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.

Swallowing dysfunction in infants less than 1 year of age.

BACKGROUND: Gastroesophageal reflux (GER) occurs frequently in infants and children and is implicated as a trigger for reactive airways disease. While evaluating patients for GER by upper gastrointestinal studies (UGI), we frequently noticed laryngeal penetration or tracheal aspiration in infants < 1 year of age. We conducted this prospective study to assess the incidence of swallowing dysfunction in infants with vomiting or respiratory symptoms. METHODS: Between February 1994 and August 1997, 1,003 UGI in infants < 1 year of age were performed by two experienced pediatric radiologists. Fluoroscopy of swallowing using an appropriate image intensifier was observed as part of the UGI in all patients. In addition to evaluating premature infants, former premature infants, and infants with underlying conditions such as bronchopulmonary dysplasia (BPD), congenital heart disease (CHD), esophageal atresia and/or tracheoesophageal fistula (EA), and neurologic disorders, we assessed swallowing in 472 full-term infants in the general population who had respiratory symptoms or suspected GER, but no other apparent abnormalities. Swallowing was not assessed in patients with congenital bowel obstruction. The presence of normal swallowing or swallowing dysfunction was recorded immediately following the study. Chest radiographs obtained on the same day as the UGI were evaluated in the study. Forty-four videotaped modified barium-swallow studies (MBSS) were obtained in 25 general-population infants and reviewed frame-by-frame to determine the length of time that barium could be visualized in the subglottic trachea. RESULTS: The incidence of swallowing dysfunction is significant in premature and former premature infants, those with BPD, CHD, EA, various syndromes, and neurologic abnormality. In the general population of full-term infants referred for evaluation of vomiting or respiratory symptoms, 63 (13.4 % of 472) had swallowing dysfunction. Forty-four had tracheal aspiration (TA) and 19 had laryngeal penetration (LP). Gastroesophageal reflux was found in 79.5 % with TA and in 68.4 % with LP. The MBSS confirmed swallowing dysfunction in all patients shown to have vocal cord penetration or tracheal aspiration by UGI. CONCLUSIONS: Careful evaluation of swallowing during an UGI can identify swallowing dysfunction in full-term infants who have respiratory problems, as well as in infants with an abnormality that predisposes the patient to aspiration. Episodes of tracheal aspiration may be fleeting and overlooked if swallowing is not assessed carefully. An MBSS can confirm the observation of swallowing dysfunction found during an UGI and assist in planning appropriate dietary therapy that minimizes the likelihood of tracheal aspiration during feeding.

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.

Fluoroscopy-guided retrieval of a sheared endotracheal stylet sheath from the tracheobronchial tree in a premature infant.

Endotracheal intubation of premature infants with respiratory distress is a commonly performed procedure in the neonatal intensive care unit. We report a rare complication of this procedure, shearing of the plastic sheath that is bonded to and surrounds the stylet used to assist intubation and lodging of the sheared stylet in the tracheobronchial tree of a small premature infant. We suggest a method for removing the plastic foreign body using fluoroscopy and an Amplatz gooseneck snare directed through the existing endotracheal tube, a technique not previously reported.

Orbital myositis due to Kawasaki's disease.

Kawasaki's disease is an inflammatory syndrome of young children that affects multiple organ systems. The most common ophthalmologic manifestations of Kawasaki's disease are bilateral conjunctival injection and nongranulomatous iridocyclitis. To our knowledge, this patient is the first with Kawasaki's disease to demonstrate extraocular muscle palsy and orbital myositis.

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.

Neonatal pharyngeal pseudodiverticulum mimicking esophageal atresia.

Pseudodiverticulum of the hypopharynx is an infrequent but potentially serious complication of orogastric or nasogastric tube insertion and endotracheal intubation. We report two cases of injury to the hypopharynx resulting in a pseudodiverticulum of the hypopharynx that was initially diagnosed as esophageal atresia. Both cases were managed successfully by conservative therapy. We also review the literature regarding neonatal pharyngeal pseudodiverticulum.

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.

Primary chylous vaginal discharge in a 9-year-old girl: CT-lymphangiogram and MR appearance.

Chylous reflux is a manifestation of primary or secondary lymphatic obstruction. Primary lymphatic obstruction is defined as lymphangiectasia and incompetency of lymphatic valves without an underlying cause. Lymphangiectasia resulting from trauma, neoplasm, irradiation, or inflammation characterizes secondary lymphatic obstruction. Leakage of chyle into the uterus, vagina, bladder, or rectum can occur with either primary or secondary lymphatic obstruction. We report a patient with chylous vaginal discharge, a rare presentation of primary chylous reflux syndrome. CT-lymphangiography and magnetic resonance imaging clearly depicted this disorder. To our knowledge, only 20 cases of chylous vaginal discharge have been reported previously; chylous vaginal drainage occurred in the absence of chylous uterine reflux in only three. Although this is a rare anomaly, chylous reflux should be considered in a child with chronic vaginal discharge and lower extremity swelling.

Hemangioma of the temporal bone in a patient presumed to have Ménière's syndrome.

This case report describes a patient with a facial nerve hemangioma of 8 years' duration that initially caused most of the symptoms of Ménière's syndrome: fullness, sensorineural hearing loss, dizziness, tinnitus, and disruption of balance. The hearing loss was in the high-frequency range (> or = 3,000 Hz); typically, the initial hearing loss in Ménière's syndrome is in the low-frequency range. Mild facial nerve weakness and punctate keratitis due to corneal exposure appeared 8 years later. Contrast-enhanced magnetic resonance imaging and high-resolution computed tomography depicted the lesion and made preoperative diagnosis possible. With meticulous surgical removal of the tumor, which was intertwined with the facial nerve, facial nerve function was preserved.

Unilateral pulmonary agenesis without mediastinal displacement.

A radiographic hallmark in pulmonary agenesis is opacification of the ipsilateral hemithorax with displacement of the mediastinum in the direction of the agenetic lung. We believe this case report is the first in which the mediastinum was not displaced; instead, the liver and intact hemidiaphragm were displaced cephalad, preventing cardiac malposition. Contrast-enhanced computed tomography enabled us to diagnose this anomaly precisely.

Combined sequestration, bronchogenic cyst, and dysgenetic lung simulating congenital lobar emphysema.

We report the case of a newborn with bronchopulmonary sequestration, bronchogenic cyst, and dysgenetic lung that radiographically simulated congenital lobar emphysema. We discuss congenital malformations of the lungs and the concept of a continuum in the development of pulmonary anomalies.

Tracheobronchial foreign body aspiration in children.

In this retrospective study, we reviewed the demographic and radiographic findings of 155 children with bronchoscopy-proven tracheobronchial foreign body aspiration (FBA). Two thirds of the patients were male, and most were children between 1 and 2 years of age. An aspirated peanut accounted for one third of all cases. Foreign body location was distributed nearly evenly to the right and left primary bronchi; tracheal foreign body was noted in 16 patients. The most frequent symptoms of FBA were cough (85 patients) and wheezing (60 patients). Although most patients were seen within 1 day of aspiration, 30 patients had symptoms that lasted at least 1 week before diagnosis. The most common radiographic findings were unilateral or segmental hyperlucency (59) or atelectasis (38). The trachea was the site of the foreign body in one half of children with a normal chest radiograph and FBA.

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.

Transverse colon volvulus in pediatric patients.

Volvulus of the transverse colon is rare in the pediatric population. We present the tenth known case of a volvulus of the transverse colon in a child. A barium enema demonstrated the bird beak appearance of the colon and showed an air-contrast mirror image in the proximal end. The 360 degrees volvulus found at surgery was treated successfully by detorsion of the bowel.

Nephrocalcinosis in a child with autosomal dominant polycystic kidney disease and a prolapsing ectopic ureterocele.

Although autosomal dominant polycystic kidney disease commonly presents in adults, it can occur in children. Usually, renal calcification in patients with autosomal dominant polycystic kidney disease is manifested as calculi or as hemorrhage into a renal cyst. An ectopic ureterocele is a well-known finding in patients with renal duplication. To our knowledge, this is the first case report of a child who had combined findings of autosomal dominant polycystic kidney disease, nephrocalcinosis, and an obstructing ectopic ureterocele.

Cervical thymic cysts: CT appearance of two cases including a persistent thymopharyngeal duct cyst.

The differential diagnosis of cervical cysts in children includes common entities such as branchial cleft cysts, thyroglossal duct cysts, and cystic hygromas. Congenital thymic cysts are uncommon and often misdiagnosed as either branchial cleft cysts or cystic hygromas. However, they may have an appearance on CT that can be characteristic. The course of the descent of embryologic thymic tissue in the neck to the mediastinum indicates the potential site of deposition of an ectopic cervical thymic cyst. In a child, a cystic lesion that has an intimate relationship to the carotid sheath is likely to be a thymic cyst. Of the approximately 100 cases of vestigial cervical thymus or thymic cysts that have been reported in children, only 5 cases of a persistent thymopharyngeal duct cyst have been described [1-5]. In two of these five, the persistent thymopharyngeal duct cyst was demonstrated by CT [1,2]. We report one additional case of a cervical thymic cyst and one case of a persistent thymopharyngeal duct cyst both depicted by CT.