A Delphi panel to build consensus on assessing disease severity and disease progression in adult patients with hypophosphatasia in the United States.

BACKGROUND: Hypophosphatasia (HPP) is an inborn error of metabolism with a variable presentation. We conducted a modified Delphi panel to obtain expert consensus on knowledge gaps regarding disease severity and progression in adult patients with HPP. METHODS: Healthcare professionals (HCPs) with experience managing adult patients with HPP were recruited to participate in a 3-round Delphi panel (round 1: paper survey and 1:1 interview; rounds 2-3: email survey). Panelists rated the extent of their agreement with statements about disease severity and progression in adult patients with HPP. Consensus was defined as ≥ 80% agreement. RESULTS: Ten HCPs completed round 1; nine completed rounds 2 and 3. Consensus was reached on 46/120 statements derived from steering committee input. Disease severity markers in adult patients with HPP can be bone-related (recurrent/poorly healing fractures, pseudo-fractures, metatarsal fractures, osteomalacia) or involve dentition or physiologic/functional manifestations (use of mobility devices/home modifications, abnormal gait, pain). Disease progression markers can include recurrent/poorly healing low-trauma fractures, development of ectopic calcifications, and/or impairment of functional activity. Panelists supported the development of a tool to help assess disease severity in the clinic and track changes in severity over time. Panelists also highlighted the role of a multidisciplinary team, centers with expertise, and the need to refer patients when disease severity is not clear. CONCLUSIONS: These statements regarding disease severity, progression, and assessment methods address some knowledge gaps in adult patients with HPP and may be helpful for treating HCPs, although the small sample size affects the ability to generalize the healthcare provider experience.

Dietary diversity scores, nutrient intakes and biomarkers vitamin B12, folate and Hb in rural youth from the Pune Maternal Nutrition Study.

Hidden hunger is widespread in India. Individual dietary diversity score (IDDS) is a measure of the nutrient adequacy of the diet. The FAO has set guidelines for the measurement of dietary diversity: the IDDS and the minimum dietary diversity score for women (MDD-W) to assess nutritional deficiency, but validation against nutritional biomarkers is required. Using available data among rural youth (17 years) from the Pune Maternal Nutrition Study, the validity of DDS was assessed to measure deficiencies of vitamin B12, folate and Hb. Of the 355 boys and 305 girls, 19 % were classified as underweight, 57 % as vitamin B12 deficient (<150 pmol/l) and 22 % as anaemic (<120/130 g/l). Cereals, legumes and 'other-vegetables' were the most frequently consumed foods. More boys than girls consumed milk, flesh, eggs and micronutrient-dense foods. Median IDDS of 4 (interquartile range (IQR) 3-4) and MDD-W of 6 (IQR 5-7) were low. Youth with vitamin B12 deficiency had a higher likelihood of an IDDS ≤ 4 (1·89; 95 % CI 1·24, 2·87) or an MDD-W ≤ 5 (1·40; 95 % CI 1·02, 1·94). Youth with anaemia were more likely to have an IDDS ≤ 4 (1·76; 95 % CI 1·01, 3·14) adjusted for socio-economic scores, BMI, energy intake and sex. Folate deficiency was low (3 %) and was not associated with either score. Youth with lowest plasma vitamin B12 and Hb infrequently or never consumed dairy products/non-vegetarian foods. These rural Indian youth were underweight, had low DDS and consumed foods low in good-quality proteins and micronutrients. Associations of DDS with circulating micronutrients indicate that DDS is a valid measure to predict vitamin B12 deficiency and anaemia.

Timing of Atlantic salmon Salmo salar smolt migration predicts successful passage through a reservoir.

Around 30% of Atlantic salmon Salmo salar smolts successfully survived passage through Loch Meig, a reservoir in the north of Scotland, en route to the sea. However, this survival rate was in turn dependent on the timing of migration, with the earliest migrants in the spring having the best chance of survival. This could have implication for fisheries management, since the estimation of smolt downstream survival may be influenced by which time period of the smolt run is analysed.

Growing skull fracture in a red-tailed hawk (Buteo jamaicensis).

Growing skull fractures have been reported in humans for many years, usually resulting from injury to the soft skull during the rapid growth period of an infant's life. Nestling raptors have thin, fragile skulls, a rapid growth rate, and compete aggressively for food items. Skull trauma may occur, which may lead to the development of a growing skull fracture. Growing skull fractures may be under-diagnosed in raptor rehabilitation facilities that do not have access to advanced technologic equipment. Three-dimensional (3-D) computed tomography was used to diagnose a growing skull fracture in a red-tailed hawk (Buteo jamaicensis). The lesion was surgically repaired and the animal was eventually returned to the wild. This is the first report of a growing skull fracture in an animal. In this case, 3-D computed topographic imaging was utilized to diagnose a growing skull fracture in a red-tailed hawk, surgical repair was performed, and the bird recovered completely and was ultimately released.

Enzogenol for cognitive functioning in traumatic brain injury: a pilot placebo-controlled RCT.

BACKGROUND AND PURPOSE: Enzogenol, a flavonoid-rich extract from Pinus radiata bark with antioxidant and anti-inflammatory properties has been shown to improve working memory in healthy adults. In traumatic brain injury (TBI), oxidation and inflammation have been linked to poorer cognitive outcomes. Hence, this phase II, randomized controlled trial investigated safety, compliance and efficacy of Enzogenol for improving cognitive functioning in people following mild TBI. METHODS: Sixty adults, who sustained a mild TBI, 3-12 months prior to recruitment, and who were experiencing persistent cognitive difficulties [Cognitive Failures Questionnaire (CFQ) score > 38], were randomized to receive Enzogenol (1000 mg/day) or matching placebo for 6 weeks. Subsequently, all participants received Enzogenol for a further 6 weeks, followed by placebo for 4 weeks. Compliance, side-effects, cognitive failures, working and episodic memory, post-concussive symptoms and mood were assessed at baseline, 6, 12 and 16 weeks. Simultaneous estimation of treatment effect and breakpoint was effected, with confidence intervals (CIs) obtained through a treatment-placebo balance-preserving bootstrap procedure. RESULTS: Enzogenol was found to be safe and well tolerated. Trend and breakpoint analyses showed a significant reduction in cognitive failures after 6 weeks [mean CFQ score, 95% CI, Enzogenol versus placebo -6.9 (-10.8 to -4.1)]. Improvements in the frequency of self-reported cognitive failures were estimated to continue until week 11 before stabilizing. Other outcome measures showed some positive trends but no significant treatment effects. CONCLUSIONS: Enzogenol supplementation is safe and well tolerated in people after mild TBI, and may improve cognitive functioning in this patient population. This study provides Class IIB evidence that Enzogenol is well tolerated and may reduce self-perceived cognitive failures in patients 3-12 months post-mild TBI.

Implantation of a titanium partial limb prosthesis in a white-naped crane (Grus vipio).

A female white-naped crane (Grus vipio) was presented with an open, oblique fracture of the distal right tarsometatarsus and concomitant vascular and nerve damage. Conventional fracture fixation repairs failed, which led to implantation of a custom titanium limb prosthesis. After subsequent revisions with 2 different prosthetic devices, limb function was ultimately restored but a later yolk embolism caused a circulatory compromise in the opposite leg, which necessitated euthanasia. Histopathologic results revealed limited ingrowth of bone into the porous coated implant, which indicated that a limb prosthesis may provide salvage for long-legged, heavy-bodied birds with fractures of the tarsometatarsus.

Energy intake and expenditure during a 6-day cycling stage race.

Energy intake (EI) and energy expenditure (EE) are relatively easy to measure accurately over short periods in a laboratory setting, but less so during a multi-day competition. Our goal was to measure EI and EE as accurately as possible during a 6-day, 10-stage cycling race. We prepared all meals and supplements, assessed EI (weighed diet-records) and macrontrient intake, total EE (doubly labelled water), resting metabolic rate (respiratory gas exchange), exercise EE (power meters), and body mass. Body composition was measured several days before and after racing (dual x-ray absorptiometry). Body mass remained stable over the course of the race. The mean EI (27.3+/-3.8 MJ/day) nearly matched EE (27.4+/-2.0 MJ/day). The majority (62%) of EE was exercise EE. Macronutrient intake was within or exceeded the recommendations. Lean body mass increased and fat mass decreased in most of our participants. Our study indicates that EI can match high EE with adequate macronutrient intake during multi-day cycle racing and may be facilitated by appropriate foods being available at appropriate times. This optimization of nutritional provision supports positive changes in body composition.

Application of the 2006 WHO growth standard from birth to 4 years to Pacific Island children.

BACKGROUND: Pacific adults and children have very high rates of obesity. OBJECTIVE: Body size at birth, 2- and 4 years for the whole cohort, compliant (not smoking and breastfed) and non-compliant children was compared to the 2006 World Health Organization (WHO) growth standard using z-scores. DESIGN: Longitudinal data (n=659) from the 2000 Pacific Island family birth cohort study of weight at birth and weight and height at 2- and 4 years was analysed. RESULTS: At birth the average child was 3.673+/-0.501 kg; z-score 0.605 units higher (P<0.000001) than the WHO standard. At 2- and 4 years, average z-scores for weight and body mass index (BMI) were significantly different from 0 (mean z-scores for weight +1.062 and +1.688, for BMI +1.701 and +1.969 respectively, P<0.000001). Mean height was significantly lower (P<0.000001) z-score=-0.232 at 2 years but higher (P<0.000001) at 4 years, z-score=+0.626. Over 4 years, the daily weight gain was 11.2 g day(-1) compared with 8.9 g day(-1) for the WHO child. Compliant (n=287) compared to non-compliant (n=372) weighed less and were slightly shorter at 2- and 4 years measurement points. Non-compliant children categorized as non-smoking (n=229) weighed more than smoking mothers' (n=143) children at birth, 2- and 4 years. CONCLUSION: Pacific children are born heavy, over 4 years increase in weight is faster and between 2- and 4 years increase in height is faster than the reference breastfed child, independent of pre- and postnatal factors. Smoking decreases the rate of weight gain and children who are not breastfed gain weight faster. Interventions to limit weight gain need to start with the family before conception.

Point-of-care testing as a tool for screening for diabetes and pre-diabetes.

AIM: To determine the utility of finger-prick point-of-care testing (POCT) of blood glucose for the detection of dysglycaemia. METHODS: A fasting POCT and an oral glucose tolerance test (OGTT) with laboratory assays were performed as part of the baseline screening for 5309 participants enrolled in the Te Wai o Rona Diabetes Prevention Strategy. Participants were aged 46 +/- 19 years with no self-reported diabetes. Dysglycaemia, including diabetes, was defined using World Health Organization criteria. Agreement between the two fasting plasma glucose measurements and their screening properties (with sensitivity and specificity for cut points) were compared using receiver operator characteristic analysis. RESULTS: A total of 3225 participants had both capillary and venous fasting blood sampled within 30 min and then underwent OGTT. New diabetes was found in 161 participants (5.0%) and pre-diabetes in 414 [impaired glucose tolerance 299 (9.3%), impaired fasting glucose 115 (3.6%)]. The mean difference in capillary and venous measures was 0.02 mmol/l (95% confidence interval -0.04 to +0.01; limits of agreement -1.37 to 1.33 mmol/l). Capillary POCT was a poorer predictor of dysglycaemia and impaired glucose tolerance and new diabetes (area under curve 0.76 and 0.71) than venous laboratory analysis (area under curve 0.87 and 0.81 respectively). Optimal screening criteria were best at a venous glucose of 5.4 mmol/l; 77% sensitivity/specificity. CONCLUSIONS: POCT significantly underestimated the true blood glucose at diagnostic levels for diabetes. POCT cannot be recommended as a means of screening for or diagnosing diabetes or pre-diabetes.

Cohort profile: Pacific Islands Families (PIF) growth study, Auckland, New Zealand.

PURPOSE: This article profiles a birth cohort of Pacific children participating in an observational prospective study and describes the study protocol used at ages 14-15 years to investigate how food and activity patterns, metabolic risk and family and built environment are related to rates of physical growth of Pacific children. PARTICIPANTS: From 2000 to 2015, the Pacific Islands Families Study has followed, from birth, the growth and development of over 1000 Pacific children born in Auckland, New Zealand. In 2014, 931 (66%) of the original cohort had field measures of body composition, blood pressure and glycated haemoglobin. A nested subsample (n=204) was drawn by randomly selecting 10 males and 10 females from each decile of body weight. These participants had measurement of body composition by dual-energy X-ray absorptiometry, food frequency, 6 min walk test and accelerometer-determined physical activity and sedentary behaviours, and blood biomarkers for metabolic disease such as diabetes. Built environment variables were generated from individual addresses. FINDINGS TO DATE: Compared to the Centres for Disease Control and Prevention (CDC) reference population with mean SD scores (SDS) of 0, this cohort of 931 14-year-olds was taller, weighed more and had a higher body mass index (BMI) (mean SDS height >0.6, weight >1.6 and BMI >1.4). 7 of 10 youth were overweight or obese. The nested-sampling frame achieved an even distribution by body weight. FUTURE PLANS: Cross-sectional relationships between body size, fatness and growth rate, food patterns, activity patterns, pubertal development, risks for diabetes and hypertension and the family and wider environment will be examined. In addition, analyses will investigate relationships with data collected earlier in the life course and measures of the cohort in the future. Understanding past and present influences on child growth and health will inform timely interventions to optimise future health and reduce inequalities for Pacific people.

Differentiation of t(5;17) variant acute promyelocytic leukemic blasts by all-trans retinoic acid.

All-trans retinoic acid (ATRA) induces differentiation of acute promyelocytic leukemic (APL) blasts from patients with t(15;17) APL. However, blasts from patients with the t(11;17) variant do not differentiate in response to ATRA. Our group has identified a variant of APL characterized by t(5;17) and expression of the NPM-RAR fusion gene product. From case reports it has been difficult to establish whether ATRA induces clinical responses in patients with this variant. In order to determine whether t(5;17) blasts differentiate with ATRA, we harvested mononuclear bone marrow cells from a patient with t(5;17) APL at time of relapse and cultured them in medium containing ATRA. Morphologic analysis of cytospins after 7 days of culture revealed that 60% of cells in the ATRA-treated culture had differentiated into mature neutrophilic forms, as opposed to less than 1% in the control culture. Seventy-three percent of cells acquired NBT positivity after exposure to ATRA, compared with 1% in the control culture. These results indicate that t(5;17) blasts retain the ability to terminally differentiate in response to retinoic acid.

Calibration of densitometers for indicator dye dilution.

A systematic investigation was undertaken to determine which factors affect the calibration of a Gilford monochromatic densitometer used for recording indicator-dilution curves with indocyanine green. Calibration was not influenced by variation of withdrawal speeds from 6.4 to 20.6 cm3/min but varied with differing sampling systems. Variation in haemoglobin from 10 to 17.5 g-dl-1 or in haematocrit from 30 to 60% did not affect calibration. Calibration lines showed both curvature and hysteresis. The opitcal properties of indocyanine green were not affected by storage of diluted dye in the dark for 24 hours but were altered by the presence of contrast media used in angiography. No systematic error resulted from the substitution of stored ACD blood for patient's blood in calibration although random error was increased. Recommendations based on these findings are made for a simple calibration technique which avoids systematic error.

The expression of cytokine activity by fracture callus.

Cytokines, a group of proteins known to regulate hemopoietic and immune functions, are also involved in inflammation, angiogenesis, and bone and cartilage metabolism. Since all of these processes occur following bone injury, or are known to contribute to wound repair mechanisms, this investigation sought to test the hypothesis that cytokines are involved in fracture healing. Two sets of 60 male Sprague-Dawley rats underwent the production of standard closed femoral fractures. The animals were then euthanized in groups of 15 on days 3, 7, 14, and 21 postfracture. A separate control group was also used for the harvesting of intact unfractured bone. At the time of euthanasia, calluses or bone specimens were explanted to organ culture and treated with either media alone or media containing the inducing agents lipopolysaccharide or concanavalin A. A titration of conditioned medium from these cultures was then added to factor-dependent clonal cell lines that are known to be specifically responsive to interleukin-1, interleukin-6, granulocyte-macrophage colony stimulating factor or macrophage-colony stimulating factor. To confirm the identities of each of these cytokines, neutralizing antibody studies were performed. The results showed that interleukin-1 is expressed at very low constitutive levels throughout the period of fracture healing but can be induced to high activities in the early inflammatory phase (day 3). Granulocyte-macrophage colony stimulating factor showed no constitutive activity but could also be induced to high activities with lipopolysaccharide. The ability of these two cytokines to be induced declined progressively as fracture healing proceeded. Interleukin-6 showed high constitutive activity early in the healing process (day 3), and treatment with inducing agent did not increase the activity of this cytokine at this timepoint. Lipopolysaccharide did increase interleukin-6 activity in day 7 and 14 fracture calluses. Although macrophage-colony stimulating factor is thought to be involved in a variety of metabolic bone conditions, it could not be detected or induced from any of the callus samples. Moreover, none of the samples of unfractured bone showed constitutive or inducible activities for any of these cytokines. A separate experiment in which calluses and samples of unfractured bone from similar cultures were examined histologically and tested for DNA or protein synthesis at two timepoints in the culture period (days 1 and 4) showed that tissue viability was maintained. Thus the inability to detect macrophage colony-stimulating factor in fracture callus or any cytokine activity in unfractured bones was not due to cell death.(ABSTRACT TRUNCATED AT 400 WORDS)

Energy expenditure of young Polynesian and European women in New Zealand and relations to body composition.

BACKGROUND: Reduced energy expenditure and excessive energy intake have been hypothesized to cause obesity. New Zealanders of Polynesian origin have a higher prevalence of obesity than do those of European origin. OBJECTIVE: We investigated relations between components of energy expenditure and body composition. DESIGN: We measured total energy expenditure (TEE) and resting metabolic rate (RMR) in 80 young women [40 New Zealand (NZ) Polynesian and 40 NZ European] aged 18-27 y by the doubly labeled water method and indirect calorimetry, respectively. Each group was partitioned into nonobese and obese on the basis of percentage body fat. RESULTS: TEE and body weight were highly correlated in nonobese NZ Europeans (n = 23, r = 0.76, P < 0.001), obese NZ Europeans (r = 0.58, P = 0.016), and nonobese NZ Polynesians (n = 25, r = 0.59, P = 0.002) but not in obese NZ Polynesians (r = 0.11, P = 0.70). Activity energy expenditure (AEE = TEE - RMR) was similar in obese Polynesians and Europeans (mean+/-SD: 5.5+/-2.2 and 5.2+/-1.9 MJ/d, respectively), but significantly higher in nonobese Polynesians (5.7+/-2.5 MJ/d) than in their European counterparts (3.8+/-1.9 MJ/d, P = 0.005). Similar trends were seen when AEE adjusted for body weight and TEE/RMR were compared among the subgroups. Body weight and RMR together accounted for 66% of the variation in TEE for the European group but only 17% for the Polynesian group. CONCLUSION: Care should be taken in applying "Caucasian norms" relating to energy expenditure to NZ Polynesian people.

Prediction of percentage body fat from anthropometric measurements: comparison of New Zealand European and Polynesian young women.

The prediction of total body fat from simple anthropometric measurements was examined in 42 white (New Zealand European and 40 Polynesian women aged 18-27 y. Percentage body fat (%BF) was determined from measurements of total body water (TBW) by 18O dilution. Mean (+/- SD) body mass index (BMI; in kg/m2) averaged 29.2 +/- 7.9 (range: 16.5-48.0) for the New Zealand European group and 31.2 +/- 7.9 (range: 19.8-51.8) for the Polynesian group, %BF calculated from TBW was similar in the two groups (40.5 +/- 9.9% for the New Zealand European compared with 39.1 +/- 7.5% for the Polynesian group). BMI was significantly correlated with height in the Polynesian group but not in the New Zealand European group. The relation between BMI and %BF was curvilinear for both groups. At a fixed %BF, BMI was higher in the Polynesian group than in the New Zealand European group. A BMI of 30 for the New Zealand European group corresponded to a BMI of 34 for the Polynesian group at an equivalent %BF (42%). Prediction equations for %BF developed from skinfold thicknesses or girth measurements were ethnicity dependent. We conclude that the BMI criterion for obesity in whites requires revision for use in Polynesians.

Reduction of NMDA receptors with dithiothreitol increases [3H]-MK-801 binding and NMDA-induced Ca2+ fluxes.

1. We have investigated the modulation of N-methyl-D-aspartate (NMDA) receptor activation by the sulphydryl redox reagents dithiothreitol (DTT) and 5,5-dithio-bis-2-nitrobenzoic acid (DTNB). 2. Increases in [3H]-MK-801 binding produced by glutamate, glycine and spermidine were enhanced by DTT (2mM) and diminished by DTNB (0.5 mM). 3. The inhibition of [3H]-MK-801 binding by CGS 19755 and 7-chlorokynurenate was not altered by 2 mM DTT. However, the potency of the competitive polyamine antagonist, arcaine, was decreased by DTT. 4. NMDA-induced Ca2+ fluxes into primary cultures of rat forebrain neurones were enhanced by DTT in a DTNB-reversible fashion. In addition to augmenting the magnitude of NMDA-induced increase in intracellular free Ca2+, 10 mM DTT also prolonged the duration of the Ca2+ signal. However, DTT had no effect on the increase in Ca2+ produced by depolarizing neurones with 50 mM KCl. 5. These studies show that the reduction of disulphide bonds on the NMDA receptor complex by DTT increases activation. The precise site of these groups remains unclear but they are unlikely to form an integral part of the glutamate, glycine or polyamine binding domains. The enhancement of the activation of the NMDA receptor by DTT is associated with increased Ca2+ fluxes. The possible pathophysiological consequences of receptor reduction are discussed.

Analysis of MTS1/CDK4 in female breast carcinomas.

Multiple factors, both environmental and genetic, are thought to play roles in breast carcinogenesis. The recently cloned multiple tumor suppressor gene (MTS1), the product of which interacts with CDK4 to regulate cell growth, has been found to be mutated with high frequency in a variety of cell lines as well as primary tumors of different histologic types. Using PCR-SSCP, we analyzed exons one (126 bp) and two (307 bp) of the MTS1 gene to determine the incidence of mutation in a population of 50 primary breast adenocarcinomas and corresponding normal tissue. Analysis of five breast tumor cell lines was also performed. We found no mutations in the MTS1 gene in the primary breast tumor samples. One cell line was found to have a homozygous deletion of the gene. Our results suggest that the MTS1 gene is not mutated with increased frequency in primary breast tumors, and thus may not play a major role in breast carcinogenesis.

Estimation of body fatness from body mass index and bioelectrical impedance: comparison of New Zealand European, Maori and Pacific Island children.

OBJECTIVE: To compare percentage body fat (%BF) for a given body mass index (BMI) among New Zealand European, Maori and Pacific Island children. To develop prediction equations based on bioimpedance measurements for the estimation of fat-free mass (FFM) appropriate to children in these three ethnic groups. DESIGN: Cross-sectional study. Purposive sampling of schoolchildren aimed at recruiting three children of each sex and ethnicity for each year of age. Double cross-validation of FFM prediction equations developed by multiple regression. SETTING: Local schools in Auckland. SUBJECTS: Healthy European, Maori and Pacific Island children (n=172, 83 M, 89 F, mean age 9.4+/-2.8(s.d.), range 5-14 y). MEASUREMENTS: Height, weight, age, sex and ethnicity were recorded. FFM was derived from measurements of total body water by deuterium dilution and resistance and reactance were measured by bioimpedance analysis. RESULTS: For fixed BMI, the Maori and Pacific Island girls averaged 3.7% lower %BF than European girls. For boys a similar relation was not found since BMI did not significantly influence %BF of European boys (P=0.18). Based on bioimpedance measurements a single prediction equation was developed for all children: FFM (kg)=0.622 height (cm)(2)/resistance+0.234 weight (kg)+1.166, R(2)=0.96, s.e.e.=2.44 kg. Ethnicity, age and sex were not significant predictors. CONCLUSIONS: A robust equation for estimation of FFM in New Zealand European, Maori and Pacific Island children in the 5-14 y age range that is more suitable than BMI for the determination of body fatness in field studies has been developed.

Late surgical complications of choledochal cystoenterostomy.

Choledochal cyst is a rare congenital abnormality of the biliary tract characterized by dilatation and stasis. Cyst excision is now preferred to internal drainage because of the predilection for development of cancer in the unresected cyst wall. We report on four patients who required reoperations for complications of prior cystoenteric drainage from 14 to 21 years after the original operations. Gastrointestinal bleeding from cyst ulceration as occurred in one patient is heretofore unreported. This reoperative experience emphasizes the importance of cyst excision as primary therapy and underscores these principles: 1) The spectrum of complications, including infection, pancreatitis, cancer, and bleeding may occur with or without intracyst and ductal stones; 2) Radical operative procedures may be required for treatment of the complications; 3) Despite these, cholangiocarcinoma has a dismal prognosis; 4) Patients whose cysts remain unexcised require meticulous lifelong scrutiny and strong consideration for planned reoperation at the time of the first complication.