the case volumes for these procedures are low and therequired follow-up is lengthy, these combined requirementsmake such studies somewhat prohibitive.

Dominic Lee, M.D.Benjamin E. Dillon, M.D.

Philippe E. Zimmern, M.D.University of Texas Southwestern Medical Center

Dallas, TX

References

1. Ragnekar NR, Ali NI, Kaul SA, Pathak HR. Role of Martius pro-cedure in the management of urinary-vaginal fistulas. J Am Coll Surg.2000;191:259-263.

2. Petrou SP, Jones J, Parra RO. Martius flap harvest site: patient self-perception. J Urol. 2002;167:2098-2099.

3. Pitel S, Lefevre JH, Parc Y, et al. Martius advancement flap for lowrectovaginal fistula: short- and long-term results. Colorectal Dis. 2011;13:e112-e115.

Re: Lu et al.: Different Cystic FibrosisTransmembrane Conductance RegulatorMutations in Chinese Men With CongenitalBilateral Absence of the Vas Deferens andOther Acquired Obstructive Azoospermia(Urology 2013;82:824-828)

DEAR SIR,

An article entitled “Different Cystic Fibrosis Trans-membrane Conductance Regulator Mutations in Chi-nese Men With Congenital Bilateral Absence of the VasDeferens and Other Acquired Obstructive Azoospermia”was recently published in this journal.1 Deoxyribonucleicacid (DNA) samples of 601 Chinese men (158 congenitalbilateral absence of the vas deferens [CBAVD], 243 otheracquired obstructive azoospermia, 200 controls) wereexamined in this study. Exons 10 and 11 of the cysticfibrosis transmembrane conductance regulator (CFTR)gene were sequenced to identify disease-associated mu-tations. In the CBAVD group, 6 heterozygous (I556V,M469V, E527N, F508del, S485C, and I558S) and 1homozygous mutation (I556V) were detected. Elevenacquired obstructive azoospermia patients carried theI556V or the M469V mutations in heterozygous form.Mutation frequency was 12.7% in the CBAVD group,and no mutations were identified in the controls. On thebasis of these results, the authors concluded “I556V is themajor common type of CFTR mutations in Chinese pa-tients with CBAVD”.1

As Lu et al have stated in their report, the prevalence ofcystic fibrosis is highly variable between differentethnicities: 1 in 3000-1 in 3500 in Europeans and WhiteAmericans; 1 in 17,000 in African Americans; and closeto 1 in 30,000 in Asian Americans. Cystic fibrosis is

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extremely rare in Africa and Asia, with the reported dis-ease frequency being as low as 1 in 350,000 in Japan.1-3

Distribution of most CFTR mutations differs betweenCBAVD populations: the F508del mutation that is themost frequent in Europe and Northern America (12%-30%) is less prevalent in other populations.4 However, themost frequent CBAVD specific mutation, CFTR intron 8-5T (IVS8-5T) has been detected in similar or evenelevated frequencies in non-Caucasian CBAVD patients:25% in Indian, 44% in Egyptian, 44% in Taiwanese, and30% in Japanese patients compared with 21% in Cauca-sians.4,5 Moreover, 2 recent articles reported a high CFTRmutation prevalence in Chinese CBAVD patients.6,7

Ni et al7 analyzed deoxyribonucleic acid (DNA) samplesof 109 Chinese CBAVD men and 104 controls anddetected a significantly increased IVS8-5T allelic fre-quency in patients compared with controls (44.5% vs13.5%). Li et al6 sequenced the coding region of theCFTRgene in 73 Chinese CBAVD patients, and found CFTRmutations in most of these patients (60.3%). The IVS8-5T allelic frequency was 34.2% in this CBAVD group,and mutations were found in multiple exons of the gene.

Lu et al have selected 2 CFTR exons to analyze inChinese CBAVD patients on the basis of 15-year-olddata from Caucasian CBAVD patients.8 It has been sinceshown that IVS8-5T CFTR mutation frequency in Chi-nese CBAVD patients is similar to other ethnicities, andmutations are localized throughout the gene. Examina-tion of exclusively exons 10 and 11 sequence results inunderreporting true mutation frequency. Furthermore,the statement of I556V being the most frequent mutationin these patients is not valid because the sequence datapresented in the article do not provide adequate evidencefor this conclusion to be drawn. Analyzing the intron8-exon 9 junction of the CFTR gene e and preferably allcoding exons e is crucial for the correct diagnosis ofCBAVD in all ethnicities, including Chinese.

Yours sincerely,

Viktoria Havasi, M.D.Gregory Fleming James Cystic Fibrosis Research Center

Division of EndocrinologyDepartment of Pediatrics

University of Alabama at BirminghamBirmingham, AL

References

1. Lu S, Yang X, Cui Y, et al. Different cystic fibrosis transmembraneconductance regulator mutations in Chinese men with congenitalbilateral absence of vas deferens and other acquired obstructiveazoospermia. Urology. 2013;82:824-828.

2. Lucarelli M, Pierandrei S, Bruno SM, et al. The genetics of CFTR:genotype-phenotype relationship, diagnostic challenge and thera-peutic implications. In: Sriramulu D, ed. Cystic fibrosis-renewed hopethrough research. Rijeka: InTech; 2012:91-122.

3. Scotet V, Dugueperoux I, Saliou P, et al. Evidence for decline in theincidence of cystic fibrosis: a 35-year observational study in Brittany,France. Orphanet J Rare Dis. 2012;7:14.

4. Bombieri C, Claustres M, De Boeck K, et al. Recommendations forthe classification of diseases as CFTR-related disorders. J Cyst Fibros.2011;10(Suppl 2):S86-102.

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5. Cuppens H, Cassiman JJ. CFTR mutations and polymorphisms inmale infertility. Int J Androl. 2004;27:251-256.

6. Li H,WenQ, Li H, et al. Mutations in the cystic fibrosis transmembraneconductance regulator (CFTR) in Chinese patients with congenitalbilateral absence of vas deferens. J Cyst Fibros. 2012;11:316-323.

7. Ni WH, Jiang L, Fei QJ, et al. The CFTR polymorphisms poly-T,TG-repeats and M470V in Chinese males with congenital bilateralabsence of the vas deferens. Asian J Androl. 2012;14:687-690.

8. Petreska L, Koceva S, Plaseska D, et al. Molecular basis of cy-stic fibrosis in the Republic of Macedonia. Clin Genet. 1998;54:203-209.

Reply by the Authors

TO THE EDITOR:

In this study, we analyzed exon 10 and exon 11 of cysticfibrosis transmembrane conductance regulator (CFTR)gene in congenital bilateral absence of the vas deferensand other acquired obstructive azoospermia, becausecommon mutations such as F508del, O1507, G551D,G542X, R560T, and R553X associated with cysticfibrosis in Caucasians were frequently identified in theseexons. Of course, it will be better if more exons or DNAregions in this gene could be chosen for analysis, but thecost will be high.

Furthermore, our results show that 31 of 401 screenedpatients were observed to haveCFTRmutations, including30 of heterozygous mutations and 1 of homozygous muta-tion, and the rate of CFTR mutations was 7.7%. Of thesemutations, nearly 77.4%mutations (24 of 31) were I556V,including 23 of heterozygous mutations and 1 of homozy-gous mutation. F508del, which was the most commonmutation in European populations, was found in only 1 of158 patients (0.6%) with congenital bilateral absence ofthe vas deferens in our study. These results show thatI556V, other than F508del,might be themajormutation inChinese patients.

Zi-Jiang Chen, M.D., Ph.D.Center for Reproductive Medicine

Provincial Hospital Affiliated to Shandong UniversityJinan, Shandong, China

Re: Li et al.: Percutaneous NephrolithotomyUnder Local Infiltration Anesthesia: ASingle-center Experience of 2000 ChineseCases (Urology 2013;82:1020-1025)

TO THE EDITOR:

We appreciate the authors1 for using local anesthesia(LA) þ sedation for percutaneous nephrolithotomy

UROLOGY 83 (3), 2014

(PCNL) in a large series. However, certain issues needclarifications and discussion.

The authors report a well-tolerated procedure in all pa-tients. One may be skeptical about this for many reasons.First, the objective criteria for failure or inadequacy of LAand aborting the procedure (if required) were not defined.These could have been either level or duration of intra-operative pain or frequency of top-up instillations of LAandsedation. Intraoperative tolerance was judged subjectively.Patients were prepared for intraoperative potential pain bypreoperative explanation. Apart from the increasing painthreshold, this may also increase chances of a biased sub-jective reporting of pain scores (reporting them lower) andtolerability (reporting it good). Second, the study reports adefinite intraoperative pain with a mean score of 3.62. Theactual pain would have beenmuch higher in some patients.Third, the study did not mention about offering any intra-operative option of alternative anesthesia (general orregional anesthesia in fit ones) or immediate alternativetreatments (shockwave lithotripsy and/or retrograde intra-renal surgery in suitable cases), if the patients felt intra-operative pain.Without such alternatives, a patientmay tryto tolerate the intraoperative discomfort up to his worstpossible time, considering even a quite unpleasant experi-ence to be the inherent part of the only available stonetreatment, especially in a busy health care setting.

In our limited personal experience (unpublished),PCNL under LA þ sedation was associated with pain anddiscomfort in many patients. Even for PCNL underepidural or spinal anesthesia, at times, we have notedintraoperative ipsilateral-referred shoulder pain, nausea,and discomfort with supracostal tracts. This is probablybecause of the irritation of diaphragm at the time ofamplatz sheath angulation and movements. We havealso noted intraoperative chest discomfort in case of pleuralviolation. In case of extravasation of fluid outside kidney,irritation of renal capsule, retroperitoneum, and nearbyperitoneum would cause pain. Control of intraoperativepain because of the irritation of diaphragm, pleura, orretroperitoneum may not be optimal by LA þ sedation.

Adequate analgesia, amnesia, and required musclerelaxation are components of anesthesia for any majorsurgical procedure. The long-term psychological impactsof unpleasant intraoperative pain experience are wellknown. In the absence of muscle relaxation, any intra-operative pain or chills (reported in some patients in thestudy) are likely to cause stiffness of back muscles andmake patients uncooperative. This may lead to the re-striction of movements of amplatz sheath.

Furthermore, intraoperative pain episodes while onlocal anesthesia may cause derangements of hemody-namic status. These may be risky in unfit patients (forgeneral and/or regional anesthesia) because they usuallyhave severe systemic or cardiac disease.

Thus, despite this large study, the key issues ofsuitability and practical utility of LA for PCNL remainunresolved especially from patient perspectives. Untilwell-designed comparative studies prove its worth, one

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