Evolving Management of Breast Cancer in the Era of Predictive Biomarkers and Precision Medicine.

Breast cancer is the most common cancer among women in the world as well as in the United States. Molecular and histological differentiation have helped clinicians optimize treatments with various therapeutics, including hormonal therapy, chemotherapy, immunotherapy, and radiation therapy. Recently, immunotherapy has become the standard of care in locally advanced triple-negative breast cancer and an option across molecular subtypes for tumors with a high tumor mutation burden. Despite the advancements in personalized medicine directing the management of localized and advanced breast cancers, the emergence of resistance to these therapies is the leading cause of death among breast cancer patients. Therefore, there is a critical need to identify and validate predictive biomarkers to direct treatment selection, identify potential responders, and detect emerging resistance to standard therapies. Areas of active scientific and clinical research include novel personalized and predictive biomarkers incorporating tumor microenvironment, tumor immune profiling, molecular characterization, and histopathological differentiation to predict response and the potential emergence of resistance.

Downregulation of homeobox B8 in attenuating non-small cell lung cancer cell migration and invasion though the epithelial-mesenchymal transition pathway.

Background: Homeobox (HOX) family genes have been identified as regulators of cancer development. No research exists concerning the mechanisms underlying homeobox B8 (HOXB8) activity in non-small cell lung cancer (NSCLC). In this study, we investigated expression and biological function in NSCLC to determine whether it is an important marker of patient prognosis. Methods: HOXB8 expression in NSCLC tissues was investigated using immunohistochemistry (IHC) and Western blot assays. In addition, HOXB8 was knocked down in NSCLC cells to assess its biological functions in this context. The invasive and migratory potential of cells was evaluated by using Transwell (BD, Franklin Lakes, NJ, USA) inserts with 8-µm pores. Furthermore, Western blotting was used to explore whether HOXB8 can influence epithelial-mesenchymal transition (EMT). Results: HOXB8 was expressed at high levels in NSCLC tissues and cell lines compared with adjacent normal tissues. Patients with high HOXB8 expression had shorter survival time and worse prognosis. HOXB8 expression was associated with pathological grading, tumor size, and lymph node metastasis. HOXB8 was prognostic in patients with NSCLC. After knockdown of HOXB8 via small interfering RNA, the proliferation, migration and invasion ability of the cells were significantly reduced compared with the control group. Moreover, EMT was inhibited by the downregulation of HOXB8 expression, as the expressions of E-cadherin was upregulated and that of the N-cadherin, vimentin, matrix metalloproteinase 2 (MMP2), and twist were downregulated. HOXB8 is a member of the ANTP homeobox family and encodes a nuclear protein with a homeobox DNA-binding domain. It is included in a cluster of homeobox B genes located on chromosome 17. The encoded protein functions as a sequence-specific transcription factor that is involved in development. Conclusions: HOXB8 is highly expressed in NSCLC and may predict prognosis of patients with this type of cancer. Furthermore, HOXB8 may promote NSCLC progression through the regulation of the EMT process.

Rare immune-related adverse events in a patient with metastatic melanoma: a case report highlighting sarcoidosis-like reactions triggered by immune-checkpoint inhibitors.

Pembrolizumab and ipilimumab/nivolumab (ipi/nivo) combination are FDA-approved immune checkpoint inhibitor (ICI) therapies for metastatic melanoma. ICIs could result in various inflammation responses known as immune-related adverse events (IRAEs). We report a patient with metastatic melanoma who developed multiple IRAEs including sarcoidosis-like reaction (SLR), diabetic ketoacidosis (DKA), and worsening hypothyroidism on ICIs. A 71-year-old man with stage IIIC melanoma and lymph node metastasis began adjuvant therapy with pembrolizumab in May 2021. A surveillance positron emission tomography-computed tomography (PET-CT) scan four months later showed diffuse nodal uptake indicating potential metastases although the patient remained asymptomatic. His treatment was temporarily switched to ipi/nivo before biopsy was obtained for definitive diagnosis, which revealed non-caseating granulomas consistent with SLR. After resuming pembrolizumab, he developed DKA and worsening hypothyroidism in November 2021, both of which were attributed to IRAEs. His surveillance PET scan in March 2022 again revealed new hypermetabolic activity in several bones, subcutaneous tissue, and the left inguinal lymph node. Left inguinal node biopsy showed disease recurrence, while biopsies of hypermetabolic subcutaneous nodules and bone demonstrated non-caseating granulomas. Our case described a patient on ICIs who developed several IRAEs. SLR is often asymptomatic but remains a diagnostic challenge due to its indistinguishable appearance on imaging studies compared to metastasis. Better understanding of IRAEs and improved surveillance strategies are needed for optimal patient outcomes.

Overexpression of MRPL19 in predicting poor prognosis and promoting the development of lung adenocarcinoma.

Background: Mitochondrial ribosomal protein L19 (MRPL19) is a member of the mitochondrial ribosomal protein (MRP) family. MRPs have a role in the progression of many cancers. However, the role of MRPL19 in lung adenocarcinoma (LUAD) is yet unknown. Methods: The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets, real-time polymerase chain reaction, and immunohistochemistry (IHC) were used to assess MRPL19 expression and clinical relevance. Gene Expression Profiling Interactive Analysis (GEPIA) and the online Kaplan-Meier (KM) Plotter database were used to determine the prognostic significance. Through use of LinkedOmics, genes that were coexpressed with MRPL19 and its regulators were identified. The biological roles of MRPL19 were investigated through R-implemented packages and RNA interference. The Tumor Immune Estimation Resource (TIMER) was employed to assess the connection between MRPL19 expression and infiltrated immune cells in LUAD. Results: MRPL19 expression in LUAD was upregulated and was correlated with lymph node metastasis, differentiation level, and tumor status. MRPL19 was prognostic and associated with poor prognosis. Functional network analysis revealed that MRPL19 may be associated with the cell cycle, cell adhesion molecules, spliceosome, and T-helper cell differentiation and was regulated by several microRNA and the E2F family. The gene set enrichment analysis (GSEA) and protein-protein interaction (PPI) network indicated that MRPL19 was correlated with cancer proliferation signaling pathways. The immune infiltration analysis revealed a correlation between MRPL19 expression and the extent of B cells, CD4+ T cells, and dendritic cells' infiltration in LUAD. Additionally, MRPL19 knockdown in LUAD cells substantially reduced cell growth, migration, and invasion of malignant cells. Conclusions: The poor prognosis and immunological infiltration in LUAD were significantly associated with MRPL19, which may have pro-oncogenic effects on the disease.

Complete response of a large basosquamous carcinoma following treatment with cemiplimab and vismodegib.

The anti-PD-1 antibody cemiplimab has demonstrated effectiveness in the setting of locally advanced basal cell carcinoma (BCC) and squamous cell carcinoma. We describe a case of a large, locally invasive basosquamous carcinoma, an aggressive type of BCC, invading the left sternocleidomastoid muscle with near compression of the left internal jugular vein producing a severe anaemia secondary to ulceration and chronic blood loss. The patient was initially started on vismodegib monotherapy but failed to respond. He was then started on cemiplimab in addition to vismodegib. Improvement was noted after one cycle. After 21 cycles of cemiplimab, the left shoulder ulcerated lesion was completely re-epithelialised. He remains in complete remission after 31 cycles of cemiplimab in addition to vismodegib.

Does denosumab offer survival benefits? -Our experience with denosumab in metastatic non-small cell lung cancer patients treated with immune-checkpoint inhibitors.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of non-small-cell lung cancer (NSCLC). Denosumab is a humanized monoclonal antibody to RANK ligand used to prevent skeletal-related events of bone metastases in solid tumors. We are reporting the clinical outcomes in our NSCLC patients who received RANKL inhibitor in combination with ICIs. METHODS: This observational study used retrospective data from a tertiary cancer center from 2015-2020. Stage IV non-small cell lung cancer patients who received denosumab within 30 days of ICIs (pembrolizumab, nivolumab, atezolizumab, ipilimumab) were included. Kaplan-Meier curves were obtained for survival analysis. RESULTS: We identified 69 patients and all had skeletal metastases, and 37.7% had brain metastases. Median OS was 6.3 months and median PFS was 2.8 months, with overall response rate (ORR) of 18.8% and disease control rate (DCR) of 40.6%. Median OS in patients with concomitant denosumab and ICIs more than 3 months was 11.5 months, comparing to 3.6 months in patients with <3 months of concomitant therapy (P=0.0005). OS and PFS did not differ with respect to brain metastases or number of skeletal metastases. However, the duration of ICIs and denosumab overlap was associated with improved OS and PFS. Among the 18.8% of patients who achieved complete response (CR) and partial response (PR), six-month survival rate was 100% and one-year survival rate was 69.2%. Most of the patients tolerated denosumab well, and hypocalcemia was the most commonly reported side effect. CONCLUSIONS: Patients receiving combination therapy did not perform poorly comparing to published studies despite of poor prognostic features such as brain metastases and numerous skeletal metastases. Although we did notice potential benefit of the longer duration of concomitant use of ICI and denosumab, future prospective clinical trials are needed to evaluate the synergistic effect of RANKL inhibitors/ICI and if duration of RANKL inhibitors matters.

Ipilimumab and nivolumab induced immune-related adverse events in metastatic mucosal melanoma.

Mucosal melanoma is a rare subtype of melanoma and represents a unique diagnosis and treatment challenge. Immune-checkpoint inhibitors (ICIs) have revolutionised metastatic melanoma treatment, and one of the leading regimens is the combination of ipilimumab (anti-cytotoxic T lymphocyte-associated antigen 4: CTLA4) and nivolumab (anti-programmed cell death protein 1: PD1). We report a case of a patient with metastatic mucosal melanoma treated with ipilimumab and nivolumab who developed multiple immune-related adverse events (irAEs) including uveitis, type I diabetes complicated by diabetic ketoacidosis, destructive thyroiditis, hepatitis and vitiligo. Endocrinopathies including type 1 diabetes and hypothyroidism were treated with insulin and levothyroxine. Hepatitis was responsive to steroids. She had sustained complete response 12 months after discontinuation of the combination therapy. With the wide usage of ICIs in multiple types of malignancies, it is important for general practioners to recognise common and serious irAEs due to ICIs.

Neoadjuvant programmed cell death protein 1 inhibitors combined with chemotherapy in resectable non-small cell lung cancer: an open-label, multicenter, single-arm study.

BACKGROUND: Neoadjuvant therapy has significantly improved the 5-year overall survival (OS) of patients with resectable non-small cell lung cancer (NSCLC). The CheckMate 159 trial showed that neoadjuvant therapy with a single-drug programmed cell death protein 1 (PD-1) inhibitor (nivolumab) achieved major pathological response (MPR) and pathological complete response (pCR) in 45% and 15%of participants, respectively. We conducted an open-label single-arm study to evaluate the safety and efficacy of neoadjuvant PD-1 inhibitors in combination with chemotherapy in the treatment of resectable NSCLC. METHODS: This study was conducted in a total of 2 hospitals in the Chinese cities of Xi'an and Chongqing, and included eligible patients over 18 years of age with clinically staged IIA-IIIB NSCLC. All patients were scheduled to receive surgery within 4-6 weeks after neoadjuvant treatment (3-4 cycles) consisting of PD-1 inhibitors combined with a conventional chemotherapy regimen on day 1 of each 21-day cycle. RESULTS: Twenty-three patients, 22 males, and 1 female with just one of them with no smoking habits) were diagnosed with NSCL C in a stage IIA (3 cases), IIB (3 cases), IIIA (8 cases), and IIIB (9cases) and no druggable driver mutations/translocations were addressed to receive neoadjuvant treatment between June 2018 and June 2020. The treatment was well tolerated with just 3 typical immune-related adverse events (hyperthyroidism, hyperglycemia, and rash) recorded. There was a partial response (PR) and stable disease (SD) in 17 (73.9%) and 6 (26.1%) patients, with an overall response rate (ORR) of 73.9% according to the Response Evaluation Criteria in Solid Tumors (RECIST v.1.1). Six of these patients resulted in pCR (30%) while ten of them showed a MPR (50%). Twenty patients underwent surgical resection after treatment, while further 3 refused surgery. Surgical procedure included video-assisted thoracoscopic resection (10 cases), Vinci Robot surgery (4 cases), and thoracotomy in 4 cases while there were secondary compliance-related thoracotomy in two cases. The pathology analysis revealed a R0 in 19 cases (19/20, 95%). CONCLUSIONS: Our results suggest that the neoadjuvant approach with chemotherapy and PD-1 blocking mAbs is safe and active in patients with resectable NSCLC where is associated with a promising high ORR, MPR and pCR.

The association of PD-L1 expression with the efficacy of anti-PD-1/PD-L1 immunotherapy and survival of non-small cell lung cancer patients: a meta-analysis of randomized controlled trials.

BACKGROUND: We conducted a meta-analysis to evaluate the efficacy of anti-programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) monotherapy or immunotherapy combined with chemotherapy and further estimated the value of PD-L1 expression in predicting the response from anti-PD-1/PD-L1 treatments as monotherapy or in combination with chemotherapy. METHODS: Clinical trial data were searched from electronic databases, which evaluated PD-1/PD-L1 inhibitors in non-small cell lung cancer (NSCLC) and correlated with PD-L1 expression levels. RESULTS: Fifteen randomized-controlled trials involving 10,074 patients were identified. Comparing anti-PD-1/PD-L1 monotherapy to chemotherapy, the pooled HR for overall survival (OS) was 0.77 (95% CI: 0.69-0.85, P<0.00001). Subgroup analyses revealed that patients had longer OS at ≥1%, ≥5%, ≥10% and ≥50% PD-L1 expression levels. Patients with higher PD-L1 expression may get increased benefit from PD-1/PD-L1 inhibitors. Moreover, patients with PD-L1 ≥50% had an objective response rate (ORR) improvement from anti-PD-1/PD-L1 therapy (RR =1.87, 95% CI: 1.27-2.75, P=0.001), but no ORR benefits were observed in patients with PD-L1 expression <1% (RR =0.82, 95% CI: 0.56-1.22, P=0.33) or 1-49% (RR =0.80, 95% CI: 0.64-0.98, P=0.03). OS was significantly better in patients receiving second-or-third line treatments (P<0.00001) with PD-L1 ≥1%. The efficacy of PD-1 inhibitors was similar to that of PD-L1 inhibitors, with no significant difference (P=0.63, I2=0%). Furthermore, immunotherapy combined with chemotherapy had better OS (HR =0.64, 95% CI: 0.48-0.84, P=0.001) than chemotherapy alone. Subgroup analyses showed that patients benefited from the combined chemo-IO treatment in the first-line setting regardless of PD-L1 expression level. CONCLUSIONS: PD-L1 expression may be a valuable predictor of the efficacy of anti-PD-1/PD-L1 monotherapy in certain NSCLC patients. However, the combination of chemotherapy plus immunotherapy significantly improved survival regardless of the PD-L1 expression level in the first-line treatment of NSCLC.

A tertiary care cancer center experience with carboplatin and pemetrexed in combination with pembrolizumab in comparison with carboplatin and pemetrexed alone in non-squamous non-small cell lung cancer.

BACKGROUND: Randomized phase II and III studies showed the promising results of the combination of carboplatin/pemetrexed with pembrolizumab in non-squamous non-small cell lung cancer patients. Patients with brain metastases were excluded from the phase II study. After FDA approval, this regimen was adopted early at our institution, including a use in patients with brain metastases. We report real-world use of this regimen in a single medical center. METHODS: This is a retrospective cohort study that includes patients with advanced non-squamous non-small cell lung cancer diagnosed and treated with carboplatin/pemetrexed (Cohort A) or carboplatin/pemetrexed plus pembrolizumab (Cohort B) between January 1st, 2016 till December 15th, 2017. Objective response rate (ORR) was the primary endpoint. Progression-free survival (PFS), disease control rate (DCR) were the secondary endpoints. RESULTS: A total of 54 patients were included (cohort A =37 vs. cohort B =17). ORR was 53.3% in cohort B vs. 40.5% in cohort A (P=0.41). DCR was significantly higher in cohort B (86.7% vs. 54%, P=0.02). PFS was also higher in cohort B (P= 0.009, HR 0.22). Similar proportion of patients had brain metastases in each cohort (A: 32.4% vs. B: 35.3%, P=0.83). ORR was higher in patients with brain metastases from cohort B (B: 80% vs. A: 58.3%, P=0.75). Significantly higher proportion of the patients with brain metastases progressed in cohort A (A: 91.7% vs. B: 33.3%, P=0.009). CONCLUSIONS: The combination of carboplatin and pemetrexed with pembrolizumab showed promising results in a real world setting in patients with NSCLC with and without brain metastases that are in line with the reported results of phase II and III studies. Most significant benefit was observed in preventing progression and achieving the disease control.

Efficacy of metformin in combination with immune checkpoint inhibitors (anti-PD-1/anti-CTLA-4) in metastatic malignant melanoma.

BACKGROUND: Metformin is one of the biguanides commonly used in patients with type II Diabetes Mellitus. Apart from its hypoglycemic properties, metformin also inhibits the cell cycle by restricting protein synthesis and cell proliferation via regulating the LKB1/AMPL pathway. Furthermore, it also enhances the PD-1 blockade through a reduction of tumor hypoxia. Metformin has shown a significant favorable impact on treatment-related outcomes in solid tumors, but these outcomes have not been replicated in the limited clinical studies done on malignant melanoma. Moreover, none of these studies have reported on the efficacy of the combined use of metformin and immune checkpoint inhibitors (ICIs). METHODS: This is a retrospective cohort study that includes patients diagnosed with metastatic malignant melanoma and treated with ipilimumab, nivolumab, and/or pembrolizumab (Cohort A); or ipilimumab, nivolumab, and/or pembrolizumab plus metformin (Cohort B) between January 1st 2011 through December 15th 2017. In this study, patients are stratified based on anti-PD-1 only and anti-CTLA4/anti-PD-1 combination therapies in each cohort. Objective response rate (ORR) is the primary endpoint. Disease control rate (DCR), overall survival (OS) and progression-free survival (PFS) are the secondary endpoints. RESULTS: Cohort A had 33 patients (60%), while cohort B had 22 (40%). Overall patient characteristics were similar between both cohorts. ORR was higher in cohort B (68.2% vs. 54.5%, P = 0.31). The DCR was higher in cohort B as well (77.3% vs. 60.6%, P = 0.19). Median OS (46.7 months vs. 28 months), and median PFS (19.8 months vs. 5 months) were longer in cohort B. However, on univariate and multivariate analyses, none of these differences were statistically significant. The mean number of new metastatic sites which appeared during therapy were significantly higher in cohort A (A:1.51 vs. B:0.59, P = 0.009). CONCLUSION: We have observed favorable treatment-related outcomes (ORR, DCR, median PFS and median OS) in patients who have received metformin in combination with ICIs without reaching significance, probably, due to small sample size. Hence, large prospective clinical trials are required to study the synergistic effect of metformin in combination with ICIs before it can be recommended as routine additive therapy.

Metastatic uveal melanoma showing durable response to anti-CTLA-4 and anti-PD-1 combination therapy after experiencing progression on anti-PD-1 therapy alone.

BACKGROUND: Uveal melanoma accounts for 85% of the ocular melanomas and has an increased risk of hematogenous spread, most commonly to the liver. After curative intent therapy like surgery and radiation, fifty percent of patients present with distant metastasis. Metastatic uveal melanoma (MUM) does not harbor typically targetable mutations, e.g., BRAF as in cutaneous melanoma. As a result, there is no proven therapy for MUM. Various chemotherapy and immunotherapy regimens have been tried and only partial response (PR) is the best that has been achieved in most of the cases. Here, we present a case of MUM treated with combination immune checkpoint therapy (ipilimumab and nivolumab) following the progression with single-agent nivolumab and demonstrating a durable response without recurrence more than 22 months from the last treatment. CASE PRESENTATION: A 72-year-old Caucasian man presented with ciliary body melanoma of the left eye and underwent curative-intent enucleation but six months later developed diffuse hepatic metastases. He initially was treated with nivolumab 3 mg/kg every two weeks for four cycles but restaging scan showed a significant progression of the disease with increasing LDH. With the FDA approval for the combination of nivolumab 1mg/kg with Ipilimumab 3 mg/kg every three weeks for metastatic melanoma, this combination was given for four cycles with continuous rise in LDH to 993 unit/L (110-220 unit/L) until finishing cycle four of the treatment. Three weeks later, maintainence nivolumab 3mg/kg was initiated but two weeks later, he developed grade 4 liver toxicity with ALT 1565 unit/L (0-55 unit/L). A presumptive diagnosis of autoimmune hepatitis was made, nivolumab was stopped and oral prednisone 1mg/kg was started with quick resolution of elevated transaminases. Restaging abdominal MRI one month after the first and last dose of maintenance nivolumab showed PR and continuous shrinkage of the metastatic lesions with no hypermetabolic activity even on PET/CT. He is 22 months' post-treatment and continues to do well without any evidence of active disease. CONCLUSION: Although, limited response has been shown to single agent immune checkpoint inhibitors and chemotherapy, our patient showed durable response with anti-CTLA-4 and anti-PD-1 combination therapy in MUM.

A retrospective analysis of tolerance and outcomes of cutaneous malignant melanoma in patients receiving adjuvant interferon-alpha 2B: a community oncology perspective.

INTRODUCTION: Interferon alpha 2B (IFN-α) therapy in malignant melanoma has improved relapse free survival and overall survival but is considerably toxic and lowers the overall quality of life (QoL) substantially. A significant number of patients do not complete the full duration (one year) of therapy. OBJECTIVE: The aim of this study was to evaluate patients' ability to tolerate IFN-α therapy and to compare our results to reported data in the literature. METHODS: We conducted a retrospective review of patients diagnosed with cutaneous malignant melanoma who received IFN therapy after surgical resection. Patients were divided into two groups: patient who completed therapy (CIT) and those who did not (incomplete therapy, IIT). Duration of therapy was calculated. Reason for discontinuation and experienced side effects were reported. Statistical significance was determined at p &#60; 0.05. RESULTS: A total of 64 patients were included in the review. There were 16 (25%) patients were able to complete therapy. The most common reasons for discontinuing IFN-α therapy was fatigue (81.3%), fever (40.6%), depression (28.1%) and nausea (18.8%). Patients in the CIT group were younger than those in the IIT group (47.4 ± 14.2 vs 57.8 ± 11.9 years, mean ± SD; p = 0.011). There also seemed to be an association that those with the presence of advanced disease may have been more likely to complete therapy (node positive disease at the time of diagnosis, p = 0.07). LIMITATIONS: It is a retrospective study and has to rely on physician notes for the subjective data. For the survival analyses, the median follow-up times for both of the groups were less than 3.5 years. CONCLUSIONS: Younger patients were more likely to complete therapy. There was a trend towards an association between more advanced disease and the completion of therapy. Most common causes of discontinuation of therapy were fatigue, fever, depression, and nausea.

Tumor molecular profiling in the treatment of refractory cancers.

INTRODUCTION: Molecular profiling (MP) has been used as a technique to identify treatment regimens for individual patient's cancer. The results of MP has been used to guide targeted therapy specific to each patient's tumor that resulted in a longer progression free survival (PFS) compared to the last conventional treatment. This study aims to provide further data to delineate the PFS of patients who get treated with targeted therapy based on MP. METHODS: A retrospective chart review was performed. The patients were greater than 18 years of age refractory to at least one standard treatment and enrolled in the study: "A Clinical Data Registry Study of Patients with Advanced Refractory Cancers Electing OncInsights as a Method to Support Physician Choice of Drug Therapy". The location is a West Michigan Hematology-Oncology private practice during the period of 07/2010-02/2013. We considered the molecular profiled treatment regimen a success if the PFS ratio was ≥ 1.3. RESULTS: 18 patients were included in the study. 55% were male and 45% were female with median age of 57.67 +/- 12.02 at the time of diagnosis. 4/18 (22%) patients achieved a PFS ratio >1.3. The patients with a PFS ratio ≥ 1.3 included GIST (imatinib- > sunitinib); angiosarcoma (docetaxel- > sorafenib, pravastatin); thymoma (paclitaxel- > desatinib); and angiosarcoma (gemcitabine- > sunitinib). CONCLUSION: This study demonstrates the potential value of molecular profiling in patients refractory to prior chemotherapeutic agents in a community setting. Continued work on rapid implementation of molecular profiling earlier in the care of oncology patients continues to be a future goal.

Modification of Technique for Suprapubic Catheter Placement After Robot-assisted Radical Prostatectomy Reduces Catheter-associated Complications.

OBJECTIVE: To compare the outcomes of patients undergoing robot-assisted radical prostatectomy (RARP) with urinary drainage using a modified technique for suprapubic catheter (SPC) placement with those undergoing a previously described technique for SPC placement and those with urethral catheter (UC) alone. MATERIALS AND METHODS: We reviewed the records of 225 consecutive patients who underwent RARP by a single surgeon. The most recent patients were contacted via a telephone survey with 86 responses (69%) received. RESULTS: After RARP, 174 patients had only UC placement (77%) and 51 had an SPC placed (23%). Twelve patients had SPC placement with a 4-mL balloon (SPC-4), with catheter-related complications occurring in four patients (33%). The technique was modified to use SPC with a 10-mL balloon (SPC-10). Only 2 of 39 SPC-10 patients (5%) had catheter-related complications (P = .03 vs SPC-4). Continence rates at 6 weeks were 83% and 82% for UC and SPC, respectively. Based on postoperative survey results using a 10-point scale, overall experience with RARP was rated 8.9 ± 1.7 and 8.7 ± 2.3 for UC and SPC, respectively (P = .63). Mean catheter bother was rated 5.1 ± 3.0 and 4.6 ± 2.9 for UC and SPC, respectively (P = .45). CONCLUSION: SPC provides a safe option for patients who would prefer not to have UC following RARP, with equivalent perioperative outcomes. Modification of the published technique to place a standard 16F catheter results in fewer catheter-related complications.

Utility of Lower Extremity Doppler in Patients with Lower Extremity Cellulitis: A Need to Change the Practice?

OBJECTIVES: Cellulitis and deep vein thrombosis (DVT) in the lower extremities (LE) often have similar presentations: erythema, swelling, and calf tenderness. The overlap of these symptoms often results in physicians ordering unnecessary LE Doppler ultrasounds in patients with LE cellulitis. This practice leads to subjecting patients to unwarranted procedures and results in increased healthcare costs. We aimed to determine the percentage of Doppler ultrasounds performed in patients admitted with LE cellulitis and the prevalence of DVT in that population. METHODS: A retrospective chart review was performed of the patients admitted January 1, 2009 to June 30, 2013 who had a diagnosis of LE cellulitis. The number of Doppler ultrasounds performed and the presence of DVT was recorded. Patients were divided into groups of Doppler ultrasounds with no DVT and Doppler ultrasounds that were positive for DVT to compare the risk factors. RESULTS: There were 624 patients identified using the International Classification of Diseases, 9th Revision code for LE cellulitis at the time of admission. Slightly more than half of the subjects were men (315/624) and the average age was 61.4 ± 18.8 years (mean ± standard deviation). There were 417 (66.8%) patients who underwent Doppler ultrasound. Only 25 (5.9%) patients had DVT. Multivariate analysis showed that prior cerebrovascular accident, calf swelling, and history of thromboembolism were statistically significant predictors for DVT (P < 0.05). CONCLUSIONS: A concurrent incidence of DVT and LE cellulitis is rare. In the absence of known risk factors of DVT, the yield of LE Doppler is low and Doppler ultrasound is not required as a part of a standard admission evaluation.

Spontaneous Regression of Refractory Diffuse Large B-Cell Lymphoma with Improvement in Immune Status with ART in a Patient with HIV: A Case Report and Literature Review.

BACKGROUND: Diffuse large B-cell lymphoma accounts for the large majority of AIDS-related non-Hodgkin lymphoma. Traditionally, this lymphoma has been treated with CHOP-like regimens with the recent addition of rituximab. We report a unique case where an HIV-infected patient with diffuse large B-cell lymphoma had complete regression of the lymphoma with continued antiretroviral therapy (ART) after chemotherapy was stopped. CASE REPORT: A 55-year-old man who presented with fatigue and weight loss had initial CT findings of bilateral renal masses during his workup. Biopsy revealed diffuse large B-cell lymphoma and subsequently he was also diagnosed with HIV. He completed 6 cycles of CHOP-like (4 cycles of EPOCH-R and 2 cycles of R-CHOP) first-line therapy with significant dose delays and dose reductions due to severe adverse effects. Chemotherapy was stopped due to physical deconditioning and intolerable adverse effects. He had a FDG-PET/CT showing progression of his disease 8 weeks after completing chemotherapy. He was maintained only on ART after finishing 6 cycles of chemotherapy. With this therapy alone and with improvement in his immune status, his lymphoma regressed completely. CONCLUSIONS: There are very few reported cases in which lymphoma has regressed with treatment of HIV alone, as is regression of diffuse large B-cell lymphoma. This case emphasizes that ART can lead to immune reconstitution of HIV-infected patients and can establish the anti-tumor effect, causing regression of the lymphoma.