Diabetes-by-Proxy: Virtual Embodiment of Disease by Oklahoma Choctaw Parents of Children with Type 1 Diabetes.

Childhood type 1 diabetes is increasing globally and requires meticulous at-home care due to risks for fatal outcomes if glucose levels are not continuously and correctly monitored. Type 1 diabetes research has focused on metabolism and stress measurements confirming high parental worry levels. However, research on caregivers' management strategies has lagged. We show parents' intense, all-encompassing work to preempt a disastrous drop in their child's glucose as a stress-path to the virtual embodiment of their child's condition. That is, parents acquire diabetes-by-proxy. Our findings derive from four and half years of ethnographic research with the same 19 families in the Choctaw Nation of Oklahoma. These parents were exceptionally engaged as caregivers and distressed by the potentially fatal outcome of type 1 diabetes mismanagement. Diabetes-by-proxy names the parents' experience and validates clinical attention to them as they cope with their crucial caregiving commitment.

A Cross-Sectional Review of Cervical Cancer Messages on Twitter During Cervical Cancer Awareness Month.

OBJECTIVES: The objectives of this study were to quantify personal stories about cervical cancer and to determine the proportion and sentiment (positive vs negative) of messages ("tweets") that discussed cervical cancer prevention strategies on Twitter. METHODS: This study was a cross-sectional Twitter review of English-language top tweets about cervical cancer during the Cervical Cancer Awareness month, January 2016. Theme categories were identified, and tweets were independently coded by 2 reviewers; discrepancies in coding were resolved by a third reviewer. Descriptive statistical analyses were performed. RESULTS: During January 2016, approximately 348 top tweets about cervical cancer were identified. Professional health organizations produced 20.7% of tweets, and individuals identifying themselves as health-care professionals contributed an additional 4%. In addition to the tweet, 45.1% attached a photo or video; 54.6% included links to a larger article. Only 11.2% of tweets included personal stories from cervical cancer patients. Among the top tweets, 70.3% were focused on prevention through screening and/or HPV vaccination, with 97.4% recommending such practices. A substantial proportion of the Twitter traffic (24.7%) referenced the #SmearForSmear campaign by the patient-advocate organization Jo's Cervical Cancer Trust, based in the United Kingdom. CONCLUSIONS: Analysis of top tweets during the cervical cancer awareness month showed that, although personal stories about cervical cancer were rare, cervical cancer prevention was a popular topic during the cervical cancer awareness month. This was largely driven by a picture-based twitter campaign from a single advocacy organization.

What is the role of retroperitoneal exploration in optimally debulked stage IIIC epithelial ovarian cancer? An NRG Oncology/Gynecologic Oncology Group ancillary data study.

BACKGROUND: The purpose of this study was to determine the effect of retroperitoneal (RP) exploration on progression-free survival (PFS) and overall survival (OS) in epithelial ovarian cancer (EOC) patients with stage IIIC disease who underwent optimal debulking surgery. METHODS: Data were collected from records of the Gynecologic Oncology Group 182 (GOG-182) study of stage IIIC EOC patients cytoreduced to no gross residual disease (R0) or minimal gross residual (<1 cm) disease (MGRD) at primary surgery. Patients with stage IIIC disease by intraperitoneal (IP) tumor were included and divided into 3 groups: 1) > 2 cm IP tumor without lymph node involvement (IP/RP-), 2) > 2 cm IP tumor with lymph node involvement (IP/RP+), and 3) > 2 cm IP tumor with no RP exploration (IP/RP?). The effects of disease distribution and RP exploration on PFS and OS were assessed using Kaplan-Meier and proportional hazards methods. RESULTS: There were 1871 stage IIIC patients in GOG-182 who underwent optimal primary debulking surgery. Of these, 689 (36.8%) underwent RP exploration with removal of lymph nodes from at least 1 para-aortic site, and 1182 (63.2%) did not. There were 269 patients in the IP/RP- group, 420 patients in the IP/RP + group, and 1182 patients in the IP/RP? group. Improved PFS (18.5 vs 16.0 months; P < .0001) and OS (53.3 vs 42.8 months; P < .0001) were associated with RP exploration versus no exploration. Patients with MGRD had improved PFS (16.8 vs 15.1 months, P = 0.0108) and OS (44.9 vs 40.5 months, P = 0.0076) versus no exploration. CONCLUSIONS: RP exploration at the time of primary surgery in patients with optimally debulked stage IIIC EOC is associated with a survival benefit. Cancer 2017;123:985-93. © 2016 American Cancer Society.

The effect of photobiomodulation on chemotherapy-induced peripheral neuropathy: A randomized, sham-controlled clinical trial.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of cancer therapy with few efficacious treatments. METHODS: We enrolled 70 patients with CIPN in a randomized, double-blinded, sham-controlled, cross-over trial to determine if photobiomodulation (PBM)±physiotherapy reduced the symptoms of neuropathy compared to sham treatment. At the conclusion of follow-up, sham-arm patients could cross-over into a third arm combining PBM and physiotherapy to determine if multimodal treatment had additive effects. Treatment included 30minute sessions 3-times weekly for 6weeks using either PBM or sham therapy. Neuropathy was assessed using the modified total neuropathy score (mTNS) at initiation and 4, 8, and 16weeks after initiating treatment. RESULTS: Sham-treated patients experienced no significant change in mTNS scores at any point during the primary analysis. PBM patients experienced significant reduction in mTNS scores at all time points. Mean changes in mTNS score (and corresponding percent drop from baseline) for sham and PBM-group patients respectively were -0.1 (-0.7%) and -4.2 (-32.4%) at 4weeks (p<0.001), 0.2 (0.0%) and -6.8 (-52.6%) at 8weeks (p<0.001), and 0.0 (0.1%) and -5.0 (-38.8%) at 16weeks (p<0.001). Patients who crossed over into the PBM/PT-group experienced similar results to those treated primarily; changes in mTNS score from baseline were -5.5 (-40.6%) 4weeks (p<0.001), -6.9 (-50.9%) at 8weeks (p<0.001), and -4.9 (-35.9%) at 16weeks (p<0.001). The addition of physiotherapy did not improve outcomes over PBM alone. CONCLUSION AND RELEVANCE: Among patients with CIPN, PBM produced significant reduction in neuropathy symptoms.

Ultrasound guided subcostal transversus abdominis plane (TAP) infiltration with liposomal bupivacaine for patients undergoing robotic assisted hysterectomy: A prospective randomized controlled study.

INTRODUCTION: Optimal pain control after major surgery contributes to a patient's recovery and satisfaction. The use of liposomal bupivacaine in subcostal transversus abdominis plane (TAP) blocks for postoperative pain control after robot assisted abdominal surgery has yet to be studied. METHODS: We conducted a prospective randomized controlled observer-blinded study comparing bilateral subcostal TAP blocks with bupivacaine to bilateral subcostal TAP blocks with liposomal bupivacaine. These were performed prior to the patient undergoing robot assisted hysterectomy. The patients' pain scores, opioid use, side effects, and satisfaction were followed for 72h after injection. RESULTS: Total opioid use in the first 72h after injection was significantly decreased in the group that received liposomal bupivacaine compared to bupivacaine. Patients in the liposomal bupivacaine group had significantly lower maximal pain scores at all time periods studied as well as decreased incidence of nausea/vomiting. There was a trend toward decreased length of stay in the liposomal bupivacaine group. CONCLUSION: Subcostal TAP blocks with liposomal bupivacaine decreased the total opioid requirement for the first 72h after robot assisted hysterectomy when compared to subcostal TAP blocks with bupivacaine.

Hyperthermic intraperitoneal chemotherapy with carboplatin for optimally-cytoreduced, recurrent, platinum-sensitive ovarian carcinoma: a pilot study.

OBJECTIVE: We aimed to evaluate the feasibility and tolerability of hyperthermic intraperitoneal carboplatin (HIPEC-carboplatin) following secondary cytoreduction for recurrent, platinum-sensitive ovarian cancer. METHODS: In a single institution prospective, pilot study, ten patients underwent secondary cytoreductive surgery followed by HIPEC-carboplatin at 1000 mg/m(2). Consolidation (6 cycles) was with platinum-based regimens. Adverse and quality of life were measured throughout treatment. RESULTS: Twelve patients were enrolled of which 2 were excluded (one each for extra-abdominal disease indentified before surgery and suboptimal cytoreduction). All 10 remaining patients received prescribed HIPEC-carboplatin. There were no intra-operative complications or AEs attributable to HIPEC-therapy. Grade 1/2 nausea was the most common post-operative toxicity (6/10 patients). Two patients had grade 4 post-operative neutropenia and thrombocytopenia but only one experienced transient treatment delay. The median hospital stay was 5.5 days. 69/70 (98%) of planned chemotherapy doses were ultimately delivered with 1 patient electively forgoing her final treatment. At a median (range) follow-up of 16 (6-23) months, three patients have recurred at 8, 14, and 16 months from surgery. The median disease-free and overall survivals have not been reached. Fact-O scores were significantly lower following surgery (126 vs. 108, p<.01), but improved by completion of therapy (108 vs. 113, p=0.27). CONCLUSIONS: HIPEC-carboplatin at 1000 mg/m(2) following optimal cytoreduction for ovarian cancer is feasible. Surgical complications were not observed, and post-operative AEs were largely within expected ranges. Consolidation using standard platinum-based regimens was feasible following HIPEC-carboplatin, and preliminary survival data suggests efficacy. Further investigation of HIPEC-carboplatin in the setting of debulkable cancer recurrence is warranted.

A phase II study of allogeneic natural killer cell therapy to treat patients with recurrent ovarian and breast cancer.

BACKGROUND: Natural killer (NK) cells derived from patients with cancer exhibit diminished cytotoxicity compared with NK cells from healthy individuals. We evaluated the tumor response and in vivo expansion of allogeneic NK cells in recurrent ovarian and breast cancer. METHODS: Patients underwent a lymphodepleting preparative regimen: fludarabine 25 mg/m(2) × 5 doses, cyclophosphamide 60 mg/kg × 2 doses, and, in seven patients, 200 cGy total body irradiation (TBI) to increase host immune suppression. An NK cell product, from a haplo-identical related donor, was incubated overnight in 1000 U/mL interleukin (IL)-2 prior to infusion. Subcutaneous IL-2 (10 MU) was given three times/week × 6 doses after NK cell infusion to promote expansion, defined as detection of ≥100 donor-derived NK cells/µL blood 14 days after infusion, based on molecular chimerism and flow cytometry. RESULTS: Twenty (14 ovarian, 6 breast) patients were enrolled. The median age was 52 (range 30-65) years. Mean NK cell dose was 2.16 × 10(7)cells/kg. Donor DNA was detected 7 days after NK cell infusion in 9/13 (69%) patients without TBI and 6/7 (85%) with TBI. T-regulatory cells (Treg) were elevated at day +14 compared with pre-chemotherapy (P = 0.03). Serum IL-15 levels increased after the preparative regimen (P = <0.001). Patients receiving TBI had delayed hematologic recovery (P = 0.014). One patient who was not evaluable had successful in vivo NK cell expansion. CONCLUSIONS: Adoptive transfer of haplo-identical NK cells after lymphodepleting chemotherapy is associated with transient donor chimerism and may be limited by reconstituting recipient Treg cells. Strategies to augment in vivo NK cell persistence and expansion are needed.

Effect of age and comorbidity on the treatment and survival of older patients with vulvar cancer.

OBJECTIVE: To determine the disease characteristics and comorbidities predictive of vulvar cancer specific mortality and five year overall survival among older women, ages 65 and above. METHODS: A retrospective analysis was conducted of women diagnosed with vulvar cancer at a single regional cancer center from 1989 to 2003, with a follow up to 2009. Treatment records were extracted for: demographics and treatment information, Eastern Cooperative Oncology Group (ECOG) performance status and Charlson comorbidity index score. Probability of death from vulvar cancer was estimated using cumulative incidence, treating death by other known and unknown causes as competing risks. Predictors of overall survival were determined using multivariate Cox regression analyses. RESULTS: One hundred forty-six women were identified, with a median age at diagnosis of 79 years (range 65-95). Median follow up was 5.0 years (range 0.1-16.7 years). The cumulative incidence of vulvar cancer-specific mortality was 13% (95% CI: 0.08-0.19) at year one, 24% (95% CI: 0.17-0.31) at year three and 26% (95% CI: 0.19-0.33) at year five. Use of adjuvant therapy or surgical procedure performed did not differ by age at diagnosis (p=0.807 and 0.663) according to age group (65-74, 74-84 and 85+). Increasing age, Charlson comorbidity index score, lymph node involvement and type of surgery performed were associated with increased risk of death from any cause (all p<0.05). CONCLUSION: Among women aged ≥65, vulvar cancer specific mortality was most significant in the first three years after diagnosis. Conversely other causes of mortality which can be attributed to comorbid conditions steadily increased with time.

Ifosfamide, paclitaxel, and carboplatin, a novel triplet regimen for advanced, recurrent, or persistent carcinoma of the cervix: a phase II trial.

OBJECTIVES: (1) To determine the response rate of advanced, recurrent, or persistent carcinoma of the cervix to ifosfamide, paclitaxel, and carboplatin chemotherapy; (2) to determine the progression free interval and survival rate in patients treated with this regimen; (3) to describe the toxicities associated with this regimen; and (4) to evaluate the quality of life of patients while on treatment. METHODS: Eligible patients had histologically proven stage IVB, recurrent, or persistent carcinoma of the cervix not amenable to curative treatment with surgery and/or radiation therapy. Chemotherapy was given on day 1 of a 28-day cycle: mesna (600 mg/m(2)) prior to ifosfamide (2 g/m(2)), paclitaxel (175 mg/m(2)), carboplatin (AUC 5). Response rates were determined according to RECIST criteria. Toxicity was graded according the National Cancer Institute's common toxicity criteria. Quality of life measurements were obtained using the FACT-Cx. RESULTS: Twenty-eight patients participated in this study, with 21 evaluable for response rate. Overall, 7 patients (33%) had a demonstrated objective response (4 complete responses, 3 partial responses). Stable disease was documented in 3 patients. The overall median survival for all patients was 10 months. Median progression free survival for evaluable patients was 5.0 months. Bone marrow suppression was the most common toxicity. There were no negative effects of this treatment regimen on quality of life assessments. CONCLUSION: Ifosfamide, paclitaxel, and carboplatin is an effective regimen in treating advanced or recurrent carcinoma of the cervix and has an acceptable toxicity profile.

A phase II trial of carboplatin and docetaxel followed by radiotherapy given in a "Sandwich" method for stage III, IV, and recurrent endometrial cancer.

OBJECTIVE: To determine feasibility and efficacy of administering docetaxel and carboplatin chemotherapy followed by pelvic radiotherapy and then consolidation chemotherapy in patients with advanced or recurrent endometrial cancer. METHODS: Patients with surgically staged III-IV (excluding IIIA from positive cytology alone) endometrial cancer or biopsy confirmed recurrent disease were eligible. Treatment consisted of 3 cycles of docetaxel (75 mg/m²) and carboplatin (AUC 6) on a q21 day schedule followed by involved field irradiation (45 Gy)± brachytherapy and three additional cycles of docetaxel and carboplatin. Kaplan-Meier (KM) methods estimated overall survival (OS) and progression free survival (PFS). RESULTS: Forty-two patients enrolled, 7 did not complete therapy. 95% (39/41) had primary disease. Median age=58 years (range: 21-81 years). 78% (32/41)=endometrioid histology. Stages=10 IIIA, 21 IIIC, 1 IVA, 7 IVB, (recurrent=1 IC, 1 IIA). There were 23 non-hematologic and 14 grade 3 and 16 grade 4 hematologic toxicities. Seven patients died following treatment with a median follow-up of 28 months (range: 7-70 months). KM estimates and 95% confidence intervals for OS at 1 year were 95% (82-99%), at 3 years 90% (75-96%), and at 5 years 71% (45-86%). Of the 39 with primary disease, 11 progressed or died within 5 years of study enrollment. KM estimates and 95% confidence intervals for PFS at 1 year were 87% (72-94%), at 3 years 71% (51-83%), and at 5 years 64% (42-80%). CONCLUSIONS: "Sandwiching" radiation between chemotherapy for advanced or recurrent endometrial cancer merits further development based on the reported PFS and OS.

A prospective, randomized trial of integrative medicine for women with ovarian cancer.

OBJECTIVES: Despite increased use of integrative medicine in cancer therapy, little data exist on its efficacy. This prospective, randomized, pilot trial sought to evaluate the feasibility of combined modality integrative medicine (CM-IM) in women with ovarian cancer (OvCA) and evaluate its effects on quality of life (QoL), chemotherapy toxicity and immunologic profiles. METHODS: Women with newly diagnosed OvCA requiring chemotherapy were offered enrollment. Those randomized to the experimental arm received hypnosis, therapeutic massage and healing touch with each cycle of chemotherapy. The control arm received chemotherapy without CM-IM. All patients completed QoL questionnaires prior to cycles 1, 3 and 6, and 6-months after chemotherapy. Immunologic profiles were measured. Statistical analysis was based on intent-to-treat. Student's t-test and Fischer's exact-test were used to determine differences. RESULTS: Forty-three women enrolled. All women randomized to CM-IM were successfully treated. There were no statistical differences between the groups in age, stage, grade, histologic cell type, CA125 levels, or surgical cytoreductive status. There was no difference in overall QoL measurements. Re-hospitalization rates, treatment delays, anti-emetic use, and infection rates were similar. Immunologic profiles revealed no difference between arms for WBC or salivary IgA levels. Women receiving CM-IM had consistently higher levels of CD4, CD8 and NK cells, although this did not reach statistical significance. CONCLUSIONS: Prospective clinical evaluation of integrative medicine for women with gynecologic malignancy is feasible. This first, pilot study of CM-IM in gynecologic oncology demonstrated no improvement in QoL or chemotherapy toxicity. Integrative medicine-associated improvements in immunologic profiles warrant further investigation.

Toll-like receptor-7 agonist administered subcutaneously in a prolonged dosing schedule in heavily pretreated recurrent breast, ovarian, and cervix cancers.

BACKGROUND: The primary objective was to study the antitumor activity of prolonged subcutaneous dosing of systemic 852A, a Toll-like receptor-7 agonist (TLR-7), in recurrent breast, ovarian and cervix cancer. Secondary objectives included assessment of safety and immune system activation. METHODS: Adults with recurrent breast, ovarian or cervix cancer failing multiple therapies received 0.6 mg/m(2) of 852A subcutaneously twice weekly for 12 weeks. Doses increased by 0.2 mg/m(2)/week to a maximum of 1.2 mg/m(2). Serum was collected to assess immune activation. RESULTS: Fifteen patients enrolled: 10 ovarian, 2 cervix and 3 breast. Three completed all 24 injections. There were two grade 2 (decreased ejection fractions), nine grade 3 (1 cardiovascular, 1 anorexia, 3 dehydration, 2 infections, 2 renal) and two grade 4 (hepatic and troponin elevation) unanticipated toxicities. Cardiac toxicities included three cardiomyopathies (2 asymptomatic) and one stress-related non-ST elevated myocardial infarction. Five patients discontinued therapy due to possibly associated side effects. One who had stable disease (SD) following 24 doses received 17 additional doses. A cervix patient with SD following 24 doses received chemotherapy after progressing 3 months later, and remains disease free at 18 months. Immune activation, as evidenced by increased IP-10 and IL-1ra, was observed. CONCLUSIONS: In this first human experience of a TLR-7 agonist delivered subcutaneously using a prolonged dosing schedule, 852A demonstrated sustained tolerability in some patients. Clinical benefit was modest, but immune activation was seen suggesting further study of antitumor applications is warranted. Because of cardiac toxicity; 852A should be used cautiously in heavily pretreated patients.

Learning about ovarian cancer at the time of diagnosis: video versus usual care.

OBJECTIVE: Effective patient -clinician communication at diagnosis is important, yet decreased provider time for face-to-face interactions makes traditional paradigms in cancer care difficult. We evaluated the effects of an educational video on patients' distress, cancer knowledge, coping skills and attitudes regarding learning about cancer at the time of ovarian cancer diagnosis. METHODS: An educational video was developed in which oncology professionals, women with ovarian cancer, and their relatives discussed cancer information and experiences. Women admitted for initial diagnostic surgical staging for ovarian cancer were randomized to the educational or placebo video. Before and after the video, patients completed measures of (1) ovarian cancer information, (2) emotional distress, (3) learning attitudes, and (4) coping self-efficacy. Outcomes were analyzed for differences in mean change between intervention and placebo groups using t-tests. RESULTS: Fifty-nine subjects were randomized (30 intervention/29 placebo). The majority were advanced staged, white, insured, high school educated, employed, and rated their disease seriousness as high. Anxiety, general distress and cancer-specific distress were high. Pre-post video: distress and self-efficacy between groups were unchanged, intervention subjects answered more knowledge items correctly (p=0.0004) and developed more negative learning attitudes (p=0.037). Following the educational video, patients who developed more negative attitudes also had increased intrusive thinking (p=0.046), a sign of increased distress. CONCLUSIONS: Video presentation of cancer-related information increases learning under conditions of high distress and disease threat however, it is not without risk for some. Differing information needs may affect women's emotional response under these conditions.

Parental Stress as a Child With Diabetes Transitions From Adolescence to Emerging Adulthood.

This study examined parental and caregiver distress among families caring for children with type 1 diabetes as the child transitions into Emerging Adulthood. More than 96 hours of semistructured interviews were conducted with 19 adult caregivers including parents, grandparents, and other adult family members of 10 children. Each research partner participated in multiple face-to-face, 1- to 1.5-hour long-evolving interviews over the course of 4.5 years. Paradoxically, caregivers were found to experience significant increase in distress as their child with diabetes entered the developmental stage of Emerging Adulthood, 18 to 25 years old, by which time they should be masters of self-care, and parental distress should begin to decline. This increase in familial distress was associated with the emerging adults leaving the home, being unable to maintain an acceptable level of self-care, and experiencing declining health, frequent visits to the emergency department, and repeated hospitalizations. These findings suggest that parental distress from caring for a child with diabetes continues as the child ages, matures, and transitions into adulthood and may be exacerbated when the emerging adult with type 1 diabetes leaves the home and the direct observation and care of the parent.

A phase II study of fulvestrant in the treatment of multiply-recurrent epithelial ovarian cancer.

Objective. The goal of treating recurrent ovarian cancer is disease control while minimizing toxicity. Fulvestrant, a novel estrogen receptor (ER) antagonist, has proven clinically beneficial and well-tolerated in treating recurrent breast cancer. Ovarian cancer often expresses ER and may respond to anti-estrogen therapy. We evaluated fulvestrant in women with recurrent ovarian or primary peritoneal cancer. Methods. Patients with ER-positive, multiply recurrent ovarian or primary peritoneal carcinoma and either measurable disease according to RECIST criteria or an abnormal and rising CA-125 were eligible for enrollment. Treatment consisted of single agent fulvestrant, 500 mg IM on Day 1, 250 mg IM on Day 15, and 250 mg IM on Day 29 and every 28 days thereafter until either intolerance or disease progression. Disease response was assessed by monthly physical exams and CA-125 levels as well as CT scans bimonthly. The primary endpoint was clinical benefit (CB=complete response (CR)+partial response (PR)+stable disease (SD)) at 90 days. Results. Thirty-one women were enrolled and 26 women (median age of 61) met inclusion criteria and received at least one dose. Patients had received a median of 5 prior chemotherapeutic regimens (range: 2-13). We observed one CR (4%), one PR (4%), and 9 patients with SD (35%) using modified-Rustin criteria (CA-125 level). Using modified-RECIST criteria 13 patients (50%) achieved SD. The median time to disease progression was 62 days (mean 86 days). Grade 1 toxicity included headache (1 patient) and bromidrosis (2 patients). Conclusions. Fulvestrant is well-tolerated and efficacious. Objective response rates are low, but disease stabilization was common.

Representational drawing following brain injury.

Research has shown that damage to either the left or right hemisphere can lead to deficits in visuoconstructional skills including drawing and figure copying. Nevertheless, research would suggest that the nature of the deficits arising from left and right brain injury are distinct in nature if not severity, with the right hemisphere, and parietal cortex specifically, seen as critical for obtaining accurate spatial relations and the left hemisphere important for effective organisation (i.e., executive function). Much of this work on drawing and figure copying following brain damage has rested on qualitative assessments or crude marking scales with descriptive anchors for what constitutes good or poor performance. We employed quantitative analyses of drawings developed to assess accuracy in novice and expert artists. We analyzed drawings of a cube and a star in 50 patients (23, left brain damaged: LBD; 27 right brain damaged: RBD) who had suffered strokes. Our analysis was sensitive to the presence of neglect on the cube (i.e., missing left sided details) with voxel-wise lesion symptom mapping (VLSM) highlighting involvement of expected brain regions (superior temporal and supramarginal gyri). With left-sided omissions removed from analyses, we failed to find any difference between LBD and RBD patients. While the presence of left neglect appeared to exaggerate errors, this was only significant for errors of scale and proportion for the star drawing. VLSM of the distinct error domains demonstrated white matter involvement (and a minor contribution from the right insula) with respect to scale errors of the cube only. Finally, blinded judgements of hemisphere of lesion based on qualitative assessment of the drawings were no better than chance. These results suggest that figure copying is a complex task relying on large scale neural networks involving both hemispheres. Clearly, models of visuoconstructional capacity that emphasise right hemisphere dominance are not entirely accurate.

Routine pelvic examination during front-line chemotherapy for ovarian cancer: should it play a role?

OBJECTIVE: To determine if pelvic examination affected management in patients undergoing first-line chemotherapy for ovarian cancer and to determine a threshold of change in tumor size reliably detectable by pelvic examination. STUDY DESIGN: We reviewed 501 encounters among 47 women with ovarian cancer to see if pelvic examination prompted a management change. Clinicians then evaluated synthetic model "tumors" and were retested at intervals of 3-48 hours to determine change needed for reliable detection. RESULTS: The median number of examinations was 3 during 8 cycles of chemotherapy. Fifteen examinations (10.5%) revealed palpable anomalies, attributable to known tumor in 10 instances. The most common events preceding management change were elevation in serum CA-125 (57%) or chemotherapy toxicity (20%). No changes were made based on pelvic examination alone. When assessing "tumor" volume in a model, estimates ranged from 33-309% of actual volume. Determination of volume change following a delay was poor. No reliable threshold of detection of volume change was established. CONCLUSION: Pelvic examination findings rarely dictated management changes in this study. Further, our results call into question the potential of routine pelvic examination to add significantly to clinical management during initial treatment given the wide range of error in "tumor" size estimates.

Bevacizumab plus cyclophosphamide in heavily pretreated patients with recurrent ovarian cancer.

OBJECTIVE: To investigate the efficacy and safety of bevacizumab in heavily pretreated patients with recurrent ovarian cancer. METHODS: Patients with recurrent ovarian cancer were treated with intravenous bevacizumab 10 mg/kg every other week plus oral cyclophosphamide 50 mg daily until disease progression or undue toxicity. Adverse events were graded according to the NCI Common Toxicity Criteria. Response rates were determined by CA-125 levels or changes in target lesions according to RECIST. RESULTS: Fifteen patients were treated. Median age was 57 years (range 42-69). The median number of previous chemotherapy regimens was 8 (range 5-15). The median time from the first diagnosis to treatment with bevacizumab was 68.9 months (range, 26.5-177.2). The median number of bevacizumab infusions was 8 (range, 2-12), and the total number was 113. Two patients (13.3%) had a complete response after 4 months of therapy. Six patients (40.0%) had a partial response. The median duration of this response was 3.9 months (range, 2.3-10.4). Three patients (20%) had stable disease of 4.0, 5.2 and 5.5 months' duration, and 4 patients (26.7%) had progressive disease. Despite being heavily pre-treated and having confirmed intra-abdominal cancer, no gastrointestinal perforations developed. Other toxicities included: grade 3 pancreatitis in 1 patient; grade 2 proteinuria and hypertension in another, which resolved with the cessation of bevacizumab. CONCLUSION: In our population of very heavily pre-treated patients, with at least five prior regimens, bevacizumab in combination with oral cyclophosphamide has significant activity with a response rate of 53%, without significant toxicity.

Enhanced Recovery Program and Length of Stay After Laparotomy on a Gynecologic Oncology Service: A Randomized Controlled Trial.

OBJECTIVE: To estimate whether a rapid recovery program would reduce length of stay among patients undergoing laparotomy on a gynecologic oncology service. METHODS: We conducted a prospective, randomized, controlled trial comparing an enhanced recovery after surgery protocol with routine postoperative care among women undergoing laparotomy on the gynecologic oncology service. Protocol elements included: preoperative counseling, regional anesthesia, intraoperative fluid restriction, and early postoperative ambulation and feeding. A sample size of 50 per group (N=100) was planned to achieve 80% power to detect a two-day difference in our primary outcome, length of hospital stay; secondary outcomes included: total daily narcotics used, time to postoperative milestones, and complications. RESULTS: A total of 112 women were enrolled between 2013 and 2015. Nine patients did not undergo laparotomy and were excluded, leaving 52 and 51 patients in the control and intervention groups, respectively. There was no difference in length of stay between the two groups (median 3.0 in both groups; P=.36). Enhanced recovery after surgery patients used less narcotics on day 0 (10.0 compared with 5.5 morphine equivalents in the control and intervention arms, respectively, P=.09) and day 2 (10.0 compared with 7.5 morphine equivalents, respectively; P=.05); however, there was no statistically significant difference between groups in any of the secondary outcomes. Post hoc analysis based on actual anesthesia received also failed to demonstrate a difference in time to discharge. CONCLUSION: When compared with usual care, introducing a formal enhanced recovery after surgery protocol did not significantly reduce length of stay. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT01705288.

Phase II trial of weekly single-agent paclitaxel in platinum/paclitaxel-refractory ovarian cancer.

PURPOSE: We wished to critically examine the level of activity of weekly paclitaxel in a patient population with well-characterized platinum/paclitaxel-resistant (3-week schedule) ovarian cancer. PATIENTS AND METHODS: Eligibility criteria for this phase II trial included the following: ovarian and fallopian tube cancers or primary carcinoma of the peritoneum; prior initial therapy with platinum/paclitaxel; and failure to respond to treatment (progression or stable disease as best response), or a response duration of less than 3 months, or if the response was more than 3 months, retreatment with both agents required and failure to respond a second time or the response duration was less than 3 months. Measurable or assessable disease (CA-125 response criteria) was required. Patients received weekly paclitaxel (80 mg/m(2)) until disease progression, unacceptable toxicity developed, or they elected to discontinue treatment. RESULTS: Fifty-three patients (52 assessable for toxicity and 51 for response) were entered onto this multi-institution trial. Of 248 total cycles (887 doses), only 13 (1%) were modified (dose reduction or treatment delay) because of side effects. Therapy was discontinued in five patients because of toxicity (four because of peripheral neuropathy, and one because of painful fingernail beds). Thirteen patients (25%; 95% confidence interval, 13.5% to 37.5%) achieved an objective response (four by CA-125 criteria, and nine by > or = 50% reduction of measurable disease). CONCLUSION: Weekly paclitaxel (80 mg/m(2)) is generally well tolerated and is an active second-line regimen against ovarian cancer that has demonstrated resistance to platinum/paclitaxel delivered on an every-3-week schedule.