Effect of Cigarette Smoking on Thyroid Cancer: Meta-Analysis

Background@#Although smoking is generally carcinogenic, its effect on thyroid cancers is still subject to controversy. The purpose of this study was to summarize the role of smoking in relation to thyroid cancer occurrence. @*Methods@#We performed a meta-analysis of 24 eligible studies: 21 case-control studies and three prospective cohort studies. The summary odds ratio (OR) and 95% confidence interval (CI) of all studies were acquired based on random effect model. Further subgroup analyses were conducted according to gender, histological type of thyroid cancer, and smoking status of patients for the case-control studies. @*Results@#The summary effect size indicated a negative association of smoking for thyroid cancer (OR, 0.798; 95% CI, 0.681 to 0.935). From the subgroup analyses for the case-control studies, reduced risk of thyroid cancer was observed in both men (OR, 0.734; 95% CI, 0.553 to 0.974) and women (OR, 0.792; 95% CI, 0.700 to 0.897). The protective effect of smoking was observed in studies in which thyroid cancer was limited to differentiated thyroid cancers (DTCs) (OR, 0.798; 95% CI, 0.706 to 0.902). @*Conclusion@#Our results suggests that smoking may have a protective effect on thyroid cancer, especially on DTCs. Further studies with larger sample sizes should be conducted in elucidating the dose and time dependent effect of smoking on thyroid cancer with specific focus on the types of thyroid cancers.

Evaluation of Iodine Status among Korean Patients with Papillary Thyroid Cancer Using Dietary and Urinary Iodine

Background@#Concerns have been raised regarding thyroid disorders caused by excessive iodine in Koreans, who have iodine-rich diets. This study evaluated iodine status using dietary iodine intake and urinary iodine in papillary thyroid cancer (PTC) patients. @*Methods@#Dietary data of PTC patients were assessed using a 24-hour recall and food frequency questionnaire (FFQ), and urinary iodine concentrations (UICs) were also obtained. To compare the iodine status of PTC patients, Korean adults with or without thyroid disease from the Korea National Health and Nutrition Examination Survey, which had 24-hour recall data and urinary iodine measurements, were analyzed. @*Results@#The median daily iodine intake by 24-hour recall was 341.7 μg/day in PTC patients, similar to the levels of other Korean adults. Based on UICs, the prevalence of excessive iodine was 54.4% in PTC patients, which was similar to the prevalence among subjects with thyroid disease (55.4%) but slightly higher than that in subjects without thyroid disease (47.7%). Based on dietary iodine by 24-hour recall, the prevalence of excessive iodine intake was 7.2%, which was higher than that among subjects with (4.4%) or without (3.9%) thyroid disease. The dietary iodine intake based on 24-hour recall was closely correlated with the UIC (r=0.4826) in PTC patients, but dietary iodine by FFQ was not significantly correlated with either 24-hour recall or UIC-based dietary iodine. @*Conclusion@#Excessive iodine intake was more common in PTC patients than in subjects without thyroid disease. Further longitudinal research is necessary to elucidate the role of dietary iodine in PTC.

Effect of Cigarette Smoking on Thyroid Cancer: Meta-Analysis

Background@#Although smoking is generally carcinogenic, its effect on thyroid cancers is still subject to controversy. The purpose of this study was to summarize the role of smoking in relation to thyroid cancer occurrence. @*Methods@#We performed a meta-analysis of 24 eligible studies: 21 case-control studies and three prospective cohort studies. The summary odds ratio (OR) and 95% confidence interval (CI) of all studies were acquired based on random effect model. Further subgroup analyses were conducted according to gender, histological type of thyroid cancer, and smoking status of patients for the case-control studies. @*Results@#The summary effect size indicated a negative association of smoking for thyroid cancer (OR, 0.798; 95% CI, 0.681 to 0.935). From the subgroup analyses for the case-control studies, reduced risk of thyroid cancer was observed in both men (OR, 0.734; 95% CI, 0.553 to 0.974) and women (OR, 0.792; 95% CI, 0.700 to 0.897). The protective effect of smoking was observed in studies in which thyroid cancer was limited to differentiated thyroid cancers (DTCs) (OR, 0.798; 95% CI, 0.706 to 0.902). @*Conclusion@#Our results suggests that smoking may have a protective effect on thyroid cancer, especially on DTCs. Further studies with larger sample sizes should be conducted in elucidating the dose and time dependent effect of smoking on thyroid cancer with specific focus on the types of thyroid cancers.

Evaluation of Iodine Status among Korean Patients with Papillary Thyroid Cancer Using Dietary and Urinary Iodine

Background@#Concerns have been raised regarding thyroid disorders caused by excessive iodine in Koreans, who have iodine-rich diets. This study evaluated iodine status using dietary iodine intake and urinary iodine in papillary thyroid cancer (PTC) patients. @*Methods@#Dietary data of PTC patients were assessed using a 24-hour recall and food frequency questionnaire (FFQ), and urinary iodine concentrations (UICs) were also obtained. To compare the iodine status of PTC patients, Korean adults with or without thyroid disease from the Korea National Health and Nutrition Examination Survey, which had 24-hour recall data and urinary iodine measurements, were analyzed. @*Results@#The median daily iodine intake by 24-hour recall was 341.7 μg/day in PTC patients, similar to the levels of other Korean adults. Based on UICs, the prevalence of excessive iodine was 54.4% in PTC patients, which was similar to the prevalence among subjects with thyroid disease (55.4%) but slightly higher than that in subjects without thyroid disease (47.7%). Based on dietary iodine by 24-hour recall, the prevalence of excessive iodine intake was 7.2%, which was higher than that among subjects with (4.4%) or without (3.9%) thyroid disease. The dietary iodine intake based on 24-hour recall was closely correlated with the UIC (r=0.4826) in PTC patients, but dietary iodine by FFQ was not significantly correlated with either 24-hour recall or UIC-based dietary iodine. @*Conclusion@#Excessive iodine intake was more common in PTC patients than in subjects without thyroid disease. Further longitudinal research is necessary to elucidate the role of dietary iodine in PTC.

Poorly differentiated thyroid carcinoma: An institutional experience

Purpose@#The incidence of poorly differentiated thyroid carcinoma (PDTC) is extremely low among thyroid cancers and there is no standardized treatment guideline for it. In this study, we have analyzed PDTC patients and reviewed their clinicopathological features. @*Methods@#Data of PDTC patients from our institution are collected through the electronic medical database. We analyzed them by several parameters such as basic demographics, presenting symptom, preoperative cytology results, associated pathology, surgical results, surgery type, and distant metastasis. @*Results@#We collected 23 cases in our institution. Apart from two patients who were transferred to another hospital upon diagnosis, all 21 operated cases are analyzed. The parameters we studied were age, sex, presenting symptoms, distant metastasis and pathological features such as tumor size, associated pathology, predominant pattern and so on. We also provided descriptive analyses according to the type of presentation and treatment; patients with distant metastasis, juvenile cancer, and concurrent hyperthyroidism. Furthermore, we provided different cases in which the initial surgical plans differed. @*Conclusion@#We present 21 cases of PDTC patients and clarify their clinicopathological features. Despite some limitations, this study may shed light for future research regarding treatment of PDTC patients.

Contribution of cytologic examination to diagnosis of poorly differentiated thyroid carcinoma

Background@#The cytologic diagnosis of poorly differentiated thyroid carcinoma (PDTC) is difficult because it lacks salient cytologic findings and shares cytologic features with more commonly encountered neoplasms. Due to diverse cytologic findings and paucicellularity of PDTC, standardization of cytologic diagnostic criteria is limited. The purpose of this study is to investigate and recognize diverse thyroid findings of fine needle aspiration (FNA) cytology and frozen smear cytology in diagnosis of this rare but aggressive carcinoma. @*Methods@#The present study included six cases of FNA cytology and frozen smears of histologically diagnosed PDTCs. @*Results@#PDTC showed cytologic overlap with well-differentiated thyroid carcinomas (WDTCs). Five of six cases showed dedifferentiation arising from well differentiated thyroid carcinomas. Only one de novo PDTC showed highly cellular smears composed of discohesive small cells, high nuclear/cytoplasmic (N/C) ratio, prominent micronucleoli, and irregular nuclei. Retrospectively reviewed, these findings are highly suspicious for PDTC. Cytologic findings of nuclear atypia, pleomorphism, and irregularity were frequently found, whereas scattered small cells were seen only in the de novo case. @*Conclusions@#Heterogeneous cytologic findings of PDTCs are shared with those of WDTCs and contribute to difficult preoperative cytologic diagnoses. Most PDTCs show dedifferentiation from WDTCs. Albeit rare, de novo PDTC should be considered with cytology showing discohesive small cells with high N/C ratio. This will enable precise diagnosis and prompt treatment of this aggressive malignancy

Rare PTH Gene Mutations Causing Parathyroid Disorders: A Review

Since parathyroid hormone (PTH) was first isolated and its gene (PTH) was sequenced, only eight PTH mutations have been discovered. The C18R mutation in PTH, discovered in 1990, was the first to be reported. This autosomal dominant mutation induces endoplasmic reticulum stress and subsequent apoptosis in parathyroid cells. The next mutation, which was reported in 1992, is associated with exon skipping. The substitution of G with C in the first nucleotide of the second intron results in the exclusion of the second exon; since this exon includes the initiation codon, translation initiation is prevented. An S23P mutation and an S23X mutation at the same residue were reported in 1999 and 2012, respectively. Both mutations resulted in hypoparathyroidism. In 2008, a somatic R83X mutation was detected in a parathyroid adenoma tissue sample collected from a patient with hyperparathyroidism. In 2013, a heterozygous p.Met1_Asp6del mutation was incidentally discovered in a case-control study. Two years later, the R56C mutation was reported; this is the only reported hypoparathyroidism-causing mutation in the mature bioactive part of PTH. In 2017, another heterozygous mutation, M14K, was detected. The discovery of these eight mutations in the PTH gene has provided insights into its function and broadened our understanding of the molecular mechanisms underlying mutation progression. Further attempts to detect other such mutations will help elucidate the functions of PTH in a more sophisticated manner.

A comparative study of Watson for Oncology and tumor boards in breast cancer treatment

PURPOSE: Watson for Oncology (WFO) is a computing system for considering treatment option with patients. The aim of this study is to determine the concordance rate of WFO and tumor board in treatment options of breast cancer.METHODS: One hundred and seventy breast cancer patients who were treated at Gachon University Gil Medical Center (GMC) from December 2016 to March 2018 were investigated. “Concordance” is defined that treatment provided by GMC tumor board and WFO-provided treatments (Recommend or For Consideration) were coincide. “Discordance” is defined that treatment provided by GMC tumor board and WFO-provided treatments (Not Recommended or Not Available) were coincide.RESULTS: In chemotherapy, of the total 170 patients, 23 patients were excluded, and the concordance rate was compared in 147 patients. Concordance rate was 93% (136/147). In the 11 patients who were discordant, seven patients complied with the treatment proposed by GMC tumor board due to insurance problems and age, and two patients did not follow the treatment proposed by WFO due to pregnancy and patient's choice, and one patient chose a treatment determined by WFO, last one patient was not treated with chemotherapy because it was not considered to be clinically necessary. In radiotherapy, the overall agreement rate was as high as 99% (147/148).CONCLUSION: Through this study, we found that many of the treatment proposals provided by WFO are highly reliable. Although the overall agreement is high in the radiotherapy regimen, the indication for radiotherapy by WFO is more aggressive and hypofractionated high dose intensity radiotherapy is growing trend by WFO.

Stem cell analysis with intraductally treated mammary epithelial cells

PURPOSE: The activity of mammary stem cells (MaSCs) is essential to mammary growth, differentiation and regeneration in cycles of pregnancy, lactation, and involution. The capability to recruit the mammary gland through the cycles is attributed to stem cells. It was shown that the intraductal (i.duc) injection of pegylated liposomal doxorubicin (PLD) to multiparous FVB/N mice was associated with a significantly reduced outgrowth potential of mammary gland cells. We have explored i.duc PLD's effect on stem cell number and function in mouse mammary gland and aldehyde dehydrogenase (ALDH)'s availability as a mouse MaSC marker.METHODS: The total mammary epithelium was purified from 6 to 8-month-old FVB/N control and i.duc PLD-administered mice treated twice and analyzed by flow cytometry and limiting dilution cleared mammary fat pad transplants.RESULTS: There was no significant difference in the proportions of stem cell-enriched population (CD49(fhigh)CD24(med)) between control and i.duc PLD-treated groups. However, we found a significant reduction in the outgrowth potential of CD49(fhigh)CD24(med) and CD49(fhigh)CD24(med)ALDH(+) cells from i.duc PLD-treated mammary glands. We discovered that adding ALDH to CD49(fhigh)CD24(med) had the possibility of better marker selection for MaSC of mice.CONCLUSION: We present i.duc administration of PLD to reduce MaSC function, but not the number; and ALDH activity may add further selection of MaSCs to CD49f CD24 in mouse mammary glands. Screening of chemotherapeutic drugs or other natural products by this method of stem cell analysis may provide safe i.duc treatment in breast cancer.

A comparative study of the clinical characteristics of breast cancer patients less than 35 years old and older patients

PURPOSE: In Korea, the incidence of breast cancer peaks in the fifth decade, which is younger than that observed in the Western world. We conducted this study to compare the clinical characteristics and prognostic factors of breast cancer in women < 35 and ≥35 years old.METHODS: The medical records of 969 patients treated for breast cancer at the Gil Medical Center from 2008 through 2012 were reviewed. Tumor characteristics, surgical methods, and adjuvant therapies were compared in two groups.RESULTS: Number of childbirths, family history, the proportion of postmenopausal women were lower among those aged < 35 years. However, tumor size, number of metastatic lymph nodes, and surgical procedures were similar in two groups. The rate of triple negative status in younger patients was higher than in older patients. Adjuvant chemotherapy was effective in patients positive for hormone receptors and no lymph nodal invasion, and it was effective in patients negative for hormone receptors and lymph nodal invasion in patients aged >35 years old. Postoperative radiotherapy was statistically effective in patients aged < 35 and ≥35 years old that underwent breast-conserving surgery. Pregnancy were significantly associated with survival in younger patients. While lymph node stage, presence of progesterone receptor, and triple negative status were significantly associated with survival on older patients.CONCLUSION: The prognostic factors of breast cancer in patients younger than 35 years old were pregnancy. Triple negative status rate was higher in younger patients than in older patients. Adjuvant therapy had similar effects in patients aged < 35 or ≥35 years old.

Clinicopathological markers associated with recurrence in ductal carcinoma in situ of breast by age group

PURPOSE: In the present study, factors related to the recurrence of breast ductal carcinoma in situ (DCIS) in Korean patients were identified, and the prognostic factors for each age group were explored.METHODS: The subjects were 226 patients who were diagnosed with DCIS by histopathologic examination, and the effect of representative prognostic factors that are known already, including estrogen receptor (ER), progesterone receptor (PR) and the human epidermal growth factor receptor 2 (HER2) status, Ki-67 levels, and adjuvant therapy on the recurrence of DCIS was analyzed by using the Cox proportional hazard model.RESULTS: Among the 226 subjects, 11 patients underwent the recurrence of breast cancer. The average follow-up period was 52.7±23.5 months. The average age of the subjects was 50.6±9.3 years. Among the DCIS patients, the recurrence of breast cancer was significantly higher in the ER negative patients and those who have a Ki-67 level over 20%. However, the PR and HER2 status did not significantly affect breast cancer recurrence. The result also showed that only ER negative was a significant factor before the age of 50 years and that only the Ki-67 level over 20% was a significant factor to the patients 50 years of age or older.CONCLUSION: DCIS patients should be appropriately treated and managed depending on their age and clinicopathological factors to prevent the recurrence of DCIS.

The effect of Korean traditional alternative medicine products on thyroid function level in post-total thyroidectomy patients: A pilot study

PURPOSE: Although many Koreans consume traditional alternative remedial products to alleviate symptoms of fatigue, there have been no studies on their effect on thyroid function levels in thyroidectomized patients on levothyroxine replacement. The aim of this study was to assess the effect of Korean traditional alternative remedies on thyroid function levels in post total thyroidectomy patients.METHODS: A retrospective review of medical records from a single tertiary referral center was performed on patients who received total thyroidectomy from 2010 to 2015 and became euthyroid postoperatively. Gender, age, body mass index, preoperative thyroid function test results, interval to first hypothyroidism occurrence, recurrence of hypothyroidism, number and types of alternative remedy were evaluated.RESULTS: Postoperative hypothyroidism occurred among 174 out of 917 patients (18.9%) and 100 (57.5%) of them had a history of alternative medication usage. The first episode of hypothyroidism occurred at median of 38.5 months after operation in the 100 patients. Six of the 100 patients received an increased dosage of levothyroxine due to severe hypothyroidism but the rest received the same dose and were requested not to consume alternative products. All patients recovered to euthyroid status afterwards. Thirty-three patients subsequently experienced recurrence even after being restricted from consuming alternative remedial products. Apart from thyroiditis on pathology reports (P=0.001), there were no variables significantly related to the recurrent hypothyroidism.CONCLUSION: This pilot study demonstrated the possible role of consumption patterns of traditional alternative remedial products in thyroidectomized patients under hormone supplement in restoring euthyroid status without levothyroxine increase.

Clinicopathological characteristics and treatment outcomes of 38 cases of primary thyroid lymphoma: a multicenter study

PURPOSE: Primary thyroid lymphoma (PTL) is a rare disease and it has been investigated in a limited number of studies. The present multicenter study evaluated the clinical features and treatment outcomes of PTL. METHODS: The medical records of patients diagnosed with PTL between 2000 and 2013 in three centers were retrospectively reviewed. RESULTS: The study included 11 men and 27 women with a median age of 63.3 years (range, 42-83 years). The median follow-up was 56.0 months (range, 3-156 months). Of the 38 patients included, 16 had mucosa-associated lymphoid tissue (MALT) lymphoma, six had mixed MALT and diffuse large B-cell lymphoma (DLBCL), and 16 had DLBCL. Thirty-five patients (92.1%) had early stage (stage I/II) disease. Of the 16 MALT lymphoma patients, 14 were treated by surgery, and radiotherapy (RT) or chemotherapy was combined in five patients. Two patients received RT or chemotherapy alone. Of the six mixed MALT and DLBCL patients, three underwent surgery with chemotherapy and three underwent chemotherapy alone, RT alone, or surgery with RT. All of the 16 DLBCL patients received chemotherapy, and surgery and RT was combined in 4 and 1 patients, respectively. The 5-year survival was 100% for MALT lymphoma (7 of 7) and mixed MALT and DLBCL patients (5 of 5) and 87.5% for DLBCL patients (7 of 8). CONCLUSION: Early stage PTL has an excellent prognosis when managed by single or combined treatment modalities. Clinicians should consider PTL in patients with underlying Hashimoto's thyroiditis presenting with an enlarging thyroid mass.

Early experience of laparoscopic choledochal cyst excision in children / 대한외과학회지

PURPOSE: Laparoscopic choledochal cyst excision with Roux-en-Y hepaticojejunostomy (LCE) in children is being attempted more frequently around the world, and although it has been performed in Korea, no publication has been published on it. However, cholangitis and/or pancreatitis are limitations that make open conversion more likely. The aims of this study, through a retrospective clinical analysis, were to prove the efficacy of LCE in children and to validate that preoperative management expands its indications. METHODS: From May 2011 to November 2012, 13 pediatric LCEs were performed. Demo graphics, preoperative findings, management, operative and postoperative outcomes were reviewed. RESULTS: The mean age at operation was 48.5 months and mean bodyweight 19.0 kg. Ultrasonography was conducted in all patients followed by either magnetic resonance cholangiopancreatography (8 cases) or computed tomography (5 cases). The mean diameter of the cysts was 30.2 mm. Eight patients with cholangitis and/or pancreatitis were given antibiotics preoperatively. Four had their condition resolved by administration of antibiotics, 3 underwent additional endoscopic retrograde biliary drainage or percutaneous transhepatic biliary drainage, and one, due to aggravating tenderness, underwent surgery after 4 days of administrating antibiotics without improvement of the inflammation. Two faced open conversions, one because of a very narrow bile duct, and the other because of remnant inflammation after inadequate preoperative management already mentioned above. Patients were discharged on the eighth postoperative day. There were no complications. CONCLUSION: Pediatric LCE is a feasible option for choledochal cyst. Proper preoperative management such as antibiotics and drainage procedures enhances its efficacy by broadening its indications, even with concomitant cholangitis and/or pancreatitis.