Nephrotic Syndrome in the Elderly

Though the nephrotic syndrome is generally believed to be uncommon in the elderly, patients aged 60 years or more accounted for 25 out of 100 consecutive adult cases. Six (24%) of these had the minimal change lesion, compared with 16% of the younger adults. The incidence of membranous glomerulonephritis was similar in the two age groups, but proliferative glomerulonephritis was more common in the younger (29%) than in the older group (16%). Amyloidosis did not have a higher incidence in the higher age group. Five of the elderly patients with minimal change lesion were treated with prednisone—in four a complete remission from the nephrotic syndrome followed, while the fifth patient''s course is unknown.These results suggest that, when the patient''s other circumstances allow, the nephrotic syndrome in an elderly patient should be investigated and managed as in younger age groups.     

Cytology of primary cutaneous Langerhans cell histiocytosis with a malignant phenotype. A case report

BACKGROUND: Langerhans cell histiocytosis (LCH) is a proliferative disorder of Langerhans cells, but the nature of LCH, whether reactive, benign, or malignant and neoplastic, is controversial. We encountered a case of LCH showing a malignant phenotype initially localized in the skin of an elderly woman. Since there is no other report on the cytologic appearance of primary cutaneous LCH or on LCH with a malignant phenotype, we compared the cytologic features of this case with those of benign cases at other sites reported in the literature. CASE: A 74-year-old woman presented with a gradually enlarging and partially ulcerated skin lesion expanding both sides of her right hand. On histologic and ultrastructural analyses of surgically resected tissue, we diagnosed the lesion as Langerhans cell histiocytosis originating in the skin. Although the patient had no recurrence or metastases for six months after surgical resection of the primary skin lesion and radiation therapy, the tumor extended multisystemically, and the patient died of multiple organ failure 14 months after the initial diagnosis. CONCLUSION: Imprint and scrape cytology of multiple skin lesions six months after surgery was useful in immediately diagnosing the recurrent LCH. The tumor cells had indented, twisted or grooved nuclei, and some had intranuclear inclusions. Immunocytochemically the cells were positive for CD1a and S-100 protein. Numerous eosinophils were seen in the background.     

Locomotion of T cells from patients with cutaneous T-cell lymphoma (Sezary syndrome and mycosis fungoides)

Peripheral blood T cells from eight patients with cutaneous lymphoma (four each with Sezary syndrome or mycosis fungoides) and T cells from skin tumor of one patient each with Sezary syndrome or mycosis fungoides were studied for their locomotor responses to the chemoattractant, casein. Nonmalignant peripheral blood T cells from each patient with mycosis fungoides moved normally. Malignant T cells from skin tumor of patients with mycosis fungoides or Sezary syndrome did not move in the presence of casein. Peripheral blood malignant T cells (Sezary cells) from three of four patients with Sezary syndrome either moved very poorly or did not move at all. The circulating Sezary cells from the fourth patient with Sezary syndrome responded moderately to the chemoattractant, casein. Two of three patients with Sezary syndrome with poor or no locomotor response of T cells underwent therapeutic leukopheresis without any demonstrable effect on their skin infiltration. The patient whose malignant T cells demonstrated moderate locomotor response to casein had a leukemic blast crisis and at that time her skin became free of malignant cells. A repeat study of her circulating T cells at that time demonstrated almost normal locomotor response to casein. These results demonstrate that the locomotor properties of malignant T cells in patients with Sezary syndrome may have prognostic significance.     

Cushing's syndrome in childhood

A patient with Cushing''s syndrome whose clinical manifestations began at approximately 9 years of age was followed for a period of four years. Initial laboratory studies revealed urinary 170HCS and 17 KS levels which were elevated for her age, with a normal diurnal variation of plasma cortisol and normal suppression of urinary 170HCS by 1.5 mg. of dexamethasone daily. It was not until four years after the onset of the disease that laboratory studies unequivocally supported the diagnosis of Cushing''s syndrome resulting in definitive therapy. Clinical features consisted primarily of cessation of growth, obesity, and hirsutism, with no evidence of protein depletion. It is suggested that the clinical and laboratory features of Cushing''s syndrome in childhood may present differences from those found in the adult. Failure to recognize these differences may result in delay in therapy with subsequent persisting stigmata of the disorder.     

青少年GATA2缺陷继发骨髓增生异常综合征一例并文献复习

摘要 目的：提高对青少年GATA2缺陷继发骨髓增生异常综合征（MDS）疾病的认识。方法：回顾性分析我院收治的1例青少年GATA2缺陷继发MDS患者的诊疗过程,并结合相关文献进行复习总结。结果：患者男,17岁,2018年6月于我科诊断为MDS(MDS-EB-I,IPSS中危-1;WPSS高危;IPSS-R高危),继发骨髓纤维化。完善血液遗传全外显子基因检查提示患者GATA2基因突变。修正诊断为GATA2缺陷综合征、继发MDS( MDS-EB-I,IPSS中危-1;WPSS高危;IPSS-R高危) 、继发骨髓纤维化。完善患者姐姐血常规检查提示白细胞轻度减少,检查患者姐姐GATA2基因检测到GATA2基因错义突变。患者治疗期间反复出现多部位感染。进一步检查患者父母GATA2基因提示患者父亲GATA2基因存在错义突变。患者GATA2基因突变系父系遗传。结论：对于青少年MDS患者,应对其进行血液遗传学全外显子基因检查以确认其有无先天性疾病;对于存在先天性基因突变的患者,建议行家系筛查,并尽早行造血干细胞移植治疗。     

Gastric carcinoma and thrombotic thrombocytopenic purpura: association with plasma immune complex concentrations.

A patient with metastatic adenocarcinoma of the stomach developed microangiopathic haemolytic anaemia, thrombocytopenia, renal insufficiency, and fluctuating neurological abnormalities in association with appreciably raised plasma concentrations of immune complexes. This syndrome, similar to thrombotic thrombocytopenic purpura, occurred while the tumour was in sustained objective remission after successful treatment with fluorouracil, doxorubicin, and mitomycin. Reversal of the syndrome was achieved with plasmapheresis, azathioprine, corticosteroids, and antiplatelet treatment; this response was paralleled by a reduction in immune complex concentration, suggesting an immune aetiology for the syndrome. Antibodies eluted from the immune complexes reacted with 50% of cells from the gastric cancer but less than 10% of cells from normal gastric mucosa. There was no reactivity with either carcinoembryonic antigen or mitomycin. A 17S immune complex reacted with a glycoprotein from the patient''s autologous platelets and produced platelet aggregation. It is postulated that reducing the tumour and the pre-existing state of antigen excess by chemotherapy allowed soluble antigen-antibody complexes to form and the syndrome to develop.     

Controlled trial of plasma exchange in treatment of Raynaud's syndrome.

Twenty-seven patients with Raynaud''s syndrome had their digital vessel patency assessed by Doppler ultrasound after different thermal stresses. Digital vessel patency rates differed significantly after stresses at 15 degrees C and 45 degrees C. In a randomised controlled trial placebo and heparin had no effect either on patients'' symptoms or on the patency of their digital vessels. Plasma exchange improved both symptoms and vessel patency rates at 15 degrees C and 21 degrees C. Improvement in seven out of eight of these patients has been maintained for six months. Assessing digital vessel patency by Doppler techniques allow continuous, atraumatic, and safe evaluation of the effects of different methods of treatment on the patency of the digital vessels and has helped to indicate that plasma exchange is a useful adjunct in the management of patients with severe Raynaud''s syndrome.     

Immunostimulation and Immunoinhibition of Premalignant Lesions

Background

The immune reaction may be either stimulatory or inhibitory to tumor growth, depending upon the local ratio of immune reactants to tumor cells.

Hypothesis

A tumor-stimulatory immune response may be essential for survival of a neoplasm in vivo and for the biological progression from a premalignant lesion to a malignancy. Neither a positive nor a negative correlation between the magnitude of an immune-cell infiltrate and a cancer's prognosis can reveal whether the infiltrate was stimulating or inhibiting to the tumor's growth unless the position on the nonlinear curve that relates tumor growth to the magnitude of the immune reaction is known.

Discussion

This hypothesis is discussed in relation to the development of human malignant melanomas and colorectal cancers.     

A GMP-compliant protocol to expand and transfect cancer patient T cells with mRNA encoding a tumor-specific chimeric antigen receptor

Chimeric antigen receptors (CARs), which combine an antibody-derived binding domain (single chain fragment variable) with T-cell-activating signaling domains, have become a promising tool in the adoptive cellular therapy of cancer. Retro- and lenti-viral transductions are currently the standard methods to equip T cells with a CAR; permanent CAR expression, however, harbors several risks like uncontrolled auto-reactivity. Modification of T cells by electroporation with CAR-encoding RNA to achieve transient expression likely circumvents these difficulties. We here present a GMP-compliant protocol to activate and expand T cells for clinical application. The protocol is optimized in particular to produce CAR-modified T cells in clinically sufficient numbers under full GMP-compliance from late-stage cancer patients. This protocol allows the generation of 6.7 × 10⁸ CAR-expressing T cells from one patient leukapheresis. The CAR-engineered T cells produced pro-inflammatory cytokines after stimulation with antigen-bearing tumor cells and lysed tumor cells in an antigen-specific manner. This functional capacity was maintained after cryopreservation. Taken together, we provide a clinically applicable protocol to transiently engineer sufficient numbers of antigen-specific patient T cells for use in adoptive cell therapy of cancer.     

Exophytic growth of a neglected giant subcutaneous Leiomyosarcoma of the lower extremity. A case report

Background

Superficial leiomyosarcoma is an exceedingly uncommon malignant tumor which could be located either to cutaneous or subcutaneous tissues. Increased mass size and depth, advanced tumor staging and inadequate surgical excision are the main prognostic factors for poor result.

Case presentation

We report a rare case of a 71-year-old man with an extensive exophytic lesion (12 × 10 cm) in the anterior-medial side of the proximal right tibia. The lesion was painless and consistently neglected by the patient until a skin trauma caused ulceration of the affected area. Magnetic Resonance Imaging revealed a soft-tissue mass which was well defined from the surrounding bone and muscles. As initial biopsy in another hospital hadn't clarified the true nature of the lesion, new samples were taken and the diagnosis of leiomyosarcoma was established. Laboratory examination showed no distant metastasis and wide excision of the neoplasm was decided. After tumor resection, the remaining soft tissue and skin defect was covered with a gastrocnemius myocutaneous flap. The postoperative period was uneventful and wound healing was followed by local radiotherapy and systemic chemotherapy. At 3 years follow up, no recurrence or metastasis was identified and the patient was able to walk and stand without impairment of his ambulatory status.

Conclusion

Proper surgical management of soft tissue leiomyosarcoma continues to remain the cornerstone of treatment efficacy and the most important prognostic factor for patients' survival. Reconstruction of the remaining soft tissue defect should be always performed at the same operative time when removal of giant size tumors leaves an uncovered cavity with an inadequate sleeve of muscular and skin tissues.

     

Sarcome d’Ewing agressif apparaissant comme une lésion froide sur la scintigraphie osseuse

Ewing's sarcoma classically presents as a hot spot on bone scan as a result of increased vascularity of the tumor and new bone formation.PurposeWe report and analyze an uncommon pattern of a “cold” lesion in Ewing's sarcoma on bone scan and its physiopathologic significance.Case reportA 15-year-old boy complaining of thigh pain. CT scan evocated Ewing's sarcoma or osteitis. MRI evocated chronic osteitis. Scintigraphy showed a fairly intense and heterogeneous uptake on the femoral lesion and no abnormal uptake elsewhere. Biopsy showed none pathologic pattern. Three months later, a second biopsy concluded to Ewing's sarcoma. Bone scan showed a larger lesion with peripheral intense uptake centered by enlarged “cold” area in the left femoral diaphysis and no evident bone metastasis. The patient underwent chemotherapy and surgery. Three months later, bone scan showed extensive skeletal metastasis.ConclusionEwing's sarcoma appears usually as an intense lesion on bone scan. Nevertheless, decreased radiopharmaceutical uptake or “cold” lesion may be seen in aggressive Ewing's sarcoma with lytic tumor, growth of which is very rapid and bony reaction is minimal.     

Sarcomatoid hepatocellular carcinoma (SHC): a case report

Background

Sarcomatoid hepatocellular carcinoma (SHC) is a rare malignant hepatic tumor. Recurrent interventional therapies such as transcatheter arterial chemo-embolization (TACE), radiofrequency ablation (RFA), and percutaneous ethanol injection have been reported previously utilized in a majority of SHC cases. To date, the exact pathogenic mechanisms underlying sarcomatoid transformation of hepatocellular carcinoma (HCC) remain unknown.

Case presentation

In this study, we report a 68-year-old female SHC patient admitted to our hospital due to discrete abdominal distention for more than 20 days. Abdominal computed tomography (CT) with tri-phase enhancement revealed portal vein tumor thrombi (PVTT) and a left hepatic lobe lesion measuring 110.0 mm?×?160.0 mm. The patient subsequently underwent liver resection, after which pathological examination revealed proliferation of spindle-shaped SHC cells. A sarcomatoid, T4 stage carcinoma was eventually diagnosed. Forty-seven days after the operation, tri-phase enhanced CT detected extensive lesions in the liver, spleen, peritoneum, omentum majus, and mesentery, indicating SHC recurrence and metastases. Combination chemotherapy with pirarubicin and cisplatin was initiated for 1 cycle, but terminated due to resultant severe myelosuppression and medication intolerance. The patient was lost to therapy after 3 months of follow-up.

Conclusions

This case is unique because of hepatitis C virus infection. We should consider the possibility of this disease in patients with atypical clinical presentation.

     

Tenfibgen Ligand Nanoencapsulation Delivers Bi-Functional Anti-CK2 RNAi Oligomer to Key Sites for Prostate Cancer Targeting Using Human Xenograft Tumors in Mice

Protected and specific delivery of nucleic acids to malignant cells remains a highly desirable approach for cancer therapy. Here we present data on the physical and chemical characteristics, mechanism of action, and pilot therapeutic efficacy of a tenfibgen (TBG)-shell nanocapsule technology for tumor-directed delivery of single stranded DNA/RNA chimeric oligomers targeting CK2αα'' to xenograft tumors in mice. The sub-50 nm size TBG nanocapsule (s50-TBG) is a slightly negatively charged, uniform particle of 15 - 20 nm size which confers protection to the nucleic acid cargo. The DNA/RNA chimeric oligomer (RNAi-CK2) functions to decrease CK2αα'' expression levels via both siRNA and antisense mechanisms. Systemic delivery of s50-TBG-RNAi-CK2 specifically targets malignant cells, including tumor cells in bone, and at low doses reduces size and CK2-related signals in orthotopic primary and metastatic xenograft prostate cancer tumors. In conclusion, the s50-TBG nanoencapsulation technology together with the chimeric oligomer targeting CK2αα'' offer significant promise for systemic treatment of prostate malignancy.     

Current treatment of hepatitis C-associated rheumatic diseases

The hepatitis C virus (HCV) is both hepatotropic and lymphotropic, responsible for a great number of hepatic and extrahepatic immune-system disorders that comprise the so-called HCV syndrome. HCV-associated rheumatic diseases are characterized by frequent clinico-serological overlap; therefore, correct classification of individual patients is necessary before therapeutic decisions are made. This is particularly difficult to do, however, because of the coexistence of viral infection and complex autoimmune alterations. In this context, mixed cryoglobulinemia syndrome (MCs) represents the prototype of virus-related autoimmune-lymphoproliferative diseases. MCs can be treated at different levels by means of etiological treatment with antivirals (peg-interferon-alpha plus ribavirin) aimed at HCV eradication and/or pathogenetic/symptomatic treatments directed to both immune-system alterations and the vasculitic process (rituximab, cyclophosphamide, steroids, plasmapheresis, and so on). In clinical practice, the therapeutic strategy should be modulated according to severity/activity of the MCs and possibly tailored to each individual patient''s conditions. Cryoglobulinemic skin ulcers may represent a therapeutic challenge, which should be managed by means of both local and systemic treatments. HCV-associated arthritis should be differentiated from the simple comorbidity of HCV infection and classical rheumatoid arthritis. It may be treated with low doses of steroids and/or hydroxychloroquine; the use of biologics (rituximab) may be considered in more severe cases. Primary Sjögren''s syndrome is rarely associated with HCV infection, while sicca syndrome and myalgia are frequently detectable in hepatitis C patients, with or without cryoglobulinemic vasculitis. Other autoimmune rheumatic disorders (poly/dermatomyositis, polyarteritis nodosa, osteosclerosis, fibromyalgia, and so on) have been reported as potentially associated with HCV infection in patient populations from different countries, suggesting the role of genetic and/or environmental co-factors. The therapeutic approach to these disorders should be decided according to each individual patient''s evaluation, including hepatic, virological, and immunological findings.     

REGIONAL ISOLATION PERFUSION IN THE TREATMENT OF ADVANCED MALIGNANT DISEASE

Regional isolation perfusion with an alkylating agent was carried out in a small community hospital, using readily available equipment, ten times in nine cases of advanced malignant disease. Visible regression of tumor, either grossly or histologically, occurred in seven patients and decided subjective improvement occurred in five patients.The long range effect of the procedure could not be determined in the present series, not enough time having elapsed.Side effects included jaundice in four patients, massive necrosis of the tumor in one patient, nausea and vomiting in three patients, postoperative edema in five patients, wound infection in two patients, Horner''s syndrome in one patient, temporary alopecia in three patients, and depression of hemoglobin level in seven patients, of the leukocyte count in four patients and of the platelet count in four patients.A feature of the procedure used in the present series was a system of monitoring the escape of alkylating agent into the systemic circulation.     

Variation in response to dexamethasone of a patient with Cushing's syndrome.

A patient with Cushing''s syndrome due to a nonresectable chromophobe adenoma underwent external irradiation of the hypothalamic-pituitary area. The signs of Cushing''s syndrome ameliorated subsequently but recurred eventually, necessitating bilateral adrenalectomy 30 months after initial presentation. Response to dexamethasone suppression testing on four occasions varied greatly. These results may reflect alterations in sensitivity of the tumour or the hypothalamic-pituitary axis to feedback inhibition by glucocorticoids.     

Lung cancer following therapy for Hodgkin's disease

We describe a patient in whom lung cancer developed several years after he had received combined-modality therapy for Hodgkin''s disease. The literature concerning second malignant diseases, particularly thoracic tumours, that occur following combined-modality therapy for cancer is reviewed. It is important to recognize these entities, because chest symptoms or findings on x-ray films may be misinterpreted as representing late recrudescence of the first neo-plastic disease.