Immediate-delayed lymphatic reconstruction after axillary lymph nodes dissection for locally advanced breast cancer-related lymphedema prevention: Report of two cases.

Approximately 60%-70% of breast cancer patients in Indonesia are diagnosed in the locally advanced stage. The stage carries a higher risk of lymph node metastasis which increases susceptibility to lymph obstruction. Hence, breast cancer-related lymphedema (BCRL) could present before axillary lymph node dissection (ALND). The purpose of this case report is to describe immediate-delayed lymphatic reconstructions with lymphaticovenous anastomosis in two subclinical lymphedema cases that present before ALND. There were 51 and 58 years old breast cancer patients with stage IIIC and IIIB, respectively. Both had no arm lymphedema symptoms, but arm lymphatic vessel abnormalities were found during preoperative indocyanine green (ICG) lymphography. Mastectomy and ALND were performed and proceeded with lymphaticovenous anastomoses (LVA) in both cases. One LVA at the axilla (isotopic) was done in the first patient. On the second patient, 3 LVAs at the affected arm (ectopic) and 3 isotopic LVAs were created. The patients were discharged on the second day without complications during the follow-up. The intensity of dermal backflow was reduced, and no subclinical lymphedema progression occurred during 11 and 9 months follow-up, respectively. Based on these cases, BCRL screening might be recommended for the locally advanced stage before cancer treatment. Once diagnosed, immediate lymphatic reconstruction after ALND should be recommended to cure or prevent BCRL progression.

Lymphaticovenular Anastomosis in Breast Cancer Treatment-Related Lymphedema: A Short-Term Clinicopathological Analysis from Indonesia.

BACKGROUND: Locally advanced breast cancer is commonly found in Indonesia. In this group of patients, aggressive treatment such as axillary lymph nodes dissection (ALND) with or without regional nodal irradiation (RNI) will increase the risk of breast cancer treatment-related lymphedema (BCRL) in our patients. Lymphaticovenular anastomosis (LVA) has been established as a minimally invasive approach in lymphedema surgery. In this study, we report our first experience of LVAs in BCRL patients. METHODS: This was a cross-sectional study taken from breast cancer patients receiving ALND with or without RNI. From December 2018 until June 2020, we collected and described general patient information, tumor characteristics, diagnostic methods, and the outcome of LVA. Postoperative subjective symptoms scores (lymphedema quality-of-life score [LeQOLiS]) and lymphedematous volume (upper extremity lymphedema [UEL] index) were compared with preoperative ones. RESULTS: Seventy patients experienced BCRL with the mean age of 54.8 (9.4) years and mean body mass index of 28.1 (4.5). ALND was performed in 66 (97.1%) cases and RNI was given in 58 (82.9%) patients. Thirty-one (44.3%) patients were in the International Society of Lymphology stage 1, 24 (34.3%) in stage 2A, and 15 (21.4%) in stage 2B. The mean lymphatic vessel diameter was 0.5 (0.26) mm and 0.80 (0.54) mm for the vein. Lymphosclerosis severity was 7 (4%) in S0 type, 129 (74.1%) in S1 type, 37 (21.3%) in S2 type, and 1 (0.6%) in S3 type. In histopathology examination, S1 types were in lower grade injury, while S2 and S3 types were in the higher grade. Seven (53.8%) cases of S2 type showed severe fibrosis from trichrome staining. Postoperative LeQOLiSs were significantly lower than preoperative ones (5.6 ± 2.4 vs. 3.7 ± 2.6; p = 0.000). With the mean follow-up of 7.4 (3.7) months, the overall UEL index reduction was 9.2%; mean -11 (16.8). Postoperative UEL index was significantly lower than preoperative ones (117.7 ± 26.5 vs. 106.9 ± 18.5; p = 0.000). No complications were observed during this period. CONCLUSION: LVA reduced the subjective symptoms and UEL index in BCRL cases. Future studies using updated imaging technologies of the lymphatic system and longer follow-up time are needed to confirm our results.

The predictive value of methylene blue dye as a single technique in breast cancer sentinel node biopsy: a study from Dharmais Cancer Hospital.

BACKGROUND: Axillary lymph node dissection (ALND) has been the standard treatment of breast cancer axillary staging in Indonesia. The limited facilities of radioisotope tracer and isosulfan or patent blue dye (PBD) have been the major obstacles to perform sentinel node biopsy (SNB) in our country. We studied the application of 1% methylene blue dye (MBD) alone for SNB to overcome the problem. METHODS: This prospective study enrolled 108 patients with suspicious malignant lesions or breast cancer stages I-III. SNB was performed using 2-5 cc of 1% MBD and proceeded with ALND. The histopathology results of sentinel nodes (SNs) were compared with axillary lymph nodes (ALNs) for diagnostic value assessments. RESULTS: There were 96 patients with invasive carcinoma from July 2012 to September 2014 who were included in the final analysis. The median age was 50 (25-69) years, and the median pathological tumor size was 3 cm (1-10). Identification rate of SNs was 91.7%, and the median number of the identified SNs was 2 (1-8). Sentinel node metastasis was found in 53.4% cases and 89.4% of them were macrometastases. The negative predictive value (NPV) of SNs to predict axillary metastasis was 90% (95% CI, 81-99%). There were no anaphylactic reactions, but we found 2 cases with skin necrosis. CONCLUSIONS: The application of 1% MBD as a single technique in breast cancer SNB has favorable identification rates and predictive values. It can be used for axillary staging, but nevertheless the technique should be applied with attention to the tumor size and grade to avoid false negative results.

Prognostic Values of CD8+, PARP, and EGFR on Overall Survival in Patients with Triple-Negative Breast Cancer.

OBJECTIVE: This study aimed to investigate the associations of CD8+, PARP, and EGFR expressions with two-year survival in patients with triple-negative breast cancer (TNBC). METHODS: A retrospective cohort study was conducted in a national cancer center. All patients aged 18 years diagnosed with TNBC (2013-2017) were included and followed for 24 months or until the patients were deceased. Kaplan-Meier survival function and Cox proportional hazard model were applied for the analyses. RESULTS: The study population was followed for 24 months (2,692 person-months, N = 126). At the end of the follow-up, 27 patients were deceased. The two-year mortality rate was 10 per 1,000 person-month. Kaplan-Meier graphs showed that after approximately one year of follow-up, poorer survival was seen in patients with low CD8+, positive PARP, and positive EGFR. The adjusted analysis found staging as the main predictor of overall survival in TNBC (HR = 7.20, 95% CI= 2.07 - 25.00). CONCLUSIONS: Patients with low CD8+, positive PARP, and positive EGFR expressions seem to be associated with poorer overall survival in TNBC. After approximately one year of follow-up, higher survival was observed in patients with high CD8+, negative PARP, and negative EGFR. Staging remains the main predictor of TNBC survival. Therefore, early detection and treatment of TNBC are essential to improve survival.

Supermicrosurgery lymphaticovenous and lymphaticolymphatic anastomosis: Technical detail and short-term follow-up for immediate lymphatic reconstruction in breast cancer treatment-related lymphedema prevention.

OBJECTIVE: We describe the feasibility and short-term outcome of our surgical technique to repair the lymph vessel disruption directly after axillary lymph node dissection during breast cancer surgery. This procedure is called immediate lymphatic reconstruction to prevent breast cancer treatment-related lymphedema (BCRL), which frequently occurs after axillary lymph node dissection. The surgical technique consisted of lymphaticovenous anastomosis (LVA) or lymphaticolymphatic anastomosis. We named the procedure lymphatic bypass supermicrosurgery (LBS). METHODS: This study used a retrospective cohort design of patients with breast cancer between May 2020 and February 2023. LBS was performed by making an intima-to-intima coaptation between afferent lymph vessels and the recipient's veins (LVA) or efferent lymph vessels lymphaticolymphatic anastomosis. RESULTS: A total of 82 patients underwent lymphatic bypass. The mean age of patients was 50 ± 12 years, and most had stage III breast cancer (n = 59 [72%]). LVA was the most common type of lymphatic bypass (94.6%). The median number of LVA was 1 (range, 1-4) and 1 (range, 1-3) for lymphaticolymphatic anastomosis. The median follow-up time was 12.5 months (range, 1-33 months). The 50 patients who had postoperative indocyanine green lymphography described arm dermal backflow stage 0 in 20 (40%), stage 1 in 19 (38%), stage 2 in 2 (4%), and stage 3 in 9 (18%) cases. The proportion of BCRL was 11 (22%), and subclinical lymphedema was 19 (38%) in this period. Most cases were in stable subclinical lymphedema (10, 58.8%). The 1-year and 2-year BCRL rates were 14% (95% confidence interval, 4%-23.9%) and 22% (95% confidence interval, 10.1%-33.9%), respectively. CONCLUSIONS: Along with the emerging immediate lymphatic reconstruction, LBS is a feasible supermicrosurgery technique that may have a potential role in BCRL prevention. A randomized controlled study would confirm the effectiveness of the technique.

Pretreatment nutritional status, HPV infection, and tumor infiltrating lymphocyte as prognostic predictors in patients with head and neck squamous cell carcinoma after chemotherapy.

Background: The survival rate in head and neck cancer varies among the subtypes, yet, the factors associated with survival between studies are still conflicting. This study aimed to investigate the association between pretreatment nutritional status, human papilloma virus (HPV) infection, tumor infiltrating lymphocyte (TIL), and treatment response after chemotherapy in patients with head and neck squamous cell carcinoma (HNSCC) in Indonesia. Further, factors associated with overall survival were also assessed. Methods: This was a retrospective cohort study. Data were collected between January 2015 and January 2018. A total of 30 patients with histopathologically proven squamous cell carcinoma head and neck cancer who had received at least three cycles of chemotherapy were included. Nutritional status was assessed using body mass index (BMI). Results: The mean BMI was 21.8 kg/m2 (Standard Deviation 3.98). The underweight patients had a higher risk of progressive disease (OR = 12.1, 95% CI = 1.1-135.6, P = 0.04) compared to patients with higher BMI. Neither HPV infection nor TIL was associated with treatment response and overall survival (P > 0.05). The median survival for the underweight patients was 9 months (95% CI = 3.00-15.00), whereas the median survival for normal and obese patients was 14 months (95% CI = 9.33-18.67). Conclusion: Underweight is associated with a significantly higher risk of progressive disease and tends to have shorter overall survival in patients with HNSCC. Yet, neither HPV infection nor TIL was associated with treatment response and overall survival.

Acetic Acid and Iodine Staining for Determining Malignancy in Solid Tumors.

OBJECTIVE: Surgical margin is an important prognostic factor in solid cancer surgery. Frozen section (FS), the gold standard for intraoperative surgical margin evaluation, requires extensive waiting time and expensive FS devices. The purpose of this diagnostic study was to verify whether multi-staining (MS) method with acetic acid and iodine could be used to differentiate malignant and non-malignant lesions of solid tumor. METHODS: The study was conducted on patients with solid tumor who underwent surgery in the Surgical Oncology Division of Dr. Cipto Mangunkusumo General Hospital from December 2017 to April 2018. Samples measuring less than 5 mm, necrotic tissue sample, and patients who did not agree to participate in the study were excluded. Every specimen was divided into two, one side as unstained control and the other side as MS samples. MS samples were sprayed with 10% acetic acid combined with iodine. MS samples and unstained controls were sent for histopathologic results and the pathologist was blinded to group assignment. Acetowhitening reaction in the sample was an indication of a positive MS result, and the presence of malignant foci in the histopathology examination was classified as positive pathological results. RESULTS: Five-hundred-and-twenty samples were obtained from 150 patients. MS method was found to have sensitivity and specificity of 82%, and 63.5%, respectively. In subgroup analysis, we found that MS method has a sensitivity and specificity of 100% and 79.3%, respectively for epithelial breast tumor; 65.7% and 83.3%, respectively for thyroid nodules; and 94.1% and 33.3%, respectively for oral cavity tumors. MS method reacts positively to solid malignant tumor and negatively to benign tumor and normal tissue (from margin samples). Highest sensitivity was found for breast and oral cavity malignancy, and high specificity was found for thyroid cancers. CONCLUSION: This study provided an alternative staining method for intraoperative macroscopic surgical margin evaluation, especially for rural areas without frozen section facilities.

Clinical Utility of BRAF, NRAS, and TERT Promoter Mutation in Preoperative Thyroid Fine-Needle Aspiration Biopsy: A Diagnostic Study From Dharmais Cancer Hospital.

OBJECTIVE: Molecular testing of thyroid nodules becomes important for improving the accuracy of fine-needle aspiration biopsy (FNAB). This study aimed to investigate the diagnostic utility of BRAF, NRAS, and TERT promoter mutation in thyroid nodules at Dharmais Cancer Hospital.
Methods: We performed a prospective diagnostic study involving 50 patients with thyroid nodules who needed surgery between September 2013 and August 2014. Mutational hotspots in BRAF exon 15, NRAS exon 3, and TERT promoter region were analyzed by Sanger sequencing from FNAB specimens. Cytology and molecular data were compared to histopathology results.
Result: Of the 50 cases included in the analysis, 39 cases (78%) were thyroid malignancies. Mutations of BRAF, NRAS, and TERT promoter were detected in 31% (12/39), 18% (7/39), and 13% (5/39) cases, respectively. BRAF and NRAS mutations were found mutually exclusive, while all of TERT promoter mutation was found coexistent either with BRAF (40%) or NRAS (60%). The combination of FNAB cytology and molecular testing resulted in 69% sensitivity, 100% specificity, 100% positive predictive value, 48% negative predictive value, and 76% accuracy.
Conclusion: Molecular testing of BRAF, NRAS, and TERT mutations improve the sensitivity of thyroid FNAB and is beneficial for more definitive treatment in selective cases. However, the NPV is relatively low to avoid the need for diagnostic surgery. Therefore, further studies to identify more sensitive methods and more comprehensive molecular markers in the diagnosis of thyroid nodules are needed.

Breast cancer treatment-related lymphedema (BCRL): An overview of the literature and updates in microsurgery reconstructions.

Breast cancer is the most common cancer in Dharmais hospital. The treatment can give rise to breast cancer treatment-related lymphedema (BCRL) that will cause significant morbidities. Based on author's (BB) patient series in Dharmais hospital, BCRL occurred in 27.7% after axillary lymph nodes dissection (ALND). The development of diagnostic modalities as well as lymphatic microsurgery have become promising instruments for lymphedema treatment. To date, modern approach of lymphedema care and surgical intervention have not been recognized and established in Indonesia. A literature review in this field is needed to overcome our limitation in BRCL or lymphedema management.

The Application of 1% Methylene Blue Dye As a Single Technique in Breast Cancer Sentinel Node Biopsy.

In this study, we injected 1% methylene blue dye (MBD) into the subareolar or peritumoral space of the breast. In the case of breast conserving surgery (BCS), a separate incision in the lower axilla hairline was made to find the sentinel nodes (SNs). In mastectomy, the SNs were identified through the same mastectomy incision. The SNs were described as blue nodes or nodes with lymphatic blue channels. An anatomical landmark in the axilla was used to facilitate SNs identification. The SNs metastases were evaluated by intraoperative frozen section analysis and histopathology examination as it is a gold standard. Here, we described the MBD as the lone technique in breast cancer sentinel node biopsy (SNB) which could be useful when radioisotope tracer or patent or isosulfan blue dye (PBD) cannot be provided.

Surgical perspective of T1799A BRAF mutation diagnostic value in papillary thyroid carcinoma.

BACKGROUND: Throughout Indonesia, thyroid cancer is one of the ten commonest malignancies, with papillary thyroid carcinoma (PTC) in our hospital accounting for about 60% of all thyroid nodules. Although fine needle aspiration biopsy (FNAB) is the most reliable diagnostic tool, some nodules are diagnosed as indeterminate and second surgery is common for PTC. The aim of this study was to establish the diagnostic value and feasibility of testing the BRAF T1799A mutation on FNA specimens for improving PTC diagnosis. MATERIALS AND METHODS: This prospective study enrolled 95 patients with thyroid nodules and future surgery planned. Results of mutational status were compared with surgical pathology diagnosis. RESULTS: Of the 70 cases included in the final analysis, 62.8% were PTC and the prevalence of BRAF mutation was 38.6%. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for BRAF mutation analysis were 36%, 100%, 100% and 48%, respectively. With other data findings, nodules with "onset less than 5 year" and "hard consistency" were proven as diagnostic determinants for BRAF mutation with a probability of 62.5%. This mutation was also a significant risk factor for extra-capsular extension. CONCLUSIONS: Molecular analysis of the BRAF T1799A mutation in FNAB specimens has high specificity and positive predictive value for PTC. It could be used in the selective patients with clinical characteristics to facilitate PTC diagnosis and for guidance regarding extent of thyroidectomy.