Sarcomatous Change Research Articles

A Case of Vaginal Leiomyoma: A Rare Entity

ABSTRACT Although uterine fibroids are common, vaginal fibroids are very rare. We report one such rare case of a woman who presented with a big mass projecting in the vagina with complaints of dyspareunia, dysuria and passage of dark, altered collected blood per vaginum. Ultrasound and magnetic resonance imaging (MRI) reported it as a cervical fibroid. It was enucleated successfully through vaginal route and histopathology report confirmed diagnosis of benign vaginal leiomyoma. Diagnosis of vaginal leiomyoma is rather challenging and its complete removal should be done to prevent recurrence, rule out sarcomatous change and relieve symptoms. How to cite this article Bansal N, Jain VJ, Gupta V, Bharadwaj A. A Case of Vaginal Leiomyoma: A Rare Entity. J South Asian Feder Obst Gynae 2015;7(3):231-233.

Image Findings of Sarcomatous Intrahepatic Cholangiocarcinoma Focused on Gd-EOB-DTPA Enhanced MRI: A Case Report

Sarcomatoid changes of epithelial neoplasms are rare but found occasionally in renal cell carcinoma, squamous cell carcinoma (involving the lungs, esophagus, and skin), and adenocarcinoma of the lung (1). In the liver, transformation is very rare and has been mainly reported in hepatocellular carcinoma (about 3.9 to 9.4% in autopsy) and rarely in cholangiocarcinoma (about 4.5% in autopsy) (2, 3). Sarcomatous changes of cholangiocarcinoma are defined as sarcomatous intrahepatic cholangiocarcinoma (ICC) in the World Health Organization (WHO) classification of tumor. Sarcomatous ICC is a extremely rare disease and only a few cases are reported in the English literature (3). It has been reported that prognosis for ICC is worse than that for an ordinary ICC (4). So it is important for the radiologist to recognize and differentiate change from the ordinary ICC. In the literature, ICC have been reported as hypointensity on T1 weighted image (WI) and hyperintensity relative to liver parenchyma on T2WI. On dynamic contrast-enhanced magnetic resonance (MR) imaging, peripheral contrast enhancement is frequently seen in the arterial phase and progressive concentric filling pattern is seen in the late venous phase (5). But these findings are similar to ordinary ICC and characteristic radiologic differences are not identified yet (5). We report a case of ICC in a 79-yearold male and describe the findings of serial computed tomography (CT), EOB-DTPA This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/ by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Received: January 8, 2015 Revised: March 9, 2015 Accepted: March 10, 2015

Carcinosarcoma uterino con extensión pélvica: presentación de un caso y revisión de la literatura

<p><strong>Objetivo:</strong> se presenta un caso de carcinosarcoma uterino para hacer una revisión de la literatura publicada acerca de la epidemiologia, el diagnóstico, tratamiento y pronóstico de esta neoplasia.</p><p><strong>Materiales y métodos:</strong> se presenta el caso de una paciente de 73 años de edad, quien consultó a un centro de referencia para atención ginecoobstétrica en Cartagena (Colombia), por sangrado vaginal, pérdida de peso y masa pélvica. El análisis microscópico reveló un carcinosarcoma endometrial/ tumor mülleriano mixto maligno. Se realizó una búsqueda sistemática en las bases de datos Medline vía PubMed, Hinari, Imbiomed, ScienceDirect y EBSCO, utilizando los términos "Carcinosarcoma", "Neoplasias uterinas", "Útero". Se buscaron estudios tipo reporte de casos, revisiones de temas u otros estudios publicados en los últimos diez años, en inglés o español.</p><p><strong>Resultados:</strong> se encontraron 350 títulos de los cuales un total de 20 artículos estaban relacionados directamente con el tema, de estos se seleccionaron 18 que correspondieron a ocho reportes de casos, siete revisiones de temas, dos cohortes retrospectivas y un ensayo clínico. El carcinosarcoma uterino es una neoplasia poco frecuente que afecta especialmente a mujeres posmenopáusicas. Histopatológicamente se observa una combinación de cambios carcinomatosos y sarcomatosos; el tratamiento estándar es quirúrgico. La profundidad de la invasión miometrial ha sido sugerida como factor pronóstico muy importante, y en un 50 % de los casos presenta extensión extrauterina que se asocia con una supervivencia general muy pobre.</p><p><strong>Conclusiones: </strong>el carcinosarcoma es una neoplasia de baja frecuencia caracterizada por su población celular bifásica y mal pronóstico.</p>

A Case of Sacromatoid Hepatocellular Carcinoma Without Prior Anticancer Therapy

Introduction: Sarcomatoid hepatocelluar carcinoma (SHCC), also referred as spindle cell carcinoma, pseudosarcoma, or carcinosarcoma is a rare histological type of hepatocelluar carcinoma (HCC). Incidence of SHCC is 1.8% in surgically resected, and 3.9% to 9.4% in autopsy cases. Previous chemotherapy use is presumed to promote sarcomatous change. We report a case of SHCC without prior anticancer therapy. Case Report: A 66-year-old Hispanic male presented with complaint of abdominal distension. The patient had past medical history of cirrhosis due to hepatitis C infection, portal hypertension, esophageal varices, recurrent ascites s/p therapeutic paracentesis (last done 3 months prior), diabetes mellitus, and hypertension. The patient had a 20-pack a year smoking history, but quit 20 years ago and denied alcohol or illicit drug abuse. He had no family history of any cancer. Vital signs on presentation, blood pressure 105/58 mm hg, pulse 74 per minute, and regular, respirations rate 20 per minute, temperature 97.8 F, BMI 25.2. On physical exam, the patient was found to have distended abdomen, dull on percussion. Labs showed hemoglobin 12.5 gm/dL, white count 5700/ul, platelet count 134,000/ul, prothrombin time 15.8 seconds, INR 1.2, sodium 130 meq/L, potassium 4.1 meq/L, chloride 100 meq/L, bicarbonate 28 meq/L, glucose 218 mg/dl, BUN 18 mg/dl, creatinine 0.9 mg/dl, calcium 8.2 mg/dl. albumin 2.6 G/DL, total protein 8.2 G/DL, bilirubin total 1.20 MG/DL, alkaline phosphatase 179 U/L, AST 34 U/L, ALT 20 U/L, and alfa-feto protein 4.3 ng/mL. CT abdomen showed a 4.3-cm rim-enhancing mass in the medial segment of the left lobe of the liver in periphery along the diaphragmatic crus. Biopsy of liver mass was done, which showed areas of moderately differentiated conventional HCC and other areas of high-grade spindle tumor. Immunohistochemical stains showed both components stained for keratin. The spindle component did not stain for desmin, CD31, CD34 but was positive for vimentin. The patient underwent upper and lower gastrointestinal endoscopy, which showed no evidence of malignancy. The patient refused any further treatment, and eventually died 8 months after diagnosis. Conclusion: SHCC, compared to ordinary HCC, has relative low serum AFP levels, higher incidence of intrahepatic and adjacent organ invasion, high tendency to large tumor size with central necrosis and hemorrhage in the tumor, delayed peripheral enhancement of the tumor on CT images, resistance to treatment, early recurrence after treatment, and a poorer prognosis, with approximate life expectancy less than 1 year after diagnosis. We should consider SHCC even when a patient has not undergone anticancer therapies.

Liposarcoma in the axilla developed from a longstanding lipoma.

Liposarcoma in the axilla developed from a longstanding lipoma.

Surgical reduction of scrotal massive localized lymphedema (MLL) in obesity

Lymphedema of the penis and scrotum is physically and psychologically disabling. Obesity is a source of secondary lymphedema. When restricted to specific anatomical regions in obesity, this is termed massive localized lymphedema (MLL). Few surgical cases of specific scrotal MLL in obesity are reported in the literature. We present our case series to improve the management of this complicated pathology. This is a retrospective review of obese adult patients with clinically diagnosed scrotal MLL undergoing reduction scrotoplasty by the senior author (J.R.S.) from 1992 to 2012. Medical, social, familial, surgical, and follow-up data were extracted. Prior infection of the scrotal lymphedema, surgical details, pathologic evaluation, and postoperative complications were noted. A series of the cases is presented. Four cases met the criteria for study. The average age was 35 years with an average body mass index of 53.9. Average resection at the first procedure was 3492 g. All patients were reconstructed with laterally based scrotal flaps. The pathology for each case was consistent with chronic lymphedema; no sarcomatous changes were noted. Fifty percent of the patients had recurrence of the scrotal MLL. The average total number of operations during the follow-up period for either complication or recurrence was two. This is the largest case series specifically investigating surgical treatment for scrotal MLL in obesity. Lateral-based scrotal flaps (with or without mid-raphe Z-plasty) permit anatomic reconstruction. Complications are common and recurrence is frequent after surgical management. Excision with reconstruction improves urinary function and overall symptoms.

Unusual computed tomography features of ruptured sarcomatous hepatocellular carcinoma

Sarcomatous change in hepatocellular carcinoma (HCC) is an uncommon histologic variant of HCC, characterized by the proliferation of spindle cells or bizarre giant cells. Poor outcome has been reported in most cases after diagnosis. Here, we report the first case of a sarcomatous HCC with complete central necrosis and rupture of the liver capsule. The patient received target therapy with sorafenib, but died of progressive intra-abdominal carcinomatosis 3 months after treatment. We reviewed the published reports of 13 patients with sarcomatous HCC that included computed tomography features and found that our patient was the only one to have received sorafenib. It appears that this patient's life span was not significantly prolonged with the use of sorafenib.

Primary Cutaneous Carcinosarcomas

To present and define diagnostic criteria for primary cutaneous carcinosarcomas (CSs). Neoplasms of 6 patients with primary cutaneous CSs were retrospectively analyzed. A panel of histopathologic parameters and immunophenotypic expression of distinct markers of differentiation were investigated. All cases had medium-to-poorly differentiated squamous cell carcinoma representing the epithelial component intermingled with a variable amount of malignant sarcomatous tissue proliferation. The authors identified 3 distinct morphological criteria for the diagnosis of primary cutaneous CSs with features of (1) a clearly defined dual neoplasm with explicit morphological characterization using histology and immunohistochemistry with distinct marker panels while, (2) metastases from distant sites and true collision neoplasms must be excluded, and (3) recognition of the neoplasm as a solid coherent proliferation with careful exclusion of sarcomatous stromal changes in the surrounding neoplasm stroma has to be assured. The low incidence of this entity and a plethora of different synonymous terms in the dermatopathologic literature often cause diagnostic problems and hamper the accurate comparative analysis of cases published previously. Herein, the authors propose defining criteria and a clearly defined morphological approach to contribute to more accurate dermatopathologic diagnoses and provide an unprecedented summary on this neoplastic entity.

繰り返す局所療法後に発生した肉腫様変化を伴う肝内胆管癌再発の1例

75歳，男性．72歳時からS8を中心とした多発肝細胞癌の診断でTACEとRFAを繰り返した．画像上，横隔膜浸潤を伴う局所再発像を認め，肝中央二区域切除・横隔膜合併切除術を施行した．病理組織学的に一部に紡錘状細胞を認め，免疫染色ではCK19陽性，hepatocyte陰性，AFP陰性であったことから，肉腫様変化を伴う肝内胆管癌再発と診断した．術後12カ月後に横隔膜切除断端からの再発を認め，横隔膜・右肺部分切除術を施行した．さらに，再手術後6カ月で縦隔リンパ節転移再発を認めた．病変が小さい場合，肝細胞癌と肝内胆管癌の鑑別に難渋する場合がある．本症例のように1病変に対して局所療法を繰り返すことにより，肉腫様変化をきたす可能性も報告されている．臨床的に肉腫様変化の診断は容易ではなく，局所制御に難渋する肝腫瘍症例においては，根治を期待できる切除を積極的に考慮することが望ましいと考えられた．

A Rare Case of Gaint Cell Tumour of Distal Femur with IntraArticular Extension

A 25 year old male patient, farmer presented with symptoms of pain, swelling and restricted right knee movements since 6 months. Range of motion was severely restricted with fixed flexion deformity of 20 degrees. X-ray of knee (anterior posterior and lateral view) showed osteolytic lesion involving distal femur with intra-articular extension and MRI showed involvement of distal 10 cms of ephiphysiometaphyseal area of femur with focal intra-articular extension and into tibia. Biopsy was done initially following the standard principles. Histopathological report turned out to be gaint cell tumour without sarcomatous changes. The treatment options available were biological knee construction (i.e. arthrodesis with internal/external fixation and auto bone grafting) and megaprosthetic knee replacement. Excision of tumour followed by arthrodesis with custom made intramedullary interlocking nail with fibula and iliac bone grafting. Post operatively there was 2 cms shortening was present. On 1 year follow up patient is carrying out his daily living activities and radiographs done showing good graft consolidation and without any signs of recurrence.

Secondary Sarcomatous Transformation in Mature Cystic Teratoma: An Uncommon Cause of Acute Abdomen

Malignant transformation in a mature cystic teratoma is rare and sarcomatous change is even rarer. We report a case of 57 year old post-menopausal woman who presented with tender abdominal mass and fever. She underwent Total Abdominal Hysterectomy with Bilateral Salpingo-oophorectomy. Left ovary showed a mature cystic teratoma with solid areas. Histopathology of these solid areas showed a high grade spindle cell sarcoma which exhibited Vimentin and SMA positivity on Immunohistochemistry and was thus diagnosed as leiomyosarcoma. In most instances malignant transformation cannot be diagnosed pre-operatively. Most of these tumors are considered resistant to radiation and systemic chemotherapy and carry a poor prognosis.

急速な進展，再発を示した肉腫様肝癌の1例

急速な進展，再発を示した肉腫様肝癌の1例

Mesonephric adenocarcinoma with a sarcomatous component, a notable subtype of cervical carcinosarcoma: a case report and review of the literature

Carcinosarcoma of the uterine cervix is less common than its counterpart in the uterine corpus. On the other hand, mesonephric adenocarcinoma is also a rare neoplasm in the uterine cervix, and it has been reported that mesonephric adenocarcinomas are often accompanied by sarcomatous components. We present a case of mesonephric adenocarcinoma with a sarcomatous component which arose in a 63-year-old postmenopausal woman. The hysterectomy specimen grossly showed an exophytic mass measuring 1.8 cm in the uterine cervix. Histologically, diffuse mesonephric hyperplasia and adenocarcinoma with malignant spindle cell proliferation was recognized, and therefore the tumor was diagnosed as “mesonephric adenocarcinoma with a sarcomatous component.” The review of the literature of cervical carcinosarcoma and cervical mesonephric adenocarcinoma revealed that 16% of cervical carcinosarcoma is of mesonephric duct origin, and that mesonephric adenocarcinoma seems to be more likely to have sarcomatous change. We think the presence of a sarcomatous component in the cervical biopsy specimen could be helpful in the diagnosis of mesonephric duct origin.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1243996503911062

Intrahepatic cholangiocarcinoma with sarcomatous change producing granulocyte‐colony stimulating factor

Intrahepatic cholangiocarcinoma with sarcomatous change producing granulocyte‐colony stimulating factor

PDGFB rearrangement in dermatofibrosarcoma protuberans: correlation with clinicopathologic characteristics and clinical implications

Dermatofibrosarcoma protuberans (DFSP) is characterized genetically by the translocation t(17;22)(q22;q13), which creates a COL1A1/PDGFB fusion gene. The implications of this gene for the clinicopathologic features of the disease are not fully understood. Fifty-one cases of DFSP from 46 patients were reclassified as DFSP (n=29) and DFSP-fibrosarcomatous variant (DFSP-FS; n=22). Fluorescence in situ hybridization was performed using a dual-color break-apart probe to detect rearrangements involving PDGFB, and CD34 immunohistochemistry staining was done. The DFSP-FS was found in older patients, and the tumors were larger, with a smaller mean area of staining for CD34. PDGFB rearrangement was found in 45 cases (95.7%). The mean gene copy number was 3.82 (range 2.2-6.45) and was higher in DFSP-FS than in classic DFSP (4.54 vs. 3.47; P < .001). The PDGFB copy number showed a moderate positive correlation with the number of mitotic figures and tumor size. Patients undergoing wide excision or having no involvement of the resection margin had no relapses. These results suggest a role for COL1A1/PDGFB in sarcomatous change in DFSP over time. Detection of COL1A1/PDGFB rearrangement by fluorescence in situ hybridization is useful for confirmation of the diagnosis. Patients who present with metastatic DFSP-FS show less typical histologic findings and loss of CD34 staining, leaving PDGFB rearrangement as the preferred adjunctive method for diagnosis from small biopsies and for prediction of the value of imatinib therapy.

肝切除後極めて急激な再発を認めた肉腫様変化を伴うG-CSF産生肝内胆管癌の1例

肝切除後極めて急激な再発を認めた肉腫様変化を伴うG-CSF産生肝内胆管癌の1例

Adrenal metastasis of a phyllodes tumor of the breast: Case report and review of the literature

INTRODUCTIONA phyllodes tumor is a neoplasm of mixed mesenchymal and epithelial origin affecting the breast. It may pursue a benign or malignant evolution with distant metastases in the latter case. Sites most commonly affected by metastases are the lungs and bones. Simple mastectomy is the mainstay of treatment. This article presents the first described case of metastasis to the adrenal gland after sarcomatous transformation of a phyllodes tumor. A review of the literature is presented afterwards. PRESENTATION OF CASEA 57-year old female patient presented with a voluminous breast mass which was completely resected. Unfortunately she presented with malignant recurrence in the breast which was also resected. A later recurrence within the lung presented and was completely resected but showed aspects of sarcomatous changes. Finally a recurrence was pathologically documented within the adrenal gland. Unfortunately, disease later progressed and the patient refused further treatment at that point. DISCUSSIONWhile malignant transformation of breast phyllodes tumors and metastasis is relatively common, the prognosis for initially benign lesion that are completely excised is usually good. This case represents the first documented metastasis to the adrenal gland of a breast phyllodes tumor. CONCLUSIONWe presented the first case of adrenal metastasis of a phyllodes tumor after sarcomatous degeneration. This is an unusual presentation of a relatively uncommon but well-recognized disease of variable malignant potential.

前治療歴のない肉腫様変化を伴った肝細胞癌の1例

症例は78歳の男性で，上腹部違和感を主訴に近医を受診した．腹部USにて肝腫瘍を指摘され，当院を紹介受診した．腹部CTでは肝S4からS5にかけて最大径6.7 cmの腫瘍を認めた．腫瘍のS5寄りの部分には被膜様構造がみられ，早期に濃染し，遅延相では低吸収域となった．S4寄りの病変部は周囲との境界が不明瞭で，辺縁から徐々に造影された．MRCPではS5の胆管枝への浸潤も疑われた．腫瘍マーカーはPIVKA-IIのみが854 mAU/mlと上昇していた．以上より，混合型肝癌を第一に考え，肝拡大右葉切除術，肝外胆管切除兼胆道再建術，肝十二指腸間膜内リンパ節郭清を施行した．病理組織学的には，肝細胞癌の一部に肉腫様変化をみたが，腺癌成分は認めなかった．術後37か月が経過し，再発なく社会復帰している．比較的まれな肉腫様変化を伴った肝細胞癌の1例を経験したので，文献的考察を加え報告する．

FDG-PETで高集積を呈した肉腫様変化を伴う肝内胆管癌の1例

症例は59歳，女性．近医にて肝腫瘍を指摘されて当院紹介となった．腹部造影CTにて肝外側区域を占める長径10cm大の分葉状腫瘤性病変を認め，肝内胆管癌と診断した．明らかなリンパ節転移は認めなかったものの，FDG-PETでは高集積（SUV max＝15.30）を呈する腫瘍であり，悪性度の高い腫瘍と考えられた．同症例に対し，肝拡大外側区域切除術を行った．病理組織所見で低分化の胆管細胞癌と診断され，一部に肉腫様変化を伴っていた．免疫組織化学染色ではCK7陽性，VimentinおよびCK19陰性であった．Ki-67 Labelling Indexは28％と高値であり，細胞増殖能の亢進を反映していると考えられた．術後経過は良好で，GEMにより術後補助化学療法を施行し，術後1年現在，無再発生存中である．肉腫様変化を伴う肝内胆管癌は予後不良な疾患であり，FDG-PETでの集積との関連は報告されていない．今回，FDG-PETで高集積を呈した1例を経験したので，若干の文献的考察を加えて報告する．

Very rare case of rectal carcinosarcoma

Dear Sir, Carcinosarcoma is a rare type of malignant neoplasm, which was first described by Virchow in 1864. It is composed of two types of neoplastic cells, epithelial, and mesenchymal ones. This neoplasm has a poor prognosis and may develop in many organs, including the uterus and ovaries of older women, the head and neck region, and the lungs and kidneys. Within the gastrointestinal tract, carcinosarcoma is most commonly found in the esophagus [1] and only rarely in the large intestine. Among case reports before 2011, 16 fulfilled the criteria for carcinosarcoma of the large intestine, and of these, only 5 involved the rectum. We report a case of carcinosarcoma of the rectum with necrosis of the intestinal wall. An 83-year-old male was admitted to the surgical ward with signs of massive lower gastrointestinal tract bleeding. The patient had congestive heart failure, diabetes, and chronic respiratory failure secondary to venous thromboembolism. On digital rectal examination, a stenotic, bleeding tumor of the rectum, infiltrating the perianal tissues on the right side could be felt. The distal margin of the tumor was palpable at the level of anorectum, while its superior margin was unreachable. Anal endosonography revealed a tumor (30 mm × 53 mm × 40 mm in size) occupying the right half of the anal canal, infiltrating the sphincter muscles (internal and external), with areas of necrosis (Fig. 1). Fig. 1 a The endosonographic study shows a hyperechoic tumor, measuring 30 × 53 mm in a transversal plane, taking up the right half of the anal canal lumen, infiltrating the anal sphincters, b With anechoic areas of necrosis Due to the deterioration of the patient’s overall condition and continued signs of active bleeding from the tumor, the patient qualified for emergency surgery (ASA IV). Intraoperatively, on rectal examination, a stenotic tumor with an ulceration at the right side of the rectal wall was confirmed. The necrotic tissue was partially removed, the rectum was rinsed with normal saline, then, the site of bleeding was coagulated, and internal packing of the rectum was carried out. An exploratory laparotomy was performed through an infraumbilical midline incision. A loop sigmoidostomy was created due to necrosis of the rectal wall and perirectal tissue. The remaining abdominal organs did not reveal any abnormalities on palpation (e.g., distant metastases). There were no complications in the early postoperative period. However, due to the patient’s poor overall condition, he was not a candidate for oncological treatment. The patient was discharged home on postoperative day 14 and advised to return for the histopathology results. He died 5 weeks after the surgery, due to cardiorespiratory failure. The histopathology examination of the specimen revealed carcinosarcoma of the rectum which was confirmed by immunohistochemical staining which was positive for cytokeratin, vimentin, and smooth muscle antigen (Fig. 2). This mixed neoplasm was formed from epithelial elements of a well-differentiated adenocarcinoma as well as from mesenchymal neoplastic elements, showing differentiation toward muscle tissue. Fig. 2 a Staining using anti-cytokeratin antibodies used to identify cells of epithelial origin; b Staining using anti-vimentin antibodies to identify cells of mesenchymal-origin; c Staining using anti-SMA (smooth muscle antigen) antibodies Carcinosarcoma of the colon is a rare neoplasm composed of both carcinomatous and sarcomatous elements. It has also been called as sarcomatoid carcinoma, carcinoma with mesenchymal stroma, carcinoma with sarcomatous change, spindle cell carcinoma, and pleomorphic anaplastic carcinoma [2]. The prognosis of this carcinoma is poor because it invades deep into the bowel wall, has widespread metastases, and is resistant to multi-agent chemotherapy. Up to now, all the described cases of rectal carcinosarcoma included lymph node metastases at the time of diagnosis [3–5]. Our patient did not have any distant metastases noted at explorative laparotomy. However, the local spread of the neoplasm led to necrosis of a fragment of the rectal wall and secondary bleeding, a complication which had not been described previously. The only published case with necrosis of the intestinal wall involved the carcinosarcoma of the ascending colon [6]. Survival in the reported cases of rectal carcinosarcoma was never more than 6 months. Our patient died within a mere 5 weeks, which should be attributed to the advanced local state of the cancer at the time of diagnosis and the patient’s poor general condition which prevented further treatment. The case presented in this article is, to the best of our knowledge, the first involving bleeding into the gastrointestinal tract secondary to perforation of the rectal wall as a complication associated with this neoplasm. Therefore, the rare diagnosis of carcinosarcoma should be considered in patients with gastrointestinal bleeding.