Quantitative studies of splenic erythropoiesis in polycythaemia vera and myelofibrosis

A quantitative scanning method employing cyclotron-produced 52Fe has been developed to assess splenic erythropoiesis in patients with myeloproliferative disorders. In 12 patients with myelofibrosis splenic uptake of 52Fe was from 5.0% to 48% of the injected dose. Although a single patient with classical polycythaemia vera had a minor uptake of 2.8% of six other patients with this diagnosis showed no concentration of isotope in the splenic area. The fraction of 52Fe in the spleen of four patients with 'transitional' myeloproliferative disorders characterized by a high red cell mass, hypercellular bone marrow and a leucoerythroblastic blood film varied from 5% to 41%. No clear relationship was noted between the degree of splenic erythropoiesis as defined by this technique and the level of haemoglobin, the degree of splenomegaly, the effectiveness of erythropoiesis of traditional 59Fe surface counting. If splenectomy is considered in patients with myelofibrosis splenic 52Fe quantitation will provide more precise data on the contribution of splenic erythropoiesis than 59Fe surface counting alone.     

Splenic sepsis in sickle cell disease

We describe two patients with sickle cell disease (SCD) who developed infections situated in the spleen. One patient had a splenic abscess and there was strong clinical evidence for an infected splenic infarct in the second patient. SCD predisposes to splenic infection because of functional hyposplenism, defective phagocyte function and splenic infarction. Splenic infections can occur in patients who might be considered to have an absent spleen and the diagnosis of splenic abscess should be considered in individuals with SCD who present with fever and abdominal pain.     

A new technique for laparoscopic splenectomy with massively enlarged spleens

Splenectomy is indicated in several hematological disorders and it can be particularly challenging in children with sickle cell disease, splenomegaly, and recurrent sequestration. Over the last 6 months, we have developed a new technique for laparoscopic splenectomy (LS) for hypersplenism and splenomegaly in five children with sickle cell disease. The average age of our patients was 6 years (range, 2-11), and the average weight was 18.7 kg (range, 13.2-30.1). On preoperative ultrasound, spleen size index ranged from 0.42 to 0.76. For the LS, four trochars were placed. One patient, who also underwent a laparoscopic cholecystectomy, had six trochars placed, two of which were used for both cholecystectomy and splenectomy. After laparoscopic mobilization of the spleen and hilar vascular stapling, a Steiner electromechanical morcellator was inserted through the 12-mm port to extract cores of splenic tissue until complete splenectomy was achieved. No patient required conversion to an open procedure or creation of a larger incision to remove the massively enlarged spleen. Operative time averaged 190 minutes; the combined LS and cholecystectomy took 245 minutes. Postoperative length of stay was <2 days for all patients. There were no complications, and no patient required postoperative transfusion. Based on these early findings, we conclude that intracorporeal coring of splenic tissue allows for safe and complete laparoscopic removal of very large spleens in small children. It provides expedient recovery and minimal postoperative pain and scarring. This new technique should enable surgeons to perform LS even in patients with massive splenomegaly, eliminating the need for large and cumbersome intracorporeal bags or the creation of additional incisions to remove the spleen.     

Splenic infarct as a late complication of liver transplantation

Splenic infarct is a rare complication of portal hypertension. It has been reported as an early complication after successful liver transplantation when portal pressure returns to normal and the splenic size progressively declines. It has not been reported as a late complication of liver transplantation. We describe the case of a 19-year-old patient with a splenic infarct which occurred 11 months after successful orthotopic liver transplantation for decompensated cryptogenic liver cirrhosis. Following transplantation, the patient was in excellent general health, liver function tests were normal, there was no clinical evidence of portal hypertension and the splenic size had decreased significantly compared to the pre-transplantation period, although it remained increased. The patient presented with high fever, left pleuritic pain and vomiting. The splenic size had not changed and left pleuritic exudate fluid collection was detected. A hypoechoic region of the spleen was demonstrated in the ultrasound examination corresponding to a hypodense lesion in the computerized tomography scanning. The patient recovered completely, with the disappearance of the infarct in the imaging studies in 2 months time. This case report indicates that a symptomatic splenic infarct can occur late following successful liver transplantation for liver cirrhosis despite lack of any evidence of residual portal hypertension at a time that splenomegaly has not yet regressed. The differential diagnosis from a splenic abscess in transplanted patients can be difficult but the final prognosis seems to be good.     

Long term treatment of myeloproliferative disease with interferon-alpha-2b: feasibility and efficacy

BACKGROUND: Recombinant interferon-alpha-2b (rIFN-alpha-2b) has shown therapeutic potential in patients with chronic myelogenous leukemia and other myeloproliferative disorders (MPDs), including the ability to suppress the abnormal hematopoietic clone and to reverse myelofibrosis. This study was conducted to evaluate further the efficacy and safety of rIFN-alpha-2b in a large group of patients with polycythemia vera, essential thrombocythemia, or agnogenic myeloid metaplasia and to determine maintenance of response after treatment discontinuation. METHODS: Induction therapy began with subcutaneous rIFN-alpha-2b at 5.0 x 10(6) IU/day until a complete or partial response was achieved. Treatment continued at 2.5 x 10(6) IU/day until spleen size and hematologic parameters stabilized. RESULTS: Fifty-four patients were studied (median follow-up, 7.3 years); at last follow-up 27 patients still were participating (median follow-up, 3.8 years). Twenty-four of 24 patients with thrombocythemia (100%) and 14 of 14 patients with hyperleukocytosis (100%) responded to induction therapy, whereas 26 of 39 patients (67%) experienced > 10% decrease in splenomegaly. Thirty-nine of 54 patients (72%) maintained response for a median of 39 weeks after withdrawal of rIFN-alpha-2b; repeat courses in previously responding patients produced similar results. The survival rate at 8 years was 60%. rIFN-alpha-2b generally was well tolerated, but toxicity caused treatment withdrawal in 7 patients (13%). CONCLUSIONS: rIFN-alpha-2b can produce regression of splenomegaly and control of leukocyte and platelet counts in patients with MPD. These responses are sustained for prolonged periods in some patients after therapy discontinuation. In patients with recurrent disease, disease control can be attained again with reinitiation of rIFN-alpha-2b. Therefore this therapy should be an important treatment consideration for patients with MPD.     

The risk of non-Hodgkin's lymphoma after Hodgkin's disease, with special reference to splenic treatment

BACKGROUND AND OBJECTIVE: One of the consequences of the enormous improvement in survival rates of patients treated for Hodgkin's disease (HD) is the emergence in the long term of treatment-related complications, particularly secondary cancers. This study was undertaken to observe the occurrence of non-Hodgkin's lymphoma (NHL) in patients treated for HD and to identify the etiological role of various risk factors, especially spleen irradiation, in the pathogenesis of this illness. DESIGN AND METHODS: From 1972 to 1996, the Department of Radiation Oncology and the Hematology Section of "La Sapienza" University of Rome observed and analyzed the occurrence of NHL in 1,391 patients treated for HD. The average follow-up period was 84 months. For a more accurate calculation of the risk of the occurrence of NHL, the patients were first divided into 3 groups according to their initial treatment and also according to the total treatment they had received. Then, in order to establish the possible connection between NHL and splenic treatment the patients were also divided into 3 subgroups according to whether they had undergone splenectomy, splenic irradiation or neither of these. Two different methods of statistical analysis were used: (a) the cumulative risk (confidence interval) was evaluated in relation to treatment (initial and at the time of salvage) and (b) the Cox model was applied to identify the variables which play a role in the appearance of NHL. The cumulative risk of developing NHL was assessed using the Kaplan and Meier method. A multivariate analysis was performed using the Cox Proportional Hazard Model. RESULTS: A total of 20 cases of NHL were observed, appearing between 17 and 206 months after initial treatment. The cumulative risk was 0.8%, 1.8%, 2.6% and 3.5% at 5, 10, 15 and 20 years respectively. According to the multivariate analysis, significant risk factors were splenic irradiation and age (> 40 years). Splenic irradiation (vs no splenectomy/no splenic irradiation) showed a relative risk of 5.69, p = 0.0280, while age over 40 showed a relative risk of 3.05, p = 0.0152. INTERPRETATION AND CONCLUSIONS: From the results of this study, if appears that there is a possibility that splenic irradiation and age over 40 increase the risk of NHL in HD patients. Further studies are needed to investigate in greater depth the role of spleen irradiation in the occurrence of this illness.     

Relationships between lymphography and the histologic nodal and splenic types in Hodgkin''s disease. Considerations on clinical evolution

Trying to establish the eventual interrelations of the initial histologic nodal type and the splenic one, the general lymphographic picture, the histologic nodal type and spleen involvement, lymphographic and histologic examinations were carried out in 151 patients with Hodgkin's disease. Lympographies were performed in 139 cases, and splenectomy (followed by splenic, hepatic and abdominal lymph node biopsies) in 32. Lymphocyte depletion was found in 72.7% of the patients with lymph node obstruction diagnosed lymphographically. Splenic involvement was more frequent in cases with pathologic lymphographic picture and histologic aspects of lymphocyte predominance or nodular sclerosis. In patients with initial nodal histologic types of nodular sclerosis or lymphocyte depletion, the splenic histopathologic types were the same, but they got more severe in cases with lymphocyte predominance or mixed cellularity. Splenic biopsy might be unconclusive after protracted cytostatic treatment or splenic X-ray therapy. In the authors' opinion, early routine splenectomy is rather more advisable than differentiated splenectomy.     

Retrograde transport of nerve growth factor from olfactory bulb to olfactory epithelium

OBJECTIVE: The purposes of this study were to determine if splenic perfusion measurements obtained using dynamic CT are useful in the evaluation of portal hypertension. MATERIALS AND METHODS: Forty-four patients with chronic liver disease (29 men and 15 women, 49-81 years old) and 38 control subjects (17 men and 21 women, 21-79 years old) underwent dynamic CT of the spleen. Regions of interest were drawn on images of the spleen and aorta, and splenic perfusion was calculated by dividing the peak gradient of the splenic time-attenuation curve by the peak aortic CT measurement increase. In 11 patients with chronic liver disease and three patients with normal livers, we measured the wedged hepatic vein pressure (WHVP) of the right or right accessory hepatic vein to estimate portal vein pressure. RESULTS: Splenic perfusion was less in patients with chronic liver disease (0.894 +/- 0.324 ml/min) than in the control group (1.299 +/- 0.429 ml/min; p < .0001). We found a significant negative correlation between splenic perfusion and WHVP (r = .741; p = .0024). CONCLUSION: A significant decrease in splenic perfusion in patients with chronic liver disease negatively correlated with WHVP. Measurement of splenic perfusion may be useful in the evaluation of portal hypertension.     

"Delayed rupture of the spleen" or delayed diagnosis of the splenic injury?

Splenic rupture is the most frequent intraabdominal injury following blunt abdominal trauma. Massive hemorrhage commonly occurs from injuries to this friable vascular organ. The mortality rate from simple splenic rupture is 1%. Delayed diagnosis of a ruptured spleen increases the rate to 10%. During 1964-79, 293 patients underwent splenectomy for blunt splenic injury, of whom 278 were operated on within 24 h. All had typical signs of splenic lacerations with intraperitoneal bleeding from the time of injury. Fifteen patients were operated on more than 48 h after sustaining the injury. A detailed analysis of these 15 patients revealed that in only three did the evidence support delayed hemorrhage following traumatic rupture of the spleen. In the other 12 patients, there was a delay in recognition of the intraabdominal injury, almost entirely the result of "diagnostic error." Careful clinical inquiry and peritoneal lavage are the mainstays of early diagnosis and therapy and should help to eliminate any delay in the diagnosis of a ruptured spleen.     

Laparoscopic splenectomy in beta-thalassemia major patients. Advantages and disadvantages

BACKGROUND: Splenectomy is indicated in patients with thalassemia major when they develop hypersplenism with subsequent need for increased transfusions. Extreme splenomegaly is considered a restrictive factor for laparoscopic splenectomy in these patients. METHODS: Laparoscopic splenectomy was undertaken in 12 beta-thalassemia major patients with massive splenomegaly. The devascularization of the organ was performed with serial ligations of the splenic vessels starting from the lower pole of the organ. The spleen was extracted from the abdominal cavity through a 5-cm incision in the left iliac fossa, which incorporated two port sites. RESULTS: The procedure was concluded laparoscopically in 10 cases, while two patients were converted due to difficulty in controlling bleeding from branches of the splenic vein. The patients tolerated the procedure well and had a postoperative hospital stay of 3-6 days. CONCLUSIONS: From our limited initial experience it seems that laparoscopic splenectomy in the difficult setting of thalassemia major patients is feasible, but extreme care is required in order to avoid hemorrhagic complications.     

Splenic lymphoma with villus lymphocytes--an uncommon cause for lymphocytosis

We describe the clinical and laboratory features of four patients who presented with mild to moderate lymphocytosis but with no peripheral lymphadenopathy. These patients in the past, would have been classified as chronic lymphocytic leukaemia (CLL). However, it is now realised that chronic lymphoproliferative disorders are very heterogeneous and the clinical and laboratory features of our patients would support a diagnosis of splenic lymphoma with villus lymphocytes (SLVL) with characteristic morphological features. SLVL usually runs a benign clinical course but symptoms related a benign clinical course but symptoms related to splenomegaly or hypersplenism may be a problem. Splenectomy is considered the treatment of choice in these patients. Two of our patients had splenectomy and the other two patients are on regular follow-up without any specific treatment. It is therefore important to recognise this uncommon condition and also to differentiate it from CLL.     

Isolated splenic trauma in adults: value of Resciniti's CT scoring system to define the indications for surgery

The data of 62 adult patients with isolated blunt splenic trauma were retrospectively analysed to determine the value of a CT score-system in the choice of treatment: nonoperative treatment versus surgical management. 22 patients (35%) without hemodynamic instability presenting with pain localized in the left flank were primarily managed conservatively. 3 of them subsequently required splenectomy. 40 patients (65%) were operated immediately, 32 on the basis of clinical criteria and 8 on the basis of laboratory criteria. 45 patients with no initial haemodynamic disorders were investigated by abdominal CT-scan. Splenic injuries were retrospectively classified according to Resciniti's CT-scoring system. 13 patients had a splenic injury score > or = 5.5. All of them were operated, 11 early and 2 after failure of conservative management. According to our study this score > or = 5.5, which concerns 21% of our patients, can be considered to be an indication for surgery; in this case, a conservative approach should not be at tempted, even in the absence of immediate clinical and laboratory operative criteria.     

bcl-2 protein is strongly expressed in post-transplant lymphoproliferative disorders

BACKGROUND: Splenic complications of sickle-cell disease (SCD) are associated with morbidity, and in some it may lead to mortality. This paper presents our experience with 43 patients with SCD who had splenectomy as part of their management. PATIENTS AND METHODS: The records of 43 patients with SCD who had splenectomy were examined for age at operation, sex, hemoglobin (Hb) electrophoresis, indication for splenectomy, pre- and postoperative medications, operative procedures, and postoperative complications. RESULTS: The indications for splenectomy were acute splenic sequestration crisis (ASSC) in 21 patients, hypersplenism in 15, and splenic abscess in 7. In 17 patients, the spleen was also found to be massively enlarged causing discomfort and intervening with everyday activity. For those with hypersplenism, there was a significant postoperative increase in total Hb (P < 0.0001), hematocrit (P < 0.0001), white blood cells (P < 0.0001), and platelet count (P < 0.0001). CONCLUSIONS: With careful perioperative management and proper follow-up, splenectomy in patients with SCD is beneficial in reducing their transfusion requirements and its attendant risks, eliminating the discomfort from mechanical pressure of the enlarged spleen, avoiding the risks of ASSC, and managing splenic abscess.     

Sequential half-body irradiation in childhood

Single-dose half-body irradiation (HBI), introduced for the palliation of pain from widespread bone metasases in adults, has proved to be successful. Relief is obtained in a high proportion of patients, with upwards of two-thirds experiencing complete relief. Onset of response is fast and clinically valuable duration varies from 5 to 20 weeks. Objective evidence of tumor regression is found less frequently. The dose-limiting toxicity has proved to be acute radiation pneumonitis, with bone marrow tolerance of lesser importance, in spite of the fact that many patients received previous local irradiation and/or chemotherpy. Palliative HBI has not become a valuable treatment in pediatric malignancies, because of a shorter metastatic phase. Pediatric tumors usually have shorter cell cycle times and are more responsive to systemic agents. Results are described in selected institutions, where HBI has been used in the treatment of pediatric malignancies. A single institution pilot study was undertaken at the Princess Margaret Hospital involving 17 patients with Ewing's sarcoma of bone, without overt metastases at diagnosis. Results to date have not been obviously different from overall survival in the first intergroup Ewing's sarcoma study. Overall, the treatment has been shown to be well tolerated and can be given entirely on an out-patient basis. When compared on a historical basis with a previous single dose total body irradiation study, the one year survival rate was increased. HBI appears to be a tolerable treatment, when given concurrently with or sequential to local and systemic treatment.     

Splenic rupture: an unusual complication of colonoscopy

Splenic rupture is an uncommon complication of colonoscopy. A high index of suspicion is a crucial factor in the prompt diagnosis of this rare but potentially fatal complication. We report a case of splenic rupture diagnosed 3 days after a colonoscopy and requiring splenectomy. We also reviewed 17 reported cases of splenic rupture after colonoscopy, including our case. The presumed mechanisms of splenic rupture during colonoscopy are direct trauma to the spleen, excessive splenocolic ligament traction, and decrease in the relative mobility between the spleen and the colon. Of the 17 cases reviewed, 10 had polypectomy and/or biopsy performed during colonoscopy. Other probable risk factors are identified and tabulated. The hemodynamic status of the patient is the primary factor used to determine the therapeutic option. Computed tomographic (CT) scan of the abdomen reliably demonstrates well-contained splenic laceration and subcapsular hematoma, and differentiates these splenic complications from perisplenic clot and hemoperitoneum. Thus, CT scan may help decide which patients may be managed operatively or nonoperatively. Splenectomy is the operative procedure of choice for splenic rupture after colonoscopy. Conservative management includes broad spectrum antibiotics, intravenous fluids, blood transfusion, and close hemodynamic monitoring. The factors mandating further evaluation of persistent abdominal pain after colonoscopy are hemodynamic instability, clinical features of acute abdomen, leukocytosis, and/or acute anemia. The onset of abdominal pain associated with one or more of these critical factors is usually within 24 h after colonoscopy. An emergent CT scan of the abdomen is the modality of choice to further evaluate these clinical features, but intestinal perforation and external bleeding must first be excluded.     

Splenomegaly in 2,505 patients in a large university medical center from 1913 to 1995. 1913 to 1962: 2,056 patients

Splenomegaly was studied retrospectively at the University of California, San Francisco, School of Medicine, on all patients (N = 2,056) for the years 1913 to 1962. The patients were classified into several diagnostic groups, and these groups were tested for statistical significance (chi(2)) with many clinical and laboratory variables to determine their predictive value. Hematologic disorders were associated with 57% of cases of splenomegaly and 81% of cases of massive splenomegaly. Among patients with splenomegaly, 19% had infectious diseases, 11% had hepatic diseases, and 9% had congestive or inflammatory disorders. The residual 4% were considered to have primary splenic disorders or a disorder of unknown cause. The commonest diseases associated with splenomegaly were hematologic (acute and chronic leukemias), infectious (malaria, endocarditis, and tuberculosis), hepatic (chronic liver disease), congestive (congestive heart failure), inflammatory (thyrotoxicosis), and other (cancers not metastatic to the spleen). The diseases most frequently associated with massive splenomegaly were the chronic leukemias. The disease with the highest incidence of massive splenomegaly was myelofibrosis (23 of 29 patients, 78%). Splenectomy was performed in 154 patients (7%), primarily for hematologic amelioration and hepatic hypersplenism. Hematologic diseases showed significant associations with lymphadenopathy, generalized lymphadenopathy, massive splenomegaly, and cytoses (P .001) and with progressive splenic enlargement (P < .02). Infectious diseases showed significant association with fever, and hepatic diseases showed significant association with abnormal results of liver function tests (P < .001). The findings of this retrospective study should be validated prospectively.     

A review of pathological diagnoses made from 87 canine splenic biopsies

The pathological findings in 87 cases of canine splenic abnormality recognised clinically by abdominal palpation or radiography, or at exploratory laparotomy, are presented. The most common diagnosis was of splenic neoplasia (n = 38) and the most frequently recognised canine splenic neoplasm was haemangiosarcoma (17 of 38 cases). Benign splenic enlargement secondary to nodular hyperplasia (n = 6), haematoma (n = 16) or non-specific changes including congestion, haemorrhage, extramedullary haemopoiesis and haemosiderin deposition (n = 14) was also recognised. A diagnosis of non-specific pathology was more frequently recorded when portions of spleen, as opposed to the entire organ, were submitted for assessment. Splenic infarction, with (n = 3) or without (n = 7) torsion, abscessation (n = 2) and focal mast cell proliferation (n = 1) accounted for the remainder of the cases. Clinical follow-up was available for 35 cases and revealed good long-term survival in cases of splenic haematoma or haemangioma, with relatively poor survival with a diagnosis of splenic haemangiosarcoma or anaplastic sarcoma. A range of splenic disorders was recognised in dogs of the labrador breed (16 of 87 cases) and three of 17 cases of haemangiosarcoma occurred in German shepherd dogs. The possible predisposition of dogs of these breeds to splenic disorders is discussed.     

Clinical and roentgenographic findings in splenic abscess

A splenic abscess developed in a 16-year-old boy following a supposed viral illness and left lower thoracic trauma. Preoperative diagnosis was at first obscured, but a spleen scan suggested fractured spleen and a splenic arteriogram showed a "subcapsular hematoma" and an aneurysm of the left hepatic artery. A 1,800-gm spleen containing one large abscess and one small one was removed. Splenic abscess is rare and, before modern methods of spleen scan and arteriography, rarely diagnosed.     

Porphyria cutanea tarda and hematologic malignancy--a report of 4 cases

Porphyria cutanea tarda has been reported in association with a variety of myeloproliferative and lymphoproliferative disorders, suggesting a possible association between these conditions. We describe four patients presenting within a 12 month period with sporadic porphyria cutanea tarda shortly following the diagnosis of hematologic malignancy. A review of the literature and evidence supportive of a causal association are presented.     

Posterior tibial neuropathy from ruptured Baker''s cyst

BACKGROUND: There is epidemiological evidence that suggests there are beneficial effects of ionizing radiation at low doses. Some experimental studies confirmed this hormetic effect with doses of about 1 cGy/day, but no data concerning very low dose rates are available. OBJECTIVE: The aim of this study was to determine the life span of mice exposed to very low doses of ionizing radiation. METHODS: Six hundred female C57BL/6 mice, 1 month old, were exposed to chronic gamma irradiation at very low dose rates of 7 or 14 cGy/year. These doses are about 25 or 50 times higher than background, but much lower than the doses of about 1 cGy/day used in previous experiments. Three hundred mice living in the same room were used as controls. RESULTS: The life span, after the beginning of the experiment, determined by the survival time of 50% of each population, is increased in irradiated mice: 549 days in controls, 673 days in both irradiated groups. The differences are significant between the control and the irradiation mice. Differences between mice irradiated with 7 or 14 cGy are not significant. CONCLUSIONS: These results confirm the possibility of a nonharmful effect (hormesis) of ionizing radiation. They demonstrate that the paradigm, which states that low-dose effects can be predicted high-dose effects, cannot be systematically applied in radiation biology in general and gerontology in particular.