Case Report

Revised

Case Report: Priapism as The Clinical Presenting Feature of Chronic Myeloid Leukemia: Case Report and 20-Year Literature Review

[version 2; peer review: 1 approved, 1 approved with reservations]

Previously titled: ‘Case Report: Priapism as The Clinical Presenting Feature of Chronic Myeloid Leukemia: Case Report and 20-year Literature Review’

Siprianus Ugroseno Yudho Bintoro

^1,2, Pradana Zaky Romadhon

^1,2, Satriyo Dwi Suryantoro

^1,3, Rusdi Zakki Aminy

¹, Choirina Windradi

³, Krisnina Nurul Widiyastuti¹

Siprianus Ugroseno Yudho Bintoro

^1,2, Pradana Zaky Romadhon

^1,2, […] Satriyo Dwi Suryantoro

^1,3, Rusdi Zakki Aminy

¹, Choirina Windradi

³, Krisnina Nurul Widiyastuti¹

PUBLISHED 13 Jan 2022

Author details Author details

¹ Department of Internal Medicine, Airlangga University, Faculty of Medicine, Surabaya, East Java, 60131, Indonesia
² General Teaching Hospital Dr. Soetomo, Surabaya, East Java, 60286, Indonesia
³ Universitas Airlangga Hospital, Surabaya, East Java, 60115, Indonesia

Siprianus Ugroseno Yudho Bintoro
Roles: Conceptualization, Formal Analysis, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing

Pradana Zaky Romadhon
Roles: Conceptualization, Data Curation, Formal Analysis, Investigation, Methodology, Resources, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing

Satriyo Dwi Suryantoro
Roles: Conceptualization, Formal Analysis, Methodology, Resources, Software, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing

Rusdi Zakki Aminy
Roles: Conceptualization, Methodology, Project Administration, Writing – Original Draft Preparation, Writing – Review & Editing

Choirina Windradi
Roles: Conceptualization, Formal Analysis, Investigation, Methodology, Project Administration, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing

Krisnina Nurul Widiyastuti
Roles: Conceptualization, Data Curation, Formal Analysis, Project Administration, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing

OPEN PEER REVIEW

REVIEWER STATUS

Introduction

Priapism is a urological emergency due to persistence of an erection lasting more than 4 hours, whether or not it is related to sexual influence.¹ Priapism is a rare condition with an incidence of 1–5 cases per 100,000 people per year. Penile erection in priapism is regularly painless. There are two types of priapism, which are low-flow priapism and high-flow priapism. Low-flow priapism is provoked by a pathological condition of low venous blood flow causing stasis in the penile vessels. This condition is an emergency condition that can result in cell damage and fibrosis, thus it often requires immediate therapy. Meanwhile, high-flow priapism is caused by increased blood flow to the sinusoid arteries without offsetting the flow to the veins. One of the causes of high-flow abnormalities is penile injury, while low-flow priapism is commonly caused by blood disorders such as sickle cell anemia and chronic myeloid leukemia (CML).²^–⁴

Priapism accounts for 20% of the hematological abnormalities while 1–5% of priapism are due to leukemia. The theory behind a priapism is the dysregulation of nitric oxide (NO) in penile vascularization. This occurs due to changes in NO synthase enzyme activity which decrease NO production by the corpora cavernosa. This ischemic condition induces platelet aggregation, thrombus, and tissue damage. Decreased NO interferes with smooth muscle tone and generates the priapism. Hyperviscosity conditions due to leukocytosis and adenosine-opiorphins abnormalities is also involved in this condition.¹

Currently, the approach to treat CML patients with priapism uses a combination of systemic therapy (chemotherapy with hydroxyurea or tyrosine kinase inhibitors and leukapheresis) and local intracavernosal therapy. Some cases with late manifestations cause erectile dysfunction, gangrene and penile abscess.⁵ This case report and review aims to discuss the clinical characteristics and outcomes of CML patients who experience priapism.

Case

An 18-year-old unmarried male student, presented at the ER complaining of persistent erection of the penis. The patient complained of persistent erected penis for 20 days before admission. There was no phase without an erection in between. Previously, there was neither history of trauma to sexual stimulation, nor consumption of certain drugs. The patient also complained of mild genital pain along with the onset of erection. There were no complaints about discoloration of the penis; becoming reddish, bluish, or pale, also there was no numbness. The patient could urinate normally (see Figure 1).

Figure 1. Penis at day 2, day 6 (after intracavernosal blood aspiration), and day 9.

The patient complained of tinnitus in his right and left ears for 15 days accompanied by blurred vision. The patient also felt that his left side of stomach was slowly enlarging for 5 months. There was no bleeding and fever. Before coming to the ER, the patient was hospitalized at the regional hospital and received a blood transfusion and was diagnosed with a blood disorder.

Physical examination revealed no anemia and icterus. The spleen was palpable showing Schuffner 4 and Hackett 3. There was no enlargement of the lymph nodes. His laboratory findings were hemoglobin 10.4 g/dL; leucocytes 421,000 cells/mm³; platelets 407,000 cells/mm³; white blood cells differential 4.3/6.8/81.3/4.9/2.7; blood urea nitrogen 9 mg/dL; serum potassium 0.5 mg/dL, uric acid 6.5 mg/dL. Peripheral blood smear showed normochromic anemia, normocytic anisopoikilocytosis, leukocytosis (3% myeloblasts, 6% promyelocytes, 4% myelocytes, 2% metamyelocytes, 5% stab neutrophils, 63% segment neutrophils, 4% eosinophils, 6% basophils, 5% lymphocytes, 2% monocytes, atypical lymphocytes (+)) concluded as CML. The patient received hydroxyurea 2000 mg once daily at night, paracetamol 500 mg TID, and an urgent leukapheresis.

The patient underwent leukapheresis once per day (three times since initial admission) with gradual improvement. Unfortunately, on the fourth day of treatment the patient felt a penis erection again with pain on a scale of 0–5. Local examination of the genitalia showed a maximal erected penis, with no discoloration indicative of hyperemia, cyanosis, or pallor. Blood gas analysis showed pH 6.95, pCO₂ 64 mmHg, HCO₃ 14 mEQ/L, BE -18 unit. We concluded that the patient had ischemic priapism. Therefore, the patient underwent intracavernous aspiration producing 150 mL blood. Not long after that, the patient’s penis returned to an erection with bleeding from the puncture wound. We then decided to give leukapheresis to the patient.

On the eighth day of treatment, the erection improved with pain scale of 1. Quantitative BCR–ABL examination showed a positive result of 65%, thus the administration of hydroxyurea was stopped and replaced by imatinib 400 mg once daily at night. On the twelfth day of treatment, the erection completely resolved and the patient was successfully discharged from the hospital.

Discussion

This review presents data on patients who have priapism due to CML (see Table 1). Priapism occurred in the age ranging from 9–53. Patients usually had episodes of priapism for 18 h to 7 days. Not all patients with priapism showed a typical clinical examination of CML in the form of splenomegaly, but all of these patients had a hyperleukocytosis profile with a leukocyte count >200,000 cells/mm³. Some of them are equipped with data of peripheral blood smear with excessive blast and identification of BCR–ABL gene. A study by Minckler et al. was the only one reporting a resolved erection with a cold shower, whilst most other cases needed medical intervention.⁶ Although the duration of symptoms varied, four cases reported complications following an episode of priapism. Patients with unfavorable outcomes once received hydroxyurea, imatinib but failed to undergo urological emergency therapy such as intra-cavernosa aspiration, surgical intervention, and embolization.

Table 1. Case report review from last than twenty years.

No	Author	Country	Year	Age	Duration of priapism	Diagnosis of CML	Treatment of CML	Treatment of priapism	Outcome of the treatment
1	Gaye et al.⁴	Senegal	2020	46	48 hours	White Blood Cell: 526000/mm³, Platelets: 412000/mm³, Myelogram result: bone marrow hyperplasia. Karyotyping: Translocation between chromosomes 9 and 22	Imatinib (the dosage wasn’t mentioned)	Aspiration of corpora cavernosa, injection of phenylephrine, hydrocycarbamide	Success
1	Gaye et al.⁴	Senegal	2020	9	36 hours	White Blood Cell: 82000/mm³, Platelets: 81000/mm³, BMA: acute myeloid leukemia	Vincristine and Prednisolone	penile skin refrigeration, rehydration, puncture of corpora cavernosa, injection of phenylephrine	Success
2	Rajabto et al.⁹	Indonesia	2020	44	4 days	physical exam: pale skin, conjunctival pallor, leukemic retinopathy in both eyes. Schuffer 2.	IV fluid, Allopurinol 300 mg, Sodium bicarbonate 500 mg 3 times daily, hydrocyurea 1 gram three, Imatinib 400 mg times a day	aspiration of penile corpus, injection of epinephrine	suffered ED
						Labs: anemia, hyperleukocytosis, microcytic hypochromic, anisopoikilocytosis, fragmentocytes, polychromic erythrocytes, a left shift, platelet count (355,000/μL), and hyperleukocytosis (399.560/μL).
						Positive BCR-ABL1
						BMA: hypercellularity
3	Dhar et al.¹¹	India	2019	52	4 hours	Physical examination: massive splenomegaly of 8 cm below the left costal margin along with hepatomegaly of 3 cm below right costal margin.	Hydroxyurea 500 mg TDS, Imatinib OD, Allupurinol 300 mg OD, adequate hydration	needle aspiration –> didn’t work, went for Winters procedure	Success
						Blood count: left sided granulopoeis, total leucocyte count of 239×109/L and platelet count of 625×109/L.
						BMA: findings of CML
						positive translocation of BCR-ABL
4	Becerra et al.¹²	Mexico	2018	52	6 day evolution	WBC: 282.000, platelets: 368×10³/mm³	dastinib 100 mg/day+G15	corpora cavernosa irrigation and surgery penis shunts	Success
						BMA: acute phased CML
						translocation t (9:22)(q34;q11.2) with P210 BCR-ABL1 fusion transcriber
5	Khan et al.¹³	Pakistan	2018	16	264 hours	Leukocyte count: 614.8×10⁹, platelets 709×10¹²/L, peripheral smear: myeloid hyperplasia, neutrophilia. BMA: myeloid hyperplasia. Detection of BCR-ABL	Hydroxyurea, allopurinol	Glans-cavernosal shunt	Achieved detumescence, No info on ED
6	Qu et al.¹⁴	China	2018	18	72 hours	Hepatosplenomegaly 2-3 cm under arcus costae, blood count: white blood cell (WBC) 257×10⁹/L and platelets (PLT) 5450×10⁹/L	Imatinib	Caverosa-corpus spongiosum shunt	No ED at 3 months follow up
7	Clark et al.¹⁵	USA	2018	13	3 days	Blood count: WBC count of 350,000/mL (350×10⁹/L) and platelet count of 450×10³/mL (450×10⁹/L). Flow cytometry of blood: granulocytosis with no increase in blasts	leukapharesis, IV fluids, hydroxyurea, allupurinol, Imatinib	phenylephrine injection, three times corporeal irrigation	improved with phallus rigidity and tenderness
7	Clark et al.¹⁵	USA	2018	13	3 days	BMA: Philadephia chromosome		phenylephrine injection, three times corporeal irrigation	improved with phallus rigidity and tenderness
8	Kumar et al.¹⁶	India	2018	47	5 days	Hepatosplenomegaly, WBC: 279×109, 91.2%BCR	Hydroxyurea, Imatinib	Aspiration and irrigation with phenlyephrine, Winter’s T Shunt	Successful treatment
				42	7 days	Splenomegaly 6 cm below costal margin, WBC: 390×109/L, 70,7% BCR-ABL ratio	Hydroxyurea, Imatinib	Aspiration and irrigation	Successful treatment
				28	6 days	No hepatosplenomegaly, WBC: 206×109/L, 75.3% BCR-ABL ratio	Hydroxyurea, Imatinib	Aspiration and irrigation with phenlyephrine, Winter’s T Shunt	Successful treatment
9	Sun et al.⁵	USA	2018	27	8 years, persistent erection 9 hours	Labs: anemia, WBC 450,010, Platelets 509,000/mm³ BMA: 2% blasts, hypercellular bone marrow, granulocytic hyperplasia, small megakaryocytes. BCR-ABL did not reveal clonal evolution.	Leukapheresis, hydoxyurea 500 mg daily, allopurinol 300 mg daily, Imatinib 400 mg daily,	Corporal bpody aspiration, 1 dose of phenylephrine injection	Successful treatment
10	Huei et al.¹⁷	Malaysia	2018	28	48 hours	hepatomegaly 2cm below right costal margin, splenomegaly, anemia, WBC 294×10⁹, platelets: 94×10⁹/L Peripheral blooad smear: hyperleucocytosis, blast cells	Hydroxyurea, allupurinol, intravenous Cytarabine	Intracavernosal aspiration, phenylephrine irrigation–> detumescent –> reccurent erection –> corpoglandular shunt	Successful treatment
11	Minckler et al.⁶	USA	2017	18	3 month intermittent	WBC: 588×10³/uL, platelets: 109×10³/uL	Hydroxyurea transtition to imatinib 400 mg daily	Penile irigation and aspiration	Success
						peripheral blood: hyperleukocytosis with absolute neutrophilia and a peripheral blast count of 2%.
						bone marrow aspirate and biopsy: hypercellular marrow with 4% blasts
						FISH analysis: translocation t(9:22)
12	Nerli RB et al.⁷	India	2016	19	duration: 24 hours	WBC 296800, platelet 936,000/mm³, BMA: hypercellular, increased megakaryocytes	Hydroxyurea 1.5 gram daily, Imatinib 40 mg daily Allupurinol 300mg daily per oral	Irrigation, decompression	Successful
13	Ergenc H et al.¹⁸	Turkey	2015	18	duration: 72 hours	Hepatosplenomegaly 2-3 cm under arcus costae, anemia, WBC 100.000, platelets 1,002,000/mm, peripheral blood smear: immature leukocytes. BMA: hypercellularity with myeloid hyperplasia, positive BCR-ABL translocation	Imanitib 400 mg once daily, allopurinol 300 mg once daily, leukapharesis	not mentioned	Success
14	Shaeer et al.²	Egypt	2015	21	6 days	palpable splenomegaly, WBC 410000, Philadelphia chromosome translocation	Leukapharesis, Imatinib 400 mg daily	failed several cavernosal aspiration and injection of epinephrine –> penile prosthesis	No complication throughout 6 months-follow up
15	Osorio et al.¹⁹	Spain	2014	24	14 hours, the second episode. The first episode was 4 months ago	WBC: 177.15×109, platelet was not mentioned, cytogenic diagnosis: showing CML	Imatinib	Corpora cavernosa aspiration, intracavernosa fenilefrin injection	not mentioned
15	Osorio et al.¹⁹	Spain	2014	29	6 hours, the second episode. The first episode was less than a month ago	WBC: 402.24×109, platelet was not mentioned positive BCR-ABL	hyrdoxyurea	Corpora cavernosa aspiration, intracavernosa fenilefrin injection	not mentioned
16	Hazra et al.²⁰	India	2013	14	24 hours	Splenomegaly 6 cm below the left costal margin, anemia, WBC 226900, platelets 310,000/uL, Peripheral blood smear: immature leukocytes in various stages. BMA: CML.	Hydroxyurea 50 mg/kgBB/day, Allupurinol 300 mg/day	Cavernosal aspiration and phenylephrine irrigation	No recurrence at 2-months-follow-up
17	Veljkovic et al.²¹	Serbia	2012	16	24 hours	Splenomegaly 4 cm below costal margin, WBC 320×109/L, Platelet (Plt) 417×10⁹/L BMA: extreme hypercellularity, BCR/ABL positive	leukapharesis, cytoreductive chemotherapy	leukapharesis	no follow up
18	Paladino et al.³	Spain	2011	16	48 hours	Splenomegaly, WBC 312.000, PLT: 60.000/mm³ BMA: showing CML	no mention	Corpora cavernosa drainage	Erectile dysfunction
19	Gupta et al.²²	India	2009	12	48 hours	Hepatosplenomegaly below the costal margins, anemia, WBC: 346×109/L, platelet count of 40,000/mm³, peripheral blood smear: immature myeloid leukocytosis. Cytogenesis: philadelphia chromosome. BCR-ABL transcript was positive	hydroxyurea 4g/day IV fluid 3L/day, allopurinol, Imatinib 400mg/day, leukapharesis	Terbutaline 0.125 mg subcutaneously	Resolved by 24 h
20	Ilais Tazi²³	Morocco	2009	33	duration: 22 hours	Palpable splenomegaly 4 cm below left costal margin, WBC: 400000/mm³, platelets 1200000/mm³. Peripheral blood smear: immature leukocytes. Karyotyple analysis: Ph1 chromosome, myeloid hyperplasian in the bone marrow.	Imatinib	Aspiration	Success
21	Castagnetti et al.²⁴	Netherland	2008	9	several days	splenomegaly, anemia, WBC: 509×109/L, philadelphia chromosome, BCR-ABL +	Hydroxyurea 1.5mg/m²/day, Cyclophosphamide 250 mg/m²/day for 2 days, leukopharesis	cytoreduction, antibiotics, anticoagulants	Fully resolved after 1 month
				9	96 hours	mild splenomegaly	Hydroxyurea 1g/m²/day	LMWH 90 units/kg SQ BID for 1 month, metamizole	fully resolved after 3 months
				9	9 hours	hepatosplenomegaly	Cyclophosphamide 250 mg/m²/day for 2 days, leukapharesis	LMWH 90 units/kgBB SQ BID for 9 days, metamizole, morphine	fully resolved after 20 days
22	Yoshida et al.²⁵	Japan	2007	29	48 hours	WBC 263000	Imatinib mesylate	Winter procedure	no evidence of recurrent
23	Lopez et al.²⁶	Spain	2004	29	10 hours	WBC 414×10⁹/L, BMA: hypercellularity, PLT: 1100 × 10⁹/L	corpora cavernosa aspiration, phenylephrine injection	corpus cavernosum aspiration, fenilefrin injection	Successful treatment
24	Ponniah et al.²⁷	United Kingdom	2004	19	18 hours	WBC 513×109/L	Leukapharesis	failed cavernosal aspiration + leukapharesis	No ED on follow up
25	Dogra et al.²⁸	India	2003	18	10 days	hepatosplenomegaly, anaemic, WBC 320000, PLT was not mentioned	Intravenous hydration, furosemide, sodium bicarbonate, hydroxyurea, allopurinol, leukapharesis	Winters Procedure	impotent and enlarged penis at 3-months follow up
26	Meng-Wei Chang et al.⁸	Taipei	2003	21	19 hours	Hepatomegaly 6 cm below right arcus costae, Splenomegaly 7 cm below left arcus costae, anemia, WBC 216800, Platelet 1746,000/mm³	Interferon alfa-2a (6MIU/vial), allopurinol 300 mg daily	Aspiration, epinephrine irigation	Success
27	Guerra et al.²⁹	Spain	2002	53	12 hours	WbC 968×109/L	Hydroxyurea	Corpora cavernosa aspiration	Successful treatment
28	Murayama et al.³⁰	Japan	2001	14	4 days	WBC 510000, BMA: myeloid hyperplasia, karyotype analysis: chromosome Ph1	urokinase, hydroxyurea	embolization of bilateral pudendal artery	Reduced sexual potency
29	Rojas et al.³¹	Chilli	1998	22	duration: 36 hours	none	Leukapharesis	Surgical intervention	Unsuccessful (post treatment sexual dysfunction)

The patient in our study was 18 years old. However, based on the literature, patients in every age group are at risk of developing priapism. There are two peaks in the age distribution that tend to experience this condition. The peak in earlier age is between 5 and 10 years, especially in patients with sickle cell disease. Meanwhile, the second peak is at sexually active phase between 20 and 50 years. Apart from hypercoagulability, this condition may also be related to the abuse of erectile drugs.⁷

History and physical examination are important when encountering cases of priapism. Laboratory tests are required to check for impaired coagulation and serum electrolytes. Some patients who are at high risk for priapism include users of intracorporal injection therapy for erectile dysfunction, coagulation disorders such as sickle cell disease and CML.²^,⁴ In CML, hyperleukocytosis is thought to be the prime cause of priapism. The main mechanism is the aggregation of leukemic cells in the corpora cavernosa and dorsal veins of the penis. Other than that, mechanical pressure in the abdominal veins due to the enlargement of the spleen might also increase the risk.¹

The data needed in the management of patients with this case are erection duration, pain scale, trauma, complete blood count, peripheral blood smear, penile blood gas analysis, bone marrow and polymerase chain reaction for BCR–ABL1 if necessary.¹^,²^,⁴ In CML, the most common type of priapism is the ischemic one (veno-occlusive). Patients usually complain of painful, rigid erection, with reduced to no cavernous blood flow at all. Priapism that lasts for more than 4 hours indicates a compartment syndrome and may require emergent medical intervention.⁸

The American Urological Association recommends that systemic treatment of an underlying disorder should not be the only one therapy for ischemic priapism. In this case, the patient had an erectile episode since 20 days before the admission. This phenomenon was likely due to the compartment syndrome, hence the intra-cavernous aspiration was required.¹

The intra-cavernous aspiration procedure can be accomplished by giving the anesthetic injection first under the symphysis pubis. The penis is tied with a tourniquet followed by insertion of a 16–18-Gauge bivalve intravenous catheter into the corpus cavernosum. When the two corpora are fused, aspiration of 20–30 mL of blood can be undertaken. This procedure has 30% chances of success.⁸^,⁹

Systemic therapy is often used to reduce hyperviscosity is cytoreductive therapy such as high-dose hydroxycarbamide and tyrosine kinase inhibitors (TKI) with or without apheresis procedures. Hydroxycarbamide can be given 2–6 grams divided into four doses per day. This can reduce leukocytes by almost 60% in 24–48 h. In addition, TKI, such as imatinib, can be administered as soon as the diagnosis is confirmed. The recommended dose of imatinib is 400 mg once daily in the chronic phase, 600–800 mg once daily in the accelerated phase, and 800 mg once daily in a blast crisis.⁹ Generally, IRIS study describes the effectiveness of imatinib therapy for complete hematological response (CHR), major cytogenetic response (McyR) and complete cytogenetic response (CcyR).⁴

Leukapheresis can promote a rapid decrease in intravascular leukemic cells, improve tissue perfusion and prevent leukostasis (generally show pulmonary and central nervous system manifestations). Once leukapheresis is given, it possibly can reduce the leukocyte count by 30–60%. However, compared to the chemotherapy, several previous studies have shown that this procedure had high all-cause mortality. According to 2016 apheresis guidelines, category 2 (second-line therapy) is recommended for grade 1B of acute myeloid leukemia (strong recommendation, moderate quality evidence), while category 3 (unclear role of apahresis) is recommended for acute lymphoblastic leukemia cases grade 2C (weak recommendation, low quality evidence). In this guideline, leukapheresis is not recommended for chronic myeloid leukemia.¹⁰ Several cases of priapism in this case review reported a successful combination of leukapheresis with systemic oral CML therapy. A study by Rojas et al. was the only one reporting a failed leukapheresis.

This case report and review presents a comparative presentation of patient characteristics, clinical characteristics of CML, laboratory profile, and therapeutic intervention for CML with priapism. Clinical presentation and early intervention are pivotal keys to achieve favorable outcome and prevent complications. Systemic intervention combined with intraurethral therapy may add the success rate (see Figure 2).

Figure 2. Treatment and outcome from priapism and CML.

Eventually, further discussion and study on other causes of priapism is essential as a meta-analysis stated that priapism might also be related to lymphoproliferative disorders.³²

Consent

Written informed consent for publication of their clinical details and/or clinical images was obtained from the patient.

Data availability

All data underlying the results are available as part of the article and no additional source data are required.

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Open Access Articles

Case Report: Priapism as The Clinical Presenting Feature of Chronic Myeloid Leukemia: Case Report and 20-Year Literature Review [version 2; peer review: 1 approved, 1 approved with reservations]

BySiprianus Ugroseno Yudho Bintoro

Case Report: Priapism as The Clinical Presenting Feature of Chronic Myeloid Leukemia: Case Report and 20-Year Literature Review

Introduction

Case

Figure 1. Penis at day 2, day 6 (after intracavernosal blood aspiration), and day 9.

Discussion

Table 1. Case report review from last than twenty years.

Figure 2. Treatment and outcome from priapism and CML.

Consent

Data availability

References

By Siprianus Ugroseno Yudho Bintoro

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