Clinical Characteristics,Treatments, and Concurrent Mutations in Non–Small Cell Lung Cancer Patients With NF1 Mutations

ObjectivesMetastatic non–small cell lung cancer (mNSCLC) is characterized by complex genomic alterations. NF1 mutations may confer distinct clinical characteristics within NSCLC, and real-world evidence on concurrent mutations, treatment patterns, and health outcomes is lacking.Materials and MethodsThis retrospective study was performed in patients with mNSCLC treated in the Flatiron Health network who underwent the FoundationOne tumor-sequencing. Anticancer therapies, concurrent mutations, real-world progression-free survival (rwPFS), and overall survival (OS) were assessed.ResultsOf the 1663 patients, 103 patients were identified with NF1 mutation. Concurrent mutations with Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (16.5%) and epidermal growth factor receptor fusion (6.8%) were the most frequent. In patients with NF1 mutation only (n = 57), 42% were women, 86% patients had smoking history, and 70% had non-squamous cell carcinoma type. Most (51%) of the patients with NF1 mutations received a single line of therapy versus other mutations and the overall treated population (44%). Platinum-based chemotherapy was the predominant first-line therapy, with programmed cell death-1/programmed cell death-ligand-1 inhibitors as subsequent lines of therapy. The NF1 mutation only group had numerically the shortest median rwPFS (82 days) than other mutation groups. Median OS for the NF1 mutation group in first, second, and third lines of therapy was 321, 498, and 210 days, respectively.ConclusionsNF1 mutations confer distinct clinical characteristics in patients with mNSCLC. These patients may have different trajectories for progression and survival than seen for other mutations, experience less systemic therapy after first-line therapy, and may have shorter survival.     

Ceftibuten resistance and treatment failure of Neisseria gonorrhoeae infection

Neisseria gonorrhoeae infections have been empirically treated in Hong Kong with a single oral 400-mg dose of ceftibuten since 1997. Following anecdotal reports of the treatment failure of gonorrhea with oral extended-spectrum cephalosporins, the current study was undertaken to determine the antimicrobial susceptibility pattern and molecular characteristics of isolates of N. gonorrhoeae among patients with putative treatment failure in a sexually transmitted disease clinic setting. Between October 2006 and August 2007, 44 isolates of N. gonorrhoeae were studied from patients identified clinically to have treatment failure with empirical ceftibuten. The ceftibuten MICs for three strains were found to have been 8 mg/liter. These strains were determined by N. gonorrhoeae multiantigen sequence typing to belong to sequence type 835 (ST835) or the closely related ST2469. The testing of an additional eight archived ST835 strains revealed similarly elevated ceftibuten MICs. The penA gene sequences of these 11 isolates all had the mosaic pattern previously described as pattern X. Of note is that the ceftriaxone susceptibility results of these strains all fell within the susceptible range. It is concluded that ceftibuten resistance may contribute to the empirical treatment failure of gonorrhea caused by strains harboring the mosaic penA gene, which confers reduced susceptibility to oral extended-spectrum cephalosporins. Screening for such resistance in the routine clinical laboratory may be undertaken by the disk diffusion test. The continued monitoring of antimicrobial resistance and molecular characteristics of N. gonorrhoeae isolates is important to ensure that control and prevention strategies remain effective.     

Solitary metastasis from renal cell carcinoma presenting as diffuse pancreatic enlargement

Late metastasis of renal cell carcinoma (RCC) to the pancreas is uncommon. Diffuse pancreatic metastasis of any carcinoma rarely causes global enlargement of the pancreas. We present the case of a 73-year-old man diagnosed with metastatic RCC of the pancreas 9 years after radical nephrectomy had been performed and describe our radiologic findings. The disease involved the entire pancreas, which was hypoechoic on sonography, hypodense on CT without contrast enhancement, and markedly hyperdense after intravenous administration of a contrast agent. Color Doppler sonography showed that the involved areas of the pancreas had increased color flow signals, indicating that the metastatic tumor was characteristically hypervascular. In patients with a history of RCC, color or power Doppler sonographic demonstration of diffuse enlargement of the pancreas with evidence of hypervascularity may indicate metastasis of RCC to the pancreas.     

Can ruptured appendicitis be detected preoperatively in the ED?

PURPOSE: The purpose of this study is to determine which clinical symptoms/signs and computed tomography (CT) signs can help in distinguishing ruptured from simple appendicitis. MATERIALS AND METHODS: The medical records and CT findings of 202 consecutive patients with surgically proven acute appendicitis were retrospectively reviewed and compared between 2 groups with and without appendiceal rupture. RESULTS: Longer duration of symptoms ( P < .001), peritoneal sign ( P = .004), and higher C-reactive protein ( P < .001) are significant clinical factors for predicting appendiceal rupture in acute appendicitis. Abscess, extraluminal air, wall defect, peritoneal enhancement, extraluminal appendolith, phlegmon, localized fluid, fascial thickening, ascites, stool impaction, and 4 patterns of bowel wall thickening ( P < .001 to P = .047) are significant CT signs for predicting appendiceal rupture. The appendiceal diameter is larger in patients with ruptured appendicitis than in those with simple appendicitis (13.2 +/- 3.2 vs 11.3 +/- 2.4 mm, P < .001). The appendolith size is larger in patients with ruptured appendicitis than in those with simple appendicitis (7.1 +/- 4.4 vs 5.1 +/- 2.8 mm, P = .018). CONCLUSION: Besides some clinical findings, CT scan can accurately determine appendiceal rupture in acute appendicitis and can further demonstrate the presence of local inflammatory mass, facilitating management decision in the emergency department (ED).     

Percutaneous ethanol ablation of intrahepatic arterial pseudoaneurysm: A case report

Hepatic arterial pseudoaneurysm is a rare but potentially fatal condition that requires prompt management. We report a case of hepatic arterial pseudoaneurysm developed after radiofrequency ablation of a hepatocellular carcinoma. The patient was successfully treated with percutaneous absolute ethanol injection under ultrasound guidance. Follow-up studies with ultrasound and computed tomography for 2 years after treatment revealed no evidence of local recurrence of hepatocellular carcinoma and of the pseudoaneurysm.     

Can acute cholecystitis with gallbladder perforation be detected preoperatively by computed tomography in ED?: Correlation with clinical data and computed tomography features

Purpose

The purpose of this study is to determine which computed tomography (CT) findings and clinical data can help to diagnose gallbladder perforation in acute cholecystitis.

Materials and Methods

The medical records and CT findings of patients with surgically proven acute cholecystitis within the last recent 5 years were retrospectively reviewed and compared between 2 groups with and without gallbladder perforation.

Results

A total of 75 patients with acute cholecystitis were included in the study, and 16 patients were proven to have gallbladder perforation. Higher mortality rate was found in the perforation group (18.8% vs 1.7%; P = .029). Older age (>70 years; P = .004) and higher percentage of segmented neutrophil (>80%; P = .027) were significant clinical factors for predicting gallbladder perforation in acute cholecystitis. The significant CT signs related to gallbladder perforation included visualized gallbladder wall defect (P = .000), intramural gas (P = .043), intraluminal gas (P = .000), intraluminal membrane (P = .043), pericholecystic abscess or biloma formation (P = .009), intraperitoneal free air (P = .001), and presence of ascites in the absence of hypoalbuminemia or other intraabdominal malignancy (P = .017). In multivariate analysis, visualized gallbladder wall defect was the most significant predicting CT feature for diagnosing gallbladder perforation in acute cholecystitis.

Conclusion

Elderly patients with higher segmented neutrophil and CT signs of gallbladder wall defect associated with acute cholecystitis may have high possibility of gallbladder rupture.     

Polycythemia vera disease burden: contributing factors,impact on quality of life,and emerging treatment options

Polycythemia vera (PV) is a chronic myeloproliferative neoplasm characterized by clonal expansion of a hematopoietic progenitor, erythrocytosis, often leukocytosis and/or thrombocytosis, and nearly always an activating mutation in Janus kinase 2 (JAK2). The PV symptom burden can be considerable, in part driven by small or large vessel thrombotic tendency, splenomegaly, fatigue, pruritus, and a chronic risk of disease transformation to myelofibrosis or acute myeloid leukemia. In addition, patients with PV have an increased risk of mortality compared with the general population that often results from cardiovascular complications or disease transformation. Further, healthcare utilization and costs are higher in patients with PV than noncancer controls. First-line therapy options for high-risk patients may effectively manage PV in some instances; however, some patients do not receive adequate benefit from current treatment options and experience a more severe disease burden as a result. This may be especially true for those patients who are resistant to or intolerant of hydroxyurea or interferon-based therapies. New treatments currently being investigated in phase 3 clinical trials may alleviate disease burden in this patient population.     

Loss of heterozygosity in 7q myeloid disorders: clinical associations and genomic pathogenesis

Loss of heterozygosity affecting chromosome 7q is common in acute myeloid leukemia and myelodysplastic syndromes, pointing toward the essential role of this region in disease phenotype and clonal evolution. The higher resolution offered by recently developed genomic platforms may be used to establish more precise clinical correlations and identify specific target genes. We analyzed a series of patients with myeloid disorders using recent genomic technologies (1458 by single-nucleotide polymorphism arrays [SNP-A], 226 by next-generation sequencing, and 183 by expression microarrays). Using SNP-A, we identified chromosome 7q loss of heterozygosity segments in 161 of 1458 patients (11%); 26% of chronic myelomonocytic leukemia patients harbored 7q uniparental disomy, of which 41% had a homozygous EZH2 mutation. In addition, we describe an SNP-A-isolated deletion 7 hypocellular myelodysplastic syndrome subset, with a high rate of progression. Using direct and parallel sequencing, we found no recurrent mutations in typically large deletion 7q and monosomy 7 patients. In contrast, we detected a markedly decreased expression of genes included in our SNP-A defined minimally deleted regions. Although a 2-hit model is present in most patients with 7q uniparental disomy and a myeloproliferative phenotype, haplodeficient expression of defined regions of 7q may underlie pathogenesis in patients with deletions and predominant dysplastic features.     

Type I Choledochal Cyst Complicated With Acute Hemorrhagic Pancreatitis: A Case Report

Choledochal cysts rarely present with acute pancreatitis. We report a patient with type I choledochal cyst(s) who had concomitant acute frank hemorrhagic pancreatitis.A 14-year-old male noted with a history of recurrent abdominal pain, fever and jaundice. Ultrasonography (US) of abdomen at the Emergency Department depicted distended gall bladder with wall thickening. Apparently dilated intrahepatic ducts (IHDs) and fusiform dilatation of the common bile duct (CBD), and mild dilatation of the pancreatic duct were also noted, suggesting a type I choledochal cyst( ). Computed tomography (CT) demonstrated calcifications in the uncinate process of the pancreas in addition to the similar findings on US. He subsequently underwent choledochal cyst excision with a Roux-en-Y hepaticojejunostomy. After surgical treatment, he has been doing well for 3 years.     

Left Ulnar Artery Pseudoaneurysm and Left Hand Swelling Simulated by Elephantiasis in a Patient with Neurofibromatosis Type 1

Elephantiasis is a condition featured by gross enlargement of body parts to massive proportions. Neurofibromatosis type 1 (NF1) is a multisystem genetic disorder. Vascular anomaly is one among the complications of NF1. We report a case of NF1 who had a left hand vascular pseudoaneurysm with left hand swelling mimicking elephantiasis. The characteristics of sonography make it an excellent imaging modality to investigate this sort of superficial vascular lesion.