A Cadaveric Study on Morphometric Features of Spleen and Splenomegaly with Accessory Spleen in Hilum

Background: Anatomical knowledge regarding the external morphology of the spleen is essential for surgical intervention and radiological diagnosis. Splenomegaly is defined as pathologic enlargement of the spleen measured by size or weight. A normal spleen has a craniocaudal length of no more than 12 cm and weighs less than 200 g. It is surrounded by a thin capsule. The spleen is usually not palpable unless it is enlarged; therefore, a palpable spleen is almost always abnormal. At times the spleen may be difficult to palpate, but dullness to percussion during inspiration in the area of the lower left intercostal space in the left anterior axillary line suggests splenic enlargement. Massive splenomegaly, weight >1000 g usually occurs in lymphoma, myeloproliferative disorders, visceral leishmaniasis, and malaria. Materials and Methods: This study was conducted in different medical institutions, to find morphometric features, spenomegaly in cadaver during routine anatomy dissection as part of curriculum, 100 cadavers were observed to find out splenomegaly. Results: Out of 100 spleens studied, 81 cases wedge shaped spleen was the most common, followed by 12 tetrahedral shaped spleens and 7 oval shaped spleens. Average weight of the spleen was 175g. Average length of the spleen was 11.64cm, Average breadth of the spleen was 7.3cm and average thickness of spleen was 3.6cm. Out of 100 cadavers observed only one cadaver observed with massive splenomegaly with one accessory spleen in hilum. The spleen weight was 875gm, length was 18.15 cm, width was 8.65cm, thickness was 5.75cm and extended upto 7 rib and it is easily palpable below the rib cage from lumbar aspect. The cadaver was male and age around 55 years. Conclusion: The morphometric knowledge of spleen will helpful for surgeons and for understanding deceases related spleen. The knowledge of splenomegaly is important in finding splenic disorders and accessory spleen information helpful in understanding embryonic development of spleen. KEY WORDS: Splenomegaly, Spleen, Hilum of Spleen, Accessory spleen.

STUDY OF SPLENOMEGALY IN CHILDREN.

Splenomegaly is common clinical finding in pediatric practice. Splenic enlargement occurs when the spleen is increased by cells or tissue components or by vascular engorgement. Various etiologies can cause splenomegaly. The spleen is rarely the primary site of a disease. Splenomegaly is classified according to the length palpable below the costal margin as mild: <3 cm, moderate: 4-7 cm & massive: >7 cm. Severe/massive splenomegaly doesn't commonly occur in first 5 years of age, occurs after 5 years of age. So, clinical examination of every child is important to diagnose splenomegaly at early stages. Only in the age group of 1 to 5 years females predominated as compared to males. In present study there is obvious male predominance as male: female ratio is 1.8:1. This difference could be due to more priority to male child to seeking medical care with such chronic illness.Present study also suggested that severe/massive splenomegaly doesn't commonly occur in first 5 years of age, occurs after 5 years of age. So, clinical examination of every child is important to diagnose splenomegaly at early stages.

Sonographic Measurement of Spleen to Left Kidney Ratio among Saudi Children

Objective: Spleen length varying according to many factors such as individual height, age and weight, determination of mild splenomegaly might be extremely inaccurate. The goal of this study was to determine the spleen to left kidney ratio in different age group among school age children in Saudi Arabia. Methods: A cross sectional study was conducted on 150 healthy subjects (66 boys and 84 girls) their age ranged from 7 to 15 years. The study was conducted at the Taawon clinic in Kharj city, Saudi Arabia. The sonographic examination was performed using Siemens (Acuson X300) machine with convex probe (3.5 – 5 MHz). Spleen and left kidney lengths were measured as well as weight and height of the subjects. Results: The result of the study showed that there is no significant different between boys and girls regarding spleen and left kidney lengths (p > 0.05). The spleen to left kidney ratio was found to be about 1.1 with 1.3 as the normal upper limit in the study sample. Conclusion: Spleen to left kidney length ratio becomes a promising method to detect non palpable splenic enlargement. Mild splenomegaly is considered if the spleen to left kidney ratio is greater than 1.3 in the absence of kidney disorders.

Myeloproliferative neoplasm-driving Calr frameshift promotes the development of pulmonary hypertension in mice

Frameshifts in the Calreticulin (CALR) exon 9 provide a recurrent driver mutation of essential thrombocythemia (ET) and primary myelofibrosis among myeloproliferative neoplasms (MPNs). Here, we generated knock-in mice with murine Calr exon 9 mimicking the human CALR mutations, using the CRISPR-Cas9 method. Knock-in mice with del10 [Calrdel10/WT (wild−type) mice] exhibited an ET phenotype with increases of peripheral blood (PB) platelets and leukocytes, and accumulation of megakaryocytes in bone marrow (BM), while those with ins2 (Calrins2/WT mice) showed a slight splenic enlargement. Phosphorylated STAT3 (pSTAT3) was upregulated in BM cells of both knock-in mice. In BM transplantation (BMT) recipients from Calrdel10/WT mice, although PB cell counts were not different from those in BMT recipients from CalrWT/WT mice, Calrdel10/WT BM-derived macrophages exhibited elevations of pSTAT3 and Endothelin-1 levels. Strikingly, BMT recipients from Calrdel10/WT mice developed more severe pulmonary hypertension (PH)—which often arises as a comorbidity in patients with MPNs—than BMT recipients from CalrWT/WT mice, with pulmonary arterial remodeling accompanied by an accumulation of donor-derived macrophages in response to chronic hypoxia. In conclusion, our murine model with the frameshifted murine Calr presented an ET phenotype analogous to human MPNs in molecular mechanisms and cardiovascular complications such as PH.

Splenic enlargement induced by preoperative chemotherapy is a useful indicator for predicting liver regeneration after resection for colorectal liver metastases

Background: Conversion chemotherapy may downsize unresectable colorectal liver metastases (CRLMs), but may cause liver injury and splenic enlargement. The effect of preoperative chemotherapy on liver regeneration after liver resection remains undetermined. The aim of this study was to examine whether splenic enlargement induced by preoperative chemotherapy is an indicator to identify high-risk patients for impaired liver regeneration and liver dysfunction after resection. Methods: We retrospectively reviewed 118 Japanese patients with CRLMs. Fifty one patients had conversion chemotherapy. The other 67 patients underwent upfront liver resection. We clarified effects of conversion chemotherapy on splenic volume, liver function, and postoperative liver regeneration. Perioperative outcome was also analyzed. Results: A ratio of the splenic volume before and after chemotherapy (SP index) in the oxaliplatin-based chemotherapy group was significantly greater than other chemotherapy groups after 9 or more chemotherapy cycles. Patients whose SP index was 1.2 or more had significantly higher indocyanine green retention rate at 15 min (ICG-R15) than patients without chemotherapy. Analyses of covariance showed liver regeneration rate after resection was decreased in patients whose SP index was 1.2 or more. The incidence of postoperative liver dysfunction in patients whose SP index was 1.2 or more was significantly greater than patients without chemotherapy. Multivariate analysis showed SP index was a significant predictive factor of impaired liver regeneration. Conclusions: Splenic enlargement induced by preoperative chemotherapy was a useful indicator for impaired liver regeneration after resection and a decision-making tool of treatment strategy for unresectable CRLMs.

Splenomegaly during oxaliplatin-based chemotherapy in colon cancer.

88 Background: Splenic enlargement has been reported in patients treated with oxaliplatin. However, the characteristics of oxaliplatin-induced splenomegaly were not well studied. Here we evaluated the change of splenic volume and its clinical significance in patients treated by oxaliplatin-based regimen. Methods: Patients with stage II-IV primary colon cancer treated with oxaliplatin and capecitabine in China National Cancer Center from January 2016 to December 2017 were screened for this retrospective study. Those with complete laboratory tests and computed tomographic data before, during and up to 1.5 years after the chemotherapy were selected. The splenic size was measured by AWVolumeshare5. Splenomegaly was defined as an over 30% increase of splenic size from baseline. Recovery of splenomegaly was defined as the splenic size fell back to a 0.9 to1.1-fold range of baseline. Results: Out of a total of 144 patients, 102 (70.8%) had over 30% increase, 72 (50.0%) had over 50% increase, and 22 (15.3%) had over 100% increase in splenic size after oxaliplatin-based regimen. Among the 102 splenomegaly patients, 5 (4.9%) develop splenomegaly within 3 chemotherapy cycles, 53 (53.0%) within 6 cycles, 73 (71.6%) within 9 cycles, and 102 (100.0%) within 3 months after the last administration of oxaliplatin. Compared to the group without splenomegaly, patients with splenomegaly received more cycles of oxaliplatin administrations (median 8 vs 6, p < 0.001) and greater dose intensity (total dose per square meter) (median 822.8mg/m2 vs 629.3mg/m2, p < 0.001). Patients with splenomegaly had higher incidence of thrombocytopenia (61.7% vs 38.1%, p = 0.009) and are more likely to undergo oxaliplatin dose reduction due to thrombocytopenia (21.6% vs 7.1%, p = 0.038). The recovery rates of splenic size within 0.5, 1 and 1.5 years after the end of oxaliplatin treatment were 23.2%, 50.6% and 74.3%, respectively. Conclusions: Splenomegaly are common in patients treated with oxaliplatin-based chemotherapy, and most would recover in 1.5 years after completion of therapy. Patients with splenomegaly are prone to experience thrombocytopenia and oxaliplatin dose reduction. Further studies are needed to reveal the mechanism how oxaliplatin induce splenomegaly.

The bevacizumab plus oxaliplatin-based chemotherapy regimen is more suitable for metastatic colorectal cancer patients with a history of schistosomiasis

Background: People suffer from schistosomiasis, leading to liver fibrosis, splenomegaly and thrombocytopenia. The effects of bevacizumab plus oxaliplatin or irinotecan-based chemotherapy regimens on platelets are different, but have not been determined. We conducted a retrospective analysis in metastatic colorectal cancer (mCRC) patients evaluating the impact of bevacizumab on platelet, in order to find a more suitable plan for mCRC patients with a history of schistosomiasis.Methods: The medical records of all mCRC patients with a history of schistosomiasis who received FOLFOX or FOLFIRI with or without bevacizumab from September 1, 2017 to June 30, 2019 in Kunshan Hospital were reviewed. Platelet counts and spleen sizes were compared from the first cycle until completion of chemotherapy.Results: Evaluable splenic enlargement and thrombocytopenia results were obtained from 73 Bevacizumab-treated patients and 80 non-bevacizumab treated patients. In patients treated with oxaliplatin, the rates of splenic enlargement (19.5% vs. 66.7%, P=0.01) and thrombocytopenia (31.7% vs. 77.2%, P=0.02) were lower in the bevacizumab-treated cohort than that in the nonbevacizumab cohort. When stratified for irinotecan, there were no statistical differences of frequency of splenic enlargement between the two groups, however, the rates of thrombocytopenia were higher in the bevacizumab-treated cohort than that in the nonbevacizumab cohort (59.4% vs. 8.7%, P=0.01 ).Conclusion: The bevacizumab plus oxaliplatin-based chemotherapy regimen is more suitable for mCRC patients with a history of schistosomiasis, especially for lower platelet count patients.

Splenomegaly in Children with Sickle Cell Anemia Receiving Hydroxyurea in Sub-Saharan Africa

Introduction. Children with sickle cell anemia enrolled in Realizing Effectiveness Across Continents with Hydroxyurea (REACH, NCT01966731) received open-label hydroxyurea at maximum tolerated dose (MTD) in four countries within sub-Saharan Africa (Tshilolo et al, NEJM 2019;380:121-131). Unlike children in the United States or Europe, a substantial proportion of REACH participants had splenomegaly at enrollment, and more developed splenomegaly while receiving hydroxyurea. Splenic enlargement in association with hydroxyurea treatment in sub-Saharan Africa is previously unrecognized, and its causes and consequences remain unclear. Methods. Palpable splenomegaly was evaluated at both the mid-clavicular and mid-axillary lines at each scheduled and unscheduled sick visit. The size of the spleen, defined as the greatest distance (cm) below the subcostal margin, was recorded in the REDCap trial database at all four clinical sites. Cross-sectional analysis was performed at baseline enrollment using four spleen categories (Not Palpable, 1-4 cm, ≥5 cm, or Splenectomy) with correlations for age, sex, site, growth parameters, alpha-thalassemia trait and G6PD deficiency. This analysis was repeated using the largest spleen size over the first two years on hydroxyurea, but examining two-year laboratory values and also the hydroxyurea dose at MTD, time to MTD, dose-limiting toxicities, and clinical outcomes including acute splenic sequestration, malaria infections, and sepsis. Results. A total of 606 children started hydroxyurea study treatment, including 6 (1.0%) with previous splenectomy, 59 (9.7%) with previous splenic sequestration, and 99 (16.3%) with palpable splenomegaly at enrollment (52 children with 1-4 cm and 47 with ≥5 cm). Large spleens (≥5 cm) were commonly observed at baseline at all clinical sites except Uganda, which identified only 1 child. Compared to those with no palpable spleen, children with large spleens at baseline had similar age and growth parameters, but were significantly more likely to have alpha-thalassemia (78.7% versus 56.2%, P=0.004) and also G6PD deficiency among males (28.0% versus 17.6%, P=0.32). Children with large spleens at enrollment also had a lower hemoglobin (Hb = 6.5 versus 7.3 g/dL, P&lt;0.001) and lower platelet count (platelets = 227 versus 410 x 109/L, P&lt;0.001), but equivalent fetal hemoglobin (HbF = 10.2 versus 9.4%, P=0.82). On hydroxyurea treatment with escalation to MTD, 262 children (43.7%) had palpable splenomegaly recorded, including 120 (20.0%) with spleens ≥5 cm. These large spleens were observed at all four clinical sites, with DRC having the most (52) and Uganda with the least (14). After 24 months of hydroxyurea treatment, laboratory differences were noted according to the cumulative occurrence of splenomegaly including a significantly lower hemoglobin and platelet count, higher absolute reticulocyte count, and lower hydroxyurea dose at MTD (Table). Large spleens were associated with a high cumulative incidence of laboratory dose-limiting toxicities, as well as a significantly higher risk of having clinically symptomatic malaria and receiving blood transfusions (Table). A total of 31 children (5.2%) on hydroxyurea treatment received elective splenectomy, including one partial splenectomy using arterial embolization. Conclusion. Children with sickle cell anemia living in sub-Saharan Africa have an increased risk of having palpable splenomegaly, which is further increased while receiving hydroxyurea treatment. Large spleen at baseline were associated with lower blood counts, consistent with hypersplenism. On hydroxyurea treatment, children with large spleens had significantly lower blood counts and more dose-limiting toxicities, which lowered their eventual hydroxyurea dose at MTD but still led to robust HbF responses. Children with large spleens were also at higher risk of developing malaria infections, receiving transfusions, and requiring surgical splenectomy. Splenic enlargement in association with hydroxyurea treatment was common in children with sickle cell anemia in the REACH trial; its cause remains unclear but the consequences include substantial laboratory toxicity and clinical morbidity. Investigating the etiologies and management of children with chronically enlarged spleens is crucial before expanding hydroxyurea access across Africa for sickle cell anemia. Disclosures Ware: Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Other: Research Drug Donation; Nova Laboratories: Membership on an entity's Board of Directors or advisory committees; CSL Behring: Membership on an entity's Board of Directors or advisory committees; Novartis: Other: DSMB; Agios: Membership on an entity's Board of Directors or advisory committees; Addmedica: Other: Research Drug Donation.