results of the Salto fixed bearing design. METHODS: Twenty-three Salto fixed-bearing implants were prospectively studied. Records were reviewed for clinical outcome scores (VAS, AOFAS, SF36), subsequent surgeries, complications, radiographic data and implant survivorship. Average follow-up was 36 months. RESULTS: Statistically significant improvements in VAS, AOFAS ankle/hindfoot scores, and SF36 scores were shown at an average of 3 years postoperatively. At 3 years followup, survivorship of the implant was 82.6% with any reoperation as the endpoint and 95.6% for revision or removal of components. Seven patients had radiolucencies around the implant, one of which required revision to arthrodesis. CONCLUSION: The fixed-bearing Salto ankle replacement has comparable early radiographic and clinical results to reports of the mobile-bearing Salto of comparable followup. LEVEL OF EVIDENCE: Level IV.

Pharmacological activation of NQO1 increases NAD⁺ levels and attenuates cisplatin-mediated acute kidney injury in mice.

Cisplatin is a widely used chemotherapeutic agent for the treatment of various tumors. In addition to its antitumor activity, cisplatin affects normal cells and may induce adverse effects, such as ototoxicity, nephrotoxicity, and neuropathy. Various mechanisms, such as DNA adduct formation, mitochondrial dysfunction, oxidative stress, and inflammatory responses, are critically involved in cisplatin-induced adverse effects. As NAD(+) is a cofactor for various enzymes associated with cellular homeostasis, we studied the effects of increased NAD(+) levels by means of NAD(P)H: quinone oxidoreductase 1 (NQO1) activation using a known pharmacological activator (ß-lapachone) in wild-type and NQO1(-/-) mice on cisplatin-induced renal dysfunction in vivo. The intracellular NAD(+)/NADH ratio in renal tissues was significantly increased in wild-type mice co-treated with cisplatin and ß-lapachone compared with the ratio in mice treated with cisplatin alone. Inflammatory cytokines and biochemical markers for renal damage were significantly attenuated by ß-lapachone co-treatment compared with those in the cisplatin alone group. Notably, the protective effects of ß-lapachone in wild-type mice were completely abrogated in NQO1(-/-) mice. Moreover, ß-lapachone enhanced the tumoricidal action of cisplatin in a xenograft tumor model. Thus, intracellular regulation of NAD(+) levels through NQO1 activation might be a promising therapeutic target for the protection of cisplatin-induced acute kidney injury.

Prospective study of the treatment of adult primary hallux valgus with scarf osteotomy and soft tissue realignment.

BACKGROUND: The scarf osteotomy has been a widely practiced bunion operation, but relatively limited prospective data on its outcomes have been reported. The purpose of this investigation was to prospectively evaluate the clinical and radiographic results of treatment of adult primary hallux valgus using the scarf osteotomy of the first metatarsal with soft tissue realignment. METHODS: Hallux valgus corrections were performed on 51 patients (53 feet), who were followed for at least 1 year with an average follow-up of 24 months. Mean age at the time of surgery was 59 years, and subjects included 3 male and 48 female patients. Prospective clinical data collected included the American Orthopaedic Foot & Ankle Society (AOFAS) hallux-interphalangeal scale score, the SF-36 scores, and the visual analogue scale (VAS) for pain. Data were collected preoperatively and postoperatively. Prospective radiologic data were also collected including hallux valgus angle (HVA), first-second intermetatarsal angle (IMA), and medial sesamoid position (MSP). Clinical data were collected on complications and reoperations. RESULTS: Mean AOFAS hallux-interphalangeal score increased from 52 preoperatively to 88 postoperatively. Mean preoperative and last follow-up SF-36 physical component summary increased from 46 preoperatively to 52 postoperatively, whereas mean VAS pain scores decreased from 5.8 preoperatively to 1.1 postoperatively. All the changes in clinical outcomes were statistically significant, except the Mental Component Summary of the SF-36. Mean preoperative HVA decreased from 29 degrees preoperatively to 10.7 degrees in the initial postoperative period and was maintained at last follow-up at 10.6 degrees. The mean preoperative IMA decreased from 13.6 degrees preoperatively to 5.6 degrees in the initial postoperative period and regressed mildly at last follow-up to 7.8 degrees. The mean preoperative MSP grade of 2.3 decreased to 0.5 in the initial postoperative period and regressed mildly to 0.9 at last follow-up. All radiographic changes were statistically significant. The overall complication rate was 15% (8/53), attributable to 4 feet with symptomatic hardware, 2 feet with hallux varus, and 2 feet with progression of first MTP arthritis. Reoperations were performed in 4 feet (8%) for removal of symptomatic hardware. CONCLUSION: Scarf osteotomy was a reliable technique for correction of moderate to severe hallux valgus and had low rates of complication or recurrence. LEVEL OF EVIDENCE: Level IV, case series.

Functional disabilities and issues of concern for Asian patients before total ankle arthroplasty.

Total ankle arthroplasty is a commonly performed invasive procedure that can be distressing to patients. Therefore, surgeons should consider patients' issues of greatest interest and concerns at the time of surgery and the function that patients hope to recover. Many studies have reported surgeon concerns before total knee arthroplasty and total hip arthroplasty, but few have focused on patients. The purpose of this study was to evaluate patients' functional disabilities and issues of concern regarding total ankle arthroplasty.Between May 2008 and June 2010, eighty-five patients (52 men and 33 women; mean age, 60 years) were recruited for the study. All patients were asked to complete a questionnaire divided into 3 parts: sociodemographic data, current functional disabilities and their perceived importance, and issues concerning patients before total ankle arthroplasty. Regarding functional disability based on severity, the top 5 issues were limping, difficulty squatting, daytime pain, difficulty kneeling, and difficulty climbing stairs. Regarding functional disability based on perceived importance, the top 5 issues were daytime pain, limping, difficulty walking, difficulty kneeling, and difficulty working. Regarding issues of concern, the top 5 issues were pain intraoperatively, ability to walk as much as desired, ability to climb stairs, pain after discharge from the hospital, and pain immediately postoperatively. The most important issue before total ankle arthroplasty was pain. Patients had a strong interest in high ankle extension and increased range of motion due to the lifestyle and religious activities of Eastern populations.

Endoscopic versus open bursectomy of lateral malleolar bursitis.

PURPOSE: Compare the result of endoscopic versus open bursectomy in lateral malleolar bursitis. MATERIALS AND METHODS: Prospective evaluation of 21 patients (22 ankles) undergoing either open or endoscopic excision of lateral malleolar bursitis. The median age was 64 (38-79) years old. The median postoperative follow-up was 15 (12-18) months. RESULTS: Those patients undergoing endoscopic excision showed a higher satisfaction rate (excellent 9, good 2) than open excision (excellent 4, good 3, fair 1). The wounds also healed earlier in the endoscopic group although the operation time was slightly longer. One patient in the endoscopic group had recurrence of symptoms but complications in the open group included one patient with skin necrosis, one patient with wound dehiscence, and two patients of with superficial peroneal nerve injury. CONCLUSIONS: Endoscopic resection of the lateral malleolar bursitis is a promising technique and shows favorable results compared to the open resection. LEVEL OF EVIDENCE: Therapeutic studies-Investigating the result of treatment, Level II.

Is a thyroid follicular neoplasm a good indication for endoscopic surgery?

Endoscopic thyroidectomy is a safe and feasible alternative as compared with conventional open thyroidectomy in patients with a small thyroid cancer or a benign thyroid tumor. However, despite the many advantages of endoscopic surgery, it can result in unexpected complications. Recently, the authors experienced a case of follicular thyroid cancer recurrence that developed around the operative bed and along the port insertion site after endoscopic thyroidectomy for a large follicular neoplasm. The authors suggest that a smaller follicular neoplasm is a good indication for endoscopic thyroidectomy, but that a large follicular neoplasm should not be viewed as indicators for endoscopic surgery, because of the possibility of malignancy and rupture during manipulation.

Is robotic surgery superior to endoscopic and open surgeries in thyroid cancer?

BACKGROUND: Endoscopic thyroidectomies have been performed using various approaches, and indications have expanded with the development of new surgical techniques and instruments. Endoscopic thyroid surgery using bilateral axillo-breast approaches have excellent cosmetic results and a symmetrical, optimal operative view. However, because of the two-dimensional view and the nonflexible instruments, these approaches are not easy to use in performing a central lymph node dissection (CND). Robotic surgery has drawn attention as a potentially safe and effective method for treating thyroid cancer. The aim of the present study was to determine whether robotic surgery is superior to endoscopic and open surgery through comparing technical aspects and surgical outcomes. METHODS: From October 2008 to December 2009, 302 patients had total thyroidectomies and CND with cancer less than 1 cm. Patients were divided into three groups according to operation methods (open group; n = 138), (endo group; n = 95), (robot group; n = 69). RESULTS: Young patients preferred the robotic and endoscopic surgery. The number of retrieved lymph nodes in the open group (4.8 ± 2.8) was not different from the robot group (4.7 ± 2.7) and the endo group (4.6 ± 3.7). The operative time of the robot group was longer than the open and the endo group. The total drain amount in the robot group was more than the open and endo groups; however, there was no difference in the length of hospitalization and complication rates. There were no differences between the open (0.8 ± 2.0) and robot groups (0.8 ± 1.4), but the endo group (2.4 ± 6.3) showed higher postoperative serum thyroglobulin off thyroid hormone (Off-Tg) when compared to the open and robot groups. CONCLUSIONS: Robotic surgery was equal to open surgery except with respect to operative time and was superior to endoscopic surgery in Off-Tg levels presenting completeness of the operation in thyroid cancer surgery. Because it has excellent cosmetic results and various technical advantages, it should be considered in young, low-risk patients with thyroid carcinoma less than 1 cm.

Radioguided surgery using an intraoperative PET probe for tumor localization and verification of complete resection in differentiated thyroid cancer: a pilot study.

BACKGROUND: The major concerns in the surgical treatment of extensive or recurrent thyroid cancer include the difficulty of precise intraoperative and real-time tumor localization, the possibility of missing small metastatic lymph nodes during the operation, the need for reoperation due to recurrence, and complications. The usefulness and feasibility of an intraoperative PET probe have been reported for many other cancers; however, a standard, radioguided, operative protocol using a PET probe in thyroid cancer has not been established. The purpose of the current study was to evaluate the feasibility of an intraoperative PET probe with respect to precise tumor localization, verification of complete resection, and a decrease in unnecessary reoperations and complications. METHODS: This was a prospective, controlled study. Inclusion criteria were thyroid cancer requiring a total thyroidectomy with a modified radical neck dissection (MRND) and recurrent thyroid cancer after thyroid surgery. The types of procedures included total thyroidectomy with MRND, selective neck dissection (SND), and excision of recurrent thyroid masses. The PET probe NodeSeeker(®) is a high-energy gamma probe seeking 511 keV photons. Operative exploration was carried out between 2 and 6 h after injection of (18)F-FDG. The surgeon calculated the target-to-background ratio (T/B ratio) by checking the 10-sec accumulated count using the PET probe. We performed a re-exploration if the T/B ratio was >1.3 in the operative bed. RESULTS: Twelve patients underwent PET probe-guided operation. SNDs, mass excisions, total thyroidectomy with MRND, and MRND were performed on 7, 4, and 1 patient, respectively. All tumors were localized by the PET probe precisely in real time, and the lesions not observed on preoperative PET were detected by the PET probe in 7 patients. Furthermore, additional lymph nodes that were not identified on preoperative ultrasonography were detected in 1 patient. The mean T/B ratio of thyroid carcinoma was 1.51 ± 0.53 (range, 1.17-4.03) and the postoperative serum thyroglobulin off thyroid hormone was <2.0 ng/ml. CONCLUSION: Radioguided surgery using an intraoperative PET probe in thyroid cancer appears to be a useful method for real-time tumor localization, verification of complete excision, and minimization of the possibility of residual cancer. Therefore, an intraoperative PET probe in thyroid cancer may decrease unnecessary reoperations and complications due to persistent disease.

(18)F-FDG PET/CT Findings in a Breast Cancer Patient with Concomitant Tuberculous Axillary Lymphadenitis.

Although (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) is a sensitive modality for detecting a malignant lesion, increased (18)F-FDG uptake is also seen in infected or inflammatory processes. Here, we report the case of a breast cancer patient with concomitant tuberculous axillary lymphadenitis that showed increased (18)F-FDG uptake. A 39-year-old woman underwent preoperative (18)F-FDG PET/computed tomography (CT) as a part of the work-up for right breast cancer. (18)F-FDG PET/CT images showed a malignant lesion in the right breast with moderate (18)F-FDG uptake, and multiple enlarged right axillary lymph nodes with intense (18)F-FDG uptake. Subsequently, the patient underwent right mastectomy and right axillary lymph node dissection. Histopathological examination confirmed breast cancer and tuberculous lymphadenitis, and the patient was treated concomitantly with anti-tuberculous therapy.

Activation of lipopolysaccharide-TLR4 signaling accelerates the ototoxic potential of cisplatin in mice.

Dysfunction in immune surveillance during anticancer chemotherapy of patients often causes weakness of the host defense system and a subsequent increase in microbial infections. However, the deterioration of organ-specific function related to microbial challenges in cisplatin-treated patients has not yet been elucidated. In this study, we investigated cisplatin-induced TLR4 expression and its binding to LPS in mouse cochlear tissues and the effect of this interaction on hearing function. Cisplatin increased the transcriptional and translational expression of TLR4 in the cochlear tissues, organ of Corti explants, and HEI-OC1 cells. Furthermore, cisplatin increased the interaction between TLR4 and its microbial ligand LPS, thereby upregulating the production of proinflammatory cytokines, such as TNF-α, IL-1ß, and IL-6, via NF-κB activation. In C57BL/6 mice, the combined injection of cisplatin and LPS caused severe hearing impairment compared with that in the control, cisplatin-alone, or LPS-alone groups, whereas this hearing dysfunction was completely suppressed in both TLR4 mutant and knockout mice. These results suggest that hearing function can be easily damaged by increased TLR expression and microbial infections due to the weakened host defense systems of cancer patients receiving therapy comprising three to six cycles of cisplatin alone or cisplatin combined with other chemotherapeutic agents. Moreover, such damage can occur even though patients may not experience ototoxic levels of cumulative cisplatin concentration.