Multimodality adjuvant therapy and survival outcomes in stage I-IV uterine carcinosarcoma.

OBJECTIVES: Uterine carcinosarcoma is a rare, aggressive form of uterine cancer with a high recurrence rate and poor survival at all stages. We sought to evaluate the outcomes of patients treated with chemotherapy versus a combination of chemotherapy and radiation (chemoradiation) to determine survival. METHODS: A multicenter retrospective analysis of patients with stage I-IV carcinosarcoma was conducted from January 2000 to December 2017. Inclusion criteria were primary surgical management, defined as hysterectomy ± salpingo-oophorectomy, comprehensive surgical staging and/or tumor debulking, followed by adjuvant chemotherapy or chemoradiation. Differences in the frequencies of stage, cytoreduction status, treatment delays and sites of disease recurrence were identified using Pearson's χ2 test. Progression-free and overall survival rates were calculated using Kaplan-Meier estimates. RESULTS: Final analysis included 148 patients; 40.5% (n=60) chemotherapy and 59.5% (n=88) chemoradiation. The mean age was 67 years (range 39-89). Stage distribution included 24.3% stage I, 12.2% stage II, 37.2% stage III, and 26.3% stage IV. There was no difference in the frequency of stage (p=0.81), cytoreduction status (p=0.61), treatment delays (p=0.57), or location of recurrence (p=0.97) between cohorts. The most frequent location of recurrence was the abdomen (50.0%). The median progression-free survival favored chemoradiation over chemotherapy (15 vs 11 months, respectively), as did the median overall survival (26 vs 20 months, respectively). Chemoradiation was associated with a statistically significant improvement in 2 year progression-free survival (22.5% vs 13.6%; p=0.006) and 2 year overall survival (50.0% vs 35.6%; p=0.018) compared with chemotherapy alone. On subanalysis of patients receiving chemoradiation, 'sandwich sequencing' (chemotherapy-radiation-chemotherapy) was associated with superior overall survival compared with alternate therapy sequences (chemotherapy-radiation and radiation-chemotherapy) (34 months vs 14 months and 14 months, respectively) (p=0.038). CONCLUSIONS: Chemoradiation was associated with improvement in both progression-free and overall survival for all stages of carcinosarcoma compared with chemotherapy alone.

Prevention and management of bowel injury during gynecologic laparoscopy: an update.

PURPOSE OF REVIEW: The current article aims to briefly review recent literature on bowel injury in gynecologic surgery with a focus on minimally invasive techniques, strategies for prevention, and management of injury. RECENT FINDINGS: Recent reviews describe a low incidence of bowel injury that is likely affected by low rates of reporting and inconsistent definitions. The major risk factor for bowel injury is adhesive disease, and assessment and prevention techniques for the presence of adhesive disease are evolving. When bowel injury occurs, prompt diagnosis and intraoperative repair yields more favorable outcomes than delayed diagnosis. Repair can be performed by a gynecologic surgeon, with or without the help of a consultant depending on the extent of the injury and surgeon comfort. SUMMARY: Bowel injury is a potentially catastrophic complication in gynecologic surgery, but its rarity presents a challenge in research. A high index of suspicion and meticulous surgical technique are the cornerstones of managing a bowel injury.

Enhancement of trophoblast differentiation and survival by low molecular weight heparin requires heparin-binding EGF-like growth factor.

STUDY QUESTION: Does low molecular weight heparin (LMWH) require heparin-binding epidermal growth factor (EGF)-like growth factor (HBEGF) signaling to induce extravillous trophoblast differentiation and decrease apoptosis during oxidative stress? SUMMARY ANSWER: LMWH increased HBEGF expression and secretion, and HBEGF signaling was required to stimulate trophoblast extravillous differentiation, increase invasion in vitro and reduce trophoblast apoptosis during oxidative stress. WHAT IS KNOWN ALREADY: Abnormal trophoblast differentiation and survival contribute to placental insufficiency syndromes, including preeclampsia and intrauterine growth restriction. Preeclampsia often manifests as a pro-thrombotic state, with unsuccessful transformation of the spiral arteries that reduces oxygen supply and can produce placental infarction. LMWH improves placental function by increasing blood flow. Recent data suggest that the actions of LMWH transcend its anti-coagulative properties, but the molecular mechanism is unknown. There is evidence that LMWH alters the expression of human HBEGF in trophoblast cells, which regulates human trophoblast pathophysiology. HBEGF, itself, is capable of increasing trophoblast survival and invasiveness. STUDY DESIGN, SIZE, DURATION: First-trimester placental explants and the HTR-8/SVneo cell line, established using extravillous trophoblast outgrowths from first-trimester villous explants, were treated in vitro with LMWH to examine the effects on HBEGF signaling and trophoblast function under normal physiological and pathological conditions. A highly specific antagonist of HBEGF and other inhibitors of HBEGF downstream signaling were used to determine the relationship between LMWH treatment and HBEGF. PARTICIPANTS/MATERIALS, SETTING, METHODS: Placental tissues (n = 5) were obtained with IRB approval and patient consent from first-trimester terminations. Placental explants and HTR-8/SVneo cells were cultured on plastic or Matrigel™ and treated with a therapeutic dose of LMWH (Enoxaparin; 10 IU/ml), with or without CRM197, pan Erb-B2 Receptor Tyrosine Kinase (ERBB) inhibitor, anti-ERBB1 or ERBB4 blocking antibodies, or pretreatment of cells with heparitinase I. Extravillous differentiation was assessed by immunocytochemistry to determine the relative levels of integrins α6ß4 and α1ß1. Trophoblast invasiveness was assessed in villous explants by measuring outgrowth from villous tips cultured on Matrigel, and by invasion assays with HTR-8/SVneo cells cultured on Matrigel-coated transwell insert. Placental explants and HTR-8/SVneo cells were exposed to oxidative stress in a hypoxia-reoxygenation (H-R) model, measuring cell death by TUNEL assay, caspase 3 cleavage, and BCL-2α expression. MAIN RESULTS AND THE ROLE OF CHANCE: LMWH induced extravillous differentiation, according to trophoblast invasion assays and integrin (α6ß4-α1ß1) switching. Treatment with LMWH rescued cytotrophoblasts and HTR-8/SVneo cells from apoptosis during exposure to reoxygenation injury, based on TUNEL, caspase 3 cleavage and BCL-2α expression. Experiments using CRM197, ERBB1 and ERBB4 blocking antibodies, pan-ERBB inhibitor and removal of cell surface heparin demonstrated that the effects of LMWH on trophoblast invasion and survival were dependent upon HBEGF signaling. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: The primary limitation of this study was the use of only in vitro experiments. Patient demographics from elective terminations were not available. WIDER IMPLICATIONS OF THE FINDINGS: These data provide new insights into the non-coagulation-related aspects of perinatal LMWH treatment in the management of placental insufficiency disorders. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by grants from the National Institutes of Health (HD071408 and HL128628), the March of Dimes, and the W. K. Kellogg Foundation. There were no conflicts or competing interests.

Influence of Morbid Obesity on Surgical Outcomes in Robotic-Assisted Gynecologic Surgery.

Objective: The aim of this research was to estimate the impact of body mass index (BMI) on surgical outcomes in patients undergoing robotic-assisted gynecologic surgery. Materials and Methods: This study was a retrospective review of prospectively collected cohort data for a consecutive series of patients undergoing gynecologic robotic surgery in a single institution. BMI, expressed as kg/m2, was abstracted from the medical charts of all patients undergoing robotic hysterectomy. Data on estimated blood loss (EBL), hemoglobin (Hb) drop, procedure time, length of hospital stay, uterine weight, pain-medication use, and complications were also extracted. Results: Two hundred and eighty-one patients underwent robotic operations. Types of procedures were total hysterectomy with or without adnexal excision, and total hysterectomies with lymphadenectomies. Eighty-four patients who were classified as morbidly obese (BMI>35) were compared with 197 patients who had a BMI of<35 (nonmorbidly obese). For patients with BMI<35, and BMI>35, the mean BMI was 27.1 and 42.5 kg/m2 (p<0.05), mean age was 49 and 50 (p=0.45), mean total operative time was 222 and 266 minutes (p<0.05), console time 115 and 142 minutes (p<0.05), closing time (from undocking until port-site fascia closure) was 30 and 41 minutes (p<0.05), EBL was 67 and 79 mL (p=0.27), Hb drop was 1.6 and 1.4 (p=0.28), uterine weight was 196.2 and 227 g (p=0.52), pain-medication use 93.7 and 111 mg of morphine (p=0.46), and mean length of stay was 1.42 and 1.43 days (0.9), all respectively. No statistically significant difference was noted between the 2 groups for EBL, Hb drop, LOS, uterine weight, pain-medication use, or complications. The only statistically significant difference was seen in operating times and included docking, console, closing, and procedure times. There were no perioperative mortalities. Morbidity occurred in 24 patients (8%). In the morbidly obese group, there were 6 complications (7%) and, in the nonmorbidly obese group, there were 18 complications (9%). Conclusions: Morbid obesity does not appear to be associated with an increased risk of morbidity in patients undergoing robotically assisted gynecologic surgery. Morbid obesity is associated with increased procedure time, but otherwise appears to have no difference in outcomes. Robotic surgery offered an ideal approach, allowing minimally invasive surgery in these technically challenging patients, with no significant increase in morbidity. J GYNECOL SURG 30:81).

Endometrial stromal sarcoma: analysis of recurrence following adjuvant treatment.

OBJECTIVE: Endometrial stromal sarcoma (ESS) is a rare and indolent form of uterine cancer with ill-defined post-operative treatment guidelines. The goal of this study was to evaluate the rate of recurrence and the effect of various adjuvant treatment modalities. METHODS: Patients with ESS at 4 institutions were identified (1986-2007). Patient demographics, pathology, treatment, and follow-up information were collected. Chi-square statistical analysis was performed. RESULTS: Forty-three patients with ESS were identified. All patients initially underwent hysterectomy. Twenty-eight (66.7%) had early stage, 12 (28.6%) had advanced stage ESS, and 2 (4.8%) had no staging information. Eight patients received pelvic and or vaginal cuff radiation treatment, with or without chemotherapy. Sixteen of 43 patients experienced a recurrence at an average of 100.5months. Thirty-three patients were treated with progestin therapy alone or followed expectantly. Complete outpatient records were available for 28 of these patients. Sixteen patients (57%) were followed expectantly while 12 (43%) received progestins. Patients receiving progestins vs. expectant management had a lower rate of recurrence in stage 1 (14.3% vs 38.5%, p=0.26) and all stages (33% vs 50%, p=0.38). Twenty-three of 28 (82.1%) patients underwent initial oophorectomy. Eight of 23 (34.8%) had a recurrence, compared to 4 of 5 (80%) in those who retained their ovaries (p=0.06). CONCLUSIONS: ESS is a rare cancer that is difficult to study. We found removal of the adnexa and post-operative treatment with progestin therapy decreased recurrence rates. These two treatment strategies should be considered in the treatment of patients with all stages of ESS.

Adjuvant vaginal brachytherapy alone for high risk localized endometrial cancer as defined by the three major randomized trials of adjuvant pelvic radiation.

OBJECTIVE: Controversy exists regarding optimal management of high risk localized endometrial cancer. Given that vaginal brachytherapy (VB) alone is used routinely at our institution, we retrospectively reviewed our outcomes among high risk patients defined according to the PORTEC, GOG 99, and/or Aalders randomized trials of pelvic radiation versus observation to determine if acceptable rates of locoregional control could be achieved with vaginal brachytherapy alone in this highest risk patient population. METHODS: The Roswell Park Cancer Institute hospital tumor registry was used to identify all patients with Stage I or IIA endometrial cancer treated between January 1992 and June 2006. A total of 464 patients were identified. Of 261 patients who received post-operative RT, 225 received VB alone. Of those 225, 87 met the high risk criteria as designated by PORTEC (at least 2 of the following high risk features: age>60, Grade 3, and/or myometrial invasion >or=Occurrences of the mathematical operator' (='were changed to 'OE'. Please check.-->50%), GOG 99 (any age with 3 high risk features: Grade 2-3, >66% myometrial invasion, and/or LVSI; age >or=50 with 2 high risk features; or age >or=70 with 1 high risk feature), and/or Aalders (Stage IC, Grade 3). Descriptive recurrence statistics are provided. RESULTS: Among 87 high risk patients treated with VB alone, 36, 77, and 14 were high risk per PORTEC, GOG 99, and Aalders respectively. Forty (46%) underwent pelvic lymph node dissection. With a median follow-up of 52 months, 3 (3.4%) pelvic recurrences were observed including 1 vaginal recurrence, 1 pelvic recurrence, and 1 local recurrence involving both the vagina and pelvis. All 3 local recurrences were successfully salvaged with pelvic RT+/-surgery. CONCLUSIONS: This represents one of the largest known series of high risk localized endometrial cancer treated with VB alone. The observed 3.4% locoregional recurrence compares favorably with the 5% locoregional recurrence noted among the highest risk patients receiving pelvic RT in the PORTEC, GOG 99, and Aalders randomized trials. In this single institution experience, the 3 local recurrences were salvaged. Based on these findings, we will continue to use VB alone in the adjuvant setting for patients with high risk localized endometrial cancer.

Evaluation of the optimal sequence of adjuvant chemotherapy and radiation therapy in the treatment of advanced endometrial cancer.

OBJECTIVE: The optimal sequence of adjuvant chemoradiation in the treatment of advanced endometrial carcinoma (EC) remains unclear. We sought to evaluate the outcomes of patients treated with chemoradiation in sandwich fashion (chemotherapy-radiotherapy-chemotherapy; CRC), versus those treated sequentially (chemotherapy-radiotherapy; CR) (radiotherapy-chemotherapy; RC), to determine if there is a survival advantaged associated with a particular treatment sequence. METHODS: A multicenter retrospective analysis of patients with stage III and IV EC from 2000-2018 was conducted. Inclusion criteria were patients who had undergone comprehensive surgical staging/tumor debulking; followed by adjuvant chemoradiation. Differences in the frequencies of adverse events were evaluated using Pearson's χ² test. Progression free survival (PFS) and overall survival (OS) rates were calculated using Kaplan-Meier estimates. RESULTS: Final analysis included 152 patients; 36.8% (n=56) CRC, 28.9% (n=44) CR, and 34.2% (n=52) RC. Histology included 44.0% endometrioid, 47.5% serous and 8.5% clear cell tumors. There was no difference in the frequency of histology (p=0.973), stage (p=0.143), cytoreduction status (p=0.932), or treatment delays (p=0.571) between adjuvant therapy sequences. The most frequent location of disease recurrence was abdomen. The median PFS favored CRC versus CR or RC (36-months vs. 22-months and 24-months, respectively) (p=0.038), as did the median OS (48-months vs. 28-months and 34-months, respectively) (p=0.003). CRC demonstrated superiority over CR and RC sequencing in terms 3-year PFS (55% vs. 34% and 37%, respectively) and 3-year OS (71% vs. 50% and 52%, respectively). CONCLUSIONS: Adjuvant chemoradiation delivered in CRC sequence was associated with improvements in both PFS and OS compared to alternant therapy sequencing.

Gastroesophageal reflux disease in bronchial asthma and the response to omeprazole.

The objective of this study was to determine the incidence of gastroesophageal reflux disease (GERD) in bronchial asthma and the role of omeprazole for asthmatics with symptoms of GERD. Seventy asthmatics were screened for GERD by questionnaire. Patients with a history suggestive of GERD were confirmed by Bernstein test and further investigated for airway responsiveness to instillation of HCl in the esophagus. Symptom score, drug score and spirometric values were recorded initially and after four weeks of treatment with omeprazole. It was found that 74.28% of asthmatics had a history of GERD. Forty patients tested positive by Bernstein test and also showed airway responsiveness to instillation of HCl in the esophagus. There was a significant improvement in symptom scores (p < 0.001), drug scores (p < 0.001) and spirometric values (p < 0.001) after adding omeprazole to their treatment regimen. It was concluded that bronchial asthma and GERD are associated in the majority of patients (57.14%) and such patients are likely to improve with omeprazole.

Malignant mixed mesodermal tumor in a young woman with polycystic ovary syndrome. A case report.

BACKGROUND: Malignant mixed mesodermal tumors (MMMTs) are uncommon, highly aggressive tumors of the uterus composed of both carcinomatous and sarcomatous elements, both likely to be derived from the same original stem cell. There is a strong association between endometrial adenocarcinoma and polycystic ovary disease. However, only two cases of MMMT occurring in women with polycystic ovaries have been reported. CASE: A 36-year-old woman with polycystic ovary disease developed an MMMT of the endometrium. CONCLUSION: Some cases of MMMT may be estrogen related.

Evaluation of robotic minimally invasive surgical skills using motion studies.

Robotic Minimally Invasive Surgery, and the engendered computer-integration, offers unique opportunities for quantitative computer-based surgical-performance evaluation. In this work, we examine extension of traditional manipulative skill assessment, having deep roots in performance evaluation in manufacturing industries, for applicability to robotic surgical skill evaluation. This method relies on: defining task-level segmentation of modular sub-tasks/micro-motions called 'Therbligs' that can be combined to perform a given task; and analyzing intra- and inter-user performance variance by studying surgeons' performance over each 'Therbligs'. Any of the performance metrics of macro-motions-from motion-economy, tool motion measurements to handed-symmetry-can now be extended over the micro-motion temporal segments. Evaluation studies were based on video recordings of surgical tasks in two settings: first, we examined performance of two representative manipulation exercises (peg board and pick-and-place) on a da Vinci surgical SKILLS simulator. This affords a relatively-controlled and standardized test-scenarios for surgeons with varied experience-levels. Second, task-sequences from real surgical videos were analyzed with a list of predefined 'Therbligs' in order to investigate its overall usefulness.

Regulating functional cell fates in CD8 T cells.

The attributes of specificity and memory enable CD8(+) T cells to provide long-lasting protection against a variety of challenges. Although, the importance of CD8(+) T cells for protection against intracellular infections and transformation is well-established, the functional type; effector phenotypes (Tc1, Tc2, Tc17 and/or Tcreg) and/or memory (effector or central), of CD8(+) T cells most desirable for tumor immunity is not established. To determine the tumor efficacy of various effector types and/or memory CD8 T cells, it is imperative to better understand intrinsic and extrinsic factors that regulate CD8(+) T cell differentiation and use this information to generate and test distinct functional cell types in tumor models. The focus of our laboratory investigations is to identify the extrinsic factors such as antigen strength, co-stimulatory molecules, cytokines, and small molecule modifiers that regulate intrinsic programs for various effector and/or memory cell fate in antigen specific CD8 T cells. The use of this information to generate immunity in murine tumor models has facilitated development of new adoptive cell transfer (ACT) as well as immunization strategies for cancer treatment.

Immunologic markers of cancer progression and prognosis.

During the past decade, significant progress has been made in understanding the interactions between the immune system and cancer. The re-emergence of cancer immunosurveillance and immunoediting concepts has provided an understanding of several immunologic markers that are associated with cancer progression and prognosis. Recent studies have attempted to define the critical role of tumor infiltration by lymphocytes as a reflection of a tumor-related immune response. More recently, there has been an improved ability to demonstrate distinct subsets of tumor-infiltrating lymphocytes (TILs) in different tumor compartments. Several of these studies indicate that the presence of TILs may be associated with improved clinical outcome in several human cancers. However, this improved clinical outcome is dependent upon the intratumoral balance and quality of TILs, or infiltration of regulatory T cells or myeloid-derived suppressor cells. Immunologic markers have an important role in demonstrating intermediate end points of a therapeutic intervention and ultimately may be useful in predicting clinical outcomes. These markers are important to the development of successful immunotherapy strategies in cancer.

Intraperitoneal chemotherapy for ovarian cancer: where are we now?

Patients with advanced epithelial ovarian cancer are conventionally treated with intravenous (IV) platinum- and taxane-based chemotherapy to try to eradicate residual disease after optimal cytoreductive surgery, resulting in a median overall survival of 49 months. The Gynecologic Oncology Group (GOG) conducted 3 large randomized, phase III clinical trials of intraperitoneal (IP) chemotherapy (GOG 104, 114, and 172) that clearly showed superior progression-free and overall survival with IP chemotherapy compared with IV chemotherapy. All 3 clinical trials investigated IP cisplatin, with the last one adding IP paclitaxel. The most recent study (GOG 172) resulted in a median survival of 66 months for patients in the IP arm versus 50 months for those in the IV arm. Fewer patients in the IP arm than in the IV arm completed all 6 treatment cycles (42% vs. 83%, respectively) because of the toxic effects of chemotherapy and IP catheter-related complications. Initially, patients in the IP arm reported significantly worse quality of life than those in the IV arm. However, at 12-month follow-up, the groups experienced no difference in quality of life, except that paresthesias were more likely to persist at moderate levels among patients in the IP arm. Based on these clinical trials, the National Cancer Institute issued a clinical announcement recommending that women with stage III ovarian cancer who undergo optimal surgical cytoreduction be considered for IP chemotherapy.

Expression of Wilms tumor gene (WT1) in epithelial ovarian cancer.

OBJECTIVES: The identification of proteins that are selectively expressed in cancer and with potential to elicit an immune response is the first step towards antigen-specific immunotherapy. The Wilms tumor gene product (WT1) is inherently immunogenic and is now thought to be oncogenic. The aim of this study was to determine the expression of WT1 in epithelial ovarian cancer (EOC) and correlate with clinico-pathologic characteristics. METHODS: WT1 expression was examined using immunohistochemistry applied on a tissue microarray of normal tissues and a panel of 100 EOC tissues. The distribution of WT1 expression and clinico-pathologic variables were analyzed. Survival probabilities were estimated by Kaplan-Meier method, and statistical significance was determined by the log-rank test. RESULTS: WT1 expression was observed in 78/100 of specimens. The predominant expression pattern was homogenous, occurring in 66/100 (66%) of WT1-positive specimens, while 12/100 (12%) demonstrated heterogeneous staining. In normal tissues, WT1 expression was noted in kidneys, splenic capsule, Sertoli cells of the testis, and granulosa cells of the ovary. The median follow-up of the patient population was 30 months. Patients with WT1-positive tumors tended to have a higher grade (P = 0.006) and stage (P = 0.002) of tumor. However, there were no significant differences in the distribution of patients with WT1-positive tumors in relation to disease-free and overall survival. CONCLUSIONS: Our data demonstrate that WT1 is expressed at high frequency in patients with EOC. Since WT1 demonstrates tissue-restricted expression and is inherently immunogenic, it could represent an attractive target for antigen-specific immunotherapy in EOC.

Cyclooxygenase 2 expression in serous tumors of the ovary.

This study was designed to investigate the expression of cyclooxygenase (COX)-2 in ovarian serous tumors (benign, borderline tumors, and carcinomas) and primary peritoneal serous carcinomas. Cases diagnosed between 1995 and 2001 were reviewed; 47 benign tumors, 6 borderline tumors, and 39 carcinomas were examined, as well as 12 normal ovaries that served as controls. Blocks were stained with anti COX-2 polyclonal antibody and staining was graded qualitatively. The staining intensity was assessed as weak (score of 1), moderate (score of 2), or strong (score of 3). Normal ovarian and tubal epithelium, inclusion cysts, benign serous tumors, and borderline tumors had a uniform score 3 staining pattern. Serous ovarian carcinomas had variable staining scores, tending to correlate with the level of tumor differentiation. Well-differentiated carcinomas had more intense COX-2 staining than poorly differentiated carcinomas, which had only weak COX-2 staining. The degree of COX-2 staining was not significantly related to overall survival. In conclusion, COX-2 expression is present in serous tumors, including benign tumors, borderline tumors, and carcinomas. Similar to the findings in other neoplasms, COX-2 expression is strongest in well-differentiated tumors and is much less evident in those that are poorly differentiated. The clinical utility of these findings is related to the potential role of nonsteroidal anti-inflammatory drugs, which are COX-2 inhibitors, in treating and/or preventing some forms of ovarian carcinoma.

Capillary electrophoresis chips with a sheath-flow supported electrochemical detection system.

Microfabricated capillary electrophoresis chips containing an integrated sheath-flow electrochemical detector are developed with the goal of minimizing the influence of separation voltages on end-column detection while maintaining optimum performance. The microdevice consists of an upper glass wafer carrying the etched separation, injection, and sheath-flow channels and a lower glass wafer on which gold- and silver-plated electrodes have been fabricated. The sheath-flow channels join the end of the separation channel from each side, and gravity-driven flow carries the analytes to the electrochemical detector placed at working distances of 100, 150, 200, and 250 microm from the separation channel exit. The performance of this detector is evaluated using catechol and a detection limit of 4.1 microM obtained at a working distance of 250 microm. Detection of DNA restriction fragments and PCR product sizing is demonstrated using the electroactive intercalating dye, iron phenanthroline. Additionally, an allele-specific, PCR-based single-nucleotide polymorphism typing assay for the C282Y substitution diagnostic for hereditary hemochromatosis is developed and evaluated using ferrocene-labeled primers. This study advances the feasibility of high-speed, high-throughput chemical and genetic analysis using microchip electrochemical detection.