Describing the Medical Needs of Hawai'i's Houseless Population During COVID at Free Student Run Outpatient Clinics (Hawai'i HOME Project).

Hawai'i experiences some of the highest rates of houselessness per capita in the country. COVID-19 has exacerbated these disparities and made it difficult for these individuals to seek medical care. Hawai'i's Houseless Outreach in Medical Education (HOME) clinic is the largest student run free clinic in the state, which provides medical services to this patient population. This article reports the demographics, medical needs, and services provided to patients of Hawai'i's HOME clinic during the era of COVID-19. From September 2020 to 2021, the HOME clinic saw 1198 unique visits with 526 distinct patients. The most common chief complaints included wound care (42.4%), pain (26.9%), and skin complaints (15.7%). A large portion of the population suffered from comorbidities including elevated blood pressure (66%), a formal reported history of hypertension (30.6%), diabetes (11.6%), and psychiatric concerns including schizophrenia (5.2%) and generalized anxiety (5.1%). Additionally, a large portion of patients (57.2%) were substance users including 17.8% of patients endorsing use of alcohol, 48.5% tobacco and 12.5% marijuana. The most common services provided were dispensation of medication (58.7%), wound cleaning/dressing changes (30.7%), and alcohol or other drug cessation counseling (25.2%). This study emphasizes that the houseless are a diverse population with complex, evolving medical needs and a high prevalence of chronic diseases and comorbidities.

The association of sexual orientation with prostate, breast, and cervical cancer screening and diagnosis.

PURPOSE: Data on heterogeneity in cancer screening and diagnosis rates among lesbians/gays and bisexuals (LGBs) is lacking. Recent studies showed that LGBs have decreased healthcare utilization compared to heterosexual counterparts. Few studies have examined how sexual orientation impacts cancer screening and prevalence. We, therefore, investigated the association between sexual orientation and prevalent sex-specific cancer including prostate (PCa), breast (BC), and cervical (CC) cancer. METHODS: This was a cross-sectional survey-based US study, including men and women aged 18 + from the Health Information National Trends Survey (HINTS) database between 2017 and 2019. The primary endpoint was individual-reported prostate, breast, and cervical cancer screening and prevalence rates among heterosexual and LGB men and women. Multivariable logistic regression analyses assessed association of various covariates with undergoing screening and diagnosis of these cancers. RESULTS: Overall, 4,441 and 6,333 heterosexual men and women, respectively, were compared to 225 and 213 LGB men and women, respectively. LGBs were younger and less likely to be screened for PCa, BC, and CC than heterosexuals. A higher proportion of heterosexual women than lesbian and bisexual women were screened for CC with pap smears (95.36% vs. 90.48% and 86.11%, p ≤ 0.001) and BC with mammograms (80.74% vs. 63.81% and 45.37%, p ≤ 0.001). Similarly, a higher proportion of heterosexual men than gay and bisexual men were screened for PCa with PSA blood tests (41.27% vs. 30.53% and 27.58%, p ≤ 0.001). CONCLUSION: There were more heterosexuals than LGBs screened for CC, BC, and PCa. However, no association between sexual orientation and cancer diagnosis was found. Healthcare professionals should be encouraged to improve cancer screening among LGBs.

Clinically Advanced Pheochromocytomas and Paragangliomas: A Comprehensive Genomic Profiling Study.

Patients with clinically advanced paragangliomas (CA-Para) and pheochromocytomas (CA-Pheo) have limited surgical or systemic treatments. We used comprehensive genomic profiling (CGP) to compare genomic alterations (GA) in CA-Para and CA-Pheo to identify potential therapeutic targets. Eighty-three CA-Para and 45 CA-Pheo underwent hybrid-capture-based CGP using a targeted panel of 324 genes. Tumor mutational burden (TMB) and microsatellite instability (MSI) were determined. The GA/tumor frequencies were low for both tumor types (1.9 GA/tumor for CA-Para, 2.3 GA/tumor for CA-Pheo). The most frequent potentially targetable GA in CA-Para were in FGFR1 (7%, primarily amplifications), NF1, PTEN, NF2, and CDK4 (all 2%) and for CA-Pheo in RET (9%, primarily fusions), NF1 (11%) and FGFR1 (7%). Germline mutations in known cancer predisposition genes were predicted in 13 (30%) of CA-Pheo and 38 (45%) of CA-Para cases, predominantly involving SDHA/B genes. Both CA-Para and CA-Para had low median TMB, low PD-L1 expression levels and none had MSI high status. While similar GA frequency is seen in both CA-Para and CA-Para, germline GA were seen more frequently in CA-Para. Low PD-L1 expression levels and no MSI high status argue against strong potential for novel immune checkpoint inhibitors. However, several important potential therapeutic targets in both CA-Para and CA-Para are identified using CGP.

Importance of long-term follow-up after endoscopic management for upper tract urothelial carcinoma and factors leading to surgical management.

PURPOSE: Patients undergoing endoscopic management for upper tract urothelial carcinoma often progress to definitive therapy with radical nephroureterectomy. This study examined the rate of progression as well as risk factors for transitions in treatment over time. METHODS: Retrospective review at two institutions identified patients undergoing endoscopic management for upper tract urothelial carcinoma. Patients were assessed for progression to radical nephroureterectomy. Baseline characteristics were compared using Chi square analysis. Kaplan-Meier method analyzed the probability of patients not progressing to radical nephroureterectomy. Cox proportional hazards identified factors associated with progression to radical nephroureterectomy. RESULTS: Eighty-one patients had endoscopic management alone and 89 progressed to radical nephroureterectomy. The two groups had similar age, histories of bladder cancer, and Charlson comorbidity index. Positive urinary cytology, ureteroscopic visualization, and biopsy grade were higher in those progressing to RNU (p < 0.001). Hazard modeling demonstrated higher rates of progression to radical nephroureterectomy with positive biopsy (HR 11.8, 95% CI 2.4-59.5, p = 0.003) or visible lesion on ureteroscopy (HR 8.4, 95% CI 3.0-23.9, p < 0.001). Patients with a higher Charlson comorbidity index were less likely to have radical nephroureterectomy. On Kaplan-Meier modeling, the probability of not undergoing radical nephroureterectomy at 2 years and 5 years was 50% and 20%, respectively. CONCLUSIONS: Patients who progress to radical nephroureterectomy after endoscopic management have fewer comorbid conditions and changes in disease status including visible lesions on ureteroscopy and positive biopsies. The high rate of progression to radical nephroureterectomy reinforces the need for long-term follow-up of these patients.

The Outcome of Post-Chemotherapy Retroperitoneal Lymph Node Dissection in Patients with Metastatic Bladder Cancer in the Retroperitoneum.

PURPOSE: While a definitive cure can be achieved by radical cystectomy and pelvic lymph node dissection in select patients with regional lymphadenopathy, the benefit remains uncertain in patients who present with non-regional metastases. We analyzed the survival outcomes of post-chemotherapy retroperitoneal lymph node dissection. MATERIALS AND METHODS: We reviewed our institutional database and identified 13 patients with radiographically evident or biopsy proven retroperitoneal nodal metastases with a significant response to chemotherapy. These patients underwent consolidative surgery with concomitant or delayed retroperitoneal lymph node dissection. The primary endpoints were progression-free survival and disease-specific survival from the time of retroperitoneal lymph node dissection. RESULTS: All patients had primary urothelial cell carcinoma. Twelve patients underwent concomitant radical cystectomy, pelvic and retroperitoneal lymph node dissection. Seven patients (54%) had residual disease in the retroperitoneum and the median number of retroperitoneal nodes containing metastases was 4 (IQR 2-6). Six (86%) developed disease recurrences within 2 years of surgery and 5 (71%) died of cancer. Of the 6 patients without residual disease in the retroperitoneum, 2 (33%) developed recurrences and died of disease progression. The 2-year disease-specific survival was worse for patients with residual disease in the retroperitoneum than those without residual retroperitoneal disease (34%, 95% CI 5-68 vs 50%, 95% CI 6-85). CONCLUSIONS: The presence of retroperitoneal nodal metastases at post-chemotherapy retroperitoneal lymph node dissection is a poor prognosticator. Consolidative surgery with retroperitoneal lymph node dissection provides important prognostic information and may be therapeutic in a very small subset of these patients.

Comparative Genomic Profiling of Refractory and Metastatic Penile and Nonpenile Cutaneous Squamous Cell Carcinoma: Implications for Selection of Systemic Therapy.

PURPOSE: Metastatic penile squamous cell carcinoma is an aggressive malignancy with limited treatment options. We compared the potential therapy impacting genomic alterations between metastatic penile squamous cell carcinoma and nonpenile metastatic cutaneous squamous cell carcinoma. MATERIALS AND METHODS: DNA was extracted from 40 µ of formalin fixed, paraffin embedded samples from 78 cases of metastatic penile squamous cell carcinoma and 338 of metastatic cutaneous squamous cell carcinoma. Comprehensive genomic profiling was performed using a hybrid capture, adaptor ligation based, next generation sequencing assay to a mean coverage depth of greater than 500×. The tumor mutational burden was determined on 1.1 Mbp of sequenced DNA and microsatellite instability was determined on 114 loci. RESULTS: Potential targeted therapy opportunities in metastatic penile squamous cell carcinoma cases included alterations in the MTOR pathway ( NF1 genomic alterations in 7% and PTEN genomic alterations in 4%) and in the DNA repair pathway ( BRCA2 and ATM genomic alterations in 7% each) and tyrosine kinase ( EGFR genomic alterations in 6%, and FGFR3 and ERBB2 genomic alterations in 4% each). The tumor mutational burden was significantly higher in predominantly ultraviolet light exposed metastatic squamous cell carcinoma than in metastatic penile squamous cell carcinoma, making metastatic squamous cell carcinoma potentially more responsive to immunotherapies than metastatic penile squamous cell carcinoma. Microsatellite high status was extremely rare for metastatic penile and metastatic cutaneous squamous cell carcinoma. CD274 ( PD-L1) amplification was also rare in both tumor types. CONCLUSIONS: Metastatic penile squamous cell carcinoma is a unique subtype of squamous cell carcinoma with distinctive genomic features which contrast with those identified in metastatic cutaneous squamous cell carcinoma of nonpenile ultraviolet light exposed skin. Although not rich in predictors of the response to immunotherapy (the tumor mutational burden and microsatellite instability are low), more than a quarter of metastatic penile squamous cell carcinoma cases may potentially benefit from existing and available therapies targeting MTOR, DNA repair and tyrosine kinase pathways.

The natural history of large renal masses followed on observation.

PURPOSE: The safety and feasibility of active surveillance in comorbid patients with renal masses ≥4.0cm is uncertain. The aim of this study is to describe our institutional experience with the observation of large renal masses. MATERIALS AND METHODS: One hundred patients were identified with renal masses ≥ 4.0cm that were followed on observation for at least 6 months without surgical intervention between 1994 and 2016. Linear regression was conducted to determine predictors for renal mass growth and competing risk methods were used to estimate the probability of progression in the setting of death from other causes. RESULTS: Median age at diagnosis was 73 years and 73% of patients had a Charlson Comorbidity index ≥ 4. At presentation, the median mass size was 4.9cm. The median growth rate was 0.4cm/y and there were no significant predictors of growth. Surveillance was discontinued in 34 patients who underwent delayed intervention. Median follow up for metastasis-free survivors was 4 years. In total, 10 patients developed metastatic disease, 3 died from kidney cancer and 30 patients died from other causes. The 5-year probability of other cause mortality was 22% (95% CI: 14%-32%) compared to 6% (95% CI: 2%-13%) for metastatic progression of kidney cancer. CONCLUSION: In highly comorbid patients, the observation of large renal masses has low likelihood for metastatic progression relative to the risk of nonkidney cancer related death. This data supports the use of surveillance as an acceptable strategy for highly selected patients with competing risks from other serious illnesses.

The Prognostic Impact of a Positive Vascular Margin on pT3 Clear Cell Renal Cell Carcinoma.

PURPOSE: We examined the impact of positive vascular margins in patients with pT3 clear cell renal cell carcinoma. MATERIALS AND METHODS: After excluding patients with nonvascular positive margins, metastasis, lymph node involvement, neoadjuvant therapy or nonclear cell histology, we identified 224 patients with venous tumor invasion through our institutional database from 1999 to 2013. Kaplan-Meier analysis and log rank tests were used to evaluate whether positive vascular margins were associated with progression-free survival or cancer specific survival. RESULTS: There were 41 patients (18%) with a positive vascular margin. Margin status was directly related to the level of invasion (p <0.0001). Compared to the negative vascular margin group the positive group had a significantly worse progression-free survival (p=0.01) but not cancer specific survival (p=0.3). Similarly the level of vascular thrombus invasion was significantly associated with worse progression-free survival (p=0.02) but not cancer specific survival (p=0.4). The 3-year progression-free survival was worst with inferior vena cava invasion and best with segmental/muscular venous branch invasion (54%, 95% CI 34-70 vs 76%, 95% CI 64-85). Among patients with only main renal vein thrombus, vascular margin status was not associated with progression-free survival (p=0.5) or cancer specific survival (p=0.2). CONCLUSIONS: In patients with pT3N0/XM0 clear cell renal cell carcinoma positive vascular margins are associated with risk of disease progression. However, the risk of relapse associated with positive vascular margins is driven by the extent of vascular thrombus invasion. These findings suggest that the clinical significance of vascular margin status as currently defined in pT3 clear cell renal cell carcinoma is minimal.

Risk of Recurrence for Clinical Stage I and II Patients With Teratoma Only at Primary Retroperitoneal Lymph Node Dissection.

OBJECTIVE: To evaluate the oncologic outcomes of patients with retroperitoneal teratoma only at primary retroperitoneal lymph node dissection (RPLND) who did not receive adjuvant chemotherapy. MATERIALS AND METHODS: Between 1979 and 2010, 23 patients with clinical stage (CS) I and II disease underwent primary RPLND at our institution with teratoma only in the retroperitoneum. No patient received adjuvant chemotherapy and the minimum follow-up was 2 years. RESULTS: At the initial diagnosis, 13 patients (56.5%) had CS I disease and 10 patients (43.5%) had CS II disease. Pathologic staging demonstrated IIA in 13 patients (56.5%), IIB in 8 patients (34.8%), and IIC in 2 patients (8.7%). The 5-year disease-free survival (DFS) was 100% with a median follow-up of 5.8 years (range, 2.1-25.4). DFS was not significantly different comparing pathologic stage IIA vs IIB/IIC disease (P = .73). Two patients (14%) developed late relapses. One patient had a pelvic recurrence 11 years after primary RPLND. Final pathology from the pelvic resection demonstrated embryonal carcinoma. He remains disease free after his second surgery. The second patient had a contralateral retroperitoneal recurrence with yolk-sac tumor and teratoma 11 years after primary RPLND. He was treated with chemotherapy followed by postchemotherapy RPLND. CONCLUSION: The relapse rate for patients with teratoma only at primary RPLND is low irrespective of PS. Adjuvant chemotherapy is therefore not recommended in the management of these patients.

Risk for Clostridium difficile infection after radical cystectomy for bladder cancer: Analysis of a contemporary series.

INTRODUCTION: This study seeks to evaluate the incidence and associated risk factors of Clostridium difficile infection (CDI) in patients undergoing radical cystectomy (RC) for bladder cancer. METHODS: We retrospectively reviewed a single institution׳s bladder cancer database including all patients who underwent RC between 2010 and 2013. CDI was diagnosed by detection of Clostridium difficile toxin B gene using polymerase chain reaction-based stool assay in patients with clinically significant diarrhea within 90 days of the index operation. A multivariable logistic regression model was used to identify demographics and perioperative factors associated with developing CDI. RESULTS: Of the 552 patients who underwent RC, postoperative CDI occurred in 49 patients (8.8%) with a median time to diagnosis after RC of 7 days (interquartile range: 5-19). Of the 122 readmissions for postoperative complications, 10% (n = 12) were related to CDI; 2 patients died of sepsis directly related to severe CDI. On multivariate logistic regression, the use of chronic antacid therapy (odds ratio = 1.9, 95% CI: 1.02-3.68, P = 0.04) and antibiotic exposure greater than 7 days (odds ratio = 2.2, 95% CI: 1.11-4.44, P = 0.02) were independently associated with developing CDI. The use of preoperative antibiotics for positive findings on urine culture within 30 days before surgery was not statistically significantly associated with development of CDI (P = 0.06). CONCLUSIONS: The development of CDI occurs in 8.8% of patients undergoing RC. Our study demonstrates that use of chronic antacid therapy and long duration of antimicrobial exposure are associated with development of CDI. Efforts focusing on minimizing antibiotic exposure in patients undergoing RC are needed, and perioperative antimicrobial prophylaxis guidelines should be followed.

Incidence and risk factors of parastomal hernia in patients undergoing radical cystectomy and ileal conduit diversion.

PURPOSE: We evaluate the incidence and risk factors of parastomal hernia formation in patients undergoing radical cystectomy and ileal conduit urinary diversion. MATERIALS AND METHODS: We retrospectively reviewed the Indiana University cystectomy database between 2001 and 2011, and identified 516 patients who underwent radical cystectomy and ileal conduit diversion. Overall 199 patients had a clinical followup of at least 12 months and all underwent postoperative staging computerized tomography to confirm the presence of parastomal hernia. The incidence of parastomal hernia is reported with correlations made to demographic, patient level and perioperative risk factors. RESULTS: A parastomal hernia developed in 58 patients (29%) at a median followup of 27 months (range 12 to 125). Of these patients 26 (45%) underwent surgical repair due to abdominal discomfort (58%), acute strangulation or obstruction of the small bowel (15%), partial small bowel obstructions (15%) and elective repair for other intra-abdominal procedures (12%). Prior exploratory laparotomy (adjusted HR 1.98, 95% CI 1.97-3.36, p = 0.011) and severe obesity (adjusted HR 4.26, 95% CI 1.52-11.93, p = 0.006) were predictive of parastomal herniation. The cumulative risk of parastomal hernia formation at 1 and 2 years after cystectomy was 12.2% and 22.5%, respectively. CONCLUSIONS: We demonstrated that parastomal hernia will develop in nearly a third of patients after radical cystectomy with ileal conduit diversion. Prior laparotomy and severe obesity are independent risk factors. Preoperative counseling and preventative measures regarding parastomal hernia formation should be emphasized, particularly in these at risk patients.

Impact of ischemia and procurement conditions on gene expression in renal cell carcinoma.

PURPOSE: Previous studies have shown that ischemia alters gene expression in normal and malignant tissues. There are no studies that evaluated effects of ischemia in renal tumors. This study examines the impact of ischemia and tissue procurement conditions on RNA integrity and gene expression in renal cell carcinoma. EXPERIMENTAL DESIGN: Ten renal tumors were resected without renal hilar clamping from 10 patients with renal clear cell carcinoma. Immediately after tumor resection, a piece of tumor was snap frozen. Remaining tumor samples were stored at 4°C, 22°C, and 37°C and frozen at 5, 30, 60, 120, and 240 minutes. Histopathologic evaluation was conducted on all tissue samples, and only those with greater than 80% tumor were selected for further analysis. RNA integrity was confirmed by electropherograms and quantitated using RNA integrity number index. Altered gene expression was assessed by paired, two-sample t test between the zero time point and aliquots from various conditions obtained from the same tumor. RESULTS: One hundred and forty microarrays were conducted. Some RNA degradation was observed 240 minutes after resection at 37°C. The expression of more than 4,000 genes was significantly altered by ischemia times or storage conditions. The greatest gene expression changes were observed with longer ischemia time and warmer tissue procurement conditions. CONCLUSION: RNA from kidney cancer remains intact for up to 4 hours post surgical resection regardless of storage conditions. Despite excellent RNA preservation, time after resection and procurement conditions significantly influence gene expression profiles. Meticulous attention to preacquisition variables is of paramount importance for accurate tumor profiling.

Repeat partial nephrectomy on the solitary kidney: surgical, functional and oncological outcomes.

PURPOSE: We examined outcomes in patients with recurrent or de novo renal lesions treated with repeat partial nephrectomy on a solitary kidney. MATERIALS AND METHODS: We reviewed the records of patients who underwent nephron sparing surgery at the National Cancer Institute from 1989 to 2008. Patients were included in analysis if they underwent repeat partial nephrectomy on a solitary kidney. Perioperative, functional and oncological outcomes were assessed. Functional outcomes were evaluated using the Modification of Diet in Renal Disease equation for the estimated glomerular filtration rate. Oncological efficacy was examined by the need for subsequent repeat renal surgery and the development of metastatic disease. RESULTS: A total of 25 patients were included in the analysis. A median of 4 tumors were resected. Median estimated blood loss was 2,400 ml and median operative time was 8.5 hours. Perioperative complications occurred in 52% of patients, including 1 death and the loss of 3 renal units. There was a decrease in the estimated glomerular filtration rate at followup visit 1 within 3 months after surgery but at 1-year followup the difference was not significant (p <0.01 and 0.12, respectively). Surgical intervention was recommended in 8 patients (38%) for recurrent or de novo tumors at a median of 36 months. The average metastasis-free survival rate in the cohort was 95% at 57 months (median 50, range 3 to 196). CONCLUSIONS: Repeat partial nephrectomy in patients with solitary kidney is a high risk alternative. The complication rate is high and there is a modest decrease in renal function but most patients remain free of dialysis with acceptable oncological outcomes at intermediate followup.

Validation of volume and mass assessments for human fetal heart imaging by 4-dimensional spatiotemporal image correlation echocardiography: in vitro balloon model experiments.

OBJECTIVE: This study was designed to validate a slow-sweep real-time 4-dimensional (4D) spatiotemporal image correlation method for producing quantitatively accurate dynamic fetal heart images using an in vitro pulsatile balloon model and apparatus. METHODS: To model fetal heart chambers, asymmetric double-walled finger stalls (tips of surgical latex gloves) were used and attached to a laboratory-designed circuit that allowed calibrated changes in the inner balloon volume as well as an intermediate gel mass interposed between the 2 layers. The water-submerged model was attached to a small-volume pulsatile pump to produce phasic changes in volume within the inner balloon at a fixed rate. A sonography system with 4D spatiotemporal image correlation (STIC) capabilities was used for 3-dimensional (3D) and 4D data acquisition. Volume data were analyzed by customized radial summation techniques with 4D data analysis software and compared with known volumes and masses. RESULTS: Fifty-six individual volumes ranging from 2.5 to 10 mL were analyzed. Volume and mass measurements with 4D STIC were highly correlated (R2 > 0.90). The mean percentage error was better (<6%) for volumes exceeding 4 mL and was as low as 0.3% for 6-mL estimations. Measurements in the diastolic phase were the most accurate, followed by mass estimations equivalent to chamber walls. There was a wider range of percentage error in the lowest volumes tested (2.5 mL), which might have arisen from difficulties in spatial resolution or distortions from within the model apparatus itself. Resolution limitations of 4D technology in combination with extremely small volume targets may explain higher error rates at these small volumes. CONCLUSIONS: Four-dimensional STIC is an acceptably accurate method for volume and mass estimations in the ranges comparable with mid- and late-gestation fetal hearts. It is particularly accurate for diastolic estimations, for chamber wall mass measurements, and at volumes of greater than 2.5 mL. This study validates use of 4D STIC technology to overcome the limitations of nongated 3D technology for phasic and quantitative assessments in fetal echocardiography.

Fetal ventricular mass determination on three-dimensional echocardiography: studies in normal fetuses and validation experiments.

BACKGROUND: Estimation of ventricular volume and mass is important for baseline and serial evaluation of fetuses with normal or abnormal hearts. Direct measurement of chamber wall volumes and mass can be made without geometric assumptions by 3D fetal echocardiography. Our goals were to determine the feasibility of using fast nongated 3D echocardiography for fetal volumetric and mass assessments, to validate the accuracy of the ultrasound system and the measurement technique, and if satisfactory, to develop normal values for fetal ventricular mass during the second and third trimesters. METHODS AND RESULTS: This was a prospective outpatient study of 90 consecutive normal pregnancies during routine obstetric services at Oregon Health & Science University (Portland). Optimized 3D volumes of the fetal thorax and cardiac chambers were rapidly acquired and later analyzed for right and left ventricular mass by radial summation technique from manual epicardial and endocardial traces. Experiments to validate the ultrasound system and measurement technique were performed with modified small balloon models and in vivo and ex vivo small animal experiments. Our study established the feasibility of fetal ventricular mass measurements with 3D ultrasound technology and developed normal values for right and left ventricular mass from 15 weeks' gestation to term. CONCLUSIONS: Nongated fast 3D fetal echocardiography is an acceptable modality for determination of cardiac chamber wall volume and mass with good accuracy and acceptable interobserver variability. The method should be especially valuable as an objective serial measurement in clinical fetal studies with structurally or functionally abnormal hearts.