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PubMed2005

Bisphosphonate treatment in osteogenesis imperfecta: which drug, for whom, for how long?

Treatment with bisphosphonates has brought significant clinical improvements for children and adolescents suffering from moderate to severe forms of osteogenesis imperfecta (OI). Benefits include decreased pain, lower fracture incidence, and better mobility. Among the various bisphosphonates, intravenous pamidronate has been studied in most detail. It is unclear whether oral bisphosphonates are as effective as intravenous pamidronate. As the effect of bisphosphonates on the skeleton is largest during growth, it appears logical to start medical therapy of OI patients as early as possible. Nevertheless, the optimal treatment regimen and the long-term consequences of pamidronate treatment in children are currently unknown. Given these uncertainties, treatment with bisphosphonates should be reserved for patients who have significant clinical problems, such as vertebral compression fractures or long bone deformities. At present, bisphosphonate treatment has little justification in growing patients with mild forms of OI who have few or no clinical symptoms. Such patients should not be treated unless clear clinical benefit can be demonstrated in ongoing placebo-controlled trials.

Decision Making↗

PubMed1993

Alcohol-induced bone disease: relationship to age and parathyroid hormone levels.

Alcohol abuse leads to osteopenia and fractures. Epidemiological evidence suggests that older alcoholics are at substantially greater risk of fractures than younger alcoholics. To examine the interaction of age and alcohol abuse on bone mineral homeostasis, we studied 27 subjects with a history of 10 more years of alcohol abuse ranging in age from 26-68 years. They were evaluated for disordered bone mineral homeostasis by assessing bone density (by quantitative computed tomography of the lumbar spine), histomorphometry of a transcortical biopsy from the iliac crest, serum levels of vitamin D metabolites and parathyroid hormone, and serum and urine levels of bone minerals. Seventeen of the subjects were found to have spinal compression fractures by routine radiologic procedures. The older the subject the more likely the subject was to have such a fracture. Bone densitometry indicated a marked reduction in spinal bone density with 15 subjects below 2 SD of normal aged-matched controls. Bone density fell sharply with the age of the subject. Histomorphometry of iliac crest bone biopsies revealed no evidence of osteomalacia, but total resorption surfaces were increased. Consistent with the lack of osteomalacia were the normal levels of the vitamin D metabolites. The increased total resorption surfaces were correlated with high normal or elevated levels of parathyroid hormone as indicated both by radioimmunoassay and by urinary cAMP levels. Bone formation and active bone resorption (resorption surfaces containing osteoclasts) did not correlate with parathyroid hormone levels, however, but correlated negatively with age.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed2001

Epidemiology of thoracolumbar spine injury in blunt trauma.

OBJECTIVE: To evaluate the prevalence, distribution, and demographics of thoracolumbar (TL) spine injuries following blunt trauma. METHODS: Prospective, cross-sectional study of a consecutive sample of all blunt trauma patients presenting initially to the emergency department (ED) of a Level 1 trauma center and undergoing thoracic and/or lumbar spine radiography from August 1997 to November 1998. The age, sex, and mechanism of injury of each patient as well as location and type of spine injury were recorded for those patients with vertebral fractures, dislocations, or subluxations. RESULTS: Two thousand four hundred four blunt trauma patients were enrolled. Vertebral injuries were identified in 152 individuals (6.3%, 95% CI = 5.4% to 7.4%). Two hundred sixty distinct anatomic levels of injury were identified in these 152 individuals. Of these 260 injuries, 42 (16.2%) occurred at L1, 38 (14.6%) at L2, 29 (11.1%) at L3, and 27 (10.4%) at T12, making these the most commonly injured vertebrae. Injuries were most common (34 patients) in those aged 30-39 years and were least common (12 patients) in those under 18 years. Compression fractures (52%) were the most common injury in the thoracic spine, while transverse process fractures (48%) were the most common injuries in the lumbar spine. CONCLUSIONS: The prevalence of TL injuries in ED blunt trauma patients undergoing TL radiographs is 6.3%. The most commonly injured area of the TL spine is the thoracolumbar junction.

Adolescent↗

PubMed2002

[A case of SAPHO syndrome with paraplegia due to a thoracic kyphosis].

A 63-year-old man visited our hospital in January 1993 because of back pain, which had been present for a year and persisted. The patient was diagnosed compression fracture of thoracic spine by another hospital. Thoracic plain radiographs revealed destructive and sclerotic changes with reduction of height of T 8, T 9 vertebral body. He had kyphosis on this level. Radiographs of the chest revealed hyperostosis of bilateral proximal clavicle. We diagnosed SAPHO syndrome (synovitis, acne, pustlosis, hyperostosis, and osteomyelitis: SAPHO) with T 8, T 9 spondylodiscitis, however without any skin manifestations. Oral indomethacin was effective, however thoracic kyphosis progressed gradually. Spastic gait and paraplegia appeared from February 1998, at last on July he was unable to walk independently. MRI showed the compression of spinal cord on T 8, T 9 level. We performed circumferential decompression and fusion with instrumentation. His paraplegia improved after surgery. We describe a rare case of SAPHO syndrome with paraplegia due to a thoracic kyphosis.

Acquired Hyperostosis Syndrome↗

PubMed2005

Osteogenesis imperfecta, current and future medical treatment.

Physiotherapy, rehabilitation, and orthopedic surgery are the mainstay of treatment in moderate to severe forms of osteogenesis imperfecta (OI). Nevertheless, medical treatment with bisphosphonates can bring significant additional improvements. Benefits include decreased pain, lower fracture incidence, and better mobility. Among the various bisphosphonates, intravenous pamidronate has been studied in most detail. It is unclear whether oral bisphosphonates are as effective as intravenous pamidronate. As the effect of bisphosphonates on the skeleton is largest during growth, it appears logical to start medical therapy of OI patients as early as possible. However, the optimal treatment regimen and the long-term consequences of pamidronate treatment in children are currently unknown. Given these uncertainties, treatment with bisphosphonates during growth should be reserved for patients who have significant clinical problems, such as vertebral compression fractures or long bone deformities. Medical therapies other than bisphosphonates, such as growth hormone and parathyroid hormone, play a minor role at present. Gene-based therapy currently remains in the early stages of preclinical research.

Age Factors↗

PubMed2003

Nerve-root injections for the relief of pain in patients with osteoporotic vertebral fractures.

We have studied 58 patients with pain from osteoporotic vertebral fractures which did not respond to conservative treatment. These were 53 women and five men with a mean age of 72.5 years. They received a nerve-root injection with lidocaine, bupivicaine and DepoMedrol. The mean follow-up period was 13.5 months. The mean pain scores before treatment, at one and six months after treatment and at the final follow-up were 85, 24.9, 14.1, and 17.4, respectively. According to our modified criteria for grading results, six patients were considered to have an excellent result, 42 good and ten fair. A newly developed compression fracture was noted in three patients. There were no complications related to the injection. Our study suggests that nerve-root injections are effective in reducing pain in patients with osteoporotic vertebral fractures and that these patients should be considered for this treatment before percutaneous vertebroplasty or operative intervention is attempted.

Aged↗

PubMed2006

[Esophageal stricture following complete remission after chemotherapy for malignant lymphoma in an elderly patient].

A 75-year-old woman was given a diagnosis of malignant lymphoma (non-Hodgkin, diffuse large B cell type, stage IIA) at our hospital on August 2003. She received six courses of rituximab-based chemotherapy (R-CHOP regimen) and then she achieved complete remission. On August 16, 2004, she was readmitted in our hospital for difficulty in swallowing. Upper gastrointestinal endoscopy reveled esophageal stricture and an ulcerative lesion on the esophageal mucosa. The X-ray examination of the upper gastrointestinal tract reveled a severe esophageal stricture with niches and hiatus hernia. No malignancy was seen on CT scanning, gallium radioisotope scanning and histological examination of biopsy specimens with the upper gastrointestinal endoscopy. The physical examination showed gibbosity, and MR imaging showed multiple compression spined fractures. Finally, we diagnosed benign esophageal stricture with reflux esophagitis. She underwent laparoscopic partial esophagectomy in September 21, 2004, and the postoperative course was satisfactory. The pathological findings showed benign esophageal stricture caused by esophagitis. We report here a case of esophageal stricture following complete remission after chemotherapy for malignant lymphoma in an elderly patient.

Aged↗

PubMed1988

Occult intraosseous fracture: detection with MR imaging.

Magnetic resonance (MR) images were retrospectively evaluated in eight patients who had recent, symptomatic knee injuries and in whom plain radiographs showed no fractures. T2-weighted images revealed irregular, intraosseous areas of high signal intensity; T1-weighted and proton density images revealed speckled or linear regions of low signal intensity in corresponding areas. In the seven patients whose injuries did not result from direct contusion, abnormalities occurred in subchondral locations. Two patients underwent bone scintigraphy, which showed increased activity in locations corresponding to areas of abnormality noted on MR images. Two patients underwent follow-up MR imaging at 6 weeks and 3 months, which showed complete resolution of the abnormalities. The authors speculate that the MR imaging findings represent microscopic compression fracture of trabecular bone and discuss the related entity, stress fracture.

Adolescent↗

PubMed2004

Slipped capital femoral epiphysis. The mechanical function of the periosteum: new aspects and theory including bilaterality.

This particular ailment has many designations in the literature but none is quite adequate. Here we use the terminology slipped capital femoral epiphysis (SCFE). The anatomy of the proximal femur in all mammals reflects their growth and function. The main forces acting on the head are perpendicular to the growth plate. The thick tear-proof perichondrium-periosteum on the femoral neck is like a stocking attached to the epiphysis and the trochanter region. Growth in length causes a strong tensile stress in the periosteum, pressing the epiphysis against the metaphysis and thus stabilizing the vulnerable growth plate-the periosteum theory. Several factors may diminish the stability of the growth plate. SCFE begins with fissures, which coalesce to a fracture in the growth plate, invisible on a radiograph. As the slip progresses, an increasing angulation between the epiphysis and the remainder of the femur occurs. Weight and muscular forces displace the epiphysis posteriorly in a flexed hip. A rift in the ventral half of the periosteal stocking occurs at the border to the perichondrium and, after that, a longitudinal rift in the periosteum at the anterior midline of the femoral neck. This rift becomes broader as the epiphysis slips posteriorly, withdrawing the ruptured periosteum. Displacement of the epiphysis is due to a rotational slip and tilt, made possible by a compression fracture in the posterior part of the metaphysis. Parts of the periosteum function as reins steering the slip direction and counteracting the displacement. SCFE may be regarded as a pseudoarthrosis in the growing cartilage of the plate. The periosteum theory extended to a pseudoarthrosis theory has been supported by findings at surgery and on true lateral radiographs of usual and unusual cases of SCFE presented in this opus. On a true lateral view, the displacement can be measured as the slipping angle (SA) based on anatomical and geometrical considerations. SA values from 95 normal hips and from 22 contralateral asymptomatic hips from SCFE patients are presented in a histogram and bar graph. Statistically, SCFE is always bilateral, but in about 1/3 of the asymptomatic, contralateral hips, the physis ossifies and closes with SA below 13 degrees, and surgery is not necessary. It is most important that the position of the femur on the X-ray table is exactly defined in two dimensions: 1) the angle between the femoral shaft and the tabletop (angle of elevation), 2) the degree of rotation of the femur around its axis. A precisely defined positioning of the femur is a prerequisite for an exact reproducible measurement of the SA on a true lateral view and is also valuable for the evaluation of radiographic "signs". An aid, the Youth Hip Triangle (YHT), has been designed to facilitate positioning of the femur and measurement of SA. YHT is recommended for routine use in every X-ray facility. The method is quick, cost effective and makes it possible to diagnose SCFE in the contralateral hip before clinical signs or symptoms have occurred.

Adolescent↗

PubMed1999

Deep vein thrombosis in elderly Hong Kong Chinese with hip fractures detected with compression ultrasound and Doppler imaging: incidence and effect of low molecular weight heparin.

Seventy-eight patients of average age 78 years suffering from an unilateral non-pathological hip fracture underwent compression ultrasound and pulsed and colour Doppler examination of both legs. Twenty-three patients were randomly placed on low molecular weight heparin (LMWH). Twenty-nine (37%) suffered deep venous thrombosis (DVT). There was no statistically significant difference in the incidence of DVT between the control and LMWH groups, and the incidence of DVT in elderly Chinese patients after hip replacement for a hip fracture is similar to that in other studies in Caucasians. There were, however, some differences, namely the contiguous nature of the thrombi rather than focal segmental clots, and the absence of propagation or tail formation. Although the numbers are small, this could possibly represent a population difference. There was a significantly increased occurrence of DVTs on the operated side in both groups. Serial ultrasound examination supports evidence that DVTs occur in the 1st week postoperatively, but there were also a number of patients who developed DVTs in the 2nd week. There was no statistically significant difference in overall incidence of DVT between patients on prophylactic heparin and the control group. Patients on prophylactic heparin had no thigh DVTs in comparison to the control group. LMWH may thus be effective in preventing thigh DVTs and pulmonary emboli.

Aged↗

PubMed2004

Femoral shaft medialisation and neck-shaft angle in unstable pertrochanteric femoral fractures.

We analysed the time-dependent mean changes in the femoral neck length, neck-shaft angle and hip offset in a randomised study comprising 48 patients who were treated with the dynamic hip screw (DHS) or the proximal femoral nail (PFN) for an unstable intertrochanteric femoral fracture. As a consequence of fracture compression, the mean post-operative neck length was significantly shorter in patients treated with the DHS. During the first 6 weeks after the operation, a mean decrease of 4.6 degrees was observed in the neck-shaft angle, but there was not a significant difference between the treatment groups. The radiographic measures remained virtually unaffected during the interval from 6 weeks to 4 months in both groups. When the operated hip was compared to the opposite hip, patients who had received the DHS showed significantly greater medialisation of the femoral shaft at 4 months than those treated with the PFN. We thus recommend that unstable intertrochanteric fractures should be initially reduced in a slight valgus position in order to achieve an outcome after healing that is as normal as possible. As a result of differences in operative technique and implant stability, the PFN may be superior to the DHS in retaining the anatomical relations in the hip region in unstable intertrochanteric fractures.

Aged↗

PubMed2006

[Imaging of extradural spinal lesions].

There is a wide variety of spinal extradural tumors. In addition to real neoplasms, degenerative diseases, congenital abnormalities and inflammatory disorders can be causes of extradural masses. Due to the bony boundary of the spinal canal, both benign as well as malignant masses can cause progressive neurological deficits including paraplegia. Most of the spinal tumors are benign (hemangioma of the vertebral body, degenerative diseases). In younger patients congenital abnormalities and primary tumors of the spine have to be considered, whereas in adults the list of differential diagnoses should include secondary malignancies such as metastases and lymphomas as well as metabolic disorders such as osteoporotic vertebral compression fracture and Paget's disease. Cross-sectional imaging techniques such as magnetic resonance imaging (MRI) and computed tomography (CT) of the spine often help to make a specific diagnosis of extradural spinal lesions and represent important tools for tumor staging and preoperative evaluation.

Diagnosis, Differential↗

PubMed1996

Osteoporosis in lung transplantation candidates with end-stage pulmonary disease.

PURPOSE: Fractures, a common complication of cardiac and liver transplantation, have not been reported in association with lung transplantation. However, many patients with end-stage pulmonary disease have multiple risk factors for osteoporosis, and several studies have suggested that osteoporosis before transplantation may increase the risk of fracture after transplantation. Therefore, we evaluated a group of patients with end-stage pulmonary disease who were awaiting lung transplantation to determine the prevalence of osteoporosis. METHODS: Seventy patients (aged 18-70 years) were evaluated consecutively with bone densitometry by dual-energy x-ray absorptiometry. The patients were predominantly Caucasian (96%). Bone mass was expressed as bone mineral density (BMD; g/cm2), as the number of standard deviations (SD) below peak bone mass (T score), and as bone mineral apparent density (BMAD; g/cm3), a measurement that minimizes the effects of bone size on BMD. Spine radiographs were obtained in a subset of 50 consecutive patients to detect vertebral compression fractures. Vitamin D status was assessed with serum concentrations of 25-hydroxyvitamin D. The patients were sorted into groups by pulmonary diagnosis: chronic obstructive pulmonary disease (COPD; n = 28); cystic fibrosis (n = 11); idiopathic pulmonary fibrosis; and other lung diseases (Other; n = 31). RESULTS: In the group as a whole, osteoporosis (T score below -2.5) was present in 30% of the patients at the lumbar spine and 49% at the femoral neck. Osteopenia (T score between -1 and -2.5) was present in an additional 35% at the lumbar spine and 31% at the femoral neck. The average femoral neck T score of patients with COPD and cystic fibrosis fell into the osteoporotic range (-2.7 +/- 0.3 and -2.6 +/- 0.3, respectively), significantly (P < 0.01) below that of the patients in the Other category (-1.5 +/- 0.3). The average lumbar spine T score fell into the osteopenic range in all three groups. Low BMAD in patients with cystic fibrosis confirmed that their low BMD was not due to their smaller body size. The prevalence rate of vertebral fractures was 29% in patients with COPD and 25% in those with cystic fibrosis. Vitamin D deficiency (25-hydroxyvitamin D levels < or = 10 ng/ml) was present in 36% of patients with cystic fibrosis and 20% with COPD and Other lung diseases. Lumbar spine BMD tended to be lower in cystic fibrosis patients with vitamin D deficiency. Patients with exposure to glucocorticoids (n = 46) had significantly more vertebral fractures (P < 0.05) and duration of exposure correlated negatively with lumbar spine BMD (r = -0.398; P = 0.008). COPD and Other patients not on glucocorticoids had mild lumbar spine osteopenia (0.972 +/- 0.06 g/cm2; T = -1.2 +/- 0.6). Very few of the patients on glucocorticoids were on any regimen to prevent osteoporosis. CONCLUSIONS: Osteoporosis and vitamin D deficiency are extremely common in patients with end-stage pulmonary disease. Only 34% of patients had normal lumbar spine BMD and only 22% had normal BMD at the hip. Patients with cystic fibrosis and glucocorticoid-treated patients with COPD were most severely affected. Therapies to prevent bone loss and treat established osteoporosis are uncommonly utilized in glucocorticoid-treated patients with end-stage pulmonary disease. Candidates for lung transplantation should be evaluated for osteoporosis and vitamin D deficiency at the time of acceptance to the transplant waiting list.

Absorptiometry, Photon↗

PubMed1996

Vitamin D receptor polymorphism, bone mineral density, and osteoporotic vertebral fracture: studies in a UK population.

Bone mineral density is under strong genetic control and polymorphisms of the vitamin D receptor (VDR) have been suggested to account for some of the genetic variation in bone mass. However, the relationship between VDR polymorphisms and bone density is controversial and has not been confirmed by all workers. Since there is little information on the association between VDR genotype and bone mass in the UK, we studied VDR genotype, bone mineral density, and osteoporotic fracture in a cohort or pre- and postmenopausal women from the Northeast of Scotland. We found a highly significant "inverse" association between the VDR genotype and bone mineral density at the hip such that individuals of "bb" genotype had a femoral neck bone density of 0.79 standard deviation lower than individuals of BB genotype (p < 0.02). This contrasts with most previous studies in which the "bb" genotype has been associated with high bone density. A similar, but nonsignificant trend was seen for lumbar spine BMD. To study the clinical significance of this observation, we examined the distribution of VDR genotypes in a subgroup of patients with severe osteoporosis who had vertebral compression fractures (n = 44) as compared with with age-and gender-matched controls (n = 44). Despite the differences in BMD between genotypes, there was no significant excess of any specific VDR genotype in osteoporotic fracture patients, indicating that VDR genotyping may be of limited practical value in identifying patients at risk of vertebral fracture. This study confirms that there is a significant association between VDR genotype and bone mass in our population. The "inverse" relationship between VDR genotype noted in this, as compared with previous studies, would be consistent with a model whereby VDR polymorphisms are not the cause of reduced BMD, but rather, are in linkage disequilibrium with a disease-causing locus nearby.

Absorptiometry, Photon↗

PubMed1983

[Vertebral osteonecrosis. Apropos of 4 cases with slow spinal cord compression in 1 case].

The authors report on four cases of aseptic osteonecrosis of the vertebral body in adults (VON). Among these, one patient, in whom histological data were available, presented with a slow spinal cord compression syndrome (SSCCS). This complication is uncommon since only one other similar case has been reported so far (4). VON thus remains an underestimated etiology of SSCCS by non-tumoral compression fracture of the vertebral body. Diagnosis is based on the roentgenograms which evidence osteocondensation with "gaseous dissection" of the vertebral body, the latter being considered as pathognomonic of this disease. The etiopathogeny is still unknown. Treatment is purely symptomatic and the course has always been favorable.

Aged↗

PubMed2005

Effect of cement volume and placement on mechanical-property restoration resulting from vertebroplasty.

BACKGROUND AND PURPOSE: Concern exists that vertebral bodies augmented with cement placed laterally may be at risk of collapse on the nonaugmented side. The purpose of the current study was to determine if placing the cement laterally rather than centrally resulted in risk of collapse on the nonaugmented side. METHODS: Vertebral bodies (L2-L5) were harvested from eight osteoporotic female cadaver spines. Simulated vertebral-body compression fractures were created and stabilized by injecting 3.5 or 7.0 mL of cement centrally or laterally. Vertebral bodies were recrushed to measure their augmented strength and stiffness. Anterior, posterior, left, and right lateral heights were measured initially, after augmentation, and after recompression. RESULTS: Lateral and central 3.5-mL injections of cement restored strength, whereas 7.0-mL injections significantly increased strength compared with initial values. The stiffness of vertebral bodies receiving central 3.5-mL injections was significantly less than it was initially, although the stiffness of bodies receiving 3.5-mL laterally was not significantly different from initial values. Initial and posttreatment stiffness values did not significantly differ in vertebral bodies receiving 7.0-mL, lateral or central injections. Vertebral heights did not significantly differ between the augmented and the final compression states in any location. Height loss between central and lateral injections did not differ significantly. CONCLUSION: Vertebral bodies in which cement is placed laterally do not appear to be at risk for collapse on the unaugmented side.

Aged↗

PubMed1990

[CT evaluation of bone mineral density (BMD) of lumbar spine in patients after gastrectomy].

The late postoperative complications in patients after gastrectomy include anemia and metabolic bone disorders. We studied to determine whether gastric surgery is associated with metabolic bone disease. Vertebral BMD was measured in 55 patients after gastric resection by using DEQCT (dual energy quantitative CT). Forty patients were symptomatic, having bone or joint pain, history of bone fracture, or dental caries. The control group consisted of 161 patients without metabolic bone disorders. Forty percent of the patients with either the symptoms or history of bone fracture or dental caries, and 20% of the patients without the symptoms or the history showed decreased BMD. BMD was significantly lower in males in their 60s and in females in their 50s and 70s than BMD in age-matched control groups. When male subjects were grouped according to the years following the operation (1-5, 6-10, 11-15, 16-20 years), BMD was found to be decreased in 27%, 29%, 40% and 50% of the patients after surgery. Higher incidence of decreased BMD was found in the patients after total gastrectomy when compared with those after subtotal gastrectomy. Among the patients with subtotal gastrectomy, the incidence of decreased BMD was higher in patients with Billroth II anastomosis than in those with Billroth I anastomosis. In cases with compression fracture on thoracolumbar radiographs, BMD was significantly lower in comparison with cases with no fracture. It was difficult to differentiate between osteomalacia and osteoporosis only by the thoracolumbar radiographs.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

[Medico-surgical treatment of Pott's disease. Our attitude in Gabon].

Twenty-six of 95 adults treated for tuberculous spondylitis, between 1982 and 1993, underwent surgery. Twenty-one exhibited neurological deficits: radicular deficits: 4, and progressive spinal cord syndromes: 17 (incomplete, 13, complete, of acute onset: 4). Vertebral body compression fracture was the most prominent finding. Indications for surgery were neurologic: 11, mechanical: 1, etiologic: 1, and mixed: 13. Twelve patients had vertebrectomies, 3 laminotomies and 11 laminectomies. The average follow-up was 23 months. The neurological recovery was complete in 16 cases, partial in 4 cases and unchanged in one case. Bony consolidation occurred after 3-5 months. The medicosurgical treatment produced a very high cure rate, so rapidly, that it became the treatment of choice in our setting. Moreover, that allows to specify the diagnosis. Anterior decompression and fusion is recommended in the cervical and lumbar spine. In the thoracic segment, significant kyphosis is infrequent, so that surgical correction is rarely necessary. Laminotomy may occasionally be indicated for posterior decompression for abscess. Laminectomy is now preferred for uncommon cases of thoracolumbar posterior compression by tuberculous arachnoiditis or associated posterior vertebral tuberculosis. Indications for open biopsy are discussed.

Adult↗