Splenic Tumor Research Articles

FDG PET/CT in Papillary Intralymphatic Angioendothelioma of the Spleen.

Splenic papillary intralymphatic angioendothelioma is extremely rare. We describe FDG PET/CT and MRI findings of splenic papillary intralymphatic angioendothelioma in a young adult. The splenic tumor showed hypodensity and increased FDG uptake with SUVmax of 4 on PET/CT, heterogeneous signal intensity with internal hypointense stellate scars on T2-weighted image, and progressive centripetal enhancement on dynamic contrast-enhanced T1-weighted images. This case indicates that papillary intralymphatic angioendothelioma should be included in the differential diagnosis of FDG-avid splenic lesions.

Application of Microwave Ablation in Laparoscopic Partial Splenectomy.

Splenic hemangioma is the most common pathological classification of splenic tumors, and its surgical indication and treatment have been controversial. Before, open splenectomy was usually used to treat splenic hemangioma. Following the rapid development of laparoscopic techniques, people's requirements for minimally invasive treatment have gradually increased, and laparoscopic splenectomy has gradually become the main treatment method. However, through the deeper study of spleen function, it was found that partial splenectomy can cut down the incidence of postoperative thrombocythemia and decrease side effects on the physiological function of the body, so laparoscopic partial splenectomy came into being. However, due to the special anatomical structure, the incidence of hemorrhage during partial splenectomy is greater. Therefore, during the operation, we removed part of the splenic blood vessels, combined with microwave ablation, which perfectly solved the problem of intraoperative bleeding. Laparoscopic partial splenectomy combined with microwave ablation not only achieves the requirements of minimally invasive treatment but also reduces the risk of intraoperative bleeding, meriting clinical application and promotion.

Neoplasias mamária e esplênica em cadela

Regarding mammary and splenic neoplasms in dogs, the surgical therapeutic approach is often the method of choice, given its curative potential and the possibility of subsequent histopathological analysis. In veterinary medicine, the incidence of mammary neoplasms is high, especially in unneutered female dogs. Breast carcinoma in situ, with its histological particularities and clinical behavior, requires a careful diagnosis and a precise therapeutic approach, carrying out additional tests such as cytopathology and ultrasound to adequately define the treatment. Surgical excision, associated with the evaluation of adjacent healthy breast tissue, is essential to ensure complete removal of neoplastic tissue, plus it is also indicated to perform ovariohysterectomy (OVH) together with mastectomy. Spleen tumors are similarly common in dogs, especially hemangiosarcoma, which is notable for its aggressiveness and high metastatic rate. Therefore, early diagnosis and precise interventions are essential for a good prognosis, with the affected organ being often removed in its entirety. Therefore, we report the case of a female Shih-Tzu dog, 7 years old and weighing 4kg, who presented, upon palpation, a nodule in the left M3 measuring <1cm with absence of nodular secretion, change in color, itching local or galactorrhea. The patient was referred for regional mastectomy and OVH after cytological examination compatible with carcinoma and, in a pre-operative ultrasound examination, a singular hypoechoic nodular formation, discretely heterogeneous, vascularized on Doppler and in close contact with the splenic capsule was noted in the spleen in its medial parietal portion, measuring 0.96 cm in its longest axis. Thus, during intraoperative visual inspection after OVH and upon approval from the owner, it was decided to perform total splenectomy and, after histopathological examination, it was known that the organ was affected by hemangiosarcoma. The canine was discharged from the hospital a few hours after the end of the surgery, without the subsequent use of adjuvant therapies.

Ultrasonographic liver nodules are more often benign lesions in dogs with hemoperitoneum secondary to splenic tumor rupture.

To evaluate the reliability of preoperative abdominal ultrasonography as a staging tool for dogs with hemoperitoneum due to presumed splenic tumor rupture, focusing on the detection of metastatic lesions in the liver. 99 dogs from 20 emergency and specialty hospitals across the US. Dogs with nontraumatic hemoperitoneum secondary to splenic tumor rupture were included. A post hoc analysis was conducted on data from a nationwide prospective trial investigating novel treatments for canine hemangiosarcoma. The accuracy of preoperative staging was assessed by comparing ultrasonographic findings with intraoperative observations and histologic findings. On preoperative ultrasonography, there was a 20% incidence of liver lesions identified, with no association to liver lesions seen during operation. Notably, 22% of liver lesions observed during operation were missed on preoperative ultrasonography. The presence of liver lesions on preoperative ultrasonography was associated with a higher likelihood of a benign splenic tumor diagnosis. There was no association between the identification of liver lesions on preoperative ultrasonography and the presence of metastatic disease on liver biopsy, with a sensitivity and specificity of 19% and 82%, respectively. Additionally, ultrasound had low sensitivity in detecting intra-abdominal lesions beyond the liver and spleen, with 82% of these lesions missed preoperatively. This study challenges conventional perceptions around the approach to staging in dogs with hemoperitoneum. These findings advocate for a reevaluation of the staging approach, with more comprehensive modalities like whole-body CT or MRI potentially being more warranted.

The safety and feasibility of laparoscopic partial splenectomy: analysis of perioperative indications from different vascular subtypes and improvement of surgical approach

IntroductionWhile laparoscopic splenectomy (LS) has been widely used in benign splenic tumor, more concerns have been raised for postoperatively short-term and long-term complications. Laparoscopic partial splenectomy (LPS) is a surgical option, to preserve splenic function, and reduce postoperative complications. The aim of our study was to retrospectively identify the safety and feasibility of LPS compared with LS in patients with splenic benign tumor.Materials and methodsFrom 2014 to 2024, a total of 165 patients diagnosed with occupational splenic lesions underwent splenectomy, of whom 87 underwent LPS and 78 underwent LS. We compare the perioperative parameters and long term follow up between these two groups.ResultsThe etiology of splenic space-occupying lesions was nonparasitic splenic cysts, followed by splenic lymphangioma and splenic hemangioma. Of the patients with LPS, 55 underwent conventional surgery with blockage of the splenic arterial branch and resection along the ischemic line (RAIL), and 32 underwent with our modified total splenic blood supply blockade followed by resection alone the tumor edge (RATE). The tumor size, the operative time and estimated blood loss were comparable between the LPS and LS groups. One patient developed abnormal signs during the LPS procedure and was promptly referred for LS. The LPS group had fewer pancreatic leakage, incision infection, and pulmonary infection. As for different vascular types, patients with LS under all branches of the splenic artery had a longer time to resume postoperative feeding. As for the comparison of RAIL and RATE, estimated blood and operative time were significantly reduced in patients receiving RATE. Postoperative complications were the same in patients underwent each surgical procedures.ConclusionLPS is a viable approach for patients with splenic benign tumor. We introduce the tumor artery supply types to indicate the resection region. Our RATE technique has proven to be clinically effective and safety.

Efficacy of Doxorubicin in the Adjuvant Treatment of Canine Splenic Visceral Hemangiosarcoma

Introduction. Splenic hemangiosarcoma is a highly malignant neoplasm that affects geriatric patients. The incidence in dogs is 45–50% of all splenic tumours and about 2% of all oncological pathologies. The visceral form of splenic hemangiosarcoma is characterised by the most aggressive course of the disease and early metastasis to other organs. The average life expectancy of animals after splenectomy, according to various scientific data, is from 20 to 90 days. The article studies the efficacy of additional doxorubicin-based adjuvant chemotherapy to increase the life expectancy of dogs at different stages of the disease.Materials and Methods. To compare the life expectancy, the patients were divided into 4 groups receiving different treatments for splenic hemangiosarcoma. Examination of patients, visual diagnostics and pathomorphological diagnostics were used for making a diagnosis, determining the stage of the disease and prescribing treatment. Treatment efficacy was assessed based on the median relapse-free period, median life expectancy and survival rate of patients after 3, 6, and 12 month periods. Statistical analysis was performed using the Fisher's exact test.Results. The obtained data demonstrated a more favourable course of disease in dogs with the stage I tumour process. Splenectomy made it possible to increase the life expectancy of patients to 243 days with a 6–month survival rate in 62.5% of patients. Postoperative chemotherapy treatment combined with doxorubicin significantly improved the longterm prognosis and led to more than twofold increase in life expectancy of dogs (up to 475 days) with a one-year survival rate in 83.3% of patients. However, no substantial statistical significance was determined in the studied groups (p=0.7).Discussion and Conclusion. The results of the research have revealed the efficacy of adjuvant doxorubicin-based chemotherapy in dogs with the visceral forms of splenic hemangiosarcoma. In animals with early stages of the disease, a significant increase in life expectancy has been discovered. The development of hemagdomain and/or the presence of metastasis to abdominal organs indicate the unfavourable course of the disease and, as a consequence, early metastasis. Nevertheless, even at these stages, doxorubicin can increase the life expectancy of patients.

Splenic flexure adenocarcinoma: A national cohort analysis of extent of surgical resection and outcomes.

The optimal extent of resection for splenic flexure adenocarcinoma remains debated. These tumours straddle the left- and right-sided vasculature with lymphatic drainage in a watershed area; current guidelines recommend either segmental or extended colectomy. We analysed surgical management of splenic flexure tumours and compared outcomes between approaches. The Surveillance, Epidemiology and End Results database was searched for adults with Stage I-III splenic flexure adenocarcinoma, 2004-2019. Of 5238 patients, 55% underwent extended colectomy. Compared to segmental colectomy, these patients were more likely to have advanced stage. On multivariable analysis, age ≤ 65 years remained independently associated with extended colectomy. Although fewer nodes were examined in segmental colectomy (median 14 vs. 16, p < 0.001), the number of positive nodes (both, median 0 [interquartile ratio 0-2], p = 0.20) and the lymph node ratio were similar between cohorts. Surgical approach was not significantly associated with increased positive nodal yield in adjusted analyses. Five-year overall and disease-specific survival were 73% and 84% for segmental and 72% and 83% for extended colectomy (p > 0.4); these remained comparable after adjustment. Nationally, we observed similar rates of segmental and extended colectomy for splenic flexure adenocarcinoma. Extended colectomy was not more common in Stage III disease, indicating lack of stage migration, and was not associated with better oncological outcomes. These observations support current practice involving either approach, which should be tailored to patient-related factors and preferences, while considering technical aspects and quality of life.

HEMANGIOSARCOMA IN RED WOLVES (CANIS RUFUS) AND GRAY WOLVES (CANIS LUPUS) IN HUMAN CARE: SIX CASES.

Wolves are commonly housed in zoological institutions and captive breeding facilities that are essential for maintaining genetic diversity and for the recovery of declining populations. Neoplasia is a common cause of mortality in wolves, but hemangiosarcoma has not previously been described. This condition was diagnosed in four red wolves (Canis rufus) and two gray wolves (Canis lupus) housed at five different institutions between 2008 and 2018. Animals were 11-16 yr of age at the time of presentation. Clinical signs included loss of body condition, abdominal distension, lethargy, weakness, ataxia, and hyporexia. Three animals were mildly anemic. All animals were humanely euthanized within an average of 3 d from onset of clinical signs. Two animals had primary splenic tumors, two had pelvic tumors with one originating from the aorta, and one had a cranial mediastinal mass. Diagnosis was made on postmortem histologic examination in all cases. Four wolves had evidence of metastases with foci in the lungs, lymph nodes, mesentery, liver, subcutis/skeletal muscle, kidney, adrenal, and thyroid gland. Hemangiosarcoma should be considered in geriatric wolves presenting with nonspecific signs, particularly if abdominal distension, free peritoneal fluid, or anemia is present.

Extended procedure has no oncological benefits over segmental resection in the treatment of non-metastatic splenic flexure colon cancer, a population-based cohort study and a single center's decade-long experience.

To compare the oncological survival outcome between extended resections (ER) and segmental resection (SR) for non-metastatic splenic flexure tumors. A total of 10,063 splenic flexure colon cancers patients who underwent ER (n = 5546) or SR (n = 4517) from 2010 to 2018 were included from the Surveillance, Epidemiology, and End Results (SEER)-registered database. Additionally, we included 135 patients from our center who underwent ER (n = 54) or SR (n = 81) between 2011 and 2021. Survival rates were compared between groups. To reduce the inherent bias of retrospective studies, propensity score matching (PSM) analysis was performed. In the SEER database, patients in the ER group exhibited higher pT stage, pN stage, larger tumor size, and elevated rates of CEA level, perineural invasion, and tumor deposits compared to those in the SR group (each P < 0.05). The 5-year cancer-specific survival (CSS) rate was slightly lower in the ER group than in the SR group (79.2% vs. 81.6%, P = 0.002), while the 5-year overall survival (OS) rates were comparable between the two groups (66.2% vs. 66.9%, P = 0.513). After performing PSM, both the 5-year CSS and 5-year OS rates were comparable between the ER and SR groups (5-year CSS: 84.9% vs. 83.0%, P = 0.577; 5-year OS: 70.6% vs. 66.0%, P = 0.415). These findings were consistent in the subgroup analysis that included only patients with stage III disease or tumor size ≥ 7cm. Furthermore, although the number of harvested lymph nodes was higher in the ER group compared to the SR group (14.4 vs. 12.7, P < 0.001), the number of invaded lymph nodes remained similar between the two groups (0.5 vs. 0.5, P = 0.90). Similarly, our center's data revealed comparable 3-year OS and 3-year disease-free survival (DFS) rates between the two groups. ER have no significant oncological benefits over SR in the treatment of non-metastatic splenic flexure colon cancer, even for locally advanced cases.

Modified Rosi–Cahill technique after left extended colectomy for splenic flexure advanced tumors

Advanced splenic flexure tumors are uncommon and have a higher risk of relapse. To ensure that the resection includes the entire area of lymphatic drainage with a complete mesocolic excision (CME), a left extended colectomy is needed. In peritoneal carcinomatosis, there is often extensive involvement of the sigma and splenic flexure of the colon. In many instances, total colectomies are chosen for these patients, even when a significant portion of the colon could be preserved. The potential impact on quality of life after splenic flexure colon resection is discussed, as well as the importance of anatomical knowledge and expertise in performing this type of surgery. Overall, this work presents a modified technique that aims to improve the outcomes and quality of life for patients with splenic flexure colon cancer. Creating a tension-free anastomosis after extended left-sided colorectal resection is challenging. There is a negative impact on quality of life when an ileorectal anastomosis is created. The colorectal anastomosis performed after modified Rosi–Cahill or Deloyers’ technique allows reduced small bowel bacterial overgrowth, achieves better water and sodium absorption, and altogether permits improved stool consistency. There are potential advantages of the Rosi–Cahill technique over other popular options such as Deloyers’ procedure as there is no torsion of the ileocolic vessels and no mesenteric windows. A video was recorded showing a potential pitfall during Deloyers’ technique resulting in the creation of a mesenteric window. The proper rotation of the colon during the modified Rosi–Cahill procedure was also filmed. Overall, this work presents a modified technique for reconstruction after left extended colectomy that aims to improve the outcomes and quality of life for patients with splenic flexure colon cancer.

Clinical and morphological analysis of splenic neoplasms

The relevance of this study arises from the pressing need for a deeper investigation into the morphological aspects of identifying focal and localised lesions in the spleen. The spleen performs several vital functions, including immune, haematological, storage, metabolic, haemostatic, hormonal, and antiblastic roles, among others. Therefore, this study aimed to determine the clinical characteristics of splenic tumour lesions and their structural changes, as well as to identify the macroscopic appearance of the organ post-splenectomy. In diagnosing splenic diseases, a key instrumental method was employed – ultrasound examination with Doppler imaging – which enabled comprehensive investigation, analysis, and characterisation of parenchymal pathologies. Animals underwent clinical examinations during routine health checks or upon presentation of symptoms. When a splenic neoplasm was detected, surgical treatment was carried out, specifically through an open laparotomy and splenectomy. The surgery was performed under combined general anaesthesia (using both non-inhalational and inhalational anaesthetics). The intraoperatively collected material from the affected organ was subjected to histological examination. It was found that the pathomorphosis of splenic lesions varies, and the author's pathological and histological studies highlight the key morphological characteristics of the neoplasms. Accordingly, any splenic neoplasm can pose a life-threatening condition for several reasons: organ rupture and haemorrhage, organ torsion, and malignancy, among others. The findings are crucial for verifying splenic pathology, enabling the establishment of a definitive clinical diagnosis, facilitating treatment of the animal, and extending its lifespan. The practical significance of the results lies in identifying the need for comprehensive clinical and morphological investigations in diagnosing splenic diseases, as well as examining histological preparations for cellular and tissue changes. In veterinary medicine, the method of surgical treatment for splenic lesions in animals may be a subject of debate. In contrast, in human medicine, established protocols exist for performing organ-destructive operations such as splenectomy (by open or laparoscopic approach), organ-preserving procedures like splenic resection or splenectomy with autotransplantation of splenic tissue into the greater omentum (by open or laparoscopic approach), and percutaneous punctures for splenic cysts

Cordycepin Augments the Efficacy of Anti-PD1 against Colon Cancer.

Colon cancer has a poor clinical response to anti-PD1 therapy. This study aimed to evaluate the effect of cordycepin on the efficacy of anti-PD1 treatment in colon cancer. The viability of CT26 mouse colon carcinoma cells, cell-cycle progression, morphology, and the expression of mRNA and protein were assessed. A syngeneic animal model was established by implanting CT26 cells into BALB/c mice for in vivo experiments. Multi-parameter flow cytometry was used to analyze the splenic cell lineages and tumor microenvironment (TME). The in vitro data revealed that cordycepin, but not adenosine, inhibited CT26 cell viability. The protein, but not mRNA, expression levels of A2AR and A2BR were suppressed by cordycepin but not by adenosine in CT26 cells. The combination of cordycepin, but not adenosine, with anti-PD1 exhibited a greater tumor-inhibitory effect than anti-PD1 alone as well as inhibited the expression of A2AR and A2BR in splenic macrophages. In the TME, the combination of cordycepin and anti-PD1 increased the number of CD3+ T cells and neutrophils and decreased the number of natural killer (NK) cells. Overall, cordycepin augmented the antitumor effects of anti-PD1 against mouse colon carcinoma cells and inhibited the expression of the adenosine receptors A2AR and A2BR in splenic macrophages and intratumoral NK cells.

Improved predictability is needed for calculators used to preoperatively determine the etiology of splenic masses in dogs: an external validation study of the HeLP score and T-STAT.

To assess the predictability of the hemangiosarcoma likelihood prediction (HeLP) score and the Tufts Splenic Tumor Assessment Tool (T-STAT) for hemangiosarcoma and malignancy, respectively. 261 dogs undergoing splenectomy for a splenic mass. Medical records were retrospectively reviewed; variables for the HeLP score and T-STAT were collected, and scores were assigned. Area under the curve (AUC) was calculated for each score. The HeLP score included 141 dogs; hemangiosarcoma was diagnosed in 87 (61.7%) dogs. The median cumulative HeLP score was 51 (range, 17 to 82; IQR, 39 to 58) for dogs with hemangiosarcoma and 28 (range, 0 to 70; IQR, 17 to 41) for dogs without hemangiosarcoma. The categorical HeLP score was low (28; 32.2%), medium (31; 35.6%), and high (28; 32.2%) for dogs with hemangiosarcoma and was low (41; 75.9%), medium (9; 16.7%), and high (4; 7.4%) for dogs without hemangiosarcoma. The AUC of the cumulative and categorical HeLP scores for diagnosis of hemangiosarcoma were 0.79 (95% CI, 0.71 to 0.86) and 0.73 (95% CI, 0.65 to 0.82), respectively. The T-STAT included 181 dogs. Lesions were benign in 95 (52.5%) and malignant in 86 (47.5%) dogs. The median T-STAT score was 62% (range, 5% to 98%; IQR, 36% to 77%) for dogs with malignant lesions and 38% (range, 5% to 91%; IQR, 24% to 59%) for dogs with benign lesions. The T-STAT had an AUC of 0.68 (0.60 to 0.76) for diagnosis of malignancy. The HeLP score had acceptable performance, and the T-STAT had poor performance for diagnosis prediction. A tool with excellent or outstanding discrimination is needed to more reliably predict the presence of hemangiosarcoma or a malignant lesion preoperatively.

Clinical comparative study of laparoscopic partial splenectomy and open partial splenectomy.

The aim of the article was too investigate and compare the feasibility, safety, and early postoperative recovery associated with laparoscopic partial splenectomy (LPS) and open partial splenectomy (OPS) in patients with benign splenic tumours and traumatic splenic rupture. A retrospective analysis was conducted on clinical data from 110 patients undergoing splenic resection at our hospital between March 2019 and May 2022. Among them, 35 patients underwent OPS, 25 underwent LPS for traumatic splenic rupture, while 50 patients with benign splenic tumours underwent either OPS (n = 20) or LPS (n = 30). Preoperative, intraoperative, and postoperative data were collected and compared. Statistical analysis was conducted using SPSS software. There was no significant difference in the general data between the 2 groups of patients with benign splenic tumours and those with splenic trauma. Among patients with traumatic splenic rupture, the OPS group had a shorter operation time (p < 0.05). Regardless of whether they had traumatic splenic rupture or benign splenic tumours, the LPS group required less postoperative analgesia and had a shorter defecation recovery time (p < 0.05). Additionally, the LPS group displayed lower white blood cell count, white blood cell/lymphocyte ratio (WLR), neutrophil/lymphocyte ratio (NLR), monocyte/lymphocyte ratio (MLR), C-reactive protein (CRP), calcitonin (PCT), and interleukin-6 (IL-6) than the OPS group on the first and third days post-surgery (p < 0.05). In comparison to OPS, LPS presents significant advantages, including minimal surgical trauma, a reduced early postoperative inflammatory response, milder wound pain, and a faster recovery of gastrointestinal function.

A nonparasitic cyst of the spleen in children — is surgery a must? Two clinical cases

BACKGROUND: Non-parasitic splenic cysts is a rare pathology in children, accounting for 0.5–2% of all splenic diseases. Typically, most cysts, as a rule, are asymptomatic However, as the cyst is enlarging, clinical symptoms — such as pain, discomfort in the left abdomen, and nausea — may appear. These symptoms are indicators for surgical intervention. Splenic cysts larger than 5 cm have a higher risk of complications such as rupture, bleeding, and infection; therefore, surgical treatment is recommended in these cases. Some authors consider the surgical intervention to be appropriate for cysts sized greater than 4 cm. However, small size of splenic neoplasms can complicate their visualization and surgery, thus increasing the risk of intraoperative complications and recurrences. Currently, in cases of borderline sizes of asymptomatic non-parasitic splenic cysts, it is recommended to assess the dynamics of size changes, so as to find the optimal curative tactics for the patient. CLINICAL CASE DESCRIPTION: Two clinical examples of non-parasitic splenic cysts in children are discussed in the article. In the first case, a splenic formation with diameter 40 mm was found in a 5-y.o. girl; the diagnosis was confirmed at ultrasound and computed tomography examinations. At the recommended dynamic follow -up , it was found out that the cyst decreased to 5 mm in diameter. In the second case, a 14-y.o. boy was hospitalized for an elective surgery, because a splenic formation was diagnosed at the regular dispensary check-up. Ultrasound and computed tomography examinations of the abdominal cavity revealed a cyst of 45 mm on the visceral surface of the upper segment of the spleen. Laparoscopy failed to visualize the splenic cyst. The follow-up monitoring with a repeated ultrasound examination of the abdominal cavity in 3-6 months was recommended. Imaging diagnostic techniques have confirmed that cyst location and size remained unchanged. CONCLUSION: The two described clinical cases demonstrate the importance of dynamic follow-up monitoring in case of borderline-sized non-parasitic splenic cysts in children, as it helps to avoid unnecessary surgical interventions.

Abstract 709: Enhancing prostate cancer treatment: Synergistic effects of mechano-thermal focused ultrasound and radiation therapy

Abstract Current treatments for prostate cancer primarily rely on radiation and hormone deprivation therapy, yet they often lack effective immunotherapeutic effects. Furthermore, long-term hormone ablation has side effects, such as, impotency and osteoporosis. Addressing this gap, we introduce an innovative dual-frequency focused ultrasound (FUS) platform for non-ablative focal therapy, which induces protein unfolding, ER stress, and increases heat-shock protein expression along with translocation of endoplasmic reticular chaperone proteins (e.g., calreticulin) on the tumor cell surface, thereby sensitizing them for phagocytosis by dendritic cells for efficient antigen presentation and cross priming. We hypothesized that FUS-mediated acoustic immune priming can be combined with ablative therapies, such as, hormone ablation and/or radiation therapy (RT) for induction of tumor-specific adaptive immune response and better tumor control than monotherapy in murine prostate cancer models. Utilizing murine prostate cancer cell lines, MyC-CaP and RM1, we explored the cellular responses to androgen deprivation, observing distinct sensitivities. Twenty-four hours after FUS treatment tumor cells experienced mechano-thermal stress response with 15-fold increase in Hspa1a expression. Transmission Electron Microscopy studies showed formation of myelin figures, nuclear membrane deformation, and lipid droplet formation. In vivo, the combination of FUS (220w/cm2 intensity for 3 sec at focal point) and RT (8-10 Gy daily x two fractions) markedly delayed tumor growth and achieved complete cure in 14-17% of animals. Through multicolor flow cytometry, we detected significant alterations in the immune microenvironment, including increased CD8+ T cell infiltration and reduced tumor-associated macrophages in the tumor bed. However, we also observed a compensatory rise in pro-tumor immune cells such as PMN-MDSCs and Tregs with significant suppression of eosinophils (p&amp;lt;0.05). Interestingly, there was suppression of splenic PMN-MDSCs, Mo-MDSCs, and tumor draining lymph node macrophages, suggesting systemic immune modulation in peripheral lymphoid organs of FUS+RT-treated tumor-bearing animals. Our findings reveal that the combination therapy of FUS and RT improves tumor control in murine prostate cancer and significantly modulates the systemic and tumor immune microenvironment. This approach offers new avenues for immunotherapy, potentially transforming the treatment landscape for prostate cancer, typically resistant to conventional immunotherapeutic strategies. Citation Format: Soumya Chatterjee, Saurabh Singh, Stephen Barry, Chandan Guha. Enhancing prostate cancer treatment: Synergistic effects of mechano-thermal focused ultrasound and radiation therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 709.

Abstract 2827: Characterization of acute myeloid leukemia PDX models with hotspot gene mutations for therapeutic evaluation

Abstract Introduction: Acute myeloid leukemia (AML) is the most common acute type of leukemia in adults characterized by chromosomal abnormalities and gene mutations. While inhibitors have shown promise targeting FLT3 mutations, resistance to these inhibitors can emerge. Similarly, inhibitors targeting IDH1 and IDH2 mutations showed promise, yet the emergence of drug resistance poses a significant challenge. In this study, a panel of AML PDX models with multiple gene alterations was established to support the development of new therapies. Methods: The systemic AML PDX models were established using patients’ peripheral blood (PB) or bone morrow (BM) injected intravenously and expanded in vivo by using splenic tumor cells. One AML PDX model derived from patient skin was established subcutaneously. Expression of human CD45+ in PB cells for systemic models or tumor volume for the subcutaneous model was used to monitor the tumor burden. Leukemic loads (hCD45+ cells) were measured in PB, spleen (SP), and BM. Tumors were categorized following tumor immunophenotyping, histology, and RNA sequencing/Whole Exome Sequencing. For in vivo efficacy studies, animals were grouped 3-5 weeks after systemic tumor cells inoculation and treated with AC220 (1, 2 or 10 mg/kg, p.o., QD), Cytarabine (Ara-c, 2mg/kg, i.p., QD), 5-azacytidine (2mg/kg, i.p., QD), Sorafenib (10mg/kg, i.p., QD) and Gilteritinib (10 or 30mg/kg, p.o., QD). Results: Nine systemic and one subcutaneous AML PDX models carrying hotspot mutations (e.i. FLT3-ITD or TKD, IDH1-R132H and IDH2-R140Q) were established, showing comparable features to the clinic. Systemic AM8231 PDX model harboring FLT3-ITD mutation treated with AC220, a type II FLT3i, showed significant tumor burden reduction in PB at different time points and in SP and BM at termination, as well as a survival increase. Similarly in systemic model AM7577 with FLT3-ITD mutation treated with AC220, significant tumor burden reduction in PB was observed. Whereas using systemic model AM9626 (model with Sorafenib pretreatment history) with coexisting-FLT3-ITD/D835H TKD mutation, no significant efficacy was observed with AC220i, suggesting a FLT3-TKD mediated resistance mechanism. To overcome the resistance, Gilteritinib, a type I FLT3i, was tested in AM9626 and showed significant reduction of hCD45+ cells in PB compared to the control group, even at a lowest dose. As model AM9626 PDX also carries IDH1 mutation, the level of serum 2-HG correlated with the tumor burden. The functional effect of IDH1 inhibitor on the tumor inhibition and 2-HG level is under investigation. Conclusion: The results presented in this study showed the establishment of a panel of AML PDX models, including different subtypes and genomic features reflecting the clinic. Those models will support the preclinical evaluation of new treatments or combination modalities as well as a better understanding of drug resistance mechanisms. Citation Format: Qingzhi Liu, Jinxi Wang, Jinping Liu, Likun Zhang, Ludovic Bourre, Jingjing Wang. Characterization of acute myeloid leukemia PDX models with hotspot gene mutations for therapeutic evaluation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2827.

Primary Splenic Hodgkin Lymphoma and its Prognosis: A Report of Two Cases

Primary Splenic Lymphomas (PSL) constitute an extremely uncommon variety of splenic neoplasm and can present with grave complications such as splenic rupture. Hodgkin Lymphomas (HL), a type of hematopoietic neoplasm, are typically diagnosed between the ages of 20 and 30 years and present with supra-diaphragmatic lymphadenopathy, often accompanied by systemic B symptoms. A histopathological diagnosis involving Reed-Sternberg (RS) cells in an inflammatory background is crucial. However, other differentials such as reactive hyperplasia, infectious mononucleosis, anaplastic large cell lymphoma, or various other lymphomas may mimic Hodgkin disease both clinically and histologically. Therefore, accurate diagnostic evaluation of Hodgkin lymphoma is crucial, especially as it is highly curable with combination chemotherapy, even in higher stage disease. In this report, the authors present two cases of primary splenic HL diagnosed through histopathological and immunohistochemical examination of splenectomy specimens from January 2020 to December 2021 at the Department of Pathology, IPGME&amp;R, Kolkata, India. While reporting the histopathological sections, the authors also considered other differentials such as reactive changes, tuberculosis, and other non-Hodgkin lymphomas. Both patients were male, aged 10 years and 18 years, and presented with abdominal distension and fever, without any palpable peripheral lymph nodes, for the last six months to one year. After chemotherapy, the patients were regularly monitored to identify any signs of recurrence or relapse. Therefore, the initial recognition and proper diagnosis of Hodgkin lymphoma presenting in the spleen may vary in clinical presentation and morphology, but early accurate diagnosis carries a good prognosis, as survival is best determined by its histopathological type.

Surgical treatment of littoral cell angioma of the spleen

Littoral cell angioma is a very rare benign splenic neoplasm with typical morphological features. It is difficult to differentiate this angioma from other benign or malignant splenic tumors. It is a unique vascular tumor followed by abdominal pain or detected incidentally during examination. Incidence of this tumor is small, as only few appropriate cases were described in the literature. We present successful surgical treatment of littoral cell angioma of the spleen. The issues of clinical course, diagnosis, therapeutic tactics, morphologic and histochemical features are discussed.

Sclerosing angiomatoid nodular transformation (SANT) of the spleen can be safely diagnosed by a core percutaneous ultrasound-guided biopsy.

Sclerosing angiomatoid nodular transformation (SANT) is a rare benign lesion of the spleen. SANT cannot be distinguished from other benign or malignant splenic tumors based on imaging findings. So, diagnosis relies on histopathologic examination. Although splenectomy is frequently considered as an option, core needle biopsy tissue analysis is safe and accurate to avoid surgery.