Predictors of disease recurrence after curative surgery for nonfunctioning pancreatic neuroendocrine neoplasms (NF-PanNENs): a systematic review and meta-analysis.

PURPOSE: Patients submitted to curative surgery for non-functioning pancreatic neuroendocrine neoplasms (NF-PanNENs) exhibit a variable risk of disease relapse. Aims of this meta-analysis were to estimate the rate of disease recurrence and to investigate the risk factors for disease relapse in patients submitted to curative surgery for NF-PanNENs. METHODS: Medline/Pubmed and Web of Science databases were searched for relevant studies. A meta-regression analysis was performed to investigate the source of recurrence rate heterogeneity. Pooled hazard ratios (HRs) and 95% confidence intervals (95% CI) were used to assess the effect of each possible prognostic factor on disease-free survival. RESULTS: Fifteen studies, involving 2754 patients submitted to curative surgery for NF-PanNENs, were included. The pooled rate of disease recurrence was 21% (95% CI 15-26%). Study quality (Odds ratio, OR 0.94, P = 0.016) and G3-PanNENs rate (OR 2.18, P = 0.040) independently predicted the recurrence rate variability. Nodal metastases (HR 1.63, P < 0.001), tumor grade G2-G3 (G1 versus G2: HR 1.72, P < 0.001, G1 versus G3 HR 2.57, P < 0.001), microvascular (HR 1.25, P = 0.046) and perineural (HR 1.29, P = 0.019) invasion were identified as significant prognostic factors. T stage (T1-T2 versus T3-T4, P = 0.253) and status of resection margins (R0 versus R1, P = 0.173) did not show any significant relationship with NF-PanNENs recurrence. CONCLUSION: Disease relapse occurs in approximately one out of five patients submitted to curative surgery for NF-PanNENs. Nodal involvement, tumor grade, microvascular and perineural invasion are relevant prognostic factors, that should be taken into account for follow-up and for possible trials investigating adjuvant or neoadjuvant treatments.

Sporadic non-functioning pancreatic neuroendocrine tumours: multicentre analysis.

BACKGROUND: Outcomes after surgery for sporadic pancreatic neuroendocrine neoplasms (Pan-NENs) were evaluated. METHODS: This multicentre study included patients who underwent radical pancreatic resection for sporadic non-functioning Pan-NENs. In survival analysis, the risk of mortality in this cohort was analysed in relation to that of the matched healthy Italian population. Relative survival (RS) was calculated as the rate between observed and expected survival. Factors related to RS were investigated using multivariable modelling. RESULTS: Among 964 patients who had pancreatic resection for sporadic non-functioning Pan-NENs, the overall RS rate was 91.8 (95 per cent c.i. 81.5 to 96.5) per cent. 2019 WHO grade (hazard ratio (HR) 5.75 (s.e. 4.63); P = 0.030) and European Neuroendocrine Tumour Society (ENETS) TNM stage (6.73 (3.61); P < 0.001) were independent predictors of RS. The probability of a normal lifespan for patients with G1, G2, G3 Pan-NENS, and pancreatic neuroendocrine carcinomas (Pan-NECs) was 96.7, 54.8, 0, and 0 per cent respectively. The probability of a normal lifespan was 99.8, 99.3, 79.8, and 46.8 per cent for those with stage I, II, III, and IV disease respectively. The overall disease-free RS rate was 73.6 (65.2 to 79.5) per cent. 2019 WHO grade (HR 2.10 (0.19); P < 0.001) and ENETS TNM stage (HR 2.50 (0.24); P < 0.001) significantly influenced disease-free RS. The probability of disease-free survival was 93.2, 84.9, 45.2, and 6.8 per cent for patients with stage I, II, III, and IV disease, and 91.9, 45.2, 9.4, and 0.7 per cent for those with G1, G2, G3 Pan-NENS, and Pan-NECs, respectively. CONCLUSION: A surgical approach seems without benefit for Pan-NECs, and unnecessary for small G1 sporadic Pan-NENs. Surgery alone may be insufficient for stage III-IV and G3 Pan-NENs.

Robotic versus laparoscopic distal pancreatectomy: multicentre analysis.

BACKGROUND: The role of minimally invasive distal pancreatectomy is still unclear, and whether robotic distal pancreatectomy (RDP) offers benefits over laparoscopic distal pancreatectomy (LDP) is unknown because large multicentre studies are lacking. This study compared perioperative outcomes between RDP and LDP. METHODS: A multicentre international propensity score-matched study included patients who underwent RDP or LDP for any indication in 21 European centres from six countries that performed at least 15 distal pancreatectomies annually (January 2011 to June 2019). Propensity score matching was based on preoperative characteristics in a 1 : 1 ratio. The primary outcome was the major morbidity rate (Clavien-Dindo grade IIIa or above). RESULTS: A total of 1551 patients (407 RDP and 1144 LDP) were included in the study. Some 402 patients who had RDP were matched with 402 who underwent LDP. After matching, there was no difference between RDP and LDP groups in rates of major morbidity (14.2 versus 16.5 per cent respectively; P = 0.378), postoperative pancreatic fistula grade B/C (24.6 versus 26.5 per cent; P = 0.543) or 90-day mortality (0.5 versus 1.3 per cent; P = 0.268). RDP was associated with a longer duration of surgery than LDP (median 285 (i.q.r. 225-350) versus 240 (195-300) min respectively; P < 0.001), lower conversion rate (6.7 versus 15.2 per cent; P < 0.001), higher spleen preservation rate (81.4 versus 62.9 per cent; P = 0.001), longer hospital stay (median 8.5 (i.q.r. 7-12) versus 7 (6-10) days; P < 0.001) and lower readmission rate (11.0 versus 18.2 per cent; P = 0.004). CONCLUSION: The major morbidity rate was comparable between RDP and LDP. RDP was associated with improved rates of conversion, spleen preservation and readmission, to the detriment of longer duration of surgery and hospital stay.

Laparoscopic versus open extended radical left pancreatectomy for pancreatic ductal adenocarcinoma: an international propensity-score matched study.

BACKGROUND: A radical left pancreatectomy in patients with pancreatic ductal adenocarcinoma (PDAC) may require extended, multivisceral resections. The role of a laparoscopic approach in extended radical left pancreatectomy (ERLP) is unclear since comparative studies are lacking. The aim of this study was to compare outcomes after laparoscopic vs open ERLP in patients with PDAC. METHODS: An international multicenter propensity-score matched study including patients who underwent either laparoscopic or open ERLP (L-ERLP; O-ERLP) for PDAC was performed (2007-2015). The ISGPS definition for extended resection was used. Primary outcomes were overall survival, margin negative rate (R0), and lymph node retrieval. RESULTS: Between 2007 and 2015, 320 patients underwent ERLP in 34 centers from 12 countries (65 L-ERLP vs. 255 O-ERLP). After propensity-score matching, 44 L-ERLP could be matched to 44 O-ERLP. In the matched cohort, the conversion rate in L-ERLP group was 35%. The L-ERLP R0 resection rate (matched cohort) was comparable to O-ERLP (67% vs 48%; P = 0.063) but the lymph node yield was lower for L-ERLP than O-ERLP (median 11 vs 19, P = 0.023). L-ERLP was associated with less delayed gastric emptying (0% vs 16%, P = 0.006) and shorter hospital stay (median 9 vs 13 days, P = 0.005), as compared to O-ERLP. Outcomes were comparable for additional organ resections, vascular resections (besides splenic vessels), Clavien-Dindo grade ≥ III complications, or 90-day mortality (2% vs 2%, P = 0.973). The median overall survival was comparable between both groups (19 vs 20 months, P = 0.571). Conversion did not worsen outcomes in L-ERLP. CONCLUSION: The laparoscopic approach may be used safely in selected patients requiring ERLP for PDAC, since morbidity, mortality, and overall survival seem comparable, as compared to O-ERLP. L-ERLP is associated with a high conversion rate and reduced lymph node yield but also with less delayed gastric emptying and a shorter hospital stay, as compared to O-ERLP.

Searching for novel multimodal treatments in oligometastatic pancreatic cancer.

BACKGROUND: Metastatic pancreatic cancer has a median overall survival of less than 12 months, even if treated with chemotherapy. Selected patients with oligometastatic disease could benefit from multimodal treatments connecting chemotherapy and surgical treatment or radiofrequency ablation (RFA) of metastases. CASE PRESENTATION: We present a patient with oligometastatic pancreatic cancer recurrence who was successfully treated with a multimodal therapeutic approach. A 57-year-old male initially presenting with resectable pancreatic cancer underwent pancreatoduodenectomy. The histopathological diagnosis revealed ductal pancreatic adenocarcinoma with positive surgical resection margins and negative lymph nodes. He completed six cycles of adjuvant therapy with gemcitabine (1000 mg/mq 1,8,15q 28), followed by external radiotherapy (54 Gy in 25 fractions) associated with gemcitabine 50 mg/mq twice weekly. Three years later, the patient developed multiple liver metastases, and he started FOLFIRINOX (oxaliplatin 85 mg/mq, irinotecan 180 mg/mq, leucovorin 400 mg/mq and fluorouracil 400 mg/mq given as a bolus followed by 2400 mg/mq as a 46 h continuous infusion,1q 14) as a first-line treatment. The CT scan showed a partial response after 6 cycles. After multidisciplinary discussion, the patient underwent a laparotomic metastasectomy of the three hepatic lesions. After additional postsurgical chemotherapy with 4 cycles of the FOLFIRINOX schedule, the patient remained free of recurrence for 12 months. A CT scan showed a new single liver metastasis, which was treated with radiofrequency ablation (RFA). A second radiofrequency ablation was performed when the patient developed another single liver lesion 12 months after the first RFA; currently, the patient is free from recurrence with an overall survival of 6 years from the diagnosis. CONCLUSIONS: Our case has benefited from successful multimodal treatment, including surgical and local ablative techniques and systemic chemotherapy. A multimodal approach may be warranted in selected patients with oligometastatic pancreatic cancer and could improve overall survival. Further research is needed to investigate this approach.

Best practices for the management of local-regional recurrent chordoma: a position paper by the Chordoma Global Consensus Group.

Chordomas are rare, malignant bone tumors of the skull-base and axial skeleton. Until recently, there was no consensus among experts regarding appropriate clinical management of chordoma, resulting in inconsistent care and suboptimal outcomes for many patients. To address this shortcoming, the European Society of Medical Oncology (ESMO) and the Chordoma Foundation, the global chordoma patient advocacy group, convened a multi-disciplinary group of chordoma specialists to define by consensus evidence-based best practices for the optimal approach to chordoma. In January 2015, the first recommendations of this group were published, covering the management of primary and metastatic chordomas. Additional evidence and further discussion were needed to develop recommendations about the management of local-regional failures. Thus, ESMO and CF convened a second consensus group meeting in November 2015 to address the treatment of locally relapsed chordoma. This meeting involved over 60 specialists from Europe, the United States and Japan with expertise in treatment of patients with chordoma. The consensus achieved during that meeting is the subject of the present publication and complements the recommendations of the first position paper.

Elastofibroma of the gluteal region with a concomitant contralateral lesion: case report and review of the literature.

A 51-year-old man presented with elastofibroma (EF) of the gluteal region with a concomitant contralateral lesion. The patient presented with a slow growing mass of the proximal third of the right buttock and had swelling, discomfort in sitting, and right-hip pain during walking for 2 months. On MRI, a soft-tissue mass was noted between the gluteus maximus and the gluteus medius muscle. The mass showed similar signal intensity to the surrounding tissue on T1- and T2-weighted images and with linear hyperintense areas in its internal structure. At surgery, a soft, non-encapsulated, irregular, and rubber-like mass was found attached to the gluteus medius muscles. It was pathologically confirmed to be an EF. This unusual manifestation of an EF is discussed.

Serous cystic neoplasm of the pancreas: a multinational study of 2622 patients under the auspices of the International Association of Pancreatology and European Pancreatic Club (European Study Group on Cystic Tumors of the Pancreas).

OBJECTIVES: Serous cystic neoplasm (SCN) is a cystic neoplasm of the pancreas whose natural history is poorly known. The purpose of the study was to attempt to describe the natural history of SCN, including the specific mortality. DESIGN: Retrospective multinational study including SCN diagnosed between 1990 and 2014. RESULTS: 2622 patients were included. Seventy-four per cent were women, and median age at diagnosis was 58 years (16-99). Patients presented with non-specific abdominal pain (27%), pancreaticobiliary symptoms (9%), diabetes mellitus (5%), other symptoms (4%) and/or were asymptomatic (61%). Fifty-two per cent of patients were operated on during the first year after diagnosis (median size: 40 mm (2-200)), 9% had resection beyond 1 year of follow-up (3 years (1-20), size at diagnosis: 25 mm (4-140)) and 39% had no surgery (3.6 years (1-23), 25.5 mm (1-200)). Surgical indications were (not exclusive) uncertain diagnosis (60%), symptoms (23%), size increase (12%), large size (6%) and adjacent organ compression (5%). In patients followed beyond 1 year (n=1271), size increased in 37% (growth rate: 4 mm/year), was stable in 57% and decreased in 6%. Three serous cystadenocarcinomas were recorded. Postoperative mortality was 0.6% (n=10), and SCN's related mortality was 0.1% (n=1). CONCLUSIONS: After a 3-year follow-up, clinical relevant symptoms occurred in a very small proportion of patients and size slowly increased in less than half. Surgical treatment should be proposed only for diagnosis remaining uncertain after complete workup, significant and related symptoms or exceptionally when exists concern with malignancy. This study supports an initial conservative management in the majority of patients with SCN. TRIAL REGISTRATION NUMBER: IRB 00006477.

Embolisation of bone metastases from renal cancer.

PURPOSE: This study was done to evaluate embolisation for palliative and/or adjuvant treatment of bone metastases from renal cell carcinoma and discuss the clinical and imaging results. MATERIALS AND METHODS: We retrospectively studied 107 patients with bone metastases from renal cell carcinoma treated from December 2002 to January 2011 with 163 embolisations using N-2-butyl cyanoacrylate (NBCA). Mean tumour diameter before embolisation was 8.8 cm and mean follow-up 4 years. Clinical and imaging effects of treatment were evaluated at follow-up examinations with a pain score scale, analgesic use, hypoattenuating areas, tumour size and ossification. RESULTS: A clinical response was achieved in 157 (96%) and no response in six embolisations of sacroiliac metastases. Mean duration of clinical response was 10 (range 1-12) months. Hypoattenuating areas resembling tumour necrosis were observed in all patients. Variable ossification appeared in 41 patients. Mean maximal tumour diameter after embolisation was 4.0 cm. One patient had intraprocedural tear of the left L3 artery and iliopsoas haemorrhage and was treated with occlusion of the bleeding vessel with NBCA. All patients had variable ischaemic pain that recovered completely within 2-4 days. Postembolisation syndrome was diagnosed after 15 embolisations (9.2%). Transient paraesthesias in the lower extremities were observed after 25 embolisations (25%) of pelvis and sacrum metastatic lesions. CONCLUSIONS: Embolisation with NBCA is recommended as primary or palliative treatment of bone metastases from renal cell carcinoma. Strict adherence to the principles of transcatheter embolisation is important to avoid complications.

Tumours of the atlas and axis: a 37-year experience with diagnosis and management.

PURPOSE: This paper presents a single institution's longterm experience regarding the incidence and management of tumours of the atlas and axis and discusses clinical and imaging findings and treatment options. MATERIALS AND METHODS: We searched the registry of the Istituto Ortopedico Rizzoli for patients admitted and treated for tumours of the upper cervical spine. We identified 62 patients over 37 years, from July 1973 to October 2010. There were 39 male and 23 female patients, with a mean age of 39.5 (range 5-77) years. For each patient, we collected data on clinical presentation, imaging and treatment. Mean follow-up was 10 years. RESULTS: Benign bone tumours were diagnosed in 24 (39%) and malignant tumours in 38 (61%) patients. The most common tumours were bone metastases, followed by osteoid osteomas and chordomas. The atlas was involved in six and the axis in 52 patients; in four patients, both the atlas and axis were involved. The most common clinical presentation was pain, torticollis, dysphagia and neurological deficits. Surgical treatment was performed in 35 patients and conservative treatment, including intralesional methylprednisolone injections and halo-vest immobilisation with or without radiation therapy, chemotherapy or embolisation, in the remaining patients. One patient with osteoblastoma of the atlas had local recurrence. All patients with metastatic bone disease had local recurrence; four of the eight patients with plasmacytoma progressed to multiple myeloma within 1-4 years. All patients with chordomas had two to four local recurrences. Patients with osteosarcomas and chondrosarcoma died owing to local and distant disease progression. CONCLUSIONS: Bone tumours of the cervical spine are rare. However, they should be kept in mind when examining patients with neck pain or neurological symptoms at the extremities. In most cases, only intralesional surgery can be administered. Combined radiation therapy and chemotherapy is indicated for certain tumour histologies.

Pancreatic and extrapancreatic lesions in patients with intraductal papillary mucinous neoplasms of the pancreas: a single-centre experience.

PURPOSE: This study was performed to describe the possible presence of extrapancreatic neoplasms in patients with intraductal papillary mucinous neoplasm (IPMN) and to evaluate whether the extrapancreatic tumours were synchronous or metachronous to IPMNs. MATERIALS AND METHODS: One hundred and forty-two patients (56 men and 86 women; mean age 69.5 years, range 37-98) with IPMN diagnosed using the Sendai criteria were enrolled. Six patients (4.2%) had type I, 103 (72.5%) type II and 33 (23.2%) type III IPMN. All patients were studied using the following imaging techniques: ultrasonography (US), multidetector computed tomography (MDCT) and magnetic resonance cholangiopancreatography (MRCP). RESULTS: Pancreatic IPMN was localised in the head in 43 patients (30.3%), in the body in 13 (9.2%), in the tail in ten (7.0%), in the head-body in 17 (12.0%), in the body-tail in 15 (10.6%) diffuse throughout the gland in 44 (31.0%). The mean size of the cystic lesions was [(mean+/-standard deviation (SD)] 1.9+/-1.9 cm (range 0.5-8.0 cm). Twenty patients (14.1%) had associated pancreatic or extrapancreatic diseases. In evaluating the distribution of pancreatic or extrapancreatic diseases according to IPMN type, we found that this was not significantly different among types I, II and III (p=0.776). CONCLUSIONS: The majority of pancreatic and extrapancreatic cancers occur before the diagnosis of IPMNs is made and is not related to the type of IPMN.

The sacral chordoma margin.

OBJECTIVE: Aim of the manuscript is to discuss how to improve margins in sacral chordoma. BACKGROUND: Chordoma is a rare neoplasm, arising in half cases from the sacrum, with reported local failure in >50% after surgery. METHODS: A multidisciplinary meeting of the "Chordoma Global Consensus Group" was held in Milan in 2017, focusing on challenges in defining and achieving optimal margins in chordoma with respect to surgery, definitive particle radiation therapy (RT) and medical therapies. This review aims to report on the outcome of the consensus meeting and to provide a summary of the most recent evidence in this field. Possible new ways forward, including on-going international clinical studies, are discussed. RESULTS: En-bloc tumor-sacrum resection is the cornerstone of treatment of primary sacral chordoma, aiming to achieve negative microscopic margins. Radical definitive particle therapy seems to offer a similar outcome compared to surgery, although confirmation in comparative trials is lacking; besides there is still a certain degree of technical variability across institutions, corresponding to different fields of treatment and different tumor coverage. To address some of these questions, a prospective, randomized international study comparing surgery versus definitive high-dose RT is ongoing. Available data do not support the routine use of any medical therapy as (neo)adjuvant/cytoreductive treatment. CONCLUSION: Given the significant influence of margins status on local control in patients with primary localized sacral chordoma, the clear definition of adequate margins and a standard local approach across institutions for both surgery and particle RT is vital for improving the management of these patients.

Evaluation of patient-reported outcome in subjects treated medically for acute pancreatitis: a follow-up study.

AIMS: To explore the quality of life in patients treated medically during the acute phase of pancreatitis as well as at 2 and 12 months after discharge from the hospital. PATIENTS: 40 patients were studied. The etiology of the pancreatitis was biliary causes in 31 patients and non-biliary causes in 9; mild disease was present in 29 patients and severe disease in 11. 30 patients completed the two surveys at 2 and 12 months after hospital discharge. METHODS: The SF-12 and EORTC QLQ-C30 questionnaires were used for the purpose of the study. RESULTS: The two physical and mental component summaries of SF-12, all the domains of EORTC QLQ-C30 (except for physical functioning and cognitive functioning) and some symptom scales of EORTC QLQ-C30 (fatigue, nausea/vomiting, pain, and constipation) were significantly impaired during the acute phase of pancreatitis. There was a significant improvement in the SF-12 physical component summary, and global health, role functioning, social functioning, nausea/vomiting, pain, dyspnea, and financial difficulties (EORTC QLQ-C30) at 2 months after discharge as compared to the basal evaluation. Similar results were found after 12 months except for the mental component score at 12-month evaluation, which was significantly impaired in acute pancreatitis patients in comparison to the norms. The physical functioning of the EORTC QLQ-C30 at basal evaluation was significantly impaired in patients with severe pancreatitis in comparison to patients with mild pancreatitis. CONCLUSIONS: Two different patterns can be recognized in the quality of life of patients with acute pancreatitis: physical impairment is immediately present followed by mental impairment which appears progressively in the follow-up period.

Humeral metastasis of renal cancer: Surgical options and review of literature.

INTRODUCTION: The humerus is the second most common long bone site of metastatic disease from renal cell carcinomas (RCC) after femur. Surgery has an important role in the treatment of these lesions due to renal cell tumor's resistance to chemotherapy and radiotherapy. HYPOTHESIS: Prosthetic replacement is an effective and safe solution in treatment of renal humeral metastasis. MATERIAL AND METHODS: Fifty-six patients affected by RCC bone metastases of the humerus that underwent a surgical reconstruction were rewised. Thirty-five lesions were localized on proximal third, 12 on the shaft, 9 on distal third. Among proximal 29 were treated with resection and endoprosthetic replacement and 6 with plate and cement. Six diaphyseal lesions were stabilized with intramedullary nailing, 5 with plate and cement and 1 with an intercalary prosthesis. Regarding distal lesions, 7 elbow prostheses and 2 plates and cement were used. RESULTS: The average age was 63years. Metastasis was single in 55% of cases, and in 45% metachronous. A pathologic fracture (PF) occurred in 64% of cases. Only 9% of patients had a mechanical complication, 7% an infection and 5% neurological deficit. A local recurrence occurred in 14% of patients. An implant failure has been observed in 10 patients, 5 for mechanical complications, 2 for infections and 3 for local recurrence; of these 7 were treated with a prosthesis and 3 with plate and cement. The mean value of MSTS score was 64%, 63% and 59% respectively in patients with proximal, diaphyseal and distal humerus metastases. DISCUSSION: Solitary and metachronous bone metastases have a longer survival. Disease-free interval>2years is another important prognostic factor. Reconstruction with a modular prosthesis is recommended in proximal and distal third. Instead in diaphyseal lesions a closed reduction and fixation with intramedullary locked nailing are preferred. When surgical indications are correctly followed, good oncologic and functional outcomes are obtained, leading to markedly improvement of patients' quality of life. RETROSPECTIVE STUDY: Level of evidence: IV.

Extra-axial chordoma: a clinicopathologic analysis of six cases.

Extra-axial chordoma is an exceedingly rare tumor, with only 28 cases reported in the literature to date. Axial and extra-axial chordoma exhibits complete morphologic and immunophenotypic (expression of brachyury) overlap. However, in consideration of the non-canonical presentation, extra-axial chordoma is under-recognized and often misdiagnosed, most often as extraskeletal myxoid chondrosarcoma or myoepithelioma. To increase our understanding of the clinicopathologic features of extra-axial chordoma, six cases have been retrieved from the files of the Istituto Ortopedico Rizzoli and of the General Hospital of Treviso. The clinicoradiologic, morphologic, and molecular features have been analyzed, and the follow-up was updated. Our series included four female and two male patients; their ages ranged from 20 to 67 years (mean 45.8 years). All patients presented with a single mass localized in four cases in the soft tissue (posterior arm, left leg, dorsal aspect of the foot, and popliteal fossa), and in two cases in the bone (radius and second metacarpal bone). Grossly, the neoplasm was lobulated, with a fleshy cut surface and a diameter ranging between 0.8 and 8 cm (mean 3.4 cm). Morphologically, all six cases showed an epithelioid cell proliferation organized in nests and cords demarcated by fibrous septa and set in an abundant extracellular myxoid matrix. Neoplastic cells featured hyperchromatic nuclei and abundant vacuolated cytoplasm. Immunohistochemically, all six cases were strongly positive for EMA, cytokeratin AE1/AE3, S100, and brachyury. INI1 nuclear expression was retained. Smooth muscle actin, calponin, p63, and GFAP were all negative. Fluorescent in situ hybridization (FISH) analysis did not reveal rearrangements involving NR4A3, FUS, and EWSR1 genes. At follow-up (mean 55 months), all patients were alive without disease after local surgical treatment. One patient underwent thigh amputation following multiple local recurrences and inguinal node metastases treated with marginal resection. In conclusion, primary extra-axial chordoma is an extremely rare neoplasm with distinct morphological and immunohistochemical features. Immunomorphology and molecular analysis allow distinction from both extraskeletal myxoid chondrosarcoma and myoepithelioma. Complete surgical resection appears to be curative.

Total elbow arthroplasty for primary and metastatic tumor.

BACKGROUND: Prostheses can be used in elbow reconstruction in both primary and metastatic lesions. Several authors have reported their experience with different types of implant, but not with modular prostheses. HYPOTHESIS: Limb salvage using an elbow prosthesis is effective in obtaining good functional results and reliable local tumor control. MATERIAL AND METHODS: Forty-seven patients treated at the Rizzoli Institute for elbow neoplasm from 1990 to 2012 were evaluated. There were 30 primary tumors (64%), 24 bone tumors and 6 soft tissue sarcomas, and 17 bone metastases. Elbow reconstruction used a modular prosthesis in 25 patients and a standard prosthesis in 22. Reconstruction was primary in 30 patients and secondary in 17. RESULTS: At last control, 15 (32%) were dead of disease (DOD) at a mean follow-up of 35 months, 12 (25%) were alive with disease (AWD) at a mean follow-up of 29 months, 19 (40%) showed no evidence of disease (NED) at a mean follow-up of 80 months. Early complications were related to unexpected neurological damage, observed in 12 patients (25%): in 5 cases the deficit resolved in a mean 6 months; in the others, no or only partial recovery was observed. Two implants (4%) developed infection: 1 was treated with antibiotic therapy, and the other required implant revision. One implant showing cement extrusion was revised. In 3 patients (6%) radiography showed a radiolucent halo around the stem (2 humeral, 1 ulnar); no measures were taken, as the patients were completely asymptomatic at every follow-up. In 3 patients (6%) partial resorption of the allograft was observed on X-ray, but remained unchanged at last follow-up, without pain or functional impairment. Seven local recurrences (15%) were observed, at a mean of 16 months after surgery; 5 were treated by resection and/or radiotherapy, and 2 by amputation. Mean functional scores on MEPS and MSTS were respectively 84% and 22/30 (73%). CONCLUSIONS: Elbow prostheses provided better function in primary than in metastatic tumor. Elbow prosthesis reconstruction after tumor resection is a viable option both for primary and secondary bone neoplasms. TYPE OF STUDY: Therapeutic. LEVEL OF EVIDENCE: IV, retrospective study.

Relationship of chemotherapy-induced necrosis and surgical margins to local recurrence in osteosarcoma.

PURPOSE AND METHODS: To assess patients with high-grade osteosarcoma treated at our institution for various prognostic factors for the development of local recurrence of disease. Follow-up data were available for all patients and the mean follow-up duration was 65 months in surviving patients. RESULTS: There were 28 local recurrences in this study (7%). Of these, only three patients (11%) were alive at the most recent follow-up point, 28, 53, and 54 months after local recurrence. None of 59 patients who were treated primarily with a radical amputation and none of 10 who underwent a rotationplasty developed local recurrence. Four of 48 patients (8%) who had wide amputations, one of whom had an intralesional amputation, and 23 of 237 (10%) who had limb-salvage surgery developed locally recurrent disease. Of 237 patients who underwent limb-sparing resection, three prognostic factors for local control were identified. The strongest association with local recurrence was chemotherapy response (P < .0001), followed closely by surgical margins (P = .0001). Older patients were more likely to have locally recurrent disease (P = .033), with each decade of life older than the first decade having a relative risk of 1.5 times greater per decade (SE = 0.16; 95% confidence interval, 0.034 to .0650). Factors that were not associated with local recurrence included sex, date of diagnosis, and anatomic site of disease. CONCLUSION: Chemotherapy-induced tumor necrosis and surgical margins are important prognostic factors for local control of patients with osteosarcoma.

Long-term outcome for patients with nonmetastatic osteosarcoma of the extremity treated at the istituto ortopedico rizzoli according to the istituto ortopedico rizzoli/osteosarcoma-2 protocol: an updated report.

PURPOSE: To provide an estimate of long-term prognosis for patients with osteosarcoma of the extremity treated in a single institution with neoadjuvant chemotherapy and observed for at least 10 years. PATIENTS AND METHODS: Patients with nonmetastatic osteosarcoma of the extremity were preoperatively treated with high-dose methotrexate, cisplatin, and doxorubicin (ADM). Postoperatively, good responders (90% or more tumor necrosis) received the same three drugs used before surgery, whereas poor responders (less than 90% tumor necrosis) received ifosfamide and etoposide in addition to those three drugs. RESULTS: For the 164 patients who entered the study between September 1986 and December 1989, surgery was a limb salvage in 136 cases (82%) and a good histologic response was observed in 117 patients (71%). At a follow-up ranging from 10 to 13 years (median, 11.5 years), 101 patients (61%) remained continuously free of disease, 61 relapsed, and two died of ADM-induced cardiotoxicity. There were no differences in prognosis between good and poor responding patients. ADM-induced cardiotoxicity (six patients), male infertility (10 of the 12 assessable patients), and second malignancies (seven patients) were the major complications of chemotherapy. Despite the large number of limb salvages performed, only four local recurrences (2.4%) were registered. CONCLUSION: With an aggressive neoadjuvant chemotherapy, it is possible to cure more than 60% of patients with nonmetastatic osteosarcoma of the extremity and amputation may be avoided in more than 80% of them. Because local or systemic relapses, myocardiopathies, and second malignancies are possible even 5 years or more after the beginning of treatment, a long-term follow-up is recommended for these patients.

Chemotherapy-induced tumor necrosis as a prognostic factor in localized Ewing's sarcoma of the extremities.

PURPOSE: This study was performed to assess the prognostic value of the proposed histopathologic method to evaluate the response of the primary tumor to preoperative chemotherapy in Ewing's sarcoma. PATIENTS AND METHODS: The response to chemotherapy was evaluated from the specimens of 118 Ewing's sarcoma patients, who were preoperatively treated by chemotherapy alone. Responses were graded I to III (macroscopic viable tumor, microscopic viable tumor, and no viable tumor cells, respectively). Follow-up data were available for all patients, with a mean follow-up duration of 86 months (range, 30 to 158). RESULTS: A statistically highly significant difference was observed in outcome among the three groups of patients. For patients with total necrosis (grade III response), the estimated 5-year disease-free survival rate was 95%, in contrast to 68% for grade II responders and 34% for grade III responders (P < .0001). This difference was also confirmed when any single group was compared with the other groups. Among the parameters tested, patient age and the size of tumor had some prognostic value. CONCLUSION: The proposed histopathologic grading, to evaluate the effect of chemotherapy on the primary tumor, had the strongest correlation to clinical outcome. This method could therefore be used to identify patients with a high risk of recurrent disease. These patients could be randomized to receive alternative postoperative treatments to investigate whether more aggressive therapies will improve outcome.

Sclerosing epithelioid fibrosarcoma of the thigh: report of two cases with synchronous bone metastases.

We report two cases of sclerosing epithelioid fibrosarcoma occurring in the deep soft tissue of the thigh, confirmed by molecular analysis and associated with bone metastases in the lumbar vertebrae and the iliac wing at the time of diagnosis. Synchronous bone metastases of sclerosing epithelioid fibrosarcoma are extremely difficult to diagnose because clinical and radiological features are not specific. In addition, the range of differential diagnoses is very wide, including metastatic carcinoma and osteosarcoma. At present, all but three published cases of sclerosing epithelioid fibrosarcoma with bone metastases showed bone metastases during follow-up. We confirm in our two cases that the distinct pattern of immunohistochemical staining for MUC4, associated with the absence of staining for both SATB2, a marker of osteoblastic differentiation, and pan-cytokeratin, allows differentiating between sclerosing epithelioid fibrosarcoma and metastatic carcinoma or osteosarcoma.