Atraumatic femoral head necrosis: a biomechanical, histological and radiological examination compared to primary hip osteoarthritis.

INTRODUCTION: Atraumatic necrosis of the femoral head (AFHN) is a common disease with an incidence of 5000-7000 middle-aged adults in Germany. There is no uniform consensus in the literature regarding the configuration of the bone in AFHN. The clinical picture of our patients varies from very hard bone, especially in idiopathic findings, and rather soft bone in cortisone-induced necrosis. A better understanding of the underlying process could be decisive for establishing a morphology-dependent approach. The aim of this study is the closer examination of the condition of the bone in the AFHN compared to the primary hip osteo arthritis (PHOA). MATERIALS AND METHODS: The preparations were obtained as part of elective endoprosthetic treatment of the hip joint. Immediately after sample collection, thin-slice CT of the preserved femoral heads was performed to determine the exact density of the bone in the necrosis zone. Reconstruction was done in 0.8-1 mm layers in two directions, coronary and axial, starting from the femoral neck axis. Density of the femoral heads was determined by grey value analysis. The value in Hounsfield units per sample head was averaged from three individual measurements to minimize fluctuations. For biomechanical and histomorphological evaluation, the samples were extracted in the load bearing zone perpendicular to the surface of the femoral head. Group-dependent statistical evaluation was performed using single factor variance analysis (ANOVA). RESULTS: A total of 41 patients with a mean age of 64.44 years were included. The mean bone density of the AFHN samples, at 1.432 g/cm3, was about 7% higher than in the PHOA group with a mean value of 1.350 g/cm3 (p = 0.040). The biomechanical testing in the AFHN group showed a 22% higher-but not significant-mean compressive strength (20.397 MPa) than in the PHOA group (16.733 MPa). On the basis of histological analysis, no differentiation between AFHN and PHOA samples was possible. CONCLUSIONS: The present study (NCT, evidence level II) shows that AFHN has a very well detectable higher bone density compared to PHOA. However, neither biomechanical stress tests nor histomorphological evaluation did show any significant difference between the groups. The results allow the conclusion that there is no "soft" necrosis at all in the AFHN group.

Prognostic value of baseline and early response FDG-PET/CT in patients with refractory and relapsed aggressive B-cell lymphoma undergoing CAR-T cell therapy.

PURPOSE: Chimeric antigen receptor (CAR)-T cells are a viable treatment option for patients with relapsed or refractory (r/r) aggressive B-cell lymphomas. The prognosis of patients who relapse after CAR-T cell treatment is dismal and factors predicting outcomes need to be identified. Our aim was to assess the value of FDG-PET/CT in terms of predicting patient outcomes. METHODS: Twenty-two patients with r/r B-cell lymphoma who received CAR-T cell treatment with tisagenlecleucel (n = 17) or axicabtagene ciloleucel (n = 5) underwent quantitative FDG-PET/CT before (PET-0) and 1 month after infusion of CAR-T cells (PET-1). PET-1 was classified as complete metabolic response (CMR, Deauville score 1-3) or non-CMR (Deauville score 4-5). RESULTS: At the time of PET-1, 12/22 (55%) patients showed CMR, ten (45%) patients non-CMR. 7/12 (58%) CMR patients relapsed after a median of 223 days, three of them (25%) died. 9/10 (90%) non-CMR patients developed relapse or progressive disease after a median of 91 days, eight of them (80%) died. CMR patients demonstrated a significantly lower median total metabolic tumor volume (TMTV) in PET-0 (1 ml) than non-CMR patients (225 ml). CONCLUSION: Our results confirm the prognostic value of PET-1. 42% of all CMR patients are still in remission 1 year after CAR T-cell treatment. 90% of the non-CMR patients relapsed, indicating the need for early intervention. Higher TMTV before CAR-T cell infusion was associated with lower chances of CMR.

Vital Hepatic Lymphoma Residuum or Excessive Immune Response? Challenging Treatment Decisions in a Patient With Systemic Lupus Erythematosus and Liver-Dominant Diffuse Large B-Cell Lymphoma: Case Report.

A 28-year-old female patient with active and difficult-to-treat systemic lupus erythematosus (SLE) was diagnosed with liver-dominant diffused large B-cell lymphoma. Repeated response 18F-FDG-PET studies showed persistently high, and, despite intensified immunochemotherapy, further increasing metabolic activity of one of the hepatic lymphoma residuals, whereas all other initial lymphoma manifestations had achieved complete metabolic remission. As biopsy of the 18F-FDG-PET-positive liver residual turned out to be inconclusive, complete resection was performed. Subsequent histopathological examination, however, revealed only necrotic tissue. Thus, no further lymphoma treatment was scheduled. The patient undergoes regular surveillance and is disease-free 13 months after resection. Similarly, treatment of SLE is no longer required due to lack of activity already after the first two cycles of lymphoma treatment. The case shows how closely SLE and diffused large B-cell lymphoma can be connected and stresses the importance of interdisciplinary treatment approaches. In the future, artificial intelligence may help to further classify 18F-FDG-PET-positive lymphoma residuals. This could lead to an increase of the positive predictive value of interim- and end-of-treatment 18F-FDG-PET. The patient's point of view enables another instructive perspective on the course of treatment, which often remains hidden to treating physicians due to lack of time in clinical routine.

Nocardiosis mimicking lung cancer in a heart transplant patient with end-stage renal disease.

Nocardiosis is a rare bacterial opportunistic infection that most commonly manifests as lung disease. However, disseminated infection and abscess formation can occur. Due to diverse radiographic findings and difficult cultivation it is not an easy diagnosis to make. Antibiotics such as Trimethoprimsulfamethoxazole alone or in combination with imipenem or imipenem in combination with amikacin need to be administered over a period of at least six to twelve weeks. We report a case of a 64-year old female heart transplant recipient requiring dialysis who suffered from dyspnea and a productive cough among other symptoms. Computed tomography revealed a tumor in the left upper lobe suggesting lung cancer. Both transbronchial and transthoracic biopsy could not confirm a malignant disease. Finally, Nocardia nova was isolated from a bronchoalveolar lavage and specific antibiotic treatment was initiated. As a result, the mass in the left upper lobe significantly regressed after a few weeks.

Invasive stratified mucin-producing carcinoma (i-SMILE) of the uterine cervix: report of a case series and review of the literature indicating poor prognostic subtype of cervical adenocarcinoma.

PURPOSE: Invasive stratified mucin-producing carcinoma (i-SMILE) represents a recently recognized subtype of cervical adenocarcinoma (AC) developing in a background of a stratified mucin-producing intraepithelial lesion (SMILE). Clinical and prognostic data on i-SMILE are limited. METHODS: We report a series of five cases with histopathological, immunohistochemical (p16) and PCR analyses. The cases as well as the patients previously published in the literature were reviewed for follow-up information. RESULTS: Thirteen cases were identified. The mean age of 47.1 years (range 34-66) was not different from the usual type of cervical AC. 10/13 cases presented with tumors > 2 cm and a polypoid-exophytic appearance. Regardless of tumor size and stage of the disease, 7 out of 11 patients developed recurrent disease after a mean of 7.8 months (range 6 weeks-36 months). Five patients developed distant metastases (three of them in the lungs). Five out of the 11 informative cases died of the disease. All reported cases were positive for high-risk HPV (mainly HPV type 18) and associated with p16-overexpression. CONCLUSION: i-SMILE represent a distinct subtype of invasive endocervical AC, associated high-risk HPV infection and strong p16-overexpression. Clinically, i-SMILE may represent an aggressive tumor with early recurrent disease and substantial risk of distant metastatic disease, especially to the lungs.

Radiological and clinical patterns of myeloid sarcoma.

Background Myeloid sarcoma (MS), also known as granulocytic sarcoma or chloroma, is a solid tumor of extramedullary localization composed of malignant primitive myeloid cells. The purpose of the study was to identify clinical and imaging features in a large patient sample. Patients and methods Overall, 71 cases (34 females (47.9%) and 37 males (52.1%) with a median age of 56 (± 16 years) of histopathologically confirmed myeloid sarcoma were included into this study. The underlying hematological disease, occurrence, localizations and clinical symptoms as well as imaging features on computed tomography and magnetic resonance imaging were investigated. Results In 4 cases (5.63%) the manifestation of MS preceded the systemic hematological disease by a mean value of 3.8 ± 2.1 months. In 13 cases, first presentation of MS occurred simultaneously with the initial diagnosis of leukemia, and 51 patients presented MS after the initial diagnosis of the underlying malignancy with a mean latency of 39.8 ± 44.9 SD months. The visceral soft tissue was affected in 26 cases, followed by the cutis/subcutis was affected in 21 cases. Further localizations were bones (n = 13), central nervous system (n = 9), lymph nodes (n = 4) and visceral organs (n = 9). Conclusions MS is a rare complication of several hematological malignancies, predominantly of acute myeloid leukemia, which can affect any part of the body. In most cases it occurs after the diagnosis of the underlying malignancy, and affects frequently the cutis and subcutis.

Endocervical adenocarcinoma in situ (AIS) with ovarian and pulmonary involvement: report of a case and review of the literature suggesting a "seed and soil hypothesis".

PURPOSE: Cervical cancer metastases to the ovary may occur with advanced tumor stage, deep cervical stromal involvement and corpus involvement. Endocervical adenocarcinoma in situ (AIS) with ovarian involvement is exceptionally rare with about twelve reported cases. METHODS: Here we present a case of endocervical AIS with ovarian and pulmonary involvement 39 months after the initial diagnosis. The characteristics of that case were compared and summarized with the eleven previously published cases. RESULTS: The patients' age ranged between 30 and 40 years (median 37.4 years). The time interval between the diagnosis of AIS and ovarian involvement was 26.7 months (range 2-84 months). Majority of the patients are alive without evidence of disease after a median time of 63.4 months (range 9-156 months). All reported cases were positive for high-risk HPV which was associated with strong p16 expression on immunohistochemistry. CONCLUSIONS: The ovarian involvement by endocervical AIS suggests the concept of a transtubal spread of the neoplastic cervical cells with or without previous colonization within the endometrium without evidence of invasive growth, suggesting a seed and soil spread of the disease. In cases with ovarian involvement by the AIS and without additional extragenital spread, the prognosis may be favorable.

Reduced bone mineral density and altered bone turnover markers in patients with non-cirrhotic chronic hepatitis B or C infection.

AIM: Previous studies suggest that loss of bone mineral density (BMD) frequently occurs in patients with chronic viral liver disease, presenting with histologically proven liver cirrhosis. However, little is known about the occurrence of bone disease in non-cirrhotic patients with chronic hepatitis B or C. Therefore, it was the aim of this study to evaluate this particular population for BMD and bone turnover markers. METHODS: Biochemical markers of bone turnover and BMD were measured in 43 consecutive patients with HCV (n = 30) or HBV (n = 13) infection without histological evidence for liver cirrhosis. Mean age was 49 years (range 26-77 years). BMD was measured by dual X-ray absorptiometry in the femoral neck (FN) and the lumbar spine (LS) region. In addition, bone metabolism markers were measured. RESULTS: BMD was lowered in 25 (58%) of the patients with chronic hepatitis B or C (FN: 0.76 (0.53-0.99); LS: 0.96 (0.62-1.23) g/cm(2)). Eight (32%) osteopenic patients were diagnosed with osteoporosis. Bone-specific alkaline phosphatase (P = 0.005) and intact parathyroid hormone (iPTH) (P = 0.001) were significantly elevated in the more advanced stages of fibrosis. Mean T-score value was lower in patients with chronic hepatitis C as compared to patients suffering from chronic hepatitis B; however, the difference was not statistically significant (P = 0.09). CONCLUSION: There was a significantly reduced BMD in non-cirrhotic patients with chronic hepatitis B or C infection. Alterations of bone metabolism already occurred in advanced liver fibrosis without cirrhosis. According to our results, these secondary effects of chronic viral hepatitis should be further investigated.

Are radiographic indices reliable indicators for quantitative bone mineral density and vitamin D status after femoral neck fractures? A retrospective study in 112 elderly patients.

BACKGROUND: Radiographic parameters and indices obtained from hip x-rays are a potential tool to promptly estimate bone quality in elderly hip fracture patients. Preoperative decision in whether to use cemented or cement augmented implants might be supported by this information and thus improve patient safety. Subsequently, this study was conducted to evaluate radiographic parameters as a prescreening tool for bone quality. METHODS: A retrospective analysis of 112 elderly patients with a femoral neck fracture after low-energy trauma was performed (81 % female, 19 % male). Three radiological indices were calculated on hip x-rays: cortical index antero-posterior CTI (ap), cortical index lateral CTI (lat) and canal to calcar ratio CCR. These indices were analyzed for correlations with DXA T-Scores and serum 25-hydroxyvitamin D (25(OH)D) using the Spearman test. RESULTS: Median age of patients was 80 (IQR 72-86) years. A linear correlation was found for CTI (lat) and T-Score at the total hip (p < 0.001, r = 0.589), femoral neck (p = 0.005, r = 0.405) and the lumbar spine (p = 0.002, r = 0.299). A significant correlation was also indicated between CTI (lat) and 25(OH)D (p = 0.002, r = 0.293). CTI (lat) at a cut-off level of 0.4 showed a sensitivity of 79 % and a specificity of 56 % in predicting a T-score ≤ -2.5 at the total hip. Gender specific analysis revealed a higher sensitivity (100 %) and specificity (73 %) of CTI (lat) at a cut-off level of 0.4 for men. For severe vitamin D deficiency (<10 ng/ml) sensitivity and specificity were 75 % and 65 %. CONCLUSION: Radiographic indices as the CTI (lat) exhibit a direct correlation to BMD and serum 25OH vitamin D levels. A CTI (lat) cut-off level of 0.4 is recommended for identifying patients at risk of osteoporosis expressed by T-Scores ≤ -2.5 and severe vitamin D deficiency.

Pancreatic neuroendocrine tumor with ectopic adrenocorticotropin production upon second recurrence.

We present a 54-yr-old woman with ectopic corticotropin syndrome caused by a neuroendocrine tumor of the pancreas. At initial presentation, the patient suffered from diarrhea, heartburn, and nonspecific abdominal pain. There was no evidence of Cushing's syndrome. A neuroendocrine tumor in the head of the pancreas with metastases into peripancreatic lymph nodes was diagnosed and completely resected. Fourteen months later, abdominal computed tomography and scintigraphy with (111)In-labeled octreotide suggested relapse of the tumor. The patient again had no evidence of Cushing's syndrome. A second in toto tumor resection was performed. Another 8 months later, the patient developed forgetfulness, depressive episodes, muscle weakness, new-onset hypertension, hypokalemia, plethora, diabetes mellitus, polyuria, and weight loss. Endocrine testing suggested a source of ectopic ACTH production. An octreotide scan showed an intense uptake ventromedial of the left kidney, an area that showed a mass lateral of the superior mesenteric artery on abdominal magnetic resonance imaging. A complete pancreatectomy with splenectomy and left-sided adrenalectomy were performed. At this second relapse, this neuroendocrine tumor clinically had changed its hormonal profile. Immunohistochemically, in contrast to primary tumor and first relapse, we found strong immunostaining for ACTH in tumor cells of the second relapse and a MIB-1 index greater than 20%. To our knowledge, this is the first report describing a pancreatic neuroendocrine tumor that started to secrete ACTH de novo at the time of the second relapse after two former complete tumor resections. This case underscores the pluripotency of neuroendocrine tumor cells and the importance of keeping in mind a possible shift in hormone production during tumor evolution and progression.

A patient with a large recurrent pheochromocytoma demonstrating the pitfalls of diagnosis.

BACKGROUND: A 59-year-old man presented for a follow-up, 6 years after surgery for a large pheochromocytoma. He had suffered from diabetes mellitus, hypertension and abdominal pain in the right flank region. Previous postoperative follow-up did not reveal tumor recurrence. INVESTIGATION: Measurement of plasma free metanephrine and normetanephrine by high-performance liquid chromatography and radioimmunoassay; 123I-metaiodobenzylguanidine (MIBG) scintigraphy; hybrid 123I-MIBG single-photon emission CT (SPECT)-CT; MRI; testing for plasma norepinephrine and epinephrine; intraoperative ultrasonography; histological staining for chromogranin A and synaptophysin; and postoperative 18F-dihydroxyphenylalanine (DOPA) PET scan. DIAGNOSIS: Recurrent pheochromocytoma. MANAGEMENT: Laparotomy with tumor resection. Reduction of antihypertensive medications. Further follow-up by MRI, hybrid 123I-MIBG SPECT-CT and testing for plasma catecholamines and free metanephrines.

Osteoporosis in juvenile idiopathic arthritis--a practical approach to diagnosis and therapy.

In all subgroups of juvenile idiopathic arthritis, a decrease in bone mass has been described in a high percentage of children. Recently, new pathogenetic concepts have identified muscle mass as the strongest predictor of bone mass and bone is now recognized as part of the musculoskeletal system. In addition, the sophisticated use of bone densitometry in pediatrics, including new measurement techniques, has provided the tools for a reliable assessment. A standardized diagnostic approach to the musculoskeletal system, including prophylaxis and therapy, is, therefore, mandatory in all children with JIA who do not achieve rapid remission. In this review, diagnostic and therapeutic options are being described and possibilities to incorporate them into clinical practice are suggested.

Percutaneous transgastric irrigation drainage in combination with endoscopic necrosectomy in necrotizing pancreatitis (with videos).

BACKGROUND: Endoscopic drainage of pancreatic acute and chronic pseudocysts and pancreatic necrosectomy have been shown to be beneficial for critically ill patients, with complete endoscopic resolution rates of around 80%. OBJECTIVE: Our purpose was to describe an improved endoscopic technique used to treat pancreatic necrosis. DESIGN: Case report. SETTING: University hospital. PATIENTS AND INTERVENTIONS: Two patients with large retroperitoneal necroses were treated with percutaneous transgastric retroperitoneal flushing tubes and a percutaneous transgastric jejunal feeding tube by standard percutaneous endoscopic gastrostomy access in addition to endoscopic necrosectomy. RESULTS: Intensive percutaneous transgastric flushing in combination with percutaneous normocaloric enteral nutrition and repeated endoscopic necrosectomy led to excellent outcomes in both patients. LIMITATIONS: Small number of patients. CONCLUSIONS: The "double percutaneous endoscopic gastrostomy" approach for simultaneous transgastric drainage and normocaloric enteral nutrition in severe cases of pancreatic necroses is safe and effective. It could be a promising improvement to endoscopic transgastric treatment options in necrotizing pancreatitis.

Diagnosis of aspergilloma in a pleural cavity (persistent pneumothorax) using classic imaging methods.

The diagnosis of pulmonary aspergillosis is based on serum-analysis, as well as histological and microbiological analysis of bronchial lavage and transbronchial biopsies. When Aspergillus develops within a preformed cavity, however, these tests are likely to be negative. In this situation, classic imaging techniques such as chest X-ray and high resolution-computed tomography (HR-CT) can be of great diagnostic use. We here describe the case of a 62-year-old woman with a history of breast cancer and subsequent ablation of the left breast and radiotherapy. The case demonstrates an example of a pleuropulmonary aspergilloma, in which sero- and micro-biological detection failed. Thorax HR-CT exhibited the cavity, a small persistent pneumothorax, partially filled by an oval density. This density clearly dislocated according to gravity following a positional change of the patient from supine to prone. The density thus revealed mobility which was typical of aspergilloma. Following excision, this diagnosis was confirmed. A density within a cavity may be differentiated by its mobility from differential diagnoses such as lung cancer which would not be expected to exhibit mobility.