CT diagnosis of ilioinguinal lymph node metastases in melanoma using radiological characteristics beyond size and asymmetry.

BACKGROUND: Diagnosis of lymph node (LN) metastasis in melanoma with non-invasive methods is challenging. The aim of this study was to evaluate the diagnostic accuracy of six LN characteristics on CT in detecting melanoma-positive ilioinguinal LN metastases, and to determine whether inguinal LN characteristics can predict pelvic LN involvement. METHODS: This was a single-centre retrospective study of patients with melanoma LN metastases at a tertiary cancer centre between 2008 and 2016. Patients who had preoperative contrast-enhanced CT assessment and ilioinguinal LN dissection were included. CT scans containing significant artefacts obscuring the pelvis were excluded. CT scans were reanalysed for six LN characteristics (extracapsular spread (ECS), minimum axis (MA), absence of fatty hilum (FH), asymmetrical cortical nodule (CAN), abnormal contrast enhancement (ACE) and rounded morphology (RM)) and compared with postoperative histopathological findings. RESULTS: A total of 90 patients were included. Median age was 58 (range 23-85) years. Eighty-eight patients (98 per cent) had pathology-positive inguinal disease and, of these, 45 (51 per cent) had concurrent pelvic disease. The most common CT characteristics found in pathology-positive inguinal LNs were MA greater than 10 mm (97 per cent), ACE (80 per cent), ECS (38 per cent) and absence of RM (38 per cent). In multivariable analysis, inguinal LN characteristics on CT indicative of pelvic disease were RM (odds ratio (OR) 3.3, 95 per cent c.i. 1.2 to 8.7) and ECS (OR 4.2, 1.6 to 11.3). Cloquet's node is known to be a poor predictor of pelvic spread. Pelvic LN disease was present in 50 per cent patients, but only 7 per cent had a pathology-positive Cloquet's node. CONCLUSION: Additional CT radiological characteristics, especially ECS and RM, may improve diagnostic accuracy and aid clinical decisions regarding the need for inguinal or ilioinguinal dissection.

Diagnostic performance of MRI and histology in assessment of deep lipomatous tumours.

BACKGROUND: Deep lipomatous tumours can be benign lipomas or intermediate/locally recurring atypical lipomatous tumours (ALTs). Differentiating between these two entities clinically and radiologically is difficult. The aims of this study were to report a series of deep lipomatous tumours, comparing the clinical, radiological and pathological features of ALTs and lipomas; and to predict the likelihood of a lipomatous tumour being ALT based on anatomical site and MRI characteristics. METHODS: This was a retrospective review of patients with deep lipomatous tumours presenting over 6 years to a tertiary sarcoma centre, with preoperative MRI, and preoperative or postoperative histology including MDM2 gene analysis. Sensitivity, specificity, predictive values and accuracy in diagnosing ALT were calculated for MRI and histopathological features. RESULTS: Some 248 patients were included; 81 (32·7 per cent) had a final diagnosis of ALT. ALTs were larger than lipomas (median 19 versus 10 cm; P < 0·001); there was no ALT smaller than 5 cm. A tumour presenting in the lower limb was more likely to be an ALT than a lesion at any other site (48·4 versus 13·5 per cent; P < 0·001). In patients with lipomatous tumours at sites other than the lower limbs, MRI had a negative predictive value of 95 per cent for excluding ALT. CONCLUSION: Despite concern, most deep lipomatous tumours (nearly 70 per cent) are benign lipomas. Certain features imply that tumours are almost never ALT: smaller than 5 cm or located outside the lower limb with no suspicious characteristics on MRI. Tumours with these features might safely and confidently be managed outside tertiary sarcoma centres.

ANTECEDENTES: Los tumores lipomatosos profundos pueden ser lipomas benignos o tumores lipomatosos atípicos (atypical lipomatous tumour, ALT) con potencial de recidiva local/intermedia. Diferenciar estas dos entidades desde el punto de vista clínico es difícil. Los objetivos de este estudio fueron presentar una gran serie de tumores lipomatosos profundos, comparando las características clínicas, radiológicas y patológicas de los ALT y de los lipomas y predecir la probabilidad de que un tumor lipomatoso sea ALT según su localización anatómica y las características de la RNM. MÉTODOS: Revisión retrospectiva de pacientes con tumores lipomatosos profundos tratados en un centro terciario de sarcoma durante un período de 6 años, en los que se dispusiese de RNM preoperatoria y análisis MDM2 en el preoperatorio o postoperatorio. Se calculó la sensibilidad, la especificidad, el valor predictivo y la precisión diagnóstica de la RNM y de las características histopatológicas para el diagnóstico de ALT. RESULTADOS: Se incluyeron 248 pacientes, de los que en solo 81 (32,7%) se estableció un diagnóstico final de ALT. Los ALT fueron más grandes que los lipomas (19 versus 10 cm, P < 0,001) y no hubo ningún ALT de tamaño menor de 5 cm. Hubo una mayor probabilidad de que un tumor fuera ALT si se presentaba en las extremidades inferiores en comparación con cualquier otra localización (48,4% versus 13,5%, P < 0,001). En pacientes con tumores lipomatosos localizados en otros lugares que no fueran las extremidades inferiores, la RMN tuvo un valor predictivo negativo del 95,5% para excluir la ALT. CONCLUSIÓN: A pesar del recelo tradicional, la mayoría (70%) de los tumores lipomatosos profundos son lipomas benignos. Algunas características, como los tumores de menos de 5 cm y aquellos ubicados fuera de las extremidades inferiores sin características sospechosas por RNM, indican que los tumores casi nunca son ALT. Los tumores con esas características pueden tratarse de manera segura y con solvencia fuera de los centros de sarcomas terciarios. En casos seleccionados, puede ser útil la prueba genética MDM2 en la biopsia.

The impact of effective systemic therapies on surgery for stage IV melanoma.

INTRODUCTION: The outcomes of patients with metastatic melanoma have significantly improved with the introduction of effective systemic therapies (ESTs). The role of surgery in the context of ESTs for stage IV melanoma is evolving. We sought to characterise the changing patterns of surgery and oncological outcomes in patients with stage IV melanoma treated before and after the establishment of ESTs. METHODS: Patients undergoing surgical resection of stage IV melanoma were identified from our institutional database from 2003 to 2015. Patients were grouped into two cohorts, those referred before EST (2003-2007) and after EST (2011-2015). Clinicopathological variables, patterns of surgery and oncological outcomes in the two groups were compared. RESULTS: A total of 138 patients underwent surgery for stage IV melanoma (n = 69 in each cohort). We observed no significant difference in the ratio of operations/patients performed. However, the pattern of operations altered, with a significant decrease in in-transit excisions (0.9% vs. 19.4%, p < 0.001) and an increase in abdominal metastasectomies (21.1% vs. 4.2%, p < 0.001), in the after-EST cohort. Novel indications for surgical intervention were noted in the after-EST cohort, with a significant increase in potentially curative operations for residual oligometastatic disease (15.9% vs. 4.3%, p = 0.045). Survival after surgery was prolonged in the after-EST cohort (median 16 months vs. 6 months, p < 0.001), with the stage at initial metastasectomy (stage 4a, hazard ratio [HR] 0.45 (0.28-0.73), p = 0.001) and treatment with immune checkpoint inhibitors (HR 0.38 (0.25-0.60), p < 0.001) associated with prolonged survival. DISCUSSION: Surgery remains important in the management of stage IV melanoma, with evolving indications and patterns of intervention after the introduction of ESTs. The combination of judicious surgery and EST may improve oncological outcomes.

The effect of age on outcomes after isolated limb perfusion for advanced extremity malignancies.

BACKGROUND: Isolated limb perfusion (ILP) is a well-established treatment for patients with advanced extremity malignancies unsuitable for limb-conserving surgery. However, little is known about the outcomes of this treatment in elderly patients. We sought to determine the effects of age on the tolerability and efficacy of ILP for advanced extremity malignancy. PATIENTS AND METHODS: Patients undergoing ILP at our institution between January 2005 and January 2018 were identified from a prospectively maintained database. Patients were stratified by pathology (melanoma, soft-tissue sarcoma, other) and age (<75 years and ≥75 years). Outcomes of interest were perioperative morbidity and mortality, locoregional toxicities, response rates and oncological outcomes. RESULTS: During the study period, a total of 189 perfusions were attempted. Successful perfusions were performed in 179 patients, giving a technical success rate of 94.7%. No difference in perfusion success rates, severe locoregional toxicity and perioperative morbidity or mortality was noted between those aged <75 years and ≥75 years. The overall response rate in melanoma was 82.4%, and no difference in response rates or oncological outcomes between age groups was noted in these patients. The overall response rate in soft-tissue sarcoma was 63.5%, with no difference in response rates noted between age groups. However, patients aged <75 years with soft-tissue sarcoma had prolonged local recurrence-free survival compared with older patients (13 versus 6 months), possibly due to the prevalence of chemosensitive subtypes in the younger age group. CONCLUSION: ILP is an effective treatment for advanced extremity malignancies in the elderly, with comparable response rates and toxicities to younger patients.

Multivisceral resection of retroperitoneal sarcomas in the elderly.

BACKGROUND: Retroperitoneal sarcomas occur in an anatomically complex location often involving several adjacent organs. Surgery with multivisceral resection constitutes the mainstay of curative therapy. This study sought to characterise the morbidity and oncological outcomes of surgery for retroperitoneal sarcoma in an elderly population. METHODS: Patients with primary, localised retroperitoneal sarcoma referred between 1st January 2008 and 31st December 2014 were identified from multidisciplinary meeting records. The proportion of patients proceeding to surgery and oncological outcomes were compared between two groups-those aged >65 years and <65 years. RESULTS: A total of 385 patients were identified. The most common histological subtypes were de-differentiated liposarcoma (40.3%), well-differentiated liposarcoma (19.5%) and leiomyosarcoma (18.2%). A greater proportion of patients aged >65 years did not undergo surgery (41.8% versus 12.0%). The rates of irresectable tumours were similar between cohorts (17.5% versus 11.0%). However, non-operative management due to comorbidities (13.4% versus 0.5%) or patient choice (8.2% versus 0.5%) was more common in patients aged >65 years. 281 patients (73.0%) proceeded to surgery. Patients aged >65 years had a higher rate of peri-operative morbidity (28.3% versus 9.5%), although no difference in peri-operative mortality or oncological outcomes was noted between age groups. The survival of patients managed non-operatively was significantly shorter than those undergoing surgery (median survival 15 versus 91 months, p < 0.001). CONCLUSION: Extended resections for primary retroperitoneal sarcoma in the elderly achieve comparable oncological outcomes but with increased rates of morbidity when compared with younger patients. The outcomes of patients unsuitable for surgery are poor regardless of age.

Patterns of disease relapse in primary extremity soft-tissue sarcoma.

BACKGROUND: Extremity soft-tissue sarcomas comprise a range of distinct histological subtypes. This study aimed to characterize the patterns of disease relapse in patients undergoing resection of primary extremity soft-tissue sarcoma. METHODS: All patients who had resection of primary extremity soft-tissue sarcoma at the Royal Marsden Hospital between January 2004 and January 2014 were identified from an institutional database. RESULTS: In the period examined, 556 patients underwent resection. The most common histological subtypes were undifferentiated pleomorphic sarcoma (169 patients, 30·4 per cent), well differentiated liposarcoma (63, 11·3 per cent), myxoid liposarcoma (62, 11·2 per cent), myxofibrosarcoma (54, 9·7 per cent) and leiomyosarcoma (39, 7·0 per cent). Local recurrence-free survival (LRFS) did not differ significantly between histological subtypes (P = 0·222). Distant metastasis-free survival (DMFS) and disease-specific survival (DSS) were found to differ significantly between subtypes (P < 0·001 for both DMFS and DSS), with the worst outcomes in patients with undifferentiated pleomorphic sarcoma (5-year survival rate: 56·8 (95 per cent c.i. 52·5 to 61·1) per cent for DMFS; 60·1 (55·6 to 64·6) per cent for DSS). However, on multivariable analysis, histological subtype was not found to be independently prognostic for LRFS, DMFS or DSS. Metastatic disease developed in 149 patients, with the lungs being the most common site of first metastasis (120 patients, 80·5 per cent). The site of first metastasis differed between subtypes, with extrapulmonary metastases predominant in myxoid liposarcoma (11 of 13 patients; P < 0·001). CONCLUSION: Although histological subtype was not found to be an independent prognostic factor for oncological outcomes, the site of first metastasis differed significantly between subtypes.

Elastofibroma dorsi: The clunking tumour that need not cause alarm.

INTRODUCTION: Elastofibromas are rare, pseudo-tumours arising at the inferior pole of the scapula that have a characteristic presentation. Due to their tissue of origin and size, they may often be mistaken for soft tissue sarcomas. We present the management of patients diagnosed with elastofibroma at a single institution. METHODS: Patients diagnosed with elastofibroma between January 1995 and January 2015 were identified from a prospectively maintained histopathology database. Electronic patient records, imaging and pathology reports were retrieved and reviewed. RESULTS: Thirty seven patients were identified, with a median age of 66 years and a male-to-female ratio of 1:1.6. All tumours occurred in the characteristic subscapular location. The median maximum tumour diameter was 8.2 cm. A synchronous contralateral lesion (15.8%) was found in six patients. Cross-sectional imaging was performed in 29 patients, with magnetic resonance imaging the most common modality (59.5%). Diagnosis was confirmed with percutaneous biopsy in all but one patient, who proceeded directly to surgery. Eighteen patients were managed non-operatively; 19 opted for surgical excision due to significant symptoms. Excision was performed in a marginal fashion and, at a median follow-up of 5 months, no functional impairment or local recurrences were observed. CONCLUSIONS: Soft tissue masses greater than 5 cm in diameter should prompt the clinician to exclude soft tissue sarcoma. The diagnosis of elastofibroma may be alluded to by its typical presentation and can be confirmed by percutaneous biopsy. After excluding malignancy, these lesions can be safely managed non-operatively, with surgery reserved for symptomatic patients.

Outcome following resection of retroperitoneal sarcoma.

BACKGROUND: Retroperitoneal sarcoma comprises a range of different histological subtypes with dissimilar behaviour and biology. This study sought to characterize the morbidity and mortality associated with multivisceral resection and oncological outcomes according to subtype. METHODS: All patients undergoing resection of primary retroperitoneal sarcoma at the Royal Marsden Hospital between January 2005 and December 2014 were identified from a database. RESULTS: Some 362 patients underwent resection, with 292 requiring multivisceral resection. The 30-day mortality rate was 1·4 per cent (5 patients), the 30-day morbidity rate was 15·7 per cent (57 patients), and 27 patients required a return to theatre. Age over 75 years was predictive of 30-day mortality (hazard ratio 1·37, 95 per cent c.i. 1·13 to 1·65). The overall disease-specific survival rate at 3 years was 81·2 per cent. For well differentiated liposarcoma, dedifferentiated liposarcoma and leiomyosarcoma, 3-year local recurrence-free survival rates were 98 (95 per cent c.i. 83 to 99), 56·7 (45·7 to 66·2) and 80 (67 to 89) per cent respectively. At 3 years the distant metastasis-free survival rate was 100, 85·9 (77·4 to 91·4) and 65 (49 to 77) per cent, and the disease-specific survival rate was 97 (89 to 99), 78·5 (74·6 to 82·4) and 79 (63 to 85) per cent for well differentiated liposarcoma, dedifferentiated liposarcoma and leiomyosarcoma respectively. CONCLUSION: Resection of retroperitoneal sarcoma was associated with a 30-day mortality rate of less than 2 per cent and a morbidity rate of 15·7 per cent. The overall 3-year disease-specific survival rate was 81·2 per cent.

Cancer surgery: risks and opportunities.

In the recent past, several papers have pointed to the possibility that tumour removal generates a permissive environment in which tumour growth is potentiated. This phenomenon has been coined "perioperative tumour growth" and whilst it represents a departure in terms of our attitude to the surgical process, this concept was first hinted at by Paget(1) himself. Despite this, the time interval immediately before and after cancer surgery (i.e. the perioperative period) remains an underutilised interval during which chemotherapeutic regimens are rarely implemented. Herein, we present a summarised review of the literature that supports the concept that tumour removal may potentiate the growth of residual neoplastic disease. We also outline current knowledge regarding underlying mechanisms and in this manner highlight potential therapeutic entry points. Finally, we emphasise the urgent need for trials of agents that could protect patients against the harmful host-tumour interactions that may occur during the perioperative period.

Excisional surgery for cancer cure: therapy at a cost.

Excisional surgery is one of the primary treatment modalities for cancer. Minimal residual disease (MRD) is the occult neoplastic disease that remains in situ after curative surgery. There is increasing evidence that tumour removal alters the growth of MRD, leading to perioperative tumour growth. Because neoplasia is a systemic disease, this phenomenon may be relevant to all patients undergoing surgery for cancer. In this review we discuss the published work that addresses the effects of tumour removal on subsequent tumour growth and the mechanisms by which tumour excision may alter residual tumour growth. In addition, we describe therapeutic approaches that may protect patients against any oncologically adverse effects of tumour removal. On the basis of the evidence presented, we propose a novel therapeutic paradigm; that the postoperative period represents a window of opportunity during which the patient may be further protected against the oncological effects of tumour removal.