MACOP-B and involved field radiation therapy is an effective therapy for primary mediastinal large B-cell lymphoma with sclerosis

PURPOSE: To evaluate the clinical features of presentation and the response to two different third-generation regimens (F-MACHOP and MACOP-B) of primary mediastinal large B-cell lymphoma (MLBCL), a recently defined distinct clinicopathological entity of non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Thirty-seven consecutive patients with MLBCL, eight male and 29 female (F/M ratio 1:3.5) with a median age of 35 years, were enrolled in the present study. Thirty-five (94.5%) patients presented disease confined to thorax, with chest symptoms of a rapidly enlarging mass in the mediastinum in 70% and superior vena cava syndrome (SCVS) in 43% of these patients. The first 10 patients received F-MACHOP and the succeeding 27 patients MACOP-B chemotherapy, associated in 24 (88.8%) with involved field radiation therapy (IFRT). 67Gallium scan was routinely performed pre- and post-IFRT in 18 patients. RESULTS: All 37 patients were assessable for response: 10 of 10 (100%) in the F-MACHOP and 26 of 27 (96.3%) in the MACOP-B group achieved overall responses (CR + PR). Three of 24 (12.5%) patients in PR after chemotherapy obtained CR after IFRT. Persistent Gallium avidity was observed in 16 patients after chemotherapy and in only four patients after IFRT. Thus far, four of the 10 F-MACHOP and two of the 26 MACOP-B responders have presented disease progression. The probability of progression-free survival (PFS) was 91% and 60% (P < 0.02) while overall survival (OS) was 93% and 70% (P = n.s.) at a mean follow-up of 27 and 52 months in the MACOP-B + IFRT and F-MACHOP groups, respectively. CONCLUSION: MACOP-B + IFRT has proved to be a highly effective and less toxic therapeutic approach for primary MLBCL and appears to be superior to other third-generation chemotherapy regimens.     

Implications of using a prognostic index to select therapy for patients with aggressive histology lymphoma

The International Non-Hodgkin's Lymphoma Prognostic Factor Index (INHLPF-Index) is a validated method of determining prognosis for patients with aggressive histology lymphoma and is now being used to identify those who might benefit most from new investigative therapies. This review assesses its usefulness and potential clinical utility in this context, and shows that several factors will determine the clinical utility of using this index, including the inherent accuracy of the index, the effect of mislabelling and the efficacy and toxicity of experimental treatment.     

A clinicopathologic study of primary gastric lymphoma of B-cell type among the Japanese with special reference to low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT)

The most common primary site of low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is the gastrointestinal tract, particularly the stomach. The relationship of MALT lymphomas, however, with the more commonly occurring large B-cell gastric lymphoma has not been directly discussed except in the report of Chan et al. (1990), which lacked clinical information regarding the behavior of these tumors. To elucidate the relationship between high-grade large-cell lymphoma and MALT lymphoma, we studied in detail the histopathological and clinicopathologic features with the survival date of 77 Japanese cases of primary gastric lymphoma (PGL) of B-cell type. Based on degree of morphologically recognizable low- or high-grade components of the tumor, PGL was divided into four types: 18 cases of pure MALT lymphoma (type I); 13 cases of MALT lymphoma with small area of high-grade lymphoma (type II); 22 cases of high-grade lymphoma with small areas of MALT lymphoma (type III); and 24 cases pure high-grade lymphoma (type IV). Corresponding to the differences in the histologic pictures of each type, there were differences in the gross appearance, pathologic stage (including depth of invasion) and prognosis. These data suggests that both MALT and high-grade lymphomas of the stomach belong to the same cell lineage and constitute a pathological spectrum and that the histological grouping of PGL is clinico-pathologically useful.     

Hodgkin disease and non-Hodgkin lymphoma: plain chest radiographs and chest computed tomography of thoracic involvement in previously untreated patients

PURPOSE: To provide further information about the presentation of thoracic involvement in Hodgkin disease and non-Hodgkin lymphoma and to compare chest radiography with chest CT findings. MATERIALS AND METHODS: We reviewed the chest radiographs and the CT images of 100 Hodgkin and 100 non-Hodgkin patients, all of them untreated. Our data were compared with those of literature series: the latest study comparing the different patterns of Hodgkin and non-Hodgkin disease appeared in 1976 and it compared chest radiography with conventional tomography, not with CT. RESULTS: Intrathoracic involvement (75% vs 48%) and adenopathy (74% vs 28%) were more frequent in Hodgkin than in non-Hodgkin lymphoma. Ninety-nine per cent of the patients with intrathoracic involvement (74/75) had nodal disease. Paratracheal/prevascular nodes were most frequently involved, namely in 72/74 Hodgkin (97%) and in 27/28 non-Hodgkin patients (96%). The lung parenchyma was more often involved in non-Hodgkin (24%) than in Hodgkin (8%) patients; it was associated with mediastinal/hilar adenopathy in all Hodgkin and in 10/24 (42%) non-Hodgkin cases. Parenchymal involvement was demonstrated with chest radiography in 7/8 Hodgkin (88%) and in 13/24 non-Hodgkin patients (54%). Chest radiography showed paratracheal/prevascular adenopathy more often in Hodgkin (54/72, 75%) than in non-Hodgkin (15/27, 56%) cases. Subcarinal and internal mammary adenopathy was poorly depicted with plain films, while hilar adenopathy was generally identified with both CT and chest radiography. Chest radiography usually missed posterior mediastinal and anterior diaphragmatic adenopathy. CONCLUSIONS: The differences in the presentation of Hodgkin vs non-Hodgkin disease are not sufficiently distinctive to permit radiographic differentiation of the two conditions, but some patterns are helpful. Recognizing the frequency of thoracic involvement and that of the additional CT findings in Hodgkin and non-Hodgkin patients makes a sound basis for lymphoma imaging.     

The use of enzymes in treating patients with malignant lymphoma with a large tumor mass]

Systemic enzymes (wobenzime and wobe-mugos) were approved, that had been prescribed as part of polychemotherapy to 24 patients with malignant lymphomas, who presented with large masses of lymphatic nodes poorly resorbable against the background of polychemotherapy and who were assigned for a high-total dose irradiation, which fact would undoubtedly entail sclerosing of adjacent intact tissues. The use of the enzymes made for the optimum realization of the polychemotherapy effect and permitted avoiding a good many of undesirable side events and complication thereof. The above systemic enzymes are well tolerated by patients; they induce no significant changes in the cellular composition or in blood biochemical indices.     

Use of the laryngeal mask airway in managing a patient with a large anterior mediastinal mass: a case report

Oscillatory potentials (OP) of the electroretinogram (ERG) of 20 subjects providing 30 normal eyes were recorded by means of Ganzfeld stimulation at 11 stimulus intensities. It was found that intensity-implicit time functions of the OP components are exponential, while the intensity-response curves are highly variable. The amplitudes of the four wavelets showed relatively large coefficients of variation and intersubject variation, while those of the implicit time are small. Thus it appears that measurement of oscillatory potential implicit time rather than amplitude may provide a more reliable index to access certain retinal condition.     

Intravascular large B-cell lymphoma: the CD5 antigen is expressed by a subset of cases

The CD5 antigen is a T-cell associated marker that is also usually expressed by two B-cell neoplasms, chronic lymphocytic leukemia/small lymphocytic lymphoma and mantle cell lymphoma. We observed CD5 antigen expression in a subset of cases of intravascular large B-cell lymphoma (IVLBL), and we report here five cases. The patients, two men and three women, ranged in age from 59 to 81 years. Biopsy specimens were obtained from kidney, lung, bone marrow, abdominal wall, and neck, the latter involving a lymphangioma. All of the cases had histologic features typical of IVLBL, with large and atypical lymphoid cells located predominantly within blood vessels. Immunohistochemical studies performed using routinely fixed, paraffin-embedded tissue sections showed that the neoplastic cells were B cells, positive for the CD20 antigen and negative for the CD3 or CD43 antigens. All cases were also positive for the CD5 antigen. One case had an immunoglobulin heavy chain gene rearrangement shown by using a polymerase chain reaction method. The finding of CD5 antigen expression in a subset of IVLBL cases adds to other evidence in the literature suggesting that IVLBL is a heterogeneous entity. We considered the possibility that these cases were related to or represented unusual histologic forms of transformation from either chronic lymphocytic leukemia/small lymphocytic lymphoma or mantle cell lymphoma. All of the cases, however, were negative for the CD23 antigen and cyclin D1 (bcl-1) protein, which is evidence against this interpretation. The biologic significance of CD5 antigen expression in cases of IVLBL is uncertain. These neoplasms might arise from a separate lineage of CD5-positive B cells or from a specific, early stage of B-cell differentiation. Alternatively, some investigators have suggested that CD5 antigen expression by B cells is a marker of activation.     

Synchronous and metachronous primary gastric lymphoma and adenocarcinoma: a clinicopathological study of 12 patients

BACKGROUND: The occurrence of both malignant gastric lymphoma and adenocarcinoma in the same patient is very rare. METHODS: The resected specimens from 12 patients who had both primary gastric lymphoma and adenocarcinoma were analyzed using immunohistochemistry and in situ hybridization. RESULTS: Two different tumors were found synchronously in 10 patients (5 with independent tumors and 5 with contiguous/collision tumors) and metachronously in 2. The size of the lymphomas (mean, 7.2 cm) was larger than that of the adenocarcinomas (mean, 3.6 cm) (P < 0.005). Histologically, 9 of the 12 lymphomas (75%) were mucosa-associated lymphoid tissue lymphomas, and all lymphomas invaded the deep portion of the submucosa or deeper. Conversely, 10 of the 12 adenocarcinomas (83%) were early carcinomas. Six adenocarcinomas were intestinal type, whereas the other 6 were diffuse type. The MIB-1 index of the adenocarcinomas (mean, 50.4%) was higher than that of the lymphomas (mean, 29.3%) (P < 0.05). Helicobacter pylori (H. pylori) was documented in all 12 patients, whereas Epstein-Barr virus-encoded RNA 1 was detected in only 2. During the follow-up period after surgery, 6 patients died, 4 due to adenocarcinoma. The survival probability of all 12 patients appeared to be similar to that of previously reported patients with gastric adenocarcinoma alone, and was significantly worse than that of the 217 patients with gastric lymphoma alone (P < 0.05). CONCLUSIONS: An H. pylori infection is considered to be associated with the development of these double malignancies. In many such synchronously observed cases, lymphomas may precede carcinogenesis, while the prognosis appears to be more closely associated with the adenocarcinoma than the lymphoma.     

Phase I study of daily times five topotecan and single injection of cisplatin in patients with previously untreated non-small-cell lung carcinoma

BACKGROUND: The objectives were to determine the dose-limiting toxicity of topotecan in combination with cisplatin, to describe the principal toxicities, and to define the maximally-tolerated doses of the drugs in previously untreated patients with advanced non-small-cell lung carcinoma. PATIENTS AND METHODS: The study was designed to evaluate escalated doses of topotecan (starting at 0.75 mg/m2/day) as a 30-minute infusion daily for five consecutive days with a fixed clinically-relevant dose of 75 mg/m2 cisplatin given on day 1, every three weeks. RESULTS: Fifteen chemotherapy-naive patients entered the study and 14 were evaluable for toxicity. All 11 patients treated at the first topotecan/cisplatin dose level of 0.75/75 mg/m2, experienced at least one episode of grade 4 neutropenia. For six patients, absolute neutrophil counts were below 500/ml for more than five days, and two of them developed a grade 4 thrombocytopenia. At the next higher topotecan/cisplatin dose level (1.0/75 mg/m2), grade 4 neutropenia lasting longer than five days occurred in all three evaluable patients, including one patient who expired due to a severe neutropenia associated with sepsis. Non-hematologic toxicities, predominantly nausea and vomiting, were mild to moderate in severity and manageable. Four patients had partial responses (30.7%; 95% confidence interval (9%-61%) of relatively short duration. CONCLUSION: Both severe neutropenia and thrombocytopenia precluded dose escalation of topotecan and cisplatin administered on this schedule. In previously untreated patients, the first topotecan/cisplatin dose level (0.75/75 mg/m2), was associated with intolerable myelosuppression, and, therefore, the dose levels evaluated in this study cannot be recommended for subsequent phase II investigations. The high toxicity of this schedule and the recent understanding of the pharmacokinetic interaction between those drugs may encourage the investigation of the alternate sequence of cisplatin after TPT in phase II studies.     

Liposarcoma: a population-based epidemiologic and prognostic study of features of 43 patients, including tumor DNA content

Different conceptions exist regarding the epidemiology and prognosis of liposarcoma, and several classification systems are in use. We analyzed a population-based, 25-year series of 43 patients with liposarcoma of the extremity or trunk wall. Follow-up was complete. The annual incidence was 0.12/10(5). The thigh was the most common location. One of 6 tumors was subcutaneous. Deep-seated tumors were larger than s.c. tumors. Among the 42 surgically treated patients, grade II (4-grade scale) was the most common malignancy grade. Four tumors were well-differentiated, 24 were predominantly myxoid, 4 predominantly round-cell, and 10 were predominantly of pleomorphic type. The 5-year metastasis-free survival rate was 69%. By univariate analysis increasing malignancy grade, tumor necrosis, vascular invasion, mitotic count, subtype other than well-differentiated, and high cellularity were prognostic for metastatic disease. However, in the multivariate analysis only tumor necrosis was an independent risk factor. Tumor necrosis should be considered when prognosis of liposarcoma of the extremity and trunk wall is evaluated.     

Secondary lymph node involvement from primary cutaneous large B-cell lymphoma of the leg: sentinel lymph nodectomy as a new strategy for staging circumscribed cutaneous lymphomas

BACKGROUND: Primary cutaneous large B-cell lymphoma of the leg (LBCLL) is a recently defined type of non-Hodgkin's lymphoma. It forms a separate category in the new classification of primary cutaneous lymphomas elaborated by the European Organization for Research and Treatment of Cancer. It is associated with a less favorable prognosis than the most frequently occurring types of primary cutaneous B-cell lymphoma. METHODS: The authors present four patients with the typical clinicopathologic constellation of LBCLL. Three of them died during the years 1993-1996. The authors reviewed their courses. The fourth patient was staged by sentinel lymph nodectomy (SLNE), i.e., the selective surgical removal and histologic examination of the first draining lymph node associated with the cutaneous tumor. RESULTS: The courses of the three previous patients were characterized by secondary involvement of regional lymph nodes followed by systemic dissemination of the lymphoma in a third step. Although the conventional staging of the fourth patient had been negative for any extracutaneous lymphoma manifestation, the SLNE revealed initial regional lymph node involvement, which had decisive implications for the choice of therapy. CONCLUSIONS: SLNE may gain a prominent role in the staging of circumscribed cutaneous lymphomas, in addition to its already established position in melanoma management. Further positive effects of SLNE are 1) better distinction of primary cutaneous lymphomas with secondary lymph node involvement from primary lymph node lymphomas with skin manifestation, and 2) better insight into the biology of different primary cutaneous lymphoma types.     

Primary diffuse large B-cell lymphoma of the mediastinum: outcome following high-dose chemotherapy and autologous hematopoietic cell transplantation

ESAT-6 is an important T-cell antigen recognized by protective T cells in animal models of infection with Mycobacterium tuberculosis. In an enzyme-linked immunosorbent assay (ELISA) with overlapping peptides spanning the sequence of ESAT-6, monoclonal antibody HYB76-8 reacted with two peptides in the N-terminal region of the molecule. Assays with synthetic truncated peptides allowed a precise mapping of the epitope to the residues EQQWNFAGIEAAA at positions 3 to 15. Hydrophilicity plots revealed one hydrophilic area at the N terminus and two additional areas further along the polypeptide chain. Antipeptide antibodies were generated by immunization with synthetic 8-mer peptides corresponding to these two regions coupled to keyhole limpet hemocyanin. Prolonged immunization with a 23-mer peptide (positions 40 to 62) resulted in the formation of antibodies reacting with the peptide as well as native ESAT-6. A double-antibody ELISA was then developed with monoclonal antibody HYB76-8 as a capture antibody, antigen for testing in the second layer, and antipeptide antibody in the third layer. The assay was suitable for quantification of ESAT-6 in M. tuberculosis antigen preparations, showing no reactivity with M. bovis BCG Tokyo culture fluid, used as a negative control, or with MPT64 or antigen 85B, previously shown to cross-react with HYB76-8. This capture ELISA permitted the identification of ESAT-6 expression from vaccinia virus constructs containing the esat-6 gene; this expression could not be identified by standard immunoblotting.     

Short and longterm outcomes for patients with systemic rheumatic diseases admitted to intensive care units: a prognostic study of 181 patients

OBJECTIVE: To determine short and longterm outcomes and prognostic factors for patients with systemic rheumatic diseases admitted to intensive care units in 4 teaching hospitals. METHODS: All adult intensive care unit admissions over a 12 year period for systemic rheumatic diseases were retrospectively assessed. One hundred and eighty-one patients with a mean age of 57 +/- 17 years were studied. RESULTS: The death rate in intensive care units was 33% (59/181) and in-hospital mortality was 43% (77/181). One hundred and four patients were discharged alive from hospital; 40 died during followup (mean 105 +/- 7 mo). The estimated 5 year survival rate for the discharged patients was 69%. The 4 factors significantly associated with in-hospital mortality by multivariate analysis were simplified acute physiologic score (p = 10(-4)), poor prior health status (p = 10(-4)), corticosteroid administration (p = 0.005), and the reason for admission; mortality was higher in the group admitted to intensive care for infectious complication (55 versus 34% for others; p = 0.006). In contrast, in-hospital mortality was not influenced by age or by systemic rheumatic diseases. Using Cox's model, only age over 60 years was a prognostic factor significantly associated with an increase in longterm mortality (p = 10(-4)). CONCLUSION: The short term outcome for patients with systemic rheumatic diseases in intensive care units was poor. The longterm prognosis after hospital discharge appeared fair, although the standardized mortality ratio was 5-fold that of a nonselected population. Short and longterm prognoses were similar for different systemic rheumatic disease groups.     

Oesophageal cancer associated with other primary cancers: a study of 31 patients

The aim of this study was to investigate the characteristics of oesophageal cancer associated with other primary cancers and the survival rate after surgery for the patients with these cancers. Of 202 patients with oesophageal cancer treated in the Second Department of Surgery, Shinshu University School of Medicine between 1981 and 1995, 31 patients (15.3%) had oesophageal cancer associated with other primary cancers. Twenty-one synchronous and 10 metachronous associated cancers were found and 25 of them were resected. Early-stage oesophageal cancer was much more frequent in the associated cases than in the non-associated cases. The stomach was the most frequently associated organ. The numbers of cases with triple and quadruple cancers were three and one, respectively. Three of these cases had intervals of over 6 years between tumours. Three cases with other primary cancers which had intervals of over 7 years after oesophagectomy were found, and two were carcinomas of the reconstructed gastric tube. In the outcome after surgery for oesophageal cancer, there was no difference between the associated and the non-associated cases, and also no difference between the synchronous and metachronous associated cases. Regarding the five-year and 10-year survival rates after surgery for the first cancers, the synchronous cases had a poorer outcome than did the metachronous cases. In conclusion, oesophageal cancer with other primary cancers is not always rare, and its outcome is not poor compared with that of the non-associated cases. These patients may achieve survival by early detection of both lesions and positive treatment. It is important to consider the risk of other primary cancers after oesophagectomy, and the success of the reconstructed gastric tube should be followed by endoscopy.     

Non-Hodgkin's lymphoma of stage I and II in elderly patients: a retrospective study in comparison with younger patients

Forty-one patients with non-hodgkin's lymphoma at stages I and II who had received radiation therapy were reviewed to analyze the prognosis and prognostic factors, with the main focus on a comparison of elderly (age > 65 years) and younger patients. In terms of clinical and histological characteristics, there were no differences between the elderly and younger patients. The 5-year-survival rate (5YS) in elderly patients was 52.8%, compared with 68.6% for younger patients. In patients treated with irradiation alone, the 5YS was 49.5% in elderly patients and 22.1% in younger patients. Combination treatment consisting of irradiation and chemotherapy improved 5YS markedly to 84.9% in the younger patients, while no apparent improvement was seen in the elderly patients, in whom 5YS was 54.1%. Using Cox's multiregression life table, two prognostic factors, the presence of symptoms and LDH, were extracted and found to have a significant influence upon the survival of the elderly patients. Complete response was 90.2% in the elderly patients, although relapse was seen in 54.1% of the complete responders. Relapse occurred overwhelmingly outside the irradiated regions. Since the prognosis of elderly patients could not be improved with the current chemotherapy regimen, some different regimen must be established to lower the high relapse rate in the area outside the irradiated field.