Improving Surgical Outcomes in Pelvic Exenteration Surgery: Comparison of Prone Sacrectomy With Anterior Cortical Sacrectomy Techniques.

OBJECTIVE: To assess the effect of changing our sacrectomy approach from prone to anterior on surgical and oncological outcomes. BACKGROUND: In patients with advanced pelvic malignancy involving the sacrum, pelvic exenteration (PE) with en-bloc sacrectomy is the only potential curative option but morbidity is high. Over time sacrectomy techniques have evolved from prone sacrectomy (PS) to abdominolithotomy sacrectomy (ALS, ≤S3) and high anterior cortical sacrectomy (HACS, >S3) to optimize surgical outcomes. METHODS: A retrospective, single institution analysis of prospectively collected data for patients undergoing PE with en-bloc sacrectomy between 1994 and 2021 was performed. RESULTS: A total of 363 patients were identified and divided into PS (n=77, 21.2%), ALS (n=247, 68.0%), and HACS (n=39, 10.7%). Indications were: locally advanced (n=92) or recurrent (n=177) rectal cancer, primary other (n=31), recurrent other (n=60), and benign disease (n=3). PS resulted in longer operating time ( P <0.01) and more blood loss ( P <0.01). Patients with HACS had more major nerve (87.2%) and vascular (25.6%) resections ( P <0.01). Vertical rectus abdominis myocutaneous flap repair was less common following HACS (7.7%) than ALS (25.5%) and PS (27.3%) ( P =0.040). R0 rate was 80.8%, 65.8%, and 76.9% following ALS, PS, and HACS, respectively ( P =0.024). Wound-related complications and re-operations were significantly reduced following ALS and HACS compared with PS. CONCLUSIONS: Changing our practice from PS to an anterior approach with ALS or HAS has been safe and improved overall surgical and perioperative outcomes, while maintaining good oncological outcomes. Given the improved perioperative and surgical outcomes, it would be important for surgeons to learn and adopt the anterior sacrectomy approaches.

The effectiveness of robotic hip and knee arthroplasty on patient-reported outcomes: A systematic review and meta-analysis.

PURPOSE: The purpose of the study is to determine the effectiveness of semi-active and active robotic hip and knee arthroplasty on post-operative patient-reported outcomes of function, pain, quality of life and satisfaction with surgery. METHODS: PubMed, Medline, Embase and CENTRAL were searched. Included were comparative studies investigating the effectiveness of semi-active or active robotic hip or knee arthroplasty compared to any other surgical intervention on function, pain, quality of life and satisfaction with surgery. Risk of bias and the strength of the evidence were assessed using the Downs and Black tool and the GRADE system, respectively. Relative risks, mean differences and 95% CI were calculated using random-effects models. RESULTS: Fourteen studies involving 1342 patients were included. All studies compared robotic to conventional surgery, with active robotic surgery evaluated in total hip or knee arthroplasty and semi-active robotic surgery in total hip or unicompartmental knee arthroplasty. Most studies presented some risk of bias, and the strength of evidence was rated as low to very low quality. Random-effects meta-analyses showed that post-operative functional outcomes were comparable between active robotic and conventional total hip and knee arthroplasty at the short-, medium- and long-term follow-up. No significant difference in pain, quality of life and satisfaction with surgery were reported in individual studies. CONCLUSIONS: This systematic and meta-analyses indicates that functional outcomes for patients undergoing active robotic total hip and knee arthroplasty were comparable to conventional surgery. Whether semi-active or active robotic hip or knee arthroplasty is effective in improving post-operative pain, quality of life and satisfaction with surgery is unclear. PROSPERO Registration Number: CRD42017059932.

Atypical Ewing sarcoma breakpoint region 1 fluorescence in-situ hybridization signal patterns in bone and soft tissue tumours: diagnostic experience with 135 cases.

AIMS: Recurrent Ewing sarcoma breakpoint region 1 (EWSR1) gene rearrangements characterize a select group of bone and soft tissue tumours. In our routine diagnostic practice with fluorescence in-situ hybridization (FISH), we have occasionally observed EWSR1 gene rearrangements in tumours not associated classically with EWSR1 translocations. This study aimed to review our institutional experience of this phenomenon and also to highlight the occurrence of unusual EWSR1 FISH signals (i.e. 5' centromeric region or 3' telomeric region signals) that do not fulfil the published diagnostic criteria for rearrangements. METHODS AND RESULTS: Using an EWSR1 break-apart probe, we performed FISH assays on formalin-fixed paraffin-embedded tissue sections from 135 bone and soft tissue specimens as part of their routine diagnostic work-up. EWSR1 gene rearrangements were identified in 51% of cases, 56% of which also showed an abnormal FISH signal pattern (in addition to classically rearranged signals). However, atypical FISH signals were present in 45% of the non-rearranged cases. In addition, we observed tumours unrelated to those described classically as EWSR1-associated that were technically EWSR1-rearranged in 6% of cases. Borderline levels of rearrangement (affecting 10-30% of lesional cells) were present in an additional 17% of these cases. CONCLUSIONS: While our study confirmed that FISH is a sensitive and specific tool in the diagnosis of EWSR1-associated tumours, atypical FISH signals and classical rearrangement in entities other than EWSR1-associated tumours can occur. Therefore, it is essential that the FISH result not be used as an isolated test, but must be evaluated in the context of clinical features, imaging, pathological and immunohistochemical findings.

The Contemporary Role of Major Amputation in the Management of Advanced Limb Melanoma.

BACKGROUND: Major amputations are rarely performed for melanoma, with limb-preserving techniques used whenever possible. This article reviews the indications for major amputation in patients with melanoma and reports outcomes with the aim of better classifying progressive and potentially curable disease patterns. METHODS: At a single institution in Australia, 55 major amputations were performed for melanoma in 51 patients treated between 1984 and 2012. Clinicopathologic characteristics, treatments before amputation, and outcomes were analyzed. RESULTS: The 55 cases included 17 upper limb (9 forequarter) and 38 lower limb (3 hindquarter) amputations. The most common reasons for amputation were progressive in-transit metastases (ITM, 67 %), troublesome limb metastases from distant sites (14 %), pain or ulceration after regional chemotherapy (14 %) and otherwise inoperable regional recurrence (6 %). Regional chemotherapy was used before amputation for 58 % of the patients, and for those with ITM, it was associated with an increased interval between ITM diagnosis and amputation. The overall 5-year survival rate (5YS) from the time of amputation was 22.8 %. For stage 3 patients with either ITM or regional recurrence, who had all known disease resected at the time of amputation, the 5YS was 38.4 %. CONCLUSION: Major amputation may be indicated for advanced limb melanoma when limb-preserving strategies have been exhausted. Although they have advanced locoregional disease, some patients undergoing potentially curative amputation can achieve long-term survival.

Surgical downstaging in an open-label phase II trial of denosumab in patients with giant cell tumor of bone.

BACKGROUND: Surgical resection with curative intent for giant cell tumor of bone (GCTB) may be associated with severe morbidity. This interim analysis evaluated reduction in surgical invasiveness after denosumab treatment in patients with resectable GCTB. METHODS: Patients with primary or recurrent GCTB, for whom the initially planned surgery was associated with functional compromise or morbidity, received denosumab 120 mg subcutaneously every 4 weeks (additional doses on days 8 and 15 of the first cycle). Planned and actual GCTB-related surgical procedures before and after denosumab treatment were reported. Patients were followed for surgical outcome, adverse events, and recurrence following resection. RESULTS: Overall, 222 patients were evaluable for surgical downstaging (54 % were women; median age 34 years). Lesions (67 % primary and 33 % recurrent) were located in the axial (15 %) and appendicular skeleton (85 %). At the data cutoff date, most patients had not yet undergone surgery (n = 106; 48 %) or had a less morbid procedure (n = 84; 38 %) than originally planned. Median (interquartile range) time on denosumab was 19.5 (12.4-28.6) months for the 106 patients who had not undergone surgery and were continuing on monthly denosumab. Native joint preservation was 96 % (n = 24/25) for patients with planned joint/prosthesis replacement and 86 % (n = 30/35) for patients with planned joint resection/fusion. Of the 116 patients who had surgery (median postsurgical follow-up 13.0 [8.5-17.9] months), local recurrence occurred in 17 (15 %) patients. CONCLUSION: For patients with resectable GCTB, neoadjuvant denosumab therapy resulted in beneficial surgical downstaging, including either no surgery or a less morbid surgical procedure.

Paget's sarcoma of the patella.

Paget's sarcoma is a rare complication of Paget's disease and isolated Paget's disease of the patella is extremely rare. We describe a unique case of Paget's sarcoma of the patella in a 69-year-old male farmer who had a remote history of a fracture in the same patella 40 years previously. In this case, imaging and pathogenesis of Paget's disease of bone is described and factors implicated in the development of Paget's disease in this patient are evaluated.

Sacral resection with pelvic exenteration for advanced primary and recurrent pelvic cancer: a single-institution experience of 100 sacrectomies.

BACKGROUND: Recurrent and advanced primary pelvic cancers present a complex clinical issue requiring multidisciplinary care and radical extended surgery. Sacral resection is necessary for tumors that invade posteriorly but is associated with increased morbidity and mortality. OBJECTIVE: This study aimed to analyze the morbidity and survival associated with pelvic exenteration involving sacrectomy for advanced pelvic cancers at a single institution. DESIGN: This study used patient demographics, operative and pathologic reports, and prospective survival data to determine factors affecting patient outcomes. SETTINGS: Data were collected for patients who had operations between July 1998 and April 2012 at Royal Prince Alfred Hospital. PATIENTS: One hundred patients underwent pelvic exenteration with a sacrectomy for advanced pelvic cancers. Sacrectomy was performed for 18 primary and 61 recurrent rectal cancers, 17 anal cancers, and 4 other cancers. MAIN OUTCOME MEASURES: This study looked at postoperative major and minor morbidity rates, as well as disease-free and overall survival rates after sacral resection. It compared the outcomes of high sacrectomy (at or above S2) versus low sacrectomy. RESULTS: Clear margins were achieved in 72 of 100 patients. The overall complication rate was 74% (43% major and 67% minor) with no 30-day or in-hospital mortality. Estimated overall and disease-free survival rates after curative resection were 38% and 30% at 5 years. Involved margins (p = 0.006), lymph node involvement (p = 0.008), and anterior organ invasion (p = 0.008) had a negative impact on patient survival. High sacrectomy increased the incidence of neurologic deficit postoperatively (p = 0.04) but did not alter the rate of R0 resection or patient survival. LIMITATIONS: Retrospective data were required to analyze patient morbidity, as well as operative and pathologic factors. CONCLUSIONS: This series supports sacral resection for curative surgery in advanced pelvic cancers, achieving excellent R0 and long-term survival rates. Cortical bone invasion and high sacrectomy were not contraindications to surgery and had acceptable outcomes.

Assessing the impact of a sacral resection on morbidity and survival after extended radical surgery for locally recurrent rectal cancer.

OBJECTIVES: To describe the experience of sacrectomy with extended radical resection in the treatment of locally recurrent rectal cancer. BACKGROUND: Resections of the bony pelvis, especially the sacrum, are becoming more common as part of extended radical exenterations for patients with recurrent rectal cancer. However, sacrectomy has been shown to carry a significant decrease in survival. Morbidity rates have been associated with the level of the sacrectomy (ie, >S3 junction). METHODS: An analysis was conducted using prospective data from patients with recurrent rectal cancer who underwent pelvic exenteration involving sacrectomy from July 1998 until June 2011. The impact of the proximal level of sacrectomy [low (≤S3) vs high (≥S2-S3 disc)] was compared. RESULTS: Of 240 exenteration patients, 79 underwent sacrectomy, with 49 for recurrent rectal cancer. An R0 margin was achieved in 36 (74%) patients. Achievement of clear operative margins (R0) conferred a large and significant benefit for disease-free survival compared with R1 and R2 resections (median 45 months vs 19 and 8 months, respectively; P = 0.045). Complications were reported in 40 (82%) patients, with major and minor complications in 19 (39%) and 38 (78%) patients, respectively. The proximal level of the sacrectomy (high vs low) did not significantly impair the ability to achieve a clear margin and was not associated with an increase in major or minor complications. CONCLUSIONS: This large, single-center series has demonstrated that extended pelvic exenteration involving sacrectomy has excellent R0 margins and survival rates for recurrent rectal cancer. A high sacrectomy has comparable results with a more distal abdominosacral resection.

MRI "row of dots sign" in gossypiboma: an enlarging mass 8 months after sarcoma resection.

The retention of foreign bodies after surgery is rare, but carries significant morbidity and mortality as well as financial and legal implications. Such retained items cause a foreign-body reaction, which in the case of cotton-based materials are called gossypibomas. We present the case of an 84-year-old woman with a pseudotumor secondary to a retained dressing gauze roll, presenting 5 months after resection of a gluteal sarcoma, which had raised concerns of local recurrence. We also outline the imaging modalities that may assist in diagnosis of a retained foreign body, and suggest the MRI "row of dots" sign as a useful radiological feature associated with gossypiboma. Awareness of the imaging appearances of retained foreign bodies allows the inclusion of this possibility in differential diagnosis of a mass in patients with a surgical history.

Custom designed and 3D-printed titanium pelvic implants for acetabular reconstruction after tumour resection.

BACKGROUND: Reconstructive procedure following resection of large pelvic tumours around the hip joint remains a complex challenge. METHODS: This study presents a retrospective case series of patients presenting with benign or malignant pelvic tumour for which an internal hemipelvectomy including the hip joint and subsequent reconstruction with a custom designed 3-dimensional printed titanium pelvic implant (3DPPI) has been performed between August 2013 and January 2018. RESULTS: 15 consecutive patients with a median age of 33.9 years (IQR 26.4-72.2) and a median BMI of 20.7 kg/m2 (IQR 19.0-33.3) were reviewed after median follow-up of 33.8 months (IQR 24.0-78.1). The majority of patients presented with a malignant tumour as their principal diagnosis (n = 13, 86.7%). The median surgical time was 5.5 hours (IQR 4.5-8.5) and median peri-operative blood loss was 5000 ml (IQR 2000-10000). The median MSTS score at follow-up was 63.3% (IQR 51.7-86.7%). The median NRS in rest was 0.0 (IQR 0.0-5.0), the median NRS during activity was 2.0 (IQR 0.5-7.0) and the median HOOS-PS was 76.6% (IQR 67.9-91.0). 4 patients had implant-specific complications (n = 4, 26.6%); 1 hip dislocation (Henderson type 1a), 3 structural complications (type 3a), 1 deep infection (type 4a) and 1 local tumour recurrence (type 5b). At follow-up, 4 out of 15 implants were classified as a failure, resulting in an implant survival rate of 73.3%. CONCLUSIONS: Acceptable peri-operative outcomes, functional results, complication rates and short-term implant survival can be achieved in a cohort of complex patients undergoing 3DPPI reconstruction after hemipelvectomy including the acetabulum.

Tenosynovial giant cell tumours: experience at an Australian tertiary referral centre for musculoskeletal tumours with minimum two-year follow-up.

Aims: Tenosynovial giant cell tumour (TGCT) is a rare benign tumour of the musculoskeletal system. Surgical management is fraught with challenges due to high recurrence rates. The aim of this study was to describe surgical treatment and evaluate surgical outcomes of TGCT at an Australian tertiary referral centre for musculoskeletal tumours and to identify factors affecting recurrence rates. Methods: A prospective database of all patients with TGCT surgically managed by two orthopaedic oncology surgeons was reviewed. All cases irrespective of previous treatment were included and patients without follow-up were excluded. Pertinent tumour characteristics and surgical outcomes were collected for analysis. Results: There were 111 total cases included in the study; 71 (64%) were female, the mean age was 36 years (SD 13.6), and the knee (n = 64; 57.7%) was the most commonly affected joint. In all, 60 patients (54.1%) had diffuse-type (D-TGCT) disease, and 94 patients (84.7%) presented therapy-naïve as "primary cases" (PC). The overall recurrence rate was 46.8% for TGCT. There was a statistically significant difference in recurrence rates between D-TGCT and localized disease (75.0% vs 13.7%, relative risk (RR) 3.40, 95% confidence interval (CI) 2.17 to 5.34; p < 0.001), and for those who were referred in the "revision cases" (RC) group compared to the PC group (82.4% vs 48.9%, RR 1.68, 95% CI 1.24 to 2.28; p = 0.011). Age, sex, tumour volume, and mean duration of symptoms were not associated with recurrence (p > 0.05). Conclusion: Recurrence rates remain high even at a tertiary referral hospital. Highest rates are seen in D-TGCT and "revision cases". Due to the risks of recurrence, the complexity of surgery, and the need for adjuvant therapy, this paper further supports the management of TGCT in a tertiary referral multi-disciplinary orthopaedic oncology service.

Mesenchymal chondrosarcoma: An Australian multi-centre cohort study.

BACKGROUND: Mesenchymal chondrosarcoma (MCS) is an ultra-rare sarcoma that follows a more aggressive course than conventional chondrosarcoma. This study evaluates prognostic factors, treatments (surgery, chemotherapy, and radiation), and outcomes in an Australian setting. METHODS: We collected demographics, clinicopathological variables, treatment characteristics, and survival status from patients with MCS registered on the national ACCORD sarcoma database. Outcomes include overall survival (OS) and progression-free survival (PFS). RESULTS: We identified 22 patients with MCS between 2001-2022. Median age was 28 (range 10-59) years, 19 (86%) had localised disease at diagnosis of whom 16 had surgery (84%), 11 received radiation (58%), and 10 chemotherapy (53%). Ten (52%) developed recurrence and/or metastases on follow-up and three patients with initial metastatic disease received surgery, radiation, and chemotherapy. At a median follow-up of 50.9  (range 0.4-210) months nine patients had died. The median OS was 104.1 months (95% CI 25.8-182.3). There was improved OS for patients with localised disease who had surgical resection of the primary (p = 0.003) and those with ECOG 0-1 compared to 2-3 (p = 0.023) on univariate analysis. CONCLUSIONS: This study demonstrates contemporary Australian treatment patterns of MCS. The role of chemotherapy for localised disease remains uncertain. Understanding treatment patterns and outcomes help support treatment decisions and design of trials for novel therapeutic strategies.

Managing patients with advanced soft tissue sarcoma: Evolving landscape from an Australian perspective.

AIM: Despite lack of advances in the first-line systemic therapy, the overall survival (OS) has continued to improve in patients with advanced soft tissue sarcoma (STS) with the recent estimation of median OS at 20 months. Several systemic therapy options are available now for the second-line and beyond, with more treatment tailored to histology and molecular subtype. The aim of this retrospective study was to characterize current patterns of care in managing patients with advanced STS (aSTS) in Australia. METHODS: Sarcoma databases from 7 Australian sarcoma services were accessed to identify patients diagnosed with locally advanced inoperable and/or metastatic STS between January 1, 2010 and December 31, 2015. Baseline clinicopathological factors and initial treatment patterns were descriptively analyzed. For the Victorian cohort where treatment of aSTS and follow-up details were available, further exploratory analysis was conducted to determine the impact of patient and tumor characteristics and the use of palliative-intent treatment OS. RESULTS: Of 2261 cases of STS, 671 were deemed as aSTS. Two thirds were relapsed disease with a mean 1.9 years from initial diagnosis. Median age at diagnosis of aSTS was 59 years (18-95 years) and 56.3% was male. Histology classification revealed four main subtypes: undifferentiated pleomorphic sarcoma (UPS) (23.1%), leiomyosarcoma (18.2%), liposarcoma (12.8%), synovial sarcoma (8.2%), and other comprising 14 STS subtypes. For the Victorian cohort (N = 361), approximately 80% of patients accessed palliative-intent treatment of various modalities. Nearly 40% of patients underwent tumor-debulking surgery or metastasectomy, of which lung wedge resection was the most common (N = 83, 47.7%). A total of 438 palliative-intent radiotherapy treatments were delivered to 259 patients (71.7%), with the majority in the form of external beam radiotherapy. Palliative-intent systemic therapy was delivered to 51.5% of patients (N = 186), mostly (73%). Anthracycline-based therapy was the most commonly delivered therapy (N = 135, 72.6%). Approximately half of the patients in each line of therapy failed to proceed to the subsequent line of systemic therapy with 29.4% receiving three or more lines of therapy (N = 55). A total of 18.3% of patient (N = 34) participated in clinical trials or accessed off-label drugs. The median OS for the Victoria cohort was 15.4 months (95% confidence interval: 12.1, 18.2). The UPS histology subtype was associated with poorer OS, whereas receiving any modality of palliative-intent treatment conferred survival benefit. CONCLUSION: In Australia, aSTS is managed with diverse treatment approaches comprising various therapy modalities. Further work is planned in describing healthcare resource utilization and estimating costs by this patient cohort.

The role of intra-operative pathological evaluation in the management of musculoskeletal tumours.

A tissue biopsy is usually a critical aspect in guiding appropriate initial management in patients with musculoskeletal tumours. We have previously outlined the role of intra-operative frozen section in both the determination of adequacy of a biopsy and for its diagnostic utility. In this article, the options and techniques for intra-operative pathological evaluation, namely frozen section, fine needle aspiration cytology and touch imprint cytology are reviewed. Frozen section examination may be applicable in the following Sections, including (1) at core biopsy, (2) at surgical margins, (3) at confirming diagnosis prior to definitive treatment or to evaluate tumour spread, and (4) at establishing a diagnosis of a metastasis prior to intramedullary nailing. There are also situations in which frozen section is inappropriate. Pitfalls associated with frozen sections are also highlighted. There are also cost implications, which we have quantified, of performing frozen sections. In our experience that the use of intra-operative pathological evaluation reduces the non-diagnostic rate of bone and soft tissue sarcoma biopsies, eliminates the need for re-biopsy hence alleviating stress, and is a useful addition to the armamentarium in evaluating musculoskeletal tumours.

Reconstruction of the proximal humerus with a composite of extracorporeally irradiated bone and endoprosthesis following excision of high grade primary bone sarcomas.

INTRODUCTION: Functional reconstruction of the shoulder joint following excision of a malignant proximal humeral tumour is a difficult proposition. METHOD: Eleven patients with primary osteosarcoma or Ewing's sarcoma underwent reconstruction with a composite of extra-corporeally irradiated autograft with the addition of a long stemmed hemiarthroplasty. At a mean follow-up of 5.8 years two patients had died from disseminated disease and one patient had undergone amputation for local recurrence. The eight patients with a surviving limb were examined clinically and radiographically. RESULT: The mean Toronto Extremity Salvage Score was 74 and Musculo-Skeletal Tumour Society score 66. Rotation was well preserved but abduction (mean 32 degrees ) and flexion (40 degrees ) were poor. There was a high rate of secondary surgery, with five out of eleven patients requiring re-operation for complications of reconstruction surgery. Radiographic estimate of graft remaining at follow up was 71%. There were no infections, revisions or radiographic failures. CONCLUSION: Whilst the reconstructions were durable in the medium term, the functional outcome was no better than with other reported reconstructive methods. The composite technique was especially useful in subtotal humeral resections, allowing preservation of the elbow joint even with very distal osteotomy. Bone stock is restored, which may be useful for future revision surgery in this young group of patients.

FISH analysis of selected soft tissue tumors: Diagnostic experience in a tertiary center.

AIM: Fluorescence in situ hybridization (FISH) is an important ancillary tool for the classification of bone/soft tissue (BST) tumors. The aim of this study was to evaluate the contribution of FISH to the final classification of common BST entities in the molecular pathology department of the Royal Prince Alfred Hospital (RPAH), which is one of the most important referral centers for the management of sarcomas in Australia. METHODS: All routine diagnostic FISH tests performed on BST formalin-fixed paraffin embedded (FFPE) tissue specimens at the RPAH in a 5-year period (February, 2010-November, 2015) were reviewed. FISH analyses presented in this study include commercial break-apart probes (SS18, FUS, DDIT3, FUS, USP6, PDGFB, TFE3 and ALK) and a single enumeration (MDM2) probe. RESULTS: There were 434 interpretable FISH assays on BST samples including MDM2 (n=180), SS18 (n=97), FUS (n=64), DDIT3 (n=37), USP6 (n=30), PDGFB (n=13), TFE3 (n=8) and ALK (n=5). Discrepancies between the histopathological diagnosis and the FISH results were seen in 12% of the cases. In this subset of discordant cases, FISH contributed to the re-classification of 7% of cases originally diagnosed as synovial sarcoma (SS18) and 6% of adipocytic neoplasms (MDM2) based on the presence or absence of the expected gene alteration. CONCLUSION: Our study confirms that paraffin FISH is a sensitive and specific ancillary tool in the diagnosis of BST neoplasms when used in the appropriate clinicopathological context. These findings highlight the need for further ancillary molecular tools in the diagnosis and characterization of challenging cases.

Isolated limb infusion for advanced soft tissue sarcoma of the extremity.

BACKGROUND: Isolated limb infusion (ILI) is a minimally invasive technique for delivering high-dose regional chemotherapy. We report our experience with ILI for the treatment of soft tissue sarcoma (STS). METHODS: From our prospective database, 21 patients with STS of the limb treated with ILI between 1994 and 2007 were identified. In all patients, a high-dose cytotoxic drug combination was used. RESULTS: There were 14 men, and the median age was 60 years (range, 18-85 years). Eighteen patients (86%) had lower limb tumors. All patients had advanced local disease. The procedure was well tolerated. Fourteen patients (67%) received ILI before definitive surgery. The overall response rate was 90% (complete response [CR] rate 57%, partial response rate 33%). The disease-specific overall survival was 61.9% (median follow-up, 28 months). Only American Joint Committee on Cancer stage was associated with overall survival. The local recurrence rate was 42%. CR and malignant fibrous histiocytoma tumor subtype were associated with a lower local recurrence rate. A lower initial skin temperature (median 35.8 degrees C) was associated with a CR (P = .033). Patients who had a steep increase in intramuscular temperature during the procedure were more likely to have a CR (P = .055). Classification tree analysis identified patients with an initial PaO(2) of >/=194 mmHg as being more likely to have a CR. Ultimately, the overall limb salvage rate was 76%. CONCLUSION: The outcomes after ILI are comparable to those achieved by conventional isolated limb perfusion. ILI is a minimally invasive alternative to isolated limb perfusion for patients with advanced STS of the extremity.

Clinical, cellular, microscopic, and ultrastructural studies of a case of fibrogenesis imperfecta ossium.

Fibrogenesis imperfecta ossium is a rare disorder of bone usually characterized by marked osteopenia and associated with variable osteoporosis and osteosclerosis, changing over time. Histological examination shows that newly formed collagen is abnormal, lacking birefringence when examined by polarized light. The case presented demonstrates these features and, in addition, a previously undocumented finding of a persistent marked reduction of the serum C3 and C4. Osteoblasts established in culture from a bone biopsy showed abnormal morphology on electron microscopy and increased proliferation when cultured with benzoylbenzoyl-ATP and 1,25-dihydroxyvitamin D, contrasting with findings in normal osteoblasts in culture. A gene microarray study showed marked upregulation of the messenger RNA (mRNA) for G-protein-coupled receptor 128 (GPR 128), an orphan receptor of unknown function and also of osteoprotegerin in the patient's osteoblasts in culture. When normal osteoblasts were cultured with the patient's serum, there was marked upregulation of the mRNA for aquaporin 1. A single pathogenetic factor to account for the features of this disorder has not been defined, but the unique findings described here may facilitate more definitive investigation of the abnormal bone cell function.