5-ALA photodynamic ablation of fibroblastic soft-tissue tumors.

BACKGROUND: Fibroblastic soft-tissue tumors share enzymatic anomalies that result in excessive intracellular conversion of 5-aminolevulinic acid (5-ALA) to protoporphyrin IX, a photosensitizer which induces cellular apoptosis upon exposure to visible red light at a wavelength of 635 nm. We hypothesized that red light illumination of the surgical bed remaining after resection of fibroblastic tumors will result in destruction of microscopic tumor residua and may decrease the likelihood of local tumor recurrence. METHODS: Twenty-four patients with desmoid tumors, solitary fibrous tumors (SFT), and dermatofibrosarcoma protuberans (DFSP) received oral 5-ALA prior to resection of their tumors. Following tumor resection, the exposed surgical bed was illuminated with red light at a wave length of 635 nm at a dose of 150 J/cm2 for 33 min. RESULTS: Treatment with 5-ALA was associated with minor side effects that included nausea and transient elevation of transaminases. Local tumor recurrence was detected in 1 of the 10 patients with desmoid tumors who had not undergone any previous surgery, none in the 6 patients who had SFT and 1 of the 5 patients who had DFSP. CONCLUSIONS: 5-ALA photodynamic therapy of fibroblastic soft-tissue tumors may result in decreased likelihood of local tumor recurrence. It is associated with minimal side effects and should be considered as adjuvant to tumor resection in these cases.

Less is better than more with resection of periacetabular tumors - A retrospective 16 years study and literature review.

Introduction: Wide resections of periacetabular tumors create a sizeable bony defect that inevitably results in severe loss of function. Reconstruction of such defects usually requires using large metal implants, a feature associated with considerable surgery extension and complications. The aim of this study is to report resection with no reconstruction of the bony defect. In this retrospective study, we reviewed a consecutive series of 16 patients diagnosed with malignant periacetabular tumors and underwent en-bloc resection without reconstructing their remaining bone defect. Methods: Records were reviewed of 16 consecutive patients diagnosed with malignant periacetabular tumors and underwent en-bloc resection without reconstructing their remaining bony defect. Measurements included: the duration of surgery, blood loss, hemoglobin levels and the need for blood transfusions, data on other hospitalization characteristics, and intraoperative and postoperative complications. Results: Sixteen patients with malignant periacetabular bone tumors and extensive bone destruction underwent wide periacetabular tumor resection with a mean follow-up of 75 months and a mean age of 53 years. The average HOOS score was 46 (range: 20 to 76), and the mean MSTS score was 13% (range: 0 to 15). The mean operative time was 4.1 h, and the mean blood loss was 1200 ml. At their most recent follow-up, patients had a mean shortening of their operated extremity of 4.8 cm, and all could ambulate with assisting devices. Conclusion: Wide resection of periacetabular tumors without reconstruction provides acceptable levels of function and was associated with shorter surgical time, less blood loss and fewer postoperative complications compared to resection with reconstruction. Therefore, this approach may be considered a viable surgical option in patients with an extensive malignant periacetabular. Level III: Retrospective study.

Adult Soft-Tissue Sarcomas of the Extremities.

➤: Soft-tissue sarcomas (STS) in adults comprise a heterogeneous group of tumors of mesenchymal origin that share similar biological patterns of local tumor growth and metastatic dissemination. ➤: The judicious use of imaging studies, biopsy techniques, and pathological evaluations is essential for accurate diagnosis and for planning treatment strategy. ➤: Wide local resection and radiation therapy form the cornerstone of management of high-grade STS. The role of adjuvant radiation therapy is questionable in the management of small (≤5 cm) superficial lesions that can be resected with negative margins. Chemotherapy given to patients who have nonmetastatic, high-grade STS results in varying benefit in terms of local tumor control and overall survival. ➤: Coordinated care by a multidisciplinary team of trained surgeons, medical oncologists, radiologists, radiation oncologists, and pathologists has been documented to improve local tumor control and the overall survival of patients with STS. ➤: Although considerable progress in tumor diagnostics and targeted therapies has been made over the past 2 decades, recommendations and controversies relating to tumor imaging and margins of resection have not changed.

Bilateral traumatic C6-C7 facet dislocation with C6 spondyloptosis and large disk sequestration in a neurologically intact patient.

Traumatic cervical spondyloptosis is an uncommon and severe form of facet joint dislocation that commonly leads to severe neurological damage. Decision making regarding the reduction and fixation technique is challenging, especially when a patient is neurologically intact, since an undiagnosed prolapsed disk at the involved level may lead to severe neurological consequences during reduction. A 24-year-old male was admitted after sustaining a severe direct axial blow to his head. Computed tomographic and magnetic resonance imaging scans revealed an acute C6C7 fracture dislocation with spondyloptosis of C6 vertebra and a large disk fragment posterior to C6 vertebral body. The patient was neurologically intact, apart from mild bilateral numbness over C6 distribution. The patient underwent C6 corpectomy to avoid acute cord compression related to the large sequestered disk behind C6 vertebra. Following C6 corpectomy, we were unable to exert enough axial pull to reduce the facet dislocation through the anterior approach. Therefore, the reduction was performed through a posterior approach with C5T1 posterior fusion, followed by anterior cage placement and C5-7 anterior fusion (front-back-front approach). At postoperative follow-up of 24 months, the patient demonstrated a full and pain-free cervical range-of-motion and remained neurologically intact. Follow-up radiographs of the cervical spine demonstrated good instrumental alignment with solid fusion at 6-month follow-up.

Primary high-grade soft-tissue sarcoma of the buttock: a rare but distinct clinical entity.

OBJECTIVE: Sarcoma arising in the region of the buttocks is a rare entity and therefore no consensus regarding management exists in the literature. METHODS: 16 patients diagnosed with localized, non-metastatic primary soft-tissue sarcoma (STS) in the buttock area, who were consecutively treated between 2005 and 2013, were retrospectively evaluated for the rate of local control, distant metastases and overall survival. RESULTS: Most tumours were classified as high grade (87.5%). The average time between the appearances of symptoms to diagnosis of sarcoma was 4.5 months. At the end of the observation period, 7 (44%) patients were alive without signs of progressive disease, 37.5% patients died as the disease progressed, 13 patients were free of disease and 3 (19%) patients were alive with signs of progressive disease. Seven (44%) patients developed local recurrence. Six (37.5%) patients developed distant metastases. The lung was the most common site of distant failure (four patients); other sites were the liver as well as the adrenal gland and kidney (one patient). Four patients had both distant and local progression, three patients experienced isolated local recurrence and two patients developed isolated distant metastases. 5-year local recurrence-free survival was 58% and 5-year distant metastases-free survival was 63%. CONCLUSION: It is unclear whether to subsume STS of the buttock under the rubric of pelvic tumours or tumours of the lower extremity. Either way, STS of the buttock seems to be characterized by local control, freedom from distant relapse and survival, which is inferior to accepted standards for either pelvic or lower extremity sarcomas. To improve this poor outcome, oncologists are encouraged to regard sarcoma of the buttock as a distinct clinical entity and to devise innovative therapeutic strategies accordingly. ADVANCES IN KNOWLEDGE: Sarcoma of the buttock area should possibly be regarded as a distinct entity.

Free fibula reconstruction of distal tibial defects after sarcoma surgery.

Distal tibial tumor ablation results in combined soft tissue and bone defect that involves the ankle joint. This area is unique and problematic because it combines low caliber limb size, relatively soft tissue deficiency, suboptimal bone and soft tissue healing ability, and the need to sustain increased mechanical loads. The management is difficult, controversial, and traditionally was treated by primary amputation. We present our experience with a limb sparing surgery using biological reconstruction.Between 2004 and 2007, 5 patients with malignant bone tumors of the distal tibia underwent tumor resection and reconstruction with free vascularized osteoseptocutaneous fibula flap. The average age was 33.2 years (range, 11-62 years). In all cases, a skin island was harvested and used for wound closure. Arthrodesis of the ankle joint was preformed in all patients. Double fixation system was used to provide stability and avoid flap rotation.All flaps survived. There were no major complications. One patient had partial loss of the skin paddle that was treated conservatively. Callous formation was documented after an average time of 4 months, partial weight bearing after an average time of 4 months, and full weight bearing after an average time of 11.5 months. All patients regained almost normal ambulation within a year.

The role of free tissue transfer in posterior neck reconstruction.

Reconstruction of the posterior neck is one of the rarer procedures performed by plastic surgeons; we used free flaps for the closure of defects in this area in six cases over the past 4 years. Six patients were located requiring posterior neck reconstruction between the years 2007 and 2013. Five of these patients required reconstruction due to oncologic resections, while one underwent serial removal of a giant congenital nevus. Five of these reconstructions involved the use of a free anterolateral thigh/vastus lateralis flap, and the sixth received a pre-expanded deep inferior epigastric perforator flap. Satisfactory dorsal neck reconstruction was achieved with the free flap approach: it produced excellent healing, contour and coverage of hardware. There was only one early minor complication, allowing early return to daily activities and continuation of planned oncologic treatment. Free flap reconstruction of the posterior neck area is a safe and relatively rapidly performed procedure that yields good results both functionally and aesthetically. In this article, we review the literature on the options available for reconstruction of the posterior neck, describe our surgical experience in such cases, and suggest an algorithm to guide in choosing the optimal approach for a given patient.

Clinical activity of mTOR inhibition in combination with cyclophosphamide in the treatment of recurrent unresectable chondrosarcomas.

OBJECTIVE: Chondrosarcomas (CS) represent a heterogeneous group of rare sarcomas, poorly responsive to chemotherapy or radiotherapy. When local therapies in recurrent or metastatic disease are exhausted, chemotherapy plays a marginal role. Different molecular pathways have been shown to be activated in CS. In this retrospective study, we summarize our experience in treating a cohort of patients with recurrent unresectable CS with a combination of sirolimus (SIR) and cyclophosphamide (CTX). PATIENTS AND METHODS: Ten consecutive patients with unresectable CS were offered off-label treatment with SIR and CTX between 2007 and 2012. Tumor response, progression-free survival (PFS), adverse events, and other relevant clinical data were analyzed. RESULTS: The median patients' age was 49 (range 28-68). Median disease-free interval since the primary diagnosis was 22.5 months. Median time from the disease recurrence to initiation of SIR and CTX treatment was 21.7 months due to additional local surgical treatments, excision of metastases, or slow asymptomatic progression. One (10 %) objective response was observed, and six (60 %) patients had stabilization of disease for at least 6 months. Three patients had progressive disease. Median PFS was 13.4 months (range 3-30.3). No significant adverse events were observed. CONCLUSIONS: Although advanced CS remains an incurable disease, our experience suggests that a combination of SIR and CTX is well tolerated and may have meaningful clinical activity with disease control rate of 70 %. Further prospective studies are warranted.

Repeated and escalating preoperative subanesthetic doses of ketamine for postoperative pain control in patients undergoing tumor resection: a randomized, placebo-controlled, double-blind trial.

BACKGROUND: Ketamine induces a short-term effect on postoperative pain when administered intravenously immediately before or during acute pain. Repeated administration of low-dose ketamine may induce long-term pain relief in chronic pain syndromes. OBJECTIVE: The aim of our study was to determine whether ketamine's effect on acute postoperative pain could be enhanced and prolonged and analgesia consumption reduced if it was administered intramuscularly in repeated and escalating subanesthetic doses many hours before surgery. METHODS: Patients who were scheduled for tumor resection under general anesthesia were randomly and blindly given preoperative IM ketamine (K) or normal saline (placebo [P]) following 1 of 3 consecutive protocols (2 groups/protocol, 20 patients/group): 1 dose (25-mg ketamine or 1-mL saline) at 4 hours preoperatively (K1 or P1); 2 doses (10- and 25-mg ketamine or 1-mL saline twice) at 11 and 4 hours (K2 or P2); or 3 doses (5-, 10-, and 25-mg ketamine or 1-mL saline thrice) at 17, 11, and 4 hours preoperatively (K3 or P3). No other preoperative medications were given. Postoperatively, all patients received morphine (1.5 mg/bolus) via an intravenous patient-controlled analgesia (PCA) device. RESULTS: A total of 120 patients took part in the study. Patients' ages ranged from 15 to 75 years; mean weight (76 [14] kg; range, 50-120), gender (69 men, 51 women), and race were equally distributed among the groups. There were no significant differences in intraoperative parameters among the groups. The patients' mean self-rated 48-hour pain scores on a numerical rating scale were lower in the K2 and K3 groups than in their corresponding placebo groups (K2: 1.67 [1.04] vs P2: 3.62 [1.93] [P = 0.0004]; K3: 2.22 [1.37] vs P3: 3.25 [1.76] [P = 0.046]). These groups also used ∼35% less morphine compared with the placebo groups (K2: 28.4 [20.4] mg, K3: 26.6 [16.0] mg vs P2: 42.4 [30.4] mg, P3: 40.9 [21.2] mg [P ≤ 0.02]). Intravenous PCA usage among K2 and K3 patients was ∼50% less than the usage among their placebo counterparts (P < 0.05). The 1-ketamine-injection patients' pain scores and analgesic consumption were similar to those of their placebo groups. The 25-mg-ketamine injections caused dizziness that lasted up to 2 minutes. CONCLUSIONS: Our 48-hour data suggest that 2 or 3 escalating subanesthetic doses of IM ketamine injected consecutively hours before surgery attenuated postoperative pain and reduced morphine consumption in these subjects.

Expandable endoprosthesis for limb-sparing surgery in children: long-term results.

PURPOSE: Most children today with bone sarcomas undergo limb-sparing surgery. When treating children younger than 12 years of age, the result is significant limb length discrepancy (LLD). One of the solutions is the use of an expandable endoprosthesis. METHODS: A retrospective analysis of 38 skeletally immature patients with bone sarcoma of the lower limb in whom different types of expandable endoprostheses were used from January 1988 to December 2005 were included. All patients were under the age of 14 years. There were 26 osteosarcoma and 12 Ewing's sarcomas. The data collected included the tumor characteristics, the surgical and other treatment modalities, complications and their treatment, and the final LLD and functional results. RESULTS: Fifty-five percent of the patients survived and had a mean follow-up of 113 months. All survivors reached skeletal maturity at the time of last follow-up. Seventy-one percent of the survivors had satisfactory function and 29% had a poor result. There were three secondary amputations due to local recurrence. Complications were documented in 58% of patients; the most common was infection that was diagnosed 56 times (primary 16% and secondary 84%). A significant correlation was found between function and final LLD (greater than 5 cm = inferior function), the number of complications, and the number of surgical procedures performed other than prosthesis elongation. The younger the patient was at definitive surgery, the shorter the time it took for the prosthesis to fail. CONCLUSION: In order to improve results, the number of operations must be reduced. This can be achieved by the use of novel non-invasive expandable endoprostheses or biological reconstruction.

Common skeletal growth retardation disorders resulting from abnormalities within the mesenchymal stem cells reservoirs in the epiphyseal organs pertaining to the long bones.

Among the objectives in writing the current chapter were the curiosity and the interest in allocating the sites and routes of migration of the reservoirs of the mesenchymal precartilaginous stem cells of the developing limbs in health and in disease. We chose to emphasize the events believed to initiate in these regions of stem cells, which may lead to growth retardation disorders. Thus, this narrow niche touches an enlarged scope of developmental biology angles and fields. The enclosed coverage sheds light on part of the musculoskeletal system, skeletogenesis, organogenesis of mobile structures and organs, the limbs, joints and digits (arthrology). It appears that the key role of the cartilage-bone regions is their responsibility to replenish the physis with committed chondrocytes, during the developmental, maturation and puberty periods. We shall start by outlining the framework of normal limb formation, the modalities, signals and the agents participating in this biological creation and regulation, illustrating potential sites that might deviate from normal development during the growth periods.

Surgical management of metastatic bone disease.

Metastatic bone disease is a major contributor to the deterioration of the quality of life of patients with cancer; it causes pain, impending and actual pathological fractures, and loss of function and may also be associated with considerable metabolic alterations. Operative treatment may be required for an impending or existing fracture and intractable pain. The goals of surgery are to provide local tumor control and allow immediate weight-bearing and function. Radiation therapy is often indicated postoperatively. Detailed preoperative evaluation is required to assess the local extent of bone destruction and soft-tissue involvement, involvement of other skeletal sites, and the overall medical and oncological status.

Space sarcomas: extra compartmental soft tissue tumors of the lower extremities a systematic approach to sarcomas of the femoral triangle, sartorial canal, and popliteal space.

BACKGROUND: Extra-compartmental soft tissue sarcomas may grow in virtual spaces in close proximity to major neurovascular structures and thus, require a complex resection. We analyzed the general principles by which these resections are planned. METHODS: We retrospectively analyzed 53 patients with sarcomas located in the femoral triangle (15), sartorial canal (16), and the popliteal fossa (22). These lesions were grouped into three categories based on involvement of spatial structure; neurovascular involvement = 13, musculofascial involvement = 19 and no involvement = 11. RESULTS: Limb sparing surgery was feasible in lesions that had either no structural or musculofascial involvement. Amputation, however, was required in 3 of 13 patients with neurovascular involvement because of gross involvement of the surrounding tissues. Overall, limb sparing was feasible in 94% (50 of 53 patients). The 2- and 5-year local recurrence rates were 10% and 14%, respectively. Five-year survival was 88%. CONCLUSIONS: Limb sparing resection of space sarcomas is feasible in the majority of extra-compartmental sarcomas by utilizing a systematic approach which emphasizes specific planes of resection.

Subanaesthetic ketamine spares postoperative morphine and controls pain better than standard morphine does alone in orthopaedic-oncological patients.

BACKGROUND: Postoperative pain in patients with bone and soft tissue cancer is different from that of other surgical patients due to the severity of the pain generated during surgery and because many of them have already been in pain preoperatively. The search for optimal intravenous pharmacologic management for this population is an ongoing one. We conducted a 10-month prospective, randomised, double blind study to compare the effects of a standard morphine dose to a 35%-lower dose plus a subanaesthetic dose of ketamine for postoperative pain control in patients undergoing bone and soft tissue cancer surgery under standardised general anaesthesia. METHODS: After extubation, when objectively awake (>or=5/10 on a 0-10 visual analogue scale (VAS)) and complaining of pain (>or=5/10 VAS), patients were connected to an intravenous patient-controlled analgesia (IV-PCA) device that delivered 1.5 mg morphine/bolus (MO group) or 1 mg morphine+5mg ketamine/bolus (MK group), with a 7 min lockout time. Rescue intramuscular diclofenac 75 mg was available Q4/day. Follow-up lasted 96 h. RESULTS: Fifty-seven patients (24 males, aged 18-74 years) completed the study. Pain scores were lower in the MK group compared to the MO patients, although MO patients (n=29) used 32.9+/-24.9 mg/patient morphine during the first 24 postoperative h compared to 14.6+/-11.4 mg/patient (P<0.05) for the MK patients (n=28). At that time point, 11 MO versus 4 MK patients still required IV-PCA (P<0.05). Diclofenac was also used more in the MO group. All vital signs were similar between the groups. The physiotherapy score was 35% higher for the MK patients (P<0.05). No patient had hallucinations. Postoperative nausea and vomiting rates were higher in the MO group. CONCLUSIONS: The use of subanaesthetic ketamine plus 2/3 the standard dose of morphine following bone and tissue resections results in 1) lower and more stable pain score, 2) approximately 60% morphine sparing effect, 3) a shorter period of postoperative IV-PCA dependence. Such therapy is also associated with better early physical performance.

The anterior popliteal approach for popliteal exploration, distal femoral resection, and endoprosthetic reconstruction.

Distal femoral resection and endoprosthetic reconstruction are sometimes associated with flap necrosis and inadequate soft tissue coverage. We evaluated the anterior popliteal surgical approach, which was designed to reduce those complications by using a posteromedial myocutaneous flap based upon the vastus medialis. A retrospective analysis of 46 consecutive patients was performed, and results were compared with historical controls. Compared with 19.4% with wound complications and 22.7% with gastrocnemius flap transfers in previous series by the senior author, 7.8% of patients in the present study had minimal superficial flap necrosis, and no gastrocnemius transfers for soft tissue coverage were required. The median Musculoskeletal Tumor Society score was 26, and the local recurrence rate 2 years or more after resection of osteosarcoma was 4%. The anterior popliteal approach to the distal femur limited wound complications and provided good soft tissue coverage of the endoprostheses.

Unacceptable complications following intra-articular injection of yttrium 90 in the ankle joint for diffuse pigmented villonodular synovitis.

BACKGROUND: Simple resection of diffuse pigmented villonodular synovitis of the ankle joint is associated with local recurrence rates as high as 50%. Thus, adjuvant treatment modalities, such as radiation or intra-articular isotope injection, are sometimes used after tumor resection. Our initial and highly satisfactory experience with the injection of radioactive yttrium 90 to treat pigmented villonodular synovitis of the ankle joint eroded with time so much so that we discontinued its use in the ankle and believe that it is important to alert our colleagues to the complications that we observed. METHODS: Between 1989 and 2006, we treated seven patients who had diffuse pigmented villonodular synovitis of the ankle joint with subtotal synovectomy followed by intra-articular injection of 15 mCi of yttrium 90. RESULTS: Two of the study patients had full-thickness skin necrosis develop around the injection site, necessitating free muscle flap transfer within three months of treatment, and a third patient had development of a draining sinus that was associated with chronic severe pain. The other four patients reported pain after the injection that was reasonably controlled by the use of nonsteroidal anti-inflammatory drugs. At the most recent follow-up evaluation, no study patient had recurrent disease. CONCLUSIONS: Because of the unacceptably high rate of serious complications associated with the injection of yttrium 90 into the ankle joint following subtotal synovectomy, we discontinued its use as a local adjuvant in the management of diffuse pigmented villonodular synovitis of the ankle.

The complexity of management of pregnancy-associated malignant soft tissue and bone tumors.

OBJECTIVE: The incidence of musculoskeletal tumors during pregnancy is very low. The aim of this study was to summarize our experience in treating a large cohort of pregnant patients diagnosed with these rare tumors. METHODS: Women diagnosed with musculoskeletal tumors during pregnancy or immediately after delivery were identified retrospectively in our database between 1996 and 2006. Relevant maternal and neonatal data were collected. RESULTS: Twenty patients, 8 with bone sarcomas (BS) and 12 with soft tissue sarcomas (STS) were identified. Two women were treated by wide excision of mass during pregnancy. In all other cases oncological treatment was delayed until delivery or termination of pregnancy. Vaginal delivery was possible in 9 patients, cesarean section was performed in 7, spontaneous abortion occurred in 1, and 3 underwent termination of pregnancy. Three newborns were premature, but normal growth and development were observed. Different techniques of fertility preservation were used in our patients. Five patients with BS and 5 patients with STS received preoperative chemotherapy, with different grades of toxicity. The degree of tumor necrosis tended to correlate with dose-intensity of chemotherapy. Seven patients with BS received adjuvant chemotherapy. Two patients with STS received adjuvant chemotherapy, two - radiotherapy, and four - both modalities. Median disease-free survival was 15.1 months, median overall survival - 25.4 months. CONCLUSIONS: Musculoskeletal tumors diagnosed during pregnancy, or after delivery, do not appear to have a significant impact on the prognosis. A multidisciplinary team should tailor the oncological approach individually.