Efficacy of immune checkpoint inhibitors for the treatment of advanced melanoma in patients with concomitant chronic lymphocytic leukemia.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized the management of advanced melanoma (AM). However, data on ICI effectiveness have largely been restricted to clinical trials, thereby excluding patients with co-existing malignancies. Chronic lymphocytic leukemia (CLL) is the most prevalent adult leukemia and is associated with increased risk of melanoma. CLL alters systemic immunity and can induce T-cell exhaustion, which may limit the efficacy of ICIs in patients with CLL. We, therefore, sought to examine the efficacy of ICI in patients with these co-occurring diagnoses. PATIENTS AND METHODS: In this international multicenter study, a retrospective review of clinical databases identified patients with concomitant diagnoses of CLL and AM treated with ICI (US-MD Anderson Cancer Center, N = 24; US-Mayo Clinic, N = 15; AUS, N = 19). Objective response rates (ORRs), assessed by RECIST v1.1, and survival outcomes [overall survival (OS) and progression-free survival (PFS)] among patients with CLL and AM were assessed. Clinical factors associated with improved ORR and survival were explored. Additionally, ORR and survival outcomes were compared between the Australian CLL/AM cohort and a control cohort of 148 Australian patients with AM alone. RESULTS: Between 1997 and 2020, 58 patients with concomitant CLL and AM were treated with ICI. ORRs were comparable between AUS-CLL/AM and AM control cohorts (53% versus 48%, P = 0.81). PFS and OS from ICI initiation were also comparable between cohorts. Among CLL/AM patients, a majority were untreated for their CLL (64%) at the time of ICI. Patients with prior history of chemoimmunotherapy treatment for CLL (19%) had significantly reduced ORRs, PFS, and OS. CONCLUSIONS: Our case series of patients with concomitant CLL and melanoma demonstrate frequent, durable clinical responses to ICI. However, those with prior chemoimmunotherapy treatment for CLL had significantly worse outcomes. We found that CLL disease course is largely unchanged by treatment with ICI.

Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients.

Preclinical mouse models suggest that the gut microbiome modulates tumor response to checkpoint blockade immunotherapy; however, this has not been well-characterized in human cancer patients. Here we examined the oral and gut microbiome of melanoma patients undergoing anti-programmed cell death 1 protein (PD-1) immunotherapy (n = 112). Significant differences were observed in the diversity and composition of the patient gut microbiome of responders versus nonresponders. Analysis of patient fecal microbiome samples (n = 43, 30 responders, 13 nonresponders) showed significantly higher alpha diversity (P < 0.01) and relative abundance of bacteria of the Ruminococcaceae family (P < 0.01) in responding patients. Metagenomic studies revealed functional differences in gut bacteria in responders, including enrichment of anabolic pathways. Immune profiling suggested enhanced systemic and antitumor immunity in responding patients with a favorable gut microbiome as well as in germ-free mice receiving fecal transplants from responding patients. Together, these data have important implications for the treatment of melanoma patients with immune checkpoint inhibitors.

Paraganglioma of urinary bladder in patient with neurofibromatosis.

Pheochromocytoma in patients with von Recklinghausen's neurofibromatosis is a well-known association. However, extra-adrenal pheochromocytoma with this association is rare. Herein we report a case of urinary bladder paraganglioma in a patient with neurofibromatosis.

Hamartoma of the tuber cinereum: a comparison of MR and CT findings in four cases.

Hamartoma of the tuber cinereum is a well-recognized cause of central precocious puberty. We report three patients with an isodense, nonenhancing mass within the interpeduncular cistern identified by CT. In a fourth patient, the CT scan was normal. MR imaging was obtained in all cases and demonstrated a sessile or pedunculated mass of the posterior hypothalamus arising from the region of the tuber cinereum. The smallest mass was 2 mm in diameter and was found in the patient in whom the CT scan was normal. The signal intensity of the masses was generally homogeneous and isointense relative to gray matter on T1- and intermediate-weighted images, and hyper-intense on T2-weighted images. MR imaging accurately diagnoses hypothalamic hamartomas, identifies small hamartomas of the tuber cinereum more sensitively than CT does, and provides optimal imaging for serial evaluation while the patient is being treated medically.

Interstitial pulmonary edema in children and adolescents with diabetic ketoacidosis.

The acute complications of diabetic ketoacidosis in children and adolescents are well recognized but not completely understood. Clinical studies have focused primarily on brain edema. We have investigated the prevalence and course of interstitial pulmonary edema in patients with severe diabetic ketoacidosis all of whom had uneventful clinical courses. High resolution computed tomography scans of the lungs were analyzed by determining the Hounsfield attenuation level and then converting to physical density values. All seven patients had evidence of interstitial pulmonary edema on the first scan, which was performed within 1 h of hydration and prior to receiving insulin; six of the seven patients had increased pulmonary density 6-8 h into treatment, and all had complete resolution of the interstitial changes at discharge. Our study suggests that subclinical interstitial pulmonary edema may be a frequent occurrence in children and adolescents with severe diabetic ketoacidosis and may very well be present prior to treatment. The study also supports the philosophy of cautious rehydration and the close monitoring of children and adolescents with diabetic ketoacidosis until a more complete understanding of this pathophysiologic event is achieved.

Perinatal pathology casebook.

Citrullinemia, a rare inborn error of metabolism, is characterized by a deficiency of argininosuccinic acid synthetase that results in large increases in plasma ammonia, citrulline, and glutamine, with normal acid-base balance. The neurologic symptoms vary from poor feeding, vomiting, and irritability to hypotonia, apnea, and death. The most common pathologic findings at autopsy are cerebral edema and focal neuronal necrosis. We describe a case of fulminant citrullinemia in an infant in whom the major pathologic findings included diffuse cerebral edema and a lack of overt metabolic derangement characteristic of neonates with a urea cycle defect. Our case differs from the classic presentation of citrullinemia in that subarachnoid hemorrhage was identified early in the clinical course. We report the first observation of subarachnoid hemorrhage in an infant with a urea cycle defect.

Thoracic empyema in a patient with acute appendicitis: a rare association.

Thoracic empyema and appendicitis rarely are concomitant. This is the first report of ultrasonography and computed tomography being used preoperatively to establish the diagnosis of ruptured appendicitis in a child with thoracic empyema. The perforated appendicitis was identified after gastrointestinal flora were cultured from the thoracostomy drainage of the empyema.

Preduodenal portal vein: surgery and radiographic appearance.

Preduodenal portal vein is rare, with 63 cases reported in the literature. In general, this anomaly occurs in children with associated small bowel obstruction. We report a newborn infant who presented with duodenal stenosis, mongolism, and preduodenal portal vein. Treatment consisted of a duodenoduodenal anastomosis without mobilizing the portal vein. The correlation between imaging techniques and the operative findings is discussed. Because identification of preduodenal portal vein at surgery is important, preoperative sonography may be useful in selected cases to define the position of the vein.

Neurenteric cyst: surgery and diagnostic imaging.

Neurenteric cysts are rare, with fewer than 30 cases noted in the literature. We report the case of a newborn infant with respiratory distress caused by a large neurenteric cyst that was identified by prenatal ultrasound. Treatment consisted of excision of the mass through a right posterolateral thoracotomy. The cyst adhered to the spine at the level of the first thoracic vertebra and communicated with the jejunum through a posterior diaphragmatic defect. Postoperative studies with magnetic resonance imaging (MRI) and computed tomography (CT) disclosed an anterior meningocele and tethering of the spinal column. This is the second reported case of a neurenteric cyst demonstrated by prenatal ultrasound. The presence of an intrathoracic cyst associated with spinal abnormalities is characteristic of this anomaly. With imaging techniques such as MRI and CT, we may detect residual intraspinal disease associated with neurenteric cysts.

Organoaxial gastric volvulus detected by Meckel scan.

A case of chronic gastric organoaxial volvulus, gastroesophageal reflux, esophagitis, and chronic anemia is presented. Reflux esophagitis and chronic anemia have not been reported previously as clinical signs associated with gastric volvulus in a child. A Meckel's scan is used to diagnose the displaced stomach.

Repeated systemic mercury embolization.

Mercury embolization is an uncommon phenomenon that is easily diagnosed roentgenographically. We have reported a case of repeated self-administration of metallic mercury into the subcutaneous tissues. An intravenous component of the injection occurred, with systemic embolization to the lungs, CNS, pericardium, and diaphragm. These findings were demonstrated by plain films and CT, and were followed over a period of 15 months.

Stress fracture of the great toe sesamoid in a ballerina: MRI appearance.

This case is the first to depict a stress fracture of the great toe sesamoid bone using magnetic resonance imaging. We used a 3" surface coil to produce high resolution images of the sesamoid.

Cerebro-costo-mandibular syndrome with stippled epiphysis and cystic fibrosis.

We present a patient with cerebro-costo-mandibular syndrome who also had cystic fibrosis, hydrocephalus, and multiple ossification centers of the calcaneus.

Sonography of the circumrenal and horseshoe adrenal gland in the newborn.

The adrenal gland can be visualized using ultrasonography in at least 90% of fetuses of more than 26 weeks gestation. The fetal and neonatal adrenal gland is described as a structure having a characteristic V or Y shape. Despite the frequency of visualization of the neonatal adrenal gland, few reports of adrenal anomalies are present in the radiologic literature. The purpose of this paper is to describe and depict the sonographic appearance of the "horseshoe" and the "circumrenal" adrenal gland and to discuss adrenal anomalies in general.

Malrotation in twins: a rare occurrence.

Although malrotation is commonly found in infants with intestinal obstruction, the presence of malrotation in twins is rare. We report a set of twins who each had malrotation and non-bilious vomiting on the first day of life.

Pneumatosis intestinalis in a child with AIDS and pseudomembranous colitis.

Pneumatosis intestinalis (PI) was first reported in three children and one adult with acquired immune deficiency syndrome (AIDS) in 1990. The microorganisms cultured from these patients included Cryptosporidium, rotavirus, cytomegalovirus, and Pseudomonas. We report the fourth child with AIDS and PI, and the first with PI to be associated with Clostridium difficile colitis.

Pancreatic pseudotumor in an 11-year-old child: imaging findings.

BACKGROUND: An inflammatory pseudotumor is a benign, solid lesion of unclear etiology. Some authors believe it is a true neoplasm, while others consider it a post-infectious or post-traumatic process. It is most commonly found in the lung; an inflammatory pseudotumor of the pancreas is rare. This case report is the sixth of a pancreatic pseudotumor in a child. PATIENTS AND METHODS: An 11-year-old girl presented with obstructive jaundice due to a mass in the head of the pancreas. The mass was identified by sonography. This was confirmed by MRI and CT. The mass enhanced with gadolinium, but its enhancement at CT was similar to the remainder of the pancreas. RESULTS: At operation, a pancreatic inflammatory pseudotumor was totally resected.

Hepatic adenomatosis: rapid sequence MR imaging following gadolinium enhancement: a case report.

Hepatic adenomas are primary liver tumors usually associated with underlying metabolic disease or with anabolic steroid or oral contraceptive use. Hepatic adenomatosis (HA) is defined as the presence of more than four adenomas. Only 13 cases of HA have been reported in patients without glycogen storage disease or steroid use. We report a case of HA imaged by postcontrast T1-weighted images obtained during a breath-holding series. The lesions were most conspicuous 3-4 min after contrast administration; 4 of the 5 tumors were not identified on T2-weighted images. Unlike previous reports of HA in which the lesions remained hyperintense during sequential postcontrast imaging, the smaller lesions in this case demonstrated contrast washout, thereby distinguishing them from hemangiomata.