Development of crizotinib-associated renal cyst in a non-small cell lung cancer patient with ALK fusion: a case report and review of the literature.

BACKGROUND: Crizotinib, an oral first-generation tyrosine kinase inhibitor (TKI), is superior to systemic chemotherapy for the treatment of non-small cell lung cancer (NSCLC) with positive rearrangement of anaplastic lymphoma kinase (ALK). However, an increased incidence of renal and hepatic cysts has been reported in the patients on crizotinib treatment. CASE PRESENTATION: Here, we describe a case of a 71-year-old Chinese women developed multiple cystic lesions in kidney and liver during crizotinib treatment for the primary and metastatic NSCLC. The renal and hepatic cysts were noted by CT scan 3 months after crizotinib treatment, which were spontaneously and significantly regressed after stopping crizotinib. CONCLUSIONS: Based on literature review and our experience in this case report, we concluded that crizotinib-associated renal cyst (CARCs) has features of malignancy and abscess in radiographic imaging, and thus, pathological confirmation is necessary to avoid inappropriate treatment decision. In addition, to benefit the patients with progress-free survival (PFS), switching from crizotinib to alectinib is recommended for the treatment of NSCLC patients who developed CARCs.

Albendazole Monotherapy for Pediatric Cystic Echinococcosis: A Case Series.

BACKGROUND: Data regarding albendazole monotherapy for cystic echinococcosis (CE) are scarce, especially in children. We report our experience treating CE in children with albendazole monotherapy. METHODS: A retrospective case series, 2005-2021, assessing factors leading to albendazole monotherapy, demographic, clinical, duration of treatment and follow-up, and outcome (changes in cyst size and side effects) characteristics. RESULTS: Overall, we identified 18 patients with 31 cysts; liver: 68% (n = 21), lungs: 29% (n = 9), and kidney: 3% (n = 1). Mean cyst size was 4.5 ± 2.6 cm. Reasons for administrating albendazole monotherapy were small (< 4 cm) cyst size (56%), difficulty to operate (33%) and comorbidity (22%). Duration of treatment (range 1-32 months) was 1, 2-3, 4-6 and > 6 months in 28% (n = 5), 39% (n = 7), 17% (n = 3) and 17% (n = 3) of children, respectively. Duration of follow up (range 1-87 months) was 1, 2-3, 4-6 and > 6 months in 11% (n = 2), 11% (n = 2), 17% (n = 3) and 61% (n = 11) of children, respectively. Overall, 83% (n = 15) of patients experienced lack of cyst growth, and 72% (n = 13) experienced reduction in cyst size, while 44% (n = 8) experienced reduction larger than 50%. Full resolution was noted in 22% (n = 4) of patients. In three cases (17%) treatment failure was recorded: one (6%) recurrence, and two cases (11%) of cyst growth. Neutropenia was recorded in two patients (11%), and liver enzymes elevation was recorded in six patients (33%). CONCLUSIONS: Albendazole monotherapy may be an adequate treatment for selected cases of CE disease in children, especially in CE with small, hepatic cysts.

The Efficacy of Dienogest in Reducing Disease and Pain Recurrence After Endometriosis Surgery: a Systematic Review and Meta-Analysis.

The objective of this study is to determine whether dienogest therapy after endometriosis surgery reduces the risk of recurrence compared with placebo or alternative treatments (GnRH agonist, other progestins, and estro-progestins). The design used in this study is systematic review with meta-analysis. The data source includes PubMed and EMBASE searched up to March 2022. A systematic review and meta-analysis were performed in accordance with guidelines from the Cochrane Collaboration. Keywords such as "dienogest," "endometriosis surgery," "endometriosis treatment," and "endometriosis medical therapy" were used to identify relevant studies. The primary outcome was recurrence of endometriosis after surgery. The secondary outcome was pain recurrence. An additional analysis focused on comparing side effects between groups. Nine studies were eligible, including a total of 1668 patients. At primary analysis, dienogest significantly reduced the rate of cyst recurrence compared with placebo (p < 0.0001). In 191 patients, the rate of cyst recurrence comparing dienogest vs GnRHa was evaluated, but no statistically significant difference was reported. In the secondary analysis, a trend toward reduction of pain at 6 months was reported in patients treated with dienogest over placebo, with each study reporting a significantly higher reduction of pain after dienogest treatment. In terms of side effects, dienogest treatment compared with GnRHa significantly increased the rate of spotting (p = 0.0007) and weight gain (p = 0.03), but it was associated with a lower rate of hot flashes (p = 0.0006) and a trend to lower incidence of vaginal dryness. Dienogest is superior to placebo and similar to GnRHa in decreasing rate of recurrence after endometriosis surgery. A significantly higher reduction of pain after dienogest compared with placebo was reported in two separate studies, whereas a trend toward reduction of pain at 6 months was evident at meta-analysis. Dienogest treatment compared with GnRHa was associated with a lower rate of hot flashes and a trend to lower incidence of vaginal dryness.

Efficacy and safety of antiparasitic therapy for neurocysticercosis in rural Tanzania: a prospective cohort study.

PURPOSE: Neurocysticercosis is common in regions endemic for Taenia solium. Active-stage neurocysticercosis can be treated with antiparasitic medication, but so far no study on efficacy and safety has been conducted in Africa. METHODS: We conducted a prospective cohort study on treatment of neurocysticercosis in Tanzania between August 2018 and January 2022. Patients were initially treated with albendazole (15 mg/kg/d) for 10 days and followed up for 6 months. Additionally in July 2021, all participants who then still had cysts were offered a combination therapy consisting of albendazole (15 mg/kg/d) and praziquantel (50 mg/kg/d). Antiparasitic treatment was accompanied by corticosteroid medication and anti-seizure medication if the patient had experienced epileptic seizures before treatment. RESULTS: Sixty-three patients were recruited for this study, of whom 17 had a complete follow-up after albendazole monotherapy. These patients had a total of 138 cysts at baseline, of which 58 (42%) had disappeared or calcified by the end of follow-up. The median cyst reduction was 40% (interquartile range 11-63%). Frequency of epileptic seizures reduced considerably (p < 0.001). Three patients had all active cysts resolved or calcified and of the remaining 14, eight received the combination therapy which resolved 63 of 66 cysts (95%). Adverse events were infrequent and mild to moderate during both treatment cycles. CONCLUSION: Cyst resolution was unsatisfactory with albendazole monotherapy but was very high when it was followed by a combination of albendazole and praziquantel.

Postoperative Lumbar Fusion Bone Morphogenic Protein-Related Epidural Cyst Formation.

Bone morphogenetic protein is broadly used in spinal surgery to enhance fusion rates. Several complications have been associated with the use of bone morphogenetic protein, including postoperative radiculitis and pronounced bone resorption/osteolysis. Bone morphogenetic protein-related epidural cyst formation may represent another complication that has not been described aside from limited case reports. In this case series, we retrospectively reviewed imaging and clinical findings of 16 patients with epidural cysts on postoperative MR imaging following lumbar fusion. In 8 patients, mass effect on the thecal sac or lumbar nerve roots was noted. Of these, 6 patients developed new postoperative lumbosacral radiculopathy. During the study period, most patients were managed conservatively, and 1 patient required revision surgery with cyst resection. Concurrent imaging findings included reactive endplate edema and vertebral bone resorption/osteolysis. Epidural cysts had characteristic findings on MR imaging in this case series and may represent an important postoperative complication in patients following bone morphogenetic protein-augmented lumbar fusion.

Efficacy and safety of praziquantel in the treatment of neurocysticercosis in Vietnam.

Neurocysticercosis (NCC) is a parasitic infection of the nervous system and is responsible for considerable morbidity and mortality. Praziquantel (PZQ) is one of the antiparasitics mostly used in managing NCC, however, there have been only a few studies on the treatment outcome of this drug. The present study aimed to evaluate the efficacy and safety of PZQ in patients with NCC. Sixty patients with typical characteristics of NCC received three 10-day cycles of PZQ and the interruption between these cycles was 10 days. Additional treatment included antiinflammation (steroids), antiepileptics and analgesics. Clinical and imaging studies were done at baseline and six months after therapy to assess the efficacy of treatment. Laboratory evaluation was done before and after each cycle to investigate laboratory safety profiles. By six months after finishing therapy, all patients had clinical improvement and 75% of them were free of symptoms. The rates of complete, partial or no resolution of cysts on brain magnetic resonance imaging were 61.7%, 28.3% and 10% respectively. The efficacy of therapy was not associated with the number of cysts. There was no difference between the levels of aspartate aminotransferase, alanine aminotransferase, urea and creatinine before and after treatment. Conclusion: Praziquantel is effective and safe in the treatment of patients with neurocysticercosis.

Deletion of kif3a in CK19 positive cells leads to primary cilia loss, biliary cell proliferation and cystic liver lesions in TAA-treated mice.

BACKGROUND & AIMS: Loss of primary cilia in epithelial cells is known to cause cystic diseases of the liver and kidney. We have previously shown that during experimental and human cirrhosis that primary cilia were predominantly expressed on biliary cells in the ductular reaction. However, the role of primary cilia in the pathogenesis of the ductular reaction is not fully understood. METHODS: Primary cilia were specifically removed in biliary epithelial cells (BECs) by the administration of tamoxifen to Kif3af/f;CK19CreERT mice at week 2 of a 20-week course of TAA treatment. Biliary progenitor cells were isolated and grown as organoids from gallbladders. Cells and tissue were analysed using histology, immunohistochemistry and Western blot assays. RESULTS: At the end of 20 weeks TAA administration, primary cilia loss in liver BECs resulted in multiple microscopic cystic lesions within an unaltered ductular reaction. These were not seen in control mice who did not receive TAA. There was no effect of biliary primary cilia loss on the development of cirrhosis. Increased cellular proliferation was seen within the cystic structures associated with a decrease in hepatocyte lobular proliferation. Loss of primary cilia within biliary organoids was initially associated with reduced cell passage survival but this inhibitory effect was diminished in later passages. ERK but not WNT signalling was enhanced in primary cilia loss-induced cystic lesions in vivo and its inhibition reduced the expansion of primary cilia deficient biliary progenitor cells in vitro. CONCLUSIONS: TAA-treated kif3a BEC-specific knockout mice had an unaltered progression to cirrhosis, but developed cystic lesions that showed increased proliferation.

Discriminating surgical bed cysts from bacterial brain abscesses after Carmustine wafer implantation in newly diagnosed IDH-wildtype glioblastomas.

Carmustine wafers can be implanted in the surgical bed of high-grade gliomas, which can induce surgical bed cyst formation, leading to clinically relevant mass effect. An observational retrospective monocentric study was conducted including 122 consecutive adult patients with a newly diagnosed supratentorial glioblastoma who underwent a surgical resection with Carmustine wafer implantation as first line treatment (2005-2018). Twenty-two patients (18.0%) developed a postoperative contrast-enhancing cyst within the surgical bed: 16 surgical bed cysts and six bacterial abscesses. All patients with a surgical bed cyst were managed conservatively, all resolved on imaging follow-up, and no patient stopped the radiochemotherapy. Independent risk factors of formation of a postoperative surgical bed cyst were age ≥ 60 years (p = 0.019), number of Carmustine wafers implanted ≥ 8 (p = 0.040), and partial resection (p = 0.025). Compared to surgical bed cysts, the occurrence of a postoperative bacterial abscess requiring surgical management was associated more frequently with a shorter time to diagnosis from surgery (p = 0.009), new neurological deficit (p < 0.001), fever (p < 0.001), residual air in the cyst (p = 0.018), a cyst diameter greater than that of the initial tumor (p = 0.027), and increased mass effect and brain edema compared to early postoperative MRI (p = 0.024). Contrast enhancement (p = 0.473) and diffusion signal abnormalities (p = 0.471) did not differ between postoperative bacterial abscesses and surgical bed cysts. Clinical and imaging findings help discriminate between surgical bed cysts and bacterial abscesses following Carmustine wafer implantation. Surgical bed cysts can be managed conservatively. Individual risk factors will help tailor their steroid therapy and imaging follow-up.

Spinal Syrinx Due to Lipiodol-Induced Arachnoiditis.

We present a case of a progressive symptomatic intramedullary cyst, diagnosed decades after Lipiodol injection. Lipiodol was originally administered intrathecally for the radiologic diagnosis of spinal masses. A link between the lesion and the history of Lipiodol injection was never suspected. Surgical exploration revealed a membrane above the lesion, separating the intradural space in a cranial and caudal compartment. On the level of the cyst, we identified glassy pearls containing a fatty liquid, compatible with Lipiodol deposits. We hypothesize that the syrinx is secondary to the impact of cerebrospinal fluid pulsations on the reactive membrane and that this membrane originated from an arachnoiditis caused by Lipiodol deposits. Lipiodol was indeed abandoned after it was found to cause arachnoiditis and neurologic sequelae. Despite the cessation of its usage, the causal role of Lipiodol in arachnoiditis and spinal cyst formation should still be considered, as symptoms may arise many years after Lipiodol administration.

LINEZOLID-INDUCED MITOCHONDRIAL TOXICITY PRESENTING AS RETINAL NERVE FIBER LAYER MICROCYSTS AND OPTIC AND PERIPHERAL NEUROPATHY IN A PATIENT WITH CHRONIC GRANULOMATOUS DISEASE.

PURPOSE: To report a case with unique changes in the retinal nerve fiber layer observed on optical coherence tomography in a 22-year-old patient on chronic linezolid therapy for recurrent pyogenic liver abscesses with underlying chronic granulomatous disease. METHODS: History and clinical examination, laboratory evaluation, fluorescein angiography, and optical coherence tomography. RESULTS: The patient presented with best-corrected visual acuity of 20/200 in the right eye and 20/125 in the left eye. He had moderate optic disk edema and superotemporal field defects bilaterally. Swept-source optical coherence tomography revealed the presence of retinal nerve fiber layer microcystic spaces. Laboratory tests showed no positive findings except for an elevated lactic acid level. Linezolid-induced optic neuropathy was suspected, and the drug was discontinued. Six weeks after termination of oral linezolid therapy, the optic disk edema and the microcystic spaces in the retinal nerve fiber layer resolved, and the best-corrected visual acuity improved to 20/50 in the right and 20/40 in the left eye, respectively. CONCLUSION: Linezolid is a widely used antibiotic with broad-spectrum action. However, chronic use can lead to mitochondrial toxicity that may have protean manifestations. Ocular examination, particularly of the optic nerve and nerve fiber layer using multimodal imaging, is critical in diagnosing such toxicity.

[Development of a large intraprostatic cyst following the use of a GnRH agonist-implant in a male dog with benign prostatic hyperplasia]. / Entwicklung einer großen intraprostatischen Zyste nach Einsatz eines GnRH-Agonist-Implantats bei einem Rüden mit benigner Prostatahyperplasie.

A male dog with benign prostatic hyperplasia and several small intraprostatic cysts was treated with a GnRH-agonist implant containing 4,7 mg deslorelin (Suprelorin®). Within 2 weeks after the implantation, the prior urethral bleeding worsened. A large intraprostatic cyst was detected sonographically. The patient was subsequently treated with osaterone acetate (0.4 mg/kg p. o. once a day for 7 days) and enrofloxacin (5 mg/kg p. o. once a day for 21 days). The clinical symptoms receded within 10 days. Within one month, the cyst regressed completely. The mechanisms of cyst enlargement are discussed.

Polycystic Liver Disease in a Patient With Metastatic Renal Cell Carcinoma: A Case Report.

We report a case of rapid evolution of polycystic liver disease in a 76-year-old patient with metastatic renal cell carcinoma who underwent treatment with numerous antineoplastic agents. The aim was to identify a causative etiology for these hepatic cysts of unclear origin. The cystic lesions of the patient were ultimately innumerable and developed rapidly, more than tripling the total liver volume from complete absence over the course of 24 months. The hepatic lesions continued to grow despite an otherwise moderate tumor response. Prior to patient death, the patient remained relatively asymptomatic from the cyst burden and was without signs of grossly metastatic disease. This rapid development of polycystic liver disease most likely represents a previously unseen medication side-effect of cabozantinib or pazopanib. It is important to identify adverse effects of novel antineoplastic agents in this time of oncological medical discovery.

Multiple cystic lung lesions and autoimmune thrombocytopaenia developing after chemotherapy for pulmonary indolent B-cell lymphoma with plasmacytic differentiation.

Among lung malignancies, primary pulmonary lymphoma is rare and many of them are indolent B-cell lymphomas. We describe a case of primary pulmonary indolent B-cell lymphoma with plasmacytic differentiation, which exacerbated with the manifestation of macroglobulinaemia and was successfully treated using chemotherapy. The patient subsequently developed pulmonary cysts and thrombocytopaenia due to autoimmune pathology and was successfully treated using prednisolone. This case suggests that in indolent B-cell lymphoma with plasmacytic differentiation, immunoglobulin M level should be carefully followed even if it is within the normal range at lymphoma onset. Additionally, new cystic pulmonary infiltrates that develop during the post-treatment follow-up of an indolent pulmonary B-cell lymphoma may indicate pulmonary lymphoma recurrence, but there is also a possibility of an immunological complication.

The influence of carmustine wafer implantation on tumor bed cysts and peritumoral brain edema.

The development of perifocal edema and tumor bed cyst has been reported after implantation of biodegradable carmustine wafers for the treatment of malignant gliomas. We retrospectively evaluated these changes in a series of patients; 19 consecutive patients with malignant glioma who received carmustine wafer implantation at our hospital from January 2013 through July 2013, and 28 patients who underwent surgery prior to our institution's initiation of carmustine wafer implantation, as historical controls. The volume of the tumor bed cyst and perifocal edema was calculated on MRI acquired at four time points: ⩽72hours after surgery for baseline, and at 1-4, 5-8, and 9-12weeks after surgery. The volume of the tumor bed cyst in the wafer group increased significantly relative to the control group at all time points (p=0.04). Opening of the ventricle was inversely correlated with enlargement of the tumor bed cyst in the wafer group (p=0.04). The change in the volume of perifocal edema in the wafer group was not significantly different (p=0.48), but exhibited a considerable increase in patients with anaplastic oligodendroglioma relative to glioblastoma patients in the wafer group (p=0.01). We demonstrated significant enlargement of the tumor bed cyst volume after carmustine wafer implantation, as well as the development of marked perifocal edema in patients with anaplastic oligodendroglioma.

The renal effects of ALK inhibitors.

Anaplastic lymphoma kinase 1 (ALK-1) is a member of the insulin receptor tyrosine kinase family. In clinical practice, three small molecule inhibitors of ALK-1 are used, namely crizotinib, ceritinib and alectinib. Several more agents are in active pre-clinical and clinical studies. Crizotinib is approved for the treatment of advanced ALK-positive non-small cell lung cancer (NSCLC). According to the package insert and published literature, treatment with crizotinib appears to be associated with kidney failure as well as an increased risk for the development and progression of renal cysts. In addition, this agent is associated with development of peripheral edema and rare electrolyte disorders. This review focuses on the adverse renal effects of Crizotinib in clinical practice.