Quantification of T-Cell Receptor Excision Circles (TRECs).

Aging is a natural process that compromises the immune system's functionality increasing the risk of infectious, tumors, and autoimmune diseases. The thymus involution is an age-dependent process characterized by decreased cellularity, peripheral lymphocyte infiltration into the perivascular space, and expansion of adipose tissue. All those modifications hamper the functionality of the organ and lead to a decline of naïve T-cell production with a shrinking of the T-cell repertoire. Thymus atrophy is described in several disorders including autoimmune diseases. The quantification of T-cell receptor excision circles (TRECs) in recent thymus emigrants is a standard procedure to investigate the thymic function. In this chapter, we discuss the methodology used to quantify this molecule in peripheral blood mononuclear cells and isolated CD4+ and CD8+ T cells.

Decoding a Rare Case of Pleomorphic Adenoma: A Case Report and Review of the Literature.

Diagnosing palatal swellings is crucial for various reasons, mainly because these swellings can signal a range of health problems, from benign conditions to more serious diseases. Here, we have reported an interesting case of long-standing palatal swelling. Accurate diagnosis typically involves a combination of clinical examination, patient history, imaging studies, and possibly biopsy or other laboratory tests. Since each condition has unique characteristics and treatment approaches, differential diagnosis is essential for ensuring effective management. This case highlights the importance of considering pleomorphic adenoma in the differential diagnosis of palatal tumors and demonstrates the effectiveness of surgical management. A literature review is also presented, discussing the clinical, radiological, and histopathological features of this rare entity. Accurate diagnosis and timely intervention are crucial for effective treatment and maintaining overall oral health.

Transanal intersphincteric under direct view in the jackknife position combined with laparoscopic total mesorectal excision for treating ultra-low rectal cancer.

Aim: To investigate the effect and clinical advantage of transanal intersphincteric (ISR) under direct view in the jackknife position combined with laparoscopic total mesorectal excision (TME) for treating ultra-low rectal cancer. Additionally, the feasibility of this surgical technique was evaluated. Method: This was a retrospective, single-center, single-arm pilot study. Ten patients with ultra-low rectal cancer underwent treatment by the same surgical team for direct view transanal ISR combined with laparoscopic TME in the Department of Anorectal Surgery, Huizhou Central People's Hospital between January 2021 and June 2021. The relevant clinical data were collected and analyzed. Results: All the patients underwent complete mesenteric resection without conversion to laparotomy. The circumferential and distal resection margins (CRM and DRM) were negative. The mean distance between the lower margin of the tumor and the anal margin was 2.8 ± 0.8 cm, and the mean margin of distal resection was 1.2 ± 0.2 cm. TNM pathological stages I, II, III, and IV were observed in 6, 2, 2, and 0 cases, respectively. The median follow-up period was 15 months (interquartile range, 8 months). The mean Wexner and Low Anterior Resection Syndrome scores at 12 months after ileostomy were 8.1 ± 2.1 and 22.4 ± 5.7, respectively. Conclusion: Transanal ISR under direct view in the jackknife position combined with laparoscopic TME is safe and feasible for the treatment of ultralow rectal cancer.

Peri anal region is an overlooked location for pilonidal recurrence after surgical excision and closure - A case series.

INTRODUCTION AND IMPORTANCE: Patients with pilonidal disease (PD) often undergo wide excision of pilonidal sinuses and flap-based closures. Patients who failed these procedures can have recurrent perianal wounds obscured by hair and unrecognized even by the treating physicians. In this report, we describe a series of pilonidal patients with recurrent disease and perianal wounds. CASE PRESENTATION: Five pilonidal patients with recurrent disease after surgical excision and flap closure were referred to our Pilonidal Care Clinic. All five were found to have perianal wounds. Each patient was treated with regular manual and laser epilation and only one patient required a Gips procedure. All wounds were successfully healed. CLINICAL DISCUSSION: After removal of hair at the perianal region, patients with recurrent pilonidal disease can expose a pilonidal sinus that was previously unrecognized. Peri-anal wounds can have poor wound healing due to the close proximity of the wound to the anal verge, risk of contamination, difficulty of consistent observation of the wound, and moist environment of the anus that retains bacteria. Careful consideration of proper wound care post-excision of perianal pilonidal sinuses should be prioritized. CONCLUSIONS: Pilonidal perianal wounds after previous surgical excision and flap closure can be obscured by hair, resulting in recurrent pain and drainage. The perianal wounds can be successfully healed with regular manual and laser epilation and selectively excised using Gips procedure.

Direct Excision of Malar Bags: Back to the Basics.

INTRODUCTION: The pursuit of periorbital rejuvenation to counteract signs of aging is a focal point in cosmetic surgery, with eyelid surgery being a prominent choice among patients. Addressing inferior blepharoplasty, especially in cases involving chronic malar edema, malar mounds, and festoons, presents unique challenges. The terminology and classification of these conditions vary, hindering effective management. In this study, we use the term "malar bags" to encompass the spectrum of fluid-associated mounds over the malar eminence. OBJECTIVES: This study aims to demonstrate the effectiveness of direct excision as a surgical choice for treating the aesthetic concerns associated with malar bags. MATERIALS AND METHODS: A retrospective study was conducted on 53 patients who underwent direct excision of malar bags between 2013 and 2023 at our clinic. RESULTS: No major complications were encountered, overall high level of satisfaction for both patients and surgeons. CONCLUSION: Direct excision of malar bags proved to be a safe and effective technique, yielding satisfactory results in terms of both aesthetic outcomes and patient satisfaction. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Pseudoangiomatous stromal hyperplasia (PASH) of the breast: A case series.

Pseudoangiomatous stromal hyperplasia (PASH) is a benign mesenchymal proliferative lesion of the breast. In 2005, only 109 cases have been reported since its initial description in 1986 by Vuitch et al. when it presented in one patient as a palpable breast mass. We retrospectively reviewed data from 2020 to 2023 of patients diagnosed with PASH by surgical excision. Our 13 cases represent one of the most numerous reported from a single institution. All histologic specimens were examined by a single pathologist. All patients had breast masses on imaging or were clinically evident. Eleven of the patients (84.6%) were diagnosed by surgical excision, whilst only two (15.4%) were diagnosed by core needle biopsy. Imaging revealed no strongly distinctive features for PASH. The age of the patients ranged from 25 to 68 years. All but one of the women were premenopausal at the time of diagnosis. This study suggests that PASH is a lesion whose diagnosis is often incidental and the recommended treatment is more commonly surgical.

Role of Adjuvant Chemotherapy After Curative Resection in Stage II and III Rectal Cancer.

INTRODUCTION: Patients with resected locally advanced rectal cancer (LARC) and an incomplete total mesorectal excision (TME) have worse oncologic outcomes. The associations between TME grade, adjuvant therapy receipt, and oncologic outcomes have not been well-studied. We aimed to determine the association between adjuvant chemotherapy and oncologic outcomes in patients who underwent neoadjuvant chemoradiation (CRT) or short-course radiotherapy (SCRT) followed by proctectomy and to evaluate this association stratified by TME grade. MATERIALS AND METHODS: We analyzed a retrospective multi-institutional cohort of primary LARC patients diagnosed between 2010 and 2018 who received neoadjuvant CRT/SCRT followed by proctectomy. Complete TME was defined as complete mesorectal excision, and noncomplete TME was defined as near-complete or incomplete TME. We used adjusted Cox proportional hazards regression to test the association between adjuvant chemotherapy and mortality or locoregional recurrence (LRR) across groups. RESULTS: We identified 746 eligible patients. On final pathology, 101 (13.5%) had noncomplete and 645 (86.5%) had complete TME. Rates of adjuvant chemotherapy receipt were similar between noncomplete and complete TME groups (70.3% and 69.5%, respectively). Mean follow-up interval was 35 mo. Adjuvant chemotherapy was associated with lower risk of mortality (HR 0.27, 95% CI 0.19-0.39, P < 0.001); the same association existed when stratifying patients by TME grade. For patients with a complete TME, adjuvant chemotherapy was associated with lower LRR (HR 0.08, 95% CI 0.01-0.56, P = 0.01). The LRR model for the noncomplete TME group did not converge due to few captured recurrences. CONCLUSIONS: These data show an association between adjuvant chemotherapy and positive outcomes in LARC patients receiving neoadjuvant CRT/SCRT followed by proctectomy.

Volume changes in the contralateral submandibular gland following unilateral gland excision in oral cancer patients.

BACKGROUND: The effects of unilateral submandibular gland excision on the size of the contralateral gland are not well understood, with no human studies reported to date. This study aims to investigate the impact of unilateral submandibular gland excision on the contralateral gland's size, providing insights into compensatory mechanisms and their clinical implications. METHOD: This retrospective study involved patients with oral cancer who underwent unilateral submandibular gland excision and ipsilateral neck dissection at Gangneung-Wonju National University Dental Hospital between 2008 and 2023. Patients were included if they had preoperative and follow-up 3D radiological images. The contralateral submandibular gland volume was measured using 3D Slicer software on preoperative, post-operative, and follow-up radiographic data. RESULTS: The mean volume change of the contralateral submandibular gland was 1.35 ± 2.06 cm3, with a mean change ratio of 1.18 ± 0.24. These changes were statistically significant (p = 0.006). Other factors such as age, gender, and radiotherapy did not significantly affect the volume change ratio (p > 0.05). CONCLUSION: The contralateral submandibular gland exhibits a statistically significant increase in volume following unilateral gland excision, indicating compensatory hypertrophy. This morphological adaptation should be considered in post-operative care and surgical planning for oral cancer patients to optimize outcomes.

Intraosseous Lipoma of Calcaneus An Uncommon Cause of Heel Pain: A Case Report.

ABSTRACT: Intraosseous lipoma of calcaneum is a rare cause of heel pain. Calcaneum is a typical site of involvement of IOL. There are only a few published articles regarding calcaneal intraosseous lipoma and one has been reported from Nepal. We report a case of 35 years female who presented with left heel pain for 1 year. The pain was gradually increasing in intensity and was severe enough to refrain her from activities of daily living. She was surgically operated with curettage and filling the defect with bone cement. There is no residual pain at 2.5 years follow up. We briefly review the postulated pathogenesis, clinical manifestations, diagnosis and various modalities of treatment of intraosseous lipoma. An orthopedic surgeon should have high degree of suspicion regarding the uncommon cause of heel pain and its possible management. When conservative methods do not relieve symptoms, surgical excision and filling the defect with bone cement provides long term relief.

Partial excision of infrapatellar fat pad for the treatment of knee osteoarthritis.

AIMS: Knee osteoarthritis (KOA) is a common degenerative joint disease characterized by pain and functional limitations. Current treatments offer symptomatic relief but do not address the underlying pathology. This study explores the role of the infrapatellar fat pad (IFP) in KOA and evaluates the efficacy of its partial arthroscopic excision. METHODS: A retrospective review was conducted on 37 KOA patients who underwent partial IFP excision. Pain and function were assessed using the WOMAC and VAS scores, while MRI evaluations focused on cartilage health. RESULTS: Significant postoperative improvements were observed in both pain and functional outcomes, with substantial reductions in WOMAC and VAS scores (P < 0.001). MRI findings demonstrated notable enhancements in cartilage integrity, reflected in significantly improved WORMS scores (P < 0.001). CONCLUSIONS: Partial excision of the IFP significantly reduces pain and improves function in KOA patients, while also promoting cartilage health. These findings support the IFP's role in KOA pathology and highlight the potential benefits of targeted surgical intervention.

Diagnostic pitfall in radiological imaging after vacuum-assisted excision of B3 breast lesion: A case report.

The management of B3 breast lesions using vacuum-assisted excision (VAE) is gaining increasing traction in clinical practice. However, it is infrequently reported in the literature how this technique may affect long-term imaging appearances. We present a challenging case in which the previous VAE site displayed a mass-like appearance that mimicked breast cancer. The purpose of this case report is to share our experience and illustrate the ultrasound and mammographic characteristics of the residual cavity after VAE, in order to contribute to expanding knowledge regarding radiological imaging post-VAE, which is currently still limited.

Intramuscular Hydatid Cyst of the Thigh: A Rare Presentation in an Elderly Patient.

Intramuscular hydatid cysts are an uncommon presentation of echinococcosis, with most cases occurring in the liver and lungs. This case report describes an 81-year-old male who presented with a painless, progressively enlarging swelling in the right thigh noticed over the past year. The patient's history included trauma to the area from an animal-related incident five years earlier. Physical examination revealed a firm, irregular, and non-tender mass. Ultrasonography suggested a multiloculated cystic lesion with calcification, raising suspicions of a hematoma or hydatid cyst. Fine-needle aspiration cytology indicated an organized hematoma with secondary calcification. Given the diagnostic uncertainty, surgical excision revealed a 3x3 cm hydatid cyst in the intramuscular plane. A histopathological examination confirmed the diagnosis. The patient's postoperative course was uneventful, with no signs of recurrence at the three-month follow-up. This case underscores the importance of considering hydatid disease in the differential diagnosis of intramuscular swellings, particularly in patients with relevant exposure histories.

Vulval leiomyoma with acute postoperative delirium.

Leiomyomas are benign, well-circumscribed mesenchymal tumours. While uterine leiomyomas are common, vulval leiomyomas are rare. We report the challenging case of vulval leiomyoma in a multiparous woman, who also developed acute postoperative delirium. A 41-year-old multiparous woman presented with a mass in the perineum of one year duration and discomfort in a sitting position since a month ago. Her menstrual history, family history, and personal history were unremarkable. On examination of the vulva, there was a firm mass of size 10 x 8 cm on the left side, involving the labium majus and minus, which was distorting the introitus. The uterus and ovaries were normal. Preoperative ultrasound was suggestive of a vulval solid lobulated lesion, probably leiomyoma. Excision of the mass was performed. The patient developed postoperative delirium at 3 hours and was treated with an injection of haloperidol, antibiotics, and electrolyte correction. She recovered well and was discharged on the sixth postoperative day. Histopathology confirmed leiomyoma of the vulval mass, with areas of cystic degeneration. At 6-month follow-up the patient was asymptomatic and had no recurrence. To conclude, vulval leiomyoma is rare and treated by excision. The occurrence of postoperative delirium adds to the surgical morbidity, and gynaecologists should be aware of these conditions for optimal outcomes.

Local excision versus total mesorectal excision for rectal cancer patients with clinical complete or near-complete response after neoadjuvant chemoradiotherapy.

PURPOSE: Local excision is an effective approach for managing rectal cancer exhibiting substantial regression after neoadjuvant chemoradiotherapy. The purpose of this study is to compare the outcomes between local excision and total mesorectal excision in rectal cancer patients achieving clinical complete or near-complete response after neoadjuvant chemoradiotherapy. METHODS: This is a retrospective cohort study that includes a consecutive series of rectal cancer patients who responded well to neoadjuvant chemoradiotherapy followed by surgery. A total of 180 rectal cancer patients at a single institution during a 12-year period are included. The main outcomes include short-term outcomes, oncological outcomes, and functional outcomes between the two groups. RESULTS: A total of 180 patients were included in the study. Sixty-one (33.9%) received local excision and 119 (66.1%) received total mesorectal excision. The baseline characteristics were generally balanced between the two groups. The local excision group demonstrated a significantly shorter operative time, less blood loss, and shorter hospital stay (p < 0.001). 3-year overall survival rates were 97.5% (95% CI, 0.93-1.00) and 95.5% (95% CI, 0.91-1.00) between the two groups (p = 0.38). The local excision group exhibited significantly higher 3-year local recurrence rates 15.7% (95% CI, 0.74-0.97) vs 4.2% (95% CI, 0.92-1.00) (p = 0.017), yet lower 3-year distant metastasis rates 9.6% (95% CI, 0.82-1.00) vs 12.6% (95% CI, 0.81-0.94) (p = 0.33) and lower 3-year disease-free survival rates 76.8% (95% CI, 0.64-0.92) vs 84.7% (95% CI, 0.78-0.92) (p = 0.56) comparing with the total mesorectal excision group. The local excision group demonstrated significantly better functional outcomes compared with the total mesorectal excision group (p < 0.001). CONCLUSION: Patients who achieve either clinical complete or near-complete response after neoadjuvant chemoradiotherapy are suitable candidates for local excision. The local excision group demonstrated superior short-term and functional outcomes, and the oncological outcomes were not compromised.

Base-excision repair pathway regulates transcription-replication conflicts in pancreatic ductal adenocarcinoma.

Oncogenic mutations (such as in KRAS) can dysregulate transcription and replication, leading to transcription-replication conflicts (TRCs). Here, we demonstrate that TRCs are enriched in human pancreatic ductal adenocarcinoma (PDAC) compared to other common solid tumors or normal cells. Several orthogonal approaches demonstrated that TRCs are oncogene dependent. A small interfering RNA (siRNA) screen identified several factors in the base-excision repair (BER) pathway as main regulators of TRCs in PDAC cells. Inhibitors of BER pathway (methoxyamine and CRT) enhanced TRCs. Mechanistically, BER pathway inhibition severely altered RNA polymerase II (RNAPII) and R-loop dynamics at nascent DNA, causing RNAPII trapping and contributing to enhanced TRCs. The ensuing DNA damage activated the ATR-Chk1 pathway. Co-treatment with ATR inhibitor (VX970) and BER inhibitor (methoxyamine) at clinically relevant doses synergistically enhanced DNA damage and reduced cell proliferation in PDAC cells. The study provides mechanistic insights into the regulation of TRCs in PDAC by the BER pathway, which has biologic and therapeutic implications.

Uncovering the effects of non-lethal oxidative stress on replication initiation in Escherichia coli.

Cell cycle adaptability assists bacteria in response to adverse stress. The effect of oxidative stress on replication initiation in Escherichia coli remains unclear. This work examined the impact of exogenous oxidant and genetic mutation-mediated oxidative stress on replication initiation. We found that 0-0.5 mM H2O2 suppresses E. coli replication initiation in a concentration-dependent manner but does not lead to cell death. Deletion of antioxidant enzymes SodA-SodB, KatE, or AhpC results in delayed replication initiation. The antioxidant N-acetylcysteine (NAC) promotes replication initiation in ΔkatE and ΔsodAΔsodB mutants. We then explored the factors that mediate the inhibition of replication initiation by oxidative stress. MutY, a base excision repair DNA glycosylase, resists inhibition of replication initiation by H2O2. Lon protease deficiency eliminates inhibition of replication initiation mediated by exogenous H2O2 exposure but not by katE or sodA-sodB deletion. The absence of clpP and hslV further delays replication initiation in the ΔktaE mutant, whereas hflK deletion promotes replication initiation in the ΔkatE and ΔsodAΔsodB mutants. In conclusion, non-lethal oxidative stress inhibits replication initiation, and AAA+ proteases are involved and show flexible regulation in E. coli.

AP endonuclease 1: Biological updates and advances in activity analysis.

Apurinic/apyrimidinic endodeoxyribonuclease 1 (APE1, APEX1, REF1, HAP1) is an abasic site-specific endonuclease holding critical roles in numerous biological functions including base excision repair, the DNA damage response, redox regulation of transcription factors, RNA processing, and gene regulation. Pathologically, APE1 expression and function is linked with numerous human diseases including cancer, highlighting the importance of sensitive and quantitative assays to measure APE1 activity. Here, we summarize biochemical and biological roles for APE1 and expand on the discovery of APE1 inhibitors. Finally, we highlight the development of assays to monitor APE1 activity, detailing a recently improved and stabilized DNA Repair Molecular Beacon assay to analyze APE1 activity. The assay is amenable to analysis of purified protein, to measure changes in APE1 activity in cell lysates, to monitor human patient samples for defects in APE1 function, or the cellular and biochemical response to APE1 inhibitors.

Recovery of insect-pathogenic fungi from solar UV damage: Molecular mechanisms and prospects.

Molecular mechanisms underlying insect-pathogenic fungal tolerance to solar ultraviolet (UV) damage have been increasingly understood. This chapter reviews the methodology established to quantify fungal response to solar UV radiation, which consists of UVB and UVA, and characterize a pattern of the solar UV dose (damage) accumulated from sunrise to sunset on sunny summer days. An emphasis is placed on anti-UV mechanisms of fungal insect pathogens in comparison to those well documented in model yeast. Principles are discussed for properly timing the application of a fungal pesticide to improve pest control during summer months. Fungal UV tolerance depends on either nucleotide excision repair (NER) or photorepair of UV-induced DNA lesions to recover UV-impaired cells in the darkness or the light. NER is a slow process independent of light and depends on a large family of anti-UV radiation (RAD) proteins studied intensively in model yeast but rarely in non-yeast fungi. Photorepair is a rapid process that had long been considered to depend on only one or two photolyases in filamentous fungi. However, recent studies have greatly expanded a genetic/molecular basis for photorepair-dependent photoreactivation that serves as a primary anti-UV mechanism in insect-pathogenic fungi, in which photolyase regulators required for photorepair and multiple RAD homologs have higher or much higher photoreactivation activities than do photolyases. The NER activities of those homologs in dark reactivation cannot recover the severe UV damage recovered by their activities in photoreactivation. Future studies are expected to further expand the genetic/molecular basis of photoreactivation and enrich principles for the recovery of insect-pathogenic fungi from solar UV damage.

Node-sparing modified short-course Radiotherapy Combined with CAPOX and Tislelizumab for locally Advanced MSS of Middle and low rectal Cancer (mRCAT): an open-label, single-arm, prospective, multicentre clinical trial.

BACKGROUND: Neoadjuvant chemoradiotherapy followed by total mesorectal excision is a standard treatment for locally advanced rectal cancer. Mismatch repair-deficient locally advanced rectal cancer (LARC) was highly sensitive to PD-1 blockade. However, most rectal cancers are microsatellite stable (MSS) or mismatch repair-proficient (pMMR) subtypes for which PD-1 blockade is ineffective. Radiation can trigger the activation of CD8 + T cells, further enhancing the responses of MSS/pMMR rectal cancer to PD-1 blockade. Radioimmunotherapy offers a promising therapeutic modality for rectal cancer. Progenitor T exhausted cells are abundant in tumour-draining lymph nodes and play an important role in immunotherapy. Conventional irradiation fields include the mesorectum and regional lymph nodes, which might cause considerable damage to T lymphocytes and radiation-induced fibrosis, ultimately leading to a poor response to immunotherapy and rectal fibrosis. This study investigated whether node-sparing modified short-course irradiation combined with chemotherapy and PD-1 blockade could be effective in patients with MSS/ pMMR LARC. METHODS: This was a open-label, single-arm, multicentre, prospective phase II trial. 32 LARC patients with MSS/pMMR will receive node-sparing modified short-course radiotherapy (the irradiated planned target volume only included the primary tumour bed but not the tumour-draining lymph nodes, 25 Gy/5f, 5 Gy/f) followed by CAPOX and tislelizumab. CAPOX and tislelizumab will be started two days after the completion of radiotherapy: oxaliplatin 130 mg/m2 intravenous infusion, day 1; capecitabine 1000 mg/m2 oral administration, days 1-14; and tislelizumab 200 mg, intravenous infusion, day 1. There will be four 21-day cycles. TME will be performed at weeks 14-15. We will collect blood, tumour, and lymphoid specimens; perform flow cytometry and in situ multiplexed immunofluorescence detection; and analyse the changes in various lymphocyte subsets. The primary endpoint is the rate of pathological complete response. The organ preservation rate, tumour regression grade, local recurrence rate, disease-free survival, overall survival, adverse effects, and quality of life will also be analysed. DISCUSSION: In our research, node-sparing modified radiotherapy combined with immunotherapy probably increased the responsiveness of immunotherapy for MSS/pMMR rectal cancer patients, reduced the occurrence of postoperative rectal fibrosis, and improved survival and quality of life. This is the first clinical trial to utilize a node-sparing radiation strategy combined with chemotherapy and PD-1 blockade in the neoadjuvant treatment of rectal cancer, which may result in a breakthrough in the treatment of MSS/pMMR rectal cancer. TRIAL REGISTRATION: This study was registered at www. CLINICALTRIALS: gov . TRIAL REGISTRATION NUMBER: NCT05972655. Date of registration: 31 July 2023.

Are Positive Biopsy Margins in Melanoma Significant?: A Cohort Study of Micro- Versus Macroscopic Margin Status and Their Impact on Residual Disease and Survival.

BACKGROUND: Presence of positive biopsy margins in melanoma can provoke anxiety over potential disease progression from delays to surgical excision, but their impact on outcomes is unknown. We aimed to compare the presence of residual melanoma in the surgical excision specimen and survival between patients with negative, microscopically positive, and macroscopically positive biopsy margins. METHODS: Patients with cutaneous melanoma who underwent surgical excision over a 13-year period were included. Biopsy characteristics, residual disease in the surgical specimen, and overall and recurrence-free survival were compared between patients with negative, microscopically positive (only scar visible), and macroscopically positive (visible remaining melanoma) biopsy margins. RESULTS: Of 901 patients, 42.4%, 33.3%, and 24.3% had negative, microscopically positive, and macroscopically positive margins, respectively. The incidence of residual invasive melanoma in the surgical specimen varied (P < 0.001), occurring in 5.5%, 17.0%, and 74.9% of patients, respectively. Both microscopically and macroscopically positive margins were associated with residual disease (P < 0.001) but only the latter predicted worse overall (P = 0.013) and recurrence-free survival (P = 0.009). Kaplan-Meier estimated survival was comparable between those with negative and microscopically positive margins, but overall (P = 0.006) and recurrence-free survival (P = 0.004) were significantly worse in the macroscopically positive margin group. These patients had worse prognosis melanoma, with 33.8% being stage III disease, and 23.2% having positive sentinel lymph nodes. CONCLUSIONS: Patients and physicians may be reassured in the presence of microscopically positive biopsy margins which are not associated with worse survival, However, patients with macroscopically positive margins have poorer prognosis and should be treated within an acceptable time frame.