Successful preoperative diagnosis of heterotopic pancreas in the duodenum.

INTRODUCTION: Heterotopic pancreas (HP) is a relatively rare entity occurring in approximately 5% of the general population. It most commonly presents as an asymptomatic mass incidentally picked up on unrelated scans. HP most commonly occurs intra-abdominally, but has been known to occur in extra-abdominal sites such as the lung and brain. It is widely considered to bear little to no malignant potential. Difficulty and ambiguity in the diagnosis of HP commonly results in interventional dilemma and delay. PRESENTATION OF CASE: We present a case of uncomplicated HP that was ultimately treated conservatively. DISCUSSION: A literature review is made of the typical workup in a patient with suspected HP, and the characteristic radiological and endoscopic findings commonly used for diagnosis of this rare condition. A succinct summary of management guidelines for HP is reviewed. CONCLUSION: HP is most commonly an incidental finding. Ambiguity surrounding its diagnosis commonly gives rise to interventional dilemma and delay. The gold standard for diagnosis remains that of EUS and FNA with histological confirmation. This report has been written in concordance with the SCARE criteria Agha et al. [1].

Orbicularis Retaining Ligament Release in Lower Blepharoplasty: Assessing Efficacy and Complications.

PURPOSE: Release of the orbicularis retaining ligament (ORL) has been advocated as a technique to address tear trough deformities. This study sought to compare the effectiveness and morbidity of lower blepharoplasty with and without ORL release. METHODS: Retrospective chart review of 53 lower blepharoplasty patients. Twenty-six patients had ORL release and 27 patients did not. Three independent masked experienced cosmetic surgeons reviewed preoperative and postoperative photographs to assess degree of swelling, ecchymosis, change in steatoblepharon and tear trough deformity, and overall aesthetic result. RESULTS: There were no significant differences in overall aesthetic result, change in steatoblepharon or tear trough deformity, and postoperative ecchymosis in patients who had ORL release compared with those who did not. Patients who had ORL release had postoperative swelling and chemosis of significantly longer duration and a higher likelihood of developing postoperative ectropion. CONCLUSIONS: Orbicularis retaining ligament release does not appear to result in additional aesthetic benefit in lower blepharoplasty patients and may increase morbidity in the form of ectropion and prolonged swelling and chemosis.

Endoscope-assisted repair of CSF otorrhea and temporal lobe encephaloceles via keyhole craniotomy.

OBJECTIVE Temporal lobe encephaloceles and cerebrospinal fluid otorrhea from temporal bone defects that involve the tegmen tympani and mastoideum are generally repaired using middle fossa craniotomy, mastoidectomy, or combined approaches. Standard middle fossa craniotomy exposes patients to dural retraction, which can lead to postoperative neurological complications. Endoscopic and minimally invasive techniques have been used in other surgeries to minimize brain retraction, and so these methods were applied to repair the lateral skull base. The goal of this study was to determine if the use of endoscopic visualization through a middle fossa keyhole craniotomy could effectively repair tegmen defects. METHODS The authors conducted a retrospective review of 6 cases of endoscope-assisted middle fossa repairs of tegmen dehiscences at a tertiary care medical center within an 18-month period. RESULTS All cases were successfully treated using a keyhole craniotomy with endoscopic visualization and minimal retraction. Surgical times did not increase. There were no major postoperative complications, recurrences of encephaloceles, or cerebrospinal fluid otorrhea in these patients. CONCLUSIONS Endoscopic visualization allows for smaller incisions and craniotomies and less risk of brain retraction injury without compromising repair integrity during temporal encephalocele and tegmen repairs.

Recurrence of immature ovarian teratoma as malignant follicular carcinoma with liver and peritoneal metastasis 22 years after completion of initial treatment.

Growing tumour syndrome (GTS) is a rare event in which germ cell tumours treated with chemotherapy undergo maturation, acquire resistance to chemotherapy and regrow. The optimum treatment strategy is complete surgical excision. We report on a case of GTS with malignant metastases to the liver presenting 22 years after completion of treatment for immature teratoma, successfully managed with surgical resection alone.

The role of serial physical examinations in the management of angioedema involving the head and neck: A prospective observational study.

OBJECTIVE: To elucidate the progression of angioedema of the head and neck with routine management and to assess the utility of serial physical exams and fiberoptic laryngoscopy in its management. METHODS: This study was a prospective observational research. From 2013 to 2014, a prospective observational study was conducted at a tertiary referral center. Forty patient were approached, 7 refused, 33 (18-90 years old) were enrolled. Patients presented with angioedema involving the head and neck over a 12 month period were asked to participate in the study. Physical examination and fiberoptic laryngoscopy were performed at presentation and then repeated at least 1 h later. RESULTS: Thirty-three patients with head and neck angioedema from any cause were enrolled (mean age 58, range 23-89 years). The upper lip was the most commonly involved site (58%). On reevaluation, 82% of patients reported subjective improvement in symptoms. The association between subjective improvement and the physical exam, including fiberoptic laryngoscopy findings, was statistically significant (P < 0.001). CONCLUSION: In stable patients with angioedema of any head and neck subsite, self-reported symptoms are associated with clinical stability or improvement as assessed by physical signs and fiberoptic laryngoscopy. Patients' symptoms may be an appropriate surrogate to monitor clinical status without the need for routine serial physical examinations or fiberoptic laryngoscopy, though further study is needed.

Angiotensin converting enzyme inhibitor-related angioedema: onset, presentation, and management.

OBJECTIVE: This study aimed to determine the duration of use, presentation, and management of angiotensin converting enzyme (ACE) inhibitor-related angioedema patients at an urban academic medical center. METHODS: Retrospective chart review. RESULTS: Eighty-eight patients who presented with ACE inhibitor-related angioedema between January 1, 2012, and December 31, 2012, were identified. They presented anywhere from 1 day to 20 years after starting an ACE inhibitor. About half the patients (50.7%) presented after taking an ACE inhibitor for at least 1 year. Fifty-five patients were female (62.5%). Twenty-eight patients (31.8%) had an airway intervention with 27 intubated and 1 requiring cricothyroidotomy. Six patients were intubated after more than 1 flexible laryngoscopy. The percentage of patients with involvement of the face, lips, tongue, floor of mouth, soft palate/uvula, and larynx were 12.5%, 60.2%, 39.7%, 6.8%, 17.0%, and 29.5%, respectively. Sixty-eight percent of patients with laryngeal edema were intubated. The majority of patients were treated with a corticosteroid and H1 and H2 receptor antagonists. CONCLUSION: Angioedema can occur at any time after starting ACE inhibitor use, with nearly half occurring after 1 year of use. Laryngeal involvement occurred in a minority of patients, but most of these patients were felt to require airway protection.

Hypoxia provokes base excision repair changes and a repair-deficient, mutator phenotype in colorectal cancer cells.

UNLABELLED: Regions of acute and chronic hypoxia exist within solid tumors and can lead to increased rates of mutagenesis and/or altered DNA damage and repair protein expression. Base excision repair (BER) is responsible for resolving small, non-helix-distorting lesions from the genome that potentially cause mutations by mispairing or promoting DNA breaks during replication. Germline and somatic mutations in BER genes, such as MutY Homolog (MUTYH/MYH) and DNA-directed polymerase (POLB), are associated with increased risk of colorectal cancer. However, very little is known about the expression and function of BER proteins under hypoxic stress. Using conditions of chronic hypoxia, decreased expression of BER proteins was observed because of a mechanism involving suppressed BER protein synthesis in multiple colorectal cancer cell lines. Functional BER was impaired as determined by MYH- and 8-oxoguanine (OGG1)-specific glycosylase assays. A formamidopyrimidine-DNA glycosylase (Fpg) Comet assay revealed elevated residual DNA base damage in hypoxic cells 24 hours after H2O2 treatment as compared with normoxic controls. Similarly, high-performance liquid chromatography analysis demonstrated that 8-oxo-2'-deoxyguanosine lesions were elevated in hypoxic cells 3 and 24 hours after potassium bromate (KBrO3) treatment when compared with aerobic cells. Correspondingly, decreased clonogenic survival was observed following exposure to the DNA base damaging agents H2O2 and MMS, but not to the microtubule interfering agent paclitaxel. Thus, a persistent downregulation of BER components by the microenvironment modifies and facilitates a mutator phenotype, driving genetic instability and cancer progression. IMPLICATIONS: Aberrant BER is a contributing factor for the observed genetic instability in hypoxic tumor cells.

Vibration anesthesia for the reduction of pain with facial dermal filler injections.

BACKGROUND: Vibration anesthesia is an effective pain-reduction technique for facial cosmetic injections. The analgesic effect of this method was tested in this study during facial dermal filler injections. The study aimed to evaluate the safety and efficacy of vibration anesthesia for these facial injections. METHODS: This prospective study analyzed 41 patients who received dermal filler injections to the nasolabial folds, tear troughs, cheeks, and other facial sites. The injections were administered in a randomly assigned split-face design. One side of the patient's face received vibration together with dermal filler injections, whereas the other side received dermal filler injections alone. The patients completed a posttreatment questionnaire pertaining to injection pain, adverse effects, and preference for vibration with future dermal filler injections. RESULTS: The patients experienced both clinically and statistically significant pain reduction when a vibration stimulus was co-administered with the dermal filler injections. No adverse events were reported. The majority of the patients (95 %) reported a preference for vibration anesthesia with subsequent dermal filler injections. CONCLUSIONS: Vibration is a safe and effective method of achieving anesthesia during facial dermal filler injections. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Current treatment strategies for epistaxis: a multidisciplinary approach.

Epistaxis is a common clinical complaint with a spectrum of severity ranging from spontaneous cessation to unrelenting, life threatening hemorrhage requiring surgical treatment. Both otolaryngologic and neurointerventional techniques are discussed to provide a comprehensive paradigm to treat patients with epistaxis. An exhaustive review of the anatomic basis for the two main subtypes of epistaxis is provided as well as a graduated approach to appropriate clinical management.

High-resolution computed tomography analysis of variations of the sphenoid sinus.

Purpose The sphenoid sinus is a complex structure with key variations that are important for endoscopic parasellar approaches. In this study, high-resolution computed tomography (HRCT) scans were analyzed for the frequency of these variations. Methods A retrospective radiographic analysis was conducted on patients undergoing HRCT between July 2008 and September 2010. Results Sphenoid sinus pneumatization was defined as conchal, presellar, sellar, and postsellar based on pneumatization relative to the anterior and posterior face of the sella. The distribution ranged from 1.8%, 7.3%, 47.6%, and 43.3%, respectively. We found a greater preponderance of sellar and postsellar variation than previously reported. No differences were found in regard to age, gender, and ethnicity (African American, Caucasian, Asian, and Hispanic) (p > 0.05). The prevalence of optic nerve, maxillary nerve, and internal carotid artery protrusion was 26.1%, 25.9%, and 28.2%, respectively, and dehiscence was 2.1%, 7.4%, and 2.9%, respectively. Accessory septae were present in 43.5% of cases. A lateral recess was identified in 72.4% and clinoid pneumatization in 20% of patients. Conclusion This study demonstrates a greater prevalence of sphenoid sinus pneumatization and variations than previously reported. This has important implications in terms of preparation and anticipation of possible variations to avoid complications.

AZD5438, an inhibitor of Cdk1, 2, and 9, enhances the radiosensitivity of non-small cell lung carcinoma cells.

PURPOSE: Radiation therapy (RT) is one of the primary modalities for treatment of non-small cell lung cancer (NSCLC). However, due to the intrinsic radiation resistance of these tumors, many patients experience RT failure, which leads to considerable tumor progression including regional lymph node and distant metastasis. This preclinical study evaluated the efficacy of a new-generation cyclin-dependent kinase (Cdk) inhibitor, AZD5438, as a radiosensitizer in several NSCLC models that are specifically resistant to conventional fractionated RT. METHODS AND MATERIALS: The combined effect of ionizing radiation and AZD5438, a highly specific inhibitor of Cdk1, 2, and 9, was determined in vitro by surviving fraction, cell cycle distribution, apoptosis, DNA double-strand break (DSB) repair, and homologous recombination (HR) assays in 3 NSCLC cell lines (A549, H1299, and H460). For in vivo studies, human xenograft animal models in athymic nude mice were used. RESULTS: Treatment of NSCLC cells with AZD5438 significantly augmented cellular radiosensitivity (dose enhancement ratio rangeing from 1.4 to 1.75). The degree of radiosensitization by AZD5438 was greater in radioresistant cell lines (A549 and H1299). Radiosensitivity was enhanced specifically through inhibition of Cdk1, prolonged G(2)-M arrest, inhibition of HR, delayed DNA DSB repair, and increased apoptosis. Combined treatment with AZD5438 and irradiation also enhanced tumor growth delay, with an enhancement factor ranging from 1.2-1.7. CONCLUSIONS: This study supports the evaluation of newer generation Cdk inhibitors, such as AZD5438, as potent radiosensitizers in NSCLC models, especially in tumors that demonstrate variable intrinsic radiation responses.

High-resolution computed tomography analysis of the prevalence of Onodi cells.

OBJECTIVES/HYPOTHESIS: Onodi cells are the posterior-most ethmoid air cells that lie superior to the sphenoid sinus. Identification of these cells is essential prior to endoscopic sinus and skull base surgery due to their intricate relationship with the optic nerves and carotid arteries, which may lead to deleterious complications. In this study, high-resolution computed tomography (HRCT) scans from 170 adult-patients were analyzed by two independent observers for the presence of Onodi cells. STUDY DESIGN: Radiographic analysis at a tertiary care medical center. METHODS: A retrospective analysis was performed on patients undergoing HRCT between July 2008 and September 2010. Incidence of Onodi cells and demographic data were collected. RESULTS: The overall prevalence of Onodi cells in this cohort was 65.3%. Subgroup analysis based on ethnicity showed a rate of Onodi cells of 83.3% in Asians, 73.1% in whites, 57.0% in African Americans, and 62.7% in Hispanics. The prevalence of Onodi cells was not significantly different among the different ethnicities (P > .05). However, this was limited by a small sample size in some ethnic groups. Onodi cell prevalence was equivalent among males and females: 62.2% and 63.5% respectively (P > .05). Overall, our results show a greater prevalence of Onodi cells than previously reported. CONCLUSIONS: We found a higher prevalence of Onodi cells in our cohort than previously reported in the literature. Therefore, it is important for surgeons to anticipate the presence of these cells during endoscopic sinus and skull base procedures to prevent potential complications.

PTEN deletion in prostate cancer cells does not associate with loss of RAD51 function: implications for radiotherapy and chemotherapy.

PURPOSE: PTEN deletions in prostate cancer are associated with tumor aggression and poor outcome. Recent studies have implicated PTEN as a determinant of homologous recombination (HR) through defective RAD51 function. Similar to BRCA1/2-defective tumor cells, PTEN-null prostate and other cancer cells have been reported to be sensitive to PARP inhibitors (PARPi). To date, no direct comparison between PTEN and RAD51 expression in primary prostate tumors has been reported. EXPERIMENTAL DESIGN: Prostate cancer cell lines and xenografts with known PTEN status (22RV1-PTEN(+/+), DU145-PTEN(+/-), PC3-PTEN(-/-)) and H1299 and HCT116 cancer cells were used to evaluate how PTEN loss affects RAD51 expression and PARPi sensitivity. Primary prostate cancers with known PTEN status were analyzed for RAD51 expression. RESULTS: PTEN status is not associated with reduced RAD51 mRNA or protein expression in primary prostate cancers. Decreased PTEN expression did not reduce RAD51 expression or clonogenic survival following PARPi among prostate cancer cells that vary in TP53 and PTEN. PARPi sensitivity instead associated with a defect in MRE11 expression. PTEN-deficient cells had only mild PARPi sensitivity and no loss of HR or RAD51 recruitment. Clonogenic cell survival following a series of DNA damaging agents was variable: PTEN-deficient cells were sensitive to ionizing radiation, mitomycin-C, UV, H(2)O(2), and methyl methanesulfonate but not to cisplatin, camptothecin, or paclitaxel. CONCLUSIONS: These data suggest that the relationship between PTEN status and survival following DNA damage is indirect and complex. It is unlikely that PTEN status will be a direct biomarker for HR status or PARPi response in prostate cancer clinical trials.

Risk factors for cervical abnormalities among Hong Kong Chinese women: a large-scale community-based cervical screening program.

BACKGROUND: We sought to identify the prevalence of and risk factors associated with cervical abnormalities among Chinese women in Hong Kong. METHODS: A community-based cervical screening program was offered free of charge in Hong Kong. Information on the demographics, sexual experience, and obstetrical history of women who attended the Cervical Screening Clinic were collected and tabulated with their Pap smear results to establish the risk factors associated with cervical abnormalities among Hong Kong Chinese women. RESULTS: A total of 44,219 women attended the Cervical Screening Clinic for their first Pap smear tests over an 8-year period, with the prevalence of cervical abnormality at 4.51%. Adjusted for all associating factors, the significant risk factors of cervical abnormalities identified among Hong Kong Chinese women are being aged 40-49 (odds ratio [OR] 1.53), being single (OR 1.52) or cohabiting (OR 1.52), having received primary school education only (OR 1.53), having had three or more sexual partners (OR 1.52), onset of sexual activity at age ≤18 (OR 1.53), having reported bleeding after intercourse (OR 1.44), and having had more than three pregnancies (OR 1.47). Condom use was identified as the single most significant protective factor reducing the risk of cervical abnormalities among these women (OR 0.76). CONCLUSIONS: This first population study in Hong Kong provides a better understanding of the risk factors associated with cervical abnormalities among Hong Kong Chinese women. A primary preventive strategy to reduce cervical cancer incidence should focus on modifying these preventable risk factors, complemented by population-based cervical screening programs to increase the coverage rate to 80% in the long term, together with human papillomavirus (HPV) vaccination.

Contextual synthetic lethality of cancer cell kill based on the tumor microenvironment.

Acute and chronic hypoxia exists within the three-dimensional microenvironment of solid tumors and drives therapy resistance, genetic instability, and metastasis. Replicating cells exposed to either severe acute hypoxia (16 hours with 0.02% O(2)) followed by reoxygenation or moderate chronic hypoxia (72 hours with 0.2% O(2)) treatments have decreased homologous recombination (HR) protein expression and function. As HR defects are synthetically lethal with poly(ADP-ribose) polymerase 1 (PARP1) inhibition, we evaluated the sensitivity of repair-defective hypoxic cells to PARP inhibition. Although PARP inhibition itself did not affect HR expression or function, we observed increased clonogenic killing in HR-deficient hypoxic cells following chemical inhibition of PARP1. This effect was partially reversible by RAD51 overexpression. PARP1(-/-) murine embryonic fibroblasts (MEF) showed a proliferative disadvantage under hypoxic gassing when compared with PARP1(+/+) MEFs. PARP-inhibited hypoxic cells accumulated γH2AX and 53BP1 foci as a consequence of altered DNA replication firing during S phase-specific cell killing. In support of this proposed mode of action, PARP inhibitor-treated xenografts displayed increased γH2AX and cleaved caspase-3 expression in RAD51-deficient hypoxic subregions in vivo, which was associated with decreased ex vivo clonogenic survival following experimental radiotherapy. This is the first report of selective cell killing of HR-defective hypoxic cells in vivo as a consequence of microenvironment-mediated "contextual synthetic lethality." As all solid tumors contain aggressive hypoxic cells, this may broaden the clinical utility of PARP and DNA repair inhibition, either alone or in combination with radiotherapy and chemotherapy, even in tumor cells lacking synthetically lethal, genetic mutations.

Poly(ADP-ribose) polymerase inhibition as a model for synthetic lethality in developing radiation oncology targets.

DNA double-strand breaks (DSBs) induced during clinical radiotherapy are potent inducers of cell death. Poly(ADP-ribose) polymerase (PARP)-1 is a 113-kD nuclear protein that binds to both single- and double-strand DNA breaks and is actively involved in DNA single-strand break repair and base excision repair. Recently, potent and specific chemical inhibitors of PARP activity have been developed that are effective tumor cell radiosensitizers in vitro and in vivo. Because of synthetic lethality, PARP inhibitors may be highly effective as a single agent in patients whose tumors have germline or somatic defects in DNA damage and repair genes (eg, ATM, BRCA1, BRCA2, and NBS1) or defects in genes involved in phosphatase and tensin homolog gene (PTEN) signaling. Defects in specific DNA repair pathways also appear to enhance the radiosensitizing effects of PARP inhibition. In addition to inherent genetics, tumor cells may also be preferentially sensitized to radiotherapy by diverse mechanisms, including proliferation-dependent radiosensitization, targeting of the endothelium and tumor vasculature, and increased sensitivity to PARP inhibitors within repair-deficient hypoxic cells. Because biologically active doses of PARP inhibitors caused minimal toxicity in phase I to II clinical trials, careful scheduling of these agents in combination with radiotherapy may maintain the therapeutic ratio and increase tumor radiocurability.

"Contextual" synthetic lethality and/or loss of heterozygosity: tumor hypoxia and modification of DNA repair.

Hypoxia exists in every solid tumor and is associated with poor prognosis because of both local and systemic therapeutic resistance. Recent studies have focused on the interaction between tumor cell genetics and the dynamic state of oxygenation and metabolism. Hypoxia generates aggressive tumor cell phenotypes in part owing to ongoing genetic instability and a "mutator" phenotype. The latter may be due to suppression of DNA mismatch repair (MMR), nucleotide excision repair (NER), and double-strand break (DSB) repair. We propose a theoretical model in which hypoxia-mediated defects in DNA repair can lead to "contextual loss of heterozygosity" and drive oncogenesis. Additionally, hypoxia-mediated repair defects can be specifically targeted by DNA damaging agents and/or "contextual synthetic lethality" to kill repair-deficient cells and preserve the therapeutic ratio. These proposed concepts support the interrogation of solid tumors to document repair defects in both oxic and hypoxic tumor subregions as a conduit to novel clinical trials within the context of personalized medicine.