Laparoscopy and laparotomy combined with bone marrow biopsy in staging Hodgkin's disease.

The relative merits of laparoscopy with liver and spleen biopsy and staging laparotomy were studied in 91 unselected patients with Hodgkin''s disease. Laparoscopy with liver and spleen biopsy were combined with needle biopsy of the bone marrow and laparotomy was combined with open bone marrow biopsy. In 65 untreated patients six out of seven with liver or marrow disease, or both, were shown to have extranodal lymphomas in these sites by laparoscopy plus needle marrow biopsy. Among 26 patients who had been treated this finding occurred in six out of 10 patients. Spleen biopsies during laparoscopy detected infiltration by lymphoma in 14 out of 37 (38%) patients with diseases spleens. Morbidity was higher after laparotomy than after laparoscopy. Laparoscopy produced abdominal bleeding secondary to splenic biopsy in two patients. All patients with Hodgkin''s disease should be subjected to laparoscopy plus needle marrow biopsy before undergoing laparotomy.     

Computed tomography of abdomen in staging and clinical management of lymphoma.

During July 1976 to Demember 1977, 150 patients with Hodgkin''s disease and 138 with non-Hodgkin''s lymphoma were examined by computed tomography (CT). In 45 cases 50 repeat examinations were conducted. Concurrent laparotomy and lymphography were performed on 68 and 56 patients respectively. The overall incidence of false-positive CT examinations as confirmed by laparotomy was 7.4%. In 18 patients with non-Hodgkin''s lymphoma in the abdomen there was good correlation between the two techniques. Of the 50 patients with Hodgkin''s disease who underwent laparotomy, 17 had splenic disease and 14 minimally enlarged lymph nodes in 20 areas; CT, however, detected only four diseased spleens and five minimally enlarged lymph nodes. Nevertheless, CT often detected enlarged lymph nodes missed by lymphography and was 23% more efficient than lymphography in detecting unsuspected disease. CT also detected unsuspected disease in patients with relapse of lymphoma. CT may replace other non-invasive investigations of abdominal disease in patients with lymphoma and give a reliable guide to prognosis. It does not, however, eliminate the need for laparotomy in staging Hodgkin''s disease.     

Observations on Abnormal Cells in the Peripheral Blood and Spleen in Hodgkin's Disease

The occurrence of abnormal cells in the peripheral blood of patients with Hodgkin''s disease has been described in the literature. In the present investigation several varieties of cells were found, two of which are believed to be typical of the disease. The significance of these cells in the peripheral blood is not yet clear, but there seems to be a correlation between the presence of these characteristic cells in the blood and involvement of the spleen by the disease as determined by microscopical examination. In 11 patients both abnormalities proved to be absent; 13 out of 14 other patients showed both the abnormal cells in the blood and Hodgkin lesions in the spleen.If circulating abnormal cells are indeed an indication of the presence of Hodgkin''s disease in the spleen, involvement of this organ is likely to be due to or to give rise to haematogenous dissemination. The other possibility remains that both the occurrence of abnormal cells in the peripheral blood and splenic involvement are due to a multicentric origin of the disease. It seems most unlikely that the splenic lesions are consistent with localized disease still restricted to the lymphoid system. These findings challenge the validity of the present widely used so-called Rye classification of clinical stages in Hodgkin''s disease.     

Intensive investigation in management of Hodgkin's disease.

Ninety-eight patients with clinically localised Hodgkin''s disease underwent laparotomy and splenectomy to determine the extent of microscopic spread. In 68 patients the procedure was carried out for untreated disease apparently confined above the diaphragm. Abdominal disease cannot be confidently excluded on the basis of non-invasive investigation at presentation. Clinical assessment of splenic disease was unreliable unless gross splenomegaly was present. Pedal lymphography was accurate in assessing para-aortic and iliac disease but of no value in assessing other intra-abdominal lymph node involvement, including that of the mesenteric lymph node. Trephine bone marrow biopsy findings were normal in all patients before surgery, and only one patient was found to have diseased bone marrow by Stryker-saw biopsy at operation. Liver disease was identified at operation in nine patients, some of whom were asymptomatic with clinically undetectable splenic and nodal disease. Detailed clinical staging failed to detect disease in one-third of patients who underwent laparotomy. These studies show that if radiotherapy is to remain the treatment of choice for disease truly localised to lymph nodes a detailed staging procedure, including laparotomy and splenectomy, remains essential. The value of this potentially curative treatment is considerably diminished in the patient who has been inadequately staged.     

Curative Radiotherapy in Hodgkin's Disease: Significance of Haematogenous Dissemination Established by Examination of Peripheral Blood and Spleen

Studies of peripheral blood leucocyte concentrates in patients with Hodgkin''s disease showed two types of cells believed to be typical for the disease in a number of patients. Involvement of the spleen as diagnosed after splenectomy and histological examination showed a close correlation with the presence of these characteristic cells in the peripheral blood. This is believed to be an argument for haematogenous spread or a multicentric origin of the disease in these cases. The results of attempted curative high-voltage radiotherapy with total node irradiation in 24 patients seem to support this concept. On the basis of the Rye classification of clinical stages the results of radiotherapy are not predictable. Six patients in stage II and seven in stage III were in remission, one in each of stages II and IV, and six in stage III had recurrences of the disease within one year. A division into localized or disseminated forms of the disease based on the investigations of blood and spleen showed all localized cases in remission; of the disseminated cases one reached a remission and all others had recurrences. In three patients the therapy could not be completed. These preliminary treatment results are believed to support the idea of a special role of the spleen in the dissemination of the disease. A new classification of clinical stages in Hodgkin''s disease is proposed.     

Survival rates among patients with cancer in Alberta in 1974-78.

We calculated 5-year crude and relative survival rates, by age and sex, for patients in Alberta in whom cancer was diagnosed between 1974 and 1978. Cancers with low overall 5-year relative survival rates (less than 35%) included stomach cancer, cancer of the pancreas, lung cancer, brain cancer, multiple myeloma and myeloid leukemia. Cancers with high overall 5-year relative survival rates (more than 70%) included melanoma, breast cancer, cancer of the uterus, cancer of the bladder and Hodgkin''s disease. Five-year relative survival rates were generally lower in the highest age group (75 years or more). A strong inverse relation between age and survival was noted for brain cancer, non-Hodgkin''s lymphoma, Hodgkin''s disease and myeloid leukemia.     

La forme scléronodulaire de la maladie de Hodgkin: expérience du CHU de Sherbrooke

Scleronodular type of Hodgkin''s disease: experience at the Centre hospitalier universitaire de SherbrookeThe nodular sclerosis type of Hodgkin''s disease appears to be a distinct clinical entity. However, the incidence, the initial localization of the tumour and the survival of the patients are variable. The present study was carried out on a group of 17 patients, all French Canadians living in the province of Quebec, from a total of 31 with Hodgkin''s disease, an incidence of 55%. There were more males (10) than females (7). The mean age of the group was 37 years, but that of the females was lower than that of the males. The mediastinum was involved at the onset in 47% of the patients. The initial staging (according to the classification of Rye) in 76% of the patients was I or II.Four patients showed disease below the diaphragm. The lungs were infiltrated three times, the spleen six times, and the liver five times. The duration of survival of the 17 patients was twice that of the patients with the three other types of the disease.     

La TEP-TDM dans la maladie de Hodgkin : expérience clermontoise

The aim of this study was to evaluate the standardized uptake value (SUV) of ¹⁸FDG in Hodgkin's disease according to various histopathologic parameters as well as the impact of the examination on stadification and follow-up. A total of 37 patients profited from a pretherapeutic PET-CT. Standardized uptake value was calculated a posteriori. This one is higher in mixed cellularity Hodgkin's disease compared to nodular sclerosing Hodgkin's disease. In addition, the examination involved a change of stage in 35% of the cases compared to the injected CT. The specificity of the PET-CT at the end of the treatment was 96% and its exactitude of 93%, both significantly higher than those found in CT.     

Decreased tuftsin concentrations in patients who have undergone splenectomy.

Serum tuftsin concentrations were measured, using a radioimmunoassay developed in Israel, in normal subjects and in patients who had undergone splenectomy. Concentrations in those who had undergone traumatic and elective splenectomy were much lower. The tuftsin concentration in 38 patients with Hodgkin''s disease who had undergone splenectomy during staging laparotomy was not significantly different from the mean concentration in other patients who had had elective splenectomy. In four patients who underwent splenectomy for non-malignant haematological disorders measurements made before and after operation showed that tuftsin concentrations fell significantly in the days after operation. The increased susceptibility to overwhelming infections of patients with Hodgkin''s disease and others who have undergone splenectomy may be related to the low tuftsin concentrations. As pre-splenectomy tuftsin concentrations in patients with Hodgkin''s disease were normal, the practice of performing staging laparotomy and splenectomy in patients with Hodgkin''s disease should perhaps be reconsidered.     

Radiotherapy in the treatment of Hodgkin's disease.

Eighty-seven untreated patients with localised Hodgkin''s disease seen from 1969 to 1975 were treated by megavoltage radiotherapy. All were followed for at least 33 months. Thirty-three patients were staged clinically and 54 underwent more extensive investigation by lapaortomy and splenectomy. The projected five-year disease-free survival figures for patients staged surgically were 100% for the 17 with stage IA disease, 70% for the 19 with stage IIA disease, and 73% for the 15 with stage IIIA disease. These results were consistently better than those obtained in clinically staged patients. Five patients died, one of them without evidence of Hodgkin''s disease. As irradiation seems to produce excellent disease-free survival in most patients who are staged accurately at diagnosis, caution should be exercised in the routine use of adjuvant chemotherapy until the full risks of such treatment are clear. Combined modality therapy may be appropriate for patients with unfavourable features at presentation.     

Correlation of anemia with infradiaphragmatic involvement in Hodgkin's disease and other malignant lymphomas

A staging laparotomy and splenectomy were performed in 41 patients with Hodgkin''s disease and 11 with other malignant lymphomas. There was a significant correlation (P = 0.025) between the presence of unexplained anemia and involvement of the spleen or abdominal lymph nodes by tumour. The anemias were of mild degree; hemolysis was documented in three and iron deficiency in four, while 21 cases were unexplained. Bone marrow was not involved by lymphoma in this series. The complication rate in exploratory laparotomy was higher than previously reported. Severe complications were observed in 17% of these patients while another 15% had minor complications. The association we have discovered may be helpful in the staging of patients who cannot tolerate an operative procedure. The absence of infradiaphragmatic involvement is suggested in the presence of normal hemoglobin concentrations.     

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.     

Cellular immunity to Hodgkin's splenic tissue measured by leucocyte migration inhibition.

Patients with lymphoreticular malignancy were shown by a leucocyte migration inhibition technique to have cellular immunity to Hodgkin''s splenic tissue. Migration was significantly inhibited in 31 out of 55 patients with Hodgkin''s lymphoma and 19 out of 39 patients with other types of lymphoma. Inhibition was also shown in only three out of 29 patients with other malignancy, one out of 23 normal volunteers, and one out of 25 patients with non-malignant disease. The splenic factor that inhibits leucocyte migration, which has yet to be isolated and identified, may be a helpful diagnostic tool in patients with suspected lymphoma.     

Breast cancer in the eastern province of Saudi Arabia

In the Kingdom of Saudi Arabia (KSA), hospital and population based statistics have shown that breast cancer has the highest crude frequency rate among Saudi women. The scarcity of reports about the disease in the KSA has been the impetus to this analysis about breast cancer in the eastem province of KSA. Data on female patients with invasive breast carcinoma seen at King Fahd Hospital of the University in the eastern province of KSA, were retrospectively reviewed. The analysis intended to examine the pattern of the disease and the outcome for patients. Between 1985 and 1995, 292 patients were identified. Their median age±SD (standard deviation) was 42±10.5 years. Most patients were younger than 50 years (78%) and were predominantly premenopausals (79%). Only 25 (9%) of patients had stage I cancer, whilst 130 (44%), 90 (30%), and 47 (16%) had stage II, III, and IV, respectively. Among patients with known axillary nodal status (242 patients), only 37% were node-negative whilst 32% and 31% had 1–3, and ≥4 positive nodes, respectively. Adjuvant chemotherapy and tamoxifen were commonly offered; nonetheless, other adjuvant modalities were rarely utilised. The median follow-up ±SD of all patients was 62.3±8.9 months: 152 patients (52%) were alive with no evidence of disease, 25 (9%) were alive with evidence of disease, and 115 (39%) were dead from breast cancer or its related complications. The median survival of the entire group was not obtained, but the 10-year projected survival was 55%. For stage I and II patients, 118 (76%) were alive with a projected 10-year actuarial survival of 64%. On the other hand, only 51 (57%) of patients with stage III disease were alive with a median survival of 41.5 months (95% Confidence interval (CI), 18.9 to 51.3). Patients with stage IV disease demonstrated a poor outcome with a median survival of 23.5 (95%, CI 12.2 to 31.4). Multivariate analyses were performed to explore the influence of independent variables on overall survival (OS) for patients with non-metastatic disease. Besides the expected adverse effect of disease progression, the favourable influence of adjuvant chemotherapy and tamoxifen prevailed. The amount of benefit gained from tamoxifen, however, was small. Similar analyses were undertaken to determine the influence of independent variables on progression-free survival (PFS). These analyses ascertained the adverse effects of advanced stage and the favourable impact of adjuvant chemotherapy. Breast cancer in the KSA has features that are distinctive from those of industrialised countries. Survival data, however, were comparable. The favourable influence of adjuvant chemotherapy was evident on both OS and PFS. Adjuvant tamoxifen, however, had little effect. Due to its infrequent use, the role of other adjuvant modalities could not be asserted.     

Lymphangiography: Its Practical Value in Surgically Staged Patients with Hodgkin's Disease

Since the introduction of “staging laparotomy” (to determine the disease''s stage) in assessing Hodgkin''s disease, some observers have argued that lymphangiography could be safely omitted in the initial diagnostic evaluation.To test these opinions a series of 75 patients with Hodgkin''s disease who had a staging laparotomy and histological correlation with lymphangiograms was reviewed. Of 16 examinations with positive results, one proved to be a false positive. Of the 14 examinations with equivocal results, one proved histologically positive. In the remaining 45 lymphangiograms, five were falsely negative. In all five of these patients abdominal lymph nodes were involved, but in areas that do not routinely opacify on lower extremity lymphangiography. The overall accuracy was 90 percent.Therapeutically, the lymphangiogram permits accurate planning for treatment by radiation therapy so that all known disease is treated and yet bone marrow is not excessively irradiated. Changes in lymph node architecture after therapy provide valuable information as to regression of the disease or signs of its early recurrence.     

Early-stage Hodgkin's disease: current approaches to treatment.

Most patients with early-stage Hodgkin''s disease can now be cured by one of several therapeutic approaches. This review highlights the developments in the diagnosis and treatment of the disease that have led to long-term survival rates greater than 90%. Past and present radio-therapy (RT) planning and treatment practices are discussed in the context of both clinical and pathological staging. The role of initial bimodal therapy (RT and chemotherapy [CT]) and the use of CT in patients who suffer relapse after initial treatment with RT alone are reviewed. On the basis of prognostic factors, subgroups of patients for whom bimodal therapy is recommended, including those with a bulky mediastinal mass, have now been identified. Although treatment is highly successful, debilitating consequences of RT and CT, such as infertility, infection and second malignant diseases, remain. Newer treatment regimens may reduce morbidity and have similar or better long-term results with respect to survival and quality of life.     

Survival after intratumoral interleukin-2 treatment of 72 melanoma patients and response upon the first chemotherapy during follow-up

Systemic high-dose interleukin-2 (IL-2) treatment achieves long-term survival in a subset of advanced patients with melanoma. As we reported previously, intratumoral IL-2 induced complete local responses in more than 60% of melanoma patients. This study aimed to analyze the long-term outcome of 72 patients treated in two prior trials. Melanoma patients (49 stage III, 23 stage IV) with injectable metastases received intratumoral IL-2 injections thrice weekly at individually escalated doses (median duration, 6.5 weeks; median total IL-2 dose, 72 MIU; median number of injected metastases, 10). The observed 2-year overall survival rates were 95.5% for stage III patients with cutaneous metastases only (stage IIIB), 72% for those with combined cutaneous and lymph node involvement (stage IIIC), 66.7% for stage IV patients with disease limited to distant soft-tissue metastases (stage IV M1a), and 9.1% for those with visceral metastases (stage IV M1b and stage IV M1c). Thirty patients who reported recurrence of unresectable distant metastases subsequently received chemotherapy in the further course of disease and showed an overall response rate of 36.7% (16.7% complete responses, 20% partial responses). A high total dose of IL-2 and a dacarbazine/temozolomide-based chemotherapy regimen were variables correlated with a clinical response. In conclusion, patients with cutaneous metastasis without lymph node involvement in stage III and with soft-tissue metastasis without visceral involvement in stage IV showed unexpected favorable survival rates after intratumoral treatment with IL-2. Furthermore, the intratumoral IL-2 treatment seemed to be associated with increased complete and partial responses in subsequent chemotherapies.     

Net survival in recurrence-free colon cancer patients

PurposeConditional net survival in recurrence-free patients (CNS-RF) provides relevant clinical information and has never been assessed yet in a non-selected colon cancer population. We aimed to estimate conditional 5-year net survival in recurrence-free patients with colon cancer in the population-based Digestive Cancer Registry of Burgundy (France).MethodsCNS-RF was estimated in the 3736 patients resected for cure for primary colon cancer between 1976 and 2006, using a flexible parametric model of net survival for every additional year survived at diagnosis and from 1 to 5 years thereafter.ResultsThe net probability of surviving 5 more years increased from 72% at diagnosis to 92% for recurrence-free patients who survived 5 years after diagnosis. CNS-RF was over 90% 3 years after diagnosis in patients aged 75 and below. CNS-RF was over 95% in patients diagnosed after 2000 who were recurrence-free 3, 4 or 5 years after diagnosis. CNS-RF was similar between patients with stage I and II disease from 2 years after diagnosis and patients with stage III disease from 5 years after diagnosis. The initial differences in net survival related to gross features, clinical presentation, number of harvested nodes in stage II, and number of involved nodes in stage III disappeared after 2 years.ConclusionsCNS-RF is a relevant measure of prognosis in patients who have already achieved a period of remission. Providing an updated estimation of prognosis in the years following diagnosis may improve the survivors’ quality of life and access to credit or insurance.     

Combination Chemotherapy in Generalized Hodgkin's Disease

Fifty-two patients with generalized Hodgkin''s disease were treated with a combination of mustine hydrochloride, vinblastine, procarbazine, and prednisolone. Complete remissions were obtained initially in six out of seven patients (86%) who had previously received no treatment, in 15 out of 19 (79%) who had had only radiotherapy in the past, and in 9 out of 26 (35%) who had previously been given chemotherapy with or without radiotherapy. Of these 30 patients in whom a complete remission was obtained 22 have been free of any symptoms or signs of disease for periods ranging from 4 to 22 months. The response to treatment was rapid, and toxicity was not a major problem, except in those who had previously been treated with cytotoxic drugs used continuously and not in courses. A comparative trial of radiotherapy and combination therapy in the treatment of Stage III Hodgkin''s disease is strongly recommended.     

Efficacy and Safety of Nimotuzumab Plus Radiotherapy With or Without Cisplatin-Based Chemotherapy in an Elderly Patient Subgroup (Aged 60 and Older) With Nasopharyngeal Carcinoma

OBJECTIVE: This study was conducted to assess the efficacy and safety of nimotuzumab combined with radiotherapy (RT) in elderly patients with nasopharyngeal carcinoma. MATERIALS AND METHODS: The clinical data of 75 nasopharyngeal carcinoma patients, who were initially treated with nimotuzumab combined with RT, were collected and retrospectively reviewed from December 2008 to April 2014. They were aged 60 to 81 years (median 64 years). The distribution of disease was stage II in 10 (13.3%), stage III in 33 (44.0%), and stage IV in 32 (42.7%). Among these patients, 59 cases received cisplatin-based chemotherapy. Survival outcomes and treatment toxicity were analyzed using IBM SPSS 19.0 software. RESULTS: With a median follow-up of 45 months (range, 13-78 months), the estimated 3-year local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), distant metastasis-free survival (DMFS), progression failure-free survival (PFS), and overall survival (OS) rates were 95.6%, 95.5%, 98.6%, 89.7%, and 89.2%, respectively. In the subgroup, 3-year OS rate in the patients with concurrent chemotherapy was 90.5% and 77.4% in patients without concurrent chemotherapy (Log-Rank = 1.795, P = .180). Univariate analysis showed that T stage and clinical stage were correlated with OS. Multivariate analysis indicated that age, T stage and tumor response at the end of treatment were independent prognosticators. Nine patients experienced grade 3 to 4 acute mucositis and 26 patients experienced grade 3-4 leukocytopenia, with no cases of skin rash and infusion reaction. Twelve patients developed mild liver function damage. No serious gastrointestinal or renal toxicities were observed. CONCLUSION: The efficacy of combined nimotuzumab with RT in elderly NPC patients was encouraging and the toxicities were accepted. In addition, nimotuzumab provides a better option for elderly patients who cannot be tolerate chemotherapy.