Incidence, Risk Factors, and Clinical Implications of Delayed Hypoparathyroidism on Postoperative Day two Following Total Thyroidectomy for Papillary Thyroid Carcinoma.

OBJECTIVE: This study aimed to investigate the incidence rates, risk factors, and clinical implications of delayed hypoparathyroidism on postoperative day 2 (POD-2) after total thyroidectomy in patients with papillary thyroid carcinoma. METHODS: This study included 410 patients with normal serum intact parathyroid hormone (iPTH) and calcium levels on postoperative day 1 (POD-1) who were classified into 2 groups according to the presence or absence of delayed hypoparathyroidism on POD-2. RESULTS: Of the 410 patients, 98 experienced delayed hypoparathyroidism on POD-2 (23.9%). The significant risk factors for delayed hypoparathyroidism on POD-2 included female gender, age older than 45 years, central lymph node dissection, increased number of excised lymph nodes, and low POD-1 versus preoperative iPTH ratios. Additionally, delayed hypoparathyroidism on POD-2 was found to be a significant risk factor for hypocalcemia on POD-2 and permanent hypoparathyroidism. CONCLUSION: Prophylactic calcium supplementation and long-term surveillance for permanent hypoparathyroidism should be considered in patients with risk factors for delayed hypoparathyroidism on POD-2. ABBREVIATIONS: CI = confidence interval; iPTH = intact parathyroid hormone; OR = odds ratio; POD-1 = postoperative day 1; POD-2 = postoperative day 2; PTC = papillary thyroid carcinoma; ROC = receiver operating characteristic.

Volume replacement with diced acellular dermal matrix in oncoplastic breast-conserving surgery: a prospective single-center experience.

BACKGROUND: Several studies have reported the use of acellular dermal matrix in breast reconstruction. However, the primary role of acellular dermal matrix in these studies was to support the implant; there are no reports on the use of acellular dermal matrix exclusively as volume replacement. Thus, we aimed to evaluate the safety and effectiveness of filling of the defect with acellular dermal matrix in oncoplastic breast-conserving surgery. METHODS: We prospectively recruited 120 adult breast cancer patients who were scheduled to undergo oncoplastic breast-conserving surgery with acellular dermal matrix filling from 2017 to 2018. Intraoperatively, diced human acellular dermal matrix measuring 3-5 mm was used on each side to fill in the excisional defect immediately. After 6 months, satisfaction of the patients and surgeons with overall and cosmetic outcomes was evaluated with a survey using a 10-point scale. Postoperative complications were assessed at 2 weeks and 6 months postoperatively. RESULTS: Of the 117 patients who were evaluated for their satisfaction, 94.0% were strongly satisfied with the cosmetic outcomes and 90.4% were strongly satisfied overall. Patient overall satisfaction scores were higher than surgeon satisfaction scores (p < 0.001). Of the 117 patients who underwent evaluation of complications 6 months postoperatively, six (5.1%) had hematoma and seven (6.0%) had seroma. The overall reoperation rate due to complications was 8.5%. Only two patients needed acellular dermal matrix removal due to hematoma and inflammation. CONCLUSION: Oncoplastic breast-conserving surgery with acellular dermal matrix filling of defects can be performed safely with high cosmetic satisfaction. TRIAL REGISTRATION: ICTRP, KCT0003886; retrospectively registered May 3, 2019, http://apps.who.int/trialsearch/Trial2.aspx?TrialID=KCT0003886.

Evaluation of Esthetic Results after Mass Removal with Elliptical Skin Excision Using Ultrasonography to Measure Skin Thickness.

Background: The growth of benign cutaneous masses causes the overlaying skin to expand and become thinner, especially at the central, most projected point. In this retrospective study, a surgical technique comprising an elliptical skin excision was employed to account for these skin changes. Methods: This retrospective study enrolled 980 patients with benign masses. Preoperatively, all patients underwent ultrasonography to evaluate the mass depth and thickness of the attached skin, and mass excision was performed using the elliptical skin-excision method. The operative time was recorded, and complications and esthetic outcomes were assessed using the Cutometer® and the modified Vancouver Scar Scale (mVSS) during 1- and 3-month follow-up visits. Results: The mean operative time (17.48 ± 3.46 min) was significantly shorter than that of conventional methods (p < 0.05). Cutometer parameters showed no significant differences from those of intact skin. The average mVSS scores were 5.21 ± 1.42 and 3.50 ± 1.79 at 1- and 3-month follow-ups, respectively. Conclusions: Mass excision with an elliptical skin attachment resulted in improved esthetic results and easy removal. The attached skin enabled convenient handling without damaging the capsule or other adjacent structures, leaving a thick dermis on both wound edges. Thus, this technique resulted in minimal scarring.

Evaluation of the Pinhole Method Using Carbon Dioxide Laser on Facial Telangiectasia.

Facial telangiectasias are small, dilated blood vessels frequently located on the face. They are cosmetically disfiguring and require an effective solution. We aimed to investigate the effect of the pinhole method using a carbon dioxide (CO2) laser to treat facial telangiectasias. This study included 155 facial telangiectasia lesions in 72 patients who visited the Kangnam Sacred Heart Hospital, Hallym University. Treatment efficacy and improvement were evaluated by quantitative measurements performed by two trained evaluators who assessed the percentage of residual lesion length using the same tape measure. Lesions were evaluated before laser therapy and 1, 3, and 6 months after the first treatment. Based on the initial lesion length (100%), the average percentages of the residual length at 1, 3, and 6 months were 48.26% (p < 0.01), 4.25% (p < 0.01), and 1.41% (p < 0.01), respectively. Complications were evaluated using the Patient and Observer Scar Assessment Scale (POSAS). The average POSAS scores improved from 46.09 at the first visit to 23.42 (p < 0.01), and 15.24 (p < 0.01) at the 3- and 6-month follow-up. No recurrence was noted at the 6-month follow-up. CO2 laser treatment using the pinhole method to treat facial telangiectasias is a safe, inexpensive, and effective treatment that provides patients with excellent aesthetic satisfaction.

A Comparison of the Prognostic Effects of Fine Needle Aspiration and Core Needle Biopsy in Patients with Breast Cancer: A Nationwide Multicenter Prospective Registry.

(1) Background: Breast core needle biopsy (CNB) is preferred over fine needle aspiration (FNA) as it has higher sensitivity and specificity and enables immunohistochemical evaluation. However, breast FNA remains widely used because of its low cost, minimally invasive nature, and quick results. Studies analyzing the effects of each test on the prognoses of patients with breast cancer are scarce and controversial, and the criteria for test selection remain unknown. (2) Methods: This study included adult female patients who underwent breast cancer surgery at 102 general hospitals. The trend of breast biopsies over time was analyzed, and the prognoses of patients with breast cancer who underwent CNB and FNA were compared. (3) Results: This study included 73,644 patients who underwent FNA (n = 8027) and CNB (n = 65,617). A multivariate Cox regression analysis showed that patients diagnosed using FNA had significantly worse overall survival (OS) and breast-cancer-specific survival (BCSS) than those diagnosed using CNB. In the subgroup analysis, patients with breast imaging reporting and data system (BI-RADS) 5 lesions, palpable tumors, or centrally located tumors had significantly worse OS and BCSS with FNA than with CNB. (4) Conclusions: CNB should be performed preferentially instead of FNA in patients with BI-RADS 5 lesions and nonpalpable or centrally located tumors.

COVID-19 Prevention Guidance and the Incidence of Febrile Neutropenia in Patients with Breast Cancer Receiving TAC Chemotherapy with Prophylactic Pegfilgrastim.

Chemotherapy-induced febrile neutropenia (FN) is a medical emergency that causes severe adverse effects and death. Respiratory infections are one of the main causes of fever in patients with FN. We studied whether infection prevention and control (IPC) guidance for coronavirus 2019 disease reduced the incidence of FN. We reviewed female patients with breast cancer treated with adjuvant docetaxel, doxorubicin, and cyclophosphamide with prophylactic pegfilgrastim between 2019 and 2021. IPC guidance was implemented in April 2020. There was no difference in the incidence of chemotherapy-induced neutropenia between patients with and without IPC. In patients with IPC, the incidence of FN (9.5%) was lower than that of patients without IPC (27.9%). The hospitalization duration (0.7 ± 1.5 days) and total hospital cost (279.6 ± 42.6 USD) of the IPC group were significantly lower than that of the non-IPC group (2.0 ± 3.8 days and 364.7 ± 271.6 USD, respectively). IPC guidance should be implemented to prevent FN in high-risk patients with breast cancer.

Survival of women with pregnancy-associated breast cancer according to clinical characteristics: A propensity score matching study.

In recent years, postponing childbearing has increased the prevalence of pregnancy-associated breast cancer (PABC). PABC has a poorer prognosis than breast cancer not associated with pregnancy (non-PABC) due to delayed diagnosis and aggressive subtype. Additionally, pregnancy itself predicts a poor prognosis; but, this is a subject of debate. Thus, we analyzed the effects of known prognostic factors and pregnancy on the prognosis of PABC. We retrospectively analyzed women aged 20 to 49 years who were diagnosed with breast cancer (BC) between 1989 and 2014. Patients were distributed into PABC and non-PABC groups, and 1:4 propensity score matching was performed to adjust for baseline characteristics. Primary endpoints were overall survival (OS) and BC-specific survival (BCSS). Secondary endpoint was the difference in prognosis according to BC subtype. Of the 34,970 recruited patients with BC, 410 (1.2%) had PABC. Patients with PABC were younger and tended to have triple-negative BC (TNBC) subtype than non-PABC patients. The 1640 matched non-PABC patients showed a significantly worse mean survival rate than the unmatched non-PABC patients. Patients with PABC had a significantly worse OS and BCSS than those with non-PABC. In multivariate analyses, patients with PABC of luminal B (Ki-67 ≥14.0%) and TNBC subtypes had worse OS and BCSS than patients with non-PABC. Patients with PABC had poorer prognosis than non-PABC patients after adjusting for several prognostic factors. This difference was particularly significant in patients with the luminal B and TNBC subtypes.

Nomogram for the Prediction of Biochemical Incomplete Response in Papillary Thyroid Cancer Patients.

PURPOSE: To develop a nomogram for predicting biochemical incomplete response (BIR) in the dynamic risk stratification (DRS) of papillary thyroid carcinoma (PTC) patients without structural recurrence, and to investigate its validity. PATIENTS AND METHODS: Overall, 1705 (1005 and 700 in the training and validation cohorts, respectively) PTC patients treated with total thyroidectomy without structural recurrence were included. multivariate logistic regression analyses were performed to determine the significant predictors of BIR in the training cohort. A nomogram was subsequently constructed for BIR risk prediction. Assessments for the predictive accuracy, discrimination, and calibration of the nomogram were performed. Subsequently, internal and external validations were conducted. RESULTS: In the multivariate analysis, age, sex, lymph node metastasis site, extrathyroidal extension, and lymphovascular invasion showed significant predictive value; using these predictive factors and tumor size, a nomogram for BIR risk prediction was constructed. In the training cohort, the nomogram showed good predictive performance and discrimination in the receiver operating characteristic (ROC) curve analysis, with an area under the curve (AUC) of 0.765. In internal validation, the bootstrap-corrected AUC was 0.76. The calibration plot showed good agreement between the predicted and actual observation. The Hosmer-Lemeshow (HL) test did not suggest a lack of fit (p=0.1613). In the external validation, the AUC was 0.828 in the ROC curve analysis; the calibration plot showed good quality, and the HL test did not suggest a lack of fit (p=0.2161). CONCLUSION: The constructed nomogram may effectively predict the risk of BIR in DRS in PTC patients without structural recurrence. LEVEL OF EVIDENCE: Level 4.

Clinical utilization of long-acting granulocyte colony-stimulating factor (pegfilgrastim) prophylaxis in breast cancer patients with adjuvant docetaxel-cyclophosphamide chemotherapy.

PURPOSE: Treatment with 4 cycles of docetaxel and cyclophosphamide (TC) in the adjuvant setting is associated with better outcomes than treatment with doxorubicin and cyclophosphamide (AC). However, Western guidelines have indicated that TC confers a high risk (>20%) of febrile neutropenia (FN), while AC confers an intermediate risk (10%-20%) of FN. Threrefore, we evaluated the incidence of FN and the clinical utilization of pegfilgrastim prophylaxis after adjuvant TC chemotherapy. METHODS: We categorized 201 patients who received adjuvant TC chemotherapy into 3 groups according to the method of prophylaxis and compared neutropenic events, other adverse events, and hospital care costs in the 3 groups. RESULTS: The incidence of grade 4 neutropenia decreased from 93.0% in patients without prophylaxis to 82.4% in those who received secondary prophylaxis and 16.7% in those who received primary prophylaxis. Although the incidence of FN was not different between patients without prophylaxis and patients who received secondary prophylaxis (15.7% and 14.9%), none of the patients who received primary prophylaxis developed FN. Moreover, a decrease in neutropenic events resulted in a significant decrease in the mean duration of neutropenia (2.50 days to 0.08 days, P < 0.001), the risk of hospitalization (29.8% to 2.2%, P < 0.001), and the mean total hospital care cost for all chemotherapy cycles (790.80 to 486.00 US dollars, P < 0.001). CONCLUSION: The use of pegfilgrastim prophylaxis during adjuvant TC chemotherapy is associated with significant decreases in the incidence of neutropenic events, hospitalization, and hospital care cost compared to those seen in patients without prophylaxis.

Clinical Implications of Serum 25-Hydroxyvitamin D Status after 5-Year Adjuvant Endocrine Therapy for Late Recurrence of Hormone Receptor-positive Breast Cancer.

PURPOSE: The prognostic implications of serum vitamin D status after a 5-year adjuvant endocrine therapy on the risk of late recurrence among hormone receptor (HR)-positive breast cancer patients remain unclear. Hence, we investigated this among Korean HR-positive breast cancer patients. METHODS: A total of 455 patients with HR-positive stage I-III invasive breast cancer who underwent curative surgery at St. Vincent's Hospital between February 2004 and April 2012 were included in this retrospective study. Patients were categorized based on their serum 25-hydroxyvitamin D (25(OH)D) levels after the 5-year adjuvant endocrine therapy. Initial recurrence sites were categorized. The primary clinical outcome was late recurrence-free survival (LRFS). RESULTS: Among the 455 patients, 242 and 213 were included in the 25(OH)D-deficient group and 25(OH)D-sufficient group, respectively. Forty-eight patients experienced late recurrence. Across all recurrence sites, the 25(OH)D-deficient group showed significantly worse LRFS rates than the 25(OH)D-sufficient group (hazard ratio [HR], 2.284; 95% confidence interval [CI], 1.155-4.515; p = 0.018). After patient subgrouping based on recurrence site, the 25(OH)D-deficient group also showed significantly worse LRFS rates in terms of regional lymph node (LN) (HR, 17.453; 95% CI, 2.46-128.83; p = 0.005), bone (HR, 2.394; 95% CI, 1.024-5.599; p = 0.044), and visceral (HR, 2.735; 95% CI, 1.182-6.328; p = 0.019) recurrence. However, there was no significant difference between the 2 groups in terms of local recurrence (p = 0.611). CONCLUSIONS: We found that 25(OH)D deficiency after the 5-year adjuvant endocrine therapy was associated with worse LRFS among HR-positive breast cancer patients, particularly with respect to regional LN, bone, and visceral recurrence.

Clinical Impact of Primary Prophylactic Pegfilgrastim in Breast Cancer Patients Receiving Adjuvant Docetaxel-Doxorubicin-Cyclophosphamide Chemotherapy.

PURPOSE: The regimen including concurrent docetaxel, doxorubicin, and cyclophosphamide (TAC) has been categorized as an important risk factor for febrile neutropenia (FN). This comparative study examined the clinical impact of long-acting granulocyte colony-stimulating factor (G-CSF) (pegfilgrastim) during adjuvant TAC chemotherapy in Korean patients with advanced breast cancer. METHODS: We analyzed data from 239 patients who received 6 cycles of adjuvant TAC chemotherapy. We categorized patients into 2 groups according to the use of primary prophylactic pegfilgrastim and compared the incidence and risk of FN, hospital care costs, and survival in the 2 groups. RESULTS: The incidence of FN decreased from 54.2% to 21.2% in all patients, after the use of pegfilgrastim. The analysis of a total of 1,432 chemotherapy cycles showed that the incidence of FN decreased from 36.1% to 9.1% after the use of pegfilgrastim. Moreover, the decrease in the incidence of FN with the use of pegfilgrastim resulted in a significant decrease in the mean duration of neutropenia (4.15 to 1.29 days), the risk of hospitalization (99.5% to 29.7%) and the mean total hospital care cost (USD 3,038 to USD 2,347). High relative dose intensity (RDI) in patients treated with pegfilgrastim than in those not treated with pegfilgrastim (99.18% vs. 93.85%) was associated with a better overall survival (p = 0.033). CONCLUSIONS: The use of pegfilgrastim during adjuvant TAC chemotherapy was significantly associated with a decrease in the incidence and risk of FN, hospital care costs, and risk of death compared to the use of adjuvant TAC without primary prophylaxis.

Relative Survival Benefit by Hormonal Receptor Status of Adding Trastuzumab to Neoadjuvant Chemotherapy in Breast Cancer Patients.

PURPOSE: Neoadjuvant chemotherapy (NAC) involving trastuzumab markedly increases pathologic complete response (pCR) rates in patients with human epidermal growth factor receptor 2-positive (HER2+) breast cancer. Despite increasing pCR rates, long-term survival gains are controversial owing to distinctive biologic behavior mediated by the presence of hormonal receptors (HRs) that may interact with HER2 receptors. We, therefore, investigated the differences in relative survival gain provided by neoadjuvant trastuzumab-based chemotherapy on HR positive (HR+) status of patients. METHODS: We retrospectively analyzed women with stage II or III HER2+ breast cancer who underwent NAC followed by a breast cancer surgery between 2008 and 2013. The survival benefits of adding trastuzumab to NAC were analyzed by classifying patients into HR+ and HR negative (HR-) groups. RESULTS: Of 666 patients included in the study, 374 (52.1%) were HR+ and 319 (47.9%) were HR-. In the HR+ group, trastuzumab treatment led to higher pCR rates and significantly better breast cancer specific survival (BCSS) and overall survival (OS) than no trastuzumab treatment. However, among patients with HR- breast cancer, trastuzumab treatment showed no statistically significant difference between BCSS and OS following multivariate analysis. CONCLUSION: We found that the addition of trastuzumab to NAC improved relative survival benefit in HER2+/HR+ patients than in HER2+/HR- patients, even though the pCR rate increases were lower. Although pCR has been regarded as a surrogate marker for estimating long-term survival benefits after NAC, it alone may not translate into real long-term oncologic outcomes in particular cancer subtypes after trastuzumab-based NAC. Further longer-term evaluation of the objective survival benefit after NAC driven by a dual HER2 block according to HR status is warranted.

Synergistic anticancer effects of ruxolitinib and calcitriol in estrogen receptor­positive, human epidermal growth factor receptor 2­positive breast cancer cells.

The Janus kinase (JAK)1 and JAK2 inhibitor, ruxolitinib, and the active form of vitamin D (calcitriol) were previously reported to possess anticancer effects in breast cancer. The present study investigated the combined effects of ruxolitinib and calcitriol on an estrogen receptor (ER)­positive, human epidermal growth factor receptor 2 (HER2)­positive, breast cancer cell line. The ER and HER2­positive MCF7­HER18 breast cancer cell line was used to investigate the combination effect of ruxolitinib and calcitriol. A bromodeoxyuridine (BrdU) assay was used to investigate cell growth inhibition. The synergism of this combination therapy was examined using the Chou­Talalay method. Cell cycle analysis was performed by flow cytometry, and apoptosis was evaluated by flow cytometry following Annexin V­fluorescein isothiocyanate (FITC) and propidium iodide (PI) staining. Alterations in protein expression levels were analyzed by western blotting. The BrdU assay indicated that combination treatment using ruxolitinib and calcitriol produced a synergistic anti­proliferative effect in MCF7­HER18 breast cancer cells. Annexin V­FITC/PI staining and cell cycle analysis identified a synergistic increase in apoptosis and sub­G1 arrest in the presence of ruxolitinib and calcitriol. Western blot analysis revealed that these synergistic effects of ruxolitinib and calcitriol were associated with reduced protein levels of JAK2, phosphorylated JAK2, c­Myc proto oncogene protein, cyclin­D1, apoptosis regulator Bcl­2 and Bcl­2­like protein 1, and with increased levels of caspase­3 and Bcl­2­associated agonist of cell death proteins. The results of the present study demonstrated the synergistic anticancer effects of ruxolitinib and calcitriol in ER and HER2­positive MCF7­HER18 breast cancer cells. Based on these findings, ruxolitinib and calcitriol may have potential as a combination therapy for patients with ER and HER2­positive breast cancer.

The effect of adjuvant chemotherapy on survival in Korean patients with node negative T1c, triple negative breast cancer.

BACKGROUND: The present study investigated the prognostic role of adjuvant systemic chemotherapy in patients with node negative, T1c triple negative breast cancer (TNBC) from a nationwide cohort. In addition, the prognostic effect between 3 different chemotherapy regimens were compared in node-negative T1c TNBC patients by subgroup analysis. METHODS: From the Korean breast cancer registry database, 1,151 T1c node negative TNBC patients were included in this study. Patients were categorized into four treatment groups according to chemotherapy regimen: (1) no chemotherapy, (2) adriamycin plus cyclophosphamide (AC), (3) adriamycin/epirubicin plus cyclophosphamide plus 5-FU (FAC/FEC), and (4) cyclophosphamide plus 5-FU plus methotrexate (CMF). Overall survival (OS) was evaluated between each patient group. RESULTS: Of the 1,151 T1c node negative TNBC patients, 1,006 received adjuvant chemotherapy, while 145 received no chemotherapy. Among the patients receiving adjuvant chemotherapy the distribution of regimens was: 586 AC, 168 FAC/FEC (126 FAC, 42 FEC), and 252 CMF. The mean follow-up time of the full study cohort was 87.98 ± 33.56 months (range = 6-192 months). Patients in the no chemotherapy group showed significantly worse OS compared to each chemotherapy regimen group. However, when OS was compared between each chemotherapy regimen, no significant difference was found. CONCLUSIONS: This study showed that adjuvant systemic chemotherapy improved OS in T1c node negative TNBC patients, regardless of chemotherapy between AC, FAC/FEC, and CMF regimens.