Publications by authors named "Anjali Kumar"

80 Publications

Evaluating the Regional Uptake of Minimally Invasive Colorectal Surgery: a Report from the Surgical Care Outcomes Assessment Program.

J Gastrointest Surg 2020 Nov 18. Epub 2020 Nov 18.

Department of Surgery, Virginia Mason Medical Center, 1100 9th Ave, C6-GS, Seattle, WA, 98101, USA.

Background: Minimally invasive surgery (MIS) for colorectal disease has well-known benefits, but many patients undergo open operations. When choosing an MIS approach, robotic technology may have benefits over traditional laparoscopy and is increasingly used. However, the broad adoption of MIS, and specifically robotics, across colorectal operations has not been well described. Our primary hypothesis is that rates of MIS in colorectal surgery are increasing, with different contributions of robotics to abdominal and pelvic colorectal operations.

Methods: Rates of MIS colorectal operations are described using a prospective cohort of elective colorectal operations at hospitals in the Surgical Care Outcomes Assessment Program (SCOAP) from 2011 to 2018. The main outcome was proportion of cases approached using open, laparoscopic, and robotic surgery. Factors associated with increased use of MIS approaches were described.

Results: Across 21,423 elective colorectal operations, rates for MIS (laparoscopic or robotic surgery) increased from 44% in 2011 to 75% in 2018 (p < 0.001). Approaches for abdominal operations (n = 12,493) changed from 2 to 11% robotic, 43 to 63% laparoscopic, and 56 to 26% open (p < 0.001). Approaches for pelvic operations (n = 8930) changed from 3 to 33% robotic, 40 to 42% laparoscopic, and 57 to 24% open(p < 0.001). These trends were similar for high-(100 + operations/year) and low-volume hospitals and surgeons.

Conclusions: At SCOAP hospitals, the majority of elective colorectal operations is now performed minimally invasively. The increase in the MIS approach is primarily driven by laparoscopy in abdominal procedures and robotics in pelvic procedures.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11605-020-04875-1DOI Listing
November 2020

No Laughing Matter: How Humor Styles Relate to Feelings of Loneliness and Not Mattering.

Behav Sci (Basel) 2020 Oct 27;10(11). Epub 2020 Oct 27.

Management and Organizational Studies, Faculty of Social Science, The University of Western Ontario, London, ON N6A 5C2, Canada.

Loneliness and feeling that one does not matter are closely linked, but further investigation is needed to determine differentiating features. The relationship between not mattering to others (anti-mattering) and loneliness was explored by assessing how the two constructs correlated with an interpersonal dimension, specifically four humor styles (affiliative, self-enhancing, self-defeating, and aggressive). One hundred and fifty-eight women and 96 men completed a three-item loneliness scale, a new measure of anti-mattering, and a humor styles questionnaire. Confirmatory factor analysis results indicated that the new anti-mattering measure is a unidimensional scale. Loneliness and anti-mattering were strongly correlated, and each correlated in the same direction with approximately the same magnitude as the four humor styles. The discussion concludes that anti-mattering and loneliness are strongly linked, a finding which may be important in psychological treatment. Humor styles also play a role in psychological well-being and present a unique pathway to mental health.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/bs10110165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693932PMC
October 2020

Mothers' sense of coherence and oral health-related quality of life in cleft lip and palate children visiting a private dental college: A Survey.

J Family Med Prim Care 2020 Aug 25;9(8):4386-4390. Epub 2020 Aug 25.

Department of Prosthodontics, Patna Dental College and Hospital, Patna, Bihar, India.

Background: In addition to an adjusting physical appearance, children with cleft lip and palate also deal with psychological and psychosocial limitation. Mothers' sense of coherence (SOC) could be a psychosocial determinant of oral health quality of life (OH-QoL) of cleft lip and palate patients. Hence, the present study was done to assess the relationship of mothers' SOC on OH-QoL in cleft lip and palate patients.

Materials And Methods: The present cross-sectional questionnaire study was conducted on mothers of cleft lip and palate children. The first part consisted of demographic details. The second part of scale was the early childhood and oral health impact scale (ECOHIS) which had a total 13 questions with responses on a 4-point Likert scale. The third part was to assess mothers' SOC using a short version of SOC-13 consists of 13 items on a 7-point Likert scale. Chi-square test was applied to assess the association between mothers' SOC, sociodemographic characteristic, and children's OHRQoL. In the analysis, < 0.05 was considered significant.

Results: Out of 69% of low SOC population, 21.73% were rural, 20.39% were from peri-urban, and 57.97% population was from urban areas. Out of 150 participants, 2.40% in high ECOHIS were illiterate/primary school, "31.32% were high school/intermediate/diploma had high ECOHIS while 66.26% were high school/intermediate/diploma" had low ECOHIS, and 25.37% were graduate/postgraduate. Mothers' education and locality were statistically significant < 0.001.

Conclusion: Action to enhance mothers' SOC might form part of oral health promotion and help to improve the oral health quality of life of cleft lip and palate patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/jfmpc.jfmpc_1129_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7586524PMC
August 2020

Structural Alterations in Deep Brain Structures in Type 1 Diabetes.

Diabetes 2020 11 24;69(11):2458-2466. Epub 2020 Aug 24.

Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN

Even though well known in type 2 diabetes, the existence of brain changes in type 1 diabetes (T1D) and both their neuroanatomical and clinical features are less well characterized. To fill the void in the current understanding of this disease, we sought to determine the possible neural correlate in long-duration T1D at several levels, including macrostructural, microstructural cerebral damage, and blood flow alterations. In this cross-sectional study, we compared a cohort of 61 patients with T1D with an average disease duration of 21 years with 54 well-matched control subjects without diabetes in a multimodal MRI protocol providing macrostructural metrics (cortical thickness and structural volumes), microstructural measures (T1-weighted/T2-weighted [T1w/T2w] ratio as a marker of myelin content, inflammation, and edema), and cerebral blood flow. Patients with T1D had higher T1w/T2w ratios in the right parahippocampal gyrus, the executive part of both putamina, both thalami, and the cerebellum. These alterations were reflected in lower putaminal and thalamic volume bilaterally. No cerebral blood flow differences between groups were found in any of these structures, suggesting nonvascular etiologies of these changes. Our findings implicate a marked nonvascular disruption in T1D of several essential neural nodes engaged in both cognitive and motor processing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2337/db19-1100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576566PMC
November 2020

Infusion of N-acetyl cysteine during hypoglycaemia in humans does not preserve the counterregulatory response to subsequent hypoglycaemia.

Endocrinol Diabetes Metab 2020 Jul 15;3(3):e00144. Epub 2020 May 15.

Division of Diabetes, Endocrinology and Metabolism Department of Medicine University of Minnesota Minneapolis MN USA.

Aim: Administration of N-acetyl cysteine (NAC) during hypoglycaemia will preserve the counterregulatory response to subsequent hypoglycaemia in healthy humans.

Methods: This was a randomized double-blind cross over study where humans were given either a 60-minute infusion of NAC (150 mg/kg) followed by a 4-hour infusion of NAC (50 mg/kg) or saline starting 30 minutes before the initiation of a 2-hour hypoglycaemic (HG) clamp at 8 am. After rest at euglycaemia for ~2 hours, subjects were exposed to a 2nd HG clamp at 2 pm and discharged home in euglycaemia. They returned the following day for a 3rd HG clamp at 8 am.

Results: Twenty-two subjects were enrolled. Eighteen subjects completed the entire protocol. The epinephrine response during clamp 3 (171 ± 247 pg/mL) following clamp 1 NAC infusion was lower than the response during the clamp 1 NAC infusion (538 ± 392 pg/mL) (clamp 3 to clamp 1 NAC:  = .0013). The symptom response during clamp 3 (7 ± 5) following clamp 1 NAC infusion was lower than the response during the clamp 1 NAC infusion (16 ± 10) (clamp 3 to clamp 1 NAC:  = .0003). Nine subjects experienced rash, pruritus or nausea during NAC infusion.

Conclusion: We found no difference in the hormone and symptom response to experimental hypoglycaemia measured in subjects who were administered NAC as opposed to saline the day before. This observation suggests that further development of NAC as a therapy for impaired awareness of hypoglycaemia in patients with diabetes may be unwarranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/edm2.144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7375074PMC
July 2020

Efficacy of quality improvement and patient safety workshops for students: a pilot study.

BMC Med Educ 2020 Apr 23;20(1):126. Epub 2020 Apr 23.

Department of Emergency Medicine, Baylor College of Medicine, Houston, TX, USA.

Background: While the Association of American Medical Colleges encourages medical schools to incorporate quality improvement and patient safety (QI/PS) into their curriculum, medical students continue to have limited QI/PS exposure. To prepare medical students for careers that involve QI/PS, the Institute for Healthcare Improvement chapter at an allopathic medical school and school of allied health professions initiated self-directed learning by offering student-led workshops to equip learners with skills to improve the quality and safety of healthcare processes.

Methods: In this prospective cohort study, workshops were hosted for medical students between 2015 and 2018 on five QI/PS topics: Process Mapping, Root-Cause Analysis (RCA), Plan-Do-Study-Act (PDSA) Cycles, Evidence Based Medicine (EBM), and Patient Handoffs. Each workshop included a hands-on component to engage learners in practical applications of QI/PS skills in their careers. Change in knowledge, attitudes, and behaviors was assessed via pre- and post-surveys using 5-point Likert scales, and analyzed using either the McNemar test or non-parametric Wilcoxon signed-rank test. Surveys also gathered qualitative feedback regarding strengths, future areas for improvement, and reasons for attending the workshops.

Results: Data was collected from 88.5% of learners (n = 185/209); 19.5% of learners reported prior formal instruction in these topics. Statistically significant improvements in learners' confidence were observed for each workshop. Additionally, after attending workshops, learners felt comfortable teaching the learned QI/PS skill to colleagues (mean pre/post difference 1.96, p < 0.0001, n = 139) and were more likely to pursue QI/PS projects in their careers (mean pre/post difference 0.45, p < 0.0001, n = 139). Lastly, learners demonstrated a statistically significant increase in knowledge in four out of five skills workshop topics.

Conclusion: Few medical students have formal instruction in QI/PS tools. This pilot study highlights advantages of incorporating an innovative, student-directed modified 'flipped classroom' methodology, with a focus on active experiential learning and minimal didactic instruction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12909-020-1982-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7181569PMC
April 2020

Improving Influenza Vaccination in Hospitalized Children With Asthma.

Pediatrics 2020 03;145(3)

Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas.

Objectives: Children with asthma are at increased risk of complications from influenza; hospitalization represents an important opportunity for vaccination. We aimed to increase the influenza vaccination rate among eligible hospitalized patients with asthma on the pediatric hospital medicine (PHM) service from 13% to 80% over a 4-year period.

Methods: Serial Plan-Do-Study-Act cycles were implemented to improve influenza vaccination rates among children admitted with status asthmaticus and included modifications to the electronic health record (EHR) and provider and family education. Success of the initial PHM pilot led to the development of a hospital-wide vaccination tracking tool and an institutional, nurse-driven vaccine protocol by a multidisciplinary team. Our primary outcome metric was the inpatient influenza vaccination rate among PHM patients admitted with status asthmaticus. Process measures included documentation of influenza vaccination status and use of the EHR asthma order set and a history and physical template. The balance measure was adverse vaccine reaction within 24 hours. Data analysis was performed by using statistical process control charts.

Results: The inpatient influenza vaccination rate increased from 13% to 57% over 4 years; special cause variation was achieved. Overall, 50% of eligible patients were vaccinated during asthma hospitalization in the postintervention period. Documentation of influenza vaccination status significantly increased from 51% to 96%, and asthma history and physical and order set use also improved. No adverse vaccine reactions were documented.

Conclusions: A bundle of interventions, including EHR modifications, provider and family education, hospital-wide tracking, and a nurse-driven vaccine protocol, increased influenza vaccination rates among eligible children hospitalized with status asthmaticus.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1542/peds.2019-1735DOI Listing
March 2020

Disparities in Access to Oral Health Care.

Annu Rev Public Health 2020 04 3;41:513-535. Epub 2020 Jan 3.

NYU Langone Dental Medicine-Brooklyn, Postdoctoral Residency Program, Brooklyn, New York 11220, USA; email:

In the United States, people are more likely to have poor oral health if they are low-income, uninsured, and/or members of racial/ethnic minority, immigrant, or rural populations who have suboptimal access to quality oral health care. As a result, poor oral health serves as the national symbol of social inequality. There is increasing recognition among those in public health that oral diseases such as dental caries and periodontal disease and general health conditions such as obesity and diabetes are closely linked by sharing common risk factors, including excess sugar consumption and tobacco use, as well as underlying infection and inflammatory pathways. Hence, efforts to integrate oral health and primary health care, incorporate interventions at multiple levels to improve access to and quality of services, and create health care teams that provide patient-centered care in both safety net clinics and community settings may narrow the gaps in access to oral health care across the life course.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-publhealth-040119-094318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7125002PMC
April 2020

A survey of caregiver acculturation and acceptance of silver diamine fluoride treatment for childhood caries.

BMC Oral Health 2019 10 24;19(1):228. Epub 2019 Oct 24.

NYU Langone Dental Medicine, 5800 Third Avenue, Brooklyn, NY, 11220, USA.

Background: Interest in aqueous silver diamine fluoride (SDF) has been growing as a treatment for caries arrest. A cross-sectional study was conducted to identify factors associated with caregiver acceptance of SDF treatment for children presenting with caries at 8 Federally Qualified Health Centers. The study purpose was to examine associations between caregiver acceptance of SDF treatment for children with caries and (1) sociodemographic and acculturation characteristics of caregivers and (2) clinical assessments of the children by dentists.

Methods: A caregiver survey collected information on: sociodemographic characteristics; acculturation characteristics, measured using the validated Short Acculturation Scale for Hispanics (SASH); perceived benefits and barriers of SDF treatment, including caregiver comfort; and perceived health-related knowledge. Chart reviews were conducted to assess: the medical / dental insurance of pediatric patients; cumulative caries experience, measured using decayed, missing, filled teeth total scores (dmft / DMFT); whether operating room treatment was needed; and a record of caregiver acceptance of SDF treatment (the outcome measure). Standard logistic regression models were developed for caregiver acceptance of SDF treatment for their children as the binary outcome of interest (yes / no) to calculate unadjusted odds ratios (OR) and adjusted ORs for covariates of interest.

Results: Overall, 434 of 546 caregivers (79.5%) accepted SDF treatment for their children. A U-shaped relationship between caregiver odds of accepting SDF treatment and age group of pediatric patients was present, where caregivers were most likely to accept SDF treatment for their children who were either < 6 years or 9-14 years, and least likely to accept SDF treatment for children 6 to < 9 years. The relationship between acculturation and caregiver acceptance of SDF treatment depended upon whether or not caregivers were born in the United States: greater acculturation was associated with caregiver acceptance of SDF treatment among caregivers born in this country, and lower acculturation was associated with caregiver acceptance of SDF treatment among caregivers born elsewhere.

Conclusions: Caregiver acceptance of SDF treatment is high; child's age and caregiver comfort are associated with acceptance. Providers need to communicate the risks and benefits of evidence-based dental treatments to increasingly diverse caregiver and patient populations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12903-019-0915-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6814040PMC
October 2019

Hippocampal Neurochemical Profile and Glucose Transport Kinetics in Patients With Type 1 Diabetes.

J Clin Endocrinol Metab 2020 02;105(2)

Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, University of Minnesota, Minneapolis, Minnesota.

Context: Longstanding type 1 diabetes (T1D) may lead to alterations in hippocampal neurochemical profile. Upregulation of hippocampal glucose transport as a result of recurrent exposure to hypoglycemia may preserve cognitive function during future hypoglycemia in subjects with T1D and impaired awareness of hypoglycemia (IAH). The effect of T1D on hippocampal neurochemical profile and glucose transport is unknown.

Objective: To test the hypothesis that hippocampal neurochemical composition is altered in T1D and glucose transport is upregulated in T1D with IAH.

Design And Participants: Hippocampal neurochemical profile was measured with single-voxel magnetic resonance spectroscopy at 3T during euglycemia in 18 healthy controls (HC), 10 T1D with IAH, and 12 T1D with normal awareness to hypoglycemia (NAH). Additionally, 12 HC, 8 T1D-IAH, and 6 T1D-NAH were scanned during hyperglycemia to assess hippocampal glucose transport with metabolic modeling.

Setting: University medical center.

Main Outcome Measures: Concentrations of hippocampal neurochemicals measured during euglycemia and ratios of maximal transport rate to cerebral metabolic rate of glucose (Tmax/CMRGlc), derived from magnetic resonance spectroscopy-measured hippocampal glucose as a function of plasma glucose.

Results: Comparison of hippocampal neurochemical profile revealed no group differences (HC, T1D, T1D-IAH, and T1D-NAH). The ratio Tmax/CMRGlc was not significantly different between the groups, T1D-IAH (1.58 ± 0.09) and HC (1.65 ± 0.07, P = 0.54), between T1D-NAH (1.50 ± 0.09) and HC (P = 0.19), and between T1D-IAH and T1D-NAH (P = 0.53).

Conclusions: Subjects with T1D with sufficient exposure to recurrent hypoglycemia to create IAH did not have alteration of Tmax/CMRglc or neurochemical profile compared with participants with T1D-NAH or HC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/clinem/dgz062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7046023PMC
February 2020

Implementing a Patient-Centered and Cost-Effective School-Based Oral Health Program.

J Sch Health 2019 12 9;89(12):1024-1027. Epub 2019 Oct 9.

Editor Emerita, American Journal of Public Health, NYU Langone Dental Medicine-Brooklyn, Postdoctoral Residency Program, Hansjörg Wyss Department of Plastic Surgery, NYU School of Medicine, 5800 Third Avenue, Room 344, Brooklyn, NY, 11220.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/josh.12842DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6834882PMC
December 2019

Caregiver satisfaction with interim silver diamine fluoride applications for their children with caries prior to operating room treatment or sedation.

J Public Health Dent 2019 12 16;79(4):286-291. Epub 2019 Aug 16.

Extramural and Special Projects, NYU Langone Dental Medicine, Brooklyn, NY, USA.

Objective: To ascertain caregiver satisfaction with silver diamine fluoride (SDF) application(s) as an intermediate care path for their children with caries.

Methods: Caregivers were recruited at two community health centers when they arrived for a previously scheduled operating room/sedation appointment for their children with caries who had previously been treated with SDF. They were asked to complete a survey regarding their satisfaction with SDF treatment while they waited during their children's dental treatment.

Results: Caregivers overwhelmingly reported that they were satisfied with SDF treatment (81.3%), and that the black mark was not an issue for their children (91.7%) or themselves (87.5%). Moreover, their perception of their children's oral health quality of life was high.

Conclusions: By arresting caries, SDF offers an intermediate care path for pediatric patients for whom OR/sedation treatment was not immediately available. Moreover, most caregivers were satisfied with SDF treatment for their children.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jphd.12338DOI Listing
December 2019

Duration and onset of action of high dose U-500 regular insulin in severely insulin resistant subjects with type 2 diabetes.

Endocrinol Diabetes Metab 2018 Oct 10;1(4):e00041. Epub 2018 Sep 10.

Department of Medicine Division of Diabetes, Endocrinology and Metabolism University of Minnesota Minneapolis Minnesota.

Aim: Although regular human U-500 insulin (U-500) is frequently used for insulin resistant type 2 diabetics, pharmacokinetic and pharmacodynamic studies in these individuals are lacking. We set out to determine the rate of onset, duration of action and total glucose lowering effect of two doses of U-500 insulin in obese insulin resistant subjects with type 2 diabetes.

Materials And Methods: Randomized double-blind crossover study was designed to study subjects who were administered either 100 or 200 units SQ of U-500 insulin once and then were provided intravenous glucose as necessary to maintain euglycaemia.

Results: A total of 12 subjects were studied. The time during which intravenous glucose was required to maintain euglycaemia following a 200-unit dose of U-500 insulin was significantly greater than the time following a 100-unit dose. No differences were found between doses in measures related to the rate of onset or in the total amount of intravenous glucose required to maintain euglycaemia for the duration of the study.

Conclusions: The duration of action of U-500 increases when dose is increased from 100 to 200 units. Neither dose of U-500 insulin has an onset of action before 2.5 hours after administration. This suggests that U-500 should not be used as a premeal bolus insulin to lower glucose two hours after a meal and that dosing intervals might need to be extended as dose is increased to avoid hypoglycaemia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/edm2.41DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6354819PMC
October 2018

Surgical Care and Outcomes Assessment Program (SCOAP): A Nuanced, Flexible Platform for Colorectal Surgical Research.

Clin Colon Rectal Surg 2019 Jan 8;32(1):25-32. Epub 2019 Jan 8.

Elson S. Floyd College of Medicine, Washington State University, Everett, Spokane, Tri-Cities, and Vancouver, Washington.

The Surgical Care and Outcomes Assessment Program (SCOAP) is a surgeon-led quality improvement (QI) initiative developed in Washington State to track and reduce variability in surgical care. It has developed into a collaboration of over two-thirds of the hospitals in the state, who share data and receive regular benchmarking reports. Data are abstracted at each site by trained abstractors. While there has some overlap with other national QI databases, the data captured by SCOAP has clinical nuances that make it pragmatic for studying surgical care. We review the unique properties of SCOAP and offer some examples of its novel applications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0038-1673351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327740PMC
January 2019

Publisher Correction: Evidence linking microRNA suppression of essential prosurvival genes with hippocampal cell death after traumatic brain injury.

Sci Rep 2018 Oct 8;8(1):14994. Epub 2018 Oct 8.

Department of Anesthesiology, University of Texas Medical Branch, Galveston, Texas, USA.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-018-31991-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6175884PMC
October 2018

Consolidation mFOLFOX6 Chemotherapy After Chemoradiotherapy Improves Survival in Patients With Locally Advanced Rectal Cancer: Final Results of a Multicenter Phase II Trial.

Dis Colon Rectum 2018 Oct;61(10):1146-1155

Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.

Background: Adding modified FOLFOX6 (folinic acid, fluorouracil, and oxaliplatin) after chemoradiotherapy and lengthening the chemoradiotherapy-to-surgery interval is associated with an increase in the proportion of rectal cancer patients with a pathological complete response.

Objective: The purpose of this study was to analyze disease-free and overall survival.

Design: This was a nonrandomized phase II trial.

Settings: The study was conducted at multiple institutions.

Patients: Four sequential study groups with stage II or III rectal cancer were included.

Intervention: All of the patients received 50 Gy of radiation with concurrent continuous infusion of fluorouracil for 5 weeks. Patients in each group received 0, 2, 4, or 6 cycles of modified FOLFOX6 after chemoradiation and before total mesorectal excision. Patients were recommended to receive adjuvant chemotherapy after surgery to complete a total of 8 cycles of modified FOLFOX6.

Main Outcome Measures: The trial was powered to detect differences in pathological complete response, which was reported previously. Disease-free and overall survival are the main outcomes for the current study.

Results: Of 259 patients, 211 had a complete follow-up. Median follow-up was 59 months (range, 9-125 mo). The mean number of total chemotherapy cycles differed among the 4 groups (p = 0.002), because one third of patients in the group assigned to no preoperative FOLFOX did not receive any adjuvant chemotherapy. Disease-free survival was significantly associated with study group, ypTNM stage, and pathological complete response (p = 0.004, <0.001, and 0.001). A secondary analysis including only patients who received ≥1 cycle of FOLFOX still showed differences in survival between study groups (p = 0.03).

Limitations: The trial was not randomized and was not powered to show differences in survival. Survival data were not available for 19% of the patients.

Conclusions: Adding modified FOLFOX6 after chemoradiotherapy and before total mesorectal excision increases compliance with systemic chemotherapy and disease-free survival in patients with locally advanced rectal cancer. Neoadjuvant consolidation chemotherapy may have benefits beyond increasing pathological complete response rates. See Video Abstract at http://links.lww.com/DCR/A739.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/DCR.0000000000001207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6130918PMC
October 2018

Presence of artisanal gold mining predicts mercury bioaccumulation in five genera of bats (Chiroptera).

Environ Pollut 2018 May;236:862-870

Department of Marine Chemistry and Geochemistry, Woods Hole Oceanographic Institution, 266 Woods Hole Rd., Woods Hole, MA, USA; Department of Ocean Sciences, University of California, Santa Cruz, 1156 High St., Santa Cruz, CA, USA. Electronic address:

Mercury, a toxic trace metal, has been used extensively as an inexpensive and readily available method of extracting gold from fine-grained sediment. Worldwide, artisanal mining is responsible for one third of all mercury released into the environment. By testing bat hair from museum specimens and field collected samples from areas both impacted and unimpacted by artisanal gold mining in Perú, we show monomethylmercury (MMHg) has increased in the last 100 years. MMHg concentrations were also greatest in the highest bat trophic level (insectivores), and in areas experiencing extractive artisanal mining. Reproductive female bats had higher MMHg concentrations, and both juvenile and adult bats from mercury contaminated sites had more MMHg than those from uncontaminated sites. Bats have important ecological functions, providing vital ecosystem services such as pollination, seed dispersal, and insect control. Natural populations can act as environmental sentinels and offer the chance to expand our understanding of, and responses to, environmental and human health concerns.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envpol.2018.01.109DOI Listing
May 2018

Type 1 Diabetes and Impaired Awareness of Hypoglycemia Are Associated with Reduced Brain Gray Matter Volumes.

Front Neurosci 2017 25;11:529. Epub 2017 Sep 25.

Department of Radiology, Center for Magnetic Resonance Research, University of MinnesotaMinneapolis, MN, United States.

In this study, we retrospectively analyzed the anatomical MRI data acquired from 52 subjects with type 1 diabetes (26M/26F, 36 ± 11 years old, A1C = 7.2 ± 0.9%) and 50 age, sex and BMI frequency-matched non-diabetic controls (25M/25F, 36 ± 14 years old). The T1D group was further sub-divided based on whether subjects had normal, impaired, or indeterminate awareness of hypoglycemia ( = 31, 20, and 1, respectively). Our goals were to test whether the gray matter (GM) volumes of selected brain regions were associated with diabetes status as well as with the status of hypoglycemia awareness. T1D subjects were found to have slightly smaller volume of the whole cortex as compared to controls (-2.7%, = 0.016), with the most affected brain region being the frontal lobe (-3.6%, = 0.024). Similar differences of even larger magnitude were observed among the T1D subjects based on their hypoglycemia awareness status. Indeed, compared to the patients with normal awareness of hypoglycemia, patients with impaired awareness had smaller volume of the whole cortex (-7.9%, = 0.0009), and in particular of the frontal lobe (-9.1%, = 0.006), parietal lobe (-8.0%, = 0.015) and temporal lobe (-8.2%, = 0.009). Such differences were very similar to those observed between patients with impaired awareness and controls (-7.6%, = 0.0002 in whole cortex, -9.1%, = 0.0003 in frontal lobe, -7.8%, = 0.002 in parietal lobe, and -6.4%, = 0.019 in temporal lobe). On the other hand, patients with normal awareness did not present significant volume differences compared to controls. No group-differences were observed in the occipital lobe or in the anterior cingulate, posterior cingulate, hippocampus, and thalamus. We conclude that diabetes status is associated with a small but statistically significant reduction of the whole cortex volume, mainly in the frontal lobe. The most prominent structural effects occurred in patients with impaired awareness of hypoglycemia (IAH) as compared to those with normal awareness, perhaps due to the long-term exposure to recurrent episodes of hypoglycemia. Future studies aimed at quantifying relationships of structural outcomes with functional outcomes, with cognitive performance, as well as with parameters describing glucose variability and severity of hypoglycemia episodes, will be necessary to further understand the impact of T1D on the brain.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnins.2017.00529DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5622182PMC
September 2017

Hypothalamic Glucose Transport in Humans During Experimentally Induced Hypoglycemia-Associated Autonomic Failure.

J Clin Endocrinol Metab 2017 09;102(9):3571-3580

Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota, Minneapolis, Minnesota 55455.

Context: Upregulated brain glucose transport in response to recurrent hypoglycemia may contribute to the development of hypoglycemia-associated autonomic failure (HAAF) and impaired awareness of hypoglycemia. Whether recurrent hypoglycemia alters glucose transport in the hypothalamus is unknown.

Objective: To test the hypothesis that hypothalamic glucose transport will increase in healthy volunteers preconditioned with recurrent hypoglycemia to induce HAAF.

Setting: University medical center.

Design And Participants: Thirteen healthy subjects underwent paired euglycemic and hypoglycemic preconditioning studies separated by at least 1 month. Following preconditioning, hypothalamic glucose transport was measured by magnetic resonance spectroscopy (MRS) in the afternoon on day 2 of each preconditioning protocol.

Outcome Measure: The ratio of maximal transport rate to cerebral metabolic rate of glucose (Tmax/CMRglc), obtained from MRS-measured glucose in the hypothalamus as a function of plasma glucose.

Results: HAAF was successfully induced based on lower epinephrine, glucagon, and cortisol during the third vs first hypoglycemic preconditioning clamp (P ≤ 0.01). Hypothalamic glucose transport was not different following recurrent euglycemia vs hypoglycemia (Tmax/CMRglc 1.62 ± 0.09 after euglycemia preconditioning and 1.75 ± 0.14 after hypoglycemia preconditioning; P was not significant). Hypothalamic glucose concentrations measured by MRS were not different following the two preconditioning protocols.

Conclusions: Glucose transport kinetics in the hypothalamus of healthy humans with experimentally induced HAAF were not different from those measured without HAAF. Future studies of patients with diabetes and impaired awareness of hypoglycemia will be necessary to determine if the existence of the diabetes state is required for this adaptation to hypoglycemia to occur.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/jc.2017-00477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5587056PMC
September 2017

Evidence linking microRNA suppression of essential prosurvival genes with hippocampal cell death after traumatic brain injury.

Sci Rep 2017 07 27;7(1):6645. Epub 2017 Jul 27.

Department of Anesthesiology, University of Texas Medical Branch, Galveston, Texas, USA.

The underlying molecular mechanisms of how dysregulated microRNAs (miRNAs) cause neurodegeneration after traumatic brain injury (TBI) remain elusive. Here we analyzed the biological roles of approximately 600 genes - we previously found these dysregulated in dying and surviving rat hippocampal neurons - that are targeted by ten TBI-altered miRNAs. Bioinformatic analysis suggests that neurodegeneration results from a global miRNA-mediated suppression of genes essential for maintaining proteostasis; many are hub genes - involved in RNA processing, cytoskeletal metabolism, intracellular trafficking, cell cycle progression, repair/maintenance, bioenergetics and cell-cell signaling - whose disrupted expression is linked to human disease. Notably, dysregulation of these essential genes would significantly impair synaptic function and functional brain connectivity. In surviving neurons, upregulated miRNA target genes are co-regulated members of prosurvival pathways associated with cellular regeneration, neural plasticity, and development. This study captures the diversity of miRNA-regulated genes that may be essential for cell repair and survival responses after TBI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-017-06341-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5532254PMC
July 2017

Local Excision of Rectal Cancer.

Surg Clin North Am 2017 Jun;97(3):573-585

Colorectal Surgery Program, Section of General, Thoracic, and Vascular Surgery, Virginia Mason Medical Center, 1100 9th Avenue Seattle, WA 98101, USA. Electronic address:

Local excision (LE) of early-stage rectal cancer avoids the morbidity associated with radical surgery but has historically been associated with inferior oncologic outcomes. Newer techniques, including transanal endoscopic microsurgery (TEM) and transanal minimally invasive surgery (TAMIS), have been developed to improve the quality of LE and extend the benefits of LE to tumors in the more proximal rectum. This article provides an overview of conventional LE, TEM, and TAMIS techniques, including indications for their use and pertinent literature on their associated outcomes for rectal cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.suc.2017.01.007DOI Listing
June 2017

Colonoscopy: Advanced and Emerging Techniques-A Review of Colonoscopic Approaches to Colorectal Conditions.

Clin Colon Rectal Surg 2017 Apr;30(2):136-144

Swedish Colon and Rectal Clinic, Seattle, Washington.

A complete colonoscopy is key in the diagnostic and therapeutic approaches to a variety of colorectal diseases. Major challenges are incomplete polyp removal and missed polyps, particularly in the setting of a difficult colonoscopy. There are a variety of both well-established and newer techniques that have been developed to optimize polyp detection, perform complete polypectomy, and endoscopically treat various complications and conditions such as strictures and perforations. The objective of this article is to familiarize the colorectal surgeon with techniques utilized by advanced endoscopists.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0036-1597312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5380462PMC
April 2017

Methods of Evaluation of Anorectal Causes of Obstructed Defecation.

Clin Colon Rectal Surg 2017 Feb;30(1):46-56

Colorectal Surgery Program, Virginia Mason Medical Center, Seattle, Washington.

Obstructed defecation is a complex disorder that results in impaired propagation of stool from the rectum. It is one of the major subtypes of functional constipation and can be secondary to either functional or anatomic etiologies. Patients with obstructed defecation typically present with symptoms of abdominal discomfort, a sensation of incomplete evacuation and rectal obstruction, passage of hard stools, the need for rectal or vaginal digitation, excessive straining, and reduced stool frequency. Evaluation of obstructed defecation is multimodal, starting with a thorough history and physical examination with focus on the abdominal, perineal, and rectal examination. Additional modalities to elicit the diagnosis of obstructed defecation include proctoscopy, colonic transit time studies, anorectal manometry, a rectal balloon expulsion test, defecography, electromyography, and ultrasound. The results from these studies should be taken in the context of each patient's clinical situation, as there is no single criterion standard for the diagnosis of obstructed defecation. Surgery is typically a last resort for these patients and the majority of patients will have good symptomatic management with diet and lifestyle changes. Patients who are found to have functional mechanisms behind their obstructed defecation also benefit from pelvic floor exercises and biofeedback therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0036-1593427DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5179274PMC
February 2017

Cerebral glycogen in humans following acute and recurrent hypoglycemia: Implications on a role in hypoglycemia unawareness.

J Cereb Blood Flow Metab 2017 Aug 1;37(8):2883-2893. Epub 2016 Jan 1.

3 Department of Medicine, University of Minnesota, Minneapolis, USA.

Supercompensated brain glycogen levels may contribute to the development of hypoglycemia-associated autonomic failure (HAAF) following recurrent hypoglycemia (RH) by providing energy for the brain during subsequent periods of hypoglycemia. To assess the role of glycogen supercompensation in the generation of HAAF, we estimated the level of brain glycogen following RH and acute hypoglycemia (AH). After undergoing 3 hyperinsulinemic, euglycemic and 3 hyperinsulinemic, hypoglycemic clamps (RH) on separate occasions at least 1 month apart, five healthy volunteers received [1-C]glucose intravenously over 80+ h while maintaining euglycemia. C-glycogen levels in the occipital lobe were measured by C magnetic resonance spectroscopy at ∼8, 20, 32, 44, 56, 68 and 80 h at 4 T and glycogen levels estimated by fitting the data with a biophysical model that takes into account the tiered glycogen structure. Similarly, prior C-glycogen data obtained following a single hypoglycemic episode (AH) were fitted with the same model. Glycogen levels did not significantly increase after RH relative to after euglycemia, while they increased by ∼16% after AH relative to after euglycemia. These data suggest that glycogen supercompensation may be blunted with repeated hypoglycemic episodes. A causal relationship between glycogen supercompensation and generation of HAAF remains to be established.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0271678X16678240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5536796PMC
August 2017

Measurement of Hypothalamic Glucose Under Euglycemia and Hyperglycemia by MRI at 3T.

J Magn Reson Imaging 2017 03 12;45(3):681-691. Epub 2016 Jul 12.

Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota, Minneapolis, Minnesota, USA.

Purpose: To evaluate the feasibility of using a clinical magnetic resonance (MR) system and MR spectroscopy (MRS) to measure glucose concentration changes in the human hypothalamus, a structure central to whole-body glucose regulation.

Subjects And Methods: A time series of MR spectra (semi-LASER, TE = 28 msec), localized to the bilateral hypothalamus (∼1.6 ml) were obtained at 3T in six healthy subjects at baseline (euglycemia) and during a ∼65-70-minute-long hyperglycemic clamp in 11-minute blocks with interleaved T FLASH images to retrospectively assess head motion, and track changes in cerebrospinal fluid (CSF) partial volume. The LCModel was used to quantify the sum of glucose and taurine concentrations, [Glc+Tau], along with their associated Cramér-Rao lower bounds (CRLB).

Results: Spectral quality allowed quantification of [Glc+Tau] (sum reported due to high negative correlation between these metabolites) with CRLB <25% in 35/36 timepoints during hyperglycemia. Increased [Glc+Tau] was observed with hyperglycemia in all subjects, but most reliably in those with plasma glucose targets ≥300 mg/dl. For these subjects, [Glc+Tau] (n = 4) was 1.5 (±0.3, SD) mM, and increased to 4.5 (±1.1) mM (n = 16) for timepoints acquired ≥25 minutes after onset of the clamp, with 15/16 timepoints having no overlap of 95% confidence intervals (CIs) between baseline and hyperglycemia. Preliminary analysis revealed a linear (1:5) relationship between hypothalamus-blood glucose concentrations.

Conclusion: It is feasible to measure glucose concentration changes in the human hypothalamus using a standard 3T scanner and a short-echo semi-LASER sequence by utilizing retrospective motion tracking, CSF correction, predetermined quality acceptance criteria, and hyperglycemic blood glucose levels ≥300 mg/dl.

Level Of Evidence: 2 J. Magn. Reson. Imaging 2017;45:681-691.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jmri.25383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5575789PMC
March 2017

Major Protein of Carcinoembryonic Antigen Gene Family - CD66c, A Novel Marker in Colon Carcinoma.

J Clin Diagn Res 2016 Feb 1;10(2):XC01-XC04. Epub 2016 Feb 1.

Professor, Department of Biochemistry, Centre of Excellence in Molecular Biology and Regenerative Medicine, JSS Medical College, JSS University , Mysore, Karnataka, India .

Introduction: In view of rising trend of the incidence of colorectal carcinoma in the Indian population due to adoption of western lifestyles and behaviours, we investigated the expression of the new emerging stem cell biomarker, CD66c in colorectal carcinoma of Indian origin.

Aim: To study the expression of CD66c in human colorectal carcinoma and to correlate level of marker expression with tumour staging.

Materials And Methods: This hospital based prospective study was conducted on 26 colorectal carcinoma patients in the age group of 20 years to 70 years. Surgically resected tumour specimens along with adjacent normal tissue were collected taking necessary precautions, paraffin embedded sections were prepared and used for histological and immunohistochemical analysis of CD66c.

Statistical Analysis: Descriptive statistical measures like mean, standard deviation, percentage was applied. Other inferential statistical tests like Chi-square, Fisher's-exact test and one-way ANOVA was applied to find out the association of CD66c with different stages. The difference were interpreted as statistically significant when p <0.05.

Results: CD66c showed differential expression with membrane positivity in normal colorectal epithelial cells and cytoplasmic expression in tumour cells. There was significant correlation between CD66c expression and tumour site (p=0.02) with colon carcinoma showing positive expression compared to the rectal carcinoma. There was no significant correlation between CD66c staining and tumour stage (p=0.947). No significant relationship was observed between CD66c expression and other clinicopathologic variables studied such as sex (p=0.552), age (p=0.713) and tumour grade (p=0.263).

Conclusion: CD66c can be specifically used for colon carcinoma and may be a novel marker in colon carcinoma stem cell isolation. The quantification of CD66c can be further verified by flow cytometry and RT-PCR. Further studies can be carried out using CD66c alone or in combination with other markers to develop cancer stem cell directed therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7860/JCDR/2016/17180.7286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4800633PMC
February 2016

Naltrexone for treatment of impaired awareness of hypoglycemia in type 1 diabetes: A randomized clinical trial.

J Diabetes Complications 2015 Nov-Dec;29(8):1277-82. Epub 2015 Aug 12.

Division of Endocrinology and Diabetes, Department of Medicine, University of Minnesota, Minneapolis, MN, United States.

Aims: Impaired awareness of hypoglycemia (IAH) is a limiting factor in the treatment of type 1 diabetes (T1D) and is a challenging condition to reverse. The objective of this study was to test the hypothesis that naltrexone therapy in subjects with T1D and IAH will improve counterregulatory hormone response and recognition of hypoglycemia symptoms during hypoglycemia.

Methods: We performed a pilot randomized double blind trial of 4weeks of naltrexone therapy (n=10) or placebo (n=12) given orally in subjects with T1D and IAH. Outcome measures included hypoglycemia symptom scores, counterregulatory hormone levels and thalamic activation as measured by cerebral blood flow using MRI during experimental hypoglycemia in all subjects before and after 4weeks of intervention.

Results: After 4weeks of therapy with naltrexone or placebo, no significant differences in response to hypoglycemia were seen in any outcomes of interest within each group.

Conclusions: In this small study, short-term treatment with naltrexone did not improve recognition of hypoglycemia symptoms or counterregulatory hormone response during experimental hypoglycemia in subjects with T1D and IAH. Whether this lack of effect is related to the small sample size or due to the dose, the advanced stage of study population or the drug itself should be the subject of future investigation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jdiacomp.2015.08.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4871128PMC
September 2016

Revisiting Glycogen Content in the Human Brain.

Neurochem Res 2015 Dec 23;40(12):2473-81. Epub 2015 Jul 23.

Department of Medicine, University of Minnesota, Minneapolis, MN, USA.

Glycogen provides an important glucose reservoir in the brain since the concentration of glucosyl units stored in glycogen is several fold higher than free glucose available in brain tissue. We have previously reported 3-4 µmol/g brain glycogen content using in vivo (13)C magnetic resonance spectroscopy (MRS) in conjunction with [1-(13)C]glucose administration in healthy humans, while higher levels were reported in the rodent brain. Due to the slow turnover of bulk brain glycogen in humans, complete turnover of the glycogen pool, estimated to take 3-5 days, was not observed in these prior studies. In an attempt to reach complete turnover and thereby steady state (13)C labeling in glycogen, here we administered [1-(13)C]glucose to healthy volunteers for 80 h. To eliminate any net glycogen synthesis during this period and thereby achieve an accurate estimate of glycogen concentration, volunteers were maintained at euglycemic blood glucose levels during [1-(13)C]glucose administration and (13)C-glycogen levels in the occipital lobe were measured by (13)C MRS approximately every 12 h. Finally, we fitted the data with a biophysical model that was recently developed to take into account the tiered structure of the glycogen molecule and additionally incorporated blood glucose levels and isotopic enrichments as input function in the model. We obtained excellent fits of the model to the (13)C-glycogen data, and glycogen content in the healthy human brain tissue was found to be 7.8 ± 0.3 µmol/g, a value substantially higher than previous estimates of glycogen content in the human brain.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11064-015-1664-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4674365PMC
December 2015

Effect of adding mFOLFOX6 after neoadjuvant chemoradiation in locally advanced rectal cancer: a multicentre, phase 2 trial.

Lancet Oncol 2015 Aug 14;16(8):957-66. Epub 2015 Jul 14.

Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Background: Patients with locally advanced rectal cancer who achieve a pathological complete response to neoadjuvant chemoradiation have an improved prognosis. The need for surgery in these patients has been questioned, but the proportion of patients achieving a pathological complete response is small. We aimed to assess whether adding cycles of mFOLFOX6 between chemoradiation and surgery increased the proportion of patients achieving a pathological complete response.

Methods: We did a phase 2, non-randomised trial consisting of four sequential study groups of patients with stage II-III locally advanced rectal cancer at 17 institutions in the USA and Canada. All patients received chemoradiation (fluorouracil 225 mg/m(2) per day by continuous infusion throughout radiotherapy, and 45·0 Gy in 25 fractions, 5 days per week for 5 weeks, followed by a minimum boost of 5·4 Gy). Patients in group 1 had total mesorectal excision 6-8 weeks after chemoradiation. Patients in groups 2-4 received two, four, or six cycles of mFOLFOX6, respectively, between chemoradiation and total mesorectal excision. Each cycle of mFOLFOX6 consisted of racemic leucovorin 200 mg/m(2) or 400 mg/m(2), according to the discretion of the treating investigator, oxaliplatin 85 mg/m(2) in a 2-h infusion, bolus fluorouracil 400 mg/m(2) on day 1, and a 46-h infusion of fluorouracil 2400 mg/m(2). The primary endpoint was the proportion of patients who achieved a pathological complete response, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00335816.

Findings: Between March 24, 2004, and Nov 16, 2012, 292 patients were registered, 259 of whom (60 in group 1, 67 in group 2, 67 in group 3, and 65 in group 4) met criteria for analysis. 11 (18%, 95% CI 10-30) of 60 patients in group 1, 17 (25%, 16-37) of 67 in group 2, 20 (30%, 19-42) of 67 in group 3, and 25 (38%, 27-51) of 65 in group 4 achieved a pathological complete response (p=0·0036). Study group was independently associated with pathological complete response (group 4 compared with group 1 odds ratio 3·49, 95% CI 1·39-8·75; p=0·011). In group 2, two (3%) of 67 patients had grade 3 adverse events associated with the neoadjuvant administration of mFOLFOX6 and one (1%) had a grade 4 adverse event; in group 3, 12 (18%) of 67 patients had grade 3 adverse events; in group 4, 18 (28%) of 65 patients had grade 3 adverse events and five (8%) had grade 4 adverse events. The most common grade 3 or higher adverse events associated with the neoadjuvant administration of mFOLFOX6 across groups 2-4 were neutropenia (five in group 3 and six in group 4) and lymphopenia (three in group 3 and four in group 4). Across all study groups, 25 grade 3 or worse surgery-related complications occurred (ten in group 1, five in group 2, three in group 3, and seven in group 4); the most common were pelvic abscesses (seven patients) and anastomotic leaks (seven patients).

Interpretation: Delivery of mFOLFOX6 after chemoradiation and before total mesorectal excision has the potential to increase the proportion of patients eligible for less invasive treatment strategies; this strategy is being tested in phase 3 clinical trials.

Funding: National Institutes of Health National Cancer Institute.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S1470-2045(15)00004-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4670237PMC
August 2015