Current pediatric cancer survivorship practices: a report from the Children's Oncology Group.

PURPOSE: The purpose of this study is to describe current survivor services provided by COG institutions. METHODS: A 190-question online survey was distributed to 209 COG member institutions over a 5-month period in 2017. Descriptive statistics were used to describe survivor services and explore their changes between 2007 and 2017. RESULTS: Representatives from 153 (73%) institutions completed the survey. Of these, 96% of institutions reported that they provide pediatric cancer survivor care either in a specialized late effects program (75%) or a regular pediatric oncology clinic (24%). However, only 29.8% of institutions reported that > 75% of eligible patients were seen in a survivorship clinic. The most prevalent reported barriers to survivor care were lack of dedicated time (58%) and lack of funding for program development (41%). In 2017, 88% of institutions provided a treatment summary compared to 31% in 2007. CONCLUSION: The majority of COG institutions have dedicated care for pediatric and young adult survivors of childhood cancer; however, at most institutions, < 75% of eligible patients access this care. Research into more efficient technology strategies is needed to ensure all survivors the opportunity to receive appropriate follow-up care. IMPLICATIONS FOR CANCER SURVIVORS: This survey provides a snapshot of the status of late effects services within COG institutions and provides information on residual gaps in services. Next steps should focus on the importance of attendance in a survivorship clinic on the physical health and psychosocial outcomes in cancer survivors.

Painless neutropenic enterocolitis in a patient undergoing chemotherapy.

CASE DESCRIPTION: A 60-year-old man developed painless neutropenic enterocolitis after induction chemotherapy for newly diagnosed acute myelogenous leukemia. The patient had recurrent fever while neutropenic, without experiencing abdominal pain or tenderness on physical examination. His diagnosis was delayed by the fact that he had no localizing symptoms. DISCUSSION: Neutropenic enterocolitis is a common complication, generally occurring in patients who are severely neutropenic; the condition presents with fever and abdominal pain. No cases of painless neutropenic enterocolitis have yet been reported. Review of the literature shows that patients can develop this condition in the absence of fever and, sometimes, neutropenia. Furthermore, few comprehensive studies or reviews have investigated the utility of computed tomography imaging in identifying a source for abdominal pain in neutropenic patients with fever. SUMMARY: Many potential causes of febrile neutropenia should be considered in chemotherapy patients.

Clinical guide to fertility preservation in hematopoietic cell transplant recipients.

With broadening indications, more options for hematopoietic cell transplantation (HCT) and improvement in survival, the number of long-term HCT survivors is expected to increase steadily. Infertility is a frequent problem that long-term HCT survivors and their partners face and it can negatively impact on the quality of life. The most optimal time to address fertility issues is before the onset of therapy for the underlying disease; however, fertility preservation should also be addressed before HCT in all children and patients of reproductive age, with referral to a reproductive specialist for patients interested in fertility preservation. In vitro fertilization (IVF) and embryo cryopreservation, oocyte cryopreservation and ovarian tissue banking are acceptable methods for fertility preservation in adult women/pubertal females. Sperm banking is the preferred method for adult men/pubertal males. Frequent barriers to fertility preservation in HCT recipients may include the perception of lack of time to preserve fertility given an urgency to move ahead with transplant, lack of patient-physician discussion because of several factors (for example, time constraints, lack of knowledge), inadequate access to reproductive specialists, and costs and lack of insurance coverage for fertility preservation. There is a need to raise awareness in the medical community about fertility preservation in HCT recipients.

Physician perceptions and practice patterns regarding fertility preservation in hematopoietic cell transplant recipients.

Physician practice variation may be a barrier to informing hematopoietic cell transplant (HCT) recipients about fertility preservation (FP) options. We surveyed HCT physicians in the United States to evaluate FP knowledge, practices, perceptions and barriers. Of the 1035 physicians invited, 185 completed a 29-item web-survey. Most respondents demonstrated knowledge of FP issues and discussed and felt comfortable discussing FP. However, only 55% referred patients to an infertility specialist. Most did not provide educational materials to patients and only 35% felt that available materials were relevant for HCT. Notable barriers to discussing FP included perception that patients were too ill to delay transplant (63%), patients were already infertile from prior therapy (92%) and time constraints (41%). Pediatric HCT physicians and physicians with access to an infertility specialist were more likely to discuss FP and to discuss FP even when prognosis was poor. On analyses that considered physician demographics, knowledge and perceptions as predictors of referral for FP, access to an infertility specialist and belief that patients were interested in FP were observed to be significant. We highlight variation in HCT physician perceptions and practices regarding FP. Physicians are generally interested in discussing fertility issues with their patients but lack educational materials.

Birth characteristics and childhood carcinomas.

BACKGROUND: Carcinomas in children are rare and have not been well studied. METHODS: We conducted a population-based case-control study and examined associations between birth characteristics and childhood carcinomas diagnosed from 28 days to 14 years during 1980-2004 using pooled data from five states (NY, WA, MN, TX, and CA) that linked their birth and cancer registries. The pooled data set contained 57,966 controls and 475 carcinoma cases, including 159 thyroid and 126 malignant melanoma cases. We used unconditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: White compared with 'other' race was positively associated with melanoma (OR=3.22, 95% CI 1.33-8.33). Older maternal age increased the risk for melanoma (OR(per 5-year age increase)=1.20, 95% CI 1.00-1.44), whereas paternal age increased the risk for any carcinoma (OR=1.10(per 5-year age increase), 95% CI 1.01-1.20) and thyroid carcinoma (OR(per 5-year age increase)=1.16, 95% CI 1.01-1.33). Gestational age < 37 vs 37-42 weeks increased the risk for thyroid carcinoma (OR=1.87, 95% CI 1.07-3.27). Plurality, birth weight, and birth order were not significantly associated with childhood carcinomas. CONCLUSION: This exploratory study indicates that some birth characteristics including older parental age and low gestational age may be related to childhood carcinoma aetiology.

Parental educational attainment as an indicator of socioeconomic status and risk of childhood cancers.

BACKGROUND: Little has been reported on socioeconomic (SES) patterns of risk for most forms of childhood cancer. METHODS: Population-based case-control data from epidemiological studies of childhood cancer conducted in five US states were pooled and associations of maternal, paternal and household educational attainment with childhood cancers were analysed. Odds ratios (ORs) and 95% confidence intervals were estimated using logistic regression, controlling for confounders. RESULTS: Although there was no association with parental education for the majority of cancers evaluated, there was an indication of a positive association with lower education for Hodgkin's and Burkitt's lymphoma and Wilm's tumour, with the ORs ranging from 1.5 to >3.0 times that of more educated parents. A possible protective effect was seen for lower parental education and astrocytoma and hepatoblastoma, with ORs reduced by 30 to 40%. CONCLUSIONS: These study results should be viewed as exploratory because of the broad nature of the SES assessment, but they give some indication that childhood cancer studies might benefit from a more thorough assessment of SES.

Birth characteristics and the risk of childhood rhabdomyosarcoma based on histological subtype.

BACKGROUND: Little is known about risk factors for childhood rhabdomyosarcoma (RMS) and the histology-specific details are rare. METHODS: Case-control studies formed by linking cancer and birth registries of California, Minnesota, New York, Texas and Washington, which included 583 RMS cases (363 embryonal and 85 alveolar RMS) and 57 966 randomly selected control subjects, were analysed using logistic regression. The associations of RMS (overall, and based on embryonal or alveolar histology) with birth weight across five 500 g categories (from 2000 to 4500 g) were examined using normal birth weight (2500-3999 g) as a reference. Large (>90th percentile) and small (<10th percentile) size for gestational age were calculated based on birth weight distributions in controls and were similarly examined. RESULTS: High birth weight increased the risk of embryonal RMS and RMS overall. Each 500 g increase in birth weight increased the risk of embryonal RMS (odds ratio (OR)=1.27, 95% confidence interval (CI)=1.14-1.42) and RMS overall (OR=1.18, 95% CI=1.09-1.29). Large size for gestational age also significantly increased the risk of embryonal RMS (OR=1.42, 95% CI=1.03-1.96). CONCLUSIONS: These data suggest a positive association between accelerated in utero growth and embryonal RMS, but not alveolar RMS. These results warrant cautious interpretation owing to the small number of alveolar RMS cases.

Peppermint oil improves the manometric findings in diffuse esophageal spasm.

BACKGROUND: Diffuse esophageal spasm (DES) is an uncommon condition that results in simultaneous esophageal contractions. Current medical treatment of DES is frequently unsatisfactory. We hypothesized that, as a smooth muscle relaxant, peppermint oil may improve the manometric findings in DES. STUDY: Eight consecutive patients with chest pain or dysphagia and who were found to have DES were enrolled during their diagnostic esophageal manometry. An eight-channel perfusion manometry system was used. Lower esophageal sphincter pressure and contractions of the esophageal body after 10 wet swallows were assessed before and 10 minutes after the ingestion of a solution containing five drops of peppermint oil in 10 mL of water. Each swallow was assessed for duration (seconds), amplitude (mm Hg), and proportion of simultaneous and multiphasic esophageal contractions. RESULTS: Lower esophageal sphincter pressures and contractile pressures and durations in both the upper and lower esophagus were no different before and after the peppermint oil. Peppermint oil completely eliminated simultaneous esophageal contractions in all patients (p < 0.01). The number of multiphasic, spontaneous, and missed contractions also improved. Because normal esophageal contractions are characteristically uniform in appearance, variability of esophageal contractions was compared before and after treatment. The variability of amplitude improved from 33.4 +/- 36.7 to 24.9 +/- 11.0 mm Hg (p < 0.05) after the peppermint oil. The variability for duration improved from 2.02 +/- 1.80 to 1.36 +/- 0.72 seconds (p < 0.01). Two of the eight patients had chest pain that resolved after the peppermint oil. CONCLUSIONS: This data demonstrates that peppermint oil improves the manometric features of DES.

Identification of a prodromal period in Crohn's disease but not ulcerative colitis.

OBJECTIVES: Irritable bowel syndrome, a common gastrointestinal diagnosis, has not been clearly studied in inflammatory bowel disease. Some of the residual symptoms in subjects treated with Crohn's disease and ulcerative colitis are thought to be related to irritable bowel syndrome. The aims of this study were 1) to describe the duration and nature of complaints before the diagnosis of Crohn's disease and ulcerative colitis (prodromal period), and 2) to determine the role of IBS in this prodromal period. METHODS: A total of 66 patients with confirmed inflammatory bowel disease were enrolled in the study. The subjects received a questionnaire to ascertain the nature and duration of symptoms preceding the diagnosis of Crohn's disease or ulcerative colitis, including features described under the Rome criteria for irritable bowel syndrome. RESULTS: Of the 66 subjects analyzed, 45 had Crohn's disease and 21 had ulcerative colitis. The prodromal period was 7.7 +/- 10.7 yr for Crohn's disease and 1.2 +/- 1.8 yr for ulcerative colitis (p < 0.05). Once patients meeting the Rome criteria for irritable bowel syndrome during the prodrome were excluded, the duration of the prodromal period (non-IBS) for ulcerative colitis dropped to 0.8 +/- 1.3 yr compared to 6.9 +/- 9.8 yr in the Crohn's disease group (p < 0.05). The symptoms of the non-IBS prodrome in subjects with Crohn's disease were bloating, diarrhea, stomach pain, heartburn, fever, weight loss, and fatigue. Further analysis demonstrated that subjects whose Crohn's disease initially began as colonic disease had a longer prodrome than with small bowel. In the non-IBS Crohn's group, there was also a correlation between the age at the time of diagnosis and the duration of prodrome (r = 0.67, p < 0.0001). CONCLUSIONS: There is a significant prodromal period before the time of diagnosis of Crohn's disease that is not found in ulcerative colitis even after exclusion of subjects with IBS.

Eradication of small intestinal bacterial overgrowth reduces symptoms of irritable bowel syndrome.

OBJECTIVES: Irritable bowel syndrome is the most common gastrointestinal diagnosis. The symptoms of irritable bowel syndrome are similar to those of small intestinal bacterial overgrowth. The purpose of this study was to test whether overgrowth is associated with irritable bowel syndrome and whether treatment of overgrowth reduces their intestinal complaints. METHODS: Two hundred two subjects in a prospective database of subjects referred from the community undergoing a lactulose hydrogen breath test for assessment of overgrowth were Rome I criteria positive for irritable bowel syndrome. They were treated with open label antibiotics after positive breath test. Subjects returning for follow-up breath test to confirm eradication of overgrowth were also assessed. Subjects with inflammatory bowel disease, abdominal surgery, or subjects demonstrating rapid transit were excluded. Baseline and after treatment symptoms were rated on visual analog scales for bloating, diarrhea, abdominal pain, defecation relief, mucous, sensation of incomplete evacuation, straining, and urgency. Subjects were blinded to their breath test results until completion of the questionnaire. RESULTS: Of 202 irritable bowel syndrome patients, 157 (78%) had overgrowth. Of these, 47 had follow-up testing. Twenty-five of 47 follow-up subjects had eradication of small intestinal bacterial overgrowth. Comparison of those that eradicated to those that failed to eradicate revealed an improvement in irritable bowel syndrome symptoms with diarrhea and abdominal pain being statistically significant after Bonferroni correction (p < 0.05). Furthermore, 48% of eradicated subjects no longer met Rome criteria (chi2 = 12.0, p < 0.001). No difference was seen if eradication was not successful. CONCLUSIONS: Small intestinal bacterial overgrowth is associated with irritable bowel syndrome. Eradication of the overgrowth eliminates irritable bowel syndrome by study criteria in 48% of subjects.

State of actin filaments is changed by anoxia in cultured rat neocortical neurons.

Cultured neocortical neurons respond rapidly to oxygen deprivation. Within minutes they demonstrate an increase in intracellular calcium and pronounced changes in their morphology. These changes include swelling, bleb formations, process retraction and a change in shape of the soma from pyramidal or ellipsoidal to round. Since the cytoskeleton is responsible for the maintenance of cell shape, we investigated the changes in state of a major component of the neuronal cytoskeleton, the actin filaments. Actin exists in a dynamic equilibrium between the monomeric and filamentous states. This equilibrium is dependent, in part, upon intracellular ATP, which is reduced during anoxia. We differentially labelled monomeric actin with Texas Red-tagged DNase-1 and the polymeric form with Bodipy-phallicidin. Using confocal microscopy and image reconstruction, we have found that the ratio of filamentous to monomeric actin increases on average three-fold following 10 min of anoxia. In addition, filamentous actin redistributes within the soma and appears to have a more homogeneous distribution than in normoxic neurons. Our results show that, in cultured neocortical neurons, actin filaments are modulated by anoxia. We believe that, although the filamentous/monomeric ratio is modulated, at least in part, by the levels of ATP and ADP, the relative distribution and amount of the filamentous to monomeric form within neurons are likely regulated by other factors such as calcium-sensitive actin-binding and severing proteins.