Click here to watch a video of different intubation techniques

Airway management may be required urgently when a patient deteriorates in an ambulance during interhospital transfer or in a prehospital setting. En-route intubation in an ambulance is challenging due to patient and environmental factors.1 These may include inadequate or over-exposed lighting, limited access to the patient, a continuously moving environment, confined space, and unanticipated patient deterioration. The success rate of en-route intubation (89.6%) is lower than that of hospital intubation (98.8%) and intubation-on-scene (94.9%) in air medical transport.2 Intubation success is more likely in a hospital setting (odds ratio [OR]=8.70) or at the scene (OR=2.3) compared with en-route intubation.2

Some studies3 4 suggest using inverse intubation in an entrapped or confined environment. In inverse intubation, the intubator crouches or kneels near the patient’s right side, while holding the laryngoscope in the right hand. Patient’s mouth is opened with the intubator’s left hand. The laryngoscope blade is gently pulled up and towards the patient’s feet at a 45° angle. The endotracheal tube is passed between the visualised vocal cords. The success rate and time of intubation of using inverse intubation in air transport were not significantly different from those with conventional intubation in air transport.5 Inverse intubation is particularly useful in circumstances where the cephalad access to the patient is limited. In addition, the mechanical advantages of pulling up the larynx with the dominant hand may, theoretically, facilitate visualisation of vocal cords of patients with difficult airways.

In recent years, portable video laryngoscope (GlideScope; Verathon Inc, Bothell [WA], US) was introduced to facilitate airway management in the prehospital setting.6 7 GlideScope was the first commercially available video laryngoscope. It uses a high-resolution camera embedded into a plastic laryngoscope blade, and a LED light for illumination. The distal angulation makes it ideally suitable for visualising and intubating over the anterior larynx. The endotracheal tube has to be used with a special stylet to match the gentle curve of 60° of the GlideScope blade. It has been proven to be a useful adjunct for intubation in both normal and difficult airways in selected settings.8 9 10

The objectives of our experimental study were: (1) to compare the effectiveness of conventional intubation by Macintosh laryngoscope in a moving ambulance versus that in a static ambulance; (2) to compare the effectiveness of inverse intubation and GlideScope laryngoscopy (model: GVL 4) with conventional intubation inside a moving ambulance.

This was a comparative experimental study conducted from June to October 2012. Altogether, 22 doctors—including emergency medicine trainees, members, and fellows—were recruited to participate voluntarily in the study. All participants were working in the accident and emergency department (AED) and had been practising emergency medicine for at least 2 months. All of them had experience in performing endotracheal intubation in patients. The approval of ethics committee was considered waived as the study was performed on manikins and did not involve patients.

Demographic data of the participating doctors including age, gender, AED working experience, previous attendance of advanced airway training workshop, past experience of using inverse intubation and GlideScope on living or dead patients were collected. Advanced airway training workshop is a full-day course organised by the Hong Kong College of Emergency Medicine. Course attendants learn the basic skills of endotracheal intubation. Various airway adjuncts such as GlideScope are demonstrated and opportunities provided for participants to practise intubation with these during the course.

The use of conventional Macintosh laryngoscopy, inverse intubation with Macintosh laryngoscope and GlideScope laryngoscopy were demonstrated to participants individually by the experiment conductor using an “AIRSIM” manikin at least 1 week before the study. The participants were allowed hands-on practice of the techniques and devices, freely, in a training room before the experiment.

The experiment was conducted in an ambulance provided by the Auxiliary Medical Service. The ambulance we used was Mercedes-Benz 516CDI measuring approximately 1.6 m in width and 2.2 m in length. The stretcher, together with the manikin, was locked on the right side of the ambulance, as in real life. The intubator would have limited room to kneel down at the vertex of the patient to perform conventional Macintosh and GlideScope intubations (Fig 1). Inverse intubation was performed on the right side of the manikin (Fig 2). The ambulance was moving at a speed of 20 km/hour, following a fixed route chosen before the experiment within the hospital compound. Moving at this relatively slow speed was only possible on the chosen route as there were a number of turnarounds and road bumpers.

The Laerdal “Adult Basic” manikin was used in the study. A neck collar was applied to the manikin to restrict the neck mobility and simulate a difficult airway. Size-3 blade was used for conventional Macintosh and inverse intubations. All intubations were performed with a 7.5-mm cuffed endotracheal tube. All participants performed intubations on the manikin in both normal and difficult airways inside a static ambulance and moving ambulance. Participants performed the conventional Macintosh, inverse Macintosh and GlideScope intubations in both normal and simulated difficult airways inside the moving ambulance in the same sequence. Neither external manipulation of the larynx nor airway management adjunct was allowed in the study.

The time required for intubation was recorded with electronic stopwatch and corrected to one decimal place. The start time was defined when the participant was asked to begin while sitting on the couch, approximately 1 metre from the manikin, with the equipment in hands. The end of the procedure was defined when the participant verbally stated that the airway was secured with inflation of the cuffed balloon of the endotracheal tube. The verification of the endotracheal tube placement was performed by direct visualisation and inflation of the artificial lung, with no air leakage from the manikin. Both oesophageal intubation and intubation with time taken longer than 60 seconds were considered to be unsuccessful procedures. Incisor breakage was reported by the participants when a “click” sound was heard during intubation; however, it was not considered an unsuccessful intubation. Participants also reported the Cormack-Lehane laryngoscopic grading system (C&L grade; grade 1-4) and their preferences for intubation techniques and devices. Eventful intubation was defined as incisor break, oesophageal intubation, or intubation taking longer than 60 seconds.

We used SPSS version 16.0 for Windows for statistical analysis. Rates of successful intubation and incisor breakage were presented in percentage. The working experience of participants and time spent on intubation were described by median and interquartile range as the data showed skewed distribution. The time required for intubation by different intubation techniques and devices were analysed by Wilcoxon signed rank test for paired data. The rates of successful intubation, complications including oesophageal intubation, incisor breakage and the subjective visualisation grading system among different intubation techniques and devices were compared using Fisher’s exact test with or without Freeman-Halton extension. Spearman’s correlation was employed to show the relationship between time of intubation and AED experience. The results were regarded as statistically significant if P<0.05.

A total of 22 AED (17 male and 5 female) doctors participated in the experiment. The median age of the participants was 30.5 years. The mean AED working experience of the participants was 4.9 years. As the technique and devices were demonstrated by the experiment conductor before beginning the experiment, all doctors had experience with using inverse intubation and GlideScope in a manikin. The details are shown in Table 1. All participants performed intubations in the eight scenarios and the success rate of each scenario was summarised in Figure 3.

The percentage of successful and unsuccessful intubations, time required for intubation, subjective glottis visualisation score, and complication rates using conventional Macintosh intubation in static and moving ambulance are shown in Table 2. In normal airways, the intubation success rates in both static (95.5%) and moving ambulances (95.5%) were high. The median intubation times for intubation in static and moving ambulances were 21.2 seconds and 26.5 seconds, respectively (P=0.268). In difficult airways, the intubation success rates in static and moving ambulances were 86.4% and 90.9%, respectively. The median intubation times in static and moving ambulances were 22.6 seconds and 20.6 seconds, respectively (P=0.488). There was no significant difference in the Cormack-Lehane grades and incidence of eventful intubation between the two groups.

The intubation performance using the conventional Macintosh laryngoscopy and inverse Macintosh intubation in a moving ambulance is shown in Table 3. In normal airways, the success rate of conventional intubation (95.5%) was significantly higher than that of inverse intubation (54.5%; P=0.004). The median intubation time with the conventional technique (26.5 seconds) was shorter than that with inverse intubation (37.8 seconds; P=0.043). The number of difficult laryngeal visualisation (ie Cormack-Lehane grade ≥3) was significantly higher with inverse intubation technique (n=8; 36.4%) versus the conventional technique (0%; P<0.001). The incidence of eventful intubation with inverse intubation (81.8%) was significantly greater than that with conventional intubation (13.6%; P<0.001). In difficult airways, the intubation success rate of conventional technique (90.9%) was also significantly higher than that of inverse intubation (40.9%; P=0.034). The median intubation time required for conventional intubation technique (20.6 seconds) was significantly shorter than that for inverse intubation (51.3 seconds; P=0.002). The number of difficult airway intubations was significantly higher with inverse technique (n=12; 54.5%) than with conventional technique (13.6%; P=0.003). The incidence of eventful intubation was significantly higher in the inverse intubation group (81.8%) than that in the conventional intubation group (36.4%; P=0.002).

The intubation performance using conventional Macintosh and GlideScope laryngoscopes in a moving ambulance is summarised in Table 4. In normal airways, the conventional intubation technique (95.5%) and GlideScope laryngoscopy (95.5%) were associated with high success rates. The median intubation time with conventional technique (26.5 seconds) was shorter than that with GlideScope (31.0 seconds; P=0.012). In difficult airways, both conventional technique (90.9%) and GlideScope (100%) were associated with high success rates. The median intubation time with conventional technique (20.6 seconds) was significantly shorter than that with GlideScope (32.4 seconds; P<0.001). None of the intubations with GlideScope in both normal and difficult airways was given Cormack-Lehane grade of ≥3 but no statistical difference could be demonstrated in the grades when compared with conventional intubation in both normal (P=0.721) and difficult airways (P=0.180). There was an obvious trend for less eventful intubation with GlideScope (9.1%) versus the conventional intubation group (36.4%; P=0.069).

The relationship between the time required for intubation and AED experience is presented in Figure 4. An experienced doctor in AED required less time for conventional intubation in both normal (P=0.043) and difficult airways (P=0.019) in a static ambulance. Also, experienced doctors did better with conventional intubation than inverse intubation in normal airways in a moving ambulance (P=0.019).

Data on the doctors' perception of the new technique and device were also collected. Overall, two (9.1%) and 17 (77.3%) doctors thought that inverse intubation and GlideScope were, respectively, useful as adjuncts in normal airways, while one (4.5%) and 19 (86.4%) thought that inverse intubation and GlideScope were, respectively, useful in difficult airways.

Previous studies found a 7% to 10% incidence of difficult intubation in prehospital emergency en-route intubations.11 12 A number of patient and environmental factors contribute towards the difficulty in en-route intubation.1 Environmental factors including restricted space, continuous movement of the ambulance, and inadequate lighting are believed to adversely affect the en-route intubation compared with intubation in a controlled hospital setting. In our study, we found that the success rates of conventional Macintosh intubation in normal and difficult airways were high in static and moving ambulances. There was no significant difference in oesophageal intubation rate, intubation time, laryngeal visualisation scores, and incisor breakage rate with conventional Macintosh intubation in static and moving ambulances. The environment of a moving ambulance did not appear to hinder the ability of conventional Macintosh intubation in our experiment. Gough et al13 also recruited 20 emergency medical technicians at the advanced-intermediate level of EMT (Emergency Medical Technician) to perform intubation on a manikin in a moving ambulance and static station. They also found no significant difference in the success rates and time required for intubation between the two groups. Stopping an ambulance or a helicopter for en-route intubation may be impossible or dangerous in real life. Our study suggests that en-route intubation is feasible in an ambulance moving at a speed of 20 km/hour.

Inverse intubation has been proposed by Hilker and Genzwuerker3 as “an important alternative for intubation in the street”. The technique was proven to be useful as adjunct in failed conventional intubation and an important backup position if access from behind the patient’s head is impossible.4 5 14 In our study, we found that inverse intubation in an ambulance was associated with higher failure rate, prolonged intubation, and more complication rates versus conventional intubation. The clinical usefulness of this technique in a moving ambulance was not established in our study. Besides, one of the reported complications of inverse intubation is pharyngeal laceration.15 If this complication is not recognised, it could result in significant haemorrhage or potentially lethal infection. Individual experience is a significant determining factor for the success of the technique. During the experiment, we also found that it was quite inconvenient for the intubators who wore spectacles to perform inverse intubation as the spectacles were likely to fall off due to the peculiar posture required when performing the procedure. Inverse intubation would be a reasonable choice for trained rescuer who cannot position himself/herself to the space above the victim’s (eg entrapment).

GlideScope has been shown to facilitate tracheal intubation by improving the laryngeal view in manikin studies,7 8 9 emergency settings,16 17 18 and a wide spectrum of selective surgeries.19 20 21 Struck et al6 conducted a retrospective observational study and survey of experiences in prehospital intubation for a 3-year period. Around 15% of the patients presented with multiple traumas or failed intubation with conventional laryngoscopy and required intubation by GlideScope. In our study, we demonstrated high intubation success and low failure rates with GlideScope laryngoscopy, but the median time for intubation was slightly longer versus that with the conventional Macintosh laryngoscopy in normal airways (P=0.012) and difficult airways (P<0.001). The finding of longer intubation time with GlideScope was also demonstrated in previous studies.16 19 20 However, some studies found no difference in the intubation time.7 22 One study8 even found that GlideScope enables faster intubation in patients with cervical spine immobilisation. The wide range of results may be attributed to the differences in experience with using GlideScope, different study settings (manikin vs real patient), and different study scenarios (normal vs difficult airway). Piepho et al23 conducted a study among paramedics who used the Macintosh and GlideScope video laryngoscopes for intubating manikins. They found that the intubation time with GlideScope was longer than that with Macintosh in the first and second attempts of intubation. However, no significant difference in time required for intubation was observed in the subsequent attempts. This confirms a rapid learning curve for intubation with GlideScope. In another manikin study with 60 anaesthetists, GlideScope was found to have a steep learning curve for intubation but, after five attempts, differences in terms of time of endotracheal intubation persisted when compared with the Macintosh laryngoscopy.24 In our study, there was a trend for less eventful intubation with GlideScope (P=0.069) in the setting of difficult airways. Thus, we recommend its use as a backup for en-route intubation, especially in difficult airway settings. In real-life practice of using GlideScope, the passage of endotracheal tube through the deeply curved and rigid stylet may be hindered. An assistant is required to thread the endotracheal tube into the trachea while the intubator holds the GlideScope in position. This is expected to be more difficult in an ambulance because of limited space.

This study had several limitations. Firstly, we used a manikin in our study rather than a real patient; thus, the results may not be transferrable to real patients. However, we believe that the use of new techniques and devices in airway management is not ethical in clinically unstable and emergency patients. A well-designed manikin-based study would be an acceptable choice for the aforementioned reasons. Secondly, only one of the difficult airway situations was tested in our study. Other difficult airway situations in daily practice such as limited mouth opening, tongue oedema, and presence of blood/vomitus were not studied. Thirdly, there was the issue of learning curve associated with new techniques and devices. Overall, one (4.5%) and eight (36.4%) of the participants had previous experience of using inverse intubation and GlideScope in clinical settings, respectively. Although we demonstrated the use of inverse intubation and GlideScope and allowed participants to practise freely at least 1 week before the experiment, we cannot demonstrate the non-inferior result associated with the use of inverse intubation in a previous study.5 We also observed that the intubation time for difficult airways in a moving ambulance was shorter than that for normal airways. The most likely explanation is the learning effect and intubation experience. The participants performed different intubation techniques in normal airways followed by the same techniques in difficult airways in a moving ambulance. The participants may have gained experience from working in a continuously moving environment. We suggest further studies with inverse intubation and GlideScope after a longer period of training and practice to examine for the reproducibility of these results. Fourthly, the study was performed inside our hospital which has imposed speed limits on vehicles moving on the road. Moving at a relatively slow speed of 20 km/hour was only possible in the chosen route as there were a number of turnarounds and road bumpers. Moreover, we limited the speed in order to avoid any danger to or fall of participants. Fifthly, GlideScope (model: GVL 4) for the experiment was chosen because it was the only model available in our hospital. Other models that are specifically designed for prehospital use such as Glidescope Ranger may be a better choice, if available. Lastly, the sample size of the study was relatively small and could have inadequate power to detect real differences between some comparison, for example, comparison of the eventful intubation rate between GlideScope and conventional intubation.

Our study demonstrates an overall high intubation success rate with conventional Macintosh and GlideScope laryngoscopes in a moving ambulance. The time required for intubation with GlideScope was longer than that with conventional laryngoscope. Application of GlideScope should be suggested as an adjunct for intubation in an ambulance in the presence of adequately trained staff. The high failure rate and prolonged time associated with the inverse intubation technique make it less useful than conventional intubation and GlideScope intubation unless the cranial access of the patient is restricted.

We would like to thank the Auxiliary Medical Service, the Hong Kong SAR Government for providing the ambulance and all physicians who participated in this experimental study.

1. Helm M, Hossfeld B, Schäfer, Hoitz J, Lampl L. Factors influencing emergency intubation in the pre-hospital setting—a multicentre study in the German Helicopter Emergency Medical Service. Br J Anaesth 2006;96:67-71. CrossRef

2. McIntosh SE, Swanson ER, McKeone A, Barton ED. Location of airway management in air medical transport. Prehosp Emerg Care 2008;12:438-42. CrossRef

3. Hilker T, Genzwuerker HV. Inverse intubation: an important alternative for intubation in the streets. Prehosp Emerg Care 1999;3:74-6. CrossRef

4. Hoyle JD Jr, Jones JS, Deibel M, Lock DT, Reischman D. Comparative study of airway management techniques with restricted access to patient airway. Prehosp Emerg Care 2007;11:330-6. CrossRef

5. Robinson K, Donaghy K, Katz R. Inverse intubation in air medical transport. Air Med J 2004;23:40-3. CrossRef

6. Struck MF, Wittrock M, Nowak A. Prehospital Glidescope video laryngoscopy for difficult airway management in a helicopter rescue program with anaesthetists. Eur J Emerg Med 2011;18:282-4. CrossRef

7. Nakstad AR, Sandberg M. The GlideScope Ranger video laryngoscope can be useful in airway management of entrapped patients. Acta Anaesthesiol Scand 2009;53:1257-61. CrossRef

8. Lim TJ, Lim Y, Liu EH. Evaluation of ease of intubation with the GlideScope or Macintosh laryngoscope by anaesthetists in simulated easy and difficult laryngoscopy. Anaesthesia 2005;60:180-3. CrossRef

9. Benjamin FJ, Boon D, French RA. An evaluation of the GlideScope, a new video laryngoscope for difficult airways: a manikin study. Eur J Anaesthesiol 2006;23:517-21. CrossRef

10. Cooper RM, Pacey JA, Bishop MJ, McCluskey SA. Early clinical experience with a new videolaryngoscope (GlideScope) in 728 patients. Can J Anaesth 2005;52:191-8. CrossRef

11. Adnet F, Jouriles NJ, Le Toumelin P, et al. Survey of out-of-hospital emergency intubations in the French prehospital medical system: a multicenter study. Ann Emerg Med 1998;32:454-60. CrossRef

12. Combes X, Jabre P, Jbeili C, at al. Prehospital standardization of medical airway management: incidence and risk factors of difficult airway. Acad Emerg Med 2006;13:828-34. CrossRef

13. Gough JE, Thomas SH, Brown LH, Reese JE, Stone CK. Does the ambulance environment adversely affect the ability to perform oral endotracheal intubation? Prehosp Disaster Med 1996;11:141-3.

14. Koetter KP, Hilker T, Genzwuerker HV, et al. A randomized comparison of rescuer positions for intubation on the ground. Prehosp Emerg Care 1997;1:96-9. CrossRef

15. Smally AJ, Dufel S, Beckham J, Cortes V. Inverse intubation: potential for complications. J Trauma 2002;52:1005-7. CrossRef

16. Platts-Mills TF, Campagne D, Chinnock B, Snowden B, Glickman LT, Hendey GW. A comparison of GlideScope video laryngoscope versus direct laryngoscopy intubation in the emergency department. Acad Emerg Med 2009;16:866-71. CrossRef

17. Mosier JM, Stolz U, Chiu S, Sakles JC. Difficult airway management in the emergency department: GlideScope videolaryngoscopy compared to direct laryngoscopy. J Emerg Med 2012;42:629-34. CrossRef

18. Sakles JC, Mosier JM, Chiu S, Keim SM. Tracheal intubation in the emergency department: a comparison of GlideScope® video laryngoscopy to direct laryngoscopy in 822 intubations. J Emerg Med 2012;42:400-5. CrossRef

19. Kim JT, Na HS, Bae JY, et al. GlideScope video laryngoscope: a randomized clinical trial in 203 paediatric patients. Br J Anaesth 2008;101:531-4. CrossRef

20. Andersen LH, Rovsing L, Olsen KS. GlideScope videolaryngoscope vs. Macintosh direct laryngoscope for intubation of morbidly obese patients: a randomized trial. Acta Anaesthesiol Scand 2011;55:1090-7. CrossRef

21. Griesdale DE, Liu D, McKinney J, Choi PT. Glidescope® video-laryngoscopy versus direct laryngoscopy for endotracheal intubation: a systematic review and meta-analysis. Can J Anaesth 2012;59:41-52. CrossRef

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Obesity was formally recognised as a global epidemic by the World Health Organization (WHO) in 1997.1 During the past decades, the prevalence of being overweight and obese has increased substantially. In Hong Kong, 17% of children were overweight/obese in 2005/6, which was a 5% increase since 1993, based on International Obesity Task Force cut-offs.2

Overweight/obese children and adolescents are more likely to have hyperinsulinaemia, hypertension, and dyslipidaemia.3 The clustering of cardiometabolic risk factors in these patients tends to track into adult life.3 However, the Diabetes Prevention Program demonstrated that lifestyle interventions could prevent or postpone the onset of type 2 diabetes mellitus (DM) by 58% in adults.4 Thus, identifying at-risk groups may allow early interventions and prevention of potential cardiometabolic complications.

Acanthosis nigricans (AN)—a hyperpigmented, thickened, and velvety dermatosis at the nape of the neck or axilla—is an easily identifiable physical sign.5 The American Diabetes Association includes it as an indicator of DM risk in overweight youths entering puberty.6 Yet, some authors have argued that it is not an independent predictor of insulin resistance (IR) if body mass index (BMI) is controlled for.7

Ethnic differences occur in obesity indices and their associated risk factors include IR.8 Local studies focusing on associations between AN with IR and other cardiometabolic co-morbidities in Chinese paediatric age-groups are sparse. In this regional centre study, we describe the demographic characteristics and IR in obese Chinese children with and without AN, with a focus on exploring the associations of AN with IR and other cardiometabolic co-morbidities.

A retrospective study was conducted by recruiting overweight/obese children and adolescents between 5 and 18 years of age who underwent obesity assessment between January 2006 and December 2010 in a regional hospital in Hong Kong. Patients were excluded if they had underlying metabolic diseases, chronic diseases, or other medical conditions resulting in obesity. Patients taking on medications that would alter metabolic profiles were also excluded.

Anthropometric data and AN status were recorded. Blood samples were collected. Ultrasound liver scans were performed on patients with elevated alanine aminotransferase (ALT) levels. Height was measured to the nearest 0.1 cm using the Harpenden stadiometer (Holtain; Crymych, UK) and body weight to the nearest 0.1 kg with light clothing using an electronic column scale (SECA-780; Seca Ltd, Hamburg, Germany). The BMI (kg/m²) percentiles of 90th and 97th centiles were used to define overweight and obesity, respectively.9 10 Local percentile standards were based on a local population survey conducted in 1993.11 The BMI z-score was calculated using this local age- and gender-specific reference. Blood pressure (BP) was measured using the standard oscillometric method (BP-8800C; Colin Electronics, Komaki, Japan) in the daytime with the children seated and rested. Average BP was obtained from two measurements. The BP z-score was calculated using the local BP reference.12 Participants were considered hypertensive if the mean systolic BP z-score and/or diastolic BP (DBP) z-score was/were greater than or equal to the 95th centiles for age and gender.

The diagnosis of AN was made by paediatricians; additional scoring for this entity was not undertaken as not all authors agreed that specific quantitative scales could improve the accuracy of IR prediction.13

Blood samples for plasma glucose, insulin, lipid profile, and liver enzymes following an overnight fasting were obtained and a standard oral glucose tolerance test (OGTT) was performed. The homeostasis model of assessment (HOMA)–IR value was used to assess IR using the following equation: fasting glucose (mmol/L) x fasting insulin (µU/mL)/22.5.14 Any HOMA value of ≥4 was considered to indicate IR. Glucose abnormalities were defined according to criteria from the WHO.15 Abnormal glucose homeostasis was referred to any combination of impaired fasting glucose, impaired glucose tolerance, or DM on the basis of fasting or 2-hour plasma glucose levels in the OGTT.16 17 Fatty liver was diagnosed by ultrasound scan affirmed by the operational definition of non-alcoholic fatty liver disease in the Asia-Pacific region.18

The statistical analyses were conducted using the Statistical Product and Service Solutions (version 17.0 for Windows 7). Taking P<0.05 as statistically significant, Student’s t test and Wilcoxon rank-sum test were used to compare results with a normal and skewed distribution, respectively. The Chi squared test or Fisher’s exact test as appropriate were used to analyse categorical variables. Multiple logistic regression analysis was then performed to identify independent factors associated with IR. To avoid multicollinearity, body weight and height were not used in the model, since both variables correlated highly with BMI. For the same reason, fasting insulin and glucose levels were not selected for the model as the HOMA-IR was derived from them. The model was simplified in a backward stepwise fashion by removing variables with P values of >0.1. Goodness-of-fit of the regression model was tested with the Hosmer-Lemeshow test.

A total of 543 overweight/obese Chinese patients were included in this study. They had a mean ± standard deviation age of 12 ± 3 years and 64% (n=346) of them were boys. The majority (77%, n=419) were obese with a BMI of >97%. In all, AN was present in 54% (n=295) of the subjects and 29% (n=156) of them had IR. Relevant data are summarised in Table 1.

Table 2 illustrates that adolescents (aged 12-18 years), compared with younger children (aged 5-11 years), were more likely to have AN (63% vs 47%; P<0.001) and IR (37% vs 25%; P=0.005). Obese children, compared with overweight children, were also more likely to have AN (59% vs 44%; P=0.005) and IR (35% vs 19%; P=0.001).

Table 3 shows baseline characteristics and biochemical parameters in children with and without AN. Apart from being older, the group with AN had higher mean 2-hour post-OGTT glucose (P=0.021), fasting insulin (P<0.001), triglyceride (P<0.001), and ALT (P=0.002) levels, but lower mean levels of high-density lipoprotein (HDL) cholesterol (P<0.001). Their BMI (P<0.001), BMI z-score (P<0.001), systolic blood pressure (SBP) [P<0.001], and HOMA-IR values (P<0.001) were also higher. Notably, the higher SBP, when converted to SBP z-score (taking into account age and gender), was no longer significant. Both DBP and DBP z-scores showed no differences between the two groups. The presence of IR and other cardiometabolic co-morbidities in subjects with and without AN are also shown in Table 3. The frequencies of IR, hypertension, fatty liver, and abnormal glucose homeostasis were all significantly higher in subjects with AN.

Further analysis of risk factors for IR using the multiple logistic regression model showed that the presence of AN (odds ratio [OR]=2.36; 95% confidence interval [CI], 1.46-3.80; P<0.001), older age (1.17; 1.07-1.28; P=0.001), higher triglyceride level (1.91; 1.33-2.74; P<0.001), and higher BMI z-score (6.95; 3.40-14.16; P<0.001) were significant independent variables predicting IR (Table 4). However, though HDL and 2-hour post-OGTT glucose level were borderline significant predictors for IR, their effect sizes were small. The Hosmer-Lemeshow test of goodness-of-fit was 0.315, indicating a good logistic regression model fit.

Obesity is a public health problem that has become epidemic worldwide. In the primary care setting, identifying children with AN may allow early implementation of interventions to prevent the development of DM and other cardiometabolic co-morbidities in overweight/obese children.16 Searching for AN over the neck is easy, non-intrusive. and acceptable to the children.19 Presence of AN can also be used as a grounds to initiate and reinforce discussions about lifestyle modification.5 19 20

An observed AN frequency of 54% in our subjects was consistent with data reported in the literature.21 22 Our adolescents were more likely to have AN than younger children, in line with hyperinsulinaemia being more severe among older individuals.22 In our study, development of AN showed no gender preference, as in a study of 1412 unselected children by Stuart et al.23 In our cohort and that in Nsiah-Kumi et al’s study,13 obese children were more likely to have AN than overweight ones.

Whilst IR is a hallmark of obesity, it is also associated with other metabolic derangements and clinical or subclinical cardiovascular diseases.24 We used the HOMA-IR value—a simple, validated, and practical marker of IR in the paediatric population—to give a more physiological estimate of glucose homeostasis,25 that was also shown to correlate well with the hyperinsulinaemic-euglycaemic glucose clamp technique, a gold standard for quantifying insulin sensitivity.24 In a local community-based cross-sectional study, it was shown that the mean HOMA-IR value was lower among Hong Kong Chinese adolescents than subjects in the United States.8 Currently, there is no worldwide consensus on defining IR among children. Some studies have chosen an HOMA-IR value as low as 2.7 while others have shown that a value of 4 can be present in pubertal children (because of the transient physiological IR during puberty).13 Although we do not have data about pubertal stage in our study subjects, an HOMA-IR of ≥4 would be a conservative but reasonable definition of IR, in parallel with the threshold used in a multicentre trial in the United States (Studies to Treat or Prevent Pediatric Type 2 Diabetes—STOPP-T2DM).26

In our study, 29% of our cohort had IR using the cut-off HOMA-IR of ≥4, and the mean value was higher among those with AN present (3.6 vs 2.6; P<0.001). Notably, IR was more common among adolescents than young children (37% vs 25%; P=0.005) as well as among obese than overweight subjects (35% vs 19%; P=0.001). Goran et al27 suggested that long-standing obesity and the physiological IR during puberty accounted for adolescents having more AN and IR. They found that pubertal transition from Tanner I to Tanner III was associated with a 32% reduction in insulin sensitivity across different genders and ethnicities, and proved that body fat was the predominant factor influencing IR whereas total and visceral fat both contributed independently to lower insulin sensitivity.27 Notably, 25% of our young (5-11 years old) overweight/obese subjects already had IR, suggesting that the onset of metabolic derangement might have started long before adolescence and indicates that screening should begin early during childhood.

In our cohort, IR and other cardiometabolic co-morbidities were more prevalent among those with AN. The relationship of AN with hypertension may not be as strong as that with fatty liver and abnormal glucose homeostasis. This might be consistent with hypertension being more closely related to obesity than to AN.28 Nevertheless, studies assessing the relationship of BP and insulin levels are conflicting.29 Some authors postulate that the underlying pathophysiology is a common genetic predisposition to both IR and hypertension, whilst also involving other mechanisms.30

Dyslipidaemia is believed to play a central role in the development of heart diseases. High level of triglyceride and low level of HDL cholesterol are commonly used criteria to define metabolic syndrome both in children and adults.31 High triglyceride levels and the IR index (HOMA-IR) were strong, independent predictors of increased carotid intima-media thickness, which was a non-invasive measure of subclinical atherosclerosis in paediatric research.32 Nevertheless, low HDL cholesterol level carried an even greater relative risk than high triglyceride levels.33 Compared with those without AN, subjects with the condition had a higher mean triglyceride level (P<0.001) but lower HDL level (P<0.001), and hence their future cardiovascular health seems to be of great concern.

Fatty liver, or non-alcoholic fatty liver disease (NAFLD), can be classified into isolated fatty liver in which there is only accumulation of fat, and non-alcoholic steatohepatitis (NASH) in which there is fat accumulation and damage to liver cells. Presence of the latter is associated with raised liver enzymes and more abnormal ultrasound scans. Our subjects with AN had higher levels of ALT (P=0.002) and a higher proportion with fatty livers. In contrast, Uwaifo et al34 reported that AN was not common among a small cohort of 28 subjects with biopsy-proven NASH, despite their high prevalence of IR. These authors therefore questioned the use of AN as an index of IR in patients with NASH. However, in our study liver ultrasounds were only performed in children with raised ALT levels. According to Sartorio et al,35 the ALT level alone was insufficient as a marker of NAFLD and the sensitivity of using its level to predict NAFLD was as low as 41% (depending on the cut-off used). Several prediction scores have been developed for non-invasive liver steatosis screening, but they have insufficient diagnostic accuracy among obese children.36

For DM, incidence, prevalence, and disease progression are believed to vary in different ethnic groups. The overall frequency of abnormal glucose homeostasis of 10% (8% impaired glucose tolerance and 2% with DM; data not shown) was lower than in a recent study by Brickman et al16 who reported a 29% frequency of abnormal glucose homeostasis among a group of 8-to-14 years old, mainly of Hispanic and African American children with AN. Another study from the United Kingdom found a higher frequency of type 2 DM among African-Caribbean and South Asian groups, while the Chinese and white Caucasians had the lowest frequencies.37 The reasons for such inter-ethnic differences are still unclear but do not seem to be solely genetic, as inter-generational social factors may also modify the evolution and biology of the disease.37 Our results, together with the recently reported sharp rise in the incidence of type 2 DM in Hong Kong children aged under 19 years after 2004,38 should alert our health care professionals as to the importance of early detection of potential predictors of abnormal glucose metabolism such as AN.

Recently, the role of IR in cardiometabolic derangements has attracted more attention. Nevertheless, there is no prediction model for IR in our local children and adolescents. Using multivariate analysis, our study demonstrates that age, AN status, triglyceride level, and BMI z-score are significant independent variables associated with IR. Hopefully, a simple and practical prediction model of IR with acceptable sensitivity and specificity can be derived by combining these clinical findings, anthropometric measurements, and biochemical markers.

Important limitations of this study included its retrospective design, being single-centred, and thus not being suitable for calculating population-based rates. In addition, the stage of puberty (not documented) may also influence IR. Moreover, several relevant risk factors (family history of metabolic derangement, maternal gestational DM, duration of obesity, socio-economic status) were not included in the analysis. As in other retrospective studies, it was not possible to retrieve every single item of data. Notably, AN status was unavailable in 11 (2%) patients while HOMA-IR information was absent in 46 (8%) of the subjects, as fasting insulin levels were not checked and might have contributed to selection bias. Our study was clinic-based and not population-based, and so an overestimate of morbidity was a possibility. Besides, establishing a relationship between cause and effect was not possible due to the cross-sectional nature of the study. Growth data collected in 1993 (HK1993) are still widely used locally and seem appropriate in Hong Kong.9 We adopted the operational BMI cut-offs for daily use locally. However, the ideal cut-offs for being overweight and having obesity remain controversial, and various definitions and operational values exist.39 These problems may also limit direct comparisons between different studies using different growth references and cut-offs.39

Local obese Chinese children with AN are at higher risk of IR and cardiometabolic co-morbidities. Primary care physicians should be vigilant for this clinical sign. If present, early attention is necessary to achieve early intervention. Further studies may be necessary to evaluate the longitudinal risk relationship between AN and cardiometabolic outcomes.

1. Caballero B. The global epidemic of obesity: an overview. Epidemiol Rev 2007;29:1-5. CrossRef

2. So HK, Nelson EA, Li AM, et al. Secular changes in height, weight and body mass index in Hong Kong Children. BMC Public Health 2008;8:320. CrossRef

3. Bao W, Srinivasan SR, Wattigney WA, Berenson GS. Persistence of multiple cardiovascular risk clustering related to syndrome X from childhood to young adulthood: the Bogalusa Heart Study. Arch Intern Med 1994;154:1842-7. CrossRef

4. Knowler WC, Barrett-Connor E, Fowler SE, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002;346:393-403. CrossRef

5. Kong AS, Williams RL, Smith M, et al. Acanthosis nigricans and diabetes risk factors: prevalence in young persons seen in southwestern US primary care practices. Ann Fam Med 2007;5:202-8. CrossRef

6. American Diabetes Association. Type 2 diabetes in children and adolescents. Diabetes Care 2000;23:381-9. CrossRef

7. Ice CL, Murphy E, Minor VE, Neal WA. Metabolic syndrome in fifth grade children with acanthosis nigricans: results from the CARDIAC project. World J Pediatr 2009;5:23-30. CrossRef

8. Kong AP, Choi KC, Ko GT, et al. Associations of overweight with insulin resistance, beta-cell function and inflammatory markers in Chinese adolescents. Pediatr Diabetes 2008;9:488-95. CrossRef

9. So HK, Nelson EA, Sung RY, Ng PC. Implications of using World Health Organization growth reference (2007) for identifying growth problems in Hong Kong children aged 6 to 18 years. Hong Kong Med J 2011;17:174-9.

10. Ng DK, Lam YY, Kwok KL, Chow PY. Obstructive sleep apnoea syndrome and obesity in children. Hong Kong Med J 2004;10:44-8.

11. Leung SS, Cole TJ, Tse LY, Lau JT. Body mass index reference curves for Chinese children. Ann Hum Biol 1998;25:169-74. CrossRef

12. Sung RY, Choi KC, So HK, et al. Oscillometrically measured blood pressure in Hong Kong Chinese children and associations with anthropometric parameters. J Hypertens 2008;26:678-84. CrossRef

13. Nsiah-Kumi PA, Beals J, Lasley S, et al. Body mass index percentile more sensitive than acanthosis nigricans for screening Native American children for diabetes risk. J Natl Med Assoc 2010;102:944-9.

14. Matthews D, Hosker J, Rudenski A, Naylor B, Treacher D, Turner R. Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985;28:412-9. CrossRef

15. Definition, diagnosis and classification of diabetes and its complications: report of a WHO consultation, part 1: diagnosis and classification of diabetes mellitus. Geneva, Switzerland: World Health Organization; 1999.

16. Brickman WJ, Huang J, Silverman BL, Metzger BE. Acanthosis nigricans identifies youth at high risk for metabolic abnormalities. J Pediatr 2010;156:87-92. CrossRef

17. Atabek ME, Pirgon O, Kurtoglu S. Assessment of abnormal glucose homeostasis and insulin resistance in Turkish obese children and adolescents. Diabetes Obes Metab 2007;9:304-10. CrossRef

18. Chitturi S, Farrell GC, Hashimoto E, et al. Non-alcoholic fatty liver disease in the Asia-Pacific region: definitions and overview of proposed guidelines. J Gastroenterol Hepatol 2007;22:778-87. CrossRef

19. Smith WG, Gowanlock W, Babcock K, et al. Prevalence of acanthosis nigricans in First Nations children in Central Ontario, Canada. Can J Diabetes 2004;28:410-4.

20. Kong AS, Williams RL, Rhyne R, et al. Acanthosis nigricans: high prevalence and association with diabetes in a practice-based research network consortium—a PRImary care Multi-Ethnic network (PRIME Net) study. J Am Board Fam Med 2010;23:476-85. CrossRef

21. Shalitin S, Abrahami M, Lilos P, Phillip M. Insulin resistance and impaired glucose tolerance in obese children and adolescents referred to a tertiary-care center in Israel. Int J Obes (Lond) 2005;29:571-8. CrossRef

22. Kluczynik CE, Mariz LS, Souza LC, Solano GB, Albuquerque FC, Medeiros CC. Acanthosis nigricans and insulin resistance in overweight children and adolescents. An Bras Dermatol 2012;87:531-7. CrossRef

23. Stuart CA, Pate CJ, Peters EJ. Prevalence of acanthosis nigricans in an unselected population. Am J Med 1989;87:269-72. CrossRef

24. Singh B, Saxena A. Surrogate markers of insulin resistance: a review. World J Diabetes 2010;1:36-47. CrossRef

25. Keskin M, Kurtoglu S, Kendirci M, Atabek ME, Yazici C. Homeostasis model assessment is more reliable than the fasting glucose/insulin ratio and quantitative insulin sensitivity check index for assessing insulin resistance among obese children and adolescents. Pediatrics 2005;115:e500-3. CrossRef

26. Studies to Treat or Prevent Pediatric Type 2 Diabetes Prevention Study Group. Prevalence of the metabolic syndrome among a racially/ethnically diverse group of U.S. eighth-grade adolescents and associations with fasting insulin and homeostasis model assessment of insulin resistance levels. Diabetes Care 2008;31:2020-5. CrossRef

27. Goran MI, Ball GD, Cruz ML. Obesity and risk of type 2 diabetes and cardiovascular disease in children and adolescents. J Clin Endocrinol Metab 2003;88:1417-27. CrossRef

28. Sorof JM, Lai D, Turner J, Poffenbarger T, Portman RJ. Overweight, ethnicity, and the prevalence of hypertension in school-aged children. Pediatrics 2004;113:475-82. CrossRef

29. Jessup A, Harrell JS. The metabolic syndrome: look for it in children and adolescents, too! Clin Diabetes 2005;23:26-32. CrossRef

30. El-Atat FA, Stas SN, McFarlane SI, Sowers JR. The relationship between hyperinsulinemia, hypertension and progressive renal disease. J Am Soc Nephrol 2004;15:2816-27. CrossRef

31. Reinehr T, de Sousa G, Toschke AM, Andler W. Comparison of metabolic syndrome prevalence using eight different definitions: a critical approach. Arch Dis Child 2007;92:1067-72. CrossRef

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Click here to watch a video of double free-flap reconstruction

The use of microvascular free flaps for the reconstruction of defects following the resection of head and neck cancer is a complex but routine procedure. However, single flaps may not be sufficient for some defects that are either too large or warrant composite tissues. In particular, resection of advanced tumours of the oral cavity results in complex oromandibular defects that often involve bone, oral lining, external skin, and soft tissue. The free fibular osteocutaneous (FO) flap is well established as a workhorse flap for mandible reconstruction,1 which provides 25 to 30 cm of straight bone of good quality that can be contoured, as well as a skin paddle for soft tissue coverage when needed. The pedicle has an acceptable length and its vessels have a good diameter. It is therefore our preferred option for restoring mandibular defects and for lining the oral cavity.

However, the size of the skin paddle is limited1 and may not be supplied by the same vessel as the bone.2 Thus, with larger composite defects, a single fibula flap cannot provide sufficient soft tissue coverage and a second skin flap may be necessary. Some surgeons nevertheless elect to avoid a second free flap by choosing either a pedicled flap or alloplastic material. We therefore set out to demonstrate the feasibility of resorting to double free flap surgery in head and neck reconstruction.

Our choice for additional soft tissue is the anterolateral thigh (ALT) flap that provides up to 630 cm² of skin.3 On occasions when the vascularity of the fibula flap skin paddle is deemed borderline, the ALT can be harvested with multiple skin islands so as to cover both the inner lining and the external skin. Harvest of the FO and ALT flaps can proceed at the same time as tumour excision, without the need for patient re-positioning, which is an important logistical advantage. Like most surgeons, whenever possible we prefer using separate anastomoses for double flaps rather than sequential linking or ‘flow through’,4 5 6 as some studies5 6 suggest that the latter has more complications (possibly due to increased thrombogenicity or a ‘steal’ phenomena).

We conducted a retrospective case review of patients in our institution with head and neck cancer who had reconstruction with planned simultaneous double free flaps over a 2.5-year period (from November 2010 to August 2013). For all cases we deployed two surgical teams; reconstructions were performed (one surgeon) at the same time as tumour excision (other surgeons). Preoperatively, handheld Doppler probes were used to locate the skin perforators for both flaps. The peroneal artery was sacrificed in the harvest of fibula flaps and adequacy of the remaining vessels was screened by palpation of the dorsalis pedis and posterior tibial pulses. An angiogram was used in only one patient with a history of peripheral vascular disease.

The FO flap was harvested first using a lateral approach; a sterile tourniquet was placed on the upper thigh but not inflated. A skin island was harvested in nine out of 10 fibula flaps. In one patient, the skin island was not perfused by the peroneal artery and thus not harvested. In another, the vascularity of the skin island was deemed suboptimal and therefore not used. The fibula flap was kept in situ after isolation of its vascular pedicle while the ALT was harvested. Intramuscular perforators to the thigh skin island were skeletonised in all cases so as to completely visualise the vessels. Once the surgical margins were deemed clear by frozen sections, the final dimensions of the ALT flaps were determined when the final defect was defined.

Whenever possible, intermaxillary fixation was used to hold the mandible and maxilla in an optimal position, and ‘by eye’ the fibula was osteotomised to fit (average 1-2 osteotomies). Two sets of mini-plates were used per osteotomy site so as to maximise rotational stability. The use of 2.5 x or 3.5 x loupes by the reconstructive surgeon allowed micro-anastomoses of the vessels, whilst insetting of the flap was completed.

A 58-year-old man was referred to our centre with a second recurrence of a squamous cell carcinoma of his tongue. Three years earlier, he had had a partial right glossectomy with a selective neck dissection for a pT2N0 lesion. One year later he underwent a complete neck dissection for a right nodal recurrence, and another year later he had had a reconstruction with a pectoralis major myocutaneous flap (PMMF) after total glossectomy for local tumour recurrence. After the tumour was resected, he had a bony defect from one angle of the mandible to the other, and a soft tissue defect that involved the entire inferior oral cavity down to the chin and anterior neck skin, which left a 3-cm rim of lower lip (Fig 1).

We used a fibula flap with its overlying skin island along with a large ALT flap (Fig 2). After anastomosis of the two sets of vessels, bleeding from the edge of the fibula flap skin island appeared rather sluggish. So the ALT was used for both intraoral lining and external skin cover. A strip of the ALT flap was de-epithelialised for suturing to the lower lip remnant (Fig 3). There were no major complications and the patient was discharged on the 14th postoperative day. There was a good contour at follow-up (Fig 4); the patient used a percutaneous endoscopic gastrostomy (PEG) for feeding preoperatively but regrettably could not resume oral feeding after this surgery and therefore remained reliant on the PEG.

All tumours were stage T4a, with nodal status ranging from N0-N3 (Table). During the study period, there were six male and six female patients who had double free flap surgery. Their ages ranged from 31 to 88 (mean, 55) years. In 10 of them, a free fibula flap was combined with an ALT flap harvested from the same limb; in eight of them a skin island was harvested with the bone. One patient had bilateral ALT flaps for reconstruction of an extensive tumour of the tongue and floor of the mouth without bone involvement. Another patient had a free fibula flap combined with an anteromedial thigh flap, due to absence of suitable perforators upon dissecting the ALT flap.

The mean total operating time was 660 minutes, which included the time for frozen section results. Postoperative hospital stays ranged from 11 to 82 days; nine patients were discharged home within 3 weeks. Patient 10 stayed 80 days. She declined further surgery for an intraoral dehiscence, which was therefore treated conservatively. Patient 7 stayed 82 days, as his recovery was complicated by a carotid blowout on the 11th postoperative day for which he had a surgery; subsequently a pseudomonas wound infection was treated with antibiotics. After surgery, seven patients were able to resume oral feeding sufficient to maintain their body weight; the remainder relied on tube feeding. Five patients received adjuvant treatment (4 had chemoradiation and 1 only had radiotherapy).

Minor postoperative complications (fluid collections, fistulae) occurred in 67% of these patients and usually resolved with conservative management. More serious complications occurred in 33% of the patients (carotid blowout, wound dehiscence/infection, and fluid collections treated surgically). In one patient, a haematoma was treated by debridement of the soft tissue portion of the free fibula flap that had been de-epithelialised and ‘buried’. There were no instances of total flap loss; two patients were taken back to theatre for exploration and their flaps were salvaged. One of them (patient 10) had venous congestion of the fibula skin flap (used for intraoral lining), which was salvaged but remained swollen and indurated. In view of a concomitant intraoral wound dehiscence, the swollen skin island was debrided and a pedicled ipsilateral pectoralis major flap was harvested to close the intraoral wound. Regrettably, although the pedicled flap survived, the intraoral wound dehisced again, and the patient declined to have further surgery so her wound was managed with daily dressings (see above).

Two (17%) out of the 12 patients had tumour recurrence during the follow-up period, and a further two (17%) had distant metastases. Survival from the time of surgery ranged from 60 to 303 days. The patient survival rate at 6 months was 91%, and at 1 year was 64%. At the time of writing this paper, only seven of the 12 patients had been followed up for at least 2 years, three (43%) of whom were still alive.

Following resection of advanced oral cancers, it is our standard practice to use double free flaps when needed for reconstruction of complex oromandibular defects, particularly those involving large defects of both bone and soft tissue. In most cases, the indication for double free flaps was the requirement for bone and soft tissue/skin not provided by the skin island of a FO flap. This practice is by no means universal; some surgeons are reluctant to contemplate a second free flap due to the perceived increase in technical complexity, operating time, and risk of complications. Alternative strategies include substitution of the fibular flap with a metal reconstruction plate, combined with a soft tissue flap for resurfacing7; combining a fibular free flap with pedicled regional flaps, such as the deltopectoral flap, PMMF,8 or latissimus dorsi myocutaneous flap. Some centres regard such cases as ‘inoperable’ and offer palliative treatment only.

However, these simpler alternatives have their drawbacks. The problems associated with an alloplastic plate with a soft tissue flap for composite mandible reconstruction are well documented,9 10 11 there being high rates of delayed plate exposure and recourse to salvage procedures.12 In the long term, use of vascularised bone (particularly in the FO flap) is more successful for mandible reconstruction,2 and was our first choice in all cases, with the possible exception of patients with a short life expectancy (<6 months). Recourse to a regional pedicled soft tissue flap instead of a free flap is based on its perceived advantage in being technically easier to harvest and involving shorter operating times.9 13 There is also a perceived lower risk of complications through avoiding a second set of microanastomoses. The PMMF is the most commonly used regional flap,14 but the vascularity of its skin paddle (like that of other regional flaps used in head and neck reconstruction) tends to be suboptimal; if the muscle is too short, more of the skin paddle results in a ‘random-pattern’. Crucially, the skin islands tend to be positioned at the most distal portions and thus have the poorest vascularity in the most critical parts.15 Chen et al16 recommends avoiding PMMFs to line the oral cavity due to a high rate of bone exposure from dehiscence.

On the contrary, surgeons such as Bianchi et al17 have actually demonstrated better outcomes with double free flaps compared to a combination of one free flap with one pedicled flap. The bulk of the muscle pedicle in regional flaps can interfere with the inset and vascularity of a concomitant free flap,13 and the tendency for muscle atrophy and gravitational effects can adversely affect the final results of reconstruction. Chen et al16 demonstrated a lower failure rate with two free flaps (2.8%) compared with the combination of one free and one pedicled flap (9%). They speculated that the bulky PMMF pedicle may actually compress the free flap pedicle, citing the 14% to 33% frequency of internal jugular vein thrombosis after radical neck dissection covered with pedicled flaps.18 19 The skin island of a regional flap also tends to be thicker, less pliable, and thus may interfere with intraoral function. Regional flaps may be limited in other ways (eg lack of necessary tissue components or specific tissue volume), which compromise the final aesthetic and functional outcomes.20

Although on average, a single free flap can take 1.5 hours longer than a PMMF to harvest, Tsue et al21 found that the operating time for double flaps can be 3 hours shorter than for a one free and one pedicled combination. They explained this by citing possible bias by surgeons choosing to use a second pedicled flap, when the resection time was longer, and surgeons working faster whenever two free flaps were anticipated. Guillemaud et al22 found no significant difference in the duration of surgery and complication rate when comparing double free and one free and one pedicled surgeries. In the end, the duration of surgery should not be a factor in determining the type of reconstruction.23

Proposed indications for the use of double free flaps are listed in the Box.20 The reconstruction of defects resulting from tumour resection in the head and neck region is a challenge, particularly when a composite of tissues is required or the defect is too large to cover by a single flap. Recourse to two free flaps allows more versatility and flexibility when reconstructing such complex defects. The best osseous and soft tissue elements may be independently selected, yielding appropriate tissue characteristics for ideal defect reconstruction. Using two separate thin pliable free flaps rather than bulky pedicled flaps may allow easier insetting and better restoration of the 3-dimensional anatomical boundaries,24 and thus both the functional and aesthetic outcomes can be addressed. With free flaps, there is also the potential for including other components such as nerves for sensate flaps.24

Good-quality soft tissue coverage is needed to reduce the risk of plate exposure12; even when the skin component of the FO flap can provide adequate surface cover, there is usually an overall shortage of soft tissue. Soft tissue reconstruction is as important as bone reconstruction25 in determining a satisfactory outcome, as deficiency of the latter tissues is poorly tolerated in the head and neck,26 and may lead to inadequate obliteration of dead spaces (eg from resection of masticators, buccal fat pad, and parotid). This causes accumulation of fluid which may become secondarily infected,16 and threaten micro-anastomoses and lead to contractures, and poor cosmetic outcomes or functionality that can lead to trismus, as well as contraction of the floor of the mouth with tethering of the tongue with difficulties in swallowing and speech.27 Therefore, even in the absence of bone loss, a double free flap reconstruction can be advantageous especially if soft tissue loss is substantial or beyond the reach of pedicled alternatives.

The use of two simultaneous free flaps undoubtedly poses technical difficulties, by increasing potential patient morbidity and is time-consuming. Although it is not our intention to promote double free flap reconstruction as a ‘routine’ reconstruction procedure, we wish to highlight it as an option, at least for tumours that are often deemed ‘inoperable’. Balasubramanian et al28 demonstrated that advanced ‘inoperable’ tumours such as T4b (in 7 of 21 cases) can be safely operated on; having double free flap reconstruction in the armamentarium allows surgeons to be more aggressive with extirpation. With careful patient selection, the duration of surgery, hospital stays, and complications need not be prohibitive compared to single free flap operations.25 Wei et al20 suggest that double free flaps should be restricted to patients with primary cancers, avoiding their use in those with recurrent cancers or second primaries. Nevertheless, in our series three patients presented with recurrent cancer. Individual patients should be assessed on a case-by-case basis—a PMMF could be considered to cover the skin of the neck, whilst reconstruction plates may be used to reconstruct short posterior or lateral mandible defects, particularly in those with a short life expectancy.

Our study shows that double free flap reconstruction can be worthwhile in patients with T4 tumours with a flap survival rate of 100% and a patient survival rate of 64% at the time of going to press. Just over half of our patients were able to resume oral feeding, which is somewhat lower than that in some other studies,28 29 and may be related to the locally advanced extent of their tumours, particularly with regard to tongue involvement.

1. Hidalgo DA, Rekow A. A review of 60 consecutive fibula free flap mandible reconstructions. Plast Reconstr Surg 1995;96:585-96. CrossRef

2. Tan BK, Wong CH. An anomalous septocutaneous perforator to the skin paddle of the fibula osteocutaneous flap originating from the posterior tibial artery. J Plast Reconstr Aesthet Surg 2009;62:690-2. CrossRef

3. Chiu T, Wong EW, Burd A, Vlantis A. Perforator transfer in the antero-lateral thigh flap. J Plast Reconstr Aesthet Surg 2013;66:1012-3. CrossRef

4. Lin PY, Kuo YR, Chien CY, Jeng SF. Reconstruction of head and neck cancer with double flaps: comparison of single and double recipient vessels. J Reconstr Microsurg 2009;25:191-5. CrossRef

5. Wei FC, Demirkan F, Chen HC, Chen IH. Double free flaps in reconstruction of extensive composite mandibular defects in head and neck cancer. Plast Reconstr Surg 1999;103:39-47. CrossRef

6. Wei FC, Celik N, Chen HC, Cheng MH, Huang WC. Combined anterolateral thigh flap and vascularized fibula osteoseptocutaneous flap in reconstruction of extensive composite mandibular defects. Plast Reconstr Surg 2002;109:45-52. CrossRef

7. Boyd JB, Mulholland RS, Davidson J, et al. The free flap and plate in oromandibular reconstruction: long-term review and indications. Plast Reconstr Surg 1995;95:1018-28. CrossRef

8. Ariyan S. The pectoralis major myocutaneous flap. A versatile flap for reconstruction in the head and neck. Plast Reconstr Surg 1979;63:73-81. CrossRef

9. Blackwell KE, Buchbinder D, Urken ML. Lateral mandibular reconstruction using soft-tissue free flap and plates. Arch Otolaryngol Head Neck Surg 1996;122:672-8. CrossRef

10. Cohen M, Schultz RC. Mandibular reconstruction. Clin Plast Surg 1985;12:411-22.

11. Shpitzer T, Gullane PJ, Neligan PC, et al. The free vascularized flap and the flap plate option: comparative results of reconstruction of lateral mandibular defects. Laryngoscope 2000;110:2056-60. CrossRef

12. Wei FC, Celik N, Yang WG, Chen IH, Chang YM, Chen HC. Complications after reconstruction plate and soft-tissue free flap in composite mandibular defects and secondary salvage reconstruction with osteocutaneous flap. Plast Reconstr Surg 2003;112:37-42. CrossRef

13. Blackwell KE, Buchbinder D, Biller HF, Urken ML. Reconstruction of massive defects in the head and neck: the role of simultaneous distant and regional flaps. Head Neck 1997;19:620-8. CrossRef

14. Lerrick AJ, Zak MJ. Oral cavity reconstruction with simultaneous free and pedicled composite flaps. Operat Tech Otolaryngol Head Neck Surg 2000;11:76-89. CrossRef

15. Shah JP, Haribhakti V, Loree TR, Sutaria P. Complications of the pectoralis major myocutaneous flap in head and neck reconstruction. Am J Surg 1990;160:352-5. CrossRef

16. Chen HC, Demirkan F, Wei FC, Cheng SL, Cheng MH, Chen IH. Free fibula osteoseptocutaneous-pedicled pectoralis major myocutaneous flap combination in reconstruction of extensive composite mandibular defects. Plast Reconstr Surg 1999;103:835-45. CrossRef

17. Bianchi B, Ferri A, Ferrari S, et al. Reconstruction of lateral through and through oro-mandibular defects following oncological resections. Microsurgery 2010;30:517-25. CrossRef

18. Fisher CB, Mattox DE, Zinreich JS. Patency of the internal jugular vein after functional neck dissection. Laryngoscope 1988;98:923-7. CrossRef

19. Brown DH, Mulholland S, Yoo JH, et al. Internal jugular vein thrombosis following modified neck dissection: implications for head and neck flap reconstruction. Head Neck 1998;20:169-74. CrossRef

20. Wei FC, Yazar S, Lin CH, Cheng MH, Tsao CK, Chiang YC. Double free flaps in head and neck reconstruction. Clin Plastic Surg 2005;32:303-8. CrossRef

21. Tsue TT, Desyatnikova SS, Deleyiannis FW, et al. Comparison of cost and function in reconstruction of the posterior oral cavity and oropharynx. Free vs pedicled soft tissue transfer. Arch Otolaryngol Head Neck Surg 1997;123:731-7. CrossRef

22. Guillemaud JP, Seikaly H, Cote DW, et al. Double free-flap reconstruction: indications, challenges, and prospective functional outcomes. Arch Otolaryngol Head Neck Surg 2009;135:406-10. CrossRef

23. Schusterman MA, Horndeski G. Analysis of the morbidity associated with immediate microvascular reconstruction in head and neck cancer patients. Head Neck 1991;13:51-5. CrossRef

24. Urken ML, Weinberg H, Vickery C, et al. The combined sensate radial forearm and iliac crest free flaps for reconstruction of significant glossectomy-mandibulectomy defects. Laryngoscope 1992;102:543-8. CrossRef

25. Urken ML, Weinberg H, Vickery C, Buchbinder D, Lawson W, Biller HF. Oromandibular reconstruction using microvascular composite free flaps. Reports of 71 cases and a new classification scheme for bony, soft-tissue, and neurologic defects. Arch Otolaryngol Head Neck Surg 1991;117:733-44. CrossRef

26. Andrades P, Bohannon IA, Baranano CF, Wax MK, Rosenthal E. Indications and outcomes of double free flaps in head and neck reconstruction. Microsurgery 2009;29:171-7. CrossRef

27. Urken ML, Buchbinder D, Weinberg H, et al. Functional evaluation following microvascular oromandibular reconstruction of the oral cancer patient: a comparative study of reconstructed and non-reconstructed patients. Laryngoscope 1991;101:935-50. CrossRef

28. Balasubramanian D, Thankappan K, Kuriakose MA, et al. Reconstructive indications of simultaneous double free flaps in the head and neck: a case series and literature review. Microsurgery 2012;32:423-30. CrossRef

29. Hanasono MM, Weinstock YE, Yu P. Reconstruction of extensive head and neck defects with multiple simultaneous free flaps. Plast Reconstr Surg 2008;122:1739-46. CrossRef

Bladder cancer is a common genitourinary malignancy. It is the fifth most frequent cancer in the US, where it accounts for 7% of all incident malignancies.1 In 2009, there were 372 newly diagnosed bladder cancer cases in Hong Kong.2 Patients with bladder cancer warrant close surveillance because of high recurrence and progression rates (50-70%).3 Due to its prolonged natural history, intensive follow-up and treatment strategies, management of this cancer is costly and is the most expensive malignancy to treat on a per-patient basis.4 5

Guidelines for bladder cancer management have been established in an attempt to improve treatment outcomes. The most commonly used are the American Urological Association (AUA), European Association of Urology (EAU), and National Comprehensive Cancer Network (NCCN) guidelines. There is no specific guideline in Hong Kong. The practice in bladder cancer treatment in Hong Kong may differ among urologists and centres. The aim of this survey was to gain better understanding of current bladder cancer management practice in Hong Kong.

An online multiple-choice questionnaire was sent to all government hospitals and major private institutions providing urological services. Senior urologists from corresponding hospitals were invited to respond to the questionnaire, which was anonymous, self-administrated, and non-validated. From each centre at least one urologist was encouraged to respond. If the hospital or centre had three or more board-certified urologists, no more than two were encouraged to complete the survey, so as to be as representative as possible. The responses from the surveyed urologists were submitted and collected over a secured connection.

The questionnaire comprised 30 questions divided into three sections: (1) General Issues and Smoking Cessation, (2) Management and Treatment, and (3) Bladder Cancer Research. The first part concerned the daily workload for bladder cancer and smoking cessation programmes. The second part (the main part of the survey) evaluated management preferences for non-muscle invasive bladder cancers (NMIBCs) and muscle invasive bladder cancers (MIBCs), and included questions regarding intravesical and systemic chemotherapy. The final part addressed the adequacy of resources and progress for bladder cancer research.

Data were presented as descriptive statistics of the main variables and analysed using Excel (Version 14.2, California, US). A frequency table was constructed to indicate the management preferences.

Between March and August 2012, 19 hospitals and institutions from both government (n=11) and private (n=8) sectors were involved in this study. Twenty-nine senior urologists from corresponding hospitals were invited to participate in the survey. Responses from 11 (100%) government hospitals and six (75%) private sector institutions were received. Of the 29 invited urologists, 18 were from public hospitals and 11 from private institutions; eventually, 25 (86%) responded to the survey and completed the questionnaires (18 [100%] from public hospitals and 7 [64%] from the private sector).

Among the surveyed urologists, 17 (68%) estimated that 10% to 25% of their clinical workload was spent on diagnosis, treatment, and surveillance of bladder cancer. Whilst cigarette smoking is a key risk factor for bladder cancer, 14 (56%) commented that there was no access to a smoking cessation programme in their hospitals. Notably, 22 (88%) seldom or never referred their patients to any smoking cessation programme. Only 11 (44%) and 10 (40%) of the respondents thought that resources for smoking cessation were readily or easily available to patients and urologists, respectively.

Guidelines from AUA and EAU remain the most useful guides for bladder cancer management. None of the surveyed urologists used the guideline published by the Chinese Urological Association. However, 12 (48%) of the respondents had a bladder cancer management guideline in their own hospital and 15 (60%) expressed the need for a local Hong Kong guideline.

Among the surveyed hospitals, immediate intravesical chemotherapy was always (56%) or often (44%) administered. All hospitals (100%) used mitomycin C as the chemotherapeutic drug of choice. Currently, international guidelines also advocate a second transurethral resection of the bladder tumour (TURBT) for patients with high-risk NMIBC or in the absence of detrusor muscle in bladder tissue specimens. While all the respondents from government hospitals adopted this concept, five (28%) of them “always”, and 13 (72%) of them “often” performed a second TURBT. On the contrary, four (57%) of the urologists in private institutions seldom practised a second procedure. Overall, the common problems of a second TURBT encountered by urologists included a tight operation schedule (48%) and refusal by patients (16%).

All the surveyed hospitals always (44%) or often (56%) prescribed intravesical bacillus Calmette-Guérin (BCG) for high-risk NMIBC patients. However, there was a great variation in the duration of intravesical immunotherapy regimens in the 17 hospitals with responding urologists. The Table shows that the durations ranged from induction with no maintenance (24%), to maintenance for 3 months (6%), 1 year (35%), 1.5 years (6%), 2 years (6%), and 3 years (24%). Of the 25 surveyed urologists, 76% (n=19) encountered problems in intravesical immunotherapy, which were related to the poor patient compliance stemming from side-effects (60%) and serious BCG-related complications (16%).

Open radical cystectomy remains the most common approach in Hong Kong. Of the 17 surveyed hospitals whose urologists responded, only three (18%) government hospitals routinely practised radical cystectomy with a minimally invasive approach. Most of the surveyed urologists thought that systemic chemotherapy was useful in selected MIBC patients in neo-adjuvant (56%) and adjuvant (76%) settings. However, all but one hospital reported that less than 10% of their patients received either neo-adjuvant or adjuvant chemotherapy. The low frequency of systemic perioperative chemotherapy could be due to patient refusal or poor tolerance of systemic chemotherapy. Oncologists’ refusal to provide chemotherapy in neo-adjuvant (28%) and adjuvant (36%) settings could also be the reason (Fig).

Among the respondents, 13 (52%) thought that current management regimens were adequate for diagnosing and preventing bladder cancer recurrence/progression, whilst 12 (48%) felt that progress on bladder cancer treatment research was poor compared to that for renal cell and prostate cancer. Most of the respondents (80%) stated that resources for bladder cancer research were inadequate, and most (96%) also expressed a need for an inter-hospital bladder cancer database to improve patient care.

Bladder cancer is among the commonest urological malignancies. Patients with bladder cancer demand close surveillance for recurrence and progression.

Thus, one fourth of the workload of urologists is spent on the diagnosis, treatment, and surveillance of bladder cancer patients. Because of the complicated treatment and follow-up strategies, it is also the most costly to treat,4 5 and there is a wide variation in the practice patterns and compliance to guidelines.6 In Hong Kong, bladder cancer incidence is on a decreasing trend in both sexes, but the crude mortality rate has not changed in the last decade.2 There are no data available regarding the preferred management patterns of Hong Kong urologists on bladder cancer. Herein, we report on the first cross-sectional survey of clinical practice for a specific urological disease category in Hong Kong. Such information can be important for urologists, health policy-makers, and patients.

Smoking is the most important preventable cause of death in Hong Kong and many countries. Diseases caused by smoking impose a heavy economic and medical burden on our society. Many countries therefore have enhanced efforts to promote smoking cessation in addition to strengthening tobacco control measures and legislation. Cigarette smoking is a well-established risk factor for bladder cancer, and accounts for up to 50% of all incident bladder cancers.7 The risk of bladder cancer in smokers is 2 to 5 times higher than that in non-smokers. Smoking cessation decreases the bladder cancer risk as well as the recurrence rate of such tumours.8 Continuing to smoke is associated with worse cancer-related outcomes than in those who quit. In this context, urologists play a vital role in influencing patient knowledge about smoking risks and encouraging cessation of the habit. Guzzo et al9 reported that 76% of bladder cancer patients in tertiary referral centres received no specific intervention to aid smoking cessation. A number of trials confirmed that interventions from trained health care professionals increase success rates in smoking cessation attempts.10 At present, there are a number of local smoking cessation clinics run by the Department of Health (Tung Wah Group of Hospitals, the Pok Oi Hospital, the Hospital Authority, and other organisations). These programmes cover a comprehensive range of activities that include smoking cessation services, education for the public, and research. In our study, 88% of the respondents seldom or never referred their patients to any smoking cessation programme, and nearly 60% claimed that smoking cessation facilities were difficult for patients and doctors to access. This is a disappointing statistic that needs to be addressed.

International guidelines set forth by the AUA, EAU, and NCCN are widely adopted by Hong Kong urologists. There is good consensus on the practice of second TURBT and perioperative intravesical chemotherapy between different guidelines for NMIBC patients.11 Evidence supports the use of single-dose, immediate postoperative intravesical instillation of mitomycin C to decrease tumour recurrence. Second TURBT within 6 weeks of initial resection enables better tissue sampling and reduces early tumour recurrence. A US study of 14 677 bladder cancer patients between 1997 and 2004 found that only 49 (0.33%) received immediate intravesical chemotherapy after TURBT.12 Cookson et al13 reported that 66% of the US-based urologists never used postoperative intravesical chemotherapy. Gontero et al14 evaluated the adherence to EAU guidelines in eight Italian referral centres and found that only 49% of high-risk patients underwent a repeat TURBT. A study based on SEER-Medicare data reported that only 7.7% of patients with high-grade NMIBC underwent a second TURBT.15 Hong Kong urologists appear to have excellent compliance with both intravesical chemotherapy and performance of a second TURBT in the management of NMIBC patients. Urologists in the private sector seem to achieve a lower rate of second TURBT, which may be due to patient preference, expectations, and financial concerns.

Intravesical instillation of BCG is a standard therapy after TURBT for intermediate or high-risk NMIBC, as there is evidence that bladder tumour recurrence or progression is prevented by such therapy.3 For optimal efficacy, an induction course followed by maintenance therapy is recommended, but the duration of maintenance therapy remains controversial. Böhle et al16 suggested that at least 1 year of maintenance BCG was required to prevent recurrence or progression. However, a meta-analysis of 20 trials was unable to determine which BCG maintenance schedule was the most effective.17 Recently, the benefit of maintenance BCG has been challenged.18 This practice is further complicated by significant toxicity and a high treatment cessation rate. Given the uncertainty surrounding the optimal intravesical immunotherapy, urologists in Hong Kong vary in how they deliver such treatment. Having a consensus on optimal intravesical BCG therapy is challenging but necessary, before further research involving randomised clinical trials is undertaken.

Minimally invasive (laparoscopic/robotic) surgical approaches have been widely used by local urologists, including for nephrectomy and prostatectomy. These help reduce morbidity, shorten hospital stays, and enhance recovery. Open radical cystectomy remains the standard treatment for MIBC patients. Laparoscopic or robot-assisted radical cystectomy is among the most challenging procedures and performed in a limited number of centres where the necessary experience and expertise exists.19 The situation in Hong Kong is similar, while open radical cystectomy is the most preferred approach.

The pattern of treatment for MIBC has changed to a multidisciplinary approach. There is growing evidence that perioperative chemotherapy provides survival benefits in such patients. Meta-analysis suggests that neo-adjuvant and probably adjuvant systemic chemotherapy too increase cancer-specific and overall survivals.20 21 Porter et al22 reported that only 2.6% of stage 2 and 12.7% of stage 4 patients with bladder cancer received either neo-adjuvant or adjuvant chemotherapy. The underutilisation of perioperative systemic therapy was also observed in our survey. Non-tumour–related factors (including patient age, co-morbidity, and oncologists’ preferences) influence treatment patterns. Such practice is not consistent with current evidence and recommendations, all of which may affect outcomes of bladder cancer patients.

While substantial progress has ensued in the field of other genitourinary malignancies, bladder cancer research lags behind. Under-enrolment, lack of specific funding for bladder cancer, and lack of cooperative group trials are some of the problems that research needs to overcome. An inter-hospital cancer database could provide important information to clinicians and health care administrators so as to formulate health care plans. Relevant outcome data could benefit both urologists and patients, when it comes to improving bladder cancer treatment.23

There are several limitations to be noted regarding this study. First, the survey was a retrospective review of practice. Second, the reported numbers and percentages were estimations without any verification, which may have introduced inaccuracy and recall bias. Third, this was a hospital-based survey instead of being individual-based, with 11 government and eight private hospitals that provide urology services. It nevertheless covered common local practice in most of the hospitals and institutions, and should be representative. Fourth, currently there are about 100 board-certified practising urologists in Hong Kong, so surveying a larger number of urologists might have yielded a broader view of practice patterns at an individual level.

This study provided important information on practice preferences in the management of bladder cancer in both public hospitals and private institutions in Hong Kong. It demonstrated great diversity in the use of intravesical immunotherapy, perioperative systemic chemotherapy, and surgical treatment of bladder cancer in different urology centres. There is a need for clear local recommendations and guidelines in these areas.

1. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin 2010;60:277-300. CrossRef

2. Hong Kong Cancer Registry, Hospital Authority. Available from: http://www3.ha.org.hk/cancereg/. Accessed 4 Nov 2012.

3. Lamm DL, Blumenstein BA, Crissman JD, et al. Maintenance bacillus Calmette-Guerin immunotherapy for recurrent TA, T1 and carcinoma in situ transitional cell carcinoma of the bladder: a randomized Southwest Oncology Group Study. J Urol 2000;163:1124-9. CrossRef

4. Botteman MF, Pashos CL, Redaelli A, Laskin B, Hauser R. The health economics of bladder cancer: a comprehensive review of the published literature. Pharmacoeconomics 2003;21:1315-30. CrossRef

5. Avritscher EB, Cooksley CD, Grossman HB, et al. Clinical model of lifetime cost of treating bladder cancer and associated complications. Urology 2006;68:549-53. CrossRef

6. Chamie K, Saigal CS, Lai J, et al. Compliance with guidelines for patients with bladder cancer. Cancer 2011;117:5392-401. CrossRef

7. Zeegers MP, Tan FE, Dorant E, van Den Brandt PA. The impact of characteristics of cigarette smoking on urinary tract cancer risk: a meta-analysis of epidemiologic studies. Cancer 2000;89:630-9. CrossRef

8. Fleshner N, Garland J, Moadel A, et al. Influence of smoking status on the disease-related outcomes of patients with tobacco-associated superficial transitional cell carcinoma of the bladder. Cancer 1999;86:2337-45. CrossRef

9. Guzzo TJ, Hockenberry MS, Mucksavage P, Bivalacqua TJ, Schoenberg MP. Smoking knowledge assessment and cessation trends in patients with bladder cancer presenting to a tertiary referral center. Urology 2012;79:166-71. CrossRef

10. Carson KV, Verbiest ME, Crone MR, et al. Training health professionals in smoking cessation. Cochrane Database Syst Rev 2012;(5):CD000214.

11. Brausi M, Witjes JA, Lamm D, et al. A review of current guidelines and best practice recommendations for the management of nonmuscle invasive bladder cancer by the International Bladder Cancer Group. J Urol 2011;186:2158-67. CrossRef

12. Madeb R, Golijanin D, Noyes K, et al. Treatment of nonmuscle invading bladder cancer: do physicians in the United States practice evidence based medicine? The use and economic implications of intravesical chemotherapy after transurethral resection of bladder tumors. Cancer 2009;115:2660-70. CrossRef

13. Cookson MS, Chang SS, Oefelein MG, Gallagher JR, Schwartz B, Heap K. National practice patterns for immediate postoperative instillation of chemotherapy in nonmuscle invasive bladder cancer. J Urol 2012;187:1571-6. CrossRef

14. Gontero P, Oderda M, Altieri V, et al. Are referral centers for non-muscle-invasive bladder cancer compliant to EAU guidelines? A report from the vesical antiblastic therapy Italian study. Urol Int 2011;86:19-24. CrossRef

15. Skolarus TA, Ye Z, Montgomery JS, et al. Use of restaging bladder tumor resection for bladder cancer among medicare beneficiaries. Urology 2011;78:1345-9. CrossRef

16. Böhle A, Jocham D, Bock PR. Intravesical bacillus Calmette-Guerin versus mitomycin C for superficial bladder cancer: a formal meta-analysis of comparative studies on recurrence and toxicity. J Urol 2003;169:90-5. CrossRef

17. Sylvester RJ, van der Meijden AP, Lamm DL. Intravesical bacillus Calmette-Guerin reduces the risk of progression in patients with superficial bladder cancer: a meta-analysis of the published results of randomized clinical trials. J Urol 2002;168:1964-70. CrossRef

18. Herr HW. Is maintenance bacillus Calmette-Guérin really necessary? Eur Urol 2008;54:971-3. CrossRef

19. Imkamp F, Herrmann TR, Rassweiler J, et al. Laparoscopy in German urology: changing acceptance among urologists. Eur Urol 2009;56:1074-81. CrossRef

20. Stadler WM, Lerner SP. Perioperative chemotherapy in locally advanced bladder cancer. Lancet 2003;361:1922-3. CrossRef

21. Advanced Bladder Cancer (ABC) Meta-analysis Collaboration. Neoadjuvant chemotherapy in invasive bladder cancer: update of a systematic review and meta-analysis of individual patient data advanced bladder cancer (ABC) meta-analysis collaboration. Eur Urol 2005;48:202-5. CrossRef

22. Porter MP, Kerrigan MC, Donato BM, Ramsey SD. Patterns of use of systemic chemotherapy for Medicare beneficiaries with urothelial bladder cancer. Urology 2011;29:252-8.

23. Chan ES, Chu SK, Lam KM, Ng CF. Radical cystectomy for the treatment of bladder cancer: What have we learnt from Surgical Outcomes Monitoring and Improvement Program reports? Surg Pract 2012;16:164-7. CrossRef

The influx of expectant mothers from Mainland China leading to overwhelming of the local obstetric and neonatal services has been a hot topic of discussion in the media in the past few years. In 2001, the Hong Kong Court of Final Appeal delivered a unanimous opinion by which Chong Fung-yuen, a Chinese baby born while his Mainland Chinese parents were in Hong Kong on two-way permits, was granted residency in Hong Kong. In addition, in 2003, the Hong Kong SAR Government introduced the Individual Visit Scheme which allowed travellers from Mainland China to visit Hong Kong and Macao on an individual basis. Since the introduction of these policies, there has been a dramatic increase in the number of ‘traveller’ mothers delivering in Hong Kong. This ‘birth tourism’—a travel to a country that practises birthright citizenship or permanent residency in order to give birth there, so that the child will be a citizen of the destination country—has significantly influenced the standard obstetric practice in Hong Kong, resulting in adverse pregnancy outcomes. We have described this phenomenon as social obstetrics.1 2 3

According to the Hospital Authority (HA) pay code, there are seven categories of non-eligible person (NEP). The categories of NE-2 (People’s Republic of China passport or two-way permit holder ‘雙非’) and NE-3 (NEP whose spouse is a Hong Kong Identity Card [HKID] holder ‘單非’) contribute to the majority of NEP deliveries in public hospitals.

In 2005, the HA launched an obstetric package to limit the number of non-local women delivering in public hospitals. The charge was HK$20 000 for 3 days and 2 nights of hospital stay including delivery. However, this policy did not discourage ‘traveller’ mothers from delivering in public hospitals.4

In February 2007, the HA launched a new obstetric package for non-local expecting mothers. This package charged almost double (HK$39 000) for the hospitalisation for 3 days and 2 nights. Those who have not booked were additionally charged.

Unfortunately, the growing number of NEP deliveries in HA hospitals outweighed the capacity of public obstetric and neonatal services. In 2010, there were about 88 000 deliveries in the territory, of which 50% were by mainland mothers (Fig 1a). The total capacity of neonatal intensive care units (NICUs; about 100 beds) in Hong Kong can only support an annual delivery rate of 75 000.5 This resulted in the formation of Hong Kong Obstetric Service Concern Group in March 2011—to urge the Hong Kong SAR Government to take action in preventing the collapse of public obstetric and neonatal services. The first remedial measure was to stop accepting new antenatal booking in HA hospitals from 8 April 2011 till the end of the year. One year later, on 26 April 2012, HA announced that there was no booking quota for non-local expecting mothers as public service was prioritised for the Hong Kong citizens to meet the surge of childbirth in the Chinese year of ‘Dragon’. The non-booked deliveries would be charged HK$90 000 for the 3-days-2-nights package. Lastly, the Government prohibited antenatal booking of non-local mothers in either public (for NE-2 and NE-3 categories) or private (for NE-2 category) sectors from 1 January 2013 onwards (Table 16 7).

However, if a pregnant woman, regardless of her identity card status, attended the accident and emergency department (AED) of a public hospital, the doctor-on-duty would assess her condition and offer admission to the obstetric unit if medically indicated. The admission rate via AED through the years varied with the implementation of obstetric package and government policy (Fig 1b). In 2005, when the first obstetric package was launched, the admission through AED for delivery was high. The second package in 2007 encouraged antenatal booking, and, thus, the AED admission rate dropped thereafter. Since April 2011, HA stopped all antenatal bookings for NEP, as a result of which the total number of NEP deliveries decreased drastically; however, the proportion of AED admissions increased.

In Kwong Wah Hospital, antenatal booking for non-local mothers had been stopped since April 2011. The NEP deliveries in our unit were mainly through AED admission or transfer from another HA or private hospital.

This retrospective study reviewed the pregnancy conditions and outcomes of a cohort of non-booked, non-local women admitted via AED of Kwong Wah Hospital over a 1-year period.

This study evaluated the demographics, peripartum events, and pregnancy outcomes of the non-local pregnant women (NE-2 and NE-3 categories) who were admitted through AED and who delivered in Kwong Wah Hospital from 1 April 2011 to 31 March 2012. This was the 1-year period after HA’s announcement (on 8 April 2011) of stopping antenatal booking for non-local women. The birth registry record of Kwong Wah Hospital was reviewed. Women who delivered in the captioned period with no HKID number were identified. Clinical records of the subjects were retrieved from the central record unit. Only women in NE-2 and NE-3 categories were recruited.

Clinical notes and electronic patient records of the subjects were reviewed. The pregnancy conditions studied included the presenting symptoms, antenatal complications, gestation at delivery, mode of delivery, intrapartum and postpartum complications, birth weight of babies, Apgar score, need for neonatal resuscitation, admission to NICU or special baby care unit, neonatal morbidities, congenital abnormalities, etc. Maternal and neonatal outcomes were further analysed according to their booking status before admission. The annual statistics of Kwong Wah Hospital 2011 were used as reference.

Skewed continuous variables and nearly normally distributed variables were presented as medians (interquartile ranges) and means (± standard deviations [SDs]), respectively. Categorical data were presented as counts and percentages. Mann-Whitney U test and independent sample t test were used for comparison of medians and means, respectively. Pearson Chi squared test or Fisher’s exact test were used for comparisons of frequencies, where appropriate. All analyses were performed with the Statistical Package for the Social Sciences (Windows version 16.0; SPSS Inc, Chicago [IL], US). A P value of less than 0.05 was regarded as statistically significant.

Ethics approval for this study was granted by the Kowloon West Cluster Clinical Research Ethics Committee.

A total of 219 maternities with delivery were identified during the study period. There were 221 live births (three pairs of twins) and one stillbirth. Two (0.9%) pregnancies had been achieved by assisted reproduction. The mean (± SD) age of women was 29.9 ± 5.6 years. Of the 219 women, 138 (63.0%) were multiparous, 28 (12.8%) of them had had one previous caesarean delivery, and one (0.5%) had had two previous Caesarean sections. Overall, 139 (63.5%) women were of NE-2 category and 53 (24.2%) were of NE-3 category; the remaining 27 (12.3%) did not provide information about their partners. A total of 138 (63.0%) women had no booking in Hong Kong; 61 (27.9%) women had antenatal booking in other HA hospitals; and 20 (9.1%) women were booked in private hospitals but were referred or chose to deliver in HA hospitals.

The reasons of admission were as follows: show or with irregular uterine contraction (n=98, 44.7%), suspected rupture of membranes (n=52, 23.7%), active phase of labour (n=40, 18.3%), and antenatal complications (n=21, 9.6%; these included 10 cases of antepartum haemorrhage, five cases of preterm prelabour rupture of membranes, three cases of concerns on fetal wellbeing, two cases of maternal pre-eclampsia, and one case of threatened preterm labour). Five women admitted for postdate pregnancy requested for delivery. Two pregnancies were delivered in an ambulance and one on arrival to AED. One pregnancy was a stillbirth diagnosed after admission.

Routine antenatal blood tests (complete blood picture, blood group and Rhesus factor, immune status for hepatitis, syphilis, rubella, and human immunodeficiency virus) were performed in 147 (67.1%) women. For the rest of the women, results of blood tests performed in another HA or private hospital were available via electronic or hard copies. Ultrasound assessment was performed for 126 (57.5%) women before delivery.

Of the 219 pregnancies, 23 (10.5%) were delivered before 37 weeks of gestation; two (0.9%) pregnancies were delivered after 42 weeks of gestation. A total of 141 (64.4%) women had spontaneous onset of labour; 32 (14.6%) needed induction of labour, and 22 (10.0%) needed augmentation of labour.

The majority of women (n=182; 83.1%) had normal vaginal deliveries. Three (1.4%) pregnancies required instrumental assistance. Caesarean section was performed in 13 (5.9%) pregnancies after labour and 21 (9.6%) without labour. The success rate of trial of vaginal delivery after one previous Caesarean section was 50%. There was no uterine scar rupture in any case. Primary postpartum haemorrhage occurred in 13 (5.9%) pregnancies. Seven (3.2%) women required blood transfusion. The mean length of postnatal hospital stay was 2.0 ± 0.4 days.

Peripartum maternal complications were divided into mild and significant. Mild complications included seven cases of gestational hypertension, two cases of mild pre-eclampsia without magnesium sulphate treatment, three cases of gestational diabetes on insulin treatment, three cases of moderate thrombocytopenia (platelet count 50-100 x 10⁹ /L), five cases of retained placenta requiring surgical exploration, five cases of postpartum haemorrhage managed by medical therapy, three cases of post-delivery urinary retention, and five cases of postpartum fever. Significant complications included six cases of severe pre-eclampsia requiring magnesium sulphate treatment, two cases of placenta abruptio, two cases of major placenta praevia type IV, one case of massive primary postpartum haemorrhage requiring surgical intervention, and two cases of severe thrombocytopenia (platelet count <50 x 10⁹ /L).

During the study period, there were 121 (54.8%) male and 100 (45.2%) female live births. The mean birth weight was 3.3 ± 0.5 kg. There were 19 (8.7%) babies with low birth weight (<2.5 kg); 13 (5.9%) were macrosomic (>4.0 kg). Two babies required neonatal resuscitation. The admission rates to the NICU and special care baby unit (SCBU) were 3.7% and 43.8%, respectively. Overall, 15 (6.8%) babies had minor congenital abnormalities. Three (1.4%) had major abnormalities, including one ventricular septal defect, one atrial septal defect, and one bilateral congenital cataract. Apart from congenital problems, 51 babies had neonatal jaundice requiring phototherapy, 22 had respiratory complications, 22 had infection episodes, five had electrolyte disturbance, three had birth trauma, three had congenital hypothyroidism, three had hypoglycaemia, one had hypothermia, one had polycythaemia, one had anaemia requiring blood transfusion, one had neonatal autoimmune thrombocytopenia requiring intravenous immunoglobulin treatment, and one had neurological complications. The composite neonatal morbidity rate was 39.8%.

The pregnancy outcomes of the study cohort were compared with the annual statistics (2011) of Kwong Wah Hospital, as shown in Table 2. Non-local mothers were of higher parity; more likely to have hypertensive disease (including pre-eclamptic toxaemia), preterm delivery (<37 weeks), babies requiring admission to SCBU, and macrosomic babies (>4.0 kg). The rate of induction of labour and caesarean section was lower in this group.

We also analysed the maternal and neonatal outcomes based on their antenatal booking before admission (ie no booking versus booking in other HA or private hospitals). We found that there was no significant difference in maternal and neonatal outcomes between the two groups. The results are shown in Table 3.

Standard obstetric practice is influenced by social behaviour such as ‘birth tourism’ resulting in adverse pregnancy outcomes; we have described this phenomenon as social obstetrics.1 2 3 Some women came because they wanted to evade the ‘one-child’ policy of Mainland China. This was reflected in our study which showed that 63% of the NEP mothers were multiparous versus 45% from the hospital annual statistics. The higher proportion of multiparity also explained the lower rate of labour induction and caesarean delivery in the study group. On the other hand, the significantly higher rates of preterm delivery, hypertensive disease, macrosomic babies, and SCBU admission suggest that the NEP mothers belonged to a high-risk group.

In this study cohort, 63.5% of women belonged to the NE-2 category. Their travelling permit only allowed a short period of stay. In principle, there could be shared care between Hong Kong and Mainland China; in reality, this form of shared care is often suboptimal because of the differences in clinical practice and culture between the two places. Some mothers could not make antenatal booking in Mainland China under the ‘one-child’ policy. Serious conditions may be detected for the first time during an emergency admission.8 This largely endangers the health of mothers and babies. We have chosen six typical cases for illustrating this issue (Table 49 10 11 12).

Over the years, two local studies have been published on the pregnancy outcomes of non-local expectant mothers delivering in public hospitals in Hong Kong.6 7 Yuk and Wong6 from Princess Margaret Hospital conducted a study between 2004 and 2006 when the HA launched the first obstetric package to the non-local women in 2005. During that period, around 35% of deliveries in Princess Margaret Hospital were attributed to non-local Chinese women. The proportion increased significantly from 27% in 2004 to 43% in 2006. Compared with local Chinese women, the NEPs were younger, of lower parity, and had fewer pre-existing medical problems. However, they had higher chances of unplanned vaginal breech deliveries, severe hypertensive disease in pregnancy, pre-eclampsia, delivering before arrival to hospital, and giving birth post-term (≥42 weeks). Neonatal complications including preterm birth, stillbirth, and neonatal death were also more frequent among the NEP women. In fact, the first obstetric package was proposed mainly to charge the NEPs for delivery service expenses; it did not cover the antenatal service. This resulted in many of them coming to the hospital only for giving birth. Many of them came at the ‘last-minute’ to reduce the length of hospital stay due to financial concerns. This created a heavy burden on the public obstetric services and increased the risk of adverse pregnancy outcomes.

The second obstetric package in 2007 encouraged the NEP mothers to receive proper antenatal checkup. Lam7 from Tuen Mun Hospital conducted a study from 2006 to 2008 investigating the impact of the package on public obstetric services and pregnancy outcomes. It was observed that the number of NEP deliveries decreased from 1868 to 1398 per year. The number of non-booked admissions through AED reduced. The rate of post-term pregnancies dropped from 3.2% to 1.8%. The reason for fewer deliveries was a shift of patients to private obstetric services after setting the quota and raising the cost. Nevertheless, this obstetric package did not improve the admission behaviour and pregnancy outcomes.

Thanks to our HA and the Hong Kong SAR Government’s policy of stopping NEP bookings altogether in HA Obstetric Units, the number of NEP deliveries during our study period (2011-2012) was significantly reduced and limited to non-booked cases admitted through AED (Fig 2). We observed that reduction in ‘quantity’ did not improve the ‘quality’ of care in this group of women. The admission pattern and pregnancy outcomes remained similar to those in previous local studies. We also observed that, although some women had prior ‘booking’ in other HA or private hospitals, their pregnancy outcomes were no better than the ‘no booking’ group (Table 3). One possible reason for this could be that their travelling permit hindered them from receiving the ‘standard’ antenatal care. It was difficult to measure the quality of the obstetric care received by the ‘booked group’ because of its heterogeneity. We have used case examples to illustrate how the common obstetric conditions could be ‘near-miss’ conditions or standard obstetric service could be compromised under this social obstetrics phenomenon. We foresee that the third obstetrics package introduced in 2012 is unlikely to make a significant improvement in pregnancy outcomes unless the NEP women attend a structured antenatal care like the local mothers do.

In our study, we compared the pregnancy outcomes of our NEP cohort admitted through A&E (n=219) with the general pregnant population from our annual statistics (n=5862). This might introduce a pre-selection bias. Our NEP cohort was also limited by its relatively small number. In the study by Yuk and Wong,6 the pregnancy outcomes of the NEP cohort (n=4657) were compared with those of the eligible-person cohort (n=8655) from 2004 to 2006. In the study by Lam,7 the pregnancy outcomes of two NEP cohorts (n=1868 in 2006/2007 vs n=1398 in 2007/2008) were compared.

Non-local expectant mothers delivering babies in Hong Kong has become a classic social obstetrics phenomenon. There is nothing wrong with these mothers who would like to have their children to be born in Hong Kong and become permanent residents of Hong Kong. Not long ago, Hong Kong mothers wanted to give birth in the US or Canada so that their children could become citizens of those countries. The problem in Hong Kong is the large volume of pregnancies which has exceeded our obstetric and neonatal capacities, thus affecting the health care of our local pregnant mothers and neonates. Although our Government now prohibits NEP bookings in both public (for NE-2 and NE-3 categories) and private (for NE-2 category) hospitals, non-local expectant mothers continue to admit themselves through AED for deliveries. Health care professionals should continue to be prepared for managing these potential near-miss clinical situations arising from this social obstetrics phenomenon. We hope this paper serves as one of the historical records in literature for this social obstetrics phenomenon in the recent obstetric history of Hong Kong.

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