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[Long-term effects of splenectomy for immune thrombopenic purpura related to human immunodeficiency virus. A retrospective study from 2 groups, with and without splenectomy].

In order to evaluate the long-term effects of splenectomy in patients with human immunodeficiency virus-related immune thrombocytopenic purpura (ITP), we studied retrospectively two populations of patients: 21 had undergone splenectomy and 18 had not. At the time of diagnosis the first population had on average lower platelet counts than the second one. After a mean follow-up of 47 +/- 9 months the situation has been reversed: the population that underwent splenectomy had significantly higher platelet counts than that without splenectomy (190.600 +/- 55.300/mm3 versus 91.500 +/- 55.300/mm3, P less than 0.001). Moreover 76 percent of the patients with splenectomy versus 50 percent in the population without splenectomy were in complete remission of ITP at the last follow-up. It therefore seems that splenectomy had a statistically positive effect on platelet counts without worsening the immune status. Indeed, the clinical course towards AIDS was the same in both populations (35 percent in patients with splenectomy and 22 percent without, P = NS). Following splenectomy, the total blood lymphocytes count was increased, especially the CD8 population, while the CD4 count remains unchanged; these findings seem to be a common feature after splenectomy.

Acquired Immunodeficiency Syndrome

Splenectomy or radiation and splenectomy for hypersplenism in lymphosarcoma.

This is a retrospective study of 14 patients with lymphosarcoma with hypersplenism. Eight patients received radiation to the spleen followed by splenectomy for recurrence of hypersplenism. Six patients underwent primary splenectomy for hypersplenism. Radiation decreases the size of the spleen but recurrence of hypersplenism is seen in an average of 8 mo. Splenectomy in these cases improves the hematological picture. Average postsplenectomy survival is 27.6 mo. Splenectomy alone in hypersplenism also improves the hematological picture. Postsplenectomy survival in this group is 13 mo. One case of primary lymphosarcoma of the spleen is reported.

Adult

[The relationship between responsiveness to splenectomy and clinical course after splenectomy in chronic idiopathic thrombocytopenic purpura (ITP)].

Fifty-four ITP patients were treated by the protocol proposed by Japanese Idiopathic Disease of Hematopoietic Organ Research Committee. Forty-eight patients were treated with corticosteroid (CS). Twenty-eight patients out of 30 patients who were refractory to CS were splenectomized. To study natural courses of splenectomized patients, 25 patients were splenectomized without elevation of platelet counts at the operation and were followed up their platelet counts and PAIgG for one month without treatment. Clinical courses after splenectomy were classified into four types by the platelet increment followed by splenectomy and the platelet counts at one month after splenectomy; type I (markedly over-shooted platelet peak and normalized platelet counts), type II (moderate platelet peak and 50 approximately 100 x 10(3)/microliters platelets), type III (minimal platelet peak and less than 50 x 10(3)/microliters platelets), and type IV (elevation of platelet counts at day 7 or later of splenectomy and normalized platelet counts). The results of analyses from 25 patients indicated that the numbers of type I, II, III and IV were 10, 5, 6 and 4, respectively. The clinical course of type IV suggests that platelet production may be impaired by anti-platelet antibodies.

Adult

A 27-year experience with splenectomy for Gaucher's disease.

Gaucher's disease is an inherited metabolic disorder caused by the defective activity of acid beta-glucosidase and the resultant accumulation of glucosyl ceramide-laden macrophages in the liver, bone, and spleen. Splenectomy is the preferred treatment for patients with Gaucher's disease who develop massive splenomegaly with accompanying hypersplenism and/or mechanical pressure symptoms. The charts of 48 patients with Gaucher's disease undergoing splenectomy at our institution between January 1963 and December 1989 were analyzed to determine the short- and long-term results of this procedure. Thirty-five (73%) patients had total splenectomy, whereas 13 (27%) patients had partial splenectomy. There was one postoperative death (after total splenectomy), and 13 patients (27%) had postoperative complications. Eleven patients (23%) presented with accelerated bone disease after total splenectomy (mean follow-up: 96 months). No patients having partial splenectomy (mean follow-up: 25 months) developed progressive bone disease. Eight patients have died since surgery. All four deaths due to malignant disease occurred in patients after total splenectomy. The results of this largest-ever reported series of splenectomy for Gaucher's disease confirm that while either total or partial splenectomy can be performed with minimal morbidity and mortality, total splenectomy is accompanied by more aggressive bone disease and a predisposition to malignancy. Prospective, randomized trials are needed to substantiate whether partial splenectomy is indeed the treatment of choice for splenomegaly associated with Gaucher's disease.

Adult

Splenectomy influences endotoxin-induced bacterial translocation.

To determine whether splenectomy affects the antibacterial defenses of the gut, experiments were performed using bacterial translocation (BT) as a marker of intestinal barrier failure. The incidence of BT was measured 8 days after splenectomy or sham-splenectomy in mice receiving or not receiving endotoxin (0.1 mg IP). Splenectomy does not appear to promote BT from the gut, since the incidence of bacterial translocation after splenectomy or sham-splenectomy (5%) were not different. A second experiment was performed to determine whether the resistance to endotoxin-induced BT was modified after splenectomy. The incidence of endotoxin-induced BT was 73% in the unoperated control group, 59% in the sham-splenectomy group, but 23% in the splenectomy group (p less than 0.002). Thus, splenectomy but not sham-splenectomy increased the resistance of otherwise healthy mice to endotoxin-induced BT.

Animals

Influence of splenectomy on platelet morphometry and function.

Functional and morphometric platelet abnormalities may be influenced by splenectomy and thus contribute to postoperative thrombohaemorrhagic complications, especially in patients with splenomegaly and/or platelet defects. We investigated platelet function, platelet secretion, and platelet morphometry before and one week after splenectomy in seven patients with normal platelet production and normal spleen size (Hodgkin's disease) and five patients with splenomegaly and platelet abnormalities (4 with myeloproliferative disorders and 1 with chronic myelomonocytic leukemia). Severe postoperative thrombohaemorrhagic complications occurred only in patients with myeloproliferative disorders, although platelet count and mean platelet volume increased in almost all patients after splenectomy. Four patients with myeloproliferative disorders had impaired platelet aggregation before splenectomy that improved in only one patient after surgery. Platelet buoyant density in this patient group was decreased before splenectomy and normalised thereafter. Concomitantly, intraplatelet concentrations of alpha-granular proteins increased. Before splenectomy, there was a positive correlation between platelet density and platelet volume in patients with Hodgkin's disease (r = 0.59, p less than 0.001), but not in patients with myeloproliferative disorders. There was no correlation between platelet density and platelet volume after splenectomy in either patient group. In conclusion, morphometric platelet abnormalities were found in all patients after splenectomy. In patients with myeloproliferative/myelodysplastic disorders, decreased platelet buoyant density normalised and intraplatelet concentrations of alpha-granule proteins were elevated after splenectomy. However, platelet function defects in this patient group were not corrected and may have been a major cause of thrombohaemorrhagic complications in the postoperative period.

Adult

Early post-splenectomy sepsis after missile injury in adults.

Early septic complications were studied in 292 patients operated on for penetrating missile injury of the abdomen with involvement of either the spleen or the liver, at Basrah Teaching Hospital between January 1983 and April 1986. Depending on associated injuries, patients with splenectomy were divided into three groups, the first with isolated splenic injury, the second with splenic and associated extra-intestinal organ injury, and the third with splenic and intestinal injuries with or without extra-intestinal organ injury. Patients with hepatic injury were classified similarly. Splenectomy was carried out for any degree of splenic injury. Grade I hepatic injuries were managed by débridement and suturing while major grades II-IV underwent segmentectomy or lobectomy. Patients were considered septic if they had any three of four clinical criteria: temperature higher than 39 degrees C; significant haemodynamic deterioration; respiratory alkalosis, or oliguria. Of the total, 79 were excluded due to: early transfer 51, incomplete records 8, perioperative death 11, and having combined splenic and hepatic injuries 9 (excluded by definition), leaving 104 (74.8%) patients with splenectomy and 109 (71.1%) with hepatic injury available for study. Sepsis developed in 48 (46.1%) of patients after splenectomy and in 28 (25.7%) with hepatic injury. This difference was significant (P greater than 0.005). In patients with isolated splenic injury, eight (25.8%) were septic while three (13.6%) of those with isolated hepatic injury developed sepsis. This was not significant (P = 0.32, Fisher's exact test). When either was associated with an injury to an extra-intestinal organ, 15 (50%) of the splenectomy group developed sepsis compared to five (23.8%) of the hepatic injury group. This did not reach significance. When either was associated with intestinal injury, sepsis developed in 25 (58.1%) of the splenectomy patients, in contrast to 20 (30.3%) of patients with hepatic injury. This was significant (P < 0.005). Gram-negative coliforms were the most common organisms isolated comprising 72.5% and 67.8%, in contrast to pneumococci isolated in 5.9% and 3.6% in the splenectomy group and hepatic injury group, respectively.In conclusion, in patients with penetrating missile injuries of the abdomen, the risk of sepsis is increased after splenectomy compared to hepatic injury, only if there was associated bowel injury. This was reflected in the type of causative organism (predominantly enteric flora) despite 'appropriate'antibiotic cover, as well as a fivefold increase in mortality among the splenectomy group. We suggest that splenic salvage, where feasible, is mandatory if associated with intestinal injury.

Adolescent

Relative merits of partial splenectomy, splenic reimplantation, and immunization in preventing postsplenectomy infection.

Partial splenectomy, splenic autotransplantation, and immunization with pneumococcal vaccine have been reported to protect patients against overwhelming postsplenectomy infection, and this study was undertaken to evaluate these therapeutic alternatives. For this purpose 136 rats were divided into experimental groups: 34 controls, 34 splenectomy, 34 partial splenectomy, and 34 splenic autotransplantation animals. Five weeks after operation, two-thirds of the animals were immunized with killed pneumococci. The effects of operation and immunization were studied by challenging the animals intravenously with pneumococci. Pneumococcal antibody titers were determined, and phagocytic uptake of pneumococci by the spleen and liver was measured. Immunization impressively increased the survival rate in all groups. At low-challenge doses autotransplantation prolonged survival. At higher-challenge doses only partial splenectomy increased survival. Partial splenectomy and control animals had higher antibody titers than did splenectomy and autotransplantation rats. Animals with the highest antibody titers had the greatest splenic and hepatic phagocytic uptake of pneumococci. Partial splenectomy was more efficient in removing pneumococci than was autotransplantation. Thus immunization is one of the most important factors contributing to survival after splenectomy. Partial splenectomy is preferable to splenic autotransplantation because it is associated with higher antibody titers after immunization, better pneumococcal splenic uptake, and improved survival rates.

Animals

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.

Adult

Evaluation of splenectomy in chronic myelogenous leukemia.

Splenectomy was performed in 45 patients with chronic myelogenous leukemia; 23 were in the chronic phase and 22 in the acute phase. Indications for operation included inability to control the disease by chemotherapy or radiation therapy, severe thrombocytopenia, frequent need for blood transfusion and extensive splenomegaly causing discomfort. Median survival time for these patients was better than survival time of other reported groups of patients who did not have a splenectomy. According to our criteria, splenectomy was beneficial to 15 patients in the chronic phase as well as to eight in the acute phase of chronic myelogenous leukemia. Median survival time after splenectomy was higher in patients who had splenectomy within two years of the diagnosis as compared with those who had the operation after two years. Splenectomy did not prevent the future onset of fatal blastic crisis. Although significant abnormalities in coagulation studies were seen in 37 of the patients, intraoperative hemorrhage was not a major problem. Considering the poor general condition, inadequate healing and susceptibility to infection, the postoperative mortality and complication rates were comparable with those reported in series in which splenectomy was performed for other diseases. It seems that splenectomy benefits a selected group of patients with chronic myelogenous leukemia; however, a randomized series would furnish better data upon which to make decisions.

Adult

[Segmental pancreatic lesions after partial or total splenectomy in rabbits].

Previous experiments on compensatory hypertrophy of the splenic parenchyma after partial splenectomy, permitted us to observe lesions of the part of the pancreas in contact with the spleen. This part of the gland is supplied only by the splenic artery and suffers from some degree of ischemia during splenectomy. The object of this research was to seek, as a routine, pancreatic disease after splenectomy. 32 adult rabbits were used. Partial splenectomy carried out in 15 cases, removed about 2/3rds of the spleen and involved ligature of 4 or 5 splenic and mesenteric arterio-venous pedicles. Total splenectomy, carried out in 17 cases, included ligature of the splenic arteriovenous trunk and 3 or 4 spleno-gastric and spleno-mesenteric arterio-venous pedicles. These operations were followed by more or less intense stasis extending to the splenic part of the pancreas. The animals were examined one week and 8 months afterwards. All the rabbits, except one, had pancreatic lesions. The most severe and extensive lesions, including large areas of cytosteato-necrosis with, in 11 cases, pseudo-cysts, with caseation, followed total splenectomy. Partial splenectomy gave rise to 6 pseudocysts including 2 containing blood and 9 cases with milder lesions including involution, rarefaction and sometimes disappearance of the gland which had suffered from ischemia. In these splenectomies, ligature of the splenic arterio-venous pedicles supplying the pancreas were responsible for pancreatic disease.

Animals

Effect of splenectomy in tumor-bearing mice and gastric cancer patients.

In order to investigate the effect of splenectomy on tumor growth, splenectomy was performed in DDS mice transplanted subcutaneously with Ehrlich ascites tumor cells before and after the transplantation. It was found that, in the first control group receiving sham operation, all the mice died of tumor; in the second group that underwent splenectomy 1 week before the transplantation the tumor regressed in every case; in the third group that received splenectomy 5 days after transplantation when tumor became established, the tumor regression was observed in 85% of the animals, and in the fourth group that underwent splenectomy 10 days after transplantation, all the animals died of tumor earlier than the sham-operated first group. In the follow-up observations of 389 patients with gastric cancer who underwent gastrectomy alone and 89 cases who received gastrectomy combined with splenectomy, the 5-year survival rate of the latter group tended to show a better prognosis in a relatively early stage. It was concluded that splenectomy might inhibit the growth of tumor in a certain early stage, in both animals and humans, and the possible mechanism of this effect of splenectomy was discussed from the immunological aspects.

Animals

Effect of splenectomy on morbidity and survival following curative gastrectomy for carcinoma.

We performed a retrospective analysis of 392 patients who underwent curative resection of gastric adenocarcinoma to evaluate the impact of splenectomy on survival from gastric cancer and postoperative morbidity. Twelve factors, including splenectomy, were associated with a poor prognosis by univariate analysis. Multivariate analysis identified six of these factors, but not splenectomy, as independently predictive of death due to gastric cancer. The apparent adverse effect of splenectomy was due to its association with other significant risk factors. Postoperative complications occurred more commonly in patients who underwent splenectomy than in those who did not (45% vs 21%); patients in the splenectomy group also had a higher percentage of infectious complications than those in the nonsplenectomy group (75% vs 47%). We conclude that splenectomy has no direct influence on survival, but that it increases the morbidity of curative gastrectomy and should be avoided unless the spleen is close to or invaded by the tumor.

Adenocarcinoma

Splenectomy does not correlate with length of survival in patients undergoing curative total gastrectomy for gastric carcinoma. Univariate and multivariate analyses.

The relationship between splenectomy and survival time after curative total gastrectomy for advanced gastric cancer was examined by reviewing retrospectively data on 252 patients treated in our clinics between 1965 and 1985. One hundred three patients (40.9%) did not undergo splenectomy and 149 (59.1%) did. In patients subjected to splenectomy, advanced stages of the malignancy were more frequent and metastasis was noticed in 8.1% of splenic hilar lymph nodes and in 10.1% of the lymph nodes associated with the splenic artery. A univariate analysis revealed that the survival time of patients with splenectomy was significantly less than those for whom splenectomy was not done (P less than 0.05). In a subgroup of our patients stratified to adjust for the stage of disease, there was no significant difference between the survival rates. Subsequently, multivariate analysis using the Cox regression analysis adjusted for sex, age, and other covariates indicated that serosa invasion, lymph node metastasis, and tumor size were the most important prognostic factors, and there was no correlation whatever with splenectomy. Our findings rule out any relationship between splenectomy and length of survival time in patients undergoing curative total gastrectomy for advanced gastric cancer.

Carcinoma

Splenectomy vs. alpha interferon: a randomized study in patients with previously untreated hairy cell leukemia.

Twenty patients with previously untreated hairy cell leukemia were randomized to undergo either splenectomy or to receive interferon alfa-N1, a highly purified natural alpha interferon, as primary therapy. A response in the peripheral blood elements to a hemoglobin greater than 110 gm/l, a granulocyte count greater than 1 x 10(9)/l, and a platelet count greater than 100 x 10(9)/l (Catovsky criteria) was noted in all ten patients receiving alpha interferon but in only three of the patients undergoing splenectomy (P = less than .01). Median time to response was longer in the ten interferon patients (153 days) than in the three splenectomy responders (20 days). Median time to treatment failure was significantly greater in the alpha interferon patients (greater than 18 months) than in the splenectomy patients (less than 1 month). Survival was no different since patients relapsing following splenectomy subsequently responded to alpha interferon. A significant decrease in leukemic bone marrow infiltration was observed in seven of ten patients receiving alpha interferon and in none of the patients undergoing splenectomy. Side effects, primarily infections, were more frequent in patients receiving interferon. Alpha interferon is preferable to splenectomy as initial treatment for hairy cell leukemia.

Adult

Splenectomy in childhood: a review in England and Wales, 1960-4.

An investigation was carried out of 821 children under the age of 16 years who were subjected to splenectomy in England and Wales during the 5 years 1960-4. A postal follow-up study provided satisfactory information concerning 96 per cent of these. Excluding early postoperative deaths, practically all the cases were followed up for 2 years or more and 70 per cent for more than 5 years. Forty-nine children had died since operation, 32 from underlying disease and 17 from infection. Fifty children (6 per cent of the survivors) had major infections considered to be due to the primary condition aggravated by splenectomy. Seven died, all from the primary disease. Sixteen children (2 per cent) developed septicaemic illnesses and 10 died. In these the effect of splenectomy was considered to be the primary factor. Fourteen of the 16 had been operated on in the first 4 years of life. Practically all the serious infections occurred within 3 years of operation and pneumococcus was the organism most frequently implicated. Ninety per cent of the splenectomies in childhood were performed for accidental injury, congenital haemolytic anaemia or idiopathic thrombocytopenic purpura. Accidental injury to the spleen rarely occurs in very young children, and in the other two conditions splenectomy can usually be safely delayed untile over the age of 3 years. If this is achieved it is estimated that the unavoidable risk of dangerous infection is less than 1 per cent. One in 10 splenectomies will be carried out for severe and potentially fatal illnesses and in this situation the risk from operation is of secondary importance. Many such conditions carry increased susceptibility to infection per se or because corticosteroids or other immune suppressants are used in their management. It is recommended that splenectomy be avoided if at all possible during the early years of life. It is further recommended that prophylactic penicillin be administered for 3 years following operation whatever its indication and whatever the age of the patient. If the underlying condition itself carries risk of infection more active and more prolonged prophylaxis may be indicated.

Adolescent

Splenectomy in advanced chronic lymphocytic leukemia: a single institution experience with 50 patients.

PURPOSE: To assess the efficacy of splenectomy in the treatment of refractory cytopenias associated with advanced chronic lymphocytic leukemia (CLL). PATIENTS AND METHODS: The histories of 57 patients with CLL who underwent splenectomy at the Mayo Clinic between 1975 and 1991 were retrospectively reviewed. Of the 57 patients, 50 underwent splenectomy for reasons directly related to their disease process such as cytopenias or symptomatic splenomegaly. The histories from these 50 patients were studied to assess the response to splenectomy and the operative morbidity and mortality. RESULTS: Ninety-four percent of patients were in Rai stage III or IV with extensive marrow infiltration, massive splenomegaly, and cytopenias refractory to chemotherapy. A positive response to splenectomy was defined at 3 months of follow-up as: (1) a hemoglobin level of 11 g/dL or greater in a patient with a preoperative value less than 11 g/dL; or (2) a platelet count of 100 x 10(3)/mm3 or greater in a patient with a preoperative value less than 100 x 10(3)/mm3. A positive response was achieved in 77% of patients with anemia, 70% of patients with thrombocytopenia, and 64% of patients with both anemia and thrombocytopenia. The response was sustained at 1 year of follow-up in 86%, 84%, and 85% of the patients, respectively. Postoperative transfusion requirements decreased correspondingly. The operative morbidity was 26%, and the operative mortality was 4%. The mean duration of hospitalization was 9.8 days (median: 9 days; range: 5 to 24 days). The actuarial median survival after splenectomy was 41 months in responders and 14 months in nonresponders. We found no preoperative parameters that were clearly predictive of a poor hematologic response. In particular, outcome was not affected by preoperative spleen size or the degree of marrow infiltration by CLL. All patients with symptomatic splenomegaly had an improved sense of well-being. CONCLUSION: In this, the largest single institution study to date, we found splenectomy to be efficacious in providing durable remissions of refractory cytopenias and in relieving symptomatic splenomegaly in the majority of patients with CLL. The procedure is associated with a low perioperative mortality. Although the impact on survival is uncertain, the improved peripheral blood counts may allow the administration of adequate doses of myelosuppressive chemotherapy.

Actuarial Analysis

Protective effect of residual splenic tissue after subtotal splenectomy.

Studies in animals and clinical experience in man have demonstrated that splenectomy leads to increased susceptibility to infection with encapsulated bacteria. Splenic tissue has an excellent ability to regenerate, even when implanted into subcutaneous tissue or the abdominal cavity. These implants, however, do not protect against bacterial challenge despite the fact that a number of other functions can be restored. We therefore studied the ability of residual splenic tissue to protect against challenge following subtotal splenectomy in Sprague-Dawley rats. Subtotal splenectomy was performed on 48 animals in which approximately 75% of the spleen was removed and left with a branch of its normal blood supply; 48 animals underwent total splenectomy and 48 had sham operations. Six months after surgery the groups were challenged intravenously with type 25 pneumococci to determine the LD50 for each group. Animals that had undergone subtotal splenectomy were more resistant to pneumococcal challenge than were asplenic animals, but they were not as resistant as normal animals. In addition, there was marked delay in death in the animals with subtotal splenectomy as compared with asplenic animals. Thus residual splenic tissue after subtotal splenectomy appears to confer some degree of protection against pneumococcal challenge.

Age Factors