Omar Ragab

Regional Correlation Among Ganglion Cell Complex, Nerve Fiber Layer, and Visual Field Loss in Glaucoma

PURPOSE To analyze the relationship among macular ganglion cell complex (GCC) thickness, peripapillary nerve fiber layer (NFL) thickness, and visual field (VF) defects in patients with glaucoma. METHODS A Fourier-domain optical coherence tomography (FD-OCT) system was used to map the macula and peripapillary regions of the retina in 56 eyes of 38 patients with perimetric glaucoma. The macular GCC and peripapillary NFL thicknesses were mapped and standard automated perimetry (SAP) was performed. Loss of GCC and NFL were correlated with the VF map on both a point-by-point and regional basis. RESULTS Correlation between GCC thickness and peripapillary NFL thickness produced a detailed correspondence map that demonstrates the arcuate course of the NFL in the macula. Corresponding regions within the GCC, NFL, and VF maps demonstrate significant correlation, once parafoveal retinal ganglion cell (RGC) displacement is taken into account. CONCLUSIONS There are significant point-specific and regional correlations between GCC loss, NFL loss, and deficits on SAP. Using these different data sources together may improve our understanding of glaucomatous damage and aid in the management of patients with glaucoma.

Pulmonary Homograft Monocusp Reconstruction of the Right Ventricular Outflow Tract: Outcomes to the Intermediate Term

BACKGROUND There is limited information on longer-term outcomes of pulmonary homograft monocusp (PHM) reconstruction of the right ventricular outflow tract (RVOT). METHODS A retrospective review of 131 consecutive patients undergoing RVOT reconstruction with PHM was completed. RESULTS Median age was 7.6 months (range, 1 day to 14 years) and weight was 7.3 kg (range, 2 to 65 kg). Most patients (108 of 131; 82%) underwent repair for Tetralogy. After PHM, median duration of mechanical ventilation was 1 day (range, 0 to 89) and hospital stay was 6.5 days (range, 2 to 137). Hospital mortality was 2% (3 of 131) with 1 patient undergoing early replacement of PHM. Echocardiogram at hospital discharge demonstrated peak RVOT gradient of 16 mm Hg (range, 4 to 64 mm Hg); and pulmonary insufficiency was absent/trivial in 40%, mild in 42%, moderate in 16%, and severe in 2%. Follow-up is completed in 91% of hospital survivors at a median of 5 years (range, 1 to 12). There were 5 late deaths, with an actuarial survival of 96% +/- 3.7%, 94% +/- 4.6%, and 89% +/- 9.2% at 1 year, 5 years, and 10 years, respectively. There were 24 reinterventions, including 10 pulmonary valve replacements. Median time to valve replacement was 1.9 years (range, 0.4 to 4.6). Actuarial freedom from pulmonary valve replacement was 97% +/- 3.0%, 90% +/- 6.1%, and 85% +/- 10.3% at 1 year, 5 years, and 10 years, respectively. Echocardiogram at last follow-up demonstrated no increase in RVOT gradient compared with hospital discharge (16 mm Hg), but there was significant increase in pulmonary insufficiency (mild 27%, moderate 39%, severe 34%). CONCLUSIONS Pulmonary homograft monocusp reconstruction is an alternative strategy for RVOT reconstruction and provides early but gradually diminishing protection against pulmonary insufficiency without a risk of stenosis. As expected, PHM function decreases over time as the RVOT grows and the homograft tissue undergoes structural deterioration.

Targeted Prostate Biopsy Gleason Score Heterogeneity and Implications for Risk Stratification

Objectives: To quantify Gleason score (GS) heterogeneity within multiparametric magnetic resonance imaging (MRI)-targeted prostate biopsies and to determine impact on National Comprehensive Cancer Network (NCCN) risk stratification. Methods: An Institutional Review Board-approved retrospective study was performed on men who underwent Artemis (MRI-transrectal–ultrasound fusion) targeted biopsy (TB) for suspected prostate cancer between 2012 and 2015. Intratarget heterogeneity was defined as a difference in GS between 2 cores within a single target in patients with ≥2 positive cores. Prostate specific antigen, maximum tumor diameter, apparent diffusion coefficient, MRI suspicion score, prostate volume, systematic biopsy (SB) GS, and T-stage were analyzed for correlation with heterogeneity. Changes in NCCN risk based on high versus low GS on TB, SB alone, and SB+TB were compared. Results: Fifty-three patients underwent TB of 73 suspected lesions. Seventy percent (51/73) had ≥2 positive cores, thus meeting inclusion criteria for heterogeneity analysis. Fifty-five percent (28/51) of qualifying targets showed GS heterogeneity. None of the evaluated factors showed a significant relationship with heterogeneity. NCCN low-risk, intermediate-risk, and high-risk groups were 30%, 49%, and 21%, respectively, with SB alone. Adding low GS TB to SB resulted in 17%, 55%, 28% in each risk group, while using high GS+SB resulted in 4%, 54%, and 42%. Overall, the addition of TB resulted in higher NCCN risk groups in 38% of cases. Conclusions: Over half of multiparametric MRI-defined targets demonstrated GS heterogeneity. The addition of high GS from TB leads to risk inflation compared with using SB alone. Further research is needed on how to integrate these findings into current risk stratification models and clinical practice.

Complete cloacal duplication imaged before and during pregnancy

The authors describe a 31 year-old female who presented emergently with abdominal pain and was found at CT to have complete genitourinary duplication including separate urinary bladders, uteri, cervices, and vaginas, and also duplication of the rectum. No etiology for abdominal pain was identified. The patient was referred to urology for further evaluation, and an intravenous urographic study was obtained, which confirmed complete lower urinary tract duplication. The patient presented emergently 9 months later during a subsequent pregnancy for further evaluation of abdominal pain. A second CT scan was ordered to rule out appendicitis. Findings consistent with cloacal duplication were again noted. There was also dilatation of the urinary collecting systems, more prominently on the right side. A Cesarean section was performed and confirmed total genitourinary and rectal duplication.

Acute toxicity of craniospinal irradiation with volumetric-modulated arc therapy in children with solid tumors

Craniospinal irradiation (CSI) is an important part of curative radiation therapy (RT) for many types of pediatric brain or solid tumors. After conventional CSI, long term survivors may experience sequelae due to unintended dose to normal tissue. Volumetric modulated arc therapy (VMAT) CSI reduces off‐target doses at the cost of greater complexity and error risk, and we describe our initial experience in a group of pediatric patients with solid tumors presenting with disseminated or recurrent disease.

Extent of pelvic lymphadenectomy and use of adjuvant vaginal brachytherapy for early-stage endometrial cancer

OBJECTIVE To examine trends of adjuvant radiotherapy choice and to examine associations between pelvic lymphadenectomy and radiotherapy choice for women with early-stage endometrial cancer. METHODS The Surveillance, Epidemiology, and End Results Program was used to identify surgically treated stage I-II endometrial cancer between 1983 and 2012 (type 1 n=79,474, and type 2 n=25,020). Piecewise linear regression models were used to examine temporal trends of intracavitary brachytherapy (ICBT) and whole pelvic radiotherapy (WPRT) use, pelvic lymphadenectomy rate, and sampled node counts. Multivariable binary logistic regression models were used to identify independent predictors for ICBT use. RESULTS There was a significant increase in ICBT use and decrease in WPRT use during the study period. ICBT use exceeded WPRT use in 2003 for type 1 stage IA, and in 2007 for type 1 stage IB and type 2 stage IA diseases. In addition, number of sampled pelvic nodes significantly increased over time in type 1-2 stage I-II diseases (mean, 7.0-12.7 in 1988 to 15.2-17.6 in 2012, all P<0.001). On multivariable analysis, extent of sampled pelvic nodes was significantly associated with ICBT use for type 1 cancer: adjusted-odds ratios for 1-10 and >10 nodes versus no lymphadenectomy in stage IA (1.38/2.40), IB (2.75/6.32), and II (1.36/2.91) diseases. Similar trends were observed for type 2 cancer: adjusted-odds ratios for stage IA (1.69/3.73), IB (2.25/5.65), and II (1.36/2.19) diseases. CONCLUSION Our results suggest that surgeons and radiation oncologists are evaluating the extent of pelvic lymphadenectomy when counseling women with early-stage endometrial cancer for adjuvant radiotherapy.

Comparison of patient‐reported acute urinary and sexual toxicity scores in a 6‐ versus 2‐fraction course of high‐dose‐rate prostate brachytherapy monotherapy

To identify differences in acute urinary and sexual toxicity between a 6‐fraction and 2‐fraction high‐dose‐rate brachytherapy monotherapy regimen and correlate dosimetric constraints to short‐term toxicity.

Brachytherapy: Where Has It Gone…Again?

TO THE EDITOR: The review by Chinn and Myers about the management of oral cavity cancer mentioned available therapeutic options, but there was one significant omission: brachytherapy. Low-dose-rate and high-dose-rate interstitial brachytherapy have historically been used to treat oral cavity cancers, either as monotherapy or in combination with external-beam radiation, and offer high local control rates and low toxicities. It is an effective technique used in centers throughout the world in the definitive, postoperative, recurrent, and salvage settings. In fact, the use of brachytherapy as a boost in the definitive setting can improve local control rates by 20% compared with external beam radiation alone. Both the American Brachytherapy Society and the Groupe Europeen de Curietherapie–European Society for Radiotherapy and Oncology have developed guidelines for the use of brachytherapy for head and neck cancers. Petereit et al appropriately stated in their article “Brachytherapy: Where has it gone?” that it is our responsibility as oncologists to educate patients, insurance companies, and policy makers about the utility of this tool. Brachytherapy has a significant, evidence-based role in the management of oral cavity cancer and should be considered for treatment in appropriately selected patients. A reply to this Correspondence was not provided.

Another solution that enables ablative radiotherapy for large liver tumors: Percutaneous interstitial high-dose rate brachytherapy.

We thank the authors for outlining an approach for ablative external radiotherapy (RT) via stereotactic body RT for liver lesions that are either large or adjacent to the hilum. We concur that unresectable liver disease warrants local treatment to improve patient outcomes. An excellent modality for ablative RT that was not mentioned is that of percutaneous interstitial high-dose rate brachytherapy. This technique can be performed with computed tomography, magnetic resonance imaging, and/or ultrasound guidance. By using an “inside out” approach, there can be significant dose escalation within the tumor complemented by rapid dose falloff. Thus, low dose spill to adjacent organs at risk is limited and smaller treatment volumes are used because the planning target volume margin is eliminated (implanted catheters move with the target). As a result, lesions that are larger or near the hilum can be treated safely. Depending on the size of the lesion, these treatments are completed in 1 or 2 single-fraction sessions. There is over a decade of literature regarding the use of this technique to treat liver metastases as well as primary liver tumors. Collettini et al treated patients with large hepatocellular carcinomas (mean, 7.1 cm [range, 512 cm]) to a mean dose of 15.8 grays with a mean of 2.7 catheters. With a mean follow-up of 12.8 months, they were able to achieve a local control (LC) rate of 93% with no major toxicities reported. In another study, Ricke et al treated patients with unfavorable large liver metastases (mean, 7.7 cm [range, 5.5-10.8 cm]) and found LC rates of 74% at 6 months and 40% at 1 year. For patients with metastatic lesions adjacent to the liver hilum, one study reported a LC rate of 88% at 1.5 years with a median overall survival of 20 months, whereas another study of liver lesions measuring >4 cm that were adjacent to the hilum demonstrated 1-year LC rates of 81% and 73% for primary and secondary lesions, respectively. Severe toxicities were observed in <5% of interventions, with no treatment-related deaths reported. Interstitial high-dose rate brachytherapy for patients with unresectable liver lesions certainly warrants further investigation and longer follow-up; however, it appears to represent a viable therapeutic option, particularly for patients with tumors that are larger or adjacent to the hilum.

Tumor-specific outcome of metachronous uterine malignancy after pelvic irradiation for cervical cancer

OBJECTIVE To examine survival of women who develop metachronous uterine malignancy after definitive pelvic radiotherapy for cervical cancer. METHODS This retrospective observational study examined the Surveillance, Epidemiology, End Results Program between 1973 and 2013. Women with cervical cancer who received definitive radiotherapy without hysterectomy were examined for the diagnosis of metachronous uterine malignancy (n = 5277). Survival was compared between metachronous and non-metachronous uterine malignancies according to tumor factors. RESULTS The 10- and 20-year cumulative incidences of metachronous uterine malignancy were 0.6% and 1.2%, respectively. When compared to non-metachronous uterine malignancy, metachronous tumor were more likely to be non-endometrioid and advanced-stage (both, P < 0.001). As a whole cohort, metachronous uterine malignancy was significantly associated with decreased overall survival (OS) compared to non-metachronous tumors (hazard ratio [HR] 4.22, P < 0.001). OS was significantly worse in metachronous compared to non-metachronous malignancies, although the magnitude of statistical significance was greater for endometrioid tumors (HRs for endometrioid versus non-endometrioid: 6.17 versus 1.92). For grade 1-2 endometrial cancer, metachronous cases had significantly decreased OS compared to non-metachronous cases, a larger difference than that seen in higher grade tumors (HRs for grade 1-2 versus 3: 7.79 versus 2.15). Similarly, in early-stage endometrial cancer, metachronous cases had significantly decreased OS, with a greater HR compared to advanced-stage disease (HRs for stage I-II versus III-IV: 5.29 versus 2.29). CONCLUSION Radiotherapy-associated metachronous uterine malignancy after cervical cancer is rare but commonly presents with aggressive tumor characteristics. The impact on survival is considerably high when metachronous uterine malignancy is endometrioid, low-grade, and early-stage.