Reconsidering the Role of Frozen Section in Sentinel Lymph Node Biopsy for Mastectomy Patients.

INTRODUCTION: Axillary lymph node dissection was recommended for mastectomy patients with more than two nodal metastases from sentinel lymph node biopsy. Conventionally, intraoperative frozen section was sent routinely to reduce the need for second-stage axillary lymph node dissection; however, recent global trend has seen decreasing usage of the intraoperative analyses. This pilot study conducted in Thailand aimed to evaluate the role of intraoperative frozen section of sentinel lymph node biopsy in early-stage breast cancer patients who underwent mastectomy. METHODS: A 5-y retrospective study of 1773 patients was conducted in Thailand. The inclusion criteria were early-stage breast cancer patients with either radiologically negative nodes, or radiographically borderline nodes found to be negative on fine needle aspiration who underwent mastectomy and sentinel lymph node biopsy. Reoperations were indicated when three or more nodal metastases were detected on the pathological analysis. The reoperation rate prevented by frozen section and the reoperation rate needed for those with permanent section alone were reported. RESULTS: Among 265 patients, 202 patients underwent concomitant intraoperative frozen section while the remaining 63 patients underwent permanent section alone. Six patients (3.0%) from the frozen section group and one patient (1.6%) from the permanent section group were found with more than two nodal metastases. Despite using intraoperative frozen sections, only one patient from each group required reoperation. There was no significant difference in the number of patients requiring reoperation between the frozen section group and the permanent section group. CONCLUSIONS: Our study provides strong evidence to all surgeons that in early breast cancer patients undergoing mastectomy, sentinel lymph node biopsy with permanent section analysis alone may not lower the standard of care compared to using additional intraoperative frozen section analysis. Adopting this practice may lead to decreased operation costs, operative time, and anesthetic side effects.

New concept in selecting blue dye injection site effect on clinical outcome of early-stage breast cancer patients: a retrospective cohort.

BACKGROUND: Clinico-anatomical review and pilot studies demonstrated that intraparenchymal injection at any site, even those not containing the index lesion, or periareolar injections should provide concordant outcomes to peritumoral injections. METHOD: This was a single-center retrospective cohort at King Chulalongkorn Memorial Hospital. The electronic medical records of patients were characterized into conventional and new injection concept groups. The inclusion criteria were patients who had either a mastectomy or BCS along with SLNB. We excluded patients who underwent ALND, received neoadjuvant therapy, or had non-invasive breast cancer. The primary outcome was the 5-year rate of breast cancer regional recurrence. Additionally, we reported on the re-operation rate, disease-free period, distant disease-free period, mortality rate, and recurrence rates both locoregional and systemic. Recurrences were identified through clinical assessments and imaging. SURGICAL TECHNIQUE: 3 ml of 1%isosulfan blue dye was injected, with the injection site varying according to the specific concept being applied. In cases of SSM and NSM following the new concept, the blue dye was injected at non-periareolar and non-peritumoral sites. After the injection, a 10-minute interval was observed without massaging the injection site. Following this interval, an incision was made to access the SLNs, which were subsequently identified, excised, and sent for either frozen section analysis or permanent section examination. RESULT: There were no significant differences in DFS, DDFS or BCSS between the two groups (p = 0.832, 0.712, 0.157). Although the re-operation rate in the NI group was approximately half that of the CI group, this difference was not statistically significant (p = 0.355). CONCLUSION: Our study suggests that tailoring isosulfan blue dye injection site based on operation type rather than tumor location is safe and effective approach for SLN localization in early-stage breast cancer. However, this study has limitations, including being a single-center study with low recurrence and death cases. Future studies should aim to increase the sample size and follow-up period.

Paradoxically Greater Persistence of HIV RNA-Positive Cells in Lymphoid Tissue When ART Is Initiated in the Earliest Stage of Infection.

Starting antiretroviral therapy (ART) in Fiebig 1 acute HIV infection limits the size of viral reservoirs in lymphoid tissues, but does not impact time to virus rebound during a treatment interruption. To better understand why the reduced reservoir size did not increase the time to rebound we measured the frequency and location of HIV RNA+ cells in lymph nodes from participants in the RV254 acute infection cohort. HIV RNA+ cells were detected more frequently and in greater numbers when ART was initiated in Fiebig 1 compared to later Fiebig stages and were localized to the T-cell zone compared to the B-cell follicle with treatment in later Fiebig stages. Variability of virus production in people treated during acute infection suggests that the balance between virus-producing cells and the immune response to clear infected cells rapidly evolves during the earliest stages of infection. Clinical Trials Registration: NCT02919306.

Is sentinel lymph node biopsy without frozen section in early stage breast cancer sufficient in accordance with ACOSOG-Z0011? A retrospective review from King Chulalongkorn Memorial Hospital.

BACKGROUND: In 2021, there is an increased global trend for sending sentinel lymph node biopsy (SLNB) specimens for permanent section (PS) without intraoperative frozen sections (FS). This pilot study conducted in Thailand determines the re-operation rate for SLNB without FS. METHOD: We retrospectively reviewed 239 SLNB cases without FS at King Chulalongkorn Memorial Hospital from April 2016 to April 2021. The patients were diagnosed with primary invasive breast cancer with clinically negative nodes. The clinical nodal status was assessed from physical examination. The re-operation rate was determined by the number of positive SLNs; where 3 more nodal metastases were subjected to a second surgical procedure. RESULT: Between April 2016 and April 2021, 239 patients who had undergone SLNB in accordance with ACOSOG Z0011 criteria with PS alone was enrolled. A total of 975 SLNs were removed from these 239 patients, with an average of 4.15 nodes per patient. Out of 239 patients, 21 (8.8%) and 6 (2.5%) had metastatic disease in 1 and 2 nodes, respectively. The remaining 212 (88.7%) patients had no nodal metastasis. None of the patients were subjected to a second surgical procedure. CONCLUSION: We conclude that the implementation of SLNB with PS analysis alone in patients who satisfy the ACOSOG Z0011 criteria, with a re-operation rate of 0%, does not have outcomes that would be altered by the standard of care additional FS analysis. With ommision of FS analysis, operation cost, operative time and anesthetic side effects are projected to decrease.

Occult bleeding from a false-in-true non-Meckelian ileal diverticulum.

Ileal diverticula can be congenital or acquired and are rare even among the already rare entity of small bowel diverticula. What has never been reported, as far as we know, is false diverticula arising within the true non-Meckelian diverticulum with mesenteric erosion causing an occult gastrointestinal bleed. We present a patient with occult gastrointestinal bleeding from a false-in-true ileal diverticulum. Multiple investigations were required to localise the bleeding site after which the patient was taken to the operating room for a laparoscopic ileocaecectomy with complete resolution of symptoms. Preoperative localisation of the bleeding site may be difficult but is critically important in occult gastrointestinal bleeding. Procedure choice for a bleeding ileal diverticulum is dictated by the distance from the ileocaecal valve and the etiopathology of the bleed.

The tunnel infection in PD: Up in the air.

Catheter-related tunnel infection may lead to peritonitis and discontinuation of performing high-quality peritoneal dialysis (PD). Tunnel infection is commonly caused by Staphylococcus aureus. Gas-forming bacterial infection is rare in patients with PD and even exceedingly rare when such a infection spreads along the PD catheter tract. The first case of emphysematous PD catheter infection is presented here.

Double versus Single Primary Malignant Neoplasm of Breast and Colorectal Cancer: A Case-Control Study.

PURPOSE: Breast cancer (BC) and colorectal cancer (CRC) are common in female. This study compared survival time between women affected with both cancers with ones with single BC or single CRC. METHOD: Medical records of subjects with both BC & CRC (June 1, 2010, to June 30, 2021) were reviewed. Age-matched subjects who had BC or CRC alone were used as control. Survival analysis using Kaplan-Meier method was performed. RESULT: There were 63 double cancers [40 BC first (DBC): 23 CRC first (DCRC), mean age±SD 60.5±9.9 and 60.9±12.2 years] and 76 subjects in single cancer group [53 SBC: 23 SCRC, mean age 57.4±11.3 and 61.1±12.5 years]. The 5-year survival rate of the double cancer group was 74.6% and the single cancer group was 63.2%. D-group had slightly longer survival time than S-group (116.5±4.0 vs. 101.3±5.5, p=0.055). In D-group, the occurrence of addition of other primary cancers were more common (p=0.015). The second cancer occurred 61.7±45.3 months later in DBC group, and 39.1±26.6 months later in DCRC group (p=0.016). SCRC had shorter survival time vs. DCRC group (p=0.031). SBC and DBC had no different in mean survival time. CONCLUSION: BC and CRC could occur as a part of multiple primary cancers. Detection of more than one cancer did not lead to decrease survival if the second cancer was early detected and treated. The occurrence of the second cancer might be beyond 5 years after the diagnosis of the first cancer. Thus, longer surveillance may be warranted. Awareness and provision of early screening should be offered to individuals diagnosed with either primary cancer. Detection of more than one cancer did not lead to shorter survival.

Weight to volume conversion: an easy and practical breast volume estimation.

Background: Accurate breast volume estimation is essential for symmetrical breast reconstruction. Easy conversion of the weight of the resected breast tissue to volume could result in precise volume measurements. This study aimed to introduce the use of a mathematical constant (k) to estimate the breast volume from the weight. Methods: Eighty-nine female patients with breast cancer who underwent surgery at King Chulalongkorn Memorial Hospital between September 2010 and February 2011 were enrolled in this prospective study. The mammographic density of each patient was classified according to the breast imaging reporting and data system (BI-RADS) into groups a, b, c, and d. The breast density number and mathematical constant (k) were calculated, and the data matched. This technique was validated by comparing the measured and calculated volumes. Results: Sixty-six, 22, and 1 patients underwent total mastectomies (TMs), skin-sparing mastectomies (SSMs), and nipple-sparing mastectomies (NSMs), respectively. The breast densities were 1.0629, 1.1545, and 1.2233 g/mL, and the constant number (k) was 0.9409, 0.8662, and 0.8175 for BI-RADS a, combined BI-RADS b and c, and BI-RADS d, respectively. The validation process showed no significant differences between the measured and calculated volumes [95% confidence interval (95% CI)]. The correlation coefficient (r) was 0.984. Conclusions: Accurate breast volume estimation is a key factor in achieving symmetry in breast reconstruction. Combining existing data, including the weight of the resected breast tissue and mammographic density findings, an easy and accurate method to calculate the resected breast volume was introduced.

Initial productive and latent HIV infections originate in vivo by infection of resting T cells.

Productively infected cells are generally thought to arise from HIV infection of activated CD4+ T cells, and these infected activated cells are thought to be a recurring source of latently infected cells when a portion of the population transitions to a resting state. We discovered and report here that productively and latently infected cells can instead originate from direct infection of resting CD4+ T cell populations in lymphoid tissues in Fiebig I, the earliest stage of detectable HIV infection. We found that direct infection of resting CD4+ T cells was correlated with the availability of susceptible target cells in lymphoid tissues largely restricted to resting CD4+ T cells in which expression of pTEFb enabled productive infection, and we documented persistence of HIV-producing resting T cells during antiretroviral therapy (ART). Thus, we provide evidence of a mechanism by which direct infection of resting T cells in lymphoid tissues to generate productively and latently infected cells creates a mechanism by which the productively infected cells can replenish both populations and maintain two sources of virus from which HIV infection can rebound, even if ART is instituted at the earliest stage of detectable infection.

Sonographic focally thick duct of breast found in screening, why is it concerning? A report of three cases.

We report three cases of focally thickened ductal lesions found on screening ultrasonography with fine needle aspiration (FNA)-proven benign cytology in order to demonstrate the different fates of this radiographic finding. All three patients, aged 74, 69 and 68 years old, had their first time mammography and concurrent ultrasonography. Their mammograms did not show abnormalities except a focal asymmetry in one case. The sonographic focally thick ducts were the lesions of concern and all the patients had long-term follow-up.One patient had a slightly decreased lesion size on follow-up, likely to be a non-proliferative alteration of the breast. One patient's FNA revealed a benign papillary lesion whose ductal diameter slightly increased in size with internal echo after two years with repeat FNA demonstrating epithelial papillae consistent with intraductal papilloma. The final patient had an alteration of the imaged ductal lesion in the third year of follow-up and the final specimen after surgical wide excision that was done in the fourth year confirmed cancer. We emphasize the importance of focally thickened ductal lesions found on screening sonography and underscore their need for scrutinized characterization and long term follow-up.

Is Routine Intraoperative Frozen Section Analysis of Sentinel Lymph Nodes Necessary in Every Early-Stage Breast Cancer?

Purpose: Clinical application of the ACOSOG Z0011 trial results allows clinically node-negative breast cancer patients who meet criteria to avoid axillary dissection even when 1-2 sentinel lymph nodes (SLNs) are positive for metastatic disease. Intraoperative frozen section (iFS) analyses of SLNs were thought to reduce re-operation rates despite variable reported sensitivity and possibility of a false negative result. This study evaluated the rate of re-operations prevented by SLN iFS in a tertiary care hospital in Bangkok, Thailand, over a 6-year time-frame. Patients and Methods: From April 2016 to April 2022, 1284 sentinel lymph node biopsy (SLNB) procedures were performed. Of these, 214 cases were breast-conserving surgery in accordance with the ACOSOG criteria with concomitant usage of iFS. Clinicopathological features of these cases were collected and analyzed. Re-operation rates prevented by the additional intervention were reported. Results: Only five additional operations were prevented with the usage of 214 iFS. The discordance rate between frozen and permanent sections in terms of presence of metastatic disease and number of total lymph nodes was around 15%. Tumor staging, node staging, Nottingham histologic grading and lymphovascular invasion are significant predictors of SLN metastasis. Conclusion: iFS results in a very low prevention rate for follow-up ALND in patients with preoperative clinically negative axillary nodes and is associated with a non-negligible discordance rate with permanent sections. Our study suggests iFS may be avoided in most cases of early-stage clinically and radiographically node-negative breast cancer patients. Doing so may reduce surgical costs and total operative time without a significant impact on the overall quality of treatment and standard of care.

Anti-HIV antibody development up to 1 year after antiretroviral therapy initiation in acute HIV infection.

Early initiation of antiretroviral therapy (ART) in acute HIV infection (AHI) is effective at limiting seeding of the HIV viral reservoir, but little is known about how the resultant decreased antigen load affects long-term Ab development after ART. We report here that Env-specific plasma antibody (Ab) levels and Ab-dependent cellular cytotoxicity (ADCC) increased during the first 24 weeks of ART and correlated with Ab levels persisting after 48 weeks of ART. Participants treated in AHI stage 1 had lower Env-specific Ab levels and ADCC activity on ART than did those treated later. Importantly, participants who initiated ART after peak viremia in AHI developed elevated cross-clade ADCC responses that were detectable 1 year after ART initiation, even though clinically undetectable viremia was reached by 24 weeks. These data suggest that there is more germinal center (GC) activity in the later stages of AHI and that Ab development continues in the absence of detectable viremia during the first year of suppressive ART. The development of therapeutic interventions that can enhance earlier development of GCs in AHI and Abs after ART initiation could provide important protection against the viral reservoir that is seeded in individuals treated early in the disease.

Abundant HIV-infected cells in blood and tissues are rapidly cleared upon ART initiation during acute HIV infection.

The timing and location of the establishment of the viral reservoir during acute HIV infection remain unclear. Using longitudinal blood and tissue samples obtained from HIV-infected individuals at the earliest stage of infection, we demonstrate that frequencies of infected cells reach maximal values in gut-associated lymphoid tissue and lymph nodes as early as Fiebig stage II, before seroconversion. Both tissues displayed higher frequencies of infected cells than blood until Fiebig stage III, after which infected cells were equally distributed in all compartments examined. Initiation of antiretroviral therapy (ART) at Fiebig stages I to III led to a profound decrease in the frequency of infected cells to nearly undetectable level in all compartments. The rare infected cells that persisted were preferentially found in the lymphoid tissues. Initiation of ART at later stages (Fiebig stages IV/V and chronic infection) induced only a modest reduction in the frequency of infected cells. Quantification of HIV DNA in memory CD4+ T cell subsets confirmed the unstable nature of most of the infected cells at Fiebig stages I to III and the emergence of persistently infected cells during the transition to Fiebig stage IV. Our results indicate that although a large pool of cells is infected during acute HIV infection, most of these early targets are rapidly cleared upon ART initiation. Therefore, infected cells present after peak viremia have a greater ability to persist.

Ergonomic assessment of optimum operating table height for hand-assisted laparoscopic surgery.

BACKGROUND: To investigate the influence of the working surface height on task performance and muscle workload in hand-assisted laparoscopic surgery. METHODS: The standard task used was closure of 5-cm enterotomy inside a hand-assisted laparoscopic surgery trainer. Surgeons were instructed to place the sutures 3-5 mm apart and from the enterotomy edge. Ten surgeons participated in each experiment and one task was performed with each level. The first experiment compared the quality of task performance and muscle workload with the working surface at: elbow level, 10 cm above, 15 cm above and 10 cm below the elbow. Further narrower levels (5 cm below, at the elbow and 5 cm above the elbow) were investigated in the second experiment. Outcome measures were execution time (s), placement error score (mm), leakage pressure (mmHg), number of execution errors, muscle workload as measured by integrated electromyography (mV x s) and visual analogue score of back discomfort (mm). RESULTS: The first experiment showed that 15 cm above the elbow level was associated with the longest execution time and similar quality of task performance. This level resulted in a higher workload of the deltoid of the extracorporeal limb, the arm extensor of the intracorporeal side and the trapezius and paraspinal muscles of both intra- and extracorporeal limbs. Also, the 10 cm above the elbow level was associated with increased muscle workload of the deltoid of extracorporeal limb and the trapezius of both limbs compared with the elbow height. The 10 cm below the elbow level was associated with increased back discomfort. The second experiment showed that 5 cm below the elbow height was associated with increased muscle workload of the arm flexor group of the intracorporeal dominant limb. CONCLUSIONS: The optimum table height for hand-assisted laparoscopic surgery allows the working surface of the extracorporal instrument handle to be at or 5 cm above the elbow level.

Brief Report: Safety and Tolerability of Inguinal Lymph Node Biopsy in Individuals With Acute HIV Infection in Thailand.

INTRODUCTION: Latent HIV reservoirs are rapidly established in lymphoid tissues during acute HIV infection (AHI). Sampling these tissues provides important information about HIV pathogenesis. This period is associated with viral replication and immune activation that may affect procedure-related adverse events (AEs). We examined the safety and tolerability of inguinal lymph node (LN) biopsy in research participants with AHI in Bangkok, Thailand. METHODS: Between 2013 and 2016, 67 AHI participants in the RV254/SEARCH010 study underwent at least one optional inguinal LN biopsy during AHI at the baseline visit and/or after antiretroviral therapy (median 48 weeks after antiretroviral therapy). Biopsy-related AEs were graded according to NIH Division of AIDS guidelines. Poisson regression was used to calculate incidence rate ratios and 95% confidence intervals to evaluate associations of demographic and HIV characteristics, procedure timing, and repetition with AE incidence. RESULTS: Of the 67 participants, 97% were male with a median age of 26. Among 78 LN biopsies (39 at baseline and 39 at follow-up), 10 (12.8%) AEs were reported: 6 (7.7%) grade 1 and 4 (5.1%) grade 2. The AEs were biopsy-site discomfort (n = 8, 10.2%) and hematoma (n = 2, 2.6%). No factors were significantly associated with AE incidence. All biopsy-related AEs were transient and self-limited. CONCLUSIONS: Inguinal LN biopsies were safe and well tolerated in mostly Thai men with AHI. As LN biopsies become an integral part of HIV research, this study provides information to participants, researchers, and institutional review boards that these samples can be safely obtained.

Serum NT-proBNP in the early detection of doxorubicin-induced cardiac dysfunction.

AIM: Cardiac dysfunction is a major limitation of anthracycline treatment in cancer patients. There are several useful serum markers in other types of cardiomyopathy, including N-terminal pro-brain-natriuretic peptide (NT-proBNP), troponin-T and creatine kinase MB isoform. We investigated the potential application of these serum biomarkers in cancer patients receiving treatment with anthracycline. METHODS: We collected data from 52 female breast cancer patients receiving doxorubicin and cyclophosphamide every 3 weeks for four cycles. Cardiac function evaluations by echocardiography were done at baseline and at the end of the fourth cycle of chemotherapy. Patients' blood samples were serially measured for cardiac biomarkers. RESULTS: The mean cumulative dose of doxorubicin in this study was 237 mg/m(2) . No symptomatic heart failure was detected during the study period. However, there were significant asymptomatic reductions of left ventricular ejection fraction (LVEF) from mean ± SD 70.7 ± 6% at baseline to 67.0 ± 5% (P < 0.001). By clinical toxicity criteria the LVEF decline was grade I in 18% and grade II in 4%. After one dose of chemotherapy, a significant rise of serum NT-proBNP occurred in patients who subsequently developed an LVEF reduction compared with patients with normal LVEF (P = 0.04). A correlation analysis demonstrated that the reduction of fractional shortening was significantly associated with elevated NT-proBNP (r = -0.016, P = 0.014). CONCLUSION: Asymptomatic reductions in cardiac function are common in breast cancer patients treated with doxorubicin. NT-proBNP may serve as a convenient serum biomarker for the early detection of cardiotoxicity induced by anthracycline.