The Impact of Tumor Laterality (Unilateral vs. Bilateral) on Presentation and Management Outcome in Patients with Retinoblastoma.

Background: This study compares the outcomes of managing retinoblastoma between patients with unilateral and bilateral presentations. Methods: The study, conducted at the King Hussein Cancer Center in Amman, Jordan, retrospectively analyzed cases of retinoblastoma treated between March 2003 and December 2019. Evaluation criteria included clinical features, disease stage, treatment methods, and overall management outcomes. Results: The study comprised 697 eyes from 478 patients with retinoblastoma, with 52% being males. Bilateral disease was observed in 70% of patients, and a family history of retinoblastoma was more prevalent in cases with bilateral disease (20%) compared to those with unilateral disease (4%). Unilateral cases had a median age at diagnosis of 28 months, whereas bilateral cases were diagnosed at a median age of 6 months. Extra-ocular retinoblastoma was detected in 1% of eyes. According to the International Intraocular Retinoblastoma Classification (IIRC), 88% of unilateral cases presented with advanced disease (IIRC group D/E), compared to 46% in bilateral cases. Primary enucleation was performed in 29% of unilateral cases and 16% of bilateral cases (p-value 0.0007). Eye salvage rates were 31% in unilateral cases and 68% in bilateral cases (p-value < 0.0001). At 120 months of follow-up, 5% of patients died from secondary neoplasms or metastases, 81% were alive, and 14% were lost to follow-up. There was no significant difference in metastasis, secondary neoplasms, or mortality between patients with unilateral and bilateral retinoblastoma. Conclusions: This study highlights the nuanced differences in clinical characteristics and outcomes between unilateral and bilateral retinoblastoma, emphasizing the necessity of customized management and early detection strategies. It demonstrates that while bilateral retinoblastoma benefits from earlier detection and has a higher rate of eye salvage, there is no significant difference in metastasis or mortality rates when compared to unilateral cases. The critical roles of primary enucleation in advanced cases, along with effective communication and patient education, are also underscored to improve treatment adherence. Overall, these findings point to the importance of tailored approaches in optimizing outcomes for the diverse patient population affected by retinoblastoma.

Ocular and Periocular Metastasis in Breast Cancer: Clinical Characteristics, Prognostic Factors and Treatment Outcome.

BACKGROUND: Breast cancer remains a leading cause of cancer-related mortality and morbidity worldwide. Ocular and periocular metastasis present as a rare but clinically significant manifestation. This study aims to explore demographics and clinical aspects of ocular and periocular metastasis in breast cancer patients. METHODS: A retrospective cohort study comprising 45 breast cancer patients with ocular or periocular metastasis treated between 2013 and 2023. Patient demographics, tumor characteristics, diagnostic methods, treatment modalities, visual outcomes, and survival data were analyzed. RESULTS: Among 9902 breast cancer patients, 0.5% developed ocular or periocular metastasis, constituting 2.4% of metastatic cases. The median age was 50 years. Ocular metastasis timing varied: 5% before breast cancer, 24% concurrent, 22% within a year, and 49% after. The most common presentations included incidental MRI findings (42%) and vision decline (31%). Metastasis involved the orbit (47%), choroid (40%), optic nerve (11%), and iris (2%), with 44% having bilateral involvement. Predictive factors included invasive lobular carcinoma (ILC) (p < 0.0001) and brain metastasis (p < 0.0001), with ILC exhibiting a sixfold higher likelihood of ocular metastasis than invasive ductal carcinoma (IDC). Primary treatment was radiation therapy (89%), yielding a 55% maintenance of excellent vision (<0.5), with 93% developing dry eye disease. Patients with ocular metastasis faced an increased risk of disease-related mortality (p < 0.0001), with 71% succumbing within 10 months post-diagnosis. CONCLUSIONS: Ocular metastasis in breast cancer is rare (0.5%) but signifies poor outcome. It is linked to ILC and concurrent brain metastasis. Primary treatment involves radiation therapy, with a favorable visual prognosis.

Metastatic esophageal carcinoma to the eye masquerading as inflammatory vitreo-retinitis: A case report and literature review.

We report an unusual case of metastatic esophageal carcinoma to the vitreous associated with focal retinitis in a 44-year-old male. A 44-year-old male patient, known case of locally advanced esophageal carcinoma, presented with a 3-day history of left eye floaters. The initial diagnosis was inflammatory vitreo-retinitis that responded to systemic steroids. Four months later, the patient presented with relapsed intraocular inflammation, vitreous biopsy using a 25G needle was performed, and cytology confirmed the presence of metastatic carcinoma consistent with his primary esophageal cancer. The patient received external beam radiotherapy to his ocular and brain metastasis, and his eye examination was stable. Five months later, the patient passed away due to progressive brain metastasis.

A qualitative focus on community pharmacists’ attitudes and barriers toward continuing professional development: implications for professional practice

Background: Continuing professional development and continuing education are important components of professional practice for pharmacists. Mandatory continuing professional development requirements have been introduced in several countries, including Jordan. However, information on the uptake of continuing professional development is lacking, particularly in the Jordanian context. Objective: This study’s principal aim was to investigate community pharmacists’ views of continuing professional development and to explore pharmacists’ perceptions of the most common facilitators and barriers to participation in continuing education. Methods: A series of seven focus group sessions were undertaken with groups of four to seven community pharmacists. Focus group transcripts were thematically analyzed using a qualitative data analysis method. Results: The study included 34 pharmacists out of 95 who received invitation letters. Four key themes were identified: (1) community pharmacists’ attitudes toward continuing professional development; (2) perceived motivating factors for continuing professional development; (3) experienced barriers to continuing professional development; (4) and potential strategies for improving pharmacists’ continuing professional development. In terms of attitudes, participants generally understood the concept of continuing professional development. Motivating factors were mainly attributed to personal, work-related, and service provision-related factors. However, experienced barriers that could prevent community pharmacists from participating in continuing professional development despite their motivation were: barriers pertaining to workload, barriers pertaining to pharmacists, and barriers related to lack of resources. (AU)

Solitary fibrous tumour of the gallbladder: A rare case report.

INTRODUCTION AND IMPORTANCE: Solitary fibrous tumours are rare mesenchymal neoplasms with limited malignant potential that can occur anywhere in the body, with a predilection towards body cavities such as the pleura. It has been reported to arise in the peritoneum and the mesentery. CASE PRESENTATION: This is a case of a female patient who presented with an incidental abdominal mass compressing the duodenum. Differential diagnosis included GIST and intra-operatively was found to be arising from the gallbladder. En-bloc cholecystectomy was done and diagnosed a solitary fibrous tumour. CLINICAL DISCUSSION: This is the second case of gallbladder solitary fibrous tumour reported in the literature. CONCLUSION: Awareness of this rare entity is important for diagnosis and treatment.

A comparison of high risk pathological features between primary and secondary enucleation for retinoblastoma.

AIM: To compare the risk and pattern of High-Risk Pathologic Features (HRPF) in retinoblastoma between primary and secondary enucleation. METHODS: A retrospective analysis of 121 eyes from 118 patients who underwent enucleation at the King Hussein Cancer Center (KHCC) Amman, Jordan, between November 2009 and January 2020. Demographic information, tumor stage, time from diagnosis-to-enucleation, results of pathology, metastasis, and mortality were retrieved. RESULTS: Patients in the secondary group (49/121 eyes, 40%) were considerably younger at diagnosis (p = 0.0014), had bilateral disease (p = 0.0001), and had less-progressed disease at presentation (p = 0.016) compared to the primary enucleation. Primarily enucleated eyes were more-likely to have massive choroidal invasion (p = 0.0315) and post-laminar optic nerve invasion (p = 0.027), in spite of the finding that the overall prevalence of HRPF was similar between the two groups (35.5 percent vs. 37.5 percent; p = 0.585). The likelihood of anterior chamber invasion, was considerably higher in secondary enucleated eyes (p = 0.013). We evaluated primary and secondary enucleation for each subgroup (D and E) of the International Intraocular Retinoblastoma Classification (IIRC) and found the prevalence of HRPF was comparable (p = 0.58, 1.0, respectively). The difference in time between diagnosis-to-enucleation in secondary enucleation did not predict HRPF (p = 0.50). There was no discernible difference between primary and secondary enucleated eyes in terms of metastasis or survival (p = 0.156 and 0.44, respectively). CONCLUSION: Systemic chemotherapy has the ability to reduce the extent of tumor expansion that has been pathologically identified. Primary and secondary enucleated eyes are comparable in low metastatic risk only when strict examination and management guidelines are followed.

Renal Spindle Cell Tumor with Thrombus Extension into the Inferior Vena Cava and the Right Atrium Depicted by PET/CT Scan.

Tumor thrombus (also called intravascular tumor extension) can be defined as tumor extending into vessel; typically a vein, it occurs in a lot of malignancies like hepatocellular carcinoma, Wilms tumor, and others. 1 Tumor thrombus has been reported to demonstrate increase in fluorine-18 fluorodeoxyglucose (FDG) uptake that would differentiate it from the benign bland thrombus which would not take up FDG on positron emission tomography/computed tomography (PET/CT) scan. 1 We present a case of spindle cell sarcoma of right kidney whose baseline contrast-enhanced CT revealed a mass replacing the right kidney and right renal vein associated with thrombus in the inferior vena cava (IVC). 18 F-FDG PET/CT imaging was done that revealed an FDG-avid hypermetabolic malignant right renal mass with hypermetabolic IVC thrombus extending to the right atrium.

Presentation and management outcomes of Retinoblastoma among Syrian refugees in Jordan.

Purpose: The humanitarian crisis in Syria has had a profound impact on the entire region. In this study, we report the patterns of presentation and management outcomes of Syrian patients with Retinoblastoma (Rb) treated at a single tertiary cancer center in Jordan. Methods and Materials: This is a retrospective comparative study of Syrian refugees and Jordanian citizens who had Rb between 2011 and 2020. Collected data included patient demographics, presentation, tumor stage, treatment modalities, eye salvage rate, metastasis, and mortality. Results: Thirty Syrian refugees (16 (53%) had bilateral disease) and 124 Jordanian citizens (51(41%) had bilateral disease) were diagnosed with Rb during this period. The median age at diagnosis for refugees was 10 and 32 months for patients with bilateral and unilateral Rb consecutively, compared to 6 and 28 months for citizens. The median lag time between signs of disease and initiation of treatment was 3 months for refugees, compared to 1 month for citizens.Refugees were more likely to present with a more advanced stage (p=0.046). Out of 46 affected eyes in refugees; 32 (70%) eyes were group D or E, while out of 175 affected eyes among citizens; 98 (56%) eyes were group D or E. Therefore, refugees with Rb were more likely to mandate primary enucleation (48%) compared to citizens (25%) (p=0.003). However, out of 24 eyes among refugees who received conservative therapy, 15 (62%) eyes were successfully salvaged, while out of 131 affected eyes among citizens who received conservative therapy, 105 (80%) eyes were successfully salvaged (p=0.06). Two (7%) of the refugees and four (3.2%) of the citizens with Rb died from metastasis. Conclusion: Syrian refugees with Rb presented with more advanced disease due to delay in diagnosis and referral that increased the treatment burden by decreasing the chance for eye globe salvage. However, patients who received the timely intervention had a similar outcome to citizens with Rb; probably a reflection of the management of all patients at a single specialized center. We advocate for the timely referral of refugees with this rare life-threatening tumor to a specialized cancer center for the best possible outcome.

Complete and Durable Response to Tamoxifen and Ovarian Ablation in the Treatment of Metastatic Breast Cancer.

Most breast cancers are hormone receptor-positive, and tamoxifen is the mainstay of endocrine therapy for such patients. However, with the introduction of aromatase inhibitors and then fulvestrant, tamoxifen became a less preferred drug, even in a premenopausal setting. Many new approaches to tackle the recently identified resistance pathways for endocrine therapy are widely used. Cyclin-dependent kinase 4/6 inhibitors such as ribociclib, palbociclib, and abemaciclib, and inhibitors of the mechanistic target of rapamycin such as everolimus, are effective but have been associated with considerably higher costs and distinctive toxicities. We describe the clinical course of a young patient with advanced-stage breast cancer living in an under-resourced region who failed to respond to chemotherapy, including both anthracyclines and taxanes, but achieved complete and durable response to tamoxifen and ovarian ablation therapy. This case demonstrates the value of well-established, low-cost endocrine therapy for breast cancer. It also highlights the need to address the sequencing of endocrine therapy for patients in low-income countries.

The Predictive Value of the Eighth Edition of the Clinical TNM Staging System for the Likelihood of Eye Salvage for Intraocular Retinoblastoma by Systemic Chemotherapy and Focal Therapy.

BACKGROUND: The American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) cTNM staging is emerging as a universal staging for all cancers, including retinoblastoma. METHODS: Here we evaluated the predictive value of the eighth edition AJCC/UICC cTNM staging in comparison with the International Intraocular Retinoblastoma Classification for eye globe salvage by primary systemic chemotherapy and focal therapy (CRD) using logistic regression model for the probability of treatment failure. RESULTS: The eye salvage rate for 565 treated eyes was 95% (n=139/147) for T1 tumors (98% for T1a and 93% for T1b), 56% (n=230/410) for T2 (81% for T2a and 53% for T2b), and 0% for T3 tumors, and was 98%, 93%, 76%, and 44% for group A, B, C, and D tumors, respectively. As estimated by odds ratios, T2 were 13.6-fold more likely to fail treatment than T1, and T1b, T2a, and T2b were 2.8-, 9.4-, and 35.1-fold more likely to fail treatment than T1a, respectively. Group B, C, and D tumors were 2.8-, 12.7-, and 50.1-fold more likely to fail treatment than group A tumors, respectively. Eye salvage rate was 62% for eyes with focal seeds (3 mm close to the tumor), and 42% for eyes with diffuse seeds (clouds more than 3 mm from tumor edge) (P<0.0001). CONCLUSION: Both, the eighth edition cTNM classification and the International Intraocular Retinoblastoma Classification systems, can effectively predict eye salvage rates for retinoblastoma by CRD. Eyes with higher cT stages are more likely to experience treatment failure. Because the cT2b group is very heterogeneous, our findings suggest further division of this group based on the severity of vitreous/subretinal seeds, this should be revised in the next edition of cTNM system.

Management and Outcomes of Unilateral Group D Tumors in Retinoblastoma.

PURPOSE: Retinoblastoma presents most commonly as advanced unilateral disease, particularly in developing countries for which primary enucleation has been the preferred method of treatment. However, with the evolution of newer treatment modalities including intravitreal chemotherapy, intra-arterial chemotherapy and newer chemotherapeutic combinations, a trend towards more conservative approaches is being observed. Our aim is to evaluate outcomes of group D eyes following conservative and non-conservative treatment options. PATIENTS AND METHODS: The ocular oncology database was used to identify eyes with unilateral retinoblastoma that fulfilled the International Intraocular Retinoblastoma Classification (IIRC) group D criteria from August 2010 to August 2018 and these were retrospectively reviewed. Overall, 39 eyes were identified. RESULTS: Nineteen (49%) eyes underwent primary enucleation and 20 (51%) received eye-conserving treatment. Eye salvage was possible in 15 (75%) eyes in the attempted salvage group. None of the patient revealed signs of metastasis. All eyes received conventional chemotherapy (carboplatin, vincristine, etoposide) and focal laser therapy. Additional treatment modalities offered included intravitreal chemotherapy, intra-arterial chemotherapy and topotecan. Three (11%) eyes in the primary enucleation group showed high-risk features on histopathology and none developed metastasis. CONCLUSION: The results of the study seem promising and conservative measures can be adopted in selected unilateral group D eyes.

Optic nerve head sarcoidosis mimicking an intraocular tumour, and occurring as the first manifestation of neuro-ocular sarcoidosis.

PURPOSE: Sarcoidosis is a chronic idiopathic granulomatous inflammatory disease that can affect many major organ systems, primarily the lungs, and hence has remarkable clinical heterogeneity. At least 50% of patients with systemic sarcoidosis develop inflammatory eye disease, and in approximately 21% of cases, it may be the first clinical manifestation. Neuro-ocular involvement occurs in <3% of all sarcoidosis cases, and rarely involves the optic nerve. We describe an unusual case of an intraocular sarcoidosis presenting as an unclear optic nerve mass. OBSERVATIONS: A 61-year-old male presented with painful gradual visual loss in the right eye. Previous history included Stage II Hodgkin lymphoma (HL) and concurrent mediastinal sarcoidosis, both in remission 5 years later. On examination, the right eye (RE) vision had no light perception, neovascular glaucoma, attenuated retinal vessels and a non-pigmented optic disc mass. The left eye was normal. The RE showed no response to oral steroids, was painful due to neovascular glaucoma and the concerns of recurrent HL with intraocular manifestations lead to RE enucleation. Macroscopic examination revealed a whitish mass at the optic disc, which histomorphologically showed a non-necrotising granulomatous inflammation consuming the optic nerve head and extending into the optic nerve resection margin. Special stains for microorganisms were negative. The uveal tract was free of inflammation. The morphological features were consistent with optic nerve sarcoidosis. A diagnosis of neuro-ocular sarcoidosis was made, and the patient was commenced on infliximab. CONCLUSION: Neuro-ocular sarcoidosis is known as the 'great imitator' because it can cause a variety of non-specific clinical signs and symptoms, mimicking many other conditions, including lymphomas. Intraocular sarcoidosis is not unusual and typically affects the uvea. Isolated optic nerve sarcoidosis is rare. The challenging aspect of intraocular sarcoidosis is the requirement of prompt treatment to reverse any eye damage and prevent permanent visual loss. Here, optic nerve sarcoidosis was very advanced, and was associated with intracerebral manifestations. IMPORTANCE: Neuro-ocular sarcoidosis is a difficult condition to diagnose and treat. Our case was complicated by the previous history of HL and concurrent mediastinal sarcoidosis which were in remission. In patients with a history of sarcoidosis with new loss of vision and neurological weaknesses oculocerebral involvement must be included in the differential diagnosis even in the absence of typical manifestations of ocular sarcoidosis as in uveal tract involvement.

Inhibition of ATM Increases the Radiosensitivity of Uveal Melanoma Cells to Photons and Protons.

Treatment of uveal melanoma (UM) is generally successful, with local primary tumour control being at 90%-95%. Localized radiotherapy in the form of plaque brachytherapy or proton beam radiotherapy is the most common treatment modality in the UK. However, the basic mechanisms of radiation response, DNA repair and tissue reactions in UM have not been well documented previously. We have investigated the comparative radiosensitivity of four UM cell lines in response to exogenous radiation sources (both X-rays and protons), and correlated this with DNA repair protein expression and repair efficiency. We observed a broad range of radiosensitivity of different UM cell lines to X-rays and protons, with increased radioresistance correlating with elevated protein expression of ataxia telangiectasia mutated (ATM), a protein kinase involved in the signaling and repair of DNA double strand breaks. The use of an ATM inhibitor in UM cell lines enhanced radiosensitivity following both X-ray and proton irradiation, particularly in cells that contained high levels of ATM protein which are otherwise comparatively radioresistant. In proton-irradiated compared with non-irradiated primary enucleated UM patient samples, there was no significant difference in ATM protein expression. Our study therefore suggests that ATM is a potential target for increasing the radiosensitivity of more resistant UM subgroups.

Clinico-pathological outcomes of post- primary and salvage chemotherapy retroperitoneal lymph node dissection for mixed germ cell tumors, King Hussein Cancer Center experience.

OBJECTIVE: We sought to characterize clinical and pathologic outcomes of advanced mixed germ cell tumors after retroperitoneal lymph node dissection for post-chemotherapy residual masses. MATERIAL AND METHODS: Between January 2006 and November 2015, 56 patients underwent retroperitoneal lymph node dissection (RPLND) for residual masses of greater than 1 cm after receiving either primary chemotherapy or salvage chemotherapy. Retrospective review of the patients' characteristics, clinical, pathological, and treatment outcomes were performed after institutional review board (IRB) and ethics committee approval. RESULTS: The mean age at diagnosis was 30 years. Ninety percent of the patients received 3-4 cycles of BEP (bleomycin/etoposide/cisplatin) as primary chemotherapy, and 29% of them salvage chemotherapy prior to lymph node dissection. The mean size of the residual masses after chemotherapy was 6 cm. The histological findings were necrosis in 30%, viable tumor in 34% and teratoma in 36% of the retroperitoneal masses. The mean time to relapse after RPLND was 11 months, out of 9 relapses, 6 were in the retroperitoneum, 1 in the lung and 1 in the kidney and 1 in the contralateral testicle. CONCLUSION: Our results indicated higher incidence of viable germ cell tumor in the retroperitoneal residual masses after primary and salvage chemotherapy when compared with previously reported global incidence rates.

Management and Outcome of Uveal Melanoma in a Single Tertiary Cancer Center in Jordan.

OBJECTIVE: The aim of this study was evaluate the features and outcome of management of uveal melanoma in King Hussein Cancer Center as an example of a referral tertiary cancer center in the Middle East. MATERIAL AND METHOD: This was aetrospective, observational case series of 46 eyes of 46 patients with uveal melanoma. Data collection required access to medical records, radiology and pathology reports, and laboratory results. The main outcome measures included age at diagnosis, tumor location and dimensions, TNM stage, treatment modality, visual outcome, metastasis, and mortality. RESULTS: There was slight female preference, and the median age at diagnosis was 45 years. Eighteen (39%) eyes were treated by primary enucleation, and 28 (61%) eyes were treated by I-125 radioactive plaque. The melanoma was in the choroid in 40 (87%) eyes and in the ciliary body in 6 (13%) eyes, with no single tumor in the iris. According to the 7th edition of the American Joint Committee on Cancer staging system (UICC/AJCC); 8 (17%) were T1, 17 (36%) were T2, 16 (35%) were T3, and 5 (11%) were T4. One (2%) patient showed lymph node metastasis (N1), and 6 (13%) patients showed distant metastasis (M1). Pathologically, 2 (10%) of the enucleated eyes were spindle cell type, 4 (20%) were epithelioid cell type, and 14 (70%) were mixed type. Extrascleral extension was seen in three (15%) eyes, and optic nerve invasion in two (10%) eyes. After brachytherapy, 26 (93%) eyes were salvaged, and 2 eyes were consecutively enucleated; one for tumor recurrence, and one for uncontrolled painful neovascular glaucoma. The eye salvage rate post plaque was 93% (26/28), and the visual acuity for the salvaged eyes was equal or better than 0.5 in 11 (42%) eyes, 0.1-0.4 in 5 (19%) eyes, and less than 0.1 in 10 (38%) eyes. CONCLUSION: The incidence of uveal melanomas in our region is low compared to that in the West with a younger age at presentation. Candidate tumors for radioactive plaque therapy were successfully controlled in 93% of cases.

Fatal case of cryptogenic organizing pneumonia associated with everolimus.

Noninfectious pneumonitis (NIP) has been reported with everolimus; however, the majority of the reported cases were mild to moderate. We report a fatal case of cryptogenic organizing pneumonia (COP) in a 61-year-old man. About 4 weeks after starting everolimus, the patient was admitted to the hospital with complaints of a 1-week history of progressive dyspnea with exertion and cough. The chest radiograph showed bilateral multifocal dense opacities, and he was started on antibiotics. However, his respiratory status deteriorated, and he was subsequently intubated and transferred to the intensive care unit. Chest computed tomography showed bronchocentric consolidation associated with widespread bilateral fine reticular opacification. Video-assisted thoracoscopic lung biopsy showed noncaseating granulomatous inflammation and features of COP. All cultures were negative for bacterial, viral, and fungal infections. Despite discontinuing everolimus and initiating corticosteroids, the patient died of progressive respiratory failure secondary to COP.