Correspondence
In the practice of evidence-based medicine, patients are afforded the most conservative interventions until alternatives are substantiated through rigorous scientific methods. When confronted with clinical features and behaviours that defy our expectations, predictions, or understanding, clinical scientists build testable hypotheses around those observations and in the interim protect patients, their caregivers, and contacts with the most conservative precautions. Our present reality concerns an expanding number of clinicians who were infected while ostensibly observing the direct contact precautions. No evidence has been provided to the contrary. Ebola observers can deduce the epidemiological implications of aerosol transmission described in extant literature, and mentioned although not referenced by Jose M Martin-Moreno and colleagues in their Letter.1 Accordingly, hospital administrators will enact more conservative precautions that either the authors 1 or the Centers for Disease Control and Prevention have prescribed. Scientists should make undiluted risk assessments and serious plans to contain, detect early, and actuate meaningful health-system responses to Ebola infection. The scientific community must argue for the most conservative infection control responses that make sense in light of the present data. I believe the authors1 and the Centers for Disease Control and Prevention have failed to do that and in so doing, have imperilled individuals unnecessarily. I declare no competing interests.
Timothy W Ryschon [email protected] Minnechaduza Medical Clinic, Loveland, CO 80538, USA 1
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Martin-Moreno JM, Llinás G, Martínez Hernández J. Is respiratory protection appropriate in the Ebola response? Lancet 2014; 384: 856.
Liver transplantation for intrahepatic cholangiocarcinoma In the Seminar by Nataliya Razumilava and Gregory Gores (June 21, p 2168)1 about individualised treatment of perihilar and intrahepatic cholangiocarcinoma, the authors state that liver transplantation is a curative option for some patients with perihilar cholangiocarcinoma but not for those with intrahepatic cholangiocarcinoma, referring to a study that compared transplantation in these patients to those with hepatocellular carcinoma.2 Although the study showed that 1-year and 5-year recurrence risks (42% and 65%, respectively) in patients with intrahepatic cholangiocarcinoma and hepatocellular cholangiocarcinoma were significantly higher than were those in patients with hepatocellular carcinoma (10% at 1 year and 17% at 5 year), these findings were obtained from a very small sample (four patients with intrahepatic cholangiocarcinomas and six patients with hepatocellular cholangiocarcinomas), and no patients received neoa d j u v a n t c h e m o t h e r a py. 2 I n a recent multi centre study of cirrhotic patients with early intrahepatic cholan giocarcinoma who underwent transplantation, 3 1-year actuarial survival was 100%, 3-year actuarial survival was 73%, and 5-year actuarial survival was 73%. For patients with locally advanced intrahepatic chol angio carcinoma given neoadjuvant chemotherapy, 5 year recurrence-free survival after trans plantation was 47% in nine patients with intrahepatic cholangiocarcinoma and two with hillar carcinoma (treatment in a single centre because of a shortage of donor organs). 4 The United Network for Organ Sharing does not provide treatment guidelines for
intrahepatic cholangiocarcinoma and the International Liver Cancer Association (ILCA) does not recommend liver transplantation for these patients. However, in the ILCA guidelines, the committee suggests that future studies should focus on standardised selection criteria for giving neoadjuvant chemotherapy with liver trans plantation for patients with intrahepatic cholangiocarcinoma. 5 Liver transplantation with neoadjuvant chemotherapy for patients with cirrhotic intrahepatic cholangiocarcinoma should be considered in clinical trials or as a treatment option in specialised centres. I declare no competing interests.
Tetsuji Fujita [email protected] Department of Surgery, Jikei University School of Medicine, Tokyo 105-8461, Japan 1 2
3
4
5
Razumilava N, Gores GJ. Cholangiocarcinoma. Lancet 2014; 383: 2168–79. Sapisochin G, Fidelman N, Roberts JP, Yao FY. Mixed hepatocellular cholangiocarcinoma and intrahepatic cholangiocarcinoma in patients undergoing transplantation for hepatocellular carcinoma. Liver Transpl 2011; 17: 934–42. Sapisochin G, Rodríguez de Lope C, Gastaca M, et al. “Very early” intrahepatic cholangiocarcinoma in cirrhotic patients: should liver transplantation be reconsidered in these patients? Am J Transplant 2014; 14: 660–67. Hong JC, Jones CM, Duffy JP, et al. Comparative analysis of resection and liver transplantation for intrahepatic and hilar cholangiocarcinoma: a 24-year experience in a single center. Arch Surg 2011; 146: 683–89. Bridgewater J, Galle PR, Khan SA, et al. Guidelines for the diagnosis and management of intrahepatic cholangiocarcinoma. J Hepatol 2014; 60: 1268–89.
Authors’ reply We thank Tetsuji Fujita for his comments about our Seminar about cholangiocarcinoma. 1 Since publication, additional data about liver transplantation for intrahepatic cholangiocarcinoma have become available. We want to emphasise that liver transplantation for any cancer should be associated with 5-year survival rates that are similar to those expected for liver transplantation in patients with cirrhosis but no www.thelancet.com Vol 384 September 27, 2014
Correspondence
www.thelancet.com Vol 384 September 27, 2014
Association guidelines 5 that these studies provide impetus for carefully carried out, protocol-driven prospective studies that will resolve these controversies. In the interim, liver transplantation for intrahepatic cholangiocarcinoma is still not yet ready to become standard treatment. We declare no competing interests.
Nataliya Razumilava, *Gregory J Gores [email protected] Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA 1 2
3
4
5
Razumilava N, Gores GJ. Cholangiocarcinoma. Lancet 2014; 383: 2168–79. Clavien PA, Lesurtel M, Bossuyt PM, Gores GJ, Langer B, Perrier A. Recommendations for liver transplantation for hepatocellular carcinoma: an international consensus conference report. Lancet Oncol 2012; 13: e11–22. Sapisochin G, de Lope CR, Gastaca M, et al. Intrahepatic cholangiocarcinoma or mixed hepatocellular-cholangiocarcinoma in patients undergoing liver transplantation: a Spanish matched cohort multicenter study. Ann Surg 2014; 259: 944–52. Garancini M, Goffredo P, Pagni F, et al. Combined hepatocellular-cholangiocarcinoma: A population-level analysis of an uncommon primary liver tumor. Liver Transpl 2014; 20: 952–59. Bridgewater J, Galle PR, Khan SA, et al. Guidelines for the diagnosis and management of intrahepatic cholangiocarcinoma. J Hepatol 2014; 60: 1268–89.
Medico-legal implications and not enough knowledge or clinical expertise might block this direction. The decree that breech presentation equals caesarean delivery is, however, not set in stone. An option to enable cephalic vaginal delivery does exist: external cephalic version (ECV). The no-option suggested by the authors in their Comment 1 is not in-line with national recommendations—that ECV should be done for all suitable women with breech presentation 3,4 and that caesarean delivery should be reserved for obstetric indications or failed ECV. Evidence suggests that adjuncts such as neuraxial anaesthesia, which are rarely used, can significantly increase the success rates of ECV; 5 vaginal delivery rates are high after successful ECV. We agree with van Roosmalen and Meguid that this issue should receive attention, but wish to suggest another pathway available for women with breech presentation.
Michelle Del Guercio/Science Photo Library
cancer. 2 This practice assures fair distribution of sparse donor organs and avoids procedure-associated and drug-associated risks to patients who will not benefit in the long term. A retrospective cohort multicentre study from Spain showed a 5-year actuarial survival rate of 51% after liver transplantation for intrahepatic cholangiocarcinoma. The 5-year cumulative risk of recurrence was 36%. 3 These rates of survival and recurrence fall below the standard of those reported in patients with cirrhosis but without cancer. Findings for patients with mixed hepatocellular-cholangiocellular carcinoma vary. Data from the cohort from Spain show outcomes after liver transplantation similar to those in patients with hepatocellular carcinoma (5-year actuarial survival rate after liver transplantation for mixed hepatocellularcholangiocellular carcinoma of 78%). The 5-year cumulative risk of recurrence for mixed carcinoma was 7%. 3 Of patients with intrahepatic cholangiocarcinoma and mixed hepatocellular-cholangiocellular carcinoma in the Spanish cohort, 52% received preoperative loco-regional tumour treatment. Analysis of a larger cohort of patients with mixed hepatocellular-cholangiocellular carcinoma from the Surveillance, Epidemiology, and End Results database showed that patients who were transplanted for mixed carcinoma had an overall 5-year survival of only 41%. 4 This 5-year survival is also suboptimum. The study from Spain provides information about the biological behaviour of intrahepatic cholangiocarcinoma after liver trans plantation and indicates poten tial benefits of neoadjuvant loco-regional therapy. Nonetheless, these retro spective studies are insufficient to change liver transplantation criteria for intrahepatic cholangiocarcinoma. We do agree with the International Liver Cancer
We declare no competing interests.
*Carolyn F Weiniger, Brendan Carvalho [email protected]
The dilemma of vaginal breech delivery worldwide We wish to remark on a Comment by Jos van Roosmalen and Tarek Meguid (May 31, p 1863). 1 The authors lament the decrease of vaginal breech delivery and express that despite much critique of the Term Breech Trial, caesarean breech delivery practice has been extensively used.2 The Comment presents a sorrowful picture of the unintended results of this practice change, with reported increases in maternal complications and mortality. More than a decade after the Term Breech Trial and its policy implementation, the way forward might no longer be the return of vaginal breech delivery.
Department of Anesthesia, 3580, Stanford University School of Medicine, Stanford, California 94305, USA (CFW, BC); and Department of Anesthesiology and Critical Care Medicine, Hadassah Hebrew University Medical Center, Ein Kerem, Jerusalem, Israel (CFW) 1
2
3
4
5
van Roosmalen J, Meguid T. The dilemma of vaginal breech delivery worldwide. Lancet 2014; 383: 1863–64. Hannah ME, Hannah WJ, Hewson SA, Hodnett ED, Saigal S, Willan AR. Planned caesarean section versus planned vaginal birth for breech presentation at term: a randomised multicentre trial. Term Breech Trial Collaborative Group. Lancet 2000; 356: 1375–83. ACOG Committee Opinion No. 340. Mode of term singleton breech delivery. Obstet Gynecol 2006; 108: 235–37. External cephalic version and reducing the incidence of breech presentation Guideline No. 20a. 2010. http://www.rcog.org.uk/files/ rcog-corp/uploaded-files/ GT20aExternalCephalicVersion.pdf (accessed April 11, 2014). Sultan P, Carvalho B. Neuraxial blockade for external cephalic version: a systematic review. Int J Obstet Anesth 2011; 20: 299–306.
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In the practice of evidence-based medicine, patients are afforded the most conservative interventions until alternatives are substantiated through rigorous scientific methods. When confronted with clinical features and behaviours that defy our expectations, predictions, or understanding, clinical scientists build testable hypotheses around those observations and in the interim protect patients, their caregivers, and contacts with the most conservative precautions. Our present reality concerns an expanding number of clinicians who were infected while ostensibly observing the direct contact precautions. No evidence has been provided to the contrary. Ebola observers can deduce the epidemiological implications of aerosol transmission described in extant literature, and mentioned although not referenced by Jose M Martin-Moreno and colleagues in their Letter.1 Accordingly, hospital administrators will enact more conservative precautions that either the authors 1 or the Centers for Disease Control and Prevention have prescribed. Scientists should make undiluted risk assessments and serious plans to contain, detect early, and actuate meaningful health-system responses to Ebola infection. The scientific community must argue for the most conservative infection control responses that make sense in light of the present data. I believe the authors1 and the Centers for Disease Control and Prevention have failed to do that and in so doing, have imperilled individuals unnecessarily. I declare no competing interests.
Timothy W Ryschon [email protected] Minnechaduza Medical Clinic, Loveland, CO 80538, USA 1
1182
Martin-Moreno JM, Llinás G, Martínez Hernández J. Is respiratory protection appropriate in the Ebola response? Lancet 2014; 384: 856.
Liver transplantation for intrahepatic cholangiocarcinoma In the Seminar by Nataliya Razumilava and Gregory Gores (June 21, p 2168)1 about individualised treatment of perihilar and intrahepatic cholangiocarcinoma, the authors state that liver transplantation is a curative option for some patients with perihilar cholangiocarcinoma but not for those with intrahepatic cholangiocarcinoma, referring to a study that compared transplantation in these patients to those with hepatocellular carcinoma.2 Although the study showed that 1-year and 5-year recurrence risks (42% and 65%, respectively) in patients with intrahepatic cholangiocarcinoma and hepatocellular cholangiocarcinoma were significantly higher than were those in patients with hepatocellular carcinoma (10% at 1 year and 17% at 5 year), these findings were obtained from a very small sample (four patients with intrahepatic cholangiocarcinomas and six patients with hepatocellular cholangiocarcinomas), and no patients received neoa d j u v a n t c h e m o t h e r a py. 2 I n a recent multi centre study of cirrhotic patients with early intrahepatic cholan giocarcinoma who underwent transplantation, 3 1-year actuarial survival was 100%, 3-year actuarial survival was 73%, and 5-year actuarial survival was 73%. For patients with locally advanced intrahepatic chol angio carcinoma given neoadjuvant chemotherapy, 5 year recurrence-free survival after trans plantation was 47% in nine patients with intrahepatic cholangiocarcinoma and two with hillar carcinoma (treatment in a single centre because of a shortage of donor organs). 4 The United Network for Organ Sharing does not provide treatment guidelines for
intrahepatic cholangiocarcinoma and the International Liver Cancer Association (ILCA) does not recommend liver transplantation for these patients. However, in the ILCA guidelines, the committee suggests that future studies should focus on standardised selection criteria for giving neoadjuvant chemotherapy with liver trans plantation for patients with intrahepatic cholangiocarcinoma. 5 Liver transplantation with neoadjuvant chemotherapy for patients with cirrhotic intrahepatic cholangiocarcinoma should be considered in clinical trials or as a treatment option in specialised centres. I declare no competing interests.
Tetsuji Fujita [email protected] Department of Surgery, Jikei University School of Medicine, Tokyo 105-8461, Japan 1 2
3
4
5
Razumilava N, Gores GJ. Cholangiocarcinoma. Lancet 2014; 383: 2168–79. Sapisochin G, Fidelman N, Roberts JP, Yao FY. Mixed hepatocellular cholangiocarcinoma and intrahepatic cholangiocarcinoma in patients undergoing transplantation for hepatocellular carcinoma. Liver Transpl 2011; 17: 934–42. Sapisochin G, Rodríguez de Lope C, Gastaca M, et al. “Very early” intrahepatic cholangiocarcinoma in cirrhotic patients: should liver transplantation be reconsidered in these patients? Am J Transplant 2014; 14: 660–67. Hong JC, Jones CM, Duffy JP, et al. Comparative analysis of resection and liver transplantation for intrahepatic and hilar cholangiocarcinoma: a 24-year experience in a single center. Arch Surg 2011; 146: 683–89. Bridgewater J, Galle PR, Khan SA, et al. Guidelines for the diagnosis and management of intrahepatic cholangiocarcinoma. J Hepatol 2014; 60: 1268–89.
Authors’ reply We thank Tetsuji Fujita for his comments about our Seminar about cholangiocarcinoma. 1 Since publication, additional data about liver transplantation for intrahepatic cholangiocarcinoma have become available. We want to emphasise that liver transplantation for any cancer should be associated with 5-year survival rates that are similar to those expected for liver transplantation in patients with cirrhosis but no www.thelancet.com Vol 384 September 27, 2014
Correspondence
www.thelancet.com Vol 384 September 27, 2014
Association guidelines 5 that these studies provide impetus for carefully carried out, protocol-driven prospective studies that will resolve these controversies. In the interim, liver transplantation for intrahepatic cholangiocarcinoma is still not yet ready to become standard treatment. We declare no competing interests.
Nataliya Razumilava, *Gregory J Gores [email protected] Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA 1 2
3
4
5
Razumilava N, Gores GJ. Cholangiocarcinoma. Lancet 2014; 383: 2168–79. Clavien PA, Lesurtel M, Bossuyt PM, Gores GJ, Langer B, Perrier A. Recommendations for liver transplantation for hepatocellular carcinoma: an international consensus conference report. Lancet Oncol 2012; 13: e11–22. Sapisochin G, de Lope CR, Gastaca M, et al. Intrahepatic cholangiocarcinoma or mixed hepatocellular-cholangiocarcinoma in patients undergoing liver transplantation: a Spanish matched cohort multicenter study. Ann Surg 2014; 259: 944–52. Garancini M, Goffredo P, Pagni F, et al. Combined hepatocellular-cholangiocarcinoma: A population-level analysis of an uncommon primary liver tumor. Liver Transpl 2014; 20: 952–59. Bridgewater J, Galle PR, Khan SA, et al. Guidelines for the diagnosis and management of intrahepatic cholangiocarcinoma. J Hepatol 2014; 60: 1268–89.
Medico-legal implications and not enough knowledge or clinical expertise might block this direction. The decree that breech presentation equals caesarean delivery is, however, not set in stone. An option to enable cephalic vaginal delivery does exist: external cephalic version (ECV). The no-option suggested by the authors in their Comment 1 is not in-line with national recommendations—that ECV should be done for all suitable women with breech presentation 3,4 and that caesarean delivery should be reserved for obstetric indications or failed ECV. Evidence suggests that adjuncts such as neuraxial anaesthesia, which are rarely used, can significantly increase the success rates of ECV; 5 vaginal delivery rates are high after successful ECV. We agree with van Roosmalen and Meguid that this issue should receive attention, but wish to suggest another pathway available for women with breech presentation.
Michelle Del Guercio/Science Photo Library
cancer. 2 This practice assures fair distribution of sparse donor organs and avoids procedure-associated and drug-associated risks to patients who will not benefit in the long term. A retrospective cohort multicentre study from Spain showed a 5-year actuarial survival rate of 51% after liver transplantation for intrahepatic cholangiocarcinoma. The 5-year cumulative risk of recurrence was 36%. 3 These rates of survival and recurrence fall below the standard of those reported in patients with cirrhosis but without cancer. Findings for patients with mixed hepatocellular-cholangiocellular carcinoma vary. Data from the cohort from Spain show outcomes after liver transplantation similar to those in patients with hepatocellular carcinoma (5-year actuarial survival rate after liver transplantation for mixed hepatocellularcholangiocellular carcinoma of 78%). The 5-year cumulative risk of recurrence for mixed carcinoma was 7%. 3 Of patients with intrahepatic cholangiocarcinoma and mixed hepatocellular-cholangiocellular carcinoma in the Spanish cohort, 52% received preoperative loco-regional tumour treatment. Analysis of a larger cohort of patients with mixed hepatocellular-cholangiocellular carcinoma from the Surveillance, Epidemiology, and End Results database showed that patients who were transplanted for mixed carcinoma had an overall 5-year survival of only 41%. 4 This 5-year survival is also suboptimum. The study from Spain provides information about the biological behaviour of intrahepatic cholangiocarcinoma after liver trans plantation and indicates poten tial benefits of neoadjuvant loco-regional therapy. Nonetheless, these retro spective studies are insufficient to change liver transplantation criteria for intrahepatic cholangiocarcinoma. We do agree with the International Liver Cancer
We declare no competing interests.
*Carolyn F Weiniger, Brendan Carvalho [email protected]
The dilemma of vaginal breech delivery worldwide We wish to remark on a Comment by Jos van Roosmalen and Tarek Meguid (May 31, p 1863). 1 The authors lament the decrease of vaginal breech delivery and express that despite much critique of the Term Breech Trial, caesarean breech delivery practice has been extensively used.2 The Comment presents a sorrowful picture of the unintended results of this practice change, with reported increases in maternal complications and mortality. More than a decade after the Term Breech Trial and its policy implementation, the way forward might no longer be the return of vaginal breech delivery.
Department of Anesthesia, 3580, Stanford University School of Medicine, Stanford, California 94305, USA (CFW, BC); and Department of Anesthesiology and Critical Care Medicine, Hadassah Hebrew University Medical Center, Ein Kerem, Jerusalem, Israel (CFW) 1
2
3
4
5
van Roosmalen J, Meguid T. The dilemma of vaginal breech delivery worldwide. Lancet 2014; 383: 1863–64. Hannah ME, Hannah WJ, Hewson SA, Hodnett ED, Saigal S, Willan AR. Planned caesarean section versus planned vaginal birth for breech presentation at term: a randomised multicentre trial. Term Breech Trial Collaborative Group. Lancet 2000; 356: 1375–83. ACOG Committee Opinion No. 340. Mode of term singleton breech delivery. Obstet Gynecol 2006; 108: 235–37. External cephalic version and reducing the incidence of breech presentation Guideline No. 20a. 2010. http://www.rcog.org.uk/files/ rcog-corp/uploaded-files/ GT20aExternalCephalicVersion.pdf (accessed April 11, 2014). Sultan P, Carvalho B. Neuraxial blockade for external cephalic version: a systematic review. Int J Obstet Anesth 2011; 20: 299–306.
1183
