Local rhBMP-2 injection after drill-hole injury in rats: does it have systemic effects?

The aim of this study is to investigate the histopathological findings of drill hole healing and interactions of parathyroid hormone (PTH), β-catenin and transcription factor-4 (TCF7L2/Tcf-4) after local application of recombinant human bone morphogenic protein-2 (rhBMP-2). Sprague Dawley rats were used in two groups of ‘femoral cortex hole model’. In the non-treated group, a hole was opened with a 3 mm K-wire in the distal and mid third junction of the right femur. In the treated group, local rhBMP-2 protein was injected into the similar femoral hole. Sterile 18M H2O was injected into the femoral hole at contralateral femur. There was more subperiosteal membranous bone reaction in the group treated with rhBMP-2 injection compared to the non-treated group. This was also proven immunohistochemically in both ipsilateral and contralateral femur with increased anti bone morphogenic protein-2 (anti BMP-2) expression. Moreover, there was an increased subperiosteal reaction at the contralateral femur. Also, in the treated group, PTH expression was increased in cells that form callus, and nuclear beta-catenin expression was increased in chondrocytes of periosteal ossification. Future studies should try to find whether the effects of rhBMP-2 on PTH and Wnt signaling pathway changes with different fracture models, also the systemic effects of local rhBMP-2 application should be investigated.

Homozygous feature of isolated triphalangeal thumb-preaxial polydactyly linked to 7q36: no phenotypic difference between homozygotes and heterozygotes.

Preaxial polydactyly is a common limb malformation in humans with variable clinical expression. Different types of triphalangeal thumb-preaxial polydactyly phenotypes were mapped to the chromosome 7q36 region. We studied a large Turkish family of 69 individuals, of whom 22 individuals were affected. In all, 11 affected family members were clinically and radiologically evaluated. All affected individuals had a triphalangeal thumb and a preaxial (hypoplastic) extra digit bilaterally, with minimal intrafamilial variation. No feet involvement was observed. Linkage and haplotype analyses using 20 informative meioses confirmed the 7q36 region contained the LIMBR1 gene. Maximum logarithm of the odds (LOD) scores were obtained with DNA markers D7S550 and D7S2423. We have further identified a novel C to T alteration at position 4909 bp in the critical zone of polarizing activity regulatory sequence (ZRS) region, in the intron 5, of the LMBR1 gene. One affected male with homozygous status and no phenotypic difference from affected family members with heterozygous status represented the first homozygote case of the triphalangeal thumb-preaxial polydactyly phenotype.

Multiple myeloma presenting as massive ascites.

Ascites is a rare complication of multiple myeloma and may occur either at presentation or more often during the disease course. Most reported cases have been associated with IgA type of myeloma. When it occurs, it is usually associated with extensive liver infiltration with plasma cells, infectious peritonitis or myelomatous peritoneal infiltration. Herein, we describe a case of IgG type multiple myeloma diagnosed by further examinations due to the presence of plasma cells in ascitic fluid.

The clinical contribution of SPECT/CT with 99mTc-HMPAO-labeled leukocyte scintigraphy in hip and knee prosthetic infections. / Aportación clínica de la SPECT/TC en la gammagrafía con leucocitos marcados con 99mTc-HMPAO en infección de prótesis de cadera y rodilla.

OBJECTIVES: White blood cell scanning with 99mTc-hexamethylpropylene amine oxime (HMPAO) has proven a sensitive and specific imaging method in the diagnosis of suspected prosthesis infection. The aim of this retrospective study was to evaluate the usefulness of SPECT/CT performed simultaneously using a hybrid imaging device of prosthesis infections. MATERIALS AND METHODS: 99mTc-HMPAO scintigraphy was performed on 37 patients (11 men and 26 women; age range 38-84 years; mean age±SD, 65.7±5.6 years). Planar scans were acquired 2.4 and 24hour after injection. SPECT/CT was obtained 4 h after injection, using a dual-head hybrid gama camera coupled with a low-power x-ray tube. In all patients, scintigraphic results were matched with the results of surgery, cultures and clinical follow-up. RESULTS: Seventeen (45,9%) out of 37 patients had prosthesis infection and 20 (54,1%) out of 37 patients had non-infectious prosthesis pathologies with 99mTc-HMPAO scintigraphy and SPECT/CT. The 99mTc-HMPAO scintigraphy was true-positive for infection in 16 of 37 patients and true-negative in 20 of 37 patients. SPECT/CT provided an accurate anatomic localization of all positive foci. With regard to the final diagnosis, SPECT/CT added a significant clinical contribution in 22 of 37 patients (59,4%). Sensitivity, specificity, negative predictive value and positive predictive values were 100%,59.1%,100%,62.5% in planar images with 99mTc-HMPAO scintigraphy and 100%,90.1%,100%,88.2% in the planar+SPECT/CT imaging, respectively. DISCUSSION: Our results indicate that SPECT/CT performed using a hybrid device can improve imaging with 99mTc-HMPAO scintigraphy in patients with suspected osteomyelitis by providing accurate anatomic localization and precise definition of the extent of infection.

Updated results from the phase 3 HELIOS study of ibrutinib, bendamustine, and rituximab in relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma.

We report follow-up results from the randomized, placebo-controlled, phase 3 HELIOS trial of ibrutinib+bendamustine and rituximab (BR) for previously treated chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) without deletion 17p. Overall, 578 patients were randomized 1:1 to either ibrutinib (420 mg daily) or placebo, in combination with 6 cycles of BR, followed by ibrutinib or placebo alone. Median follow-up was 34.8 months (range: 0.1-45.8). Investigator-assessed median progression-free survival (PFS) was not reached for ibrutinib+BR, versus 14.3 months for placebo+BR (hazard ratio [HR] [95% CI], 0.206 [0.159-0.265]; P < 0.0001); 36-month PFS rates were 68.0% versus 13.9%, respectively. The results are consistent with the primary analysis findings (HR = 0.203, as assessed by independent review committee, with 17-month median follow-up). Median overall survival was not reached in either arm; HR (95% CI) for ibrutinib+BR versus placebo: 0.652 (0.454-0.935; P = 0.019). Minimal residual disease (MRD)-negative response rates were 26.3% for ibrutinib+BR and 6.2% for placebo+BR (P < 0.0001). Incidence of treatment-emergent adverse events (including grades 3-4) were generally consistent with the initial HELIOS report. These long-term data support improved survival outcomes and deepening responses with ibrutinib+BR compared with BR in relapsed CLL/SLL.

Use of tunnelled catheters in haematological malignancy patients with neutropenia.

This prospective study analysed 83 patients (age 45 +/- 17 years) with haematological neoplasms, implanted with 93 tunnelled catheters, who were neutropenic or developed neutropenia during treatment. Catheters were implanted in the right (n = 82) or left (n = 11) jugular vein by the same surgical team using the same technique. They remained in place for 124 +/- 88 days: 29% were removed due to infection; 18% due to treatment termination and 2% due to mechanical problems. Seventeen patients died with catheters in place. At 30, 60, 90, 120 and 200 days mean catheter duration rates were 82%, 75%, 65%, 60% and 35%, respectively, and freedom from catheter removal due to infection was 92%, 88%, 80%, 77% and 67%, respectively. Patient diagnosis and history of previous catheter infection did not increase catheter infection risk, but patients undergoing stem cell transplantation had an increased infection risk. Tunnelled catheters can be used in high-risk patients with neutropenia. Systemic infections can be managed in most patients without catheter removal.

A patient with diffuse large B-cell non-Hodgkin's lymphoma and AA type amyloidosis.

AA-type amyloidosis is a consequence of a long-standing systemic inflammation and is not associated with a monoclonal protein or clonal bone marrow plasma cells. Proinflammatory cytokines such as interleukin (IL)1, IL-6, and tumor necrosis factor (TNF) stimulate the synthesis of serum amyloid A during inflammation. Although the association of non-Hodgkin's lymphoma (NHL) with AL-type amyloidosis is well known and patients with Hodgkin's lymphoma with AA amyloidosis have been described, AA-type amyloidosis with NHL is extremely infrequent. We report a case of amyloidosis associated with NHL that subsided during R-CHOP chemotherapy.

Bilateral complete avulsion of ocular globes in a Le Fort III maxillofacial fracture: a case report and review of the literature.

PURPOSE: The purpose of this paper is to demonstrate a case of bilateral complete avulsion of the globes following maxillofacial trauma. METHODS: A 23-year-old man with bilateral complete globe avulsion following a maxillofacial trauma. Both globes were luxated out of the orbit and suspended on the skin of the upper lid below the brows. No direct or indirect light reflexes or any eye movements could be noted. Computerized tomography showed complete lacerations of both optic nerves at a level just anterior to the optic canal. There were also multiple fractures corresponding to Le Fort III fracture with Le Fort II components. The brain parenchyma was normal with an exception of brain edema. As the globes were unsuitable for repositioning, both were enucleated. The maxillofacial fractures were immobilized with plates and screws. Although the patient gained consciousness with normal vital signs in the early postoperative period, he died on the ninth day due to Pseudomonas aeruginosa infection, despite invasive antibiotic treatment. DISCUSSION: The optic nerve and the globes are very resistant to mild and moderate trauma. The avulsion of the nerve at the canalicular or more posterior level may demonstrate central nervous system complications resulting in life-threatening conditions. The most critical issue in complete globe avulsions with a transected optic nerve is to rescue the vision. In total transected optic nerves the final eyes could only have had cosmetic benefits. In spite of promising experimental research on optic nerve regeneration, there are unknowns, such as the methods to eliminate the risk of anterior segment ischemia and phthisis bulbi. CONCLUSIONS: Globe avulsions with a complete optic nerve cut remain a challenging problem. More research is required to better understand the pathophysiology of optic nerve repair.

Hemophagocytic syndrome associated with inappropiate secretion of antidiuretic hormone in lymphoma and acute myeloblastic leukemia: report of two cases.

Hemophagocytic syndrome (HPS) is a rare clinicopathological disorder characterized by systemic proliferation of phagocytizing histiocytes associated with fever, cytopenias, lymphadenopathy, hepatosplenomegaly, and disseminated intravascular coagulopathy. We present the association of hemophagocytic syndrome associated with inappropriate secretion of antidiuretic hormone (SIADH) in two cases of hematological malignancies; anaplastic large cell lymphoma (ALCL) and acute myeloblastic leukemia (AML M4) In the patient with lymphoma, the diagnosis of lymphoma, HPS and SIADH were concurrent. In the patient with AML, HPS and SIADH were observed while the patient was in hematological remission. Thus it seems that patients with HPS may also carry a risk for the development of SIADH; the relationship with HPS and SIADH should be further investigated.

Triplicated thumb.

A polydactyly anomaly of the thumb with three nails, two metacarpals, and seven phalanges is presented. This anomaly is named triplicated thumb, and its place in Wassel's classification is discussed. The patient was treated according to the principles of surgery of polydactyly anomalies. Good motor function with acceptable aesthetic appearance was obtained.

Delayed effect of denervation on wound contraction in rat skin.

Neuronal supply in soft tissues may be an important part of cutaneous wound healing. In order to observe the effect of denervation on wound contraction, rectangular full-thickness skin defects were created on the dorsum of two groups of Wistar rats. In the experimental group (n = 20), spinal nerves corresponding to the area of the open wound (T11 to L2) were isolated and divided bilaterally. In the control group (n = 20), the same pairs of spinal nerves were dissected but left intact. Limits of denervation were verified by the pinprick test. Wound healing, which is primarily in the form of wound contraction in this model, was evaluated by tracing wound margins onto millimetric paper weekly. Wound contraction was delayed significantly in the experimental group (p < 0.05) at all follow-up periods when compared with the controls. Loss of neuropeptide secretion from the nerve endings in denervated tissues may be responsible for the retarded wound contraction, since neuropeptides are thought to exert trophic effects on skin wound healing.

Double free flaps in reconstruction of extensive composite mandibular defects in head and neck cancer.

Extensive composite defects of the lower jaw are defined as those that involve skin, mandible, oral mucosa, and soft tissues. The enormous size and multilayered nature of these defects challenge most of the current reconstructive techniques. For reconstruction of extensive composite mandibular defects in 36 advanced oral cancer patients, two free flaps were used simultaneously in a complementary fashion. The aim was to provide bone reconstruction and adequate soft-tissue coverage in an optimal form. Primary reconstruction was carried out in 34 of 36 cases. The fibula osteoseptocutaneous-radial forearm fasciocutaneous flap combination was most commonly used (n = 20), followed by the fibula osteoseptocutaneous-rectus abdominis myocutaneous flap (n = 11). The other combinations included the fibula osteoseptocutaneous-tensor fasciae latae, the fibula osteoseptocutaneous-rectus femoris, the iliac crest-radial forearm, and the iliac crest-tensor fasciae latae flaps. In 11 cases, the second free flaps were attached to the distal runoff of the first free flaps because of unavailability of recipient vessels. The mean operation time was 12 hours 10 minutes. The complete flap survival rate was 93 percent (67 of 72 flaps) with 2.8 percent total (2 of 72) and 4.2 percent partial (3 of 72) flap failures. Median follow-up time was 14 months, and 44 percent of the patients were alive at the time of evaluation, surviving an average of 36 months. The average survival time for those who died was 11.1 months. The authors believe that in selected cases the double free-flap procedure for one-stage reconstruction of massive mandibular defects is justified because it is safe and effective and improves the quality of life and the number of days spent outside of the hospital for these patients.

One-stage reconstruction of eye socket and eyelids in orbital exenteration patients.

Reconstruction of the exenterated orbit is a difficult problem with several advantages and disadvantages. Satisfactory reconstructive results for both the physician and the patient may need multistage operations that are time consuming and disfiguring. A simple and effective one-stage technique that combines two regional flaps is described for reconstruction of deformities of orbital exenteration. A temporalis muscle flap is transposed for orbital filling, and a prefabricated frontal island flap based on superficial temporal vessels is used for eye socket and eyelid reconstruction. For patients who oppose living with exenteration deformity and request quicker reconstruction, this new and simple technique may be used successfully.

Vulva reconstruction with a tissue expander.

A patient with exstrophy of the bladder in whom we performed vulva reconstruction using a tissue-expansion technique and local flaps was presented. The ultimate result was in concert with the anatomic characteristics of normal external genitalia with regard to type of skin, pigmentation, hair pattern, quality of circulation, and sensory supply.

Reliability of the venae comitantes in venous drainage of the free radial forearm flaps.

The radial venae comitantes are usually considered as an accessory venous outflow tract in the free radial forearm flap because of their smaller size and thinner structure when compared with those of the cephalic vein. To evaluate the reliability of the deep venous system, a single radial vena comitans anastomosis was performed to serve as the sole venous outflow tract in 94 consecutive radial forearm free flap transfers. The suprafascial dissection technique was used in flap elevation, which allowed preservation of the cephalic vein and the dorsal branch of the radial nerve. In all cases, the external diameter of at least one vena comitans was adequate (< or = 1.5 mm) to perform a smooth microvascular anastomosis; in none of the cases was a venous anastomosis failure detected. Preselected use of a single vena comitans for the venous drainage of radial forearm free flaps was proven to be reliable and was preferred because of the ease of flap dissection and better donor site appearance.

Management of secondary soft-tissue deficits following microsurgical head and neck reconstruction by means of another free flap.

Secondary soft-tissue deficits may develop following a microsurgical reconstruction in the head and neck region because of inadequate planning or chronic effects of radiotherapy. Although most cases could be managed with alternative methods, free flaps might be necessary in difficult cases. Herein are described 11 cases of microsurgical head and neck reconstruction in which secondary soft-tissue deficits required transfer of another soft-tissue free flap. All patients had malignant tumors treated with surgical resection, and their defects were reconstructed with free flaps. Seven patients received either preoperative or postoperative adjunctive radiotherapy. These patients gradually developed signs and symptoms of soft-tissue deficiency in the reconstructed area, and a soft-tissue free flap transfer was required for treatment within an average of 21.5 months of their initial reconstruction. Five rectus abdominis, one rectus femoris, one latissimus dorsi, one tensor fasciae latae myocutaneous, one radial forearm, one medial arm, and one dorsalis pedis flap were used for this purpose. All flaps survived completely. The average follow-up time was 32 months. Significant improvement was achieved in all cases, and no further major surgical procedures were required. Secondary soft-tissue deficits that could not be predicted or prevented during the initial microsurgical reconstruction may be treated successfully by a subsequent free soft-tissue transfer in selected cases.

Microsurgical reconstruction in recurrent oral cancer: use of a second free flap in the same patient.

Primary microsurgical reconstruction is the treatment of choice for ablative defects of oral carcinoma. As a result of this trend, more and more patients with recurrent oral carcinoma who have been initially treated with surgical excision and reconstructed with free flaps are being seen. However, a second microsurgical reconstruction attempt in these cases raises questions about the flap choices, availability of recipient vessels, and effects of previous treatment modalities. Herein, 35 patients with perioral carcinoma who had two successive tumor resections and reconstruction with free flaps on each occasion are presented. A total of 75 free tissue transfers were carried out for the first and second reconstructions. After the first tumor resection, 28 radial forearm fasciocutaneous flaps, 7 fibula osteoseptocutaneous flaps, 1 iliac osteomyocutaneous flap, and 2 rectus abdominis myocutaneous flaps were used. For reconstruction after the recurrence, 17 radial forearm fasciocutaneous flaps, 13 fibula osteoseptocutaneous flaps, 3 rectus abdominis myocutaneous flaps, 2 anterolateral thigh flaps, 1 jejunum flap, and 1 tensor fasciae latae flap were used. More vascularized bone transfers were performed during the second reconstruction since the excision for the recurrence frequently required segmental mandibulectomy. The complete flap survival rate was 97.3 percent and 94.6 percent with a reexploration rate of 7.9 percent and 13.5 percent for the first and second free tissue transfers, respectively. The mean follow-up time throughout the procedures was 37.5 months. Disease-free interval between reconstructions was 20.8 months. At the time of evaluation, 54.3 percent of the patients were surviving an average of 19 months since the second reconstruction. The results suggest that free flaps represent an important option in reconstruction of recurrent perioral carcinoma cases undergoing reexcision. When used in this indication they are as safe and effective as the initial procedure.

Free fibula osteoseptocutaneous-pedicled pectoralis major myocutaneous flap combination in reconstruction of extensive composite mandibular defects.

Lateral composite mandibular defects resulting from excision of advanced oral carcinoma often require mandible, intra-oral lining, external face, and soft-tissue bulk reconstruction. Ignorance of importance soft-tissue deficit in those patients may cause significant morbidity and functional loss. Such defects, therefore, can be reconstructed best with a double free flap technique. However, this procedure may not be feasible for every patient or surgeon. An alternative procedure is a free fibula osteoseptocutaneous flap combined with a pedicled pectoralis major myocutaneous flap. This combination was used in reconstruction of extensive composite mandibular defects in 14 patients with T3/T4 oral squamous cell carcinoma. All patients were men, and the average age was 54.3 years. The septocutaneous paddle of the fibula flap was used for the mucosal lining of the defects while the bony part established the rigid mandibular continuity. The pectoralis major flap then covered the external skin defect in the face and cheek, and the dead spaces left by the extirpated masticator muscles, buccal fat, and parotid gland. One free fibula flap failed totally, and one pectoralis major flap developed marginal necrosis. At the time of final evaluation, nine patients (64.3 percent) were alive, surviving an average of 25.7 months. All patients eventually regained their oral continence and an acceptable cosmetic appearance. In conclusion, the fibula osteoseptocutaneous flap plus regional myocutaneous flap choice is a successful and technically less demanding alternative to the double free flap procedures in reconstruction of extensive lateral mandibular defects.

Toe transplantation for isolated index finger amputations distal to the proximal interphalangeal joint.

Functional deficit following single distal index finger amputations has been considered insignificant, and reconstruction is usually not recommended. Herein, 19 cases of second toe transplantation for reconstruction of isolated index finger amputation distal to the proximal interphalangeal joint are presented with long-term functional results. There are 14 men and 5 women. The average age was 26 years. The toe transplantations were performed either as a primary procedure (5 patients) while the wounds were still open or as a secondary procedure (14 patients) after the wounds healed. In 11 patients, the dominant hand was involved. All toes survived completely, although re-exploration was required in three cases (16 percent). The functional evaluation included (1) sensory recovery, where the average static and moving two-point discrimination were 8 mm (range 4 to 15 mm) and 6 mm (range 2 to 15 mm); (2) motor function, where the average of index-thumb pulp-to-pulp pinch compared with the normal hand was 67.5 percent (range 36 to 96 percent); (3) average range of motion in index finger joints (extension/flexion), where metacarpophalangeal joint was 14/90, proximal interphalangeal joint was 0/94, and distal interphalangeal joint was 19/38; and (4) functional and cosmetic results, where percentage of involvement in daily activities and functional capacity of the reconstructed index were 69 percent and 70.5 in average, respectively, over a total score of 100. Average scores of aesthetic appearance and acceptability of donor-site deformity were 74 and 87.5 over a total score of 100, respectively. Toe transplantation for distal index finger amputations improved hand function when performed in selected patients with specific job requirements or high motivation.