Comparative outcomes of partial versus total penectomy for penile carcinoma: A retrospective cohort study on demographics and postoperative complications.

When feasible from an oncologic standpoint, partial penectomy (PP) is often preferred to total penectomy (TP) for penile cancer treatment, for the preservation of functional urinary outcomes. However, to date, there has not been a direct comparison of perioperative outcomes between PP and TP. Comparing treatments for penile cancer has proven difficult due to the rarity of penile cancer in the United States. We aimed to report differences in pre-operative risk factors, intra-operative outcomes, and postoperative outcomes between TP and PP for penile cancer. Using the National Surgical Quality Improvement Program database, we conducted a retrospective cohort review of penile cancer patients enlisted in the database between the years 2006-2016 using the International Classification of Diseases clinical modification 9th revision codes. A total of 260 patients, 67 TP and 193 PP patients, were included. PP patients were less likely to be transferred patients (p = 0.002), diabetic (p = 0.026), and were more likely to have preoperative laboratory values within normal limits. PP patients also had shorter lengths of stay in the hospital (p < 0.001) and operating time (p < 0.001). Significant differences were also found for inpatient stay (p < 0.001), 30-day post-surgery complications (p < 0.001), deep incisional surgical site infection (SSI) (p = 0.017), wound disruption (p = 0.017), intraoperative or postoperative transfusion (p = 0.029), and sepsis (p < 0.005). Finally, PP patients required fewer concurrent surgical procedures (p < 0.001). Demographic differences between PP and TP patients may reflect patients presenting with more advanced oncologic disease. PP is associated with fewer postoperative complications, shorter surgeries, shorter hospital stays, fewer concurrent surgical procedures, and comorbid conditions compared to TP. A gap remains in the reported data pertaining to postoperative sexual function and erectile outcomes for PP at a national level.

Seasonal shifts in gut microbiota and cold tolerance metrics in a northern population of Reticulitermes flavipes (Blattodea: Rhinotermitidae).

Eastern subterranean termites, Reticulitermes flavipes (Kollar), are widely distributed across North America where they are exposed to a broad range of environmental conditions. However, mechanisms for overwintering are not well understood. Wisconsin is a unique location to study mechanisms of cold tolerance as it represents the northern boundary for persistent R. flavipes populations. In this study, we evaluated seasonal shifts in cold tolerance using critical thermal minimum (CTmin) and supercooling point (SCP) and examined how these measurements correlate to changes in the microbial community of the termite gut. Results showed seasonal acclimatization to cold, which is consistent with the use of behavioral freeze-avoidant mechanisms. However, these insects also demonstrated an increased susceptibility to freezing later in the season, which may be tied to changes in gut microbiota. Our results found shifts in the composition of the gut microbiome in R. flavipes between mid- to late summer and early to late fall. These differences may be suggestive of a change in metabolism to adjust to a period of reduced feeding and increased metabolic stress during overwintering. Specifically, results showed an increased abundance of Methanobrevibacter sp. (Euryarchaeota) associated with cold, which may be indicative of a metabolic shift from acetogenesis to methanogenesis associated with overwintering. Further work is needed focusing on specific contributions of certain gut microbes, particularly their role in metabolic adaptability and in providing protection from oxidative stress associated with changes in environmental conditions.

Ejaculatory and erectile function outcomes following holmium laser enucleation of the prostate.

PURPOSE: Holmium laser enucleation of the prostate (HoLEP) is a surgical treatment option for benign prostatic hyperplasia (BPH). Many men develop retrograde ejaculation postprocedure, but there is conflicting evidence regarding sexual function outcomes post-HoLEP. We sought to examine significant variations in patient-reported erectile and ejaculatory function within 12 months post-HoLEP. MATERIALS AND METHODS: We conducted a retrospective study for patients who underwent HoLEP between Nov 2018 and Feb 2022. Of the reviewed patients, 277 patients met inclusion criteria and completed pre and postoperative questionnaires, which included the Male Sexual Health Questionnaire- Ejaculatory Dysfunction (MSHQ-EJD) and the International Index of Erectile Function/Sexual Health Inventory for Men (IIEF-5/SHIM). Surveys were provided to patients up to 12 months postprocedure. Demographics and comorbidities associated with sexual dysfunction were collected. Responses to each question were analyzed to detect sub-categorical variations in sexual function as the secondary objective. Data was analyzed by using a linear mixed model. RESULTS: There was a significant decline in total scores for the MSHQ-EJD (8.70 pre-HoLEP vs. 6.58 post HoLEP, p ≤ 0.001) including a significant decline (p < 0.005) in questions 1-3 which assess ejaculatory ability, strength, and volume. There was not a significant decline in question 4 which assesses bother (2.552 pre-HoLEP vs. 3.119 post-HoLEP, p = 0.526). There was not a significant decline in the IIEF-5/SHIM postoperatively (11.51 pre-HoLEP vs. 13.327 post-HoLEP, p = 0.498). CONCLUSIONS: Patients undergoing HoLEP do not experience a decline in erectile function. Patients do experience a decline in ejaculatory function but did not find this bothersome.

Case report: Successful induction of buprenorphine in medically complex patients concurrently on opioids: a case series at a tertiary care center.

Effective pain management is essential for optimal surgical outcomes; however, it can be challenging in patients with a history of opioid use disorder (OUD). Buprenorphine, a partial opioid agonist, is a valuable treatment option for patients with OUD. Initiating buprenorphine treatment in patients concurrently taking opioids can be complex due to potential adverse outcomes like precipitated withdrawal. Evolving guidelines suggest there are benefits to continuing buprenorphine for surgical patients throughout the perioperative period, however situations do arise when buprenorphine has been discontinued. Typically, in this scenario patients would be restarted on buprenorphine after they have fully recovered from post-surgical pain and no longer require opioids for pain control. Unfortunately, holding MOUD may expose the patient to risks such as opioid induced respiratory depression or addiction relapse. In this case series, we discuss a novel method to restart buprenorphine in small incremental doses, known as micro-dosing, while the patient is still taking opioids for pain. We will present two complex clinical cases when this method was used successfully at a tertiary care hospital system.

Evaluation of Renal Function Recovery After Holmium Laser Enucleation of the Prostate in Patients with Chronic Kidney Disease.

Introduction: Holmium laser enucleation of the prostate (HoLEP) has become a new surgical gold standard treatment for benign prostatic hyperplasia (BPH). It is known that untreated BPH can lead to bladder outlet obstruction (BOO). A positive correlation exists between BOO and chronic kidney disease (CKD), but stability or recovery of renal function after HoLEP remains unknown. We sought to describe changes in renal function after HoLEP in men with CKD. Methods: A retrospective study was conducted of patients who underwent HoLEP with glomerular filtration rates (GFRs) <60, CKD stages III to V. Pre- and postoperative GFRs were selected within 3 months before the operation and within 1 year postoperatively. The presence of an indwelling catheter, preoperative hydronephrosis, history of kidney stones, and prostate size were also reviewed. Data were analyzed in accordance with preoperative CKD stage. Results: Of the reviewed patients, 138 met inclusion criteria with CKD stages III to V. Each CKD group was without significant postoperative complications. There was a significant increase between pre- and postoperative GFR for patients in CKD stages III (n = 116) and IV (n = 17) (p < 0.0001 and p = 0.010, respectively). The mean increase between pre- and postoperative GFR for the CKD stages III and IV patients were 6.4 and 6.49, respectively. There was no correlation between presence of preoperative hydronephrosis, history of kidney stones, catheter dependency, nor prostate size on change in postoperative GFR (p > 0.05). Conclusion: These findings suggest that patients in CKD stages III or IV undergoing HoLEP experience an increase in GFR. It is noteworthy that there appears to be no decline in renal function postoperatively in any group. HoLEP represents an excellent surgical option for patients with preoperative CKD and may prevent further renal decline.

Adverse Events in Infants Less Than 6 Months of Age After Ambulatory Surgery and Diagnostic Imaging Requiring Anesthesia.

AAP guidelines recommend infants less than 6 months of age are monitored for at least 2 hours following surgery. This retrospective study evaluated if adherence to the 2-hour monitoring guideline decreased the risk of adverse events associated with ambulatory procedures in infants younger than 6 months. Methods: We queried the hospital's electronic medical record to identify patients younger than 6 months of age who received anesthetic care from January 2015 to March 2020. Demographic data, intraoperative adverse events, and returns to the emergency department (ED) or urgent care within 7 days were captured for each patient. We calculated the number and frequency for categorical data and median and interquartile range (IQR) for continuous data. Chi-square or Fisher's exact test were used to compare patients who experienced an adverse event to those that did not. Results: One thousand one hundred seventy-seven patients who had 1,261 unique anesthetic encounters were analyzed. Forty-four adverse events were identified, 20 (1.6%) before discharge, including 3 unplanned admissions, and 24 (1.9%) returns to the ED/UC within 7 days postoperatively. We did not observe differences in postoperative recovery time in patients who experienced an adverse event and those who did not (88 min vs. 77 min, respectively, P = 0.078). None of the ED/UC returns would have been avoided by a longer PACU stay. Conclusions: With the appropriate patient selection, once physiological discharge readiness is met, adherence to a strict 2-hour time-based discharge criteria does not increase safety for infants younger than 6 months of age after ambulatory procedures.

Surgical Complications in the Management of Benign Prostatic Hyperplasia Treatment.

PURPOSE OF REVIEW: There are a variety of treatment options for men with symptomatic benign prostatic hyperplasia (BPH); transurethral resection of the prostate (TURP) remains the gold standard surgical treatment. The field continues to evolve with the introduction of new energy and laser technologies, increasing adoption of enucleation techniques, in addition to the advent of minimally invasive surgical technologies (MIST) that enable office-based treatments. The choice in surgical management has become very nuanced depending on a variety of patient and anatomic factors. There continues to be high success rates for surgical treatment of BPH; however, the risk profiles vary across the various surgical treatments. We sought to evaluate contemporary series and summarize the experience of complications associated with BPH treatment and management of these complications. RECENT FINDINGS: A comprehensive literature review was performed, and identified 79 manuscripts, published between 2005 and 2021 characterizing the diagnosis and management of complications following BPH surgery. Commonly cited issues included bleeding, ureteral orifice injury, bladder neck injury, rectal injury, TURP syndrome, bladder neck contractures, urethral stricture disease, refractory OAB symptoms, and complications unique to new modalities of treatment. The practicing urologist has multiple surgical options to choose from in treating patients with symptomatic BPH. The surgical management of BPH is generally well tolerated with high objective success rates that allow for significant improvement in urinary quality of life. It is critical to understand the potential complications associated with these various treatment options, which will enable trainees and practicing urologists to better counsel patients and manage these potential complications.

Breast Cancers Are Immunogenic: Immunologic Analyses and a Phase II Pilot Clinical Trial Using Mutation-Reactive Autologous Lymphocytes.

PURPOSE: Metastatic breast cancer (mBrCa) is most often an incurable disease with only modest responses to available immunotherapies. This study investigates the immunogenicity of somatic mutations in breast cancer and explores the therapeutic efficacy in a pilot trial of mutation-reactive tumor-infiltrating lymphocytes (TILs) in patients with metastatic disease. PATIENTS AND METHODS: Forty-two patients with mBrCa refractory to previous lines of treatment underwent surgical resection of a metastatic lesion(s), isolation of TIL cultures, identification of exomic nonsynonymous tumor mutations, and immunologic screening for neoantigen reactivity. Clinically eligible patients with appropriate reactivity were enrolled into one cohort of an ongoing phase II pilot trial of adoptive cell transfer of selected neoantigen-reactive TIL, with a short course of pembrolizumab (ClinicalTrials.gov identifier: NCT01174121). RESULTS: TILs were isolated and grown in culture from the resected lesions of all 42 patients with mBrCa, and a median number of 112 (range: 6-563) nonsynonymous mutations per patient were identified. Twenty-eight of 42 (67%) patients contained TIL that recognized at least one immunogenic somatic mutation (median: 3 neoantigens per patient, range: 1-11), and 13 patients demonstrated robust reactivity appropriate for adoptive transfer. Eight patients remained clinically eligible for treatment, and six patients were enrolled on a protocol of adoptive cell transfer of enriched neoantigen-specific TIL, in combination with pembrolizumab (≤ 4 doses). Objective tumor regression was noted in three patients, including one complete response (now ongoing over 5.5 years) and two partial responses (6 and 10 months). CONCLUSION: Most patients with breast cancer generated a natural immune response targeting the expressed products of their cancer mutations. Adoptive transfer of TIL is a highly personalized experimental option for patients with mBrCa shown to be capable of mediating objective responses in this pilot trial and deserves further study.

The Use of Social Media for Medical Education Within Urology: a Journey Still in Progress.

PURPOSE OF REVIEW: This paper aims to discuss the growth of social media in urology over time, focusing on medical education platforms and best practices. RECENT FINDINGS: Social medial has facilitated physician and patient knowledge acquisition, conference participation, and mentorship. Several social media best practice statements are available, including from the American Urologic Association (AUA) and The European Association of Urology (EAU), to help ensure responsible use. The role of social media in urologic medical education has been amplified by the COVID-19 pandemic. Its utilization by urologists has been expanding, making it very valuable for physician and patient education. Future research should focus on ways to maximize these medical education efforts, minimize risks, and increase guideline awareness among users.

Impact of Prior Treatment on the Efficacy of Adoptive Transfer of Tumor-Infiltrating Lymphocytes in Patients with Metastatic Melanoma.

PURPOSE: Adoptive cell transfer (ACT) of autologous tumor-infiltrating lymphocytes (TIL) can mediate durable responses in patients with metastatic melanoma. This retrospective analysis provides long-term follow-up and describes the effect of prior therapy on outcomes after ACT-TIL. PATIENTS AND METHODS: Patients with metastatic melanoma underwent surgical resection of a tumor for generation of TILs and were treated with a lymphodepleting preparative regimen followed by adoptive transfer of TILs and intravenous IL2. Clinical characteristics of enrolled patients and treatment characteristics of TIL infusion products over two decades of ACT were analyzed to identify predictors of objective response. RESULTS: Adoptive transfer of TILs mediated an objective response rate of 56% (108/192) and median melanoma-specific survival of 28.5 months in patients naïve to anti-programmed cell death-1 (PD-1) therapy compared with 24% (8/34) and 11.6 months in patients refractory to anti-PD-1 (aPD-1). Among patients with BRAF V600E/K-mutated disease, prior treatment with targeted molecular therapy was also associated with a decreased response rate (21% vs. 60%) and decreased survival (9.3 vs. 50.7 months) when compared with those patients naïve to targeted therapy. With a median potential follow-up of 89 months, 46 of 48 complete responders in the aPD-1-naïve cohort have ongoing responses after a single treatment and 10-year melanoma-specific survival of 96%. CONCLUSIONS: Patients previously treated with PD-1 or MAPK inhibition are significantly less likely to develop durable objective responses to ACT-TIL. While ACT-TIL is currently being investigated for treatment-refractory patients, it should also be considered as an initial treatment option for eligible patients with metastatic melanoma. See related commentary by Sznol, p. 5156.

Prostate Cancer Lesions by Zone and Race: Does Multiparametric MRI Demonstrate Racial Difference in Prostate Cancer Lesions for African American Men?

African American (AA) men have increased risk of prostate cancer diagnosis and mortality, but the cause remains unknown. MRI fusion improves diagnosis of localized prostate cancer, particularly in anterior lesions; however, cost and access are limited in a community practice setting. By utilizing a diverse cohort of veterans with equal access to care in a single payer system, we describe prostate cancer detection. We queried a prospectively maintained institutional review board-approved database of men undergoing prostate biopsy for untreated prostate cancer. We included all consecutive patients from October 2017 to February 2020. Statistical analysis including Kaplan-Meier Curves, Fisher's exact test, and Forest plot was performed. From 246 consecutive patients, 166 were AA and 80 were non-AA. There were similar distributions of PSA, PSAD, and number of targetable lesions between the AA and non-AA cohort (p > 0.05 for all). We found no difference in location on MRI between race groups. There was similar cancer detection, focusing on anterior lesions and rate of positive Gleason grade (≥GG1) and clinically significant (≥GG2) cancer between cohorts. In a predominant AA cohort of veterans, we found similar distribution of location for MRI-targeted lesions, along with rates of tumor detection and aggressiveness of disease. In this single payer veteran population, we did not identify specific biologic differences inherent to tumor detection between AA and non-AA patients.

Changing Trends in Management Following Artificial Urinary Sphincter Surgery for Male Stress Urinary Incontinence: An Analysis of the National Surgical Quality Improvement Program Database.

OBJECTIVE: To characterize the safety and practice patterns of artificial urinary sphincter (AUS) placement on a population level. Increasingly AUS implantation has shifted to be an outpatient surgery; however, there is a lack of large-scale research evaluating factors associated with early (≤ 24 hours) versus late (>24 hours) discharges and complications in men following AUS placement. We utilized the National Surgical Quality Improvement Program (NSQIP) database to identify and compare factors and outcomes associated with each approach. METHODS: NSQIP database was queried for men undergoing AUS placement between 2007 and 2016. Patients were classified as either early discharge (ED ≤ 24 hours) and late discharge (LD > 24 hours). Baseline demographics, operating time, and complications were compared between the 2 groups. Multivariate logistic regression evaluated factors associated with discharge timing and 30-day complications. RESULTS: A total of 1176 patients were identified and were classified as ED in 232 and LD in 944 patients. Operative time was shorter in ED (83 minutes) compared to LD (95 minutes, P < .001). Hypertension was more prevalent among LD patients (60.3% vs 69.1% for ED and LD respectively, P < .001). The 30-day complication rate was similar in both groups (ED: 4.3% vs LD: 3.4%, P = .498). Multivariable analysis revealed that surgery after 2012 was associated with ED (OR = 3.66, P < .001). CONCLUSION: At the national level, there are no differences in postoperative morbidity between early and late discharges. There is a trend toward more ED, specifically after 2012. A prospective study on the feasibility and safety of outpatient AUS is needed.

Current Perspectives on Complications of Surgical Treatments for Male Stress Urinary Incontinence.

INTRODUCTION: Treatments for male stress urinary incontinence (SUI) include behavioral modifications, pelvic floor strengthening exercises, bulking agents, and surgical management. The most common surgical therapies for male stress incontinence include male slings and artificial urinary sphincters. Complications of these treatments are discussed in this review. AIM: To review the current literature on SUI diagnosis and the management of common complications that occur after surgical treatments of male SUI. METHODS: A literature search was performed using PubMed and Ovid to identify leading articles on the management of male SUI and the diagnosis and management of operative complications for male incontinence surgery. MAIN OUTCOME MEASURE: Main outcomes measured were complications and management strategies for operative complications after surgical therapies for male SUI. RESULTS: 26 publications were cited after an extensive review of the current literature on surgical treatment of male SUI. Commonly cited issues included infection, erosion, and recurrent incontinence after implantation of male slings and artificial urinary sphincters. CONCLUSION: Complications are inherent to any surgery; a thorough understanding of complications and treatment strategies after surgery for male SUI is essential for the practicing clinical urologist. Shelton TM, Brimley S, Tsambarlis P, Hellstrom WJG. Current Perspectives on Complications of Surgical Treatments for Male Stress Urinary Incontinence. Sex Med Rev 2020;8:443-449.

Immunologic Recognition of a Shared p53 Mutated Neoantigen in a Patient with Metastatic Colorectal Cancer.

Adoptive cell therapy (ACT) with T cells targeting neoantigens can mediate durable responses in patients with metastatic cancer. Cell therapies targeting common shared antigens for epithelial cancers are not yet broadly available. Here, we report the identification and characterization in one patient of T-cell receptors (TCRs) recognizing mutated p53 p.R175H, which is shared among a subset of patients with cancer. Tumor-infiltrating lymphocytes were screened for recognition of mutated neoantigens in a patient with metastatic colorectal cancer. HLA-A*0201-restricted recognition of mutated p53 p.R175H was identified, and the minimal peptide epitope was HMTEVVRHC. Reactive T cells were isolated by tetramer sorting, and three TCRs were identified. These TCRs mediated recognition of commercially available ovarian cancer, uterine carcinoma, and myeloma cell lines, as well as an NIH patient-derived esophageal adenocarcinoma line that endogenously expressed p53 p.R175H and HLA-A*0201. They also mediated recognition of p53 p.R175H+ colon, breast, and leukemia cell lines after transduction with a retrovirus encoding HLA-A*0201. This work demonstrates that common shared mutated epitopes such as those found in p53 can elicit immunogenic responses and that the application of ACT may be extended to patients with any cancer histology that expresses both HLA-A*0201 and the p53 p.R175H mutation.

A novel technique for direct visualization of reservoir placement for penoscrotal inflatable penile prostheses using a single incision.

INTRODUCTION: We aim to present a modified technique and outcomes of a novel method allowing for direct visualization of the reservoir placement during a penoscrotal inflatable penile prosthesis (IPP). METHODS: Out of165 patients who underwent IPP placement from August 2012 to March 2015, 157 underwent a modified technique and comprised the cohort of this study. A Deaver's retractor was placed lateral to the penis and over the pubic bone to allow for direct visualization of the tissues overlying the lower abdomen. After dissecting through the superficial layers, the Deaver's was slowly advanced, allowing for visualization of the fascia, which was incised. Using blunt dissection, a space for the reservoir was created between the bladder and the pubic bone. The reservoir was then placed safely into this space and the Deaver's retractor was removed. RESULTS: The causes of ED in the study cohort included postprostatectomy ED (n = 107), organic impotence (n = 40), Peyronie's disease (n = 3), ED following cystoprostatectomy (n = 2), ED due to spinal cord injury (n = 2), ED resulting from priapism (n = 2), and ED after pelvic injury (n = 1); all of which were refractory to medical management. The median age of study population was 66 years and the mean (standard deviation) operative time was 72.8 (14.7) min. Eighty percent of the procedures were performed on outpatient basis. Complication rates were low (<5%), with four infections, one proximal pump migration, one scrotal hematoma, and one urinary tract infection. CONCLUSION: The modified technique for placement of the IPP's spherical reservoir under direct visualization through a penoscrotal incision is quick, safe, and effective.

Immune recognition of somatic mutations leading to complete durable regression in metastatic breast cancer.

Immunotherapy using either checkpoint blockade or the adoptive transfer of antitumor lymphocytes has shown effectiveness in treating cancers with high levels of somatic mutations-such as melanoma, smoking-induced lung cancers and bladder cancer-with little effect in other common epithelial cancers that have lower mutation rates, such as those arising in the gastrointestinal tract, breast and ovary1-7. Adoptive transfer of autologous lymphocytes that specifically target proteins encoded by somatically mutated genes has mediated substantial objective clinical regressions in patients with metastatic bile duct, colon and cervical cancers8-11. We present a patient with chemorefractory hormone receptor (HR)-positive metastatic breast cancer who was treated with tumor-infiltrating lymphocytes (TILs) reactive against mutant versions of four proteins-SLC3A2, KIAA0368, CADPS2 and CTSB. Adoptive transfer of these mutant-protein-specific TILs in conjunction with interleukin (IL)-2 and checkpoint blockade mediated the complete durable regression of metastatic breast cancer, which is now ongoing for >22 months, and it represents a new immunotherapy approach for the treatment of these patients.

Outcomes of Adoptive Cell Transfer With Tumor-infiltrating Lymphocytes for Metastatic Melanoma Patients With and Without Brain Metastases.

Brain metastases cause significant morbidity and mortality in patients with metastatic melanoma. Although adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) can achieve complete and durable remission of advanced cutaneous melanoma, the efficacy of this therapy for brain metastases is unclear. Records of patients with M1c melanoma treated with ACT using TIL, including patients with treated and untreated brain metastases, were analyzed. Treatment consisted of preparative chemotherapy, autologous TIL infusion, and high-dose interleukin-2. Treatment outcomes, sites of initial tumor progression, and overall survival were analyzed. Among 144 total patients, 15 patients with treated and 18 patients with untreated brain metastases were identified. Intracranial objective responses (OR) occurred in 28% patients with untreated brain metastases. The systemic OR rates for patients with M1c disease without identified brain disease, treated brain disease, and untreated brain disease, and were 49%, 33% and 33%, respectively, of which 59%, 20% and 16% were durable at last follow-up. The site of untreated brain disease was the most likely site of initial tumor progression (61%) in patients with untreated brain metastases. Overall, we found that ACT with TIL can eliminate small melanoma brain metastases. However, following TIL therapy these patients frequently progress in the brain at a site of untreated brain disease. Patients with treated or untreated brain disease are less likely to achieve durable systemic ORs following TIL therapy compared with M1c disease and no history of brain disease. Melanoma brain metastases likely require local therapy despite the systemic effect of ACT.

Randomized, Prospective Evaluation Comparing Intensity of Lymphodepletion Before Adoptive Transfer of Tumor-Infiltrating Lymphocytes for Patients With Metastatic Melanoma.

PURPOSE: Adoptive cell transfer, the infusion of large numbers of activated autologous lymphocytes, can mediate objective tumor regression in a majority of patients with metastatic melanoma (52 of 93; 56%). Addition and intensification of total body irradiation (TBI) to the preparative lymphodepleting chemotherapy regimen in sequential trials improved objective partial and complete response (CR) rates. Here, we evaluated the importance of adding TBI to the adoptive transfer of tumor-infiltrating lymphocytes (TIL) in a randomized fashion. PATIENTS AND METHODS: A total of 101 patients with metastatic melanoma, including 76 patients with M1c disease, were randomly assigned to receive nonmyeloablative chemotherapy with or without 1,200 cGy TBI before transfer of tumor-infiltrating lymphcytes. Primary end points were CR rate (as defined by Response Evaluation Criteria in Solid Tumors v1.0) and overall survival (OS). Clinical and laboratory data were analyzed for correlates of response. RESULTS: CR rates were 24% in both groups (12 of 50 v 12 of 51), and OS was also similar (median OS, 38.2 v 36.6 months; hazard ratio, 1.11; 95% CI, 0.65 to 1.91; P = .71). Thrombotic microangiopathy was an adverse event unique to the TBI arm and occurred in 13 of 48 treated patients. With a median potential follow-up of 40.9 months, only one of 24 patients who achieved a CR recurred. CONCLUSION: Adoptive cell transfer can mediate durable complete regressions in 24% of patients with metastatic melanoma, with median survival > 3 years. Results were similar using chemotherapy preparative regimens with or without addition of TBI.

The influence of fipronil on Reticulitermes flavipes (Isoptera: Rhinotermitidae) feeding beyond treated plots.

A small-plot field trial was conducted to examine the area of influence of fipronil at incremental distances away from treated plots on the Harrison Experimental Forest near Saucier, MS. Small treated (water and fipronil) plots were surrounded by untreated wooden boards in an eight-point radial pattern, and examined for evidence of termite feeding every 60 d for 1 yr after treatment. Circular areas of 0, 0.28, 1.13, 2.55, 4.52, 7.07, and 10.18 m2 around the treated plots were installed to evaluate feeding damage by termites on the boards. The relationship between feeding damage to boards and area for each time interval was examined by using an exponential increase model. For both treatments and controls in nearly all periods examined, feeding was suppressed in the boards nearest to the treated plots, but increased exponentially as the area increased. Beginning 4 mo after treatment, treatment plots had lower proportions of boards with termite feeding evidence than control plots. Reduction in feeding was the only influence of fipronil observed beyond the treated plots.

Evidence of cue synergism in termite corpse response behavior.

Subterranean termites of the genus Reticulitermes are known to build walls and tubes and move considerable amounts of soil into wood but the causes of this behavior remain largely unexplored. In laboratory assays, we tested the hypothesis that Reticulitermes virginicus (Banks) would carry more sand into wooden blocks containing corpses compared to corpse-free controls. We further predicted that the corpses of predatory ants would elicit a stronger response than those of a benign beetle species or nestmates. As hypothesized, significantly more sand was carried into blocks containing corpses and this material was typically used to build partitions separating the dead from the rest of the colony. Contrary to expectations, however, this behavior did not vary among corpse types. We then tested the hypothesis that oleic acid, an unsaturated fatty acid released during arthropod decay and used by ants and other arthropod taxa in corpse recognition, would induce a similar building response in R. virginicus. To additionally determine the role of foreign objects in giving rise to this behavior, the experiment was carried out with and without imitation corpses (i.e., small glass beads). As predicted, oleic acid induced building (a tenfold increase) but only when applied to beads, suggesting strong synergism between tactile and chemical cues. Oleic acid also significantly reduced the amount of wood consumed by R. virginicus and may possess useful repellent properties.