Wide Excision Margins Research Articles

Effects of adjuvant radiotherapy on borderline and malignant phyllodes tumors: A systematic review and meta-analysis

The standard treatment for borderline and malignant phyllodes tumors is wide local excision (margins ≥1 cm), in the context of either breast-conserving surgery (BCS) or total mastectomy (TM). Due to the high risk of local recurrence (LR) following surgical intervention alone, the addition of adjuvant radiotherapy (RT) has been previously investigated; however, the conclusions have been inconsistent. This systematic review and meta-analysis was designed to assess the efficacy of adjuvant RT for borderline and malignant phyllodes tumors. Pubmed and Web of Science were systematically searched to identify relevant studies assessing the effect of adjuvant RT on borderline and malignant phyllodes tumors from the inception of this technique through May, 2014. A total of 8 studies were identified among 332 citations. In this meta-analysis, patients who received adjuvant RT had a lower relative risk of LR [hazard ratio (HR) = 0.43, 95% confidence interval (CI): 0.23-0.64]. The absolute risk difference was 10.1% (95% CI: 4.9-17.6), corresponding to a number needed to treat of 10. Our pooled meta-analysis clearly demonstrated a decreased risk of LR in patients with borderline and malignant phyllodes tumors who received RT following BCS (HR=0.31, 95% CI: -0.10-0.72). However, the combined HR for LR in the TM group did not demonstrate that adjuvant RT was superior to no RT (HR=0.68, 95% CI: -0.28-1.64). No significant differences were observed in overall survival (OS) or disease-free survival (DFS) between the two groups. Our analysis suggested that adjuvant RT for borderline and malignant phyllodes tumors decreased the LR rate in patients undergoing BCS. However, adjuvant RT was not found to exert an effect on OS or DFS.

Reappraisal of conventional risk stratification for local recurrence based on clinical outcomes in 285 resected phyllodes tumors of the breast.

To ensure a surgical margin of ≥1 cm for the effective treatment of phyllodes tumors of the breast (PTB) a second resection has been recommended, but the outcomes of an extensive series of cases employing the aforementioned criterion cast doubt on this clinical approach. The aim of this study was to identify the local recurrence (LR) risk factors of PTB and determine future optimal surgical treatment according to verified risks. All cases given a diagnosis of PTB, and resected between 1989 and 2008, were retrospectively evaluated. Clinicopathologic data and clinical outcomes were analyzed and stratified according to the risks for LR. All 285 cases were categorized as benign (191, 67.0 %), borderline (61, 21.4 %), or malignant (33, 11.6 %). Median follow-up was 6.7 years and there were 20 LRs during follow-up. All benign PTB recurred as benign PTB lesions. Mitoses (p < 0.001) and tumor size (p = 0.021) were independent prognostic factors for LR in multivariate analysis. Neither margin status (p = 0.758) nor type of surgery (p = 0.922) had any significance for LR. In the risk stratification for LR, PTB ≤5 cm in size with ≥10 mitoses/10 high-power fields (HPFs) had the highest LR rate (55.6 %) compared with all other subgroups (p < 0.001). It is recommended a wide excision and clear margin of 1 cm be ascertained in only small PTB with frequent mitoses, if necessary by means of a second surgery, which could be considered in order to avoid the risk of LR in this distinct and limited group.

Clinical and radiological presentation of pleomorphic lobular carcinoma in-situ and its association with invasive malignancy

Abstract Aims Optimal management of Pleomorphic lobular carcinoma-in-situ (PLCIS) remains a matter of debate. We aimed to identify presenting clinical, radiological and histopathological features and oncological outcome of PLCIS. Methods From a prospectively maintained histopathology database between January 2000 and June 2014, all patients with a diagnosis of PLCIS were identified, and retrospective review of case notes performed. Results Of 19 cases, only 3 presented as symptomatic lumps, however 11 had mass lesions on imaging. All patients underwent definitive cancer surgery with wide margins. In all but three cases, PLCIS was associated with additional pathologies (DCIS, ILC, IDC), highlighting the pluripotential development of breast cancer. Of the six cases with no invasion, three were oestrogen receptor negative. There were no local or systemic recurrences over the median follow up period of 66 months. Conclusion PLCIS presenting without invasion is rare and, unlike invasive cancer and ductal carcinoma-in-situ, does not appear to be predominantly associated with ER positivity. However, PLCIS is almost universally associated with invasive cancer or DCIS, and should be managed with wide excision and clear margins. Clinical practise points ●There is uncertainty surrounding the management of PLCIS as highlighted by the lack of guidelines on this unusual disease entity. ●The commonest presentation of PLCIS is in asymptomatic women through breast screening. ●PLCIS presenting without invasion is rare and unlike invasive breast cancer and DCIS, does not appear to be predominantly commonly associated with ER positivity. ●PLCIS is commonly associated with in-situ and invasive lesions, with 58% of cases associated with invasive lobular carcinoma in this current series. ●Breast conserving surgery with clear margins and adjuvant treatment as dictated by associated pathology and molecular profile is recommended for PLCIS. ●In patients presenting with a mass lesion, and pure PLCIS on diagnostic core biopsy: A re-biopsy, ideally using vacuum-assistance is recommended, to attempt to upgrade the tumour pre-operatively, as invasion is almost universal in this subset. The common association of PLCIS with the presence of invasive ductal carcinoma, invasive lobular carcinoma, ductal carcinoma in-situ and lobular carcinoma-in-situ suggests a single pluripotent stem cell origin for these cancer subtypes.

Clinical outcomes for patients with synovial sarcoma of the hand.

PurposeSoft tissue sarcoma of the hand is rare, and one of the most common histological diagnosis is synovial sarcoma. We report the clinical outcomes of patients with synovial sarcoma of the hand and discuss treatment strategies.MethodsWe reviewed five patients with synovial sarcoma of the hand treated at our institutions from 1983 to 2013. The mean patient age at the time of diagnosis was 36.6 years (range, 20–62 years). Two patients underwent marginal excision after neoadjuvant chemotherapy, followed by radiation therapy, one underwent wide local excision and two received chemotherapy and radiation therapy.ResultsThe average duration of follow-up for all patients was 88.2 months (range, 14–218 months). Two patients continuously remained disease free, two experienced local recurrence requiring additional surgery and then showed no evidence of disease, and one who had distant metastasis at diagnosis died of the disease. No patients developed lymph node metastasis. The estimated 5-year overall survival was 80%.ConclusionsOur case series suggests that patients with localised synovial sarcoma of the hand may have favourable outcomes. Wide excision or marginal excision, followed by radiation therapy combined with chemotherapy, represent acceptable treatment strategies for synovial sarcoma of the hand. Regional lymph node dissection does not seem to be essential for synovial sarcoma of the hand.

Fat and epidermal cell suspension grafting: a new advanced one-step skin regeneration surgical technique

BackgroundDystrophic skin scarring commonly occurs following skin cancer resections. In particular, the cosmetic outcome of skin graft reconstructions, following epidermoidal carcinoma removal, is generally poor due to wide marginal tumour excision, loss of subcutaneous tissues, and subsequent pigmented atrophic scarring of the graft coverage. Skin grafting sequelae need a three dimensional correction to restore either the epidermal layer or the dermal/subdermal volume and vascularization.MethodsThe surgeons combined CO2 laser ablation, subdermal lipofilling according to the Coleman’s technique and epidermal cell suspension autografting to correct wide depressed and dyschromic facial scar. The Authors applied this new technique on three nasal skin cancer resected patients: two of them actually need a longer follow-up, the third patient, a 48 yr old caucasian male, presented a skin grafting scar due to sclerodermiform basal cell carcinoma removal. This case is reported discussing pre-intra and post-operative records up to a complete twelve months follow-up.ResultsRecords at six and twelve months follow-up after surgery demonstrate a fully integrated skin graft and a good restoration of the treated area, presenting the same texture and pigmentation of the adjacent untreated skin. Optimal, stable three-dimensional skin cosmetic restoration was obtained in a single stage surgical procedure.ConclusionAutologous non-cultured epidermal cell suspension transplantation on an epidermal laser ablated skin area, in combination with lipofilling subdermal reconstruction, appears to be an effective, simple and time-saving method to correct skin graft sequelae, in skin cancer patients. This new technique allows to restore a three-dimensional morphological structure of the treated area and to recover a natural appearance of the skin at the same time. The Authors believe that this technique can be safely used to treat any kind of dystrophic scarring.

Aggressive Angiomyxoma of the Vulva: Libyan Female Case Report

Aims and Background :Aggressive angiomyxoma is rare tumorof pelvicand perineal organs,occurring usually in women ofage, and carrying a high tendency to local infiltration and relapse. Most literature about Aggressive angiomyxoma consists of isolated case reports. Presentation of Case:We reported a case of 41-year-old Libyan womancomplainingof a slow and progressive growth ofa right vulvar labia major a pedunculated tumor with long a stalk was detected, measuringof 12.0x8.0 cm. Wide surgical resection of the tumor were performed.Histopathology diagnosed a large aggressive angiomyxoma with uninvolved resection margins. Patient remains without recurrence at 8.0 -months follow- up. Discussion and Conclusion: Non Aggressive angiomyxoma is rare butshould be excluded inany large vulval mass.We expect that awareness accompanied with wide freesafe margin excision has important role to prevent the recurrence of tumor.

Eight-year update of a prospective study of wide excision alone for small low- or intermediate-grade ductal carcinoma in situ (DCIS)

Whether wide excision with margins ≥1cm is sufficient treatment for small low- or intermediate-grade ductal carcinoma in situ (DCIS) is unclear. This is an updated analysis of a phase II, single-arm, prospective trial testing this hypothesis. A total of 158 patients with low- or intermediate-grade DCIS who underwent wide excision alone (without radiation or tamoxifen) were entered onto the trial from 1995 to 2002. Entry criteria included mammographic extent ≤2.5cm, predominantly low or intermediate nuclear grade, and excision with final microscopic margins ≥1cm. Eight-year minimum potential follow-up was required for inclusion in the analysis; the final population comprised 143 patients. Cumulative incidence curves were generated to assess rates of local recurrence (LR) or other events. Median follow-up time was 11years. Nineteen patients (13%) had LR as a first event within 8years. Thirteen LR (68%) were DCIS only and six (32%) were invasive. Fourteen (74%) occurred in the original quadrant. The 10-year estimated cumulative incidence of LR was 15.6%. The estimated annual percentage rate of LR was 1.9% per patient-year. With longer follow-up, there remains a substantial and ongoing risk of LR in patients with favorable DCIS treated with wide excision margins without radiation. This information should be useful as patients and clinicians weigh the options of wide excision with and without radiation.

Preliminary Results of High-Dose Single-Fraction Radiotherapy for the Management of Chordomas of the Spine and Sacrum

En bloc wide-margin excision significantly decreases the risk of chordoma recurrence. However, a wide surgical margin cannot be obtained in many chordomas because they arise primarily in the sacrum, clivus, and mobile spine. Furthermore, these tumors have shown resistance to fractionated photon radiation at conventional doses and numerous chemotherapies. To analyze the outcomes of single-fraction stereotactic radiosurgery (SRS) in the treatment of chordomas of the mobile spine and sacrum. Twenty-four patients with chordoma of the sacrum and mobile spine were treated with high-dose single-fraction SRS (median dose, 2400 cGy). Twenty-one primary and 3 metastatic tumors were treated. Seven patients were treated for postoperative tumor recurrence. In 7 patients, SRS was administered as planned adjuvant therapy, and in 13 patients, SRS was administered as neoadjuvant therapy. All patients had serial magnetic resonance imaging follow-up. The overall median follow-up was 24 months. Of the 24 patients, 23 (95%) demonstrated stable or reduced tumor burden based on serial magnetic resonance imaging. One patient had radiographic progression of tumor 11 months after SRS. Only 6 of 13 patients who underwent neoadjuvant SRS proceeded to surgery. This decision was based on the lack of radiographic progression and the patient's preference. Complications were limited to 1 patient in whom sciatic neuropathy developed and 1 with vocal cord paralysis. High-dose single-fraction SRS provides good tumor control with low treatment-related morbidity. Additional follow-up is required to determine the long-term recurrence risk.

Evidence‐based management of primary and localized Merkel cell carcinoma: a review

Merkel cell carcinoma is a rare and often lethal cutaneous neuroendocrine malignancy with a tendency for early and frequent locoregional and distant metastasis and relapses. It is a tumor of the elderly and immunosuppressed, which most often appears on sun-exposed areas of the body. There is growing interest in characterization of the disease and the best approach to its management. Despite the lack of prospective randomized clinical trials, treatment is evolving. To provide an updated review of the most current and relevant data concerning the surgical (± radiological) management of Merkel cell carcinoma, including the role of Mohs micrographic surgery. Using relevant MeSH terms, we performed a review of the literature on the above subjects from 1981 to 2011. For primary tumors without evidence of organ metastases, surgical excision should be the primary therapy. Owing to the high rate of local metastases, a safety margin of at least 2 cm should be considered. In situations where small, localized tumors and/or special locations necessitate a smaller safety margin, compensation by complete histological examination of the excision margins and perhaps adjuvant radiation therapy should be undertaken. The literature states that benefits of Mohs micrographic surgery (over wide local excision) include tissue conservation and identification of tumors that may require extremely wide excision margins. The majority of data to date supports the use of Mohs surgery in the treatment of Merkel cell carcinoma.

Tumor filodes maligno: a propósito de un caso y revisión de la literatura

Phyllodes tumor of the breast is a rare neoplasm, representing less than 1% of all breast tumors. The definitive diagnosis of these fibroepithelial tumors is histologic. Local recurrence occurs in 20% of cases. Although uncommon, these tumors can metastasize to other organs. Treatment is surgical with wide excision and disease-free margins. We present the case of a patient with phyllodes tumor who developed lung involvement.

A case of well‐differentiated palpebral liposarcoma in a Guinea pig (Cavia porcellus)

Liposarcomas are rare malignant tumors of the adipose tissue which are well described in humans and animals. Wide margin excision is the recommended treatment for these infiltrative, slow to metastasize tumors. Primary liposarcoma with ocular localization is a very rare tumor in humans, dogs and cats. This report describes, for the first time, a palpebral liposarcoma in a 18-month old guinea pig that presented with a large palpebral mass and purulent discharge in the right eye. The ophthalmic evaluation revealed a one-centimeter infiltrating subcutaneous mass within the upper eyelid, a severe chemosis and hyperhemia of the palpebral and bulbar conjunctiva of the right eye. Cytologic examination of the mass revealed only epithelial cells. Histologic examination interpreted the lesion as a xanthogranulomatous reaction possibly secondary to meibomian gland rupture or inflammation. One month later, the mass had increased in size and the animal had stopped eating. Euthanasia was performed and a large biopsy was submitted for another histological examination. Histopathology revealed polygonal to rounded cells with a large, empty intracytoplasmic vacuole, and an ovoid, eccentrically located nucleus. The histology was consistent with a well-differentiated liposarcoma. Given the unusual location, immunohistochemistry was performed to ascertain the mesenchymal nature of the neoplasm.

Thumb reconstruction using a free osseocutaneous fibular flap following excision of an epithelioid haemangioendothelioma

Epithelioid haemangioendothelioma are a rare type of aggressive vascular tumour, which can occur in multiple areas of the body. Current treatment is surgical with wide excision of the tumour and surrounding tissue often resultant in large defects requiring reconstruction. We present the case of a patient with an epithelioid haemangioendothelioma affecting the proximal and distal phalanx of their dominant thumb. Local reconstructive options were poor given the wide excision margin including both skin and bone. After careful consideration, the decision was made to reconstruct the area using a free osseocutaneous fibula flap to provide both vascularised bone and an overlying skin paddle. We report the first documented case of a thumb reconstruction with an osseocutaneous free fibula flap following excision of an epithelioid haemangioendothelioma.

Size does matter: High volume breast surgeons accept smaller excision margins for wide local excision – A national survey of the surgical management of wide local excision margins in UK breast cancer patients

IntroductionOptimal margins for wide local excision (WLE) have not been clearly established. Larger margins lead to lower recurrence rates but at the expense of cosmetic appearance. NICE guidelines recommend a 2 mm margin for ductal carcinoma in-situ (DCIS), whilst the British Association of Surgical Oncology (BASO) recommend units develop local guidelines. There are presently no specific guidelines for invasive cancer. We surveyed members of the Association of Breast Surgeons (ABS) in order to establish current practice nationally. We hypothesised that larger units may accept narrower excision margins to the benefit of better cosmesis. Materials and methodsA postal questionnaire was sent to all ABS members in October 2010. This consisted of questions about the current practice of the surgeon and their unit. 481 questionnaires were posted in total, all questionnaires returned by April 2011 were analysed. ResultsQuestionnaire response rate was 60% (281). Surgeons operating on over 50 cancers per year accepted smaller margins than those operating on less than 50 (p < 0.02). Acceptable adequate anterior and radial margins ranged from 0 to 10 mm for DCIS and 0 to 5 mm for invasive cancer. A variety of approaches to re-excising anterior margins were reported. ConclusionsThis survey suggests that substantial variations exist in current practice with regard to the approach to WLE. Operator workload appears to influence what is deemed to be an acceptable margin. There is a need for standardised national and international guidelines.

Small cell neuroendocrine tumour of the anterior tongue: A case report

INTRODUCTIONNeuroendocrine carcinomas (NECs) are rare in the oral cavity. There is ambiguity regarding the classification of these tumours, but their aggressive nature is recognised throughout the literature. Merkel cell carcinoma (MCC) is rare and more frequent in skin, though it has also been described intra-orally. High grade neuroendocrine tumours (HGNEC) and MCCs behave aggressively and aggressive treatment strategies have been advocated. We describe the first small cell HGNEC on the anterior tongue. PRESENTATION OF CASEWe present the first report of a pT1pN1M0 small cell HGNEC in a 75 year old man on the left lateral anterior tongue. This was widely resected with 20mm peripheral and deep margins to achieve disease clearance. Selective neck dissection of levels 1–4 was also carried out. DISCUSSIONHistological analysis of the tumour confirmed a primary poorly differentiated neuroendocrine tumour of small cell type (small cell HGNEC). Resected node bearing tissue from levels 1–4 confirmed metastasis to a level III node with no extra capsular spread giving a pT1pN1M0 classification. Margins of 11.7mm from the invasive tumour to mucosal margin medially and 7.0mm for the deep margin despite surgical 20mm margin resection. To the best of our knowledge small cell neuroendocrine carcinoma has not been described in the anterior tongue. CONCLUSIONThe aggressive nature of this tumour type mandates aggressive surgical resection with margins similar to those now recommended for skin Merkel cell carcinomas. We advocate a wide excision margin of 20mm to give adequate clearance, with neck dissection in order to pathologically stage this cancer type.

Patient with Malignant Granular Cell Tumor Treated with Sunitinib Malate

Malignant granular cell tumors (MGST) are extremely rare, high-grade sarcoma of schwann cell origin. They often metastasize and are associated with short survival. We described a patient with recurred MGST after wide marginal excision followed by chemotherapy. The histologic findings revealed relapsed MGST containing rich vascular structure. The patient was treated with sunitinib ma late (50 mg/day) for three weeks. Because sunitinib malate has a potent antiangiogenic property, we surmised that it might be effective against this type of malignancy. However, he died due to progression of tumor after six weeks. Here, we report it along with the corresponding literature.

Leg swelling after inguinal sentinel lymph node biopsy and primary melanoma excision with a safety margin

Risk-factors for leg swelling following primary melanoma excision and inguinal sentinel lymphadenectomy (SLNE) have not been sufficiently investigated. We prospectively studied three parameters in 105 subjects: 1) subjectively perceived swelling, 2) clinically diagnosed swelling and 3) photo-optical measurement of volume differences between both legs. Perceived swelling, clinically diagnosed swelling, and manifest edema occurred in 31%, 15%, and 7% of patients respectively. Following inguinal SLNE, there was a mean volume increase of 1.5% in the operated leg. Both the lower leg and the thigh increased in volume. Obesity, primary melanoma location on the lower leg, and inguinal seromas were identified as significant risk factors for postoperative swelling. Wider excision margins around a primary melanoma on the thigh were also associated with a significant increase in volume. Age, sex, the number of sentinel lymph nodes, the drainage fluid volume, and the time since SLNE were non-significant. Both inguinal SLNE and primary melanoma excision may contribute to minimal fluid accumulation in the leg. More than two-thirds of patients did not have any swelling. Obesity, location of the primary melanoma at a distal site on the leg, a wide safety margin, and seromas are associated with postoperative leg swelling.

Right Kocher’s incision: a feasible and effective incision for right hemicolectomy: a retrospective study

BackgroundThe choice of surgical incision is determined by access to the surgical field, particularly when an oncological resection is required. Special consideration is also given to other factors, such as postoperative pain and its sequelae, fewer complications in the early postoperative period and a lower occurrence of incisional hernias. The purpose of this study is to compare the right Kocher’s and the midline incision, for patients undergoing right hemicolectomy, by focusing on short- and longterm results.MethodsBetween 1995 and 2009, hospital records for 213 patients that had undergone a right hemicolectomy for a right- sided adenocarcinoma were retrospectively studied. 113 patients had been operated via a Kocher’s and 100 via a midline incision. Demographic details, operative data (explorative access to the peritoneal cavity, time of operation), recovery parameters (time with IV analgesic medication, time to first oral fluid intake, time to first solid meal, time to discharge), and oncological parameters (lymph node harvest, TNM stage and resection margins) were analyzed. Postoperative complications were also recorded. The two groups were retrospectively well matched with respect to demographic parameters and oncological status of the tumor.ResultsThe median length of the midline incision was slightly longer (12 vs. 10 cm, p < 0.05). The duration of the surgery for the Kocher’s incision group was significantly shorter (median time 70 vs 85 min, p < 0.001). In three patients we performed wedge resection of liver metastasis and in one patient we performed a typical right hepatectomy that lasted 190 min. No major operative complications were noted. There was no immediate or 30- day postoperative mortality. The Kocher’s incision group had a significantly shorter hospital stay (median time 5 vs 8 days). All patients underwent wide tumor excision and clear resection margins were obtained in all cases. No significant difference was noted regarding analgesia requirements and early postoperative complications. Late postoperative complications included 2 incisional hernias and three patients presented with one episode of obstructive ileus, that resolved conservatively.ConclusionsThe Kocher’s incision approach for right- sided colon cancer is technically feasible, safe and overall very well tolerated. It can achieve the same standards of tumor resection and surgical field accessibility as the midline approach, while reducing postoperative recovery.

Re-excision of incompletely excised cutaneous squamous cell carcinoma: Histological findings influence prognosis

We have previously shown 28.6% of re-excisions for margin-positive cutaneous SCC to yield residual tumour (positive re-excision). Original tumour diameter and thickness conferred significant risks for positive re-excision. We now report a 5-year prospective follow-up of our re-excision cohort. Of 676 consecutive SCC patients, 84 underwent wider-excision for positive margins. 79 of these patients completed a mean of 28 months follow-up. Overall, 9/79 (11%) of this re-excision cohort experienced locoregional recurrence, all within 2 years of primary resection. Of the positive re-excisions, 29% experienced recurrence, vs 5% in those with negative re-excisions. Logistic-regression analysis revealed positive re-excision to predict recurrence (P<0.05, RR 10.1), independent from tumour-grade, anatomical site, size, and delay to re-excision. Factors associated with residual tumour on re-excision are similar to characteristics of high-risk SCCs; larger tumours in particular are more likely to persist and may benefit from wider excision-margins at original resection. Positive re-excision is newly identified as a significant risk for locoregional recurrence, whilst negative re-excision is associated with a return to a low-risk prognosis, for all tumours. Our findings thus support the treatment of cutaneous SCC through to completion. We also recommend re-excision where narrow or close margins are reported. Patients with a positive re-excision should be considered at high risk for recurrence, requiring extended follow-up.

A Rare Form of Melanoma Masquerading as a Diabetic Foot Ulcer: A Case Report

Background. Acral lentiginous melanoma (ALM) is a less-common form of melanoma in US, and it accounts for about 5% of all diagnosed melanomas in US. ALM is often overlooked until it is well advanced because of the lesion's location and its atypical appearance in the early stages. We present a case of ALM initially presented as a diabetic foot ulcer. Case Report. An 81-year-old man initially presented to the primary care clinic with a right foot diabetic ulcer. There was a large plantar, dark-colored ulcer that bled easy. Initial excision biopsy revealed Clark's Level IV ALM. Subsequent definitive wide excision and sentinel node biopsy confirmed ALM with metastasis to inguinal lymph nodes (stage IIIb). The treatment included wide margin excision of the lesion with en bloc amputations of 4th and 5th toes, followed by adjuvant chemotherapy. Discussion. The development of ALM may potentially relate to diabetes as a reported higher prevalence of diabetes with ALM patients. Conclusion. The difficulty in early diagnosing of ALM remains as a formidable challenge particularly in diabetic patients who commonly develop plantar foot ulcers due to the diabetic neuropathy. This case reiterates the importance of a thorough foot exam in such patients.

2-cm versus 4-cm surgical excision margins for primary cutaneous melanoma thicker than 2 mm: a randomised, multicentre trial

Optimum surgical resection margins for patients with clinical stage IIA-C cutaneous melanoma thicker than 2 mm are controversial. The aim of the study was to test whether survival was different for a wide local excision margin of 2 cm compared with a 4-cm excision margin. We undertook a randomised controlled trial in nine European centres. Patients with cutaneous melanoma thicker than 2 mm, at clinical stage IIA-C, were allocated to have either a 2-cm or a 4-cm surgical resection margin. Patients were randomised in a 1:1 allocation to one of the two groups and stratified by geographic region. Randomisation was done by sealed envelope or by computer generated lists with permuted blocks. Our primary endpoint was overall survival. The trial was not masked at any stage. Analyses were by intention to treat. Adverse events were not systematically recorded. The study is registered with ClinicalTrials.gov, number NCT01183936. 936 patients were enrolled from Jan 22, 1992, to May 19, 2004; 465 were randomly allocated to treatment with a 2-cm resection margin, and 471 to receive treatment with a 4-cm resection margin. One patient in each group was lost to follow-up but included in the analysis. After a median follow-up of 6·7 years (IQR 4·3-9·5) 181 patients in the 2-cm margin group and 177 in the 4-cm group had died (hazard ratio 1·05, 95% CI 0·85-1·29; p=0.64). 5-year overall survival was 65% (95% CI 60-70) [corrected] in the 2-cm group and 65% (40-70) in the 4-cm group (p=0·69). Our findings suggest that a 2-cm resection margin is sufficient and safe for patients with cutaneous melanoma thicker than 2 mm. Swedish Cancer Society and Stockholm Cancer Society.