HODGKIN'S DISEASE,a Clinical-Pathological Review of 150 Cases

One hundred and fifty cases of Hodgkin''s disease were analyzed in an effort to detect significant clinical-pathological correlations and to elucidate any possible factors of prognostic or etiological importance.A relatively long survival for patients with Hodgkin''s paragranuloma was not noted in this series. Instead the survival rate among them was closely parallel to that of patients with classical granuloma. Hodgkin''s sarcoma is a more malignant disease with a patient survival rate not more than half that of patients with the granuloma variety. It is not necessarily a disease of older age groups. Great caution must be exercised to avoid including non-Hodgkin''s disease tumors under the heading of Hodgkin''s sarcoma or paragranuloma.The series reported corresponds with many other reported series of Hodgkin''s disease as regards greater incidence in males and longer survival in females. In this series the cases in patients under the age of 15 were all in males. The predominance of initial enlargement of the cervical nodes was again noted in this series, as was the high proportion of negative reaction to tuberculin tests. The incidence of tuberculous lesions in patients who died of Hodgkin''s disease was only slightly greater than in those who died of other lymphoma. Site of origin of the disease apparently affects survival time. There was statistical evidence that gonadal activity might influence the equilibrium of the disease.Lymph node bacteriological cultures were not remarkable. Brucella organisms were absent. Fertile egg passages for detecting possible viral agents revealed increased egg mortality and cutaneous sensitivity reactions to the harvested amniotic fluid.     

Nodular paragranuloma and progressively transformed germinal centers. Ultrastructural and immunohistologic findings.

Ultrastructural and immunohistologic findings in a nodular variant of Hodgkin's disease with lymphocytic predominance, called nodular paragranuloma, are presented and compared with those in so-called progressively transformed germinal centers. These are large follicles with numerous lymphocytes which can be found not only in nonspecific lymphadenitis, but also in lymph nodes from patients with nodular paragranuloma. The immunoperoxidase technique was applied on paraffin sections to detect intracytoplasmic immunoglobulin and lysozyme. The so-called L & H type Sternberg-Reed cells contained IgG and one type of light chain per cell, suggesting that such cells produce immunoglobulin. The ultrastructure of the L & H type Sternberg-Reed cells favored the immunoblastic nature of these cells. It is concluded that nodular paragranuloma differs from other types of Hodgkin's disease by its localization in B-cell areas and the presence of atypical B immunoblasts.     

AIDS and associated malignancies

AIDS associated malignancies (ARL) is a major complication associated with AIDS patients upon immunosuppression. Chronically immunocompromised patients have a markedly increased risk of developing lymphoproliferative disease. In the era of potent antiretrovirals therapy (ARV), the malignant complications due to HIV-1 infection have decreased in developed nations where ARV is administered, but still poses a major problem in developing countries where HIV-1 incidence is high and ARV is still not yet widely available. Even in ARV treated individuals there is a concern that the prolonged survival of many HIV-1 carriers is likely to eventually result in an increased number of malignancies diagnosed. Malignancies that were found to have high incidence in HIV-infected individuals are Kaposi's sarcoma (KS), Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL). The incidence of NHL has increased nearly 200 fold in HIV-positive patients, and accounts for a greater percentage of AIDS defining illness in the US and Europe since the advent of HAART therapy. These AIDS related lymphomas are distinct from their counterparts seen in HIV-1 seronegative patients. For example nearly half of all cases of ARL are associated with the presence of a gamma herpesvirus, Epstein Barr virus (EBV) or human herpesvirus-8 (HHV-8)/ Kaposi's sarcoma associated herpesvirus (KSHV). The pathogenesis of ARLs is complex. B-cell proliferation driven by chronic antigenemia resulting in the induction of polyclonal and ultimately monoclonal lymphoproliferation may occur in the setting of severe immunosuppression.     

Human papillomavirus infection and neoplasia of the cervix and anogenital region in women with Hodgkin's disease

Immunosuppression has been associated with an increased incidence of condyloma and neoplasia of the cervix and anogenital region, lesions associated with human papillomavirus (HPV) infection. The role of immunosuppression as a risk factor for the development of these lesions in patients with Hodgkin's disease was studied in a series of 666 consecutive women seen at the University of Texas M. D. Anderson Hospital between 1963 and 1982. Thirty-nine patients (5.9%) of the entire series and 45.9% of the 85 women with Hodgkin's disease who had a gynecologic examination showed evidence of condyloma, dysplasia or carcinoma of the cervix or anogenital region. This is a significantly greater percentage of affected women than would be expected based on published results from Papanicolaou screening services. The evidence is compatible with immunosuppression from Hodgkin's disease or its treatment rendering a woman susceptible to persistent HPV infection and its consequences.     

Is first salvage chemotherapy the last-line chemotherapy in children with Hodgkin's disease? A tentative answer based on long observation of two patients

In 82 children affected with Hodgkin's disease, in whom a complete remission was obtained, the first relapses occurred in 13 patients, their outcome was a follows: one child died of relapse and in 12 others second complete remissions were achieved. They were durable in 10 children (median, 65.5 months). Two remaining children had further relapses, their treatment consisted of four successive salvage chemotherapies. Both patients are now in their fifth complete remission. The third-line chemotherapy was already introduced 78+ months and 39+ months ago respectively. We believe that it is not possible to determine exactly the end-stage of Hodgkin's disease in those children and adolescents who have failed the first-line salvage chemotherapy.     

Perforated Peptic Ulcer

Because no large series of perforated peptic ulcers has been reported from Canada, 402 cases from the Ottawa Civic Hospital were reviewed to study this dramatic disorder.The incidence was 15 per 100,000 population annually, or one in every 1000 hospital admissions.The incidence in females and the elderly in this series was higher than reported elsewhere. The risk of perforation increased with age, being greatest after 55; this was not due to an excess of chronic ulcers in older patients, indicating that ageing is an etiological factor.As the mortality of perforated peptic ulcer—20%—had remained unchanged over the years, fatal cases were studied to see if changes should be made in the management of this condition. The mortality for patients undergoing operation was 7.5%. Patients treated conservatively because their general condition was poor, died. Fifteen patients, in whom an incorrect diagnosis was made, died. More aggressive therapy and greater efforts at diagnosis might have saved some of these patients.     

Secondary neoplasms in two children with Hodgkin's disease]

In two out of 59 children with Hodgkin's disease treated with MVPP regimen combined with local irradiation and followed up over 10 years the secondary neoplasms were detected, i.e. in 3.4% with persisting remission of the underlying disease. Chondrosarcoma was diagnosed in one patient in the field of irradiation (after 13 years). This patient died. In the second patient two different tumors (squamous epithelioma and fibrosarcoma) developed after 7 and 9 years following irradiation of two different areas. Actually, there are not any symptoms in this female patients (working). To decrease the incidence of these serious complications of Hodgkin's disease treatment regimens introduced by the Polish Pediatric Leukemia Study Group since 1988, the use of alkylating agents in limited, and the dose of local irradiation is decreased.     

Monocyte production in Hodgkin's disease and non-Hodgkin's lymphoma.

Monocytopoietic proliferation activity was investigated in patients with untreated Hodgkin's disease, Hodgkin's disease in long-term complete remission, and untreated non-Hodgkin's lymphoma of the lymphosarcoma and reticulosarcoma type. Untreated Hodgkin's disease was found to be associated with a rise in medullary monocyte production which returned to normal during long-term complete remissions. In contrast, monocyte production was increased in only 5 out of 14 patients with lymphosarcoma and reticulum cell sarcoma, normal in 3, and reduced in 6. In neither of these lymphomas was any relation between monocyte production and stage or histology of the disease detectable.     

Bacillary angiomatosis

Bacillary angiomatosis is a bacterial disease which affects mainly immunosuppressed patients. It may compromise any tissue, especially the skin, presenting papules, nodules or angiomatous tumors. We studied three young men with AIDS, all of them with 1-2 papules, nodules or subcutaneous tumors suggesting telangiectatic granuloma, sarcoma and lipoma. Microscopically, they were misdiagnosed as telangiectatic granuloma, Kaposi's sarcoma and "angioma with secondary inflammation". After reviewing the histopathology, we saw them to be composed by vessels with prominent endothelium and stroma rich in leukocytoclastic polymorphonuclears. Fibrinoid deposits were observed in the neighborhood of vessels as well as minute eosinophilic granular interstitial masses corresponding to Bartonella aggregates, criteria which answer to the diagnosis of bacillary angiomatosis with HE staining. The Warthin-Starry stain was not useful; using resin embedded tissue from paraffin-embedded material, bacterial clusters, both in semithin section stained with toluidine blue and in thin sections observed under the electron microscope, were clearly seen, confirming bacillary angiomatosis diagnosis. Patients were successfully treated with surgery and either erythromycin or doxycycline. We reviewed the entity as well as its differential diagnoses with telangiectatic granuloma, Kaposi's sarcoma, Carrión's disease, and cat-scratch disease. In conclusion, we showed the presence of bacillary angiomatosis in three patients, illustrated its typical histopathological appearance with HE staining and demonstrated the causal bacteria in thick sections and with the electron microscope. It is essential to recognize bacillary angiomatosis, as it can be cured with antibiotics.     

Aspiration cytology of lymphocyte-depleted Hodgkin's lymphoma in a man infected with the human immunodeficiency virus. A case report.

We describe the case of a 39-year-old, human immunodeficiency virus (HIV)-positive man who was noted to have a chest wall mass on physical examination. Fine needle aspiration of the mass showed atypical spindle cells. Excisional biopsy of the mass revealed Hodgkin's lymphoma with areas of lymphocyte depletion consisting of a proliferation of myofibroblastic cells. The myofibroblastic, lymphocyte-depleted areas in the Hodgkin's lymphoma mass corresponded to the spindle cells seen in the aspirate. While the presence of spindle cells in aspirates of masses in HIV-positive patients usually suggests Kaposi's sarcoma, other entities, including lymphocyte-depleted Hodgkin's lymphoma, should be considered.     

The Incidence of Asbestos Bodies in the Lungs at Random Necropsies in Montreal

The incidence of asbestos bodies in the lungs of adult patients selected at random, who died in four Montreal hospitals, was studied by examining fresh unstained smears of lungs obtained at necropsy. Two techniques were used for preparation of the smears and an arbitrary grading system was developed to estimate the degree of contamination of the lungs by asbestos bodies.Asbestos bodies were present in 48 out of 100 necropsies; they were found in 32 of 56 men (57%) and in 16 of 44 women (34%). Men were more heavily contaminated. The proportion of positive smears depended on the technique used and the amount of lung sampled. No particular association was noted between asbestos bodies in the lungs and the presence of cancer in the 33 patients in this series with malignant disease. The high incidence in this random series suggests that asbestos is a significant air contaminant in Montreal.     

Observations on the Incidence of Gallstone Disease

In an attempt to ascertain whether a real increase in the incidence of gallstone disease existed at the Jewish General Hospital, Montreal, it was determined that, from 1935-1960 inclusive, 1846 gallbladder operations were performed. The operative mortality was 0.9%. The yearly trend in the number of gallbladder operations performed was generally found to be upward. Significant statistical increases were noted in 1959 and 1960. During the same years significant increases were noted in the proportion of males treated, particularly in the eighth decade of life. As a percentage of total surgical discharges, during 1960, the incidence of gallbladder operations exceeded that of appendectomies, which are being performed less frequently than previously. The peak incidence for gallbladder operations, for both sexes, occurred during the fifth decade of life. These observations suggest that in this hospital population a real increase in the incidence of gallbladder operations has probably occurred. It was not possible to form an opinion regarding possible changes in the clinical aspects of gallbladder disease.     

Incidence,mortality, and survival trends of soft tissue and bone sarcoma in Switzerland between 1996 and 2015

BackgroundResearch on soft-tissue sarcoma (STS) and bone sarcoma (BS) is increasingly in the focus of physicians and pharmaceutical companies. Expanding knowledge has improved the management of sarcoma and possibly survival. Here we provide the first population-based data on time trends of incidence, mortality, and survival of STS and BS diagnosed in Switzerland between 1996 and 2015.MethodsWe performed a retrospective registry study with data from the National Institute for Cancer Epidemiology and Registration (NICER) database in Switzerland between 1996 and 2015.ResultsWe identified 5384 STS patients and 940 BS patients. The three most common STS subtypes were undifferentiated/unclassified sarcoma (22.3%), liposarcoma (20.6%) and leiomyosarcoma (20.6%). Chondrosarcoma, osteosarcoma and Ewing sarcoma represented 40.4%, 27.0% and 15.2% of the BS group, respectively. The age-standardized incidence and mortality rates in 2011–2015 were 4.43 and 1.42 per 100,000 person-years for STS, and 0.91 and 0.42 for BS. Age-standardized incidence of STS in males was significantly higher during 1996–2000 than during 2001–2015; however, mortality rates did not change significantly over time. Five-year relative survival (RS) for STS improved significantly from 56.4% (95%CI 52.9–59.7 for 1996–2001) to 61.6% (95%CI 58.6–64.4 for 2011–2015) (p = 0.025). No improvement in 5-year RS for BS could be observed (RS 1996–2000: 69.6%, 95%CI 61.2–76.6; RS 2011–2015: 73.1%, 95%CI 66.6–78.6; p = 0.479).ConclusionIncidence rates of STS and BS have been stable since 2001. The longer RS in STS can be attributed to advances in sarcoma patient management.     

The role of progeny quality and male size in the nesting success of smallmouth bass: integrating field and laboratory studies

Smallmouth bass display size-specific variation in reproductive success with larger brood-guarding males in a population more likely to rear offspring to independence than smaller individuals. The exact mechanisms responsible for this size-specific increase in reproductive output have yet to be identified. To assist in this process, we investigated the relationship between the size of brood-guarding male smallmouth bass and offspring quality (in this case, egg physiology, egg morphology, egg size, hatching success and lab survival). Further, we examined how factors such as egg physiology, egg morphology and egg size influenced reproductive success in the wild and hatching success in a controlled laboratory environment. Nesting male smallmouth bass that successfully reared their offspring to independence spawned earliest in the nesting period were the largest individuals, and guarded eggs with greater concentrations of cortisol compared to males that abandoned their offspring prematurely. Offspring survival in the laboratory was not correlated with offspring survival in the wild, indicating that caution should be used interpreting studies that attempt to relate laboratory-derived survival metrics to the wild. Together, results demonstrate size-specific differences in offspring quality for nesting smallmouth bass, which are correlated with higher concentrations of cortisol in eggs. However, hatching success under laboratory conditions was dissimilar to nesting success in the field relative to cortisol concentrations.     

Survival of patients treated for end-stage renal disease by dialysis and transplantation.

The results of treatment in 213 patients with end-stage renal disease who underwent hemodialysis, peritoneal dialysis or transplantation, or a combination, between 1962 and 1975 were analysed. Comparison by censored survival analysis showed significantly better (P less than 0.01) patient survival with the integrated therapy of dialysis and transplantation than with either form of dialysis alone. There was no significant difference in survival of males and females but survival at the extremes of age was poorer. Analysis of survival by major cause of renal failure indicated best survival in patients with congenital renal disease. Graft and patient survival rates at 1 year after the first transplantation were 42% and 69%. The major cause of death in this series was vascular disease but infection was responsible for 50% of deaths after transplantation. While integration of dialysis with transplantation produces best patient survival, this course is possible only when sufficient cadaver kidneys are available.     

Mylohyoid and jugular foramen bridging in pre-Columbian Chileans

The occurrence of mylohyoid groove bridging and jugular foramen bridging was determined in a population of adult Pre-Columbian Chileans. Two hundred forty-one crania (110 males, 131 females) were examined for jugular foramen bridging and 464 mandibles (252 males and 212 females) were observed for mylohyoid groove bridging. The overall incidence of jugular foramen bridging was 14.94%, with females showing a higher occurrence (18.32%) than males (10.91%); however, no statistical significance was found between the sexes. The right side showed a greater incidence than the left, but again no statistical difference was noted and the occurrence of this trait was found to be associated between the sides. This frequency of jugular foramen bridging is higher than that found in other studies and approaches that reported in North American Eskimo populations. In the case of mylohyoid groove bridging, the incidence was 4.09% with no difference found between the sexes. This frequency of occurrence is less than the values reported previously for the other American populations of Mongoloid ancestry including the Pre-Columbian Peruvian population. The importance of nonmetric skeletal traits for defining population groups and their usefulness as anthropological tools is discussed. It is concluded that hard tissue variations such as bony bridging may be reliable markers to aid in discretely identifying population groups, but their importance can be significantly enhanced by coupling as many traits as possible in future studies.     

Secernin-1 as a novel prognostic biomarker candidate of synovial sarcoma revealed by proteomics

We aimed to develop prognostic biomarkers for synovial sarcoma employing a proteomic approach. We examined the proteomic profile of synovial sarcoma using two-dimensional difference gel electrophoresis (2D-DIGE). We identified 20 protein spots whose intensity was statistically different (p<0.01) between a group of eight patients who were alive and continuously disease-free for over five years and a group of five patients who died of the disease within two years post diagnosis. Mass spectrometric protein identification demonstrated that these 20 spots corresponded to 17 distinct gene products. Three of the 20 spots corresponded to secernin-1 and had higher intensity in the good prognosis group. The prognostic performance of secernin-1 was further examined immunohistochemically in 45 synovial sarcoma cases. The 5-year survival rate was 77.6% and 21.8% for patients with secernin-1 positive and negative primary tumors respectively (p=0.0015). The metastasis-free survival was significantly higher in the patient group with high secernin-1 expression compared to that with low expression (p=0.0012). Uni- and multivariate analyses revealed that secernin-1 expression was a powerful prognostic factor compared to other clinico-pathological parameters examined. These results indicate that secernin-1 may be used as a biomarker to predict the overall and metastasis-free survival in synovial sarcoma patients.     

Effectiveness of carboplatin and paclitaxel as first- and second-line treatment in 61 patients with metastatic melanoma

Background

Patients with metastatic melanoma have a very unfavorable prognosis with few therapeutic options. Based on previous promising experiences within a clinical trial involving carboplatin and paclitaxel a series of advanced metastatic melanoma patients were treated with this combination.

Methods

Data of all patients with cutaneous metastatic melanoma treated with carboplatin and paclitaxel (CP) at our institution between October 2005 and December 2007 were retrospectively evaluated. For all patients a once-every-3-weeks dose-intensified regimen was used. Overall and progression free survival were calculated using the method of Kaplan and Meier. Tumour response was evaluated according to RECIST criteria.

Results

61 patients with cutaneous metastatic melanoma were treated with CP. 20 patients (85% M1c) received CP as first-line treatment, 41 patients (90.2% M1c) had received at least one prior systemic therapy for metastatic disease. Main toxicities were myelosuppression, fatigue and peripheral neuropathy. Partial responses were noted in 4.9% of patients, stable disease in 23% of patients. No complete response was observed. Median progression free survival was 10 weeks. Median overall survival was 31 weeks. Response, progression-free and overall survival were equivalent in first- and second-line patients. 60 patients of 61 died after a median follow up of 7 months. Median overall survival differed for patients with controlled disease (PR+SD) (49 weeks) compared to patients with progressive disease (18 weeks).

Conclusions

Among patients with metastatic melanoma a subgroup achieved disease control under CP therapy which may be associated with a survival benefit. This potential advantage has to be weighed against considerable toxicity. Since response rates and survival were not improved in previously untreated patients compared to pretreated patients, CP should thus not be applied as first-line treatment.     

Radiotherapy for adult medulloblastoma: Long term result from a single institution. A review of prognostic factors and why we do need a multi-institutional cooperative program

AimWe retrospectively analyzed our Institution experience with these patients. The endpoints of the analysis were overall survival (OS), disease-free survival (DFS), local control (LC), metastasis free survival (MFS); results were compared with the literature.BackgroundMedulloblastoma in adult patients is a very rare disease; the 5 and 10-year overall survival rates range between 33–78% and 27–56%, respectively. The collection of more clinical data is strongly needed.Materials and methodsFrom September 1975 to October 2006, we treated 16 adult patients (9 males and 7 females) with a histological diagnosis of medulloblastoma. Acute and late toxicities were scored according to RTOG toxicity scale. Karnofski performance status (KPS) and neurological performance status (NPS) pre- and post-RT were reported.Median age was 27 years (range 18–53 years). All the patients received cranio-spinal irradiation, two patients were also given chemotherapy. Median follow-up period was 121.5 months.ResultsIn January 2014, 10/16 patients were alive without evidence of disease, 6/16 died with progressive disease (1 local and spinal, 3 spinal and 2 extraneural). Ten-year LC, OS, DFS, MFS were, respectively, 84%, 67%, 60% and 59%. Univariate analysis shows that gross total resection is associated with better survival.No acute or late G3–G4 toxicity was observed.ConclusionsThis experience and the analysis of the literature confirm the efficacy of postoperative RT but also the need of large datasets to better define prognostic factors and the possible role of the association of chemotherapy.     

EXPERIENCE WITH CORTISONE AND ACTH IN A PRIVATE CLINIC

Cortisone and ACTH are valuable agents for treating a large variety of diseases. In appropriate situations they may save life. It may be possible to prevent loss of vision in eye disease or permanent damage to important viscera in generalized disease. With ready access to these agents through the pharmacist, it is important to know that cortisone and ACTH can be used in office practice provided patients are selected carefully and followed frequently and closely. Strict observation of criteria for selection of patients limited the size of the series of patients reported upon, but by the same token the incidence of complications from therapy was exceptionally small. Every physician who elects to employ these potent hormones must become familiar with their physiological effects and with the various methods of exhibiting them. Some of these effects are noted in this paper, but the experiences reviewed here provide an incomplete picture of the wide application of cortisone and ACTH.