KRAS Mutation Variants and Co-occurring PI3K Pathway Alterations Impact Survival for Patients with Pancreatic Ductal Adenocarcinomas.

BACKGROUND: KRAS variant alleles may have differential biological properties which impact prognosis and therapeutic options in pancreatic ductal adenocarcinomas (PDA). MATERIALS AND METHODS: We retrospectively identified patients with advanced PDA who received first-line therapy and underwent blood and/or tumor genomic sequencing at the University of Washington between 2013 and 2020. We examined the incidence of KRAS mutation variants with and without co-occurring PI3K or other genomic alterations and evaluated the association of these mutations with clinicopathological characteristics and survival using a Cox proportional hazards model. RESULTS: One hundred twenty-six patients had genomic sequencing data; KRAS mutations were identified in 111 PDA and included the following variants: G12D (43)/G12V (35)/G12R (23)/other (10). PI3K pathway mutations (26% vs. 8%) and homologous recombination DNA repair (HRR) defects (35% vs. 12.5%) were more common among KRAS G12R vs. non-G12R mutated cancers. Patients with KRAS G12R vs. non-G12R cancers had significantly longer overall survival (OS) (HR 0.55) and progression-free survival (PFS) (HR 0.58), adjusted for HRR pathway co-mutations among other covariates. Within the KRAS G12R group, co-occurring PI3K pathway mutations were associated with numerically shorter OS (HR 1.58), while no effect was observed on PFS. CONCLUSIONS: Patients with PDA harboring KRAS G12R vs. non-G12R mutations have longer survival, but this advantage was offset by co-occurring PI3K alterations. The KRAS/PI3K genomic profile could inform therapeutic vulnerabilities in patients with PDA.

In utero exposure to alloantigens primes alloimmunization to platelet transfusion in mice.

BACKGROUND: Platelet transfusions remain a mainstay of treatment for many patients with thrombocytopenia, but can lead to alloantibodies to Human Leukocyte Antigens (anti-HLA) resulting in inadequate responses to subsequent platelet transfusions (refractoriness), as well as complicate transplantation. Despite substantial decreases in alloimmunization with the implementation of leukoreduction, a significant percentage of patients still become alloimmunized following platelet transfusions. It remains unclear why some patients make anti-HLA antibodies, but others do not make anti-HLA antibodies even with chronic transfusion. Antecedent pregnancy correlates with risk of alloimmunization due to platelet transfusion in humans - however, isolation of pregnancy as a single variable is not possible in human populations. STUDY DESIGN AND METHODS: A tractable murine model of pregnancy and transfusion was engineered by breeding C57BL/6 (H-2b ) dames with BALB/c (H-2d ) sires. After pregnancy, female mice were transfused with leukoreduced platelets from F1 (H-2b/d ) donors that expressed the same paternal major histocompatibility complex (MHC) H-2d alloantigens as the sires. Control groups allowed isolation of pregnancy or transfusion alone as independent variables. Alloimmunization was determined by testing serum for antibodies to H-2d MHC alloantigens. RESULTS: No alloantibodies were detected after pregnancy alone, or in response to transfusion of platelets alone; however, significant levels of alloantibodies were detected when pregnancy was followed by transfusion. CONCLUSIONS: These findings isolate antecedent pregnancy as a causal contribution to increased frequencies of alloimmunization by subsequent platelet transfusion in mice and provide a platform for ongoing mechanistic investigation.

Impact of Connective Tissue Disease on Oncologic Breast Surgery and Reconstruction.

BACKGROUND: The impact of connective tissue disease (CTD) on outcomes following breast surgery and reconstruction is unknown. The purpose of this study was to evaluate the effect of both CTDs and systemic immunomodulatory therapy on outcomes following breast surgery and reconstruction. METHODS: A retrospective review was performed of all patients from 2005 to 2010 with an active CTD who underwent breast surgery with or without reconstruction. Surgical events were assigned to 1 of 4 groups: ablative surgery alone, autologous reconstruction, implant reconstruction, and revision surgery. Logistic regression was utilized to examine the relationship between complications and type of surgery, CTD diagnosis, and immunomodulatory therapy. Four non-CTD control groups were then compiled for outcome comparison. The a priori P-value was set at P < 0.05, and all tests were 2 sided. RESULTS: Thirty-three patients with CTD underwent112 procedures. Diagnoses included psoriasis/psoriatic arthritis (n = 12), rheumatoid arthritis (n = 10), lupus (n = 4), scleroderma (n = 3), Sjogren syndrome (n = 2), mixed CTD (n = 1), and seronegative polyarthritis (n = 1). Nineteen of 33 (58%) patients who received systemic treatment for CTD in the perioperative period were less likely to experience a minor complication compared with those without treatment (odds ratio= 0.69; P = 0.019). There were no differences in postoperative complications in patients with CTD compared with control groups. CONCLUSIONS: Ablative breast surgery and reconstruction among patients with CTDs can be performed safely with low perioperative complication rates. Patients receiving systemic therapy, and continuing their regimens perioperatively, experience complication rates similar to those not requiring therapy.

Body-mass index and mortality among 1.46 million white adults.

BACKGROUND: A high body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) is associated with increased mortality from cardiovascular disease and certain cancers, but the precise relationship between BMI and all-cause mortality remains uncertain. METHODS: We used Cox regression to estimate hazard ratios and 95% confidence intervals for an association between BMI and all-cause mortality, adjusting for age, study, physical activity, alcohol consumption, education, and marital status in pooled data from 19 prospective studies encompassing 1.46 million white adults, 19 to 84 years of age (median, 58). RESULTS: The median baseline BMI was 26.2. During a median follow-up period of 10 years (range, 5 to 28), 160,087 deaths were identified. Among healthy participants who never smoked, there was a J-shaped relationship between BMI and all-cause mortality. With a BMI of 22.5 to 24.9 as the reference category, hazard ratios among women were 1.47 (95 percent confidence interval [CI], 1.33 to 1.62) for a BMI of 15.0 to 18.4; 1.14 (95% CI, 1.07 to 1.22) for a BMI of 18.5 to 19.9; 1.00 (95% CI, 0.96 to 1.04) for a BMI of 20.0 to 22.4; 1.13 (95% CI, 1.09 to 1.17) for a BMI of 25.0 to 29.9; 1.44 (95% CI, 1.38 to 1.50) for a BMI of 30.0 to 34.9; 1.88 (95% CI, 1.77 to 2.00) for a BMI of 35.0 to 39.9; and 2.51 (95% CI, 2.30 to 2.73) for a BMI of 40.0 to 49.9. In general, the hazard ratios for the men were similar. Hazard ratios for a BMI below 20.0 were attenuated with longer-term follow-up. CONCLUSIONS: In white adults, overweight and obesity (and possibly underweight) are associated with increased all-cause mortality. All-cause mortality is generally lowest with a BMI of 20.0 to 24.9.

Perioperative Chemotherapy and Chemoradiotherapy for Patients With Resectable and Borderline Resectable Pancreatic Adenocarcinoma.

OBJECTIVES: Pancreatic ductal adenocarcinoma (PDA) is the third most common cause of cancer death in the United States. Most patients who undergo resection develop recurrence. Standard treatment confers a median overall survival (OS) of 24 months. Exposure to alternate regimens may prevent chemoresistance. This study evaluated multiagent perioperative therapy for potentially resectable PDA patients to improve OS. METHODS: A single center, phase 2, trial of patients with resectable or borderline resectable PDA. Patients received neoadjuvant therapy with induction chemotherapy (gemcitabine, docetaxel, capecitabine) for 3 cycles, chemoradiation (intensity-modulated radiation therapy with capecitabine and oxaliplatin) followed by surgery, and 2 months of adjuvant gemcitabine and oxaliplatin and 2 months of gemcitabine. The primary endpoint was OS. The secondary endpoint was recurrence-free survival (RFS). RESULTS: Thirty-two eligible patients were enrolled. Twenty-two patients underwent surgical resection. After a median follow-up of 56.8 months, mOS was 31.6 months (95% confidence interval [CI], 14.2-58.1) for all patients, 58.1 months (95% CI, 31.6 to NR) for those who completed surgery. The mRFS was 31.3 months (95% CI, 12.5 to NR). CONCLUSIONS: Perioperative therapy with GTX, chemoradiotherapy, and adjuvant GemOx/Gem resulted in promising survival of 58 months for patients who underwent resection and may represent another treatment option for PDA.

Use of acupuncture with acupressure in addition to standard-of-care cryotherapy to decrease chemotherapy-associated neuropathy in patients with gastrointestinal malignancies receiving oxaliplatin-based chemotherapy: Study protocol for a randomized, controlled pilot and feasibility study.

BACKGROUND: Oxaliplatin is a key chemotherapeutic agent in the treatment of local and metastatic gastrointestinal (GI) malignancies. Dose density and treatment adherence can be limited by chemotherapy-induced peripheral neuropathy (CIPN). Early research suggests CIPN incidence and severity may be mitigated by acupuncture, but rigorous data in GI oncology patients is limited. Here, we describe the protocol of a randomized, waitlist-controlled pilot study testing the use of preemptive of acupuncture plus acupressure to decrease CIPN and chemotherapy-related toxicities. METHODS: Patients with a GI malignancy (n = 56) with planned 5-fluorouracil (5-FU) and oxaliplatin IV (FOLFOX, FOLFIRINOX) every 2 weeks are being recruited. Additional concurrent anti-neoplastic agents may be used. Enrolled patients are randomized 1:1 to a 3-month intervention of Arm A: acupuncture with acupressure and standard-of-care treatment, or Arm B: standard-of-care alone. In Arm A, on days 1 and 3 of each chemotherapy cycle a standardized acupuncture protocol is administered and patients are taught self-acupressure to perform daily between chemotherapy treatments. Patients in both arms are given standard-of-care oral and peripheral (hands/feet) ice chip cryotherapy during oxaliplatin administration. CIPN and other symptoms are assessed at baseline, 6 weeks, and 3 months from registration. The primary endpoint is CIPN severity at 3 months (EORTC-CIPN 20). Additional endpoints evaluate CIPN incidence (CTCAE, Neuropen, tuning fork); incidence of pain, fatigue, nausea, oral dysesthesia, and anxiety; and feasibility (recruitment, retention, adherence, acceptability). If warranted, trial results will inform the design of a multi-center trial to expand testing of the intervention to a larger patient cohort.

Is There a Difference Between LI-RADS 3 to LI-RADS 5 Progression Assessment Using CT Versus MR? A Retrospective, Single-Center, Longitudinal Study of Patients Who Underwent 5082 Radiologic Examinations for Surveillance of Hepatocellular Carcinoma Over a 43-Month Period.

OBJECTIVE: The Liver Imaging Reporting and Data System (LI-RADS) has been widely applied to CT and MR liver observations in patients at high-risk for hepatocellular carcinoma (HCC). We investigated the impact of CT vs MR in upgrading LI-RADS 3 to LI-RADS 5 observations using a large cohort of high-risk patients. METHODS: We performed a retrospective, longitudinal study of CT and MR radiographic reports (June 2013 - February 2017) with an assigned LI-RADS category. A final population of 757 individual scans and 212 high-risk patients had at least one LI-RADS 3 observation. Differences in observation time to progression between modalities were determined using uni- and multivariable analysis. RESULTS: Of the 212 patients with a LI-RADS 3 observation, 52 (25%) had progression to LI-RADS 5. Tp ranged from 64 - 818 days (median: 196 days). One hundred and three patients (49%) had MR and 109 patients (51%) had CT as their index study. Twenty-four patients with an MR index exam progressed to LI-RADS 5 during the follow-up interval, with progression rates of 22% (CI:13%-30%) at 1 year and 29% (CI:17%-40%) at 2 years. Twenty-eight patients with a CT index exam progressed to LI-RADS 5 during follow-up, with progression rates of 26% (CI:16%-35%) at 1 year and 31% (CI:19%-41%) at 2 years. Progression rates were not significantly different between patients whose LI-RADS 3 observation was initially diagnosed on MR vs CT (HR: 0.81, P = 0.44). DISCUSSION: MR and CT modalities are comparable for demonstrating progression from LI-RADS 3 to 5 for high risk patients.

Cigarette smoking and the risk of incident and fatal melanoma in a large prospective cohort study.

OBJECTIVE: Previous studies suggest that smoking may be inversely associated with risk of melanoma. We attempted to replicate this finding using data from the Cancer Prevention Study II (CPS-II) and CPS-II Nutrition cohort, two large prospective cohort studies of cancer mortality and incidence, respectively, with long-term follow-up. METHODS: Cox proportional hazards regression analysis was used to examine the association between smoking status and risk of melanoma mortality and incidence among Caucasians in these cohorts. Analyses were adjusted by age, occupation, latitude and educational status. RESULTS: The incidence rate of melanoma was lower in current than never smokers in both men [hazard ratio (HR): 0.70, 95% confidence interval (CI): (0.48-1.02)] and women [0.50 (0.30-0.83)]; incidence was not lower in former than in never smokers for either sex. The death rate from melanoma was lower in male current than never smokers [0.77 (0.62-0.94)], and in male and female former smokers [0.86 (0.73-1.01)] and [0.83 (0.65-1.06)], respectively. No trends in incidence or mortality were observed in male or female current smokers with years of smoking or cigarettes per day. CONCLUSIONS: This study provides limited support for the hypothesis that smoking reduces melanoma risk. The inconsistent results by smoking status and lack of clear dose-response relationships weaken the evidence for causality.

Improving patient selection for endovascular treatment of acute cerebral ischemia: a review of the literature and an external validation of the Houston IAT and THRIVE predictive scoring systems.

Outcome after intraarterial therapy (IAT) for acute ischemic stroke remains variable, suggesting that improved patient selection is needed to better identify patients likely to benefit from treatment. The authors evaluate the predictive accuracies of the Houston IAT (HIAT) and the Totaled Health Risks in Vascular Events (THRIVE) scores in an independent cohort and review the existing literature detailing additional predictive factors to be used in patient selection for IAT. They reviewed their center's endovascular records from January 2004 to July 2010 and identified patients who had acute ischemic stroke and underwent IAT. They calculated individual HIAT and THRIVE scores using patient age, admission National Institutes of Health Stroke Scale (NIHSS) score, admission glucose level, and medical history. The scores' predictive accuracies for good outcome (discharge modified Rankin Scale score ≤ 3) were analyzed using receiver operating characteristics analysis. The THRIVE score predicts poor outcome after IAT with reasonable accuracy and may perform better than the HIAT score. Nevertheless, both measures may have significant clinical utility; further validation in larger cohorts that accounts for differences in patient demographic characteristics, variation in time-to-treatment, and center preferences with respect to IAT modalities is needed. Additional patient predictive factors have been reported but not yet incorporated into predictive scales; the authors suggest the need for additional data analysis to determine the independent predictive value of patient admission NIHSS score, age, admission hyperglycemia, patient comorbidities, thrombus burden, collateral flow, time to treatment, and baseline neuroimaging findings.

Ambient air pollution and brain cancer mortality.

OBJECTIVE: Growing evidence that ultrafine particles in ambient air can cause brain lesions in animals led us to investigate whether particulate components of air pollution may be associated with brain cancer risk in humans. Air pollution has been associated with respiratory disorders and cardiovascular morbidity and mortality, but associations between air pollutants and brain cancer have not been investigated in adults. METHODS: The analyses included 1,284 deaths due to brain cancer from the Cancer Prevention Study-II, an ongoing prospective mortality study of adults in the United States and Puerto Rico conducted by the American Cancer Society. Air pollution data from national databases for metropolitan areas were combined with residential history and vital status data to estimate exposure to particulate and gaseous air pollution. RESULTS: We found no elevated risk for estimated measures of air pollutants, an unanticipated reduction in risk was found between gaseous air pollutants and brain cancer mortality. CONCLUSION: The findings do not provide evidence of increased risk of brain cancer mortality due to air pollutants.

Lung cancer occurrence in never-smokers: an analysis of 13 cohorts and 22 cancer registry studies.

BACKGROUND: Better information on lung cancer occurrence in lifelong nonsmokers is needed to understand gender and racial disparities and to examine how factors other than active smoking influence risk in different time periods and geographic regions. METHODS AND FINDINGS: We pooled information on lung cancer incidence and/or death rates among self-reported never-smokers from 13 large cohort studies, representing over 630,000 and 1.8 million persons for incidence and mortality, respectively. We also abstracted population-based data for women from 22 cancer registries and ten countries in time periods and geographic regions where few women smoked. Our main findings were: (1) Men had higher death rates from lung cancer than women in all age and racial groups studied; (2) male and female incidence rates were similar when standardized across all ages 40+ y, albeit with some variation by age; (3) African Americans and Asians living in Korea and Japan (but not in the US) had higher death rates from lung cancer than individuals of European descent; (4) no temporal trends were seen when comparing incidence and death rates among US women age 40-69 y during the 1930s to contemporary populations where few women smoke, or in temporal comparisons of never-smokers in two large American Cancer Society cohorts from 1959 to 2004; and (5) lung cancer incidence rates were higher and more variable among women in East Asia than in other geographic areas with low female smoking. CONCLUSIONS: These comprehensive analyses support claims that the death rate from lung cancer among never-smokers is higher in men than in women, and in African Americans and Asians residing in Asia than in individuals of European descent, but contradict assertions that risk is increasing or that women have a higher incidence rate than men. Further research is needed on the high and variable lung cancer rates among women in Pacific Rim countries.

Interpreting cancer trends.

The interpretation of cancer incidence trends is complicated by short-term random variation, artifactual fluctuations introduced by screening, changes in diagnosis or disease classification, completeness of reporting, and by the multiplicity of factors that may affect risk for specific cancer sites. We analyzed trends in 56 different cancer sites and subsites in the U.S. SEER registries in the period 1975-2002 using join-point analysis. The increase in cancer incidence for all sites combined that became evident with the inception of the SEER registries in the mid-1970s has abated since the early 1990s. Among the 15 most common cancer sites in men, sites with increasing incidence rates during the most recent time period include melanoma of the skin and cancers of the prostate, kidney and renal pelvis (kidney), and esophagus. Among women, incidence rates are increasing for leukemia, non-Hodgkin's lymphoma, melanoma, and cancers of the breast, thyroid, urinary bladder, and kidney. Incidence rates for all childhood cancers combined increased 0.6% per year from 1975 to 2002. Cancer mortality rates have decreased in the United States since 1991 in both men and in women; site-specific death rates have decreased in the most recent time period for 12 of the top 15 cancer sites in men and 9 of the top 15 cancer sites in women. Similar trends in cancer incidence and mortality have been reported in other industrialized countries. Possible reasons for these trends are discussed.

Job strain and risk of musculoskeletal symptoms among a prospective cohort of occupational computer users.

OBJECTIVES: Most previous studies of the association between psychosocial stress and musculoskeletal illness among computer users have been cross-sectional and have yielded inconsistent results. The association between a measure of psychosocial stress, "job strain", and incident neck-shoulder and arm-hand musculoskeletal symptoms was investigated among recently hired computer users. METHODS: The participants worked for one of several large employers and were followed prospectively for 6 months. The "job demands" and "decision latitude" subscales of the Job Content Questionnaire were used to estimate the job-strain quadrants and a ratio measure of job strain which was subsequently categorized. Incident musculoskeletal symptoms were obtained with weekly diaries. Proportional hazards models were used to estimate associations between job strain and incident musculoskeletal symptoms. RESULTS: Those in the high-strain quadrant were at increased risk of neck-shoulder symptoms [hazard ratio (HR) 1.65, 95% confidence interval (95% CI) 0.91-2.99] when compared with those in the low-strain quadrant. Those in the highest strain-ratio category were also at increased risk of neck-shoulder symptoms when compared with those in the lowest strain-ratio category (HR 1.52, 95% CI 0.88-2.62). Modification by previous years of computer use was observed, with an elevated risk observed for those in the highest job-strain ratio category who also had low previous computer use (HR 3.16, 95% CI 1.25-8.00). There did not appear to be an association between either measure of job strain and incident arm-hand symptoms. CONCLUSIONS: In this cohort, workers who reported high job strain were more likely to develop neck-shoulder symptoms.

Retrievable inferior vena cava filters in patients with cancer are safe but are they beneficial?

The availability and insertion of permanent and retrievable inferior vena cava filter devices have increased substantially over the past decade. Our retrospective study provides the first detailed assessment of the safety and efficacy of retrievable inferior vena cava filters in a large cohort of cancer patients with predominantly advanced malignancies. We retrospectively reviewed the medical records of consecutive patients with the diagnosis of cancer who underwent inferior vena cava filter placement at a single academic medical center from 2007 to 2012 with special attention to safety, recurrent venous thromboembolism, and survival data. Three hundred thirty-seven cancer patients were included in the analysis. Gastrointestinal, lung, and genitourinary malignancies were the most commonly represented malignancies [94 (27.8 %), 70 (20.8 %), and 37 (10.9 %) patients, respectively]. Immediate complications were diagnosed in one of 258 (1 %) evaluable patients following placement of a retrievable filter. Delayed complications occurred in 23 of 258 (8 %) patients. The 7, 14, 30, 90, and 365 day post-filter survival rates for patients with stage IV cancer were 0.91, 0.86, 0.71, 0.52, and 0.29, respectively. Patients with lung and gastrointestinal tumors demonstrated a significantly reduced post-filter survival rate compared with those with genitourinary, brain, and breast cancers. Retrievable and non-retrievable inferior vena cava filters are associated with an overall low rate of complications in patients with cancer. However, survival rates following filter placement are poor in this patient population.

Physical activity and risk of ovarian cancer: a prospective cohort study in the United States.

Increased physical activity may lower the risk of ovarian cancer by reducing the frequency of ovulation, decreasing body fat, or diminishing chronic inflammation. Previous epidemiological studies examining the association between physical activity and risk of ovarian cancer have been inconsistent. We investigated the association of physical activity with ovarian cancer in a prospective cohort of 27,365 individuals from the Breast Cancer Detection Demonstration Project. During 227,045 person-years of follow-up, 121 cases of ovarian cancer were ascertained. Usual physical activity during the past year was assessed by a self-administered questionnaire. After adjusting for potential risk factors for ovarian cancer, the relative risks (95% confidence intervals) across increasing quintiles of total physical activity were 1.0, 0.73 (0.43-1.25), 0.84 (0.50-1.40), 0.56 (0.31-1.00), and 0.70 (0.41-1.21), respectively (P for trend = 0.13). In this prospective cohort study among U.S. women, we found no overall significant association between physical activity and risk of ovarian cancer, although the results are suggestive of an inverse association.

Reinforcement of the abdominal wall following breast reconstruction with abdominal flaps: a comparison of synthetic and biological mesh.

BACKGROUND: Breast reconstruction using muscle-preserving abdominal flaps occasionally results in an abdominal bulge or hernia. The authors analyzed outcomes and complications following use of a synthetic or biological mesh for abdominal reinforcement following initial harvest or secondary repair of a bulge or hernia. METHODS: A retrospective review was conducted of all patients (n = 818) who had abdominal flap-based breast reconstruction between 1995 and 2011. Ninety-seven patients met inclusion criteria; 61 had synthetic mesh and 36 had biological mesh (porcine acellular dermal matrix). Complications and outcomes were reviewed. Statistical analysis was performed to determine contributing factors and differences between cohorts. RESULTS: Overall complication rates for the synthetic and biological cohorts were 6.5 and 5.5 percent (p = 0.61), respectively, with slightly higher bulge rates in patients with synthetic compared with biological mesh (18 percent versus 8.3 percent; p = 0.25). Complication rates in primary and secondary placement of synthetic mesh were 5 and 7.3 percent, respectively; bulge rates were 15 and 19.5 percent, respectively. Complication rates in primary and secondary placement of biological mesh were 6.3 and 0 percent, respectively; bulge rates were 9.4 and 0 percent, respectively. CONCLUSIONS: Synthetic and biological mesh reconstruction for primary abdominal repair and secondary contouring have similar, low complication rates. Postoperative abdominal wall laxity and bulge occurred in an equal distribution following unilateral or bilateral flap reconstruction. Early investigation demonstrates that porcine acellular dermal matrix is as effective as synthetic mesh for abdominal wall reinforcement and repair, with limited morbidity associated with each. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Evaluating long-term outcomes following nipple-sparing mastectomy and reconstruction in the irradiated breast.

BACKGROUND: Although it is well established that reconstruction of the irradiated breast is associated with diminished cosmetic results and more frequent complications, little is known about the specific effects of radiation therapy on the reconstructive outcomes after nipple-sparing mastectomy. METHODS: Patients who had nipple-sparing mastectomy and had either previous radiation therapy for breast-conservation therapy or postmastectomy radiation therapy were reviewed. Patient demographics, reconstructive details, and postoperative outcomes were analyzed. Patient photographs were used to evaluate aesthetic parameters. Fisher's exact and t tests were used for comparison of groups, with a value of p < 0.05 considered significant. RESULTS: Eighteen patients were identified as having nipple-sparing mastectomy either after breast-conservation therapy (72.2 percent) or before postmastectomy radiation therapy (27.8 percent), with an average follow-up of 3 years. First-stage complications occurred in six patients (33.3 percent). Nipple position was classified as high-riding in 55.6 percent of patients. Average time to revision was 13.3 months. Most common revisions were for correction of malposition (27.8 percent), capsular contracture (16.7 percent), and high-riding nipple (22.4 percent). Capsular contracture occurred more commonly in patients who needed postmastectomy radiation therapy compared with those who had previously undergone breast-conservation therapy (40 percent versus 7.8 percent). Maintenance of reconstruction occurred in 88.9 percent patients, with eventual implant loss occurring in two patients (11.1 percent). CONCLUSIONS: Nipple-sparing mastectomy and implant reconstruction should be approached cautiously in the setting of radiation therapy. When early complications are present, significant morbidity may occur. Late revision surgery is common in this subset of patients. Implant malposition and a high-riding nipple occur most frequently. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.