The diagnostic accuracy of mammography and ultrasonography for recurrent breast cancer after breast conserving treatment.

Objective: To evaluate the performance of mammography and breast ultrasonography to diagnose tumor recurrence in patients after breast conserving therapy. Material and Methods: Imaging findings of 130 breast cancer patients treated by breast conserving therapy (BCT) who have followed up with mammography and ultrasonography at our center between 1 st January 2010 and 1st January 2016 were interpreted by two radiologists. The information of recurrent tumor and baseline data were blinded. Imaging interpretation followed the ACR Breast imaging-reporting and data system (BI-RADS) 5th edition guideline. Findings of mammography, breast ultrasonography, demographic data and histological data were recorded and analyzed. Results: The presence of mass in mammography (P-value=0.025) and internal vascularity in mass in ultrasonography (P-value<0.001) were associated with recurrent tumor at the surgical bed. All the recurrent tumors were interpreted as BI-RADS 4 (71 patients) with sensitivity= 100%, specificity= 89.5%. BIRADS4 is significant in the diagnosis of recurrent breast cancer in BCT patients (AUC of the ROC curve = 0.742 and 95% CI=(0.7-0.79)). Conclusion: The presence of mass in mammography and internal vascularity in the mass in ultrasonography are the imaging findings which were significantly related to recurrent tumor at surgical bed in patient with breast conserving treatment.

A randomized double-blind controlled study comparing erector spinae plane block and thoracic paravertebral block for postoperative analgesia after breast surgery.

BACKGROUND: Thoracic paravertebral block (PVB) is an effective regional block for pain control after breast surgery. However, accidentally puncturing adjacent vital structures may cause undesirable complications. Erector spinae plane block (ESPB) has been considered a safer proxy of PVB for beginners. This study aimed to evaluate the analgesic effects of ultrasound-guidance PVB and ESPB after breast surgery. METHODS: This randomized control trial was conducted in patients who underwent mastectomy. Forty-four females were randomly allocated into PVB group or ESPB group. All patients received a block with 20 ml of 0.5% levobupivacaine before general anesthesia. The primary outcome was the 24-h postoperative morphine requirements. The other outcomes of interest were postoperative pain scores, time to first analgesic request, dermatome of sensory blockade, block-related complications, and opioid adverse events. RESULTS: The 24-h morphine requirements were significantly lower in PVB compared to the ESPB group (3.5 ± 3.3 vs. 8.6 ± 3.8 mg, P < 0.001). The overall pain scores were also lower in the PVB group (P < 0.001). Only 14 patients in the PVB group requested additional morphine, whereas all patients in the ESPB group requested it (P = 0.004). The dermatome of sensory blockade was wider in the PVB group (7 vs. 4 levels, P = 0.019). No serious complications occurred in either group. CONCLUSIONS: Compared to ESPB, PVB provided lower postoperative opioid requirements, lower pain scores, and wider sensory blockade after mastectomy.

Pathum Raksa Project: Addressing Disparity in Breast Cancer Care Through National Innovation in Thailand.

PURPOSE: Breast cancer is a growing public health challenge in Thailand. Pathum Raksa project was launched in 2015, as a result of higher than expected rate of triple-negative breast cancers in Thai women. The purpose of this project was to identify the cause(s) and address the issue(s), hence improving the quality of breast cancer biomarker testing in Thailand. MATERIALS AND METHODS: Nineteen hospitals across the country, with 902 breast cancer patients were enrolled in this study during 2015-2020. The pre- and post-data from Pathum Raksa initiative was only available for Khon Kaen University (KKU) and Udonthani hospitals in Northeast Thailand. We developed a resource-stratified strategic plan that included designing a unique specimen container, forming multidisciplinary teams from the Surgery and Pathology Departments, and employing locally developed innovative technologies to optimize the entire process of breast cancer diagnostics and biomarker testing. RESULTS: The rate of triple-negative breast cancers in KKU and Udonthani decreased 52.8% (p = 0.02) and 28.9% (p = 0.48), respectively. The rate of ER+ breast cancers in both hospitals increased 5% post-Pathum Raksa implementation. The rate of HER2-neu+ (score 3+) also increased in both hospitals (particularly an increased 65% rate in KKU). Luminal A/B cancers were the most common subtype in both KKU and Udonthani hospitals. CONCLUSION: Pathum Raksa project has significantly improved breast cancer biomarker testing in Thailand. As a result of this national innovation, false-negative rates of breast biomarkers have significantly decreased, resulting in improving prognosis, treatment, and survival of breast cancer women in Thailand.

Apoptosis-Inducing Factor, Mitochondrion-Associated 3 (AIFM3) Protein Level in the Sera as a Prognostic Marker of Cholangiocarcinoma Patients.

Prognosis of cholangiocarcinoma (CCA) patients is absolutely poor. Since improvement of prognosis and/or response to treatment by personalized and precision treatments requires earlier and precise diagnostic markers, discovery of prognostic markers attracts more attention. Apoptosis-inducing factor, mitochondrion-associated 3 (AIFM3) is highly expressed in several cancers including CCA. The present study investigated whether the serum AIFM3 level can be used as a potential marker for CCA prognosis. For this purpose, we first determined secretory protein nature of AIFM3 using bioinformatic tools. The results show that although AIFM3 lacks signal peptide, it can be secreted into plasma/serum via an unconventional pathway. Then, the AIFM3 levels in the sera of 141 CCA patients and 70 healthy controls (HC) were measured using a semi-quantitative dot blot assay. The results show that the AIFM3 level in the sera of CCA group was significantly higher than that of HC. When correlation between serum AIFM3 levels and the clinicopathological parameters of CCA patients were examined, serum AIFM3 levels correlated significantly with lymph node metastasis, age, and the patients' overall survival (OS). Higher AIFM3 levels were significantly associated with shorter OS, and only AIFM3 was an independent prognostic marker for CCA. In conclusion, AIFM3 can be used as a prognostic marker for CCA.

Serum Apurinic/Apyrimidinic Endodeoxyribonuclease 1 (APEX1) Level as a Potential Biomarker of Cholangiocarcinoma.

Diagnostic and/or prognostic biomarkers for cholangiocarcinoma (CCA) are still insufficient with poor prognosis of patients. To discover a new CCA biomarker, we constructed our secretome database of three CCA cell lines and one control cholangiocyte cell line using GeLC-MS/MS. We selected candidate proteins by five bioinformatics tools for secretome analysis. The inclusion criteria were as follows: having predicted signal peptide or being predicted as non-classically secreted protein; together with having no transmembrane helix and being previously detected in plasma and having the highest number of signal peptide cleavage sites. Eventually, apurinic/apyrimidinic endodeoxyribonuclease 1 (APEX1) was selected for further analysis. To validate APEX1 as a bio-marker for CCA, serum APEX1 levels of 80, 39, and 40 samples collected from CCA, benign biliary diseases (BBD), and healthy control groups, respectively, were measured using dot blot analysis. The results showed that serum APEX1 level in CCA group was significantly higher than that in BBD or healthy control group. Among CCA patients, serum APEX1 level was significantly higher in patients having metastasis than in those without metastasis. The higher level of serum APEX1 was correlated with the shorter survival time of the patients. Serum APEX1 level might be a diagnostic and prognostic biomarker for CCA.

Serum pyruvate dehydrogenase kinase as a prognostic marker for cholangiocarcinoma.

Pyruvate dehydrogenase kinase (PDK) is a Ser/Thr kinase that inactivates mitochondrial pyruvate dehydrogenase and serves a key role in aerobic glycolysis, which is a hallmark of cancer cells. The present study determined the PDK expression in cholangiocarcinoma (CCA) tissues and sera to evaluate their applicability as a biomarker for CCA. Using proteomic analysis, PDK was revealed to be the most overexpressed mitochondrial protein in CCA tissues. Then, the expression of PDK isoforms in CCA tissues was examined in 15 CCA cases by immunohistochemistry. The PDK3 isoform levels in the sera were measured using a dot blot assay for 39 patients with CCA, 20 patients with benign biliary disease and 19 healthy volunteers. The results revealed a 27-fold overexpression of PDK3 in cancerous tissues when compared with adjacent non-cancerous tissues. The immunohistochemical results demonstrated that the PDK1, 2 and 3, but not the PDK4, isoforms were overexpressed in cancerous tissues. When the PDK3 levels in the sera were examined, they were significantly higher in CCA when compared with the BBD and healthy groups. The specificity and sensitivity of PDK3 as a marker for CCA were 97.5 and 33.0%, respectively, and high PDK3 levels in the sera were correlated with a short survival time for CCA. In conclusion, PDK3 can be used as a diagnostic/prognostic marker for CCA.

Breast Cancer Incidence Trends and Projections in Northeastern Thailand.

BACKGROUND: The northeast has the lowest incidence of breast cancer of all regions in Thailand, although national rates are increasing. The heterogeneity in subnational trends necessitates a comprehensive evaluation of breast cancer incidence trends and projections to provide evidence for future region-specific strategies that may be employed to attenuate this growing burden. METHODS: Joinpoint regression and age-period-cohort modeling were used to describe trends from 1988-2012. Data was projected from three separate models to provide a range of estimates of incidence to the year 2030 by age group. RESULTS: Age-standardized rates (ASRs) increased significantly for all women from 1995-2012 by 4.5% per year. Rates for women below age 50 increased by 5.1% per year, while women age 50 years and older increased by 6% per year from 1988-2012. Projected rates show that women age 50 years and older have the largest projected increase in ASRs by 2030 compared to younger women and all women combined. CONCLUSIONS: Breast cancer trends in Khon Kaen are presently lower than other regions but are expected to increase and become comparable to other regions by 2030, particularly for women ages 50 years and older.

Complications and oncologic outcomes of pedicled transverse rectus abdominis myocutaneous flap in breast cancer patients.

BACKGROUND: There are several techniques for harvesting the pedicled transverse rectus abdominis myocutaneous (TRAM) flap after mastectomy in breast cancer patients. We examined the whole muscle with partial sheath sparing technique and determined factors associated with its complications and oncological outcomes. METHODS: We retrospectively reviewed the results of 168 TRAM flaps performed between January 2003 and December 2010, focusing on complications and oncologic outcomes. RESULTS: Among the 168 pedicled TRAM flap procedures in 158 patients, flap complications occurred in 34%. Most of the flap complications included some degree of fat necrosis. There was no total flap loss. Flap complications were associated with elderly patients and the presence of major donor site complications. Abdominal bulging and hernia occurred in 12% of patients. The bi-pedicled TRAM flap and higher body mass index (BMI) were significant factors associated with increased donor site complications. Seven patients (4%) developed loco-regional recurrence. Within a median follow-up of 27 months, distant metastasis and death occurred in 6% and 4% of patients, respectively. CONCLUSIONS: The pedicled TRAM flap using the whole muscle with partial sheath sparing technique in the present study is consistent with the results from previous studies in flap complication rates and oncological outcomes.

High expression of apoptosis-inducing factor, mitochondrion-associated 3 (AIFM3) in human cholangiocarcinoma.

Prognosis of cholangiocarcinoma (CCA) patients is absolutely poor in spite of extensive efforts for the development of chemotherapy. Mitochondrial proteins play key roles in carcinogenesis of various cancers. Therefore, mitochondria are considered as the target organelles for chemotherapy of several cancers including CCA. The purpose of this study is to identify potential candidate proteins for chemotherapy using mitochondrial proteome analysis for CCA tissues. A shotgun proteomic approach using SDS-PAGE coupled with LC-MS/MS was applied to compare the expression of mitochondrial proteins in CCA and the adjacent non-cancerous tissues. Using the proteomic analysis for the pooled mitochondrial proteins purified from three each of papillary and non-papillary types of CCA and their adjacent tissues, 281 proteins were identified as mitochondrial proteins, and 105 of them have significantly different expression levels compared with the corresponding counterparts. Among the 105 proteins, apoptosis-inducing factor, mitochondrion-associated 3 (AIFM3) was a unique protein commonly over-expressed in both papillary and non-papillary types of CCA tissues but not in the adjacent non-cancerous tissues. In conclusion, AIFM3 was aberrantly expressed only in the mitochondria of CCA tissues. This finding suggests that AIFM3 could be a potential target molecule for CCA chemotherapy.

Outcome of curative resection for perihilar cholangiocarcinoma in Northeast Thailand.

AIM: To examine survival outcomes of perihilar cholangiocarcinoma (PCCA) resection including mortality, morbidity and prognostic factors. METHODS: Multivariate analyses were carried out based on the survival data of all patients with histologically confirmed PCCA who underwent curative resection at Srinagarind Hospital from January 2006 to December 2011. RESULTS: There were 29 (19%) cases of intrahepatic CCA that involved hilar and 124 (81%) with hilar bile-duct cancer. R0 resection was carried out on 66 (43.1%) patients of whom 50 (32.7%) also had lymph node metastasis. The other patients underwent R1 resection. The overall 5-year survival rate was 20.6% (95%CI: 13.8-28.4) and median survival time was 19.9 mo. Postoperative mortality was 2%, and 30% of patients had complications. Patients without lymph node metastasis were 60% less likely to die than those with metastasis. Achieving R0 led to a 58% reduction in the chance of mortality as compared to R1. CONCLUSION: To achieve a better survival outcome, focus should center on performing radical surgery and detection of patients with early stage cancer.

A comparison of letrozole and anastrozole followed by letrozole in breast cancer patients.

BACKGROUND: We previously studied the noninferiority of anastrozole (ANZ) versus ANZ followed by letrozole (A-LTZ) due to reimbursement policy. We found that patients with A-LTZ had better overall survival (OS) than did patients with ANZ alone. This study aimed to prove that patients with A-LTZ also had better OS than patients with letrozole (LTZ) alone. METHODS: All medical records of the breast cancer patients taking LTZ with or without ANZ between 2004 and 2013 were reviewed. All patients were divided into two groups: the LTZ group included patients treated with LTZ alone, and the A-LTZ group included patients treated with ANZ who were automatically changed to LTZ due to change of the reimbursement policy. RESULTS: From 359 cases, there were 179 cases in the LTZ group and 180 cases in the A-LTZ group. The mean age of patients in the LTZ group was 53.7 years and in the A-LTZ group was 54.2 years. The distribution of clinical stages among the LTZ group versus the A-LTZ group was 21 versus 4 (stage 1), 86 versus 116 (stage 2), 55 versus 46 (stage 3), and 17 versus 14 (stage 4), respectively. Among the LTZ patients, 63.7% took aromatase inhibitor monotherapy and 36.3% had a switching strategy, while in the A-LTZ group, 53.9% took AI monotherapy and 46.1% had a switching strategy. OS of the A-LTZ group was longer than that of the LTZ group. CONCLUSION: The patients in A-LTZ, taking ANZ followed by LTZ had better OS than those in LTZ, taking LTZ alone.

Effects of switching from anastrozole to letrozole, due to reimbursement policy, on the outcome of breast cancer therapy.

BACKGROUND: Endocrine therapy is one of the standard treatments for estrogen-receptor-positive breast cancer patients. Letrozole is the only aromatase inhibitor (AI) included in Thailand's essential drug list since the change of reimbursement policy in 2008, when patients had to change their AIs (other than letrozole) to letrozole. This study aimed to prove that the efficacy of anastrozole plus letrozole is not less than anastrozole alone. METHODS: All medical records of breast cancer patients taking anastrozole between 2004 and 2013 were reviewed. Some patients were initially treated with anastrozole and then changed to letrozole (A-LTZ group), whereas the other patients were continuously treated with anastrozole until completion of therapy (ANZ group). RESULTS: In a total of 180 (55.9%) out of the 322 cases, anastrozole was replaced with letrozole. The mean age of patients in the ANZ group was 54.9 years and that of those in the A-LTZ group was 54.2 years. Clinical stages (1-4) of the ANZ versus A-LTZ patients were four versus four, 76 versus 116, 46 versus 46, and 16 versus 14, respectively. ANZ patients took AI monotherapy (46.5%) and switching strategy (53.5%), while A-LTZ patients took AI monotherapy (53.9%) and switching strategy (46.1%). The overall survival (OS) of A-LTZ patients was longer than that of ANZ patients. Stage 2 and 4 patients in the A-LTZ group also had better OS than those in the ANZ group, but stage 3 patients had similar OS in both groups. CONCLUSION: Anastrozole can be replaced by letrozole any time during endocrine therapy. The patients taking anastrozole plus letrozole surprisingly seemed to have better OS than patients taking anastrozole alone.