Resection of the trachea infiltrated by thyroid carcinoma

Twenty-four thyroid carcinoma patients with infiltration of the trachea were treated surgically. The histological diagnosis in these cases included papillary adenocarcinoma in 22 different patients, medullary carcinoma in one patient, and undifferentiated carcinoma in one patient. In 19 of the patients hemoptysis was noted, and dyspnea was present in ten patients. In 14 of the 24 patients the carcinoma was diagnosed by radiographs of the neck, while in seven patients it was demonstrated bronchoscopically. In three patients tracheal infiltration by thyroid carcinoma was diagnosed by biopsy of the tracheal wall at operation. When the tracheal wall was infiltrated by thyroid carcinoma, treatment consisted of circumferential resection of the involved segment of the trachea followed by an end-to-end anastomosis. Of the 24 patients, 17 survived and six died. In the 17 patients who survived, 13 were disease free. Of this number, six survived more than five years after the initial tracheal resection.     

Metabolism of quinine in children with global malnutrition

OBJECTIVE: To evaluate the frequency, predictive parameters and prognosis of urethral recurrence after cystoprostatectomy for urothelial bladder cancer. MATERIAL AND METHODS: From 1989 to 1994, 8 of a series of 185 patients (4.3%) treated by cystoprostatectomy for bladder carcinoma between 1988 and 1993 developed urethral recurrence revealed by urethral bleeding, with a follow-up of 6 to 36 months (m = 16). RESULTS: The initial bladder tumour was localized in 3 cases and multifocal in 5 cases. The posterior urethra was not involved in 5 cases, but presented lesions of CIS in 1 case and neoplastic infiltration also involving the prostate in 2 cases. These recurrences were treated by urethrectomy, as first-line treatment in 7 cases and after failure of endoscopic treatment in 1 case. A balanic recurrence required distal penectomy following insufficient urethral resection. The course was very rapidly unfavourable for 3 patients with generalized cancer and an intercurrent disease was fatal in 1 other case. With a follow-up of 12 to 44 months (m = 26), 4 patients are alive with no obvious signs of disease progression. CONCLUSION: The indications for prophylactic urethrectomy can be reserved to patients with positive urethral resection margins, provided all other cases are submitted to strict surveillance. In the context of a replacement bladder, it is essential to exclude neoplastic involvement of the posterior urethra or prostate, especially in patients previously treated by intravesical instillations.     

Effects of angiotensin II-receptor blockade with losartan on insulin sensitivity, lipid profile, and endothelin in normotensive offspring of hypertensive parents

BACKGROUND: Acute liver failure (ALF) secondary to malignant infiltration of the liver is rare and is diagnosed often only after death. AIMS: To determine diagnostic factors and particular clinical patterns of illness. METHODS: Review of case notes from all patients with ALF secondary to hepatic infiltration admitted to this unit over an 18 year period (1978-1995). RESULTS: From a total of 4020 admissions, 18 patients were identified with ALF attributable to hepatic infiltration. Mean age was 40.7 years. Aetiology was non-Hodgkin's lymphoma in nine patients, Hodgkin's disease in three, infiltrative metastatic carcinoma in four, and haemophagocytosis with no precipitant cause in two cases. Prodromal symptoms were non-specific, but occurred at least two to four weeks before onset of ALF, making the presence of such symptoms of value in differential diagnosis of the cause of ALF. Clinical examination and investigations were unhelpful in distinguishing these cases from more usual causes of ALF. Usually, the clinical course was of rapid deterioration and death from multiorgan failure, and only one patient survived. Diagnosis was made during life in 15 patients. Histology showed evidence of widespread hepatocellular necrosis, with diffuse infiltration by tumour cells rather than focal cellular aggregation. CONCLUSIONS: Only with accurate histological diagnosis from liver biopsy and institution of specific therapy early in the management of such patients will the best chance of recovery be achieved. In every case of ALF with prodromal symptoms or abnormal imaging, hepatic histology should be obtained by liver biopsy as soon as possible to diagnose infiltrative hepatic disease.     

The type of local treatment conditions the prognosis in patients with nonmetastatic Ewing's sarcoma of the extremities treated with adjuvant chemotherapy

The results obtained in 172 cases of non metastatic Ewing's sarcoma of the extremities are reported. The patients were advised to undergo surgical treatment, followed by radiotherapy (40-45 Gy) in case of inadequate surgical margins. 48 patients who refused surgical treatment, were locally treated with radiotherapy alone (50-65 Gy). With a mean follow-up of 8 years (R. 3-15) 101 patients (58.7%) are free of disease and 68 relapsed with metastases and/or local recurrence. A radio-induced bone sarcoma developed in two patients, one patient died of ADM cardiomyopathy. No differences in terms of risk factors were observed between patients who were or were not treated with surgery. A better DFS was observed in the patients treated with surgery (66.9%) in comparison with those treated with radiotherapy alone. The higher percentage of local recurrences observed in patients treated with radiotherapy alone seems to be responsible for the worse prognosis observed in these patients. The authors' conclusion is that the local control in patients with non metastatic Ewing's sarcoma should always be achieved by means of surgery.     

Studies on the method of the analysis of sapogenin. III. Coulometric titration of diosgenin (author''s transl)

Fifteen of 146 (10%) adult patients with non-Hodgkin's lymphoma showed clinical and pathologic evidence of involvement of the central nervous system (CNS): in 6 patients, the CNS lymphoma was present at the onset of disease, in 3 of them it was the only sign detected. In the remaining 9 cases, CNS involvement appeared during the course of systemic disease. In all cases symptoms related to infiltration of the CNS were associated with advanced disease (stage IV); bone marrow or bone involvement was found in 9 patients (60%). The histologic subtypes were mostly of high-grade malignancy according to the Kiel classification: immunoblastic (3), centroblastic (3), Burkitt type (2), lymphoblastic (1), LP immunocytoma in polymorphic variant (3), unclassifiable (3). The prominent signs and symptoms of CNS lymphoma are listed: the cranial nerve palsies are the most common finding. The principal means of detecting CNS involvement are discussed: cerebrospinal fluid cytology, brain scan and CAT scan were the most useful diagnostic procedures. The reported data allow identification of patients at high risk of CNS lymphoma: this includes histologies of high-grade malignancy, advanced stage of disease, and bone marrow or bone infiltration. Therefore, either intensive systemic chemotherapy or CNS prophylaxis are recommended for patients with high risk of CNS disease.     

Role of endorectal ultrasonography and CT in preoperative staging of rectal cancer. Personal experience]

We report our personal experience on endorectal US and CT in the preoperative staging of rectal carcinoma. Our series includes 64 cases (38 male and 26 female) evaluated with intrarectal sonography; 38 of these patients underwent also CT-study of the lower abdomen. Using both imaging techniques infiltration of the rectal wall and adjacent structures and lymph node involvement were studied. The results of our study refer to 58 patients who underwent endorectal US, 31 of whom studied also with CT. Referring to the T-parameter with ultrasound 41 correct diagnosis were obtained, in 13 cases the lesion was over-staged and in 4 cases understaged. The sensitivity, specificity and diagnostic accuracy was respectively 89.5%, 60% and 79.3%. With CT 23 diagnosis were correct, in 1 case the lesion was overstaged and in 7 cases understaged; sensitivity, specificity and diagnostic accuracy concerning rectal wall infiltration were respectively 72%, 83.3% and 74.2%. The evaluation of the N-parameter demonstrated low value of sensitivity with both US (15.8%) and CT (42.9%). Considering the results of our series, we feel that it is necessary to use both imaging techniques because results obtained are complementary referring to the T-parameter, although N-parameter were a little significant.     

Eosinophilic ulcer of the tongue

Two cases of tongue ulcers are presented. Histopathologic examination of biopsy specimens obtained from each case showed marked submucosal and muscular infiltration of polymorphonuclear eosinophils compatible with the diagnosis of eosinophilic ulcer of the tongue. The disease entity appears to be uncommon, yet, it should be recognized as benign since in both instances, healing was spontaneous.     

Surgical treatment of Basedow''s disease: total thyroidectomy

The Authors report their experience in the treatment of Graves disease. After a short review of the literature, the Authors stress the medical trait of such disease with possible spontaneous resolution. Therefore the number of cases surgically treated is necessarily low. Thirty patients, all with specific antibodies, were treated with total thyroidectomy. The therapy chosen and the results obtained are herein shown. No definitive hypoparathyroidism and inferior laryngeal nerve injuries were registered.     

Ewing's sarcoma of the ribs. A report from the cooperative Ewing's sarcoma study

31 patients with primary Ewing's sarcoma of the ribs were treated according to the protocols of CESS 81, CESS 86P and CESS 86. The results of treatment were reviewed and analysed. 24 patients presented with localised disease and 7 with regional disease. 20 of 24 localised cases and 6 of 7 regional cases underwent tumour resection. All but 2 localised cases received irradiation. The cumulative relapse-free survival (RFS) rate of 31 patients was 61% at 12.8 years. Patients with poor prognosis had tumour of the upper ribs (P = 0.0338), the posterior component of the ribs (P = 0.0597), or regional disease (P = 0.0001). Tumour size, existence of pleural effusion, type of the surgical margin and response to chemotherapy were not significant prognostic factors. Most of the localised cases could be controlled by combined treatment, but in regional cases prognosis remained poor.     

Tacalcitol ointment in the treatment of psoriasis vulgaris: a multicentre, placebo-controlled, double-blind study on efficacy and safety

Tacalcitol is a vitamin D analogue which ahs been developed for the therapy of psoriasis vulgaris. The treatment with a twice daily application of 2 micrograms/g ointment is efficacious and safe in Japanese patients. The objective of this randomized, placebo-controlled, intraindividual right-left comparison was to investigate the efficacy and safety of 8 weeks' therapy with a once daily application of a 4 micrograms/g tacalcitol ointment in Caucasian psoriatics. The data on 122 male and female patients were analysed. The score sum of erythema, infiltration and desquamation was influenced significantly more by tacalcitol ointment than by placebo (P < 0.0001) at every control point, starting from week 2. With regard to the individual symptoms of desquamation, infiltration and erythema, the treatment with tacalcitol was also superior to placebo treatment beginning at week 2. Qualitatively, the same results were obtained with the preference assessment of both treated body sides and also the global assessments of efficacy and benefit. Symptoms of local skin irritation which may be related to the active compound or the ointment base were reported by 12.3% of patients. In only one patient, irritation required discontinuation of tacalcitol treatment. Laboratory criteria, including serum calcium, serum phosphate and serum levels of calcitonin, parathormone, 1 alpha, 24-dihydroxyvitamin D3 and 25-hydroxyvitamin D3, did not reveal any changes of clinical relevance during or after treatment. Furthermore, the global assessment of tolerance was good or very good in more than 90% of cases. The results of this study demonstrate that the once daily application of a 4 micrograms/g tacalcitol ointment is an efficacious therapy for psoriasis vulgaris in Caucasian patients, and that its tolerance is good, wherever the lesion is located, including on the face.     

No advantages in the addition of ifosfamide and VP-16 to the standard four-drug regimen in the maintenance phase of neoadjuvant chemotherapy of Ewing's sarcoma of bone: results of two sequential studies

Between January 1988 and December 1990, 74 patients with localized Ewing's sarcoma of bone were treated with a new protocol that consisted of an initial 6-week period of chemotherapy with vincristine (VCR), adriamycin (ADM) and cyclophosphamide (EDX) followed by local therapy and additional chemotherapy with the same drugs previously indicated plus ifosfamide and VP-16. The rationale for the addition of ifosfamide and VP-16 to the four drugs of the standard chemotherapy of this tumor was that this drug combination was previously very effective in the treatment of metastases from Ewing's sarcoma even in patients who did not respond to cyclophosphamide. As local treatment all patients were offered surgery, when feasible (70 cases). Forty-three patients accepted and 27 refused. These patients, as the 4 patients in whom surgery was not considered feasible, were treated with radiation therapy alone (50-60 Gy). In the remaining patients amputation was performed in 4 cases, rotationplasty in 3 and resection in 36. Where conservative surgery was marginal or intralesional (30 cases), radiotherapy at lower doses (40-45 Gy) was also delivered. At a mean follow-up of 3.5 years (2-7), 43 patients (58%) remained continuously disease-free and 31 relapsed (29 with metastases and 2 with both metastases and local recurrences). These results do not differ from those obtained at our Institution in 98 patients treated between 1983 and 1988 with a neoadjuvant protocol in which only VCR, ADM, EDX and dactinomycin (DAC) were used (3-year continuously disease-free survival (CDFS) respectively of 54% and 55%). Despite the fact that these results came from a nonrandomized study, the Authors conclude that the addition of ifosfamide and VP-16 to the four-drug standard regimen did not improve the outcome of the patients with Ewing's sarcoma of bone which remains a lethal disease in about 50% of the cases. These findings stress the need to find more effective chemotherapeutic regimens for the associated treatment of this tumor.     

Surgical treatment of hydatid disease of the liver: an experience from outside the endemic area

BACKGROUND/AIMS: Hydatid disease is quite rare in European countries outside the endemic area around the Mediterranean Sea. Most of the cases observed in Central and Northern Europe occur in emigrants from the endemic area, whose number has been increasing over the last decade. In Switzerland about twenty-five new cases are being diagnosed per year, an incidence of about 0.33 cases per 10(5) inhabitants. Surgery remains the principal treatment modality of hydatid liver disease. There is still debate about conservative surgery as opposed to radical surgical treatment in which the cyst is totally removed including the pericyst by total cystoperi-cystectomy, partial hepatectomy or a combination of both. Surgeons working inside the endemic area tend to favor conservative methods, whereas those outside the endemic area have the tendency to favor radical surgery. This article reviews the results of surgery for liver hydatid disease obtained in a country outside the endemic area. PATIENTS AND METHODS: In our institution 24 patients (12 female, 12 male) have been treated for liver hydatid disease from 6/1983 to 2/1995. Twenty-two patients were immigrants from the endemic area. Surgery indication was primary liver hydatid disease in 23 patients, and recurrent disease in one. RESULTS: Twenty-one patients underwent radical procedures, and three were treated by cystectomy, unroofing and omentoplasty. Radical procedures were pericystectomy in 11 patients, partial hepatectomy in five and pericystectomy combined with partial hepatectomy in five. There was no operative mortality in 23 patients operated on for primary disease, but the only patient operated upon for recurrence died from anaphylactic shock. Eighteen of the 23 surviving patients could be followed up for a median time of 6.5 years (eight months to 12.5 years). Sixteen of 18 patients have remained free of recurrence. One has been reoperated for a retrocaval recurrence four years after right hepatectomy, and one patient is being observed for suspected recurrence after unroofing and omentoplasty. CONCLUSIONS: The policy of applying radical surgery whenever feasible can be followed with acceptable morbidity and near zero mortality. Radical surgery has, however, to be applied judiciously, and there is still an important role for conservative surgery.     

A case of mosaic Down''s syndrome with two Robertsonian translocations

A 15-year-old girl had bilateral corneal infiltration associated with diabetes insipidus which has been treated for 8 years. The correct diagnosis of histiocytosis X was obtained after histopathological examination. The strict correlation between pathological anatomy and clinical status favoured Hand-Schuller-Christian disease.     

Immunoblastic lymphadenopathy. A report of two cases

Two patients who had immunoblastic lymphadenopathy with clinical symptoms of fever, anemia, hypergammaglobulinemia, and enlarged lymph nodes were treated with chemotherapy. The lymph node biopsy specimens were originally interpreted as malignant processes because of severe immunoblastic and plasmacytic infiltration that practically obliterated the architecture of the lymph nodes. One patient recovered and was free of symptoms five years after clinical onset of the disease. The second patient died of massive gastrointestinal bleeding six weeks after the onset of disease and five weeks after administration of cytotoxic drug therapy. The cases illustrate the ineffectiveness and possible adverse effect of chemotherapy, as well as the importance of differentiation of immunoblastic lymphadenopathy from frankly malignant lymph node diseases.     

Technetium-99m-nitroimadazole uptake in a swine model of demand ischemia

BACKGROUND: Expression of changes in cell surface glycoprotein may correlate with the malignant potential and development of gastric carcinoma. Immunologic defense mechanisms of the host against the tumor can be effective in preventing the development of gastric carcinoma. The authors studied the effects of immunologic defense of the host against the tumor, using infiltration of S-100 protein positive dendritic cells (DC) as a marker. In cases with or without changes in the surface glycoprotein of tumor cells, determinations were made by binding of Helix pomatia agglutinin (HPA). METHODS: Paraffin blocks of 123 gastric carcinoma specimens were prepared for immunohistochemical staining with the antibody against HPA and S-100 protein. Clinicopathologic factors and patient prognosis were examined for each indicator. RESULTS: Patients with HPA positive tumors had a more aggressive character in several important prognostic aspects and poorer 5-year survival rates compared with patients with HPA negative tumors. The degree of infiltration of DC had no particular correlation with pathologic factors, and there was no significant difference between the prognosis of patients with slight and marked DC infiltration. In the HPA negative patients there was no significant difference in the 5-year survival rates between patients with slight and marked DC infiltration; however, in the HPA positive patients the 5-year survival rates of patients with marked infiltration of DC were higher. Further investigation showed that patients with marked DC infiltration had better 5-year survival rates than patients with slight DC infiltration, especially in patients with HPA positive and histologically advanced disease. CONCLUSIONS: Patients with a higher immunologic defense against cancer cells, as indicated by marked infiltration of DC, had a better prognosis in cases of gastric carcinomas of highly malignant potential, as indicated by a positive HPA.     

Impact of tumor extent and location on treatment outcome in patients with stage III non-small cell lung cancer treated with radiation therapy

The survival probability is 79% for patients with neuroblastoma stage 4S treated according to the German Society for Pediatric Oncology and Hematology (GPOH) treatment studies. Most of these patients (80%) have liver metastases. Patients are grouped according to their condition at diagnosis and tumour resectability to different risk groups (A, B, C). Chemotherapy is provided for patients who are initially diagnosed as critically ill, caused for example by excessive hepatomegaly due to liver metastases. The aim of this study is to clarify whether liver infiltration is associated with liver dysfunction and whether chemotherapy plays a role in this process. Hepatopathy was diagnosed when clinical signs were present and/or liver function tests revealed pathologic results. The charts of 48 patients (22 boys, 26 girls) diagnosed between 1990 and 1994 from the ongoing NB-90 treatment study were evaluated retrospectively. Median age at diagnosis was 52 days (range: 1-328). 41 patients (85%) had liver infiltration, 26 patients (54%) had bone marrow involvement and in nine patients (19%) skin metastases were found. 12 patients were in poor general condition at diagnosis (risk group C). 36 of 48 patients (75%) received chemotherapy, three children were treated with radiotherapy additionally, due to massive liver enlargement. 15 patients (31%) had signs of hepatic dysfunction at diagnosis or during their illness, 14 of these had liver metastases. All these 15 patients were treated with chemotherapy. 12 of 15 patients with hepatopathy were younger than two months at diagnosis. Five patients with liver dysfunction were not critically ill at diagnosis. Hepatomegaly > or = 6 cm was present in 10 of 15 patients with liver dysfunction. Hepatopathy was transient in eight patients, four patients died soon of multiorgan failure during progression of disease. Three children developed liver fibrosis with conversion to cirrhosis. Hepatopathy was correlated with distribution to risk groups (A and B (5/36) vs. C (10/12), p < 0.001). The appearance of hepatic dysfunction in patients with neuroblastoma stage 4S remains a serious problem especially for young children with excessive hepatic infiltration. Liver dysfunction was of short duration and reversible in most patients, however, even with age-adapted dosages of chemotherapy long-standing cases of hepatopathy were observed. A general recommendation for treatment strategy in this heterogeneous patient group is difficult. Attention should be given to for this complication.     

An expression system for the single-step production of recombinant human amidated calcitonin

The authors evaluate 32 patients affected by paranasal sinuses and nasal cavity carcinoma observed at Orl-Rt Department of Oncologic Center at Umberto l(zero) Hospital in Mestre (VE), Italy from 1985 to 1994. Among these: 16 maxillary sinus, 10 ethmoid and 6 nasal cavity carcinomas. Histologic diagnosis showed squamous cell carcinoma in 15 cases, adenocarcinoma in 8 cases, lymphoma in 2 cases, transitional cell carcinoma in 2 cases, undifferentiated carcinoma in 2 cases and adenoidocistic carcinoma in 3 cases. The mean age was 64.5 years (range 46-88 years), and mean performance status was 80 (range 60-90). Four patients had lymphonodal involvement. Eleven patients were operated, eight of them radically. All patients were treated with radiation therapy. Treatment planning was performed using Theraplan V05-B program, on extensive number of CT scans. The minimal tumor dose was 50 Gy for patients operated radically and was 60 Gy with maximum of 73-80 Gy for the others. The follow-up is 39.7 months (range 10-108). Three patients treated with radical surgery developed local relapses, two of them died. Fourteen patients treated with non radical or diagnostic surgery and radiotherapy obtained local complete remission, five of them developed local relapses inside treatment volume. Ten patients died (eight for neoplastic disease). The 3 years, 5-years and 7-years overall survival are respectively 72% and 51%. The 5-years and 7-years disease free survival rate are respectively 48% and 19% with median at 3.7 years. Complication have been minimal. Only one patient affected by glaucoma had a severe and permanent reduction of the virus. The authors conclude that 2D and 3D treatment planning can assure a better accuracy for target definition and a better precision of the treatment with a reduction of complications.     

MR imaging findings of the femoral marrow in myelodysplastic syndrome

MR imaging of the femoral marrow was performed in 30 patients with myelodysplastic syndrome (MDS), 11 cases of which evolved to acute myeloid leukemia (AML). The MRI appearance was classified into five patterns: 1) fatty marrow; 2) faint signal; 3) nodular pattern; 4) heterogeneous infiltration; and 5) diffuse infiltration. For each type of MDS, MRI patterns of the femoral marrow were evaluated and compared with those in normal subjects as well as in patients with aplastic anemia. Signal intensity alteration, a low signal on T1-weighted SE image and a high signal on STIR image, began in the proximal femoral marrow almost symmetrically in patients with MDS. The area of abnormal signal intensity tended to gradually extend towards the distal portion of the femur as the disease progressed. MRI patterns of the femoral marrow correlated with marrow cellularity, and diffuse marrow infiltration was noted in patients with a more advanced type of MDS or with severe anemia. There were limitations to making an accurate diagnosis of the MDS type on the basis of the MRI pattern. Progression of the MRI appearance in the course of MDS was thought to be a sign suggesting evolution to AML. It was difficult to differentiate hypoplastic MDS from aplastic anemia, although the nodular pattern was commonly seen in the latter disease.     

Negative regulation of Apo A-I gene expression by retinoic acid in rat hepatocytes maintained in a coculture system

Mantle cell lymphoma (MCL) is a subtype of B-cell non-Hodgkin's lymphoma recently recognised as a distinct disease entity. Little is known about the prognostic factors and optimal treatment of MCL. The aim of this study was to analyse retrospectively the clinical features and effect of treatment in 94 MCL patients diagnosed and treated in one centre between 1980 and 1996, and to find out different factors influencing the treatment results and prognosis. The median age of the patients was 66 years, and 77% were over 60 years old. Of the patients, 76% had advanced disease, the performance status (PS) was WHO 0-1 in 86%, and B symptoms were present in 35% of the cases. Bone marrow infiltration was found in 61% and overt leukaemia in 12% of the patients. Of the patients, 47% achieved complete remission with first- or second-line therapy. The median duration of remission, time to treatment failure (TTF), and survival were 28, 18, and 41 months, respectively. In multivariate analyses, age, stage and leukaemic disease were significantly associated with TTF, and age, stage, leukaemic disease and lactate dehydrogenase (LDH) with survival. Long-term prognosis is poor in MCL. None of the conventional chemotherapies seems curative. A prospective randomised trial should be made to evaluate the benefit of anthracycline-containing regimens in MCL.     

Allogeneic CD34 selected peripheral stem cell transplant for Maroteaux-Lamy syndrome (mucopolysaccharidosis type VI): rapid haemopoietic and biochemical reconstitution

AIM: To analyze the bone marrow (BM) infiltration in low-grade non-Hodgkin's lymphomas (LGNHL) and assess its association with the histopathology type, clinical behavior, and disease prognosis. METHOD: BM smears obtained by needle biopsy and stained by standard methods were analyzed in 60 patients with LGNHL using the Working Formulation. RESULTS: BM infiltration was observed in 57% of the lymphocytic lymphomas (A), in 48% of lymphoplasmocytic/ plasmocytoid lymphomas (AI), and in 31% of follicular lymphomas (follicular small cleaved cell and follicular mixed B and C). The difference was not significant. The 5-year survival rates for patients with and without bone marrow infiltration were 53% and 56% respectively, and 10-year survival rates were 31% and 45% (p>0.05). CONCLUSION: The presence of bone marrow infiltration at diagnosis did not significantly affect the prognosis of LGNHL.