- Email: [email protected]
Proof of Concept of a New Colonoscope
2248
CORRESPONDENCE
or “whom,” but “when.” Our answer is: as soon as is practical. Will the authors heed our advice? RENATO COSTI VINCENZO VIOLI LUIGI RONCORONI LEOPOLDO SARLI Dipartimento di Scienze Chirurgiche Università di Parma Parma, Italy 1. Lau JY, Leow CK, Fung TM, Suen BY, Yu LM, Lai PB, Lam YH, Ng EK, Lau WY, Chung SS, Sung JJ. Cholecystectomy or gallbladder in situ after endoscopic sphincterotomy and bile duct stone removal in Chinese patients. Gastroenterology 2006;130:96 –103. 2. Costamagna G, Tringali A, Shah SK, Mutignani M, Zuccala G, Perri V. Long-term followup of patients after endoscopic sphincterotomy for choledocholithiasis, and risk factors for recurrence. Endoscopy 2002;34:273–279. 3. Sugiyama M, Suzuki Y, Abe N, Masaki T, Mori T, Atomi Y. Endoscopic retreatment of recurrent choledocholithiasis after sphincterotomy. Gut 2004;53:1856 –1859. 4. Lai KH, Lin LF, Lo GH, Cheng JS, Huang RL, Lin CK, Huang JS, Hsu PI, Peng NJ, Ger LP. Does cholecystectomy after endoscopic sphincterotomy prevent the recurrence of biliary complications? Gastrointest Endosc 1999;49:483– 487. 5. Pring CM, Skelding-Millar L, Goodall RJR. Expectant treatment of cholecystectomy after endoscopic retrograde cholangiopancreatography for choledocholithiasis in patients over 80 years. Surg Endosc 2005;19:357–360. 6. Sarli L, Pietra N, Franzé A, Colla G, Costi R, Gobbi S, Trivelli M. Routine intravenous cholangiography, selective ERCP, and endoscopic treatment of bile duct stones before laparoscopic cholecystectomy. Gastrointest Endosc 1999;50:200 –208. 7. Boerma D, Rauws EA, Keulemans YC, Janssen IM, Bolwerk CJ, Timmer R, Boerma EJ, Obertop H, Huibregtse K, Gouma DJ. Wait-and-see policy or laparoscopic cholecystectomy after endoscopic sphincterotomy for bile-duct stones: a randomised trial. Lancet 2002;360:761–765. 8. de Vries AD, Donkervoort SC, van Geloven AA, Pierik EG. Conversion rate of laparoscopic cholecystectomy after endoscopic retrograde cholangiography in the treatment of choledocholithiasis: does the time interval matter? Surg Endosc 2005;19:996 –1001. 9. Bingener J, Richards ML, Schwesinger WH, Strodel WE, Sirinek KR. Laparoscopic cholecystectomy for elderly patients: gold standard for golden years? Arch Surg 2003;138:531–535. 10. Majeski J. Laparoscopic cholecystectomy in geriatric patients. Am J Surg 2004;187:747–750. doi:10.1053/j.gastro.2006.04.050
Reply. We thank Costi et al for their interest and more specifically their questions arising from our randomized study. Those are (1) whether cholecystectomy after endoscopic sphincterotomy for bile duct stones impacts upon patients’ long-term survival and (2) whether early cholecystectomy reduces morbidities when compared to delayed or emergency cholecystectomy. Despite the association of gallbladder cancer and cholelithiasis, gallbladder cancer is an uncommon disease. Only 1%–2% of patients who undergo cholecystectomy are diagnosed with gallbladder cancer at the time of surgery or at histologic examination of the resected specimens. In designing our study, we determined our sample size to detect a difference in the rate of gallstone complications. A trial to detect a difference in gallbladder cancer-related survival would have entailed a much larger pool of patients with significantly longer
GASTROENTEROLOGY Vol. 130, No. 7
follow-up. More than a decade ago, we reported a low mortality figure of 4.7% in patients with severe biliary sepsis treated by endoscopic drainage.1 For the same reason, a trial to detect a difference in mortality consequent to recurrent biliary sepsis would be difficult, if not impossible. We however concur with Costi et al that a liberal policy in performing cholecystectomy should be instated in localities with a high prevalence of gallbladder cancer or in patients with radiologic features of chronic cholecystitis. Early or delayed cholecystectomy after an episode of biliary sepsis has long been a subject of contention. A pooled analysis of 10 randomized studies showed that early cholecystectomy led to shorter hospital stay.2 The 2 groups did not differ in treatment-related morbidities and mortality. These randomized studies were performed in the context of acute cholecystitis. In a patient recovering well from mild biliary sepsis, it would be logical to expedite cholecystectomy. Surgery would in fact be easier if performed early before inflammatory scarring sets in. In patients with severe sepsis, it is prudent to abort septicemia by providing initial drainage.3 Prolonged instrumentation and associated raised biliary pressure can aggravate systemic sepsis. We argue that interval cholecystectomy is in fact safer allowing such patients to recuperate. A randomized study that compares early to interval cholecystectomy following endoscopic treatment of biliary sepsis is lacking in the literature and would be of great interest. JAMES Y. LAU JOSEPH J. Y. SUNG Department of Surgery Prince of Wales Hospital The Chinese University of Hong Kong Shatin, Hong Kong 1. Leung JW, Chung SC, Sung JJ, Banez VP, Li AK. Urgent endoscopic drainage for acute suppurative cholangitis. Lancet 1989;1:1307– 1309. 2. Shikata S, Noguchi ??, Fukui T. Early versus delayed cholecystectomy for acute cholecystitis: a meta-analysis of randomized controlled trials. Surg Today 2005;35:553–560. 3. Lau JY, Chung SC, Leung JW, Ling TK, Yung MY, Li AK. Endoscopic drainage aborts endotoxaemia in acute cholangitis. Br J Surg 1996;83:181–184. doi:10.1053/j.gastro.2006.04.051
Proof of Concept of a New Colonoscope Dear Sir: I read with some interest the article “The Aer-O-Scope: Proof of Concept of a Pneumatic, Skill Independent, Self-Propelling, SelfNavigating Colonoscpe” (2006:130:672– 677). The device is clearly quite neat, and a triumph of technology. There was nary a bad word about it in the entire article. However, I have several questions for the authors. The first would be whether any of the authors have a financial stake in the company GI View LTD, either as shareholders or as paid members of the firm’s scientific board. Second, I am curious about how much the disposable component of the scope may end up costing. The third question is more fundamental. The authors state that the purpose of this technology is not to remove polyps or to biopsy and that interpretation of the results will take a trained operator. Although technical improvements may make the Aer-O-Scope more efficient than a success rate of 10/12 in young and healthy volunteers, why should we invest in a new technology like this when a similar one, virtual colonoscopy, already exists and could be made widely available on a much quicker basis. While I understand that this article
June 2006
CORRESPONDENCE
is merely a description of a new technology, more context would have helped me understand why this is anything other than a cool new gadget looking for investors.
3.
IRA DANIEL BREITE Westside Medical Associates NYU School of Medicine New York, New York doi:10.1053/j.gastro.2006.04.052
4.
1. Drs. Rex, Levin, Halpern and Arber are members of the Scientific Advisory Board of GI View. As such, they have received compensation for some of their consulting work prior to this study. None of them received compensation for their participation in this study. 2. The ultimate cost of the device is not known at this time and the economic models for its use are not fully developed. 3. Certainly CT colonography (CTC) may become a viable colorectal screening strategy modality but multiple technologies may be needed to meet screening demand and variable preferences of patients if adherence increases sharply. As a diagnosis only device, the Aer-O-Scope would fill a role similar to CTC. The rationale for developing new diagnostic technologies that would compete with CTC are numerous, including the very mixed results of CTC in clinical studies,1– 4 the current high cost and relatively low costeffectiveness of CTC,5 its potential radiation risk,6 and the lack of evidence that CTC will improve compliance.7 Twelve years after its introduction, CTC lacks a CPT1 code and high quality CTC is far from being widely available. Compared to CTC, endoscopic strategies offer better sensitivity for small polyps and better specificity for polyps of all sizes. 4. From a business perspective, a self-propelled colonoscope might provide efficiencies in the endoscopy unit that would allow gastroenterologists to meet increased demand for colorectal cancer screening without the need for involvement of other specialists. 5. Our initial study merely demonstrated the feasibility of the device’s propulsion mechanism. An understanding of the sensitivity of the device for polyp detection awaits additional study. Further studies are planned to define the sensitivity of the device for polyp detection and its clinical application.
5.
Reply
BORIS VUCELIC DOUGLAS REX ROLAND PULANIC JORJE PFEFFER IRENA HRSTIC BERNARD LEVIN ZAMIR HALPERN NADIR ARBER Tel Aviv Medical Center Cancer Prevention Center Tel Aviv, Israel 1. Pickhardt P, Choi J, Hwang I. Computed tomographic virtual colonoscopy to screen for colorectal neoplasia in asymptomatic adults. N Engl J Med 2003;349:2191–2200. 2. Cotton PB, Durkalski VL, Pineau BC, Palesch YY, Mauldin PD, Hoffman B, Vining DJ, Small WC, Affronti J, Rex D, Kopecky KK, Ackerman S, Burdick JS, Brewington C, Turner MA, Zfass A, Wright AR, Iyer RB, Lynch P, Sivak MV, Butler H. Computed tomographic colonography (virtual colonoscopy): a multicenter comparison with
6.
7.
2249
standard colonoscopy for detection of colorectal neoplasia. JAMA 2004;291:1713–1719. Rockey DC, Paulson E, Niedzwiecki D, Davis W, Bosworth HB, Sanders L, Yee J, Henderson J, Hatten P, Burdick S, Sanyal A, Rubin DT, Sterling M, Akerkar G, Bhutani MS, Binmoeller K, Garvie J, Bini EJ, McQuaid K, Foster WL, Thompson WM, Dachman A, Halvorsen R. Analysis of air contrast barium enema, computed tomographic colonography, and colonoscopy: prospective comparison. Lancet 2005;365:305–311. Johnson CD, Harmsen WS, Wilson LA, Maccarty RL, Welch TJ, Ilstrup DM, Ahlquist DA. Prospective blinded evaluation of computed tomographic colonography for screen detection of colorectal polyps. Gastroenterology 2003;125:311–319. Ladabaum U, Song K. Projected national impact of colorectal cancer screening on clinical and economic outcomes and health services demand. Gastroenterology 2005;129:1151–1162. Brenner DJ, Georgsson MA. Mass screening with CT colonography: should the radiation exposure be of concern? Gastroenterology 2005;129:328 –337. Scott RG, Edwards JT, Fritschi L, Foster NM, Mendelson RM, Forbes GM. Community-based screening by colonoscopy or computed tomographic colonography in asymptomatic average-risk subjects. Am J Gastroenterol 2004;99:1145–1151. doi:10.1053/j.gastro.2006.04.055
PPAR-␥ and Crohn’s Disease in New Zealand Dear Sir: We read with interest the article “Linkage to Peroxisome Proliferator-Activated Receptor-␥ in SAMP1/YitFc Mice and in Human Crohn’s Disease” by Sugawara et al recently published in GASTROENTEROLOGY.1 This interesting article by Sugawara et al found that the 2 minor alleles SNP1 [G12350898A (rs2067819)] and SNP2 [G12359887A (rs3892175)] of the peroxisome proliferator-activated receptor-␥ (PPAR␥) gene PPARG were more common (P ⬍ 10⫺5) in unaffected controls than in Crohn’s disease (CD) patients, indicating that PPARG is a susceptibility gene for CD in the USA. We would like the authors to estimate the odds ratio or the power of the study as no genotype data were published. Further, we ask the authors to calculate whether the genotype frequencies reported for the control group are in Hardy–Weinberg equilibrium (HWE) since a single HWE P value was given, presumably to the whole study population. This request is made as the bar graph of Figure 3B tends to suggest that the control group may significantly deviate from HWE. It is difficult to draw conclusions if the observed genotype distribution does not represent the genotype distribution in healthy (non-diseased) people.2 EUPHEMIA LEUNG* JIWON HONG* ALAN FRASER‡ TONY MERRIMAN§ GEOFFREY KRISSANSEN* Departments of *Molecular Medicine & Pathology, and ‡Medicine University of Auckland Auckland, New Zealand and §Department of Biochemistry University of Otago Dunedin, New Zealand
CORRESPONDENCE
or “whom,” but “when.” Our answer is: as soon as is practical. Will the authors heed our advice? RENATO COSTI VINCENZO VIOLI LUIGI RONCORONI LEOPOLDO SARLI Dipartimento di Scienze Chirurgiche Università di Parma Parma, Italy 1. Lau JY, Leow CK, Fung TM, Suen BY, Yu LM, Lai PB, Lam YH, Ng EK, Lau WY, Chung SS, Sung JJ. Cholecystectomy or gallbladder in situ after endoscopic sphincterotomy and bile duct stone removal in Chinese patients. Gastroenterology 2006;130:96 –103. 2. Costamagna G, Tringali A, Shah SK, Mutignani M, Zuccala G, Perri V. Long-term followup of patients after endoscopic sphincterotomy for choledocholithiasis, and risk factors for recurrence. Endoscopy 2002;34:273–279. 3. Sugiyama M, Suzuki Y, Abe N, Masaki T, Mori T, Atomi Y. Endoscopic retreatment of recurrent choledocholithiasis after sphincterotomy. Gut 2004;53:1856 –1859. 4. Lai KH, Lin LF, Lo GH, Cheng JS, Huang RL, Lin CK, Huang JS, Hsu PI, Peng NJ, Ger LP. Does cholecystectomy after endoscopic sphincterotomy prevent the recurrence of biliary complications? Gastrointest Endosc 1999;49:483– 487. 5. Pring CM, Skelding-Millar L, Goodall RJR. Expectant treatment of cholecystectomy after endoscopic retrograde cholangiopancreatography for choledocholithiasis in patients over 80 years. Surg Endosc 2005;19:357–360. 6. Sarli L, Pietra N, Franzé A, Colla G, Costi R, Gobbi S, Trivelli M. Routine intravenous cholangiography, selective ERCP, and endoscopic treatment of bile duct stones before laparoscopic cholecystectomy. Gastrointest Endosc 1999;50:200 –208. 7. Boerma D, Rauws EA, Keulemans YC, Janssen IM, Bolwerk CJ, Timmer R, Boerma EJ, Obertop H, Huibregtse K, Gouma DJ. Wait-and-see policy or laparoscopic cholecystectomy after endoscopic sphincterotomy for bile-duct stones: a randomised trial. Lancet 2002;360:761–765. 8. de Vries AD, Donkervoort SC, van Geloven AA, Pierik EG. Conversion rate of laparoscopic cholecystectomy after endoscopic retrograde cholangiography in the treatment of choledocholithiasis: does the time interval matter? Surg Endosc 2005;19:996 –1001. 9. Bingener J, Richards ML, Schwesinger WH, Strodel WE, Sirinek KR. Laparoscopic cholecystectomy for elderly patients: gold standard for golden years? Arch Surg 2003;138:531–535. 10. Majeski J. Laparoscopic cholecystectomy in geriatric patients. Am J Surg 2004;187:747–750. doi:10.1053/j.gastro.2006.04.050
Reply. We thank Costi et al for their interest and more specifically their questions arising from our randomized study. Those are (1) whether cholecystectomy after endoscopic sphincterotomy for bile duct stones impacts upon patients’ long-term survival and (2) whether early cholecystectomy reduces morbidities when compared to delayed or emergency cholecystectomy. Despite the association of gallbladder cancer and cholelithiasis, gallbladder cancer is an uncommon disease. Only 1%–2% of patients who undergo cholecystectomy are diagnosed with gallbladder cancer at the time of surgery or at histologic examination of the resected specimens. In designing our study, we determined our sample size to detect a difference in the rate of gallstone complications. A trial to detect a difference in gallbladder cancer-related survival would have entailed a much larger pool of patients with significantly longer
GASTROENTEROLOGY Vol. 130, No. 7
follow-up. More than a decade ago, we reported a low mortality figure of 4.7% in patients with severe biliary sepsis treated by endoscopic drainage.1 For the same reason, a trial to detect a difference in mortality consequent to recurrent biliary sepsis would be difficult, if not impossible. We however concur with Costi et al that a liberal policy in performing cholecystectomy should be instated in localities with a high prevalence of gallbladder cancer or in patients with radiologic features of chronic cholecystitis. Early or delayed cholecystectomy after an episode of biliary sepsis has long been a subject of contention. A pooled analysis of 10 randomized studies showed that early cholecystectomy led to shorter hospital stay.2 The 2 groups did not differ in treatment-related morbidities and mortality. These randomized studies were performed in the context of acute cholecystitis. In a patient recovering well from mild biliary sepsis, it would be logical to expedite cholecystectomy. Surgery would in fact be easier if performed early before inflammatory scarring sets in. In patients with severe sepsis, it is prudent to abort septicemia by providing initial drainage.3 Prolonged instrumentation and associated raised biliary pressure can aggravate systemic sepsis. We argue that interval cholecystectomy is in fact safer allowing such patients to recuperate. A randomized study that compares early to interval cholecystectomy following endoscopic treatment of biliary sepsis is lacking in the literature and would be of great interest. JAMES Y. LAU JOSEPH J. Y. SUNG Department of Surgery Prince of Wales Hospital The Chinese University of Hong Kong Shatin, Hong Kong 1. Leung JW, Chung SC, Sung JJ, Banez VP, Li AK. Urgent endoscopic drainage for acute suppurative cholangitis. Lancet 1989;1:1307– 1309. 2. Shikata S, Noguchi ??, Fukui T. Early versus delayed cholecystectomy for acute cholecystitis: a meta-analysis of randomized controlled trials. Surg Today 2005;35:553–560. 3. Lau JY, Chung SC, Leung JW, Ling TK, Yung MY, Li AK. Endoscopic drainage aborts endotoxaemia in acute cholangitis. Br J Surg 1996;83:181–184. doi:10.1053/j.gastro.2006.04.051
Proof of Concept of a New Colonoscope Dear Sir: I read with some interest the article “The Aer-O-Scope: Proof of Concept of a Pneumatic, Skill Independent, Self-Propelling, SelfNavigating Colonoscpe” (2006:130:672– 677). The device is clearly quite neat, and a triumph of technology. There was nary a bad word about it in the entire article. However, I have several questions for the authors. The first would be whether any of the authors have a financial stake in the company GI View LTD, either as shareholders or as paid members of the firm’s scientific board. Second, I am curious about how much the disposable component of the scope may end up costing. The third question is more fundamental. The authors state that the purpose of this technology is not to remove polyps or to biopsy and that interpretation of the results will take a trained operator. Although technical improvements may make the Aer-O-Scope more efficient than a success rate of 10/12 in young and healthy volunteers, why should we invest in a new technology like this when a similar one, virtual colonoscopy, already exists and could be made widely available on a much quicker basis. While I understand that this article
June 2006
CORRESPONDENCE
is merely a description of a new technology, more context would have helped me understand why this is anything other than a cool new gadget looking for investors.
3.
IRA DANIEL BREITE Westside Medical Associates NYU School of Medicine New York, New York doi:10.1053/j.gastro.2006.04.052
4.
1. Drs. Rex, Levin, Halpern and Arber are members of the Scientific Advisory Board of GI View. As such, they have received compensation for some of their consulting work prior to this study. None of them received compensation for their participation in this study. 2. The ultimate cost of the device is not known at this time and the economic models for its use are not fully developed. 3. Certainly CT colonography (CTC) may become a viable colorectal screening strategy modality but multiple technologies may be needed to meet screening demand and variable preferences of patients if adherence increases sharply. As a diagnosis only device, the Aer-O-Scope would fill a role similar to CTC. The rationale for developing new diagnostic technologies that would compete with CTC are numerous, including the very mixed results of CTC in clinical studies,1– 4 the current high cost and relatively low costeffectiveness of CTC,5 its potential radiation risk,6 and the lack of evidence that CTC will improve compliance.7 Twelve years after its introduction, CTC lacks a CPT1 code and high quality CTC is far from being widely available. Compared to CTC, endoscopic strategies offer better sensitivity for small polyps and better specificity for polyps of all sizes. 4. From a business perspective, a self-propelled colonoscope might provide efficiencies in the endoscopy unit that would allow gastroenterologists to meet increased demand for colorectal cancer screening without the need for involvement of other specialists. 5. Our initial study merely demonstrated the feasibility of the device’s propulsion mechanism. An understanding of the sensitivity of the device for polyp detection awaits additional study. Further studies are planned to define the sensitivity of the device for polyp detection and its clinical application.
5.
Reply
BORIS VUCELIC DOUGLAS REX ROLAND PULANIC JORJE PFEFFER IRENA HRSTIC BERNARD LEVIN ZAMIR HALPERN NADIR ARBER Tel Aviv Medical Center Cancer Prevention Center Tel Aviv, Israel 1. Pickhardt P, Choi J, Hwang I. Computed tomographic virtual colonoscopy to screen for colorectal neoplasia in asymptomatic adults. N Engl J Med 2003;349:2191–2200. 2. Cotton PB, Durkalski VL, Pineau BC, Palesch YY, Mauldin PD, Hoffman B, Vining DJ, Small WC, Affronti J, Rex D, Kopecky KK, Ackerman S, Burdick JS, Brewington C, Turner MA, Zfass A, Wright AR, Iyer RB, Lynch P, Sivak MV, Butler H. Computed tomographic colonography (virtual colonoscopy): a multicenter comparison with
6.
7.
2249
standard colonoscopy for detection of colorectal neoplasia. JAMA 2004;291:1713–1719. Rockey DC, Paulson E, Niedzwiecki D, Davis W, Bosworth HB, Sanders L, Yee J, Henderson J, Hatten P, Burdick S, Sanyal A, Rubin DT, Sterling M, Akerkar G, Bhutani MS, Binmoeller K, Garvie J, Bini EJ, McQuaid K, Foster WL, Thompson WM, Dachman A, Halvorsen R. Analysis of air contrast barium enema, computed tomographic colonography, and colonoscopy: prospective comparison. Lancet 2005;365:305–311. Johnson CD, Harmsen WS, Wilson LA, Maccarty RL, Welch TJ, Ilstrup DM, Ahlquist DA. Prospective blinded evaluation of computed tomographic colonography for screen detection of colorectal polyps. Gastroenterology 2003;125:311–319. Ladabaum U, Song K. Projected national impact of colorectal cancer screening on clinical and economic outcomes and health services demand. Gastroenterology 2005;129:1151–1162. Brenner DJ, Georgsson MA. Mass screening with CT colonography: should the radiation exposure be of concern? Gastroenterology 2005;129:328 –337. Scott RG, Edwards JT, Fritschi L, Foster NM, Mendelson RM, Forbes GM. Community-based screening by colonoscopy or computed tomographic colonography in asymptomatic average-risk subjects. Am J Gastroenterol 2004;99:1145–1151. doi:10.1053/j.gastro.2006.04.055
PPAR-␥ and Crohn’s Disease in New Zealand Dear Sir: We read with interest the article “Linkage to Peroxisome Proliferator-Activated Receptor-␥ in SAMP1/YitFc Mice and in Human Crohn’s Disease” by Sugawara et al recently published in GASTROENTEROLOGY.1 This interesting article by Sugawara et al found that the 2 minor alleles SNP1 [G12350898A (rs2067819)] and SNP2 [G12359887A (rs3892175)] of the peroxisome proliferator-activated receptor-␥ (PPAR␥) gene PPARG were more common (P ⬍ 10⫺5) in unaffected controls than in Crohn’s disease (CD) patients, indicating that PPARG is a susceptibility gene for CD in the USA. We would like the authors to estimate the odds ratio or the power of the study as no genotype data were published. Further, we ask the authors to calculate whether the genotype frequencies reported for the control group are in Hardy–Weinberg equilibrium (HWE) since a single HWE P value was given, presumably to the whole study population. This request is made as the bar graph of Figure 3B tends to suggest that the control group may significantly deviate from HWE. It is difficult to draw conclusions if the observed genotype distribution does not represent the genotype distribution in healthy (non-diseased) people.2 EUPHEMIA LEUNG* JIWON HONG* ALAN FRASER‡ TONY MERRIMAN§ GEOFFREY KRISSANSEN* Departments of *Molecular Medicine & Pathology, and ‡Medicine University of Auckland Auckland, New Zealand and §Department of Biochemistry University of Otago Dunedin, New Zealand