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Annals of Surgery Journal Club
Interactive resource for surgery residents and surgeons to discuss and critically evaluate articles published in Annals of Surgery selected by a monthly guest expert who will review an article each month, offer questions and respond to reader's comments.
Friday, October 02, 2015

Moderator:Christopher L. Wolfgang, MD, PhD

Ferrone CR, Marchegiani G, Hong TS, et al. Radiological and surgical implications of neoadjuvant treatment with FOLFIRINOX for locally advanced and borderline resectable pancreatic cancer. Ann Surg. 2015;261:12-17.

This month's Journal Club is a nicely executed study by Cristina Ferrone and her colleagues that addresses several important questions related to patients with Stage III pancreatic cancer treated with induction or neoadjuvant FOLFIRINOX. It is estimated that at the time of diagnosis 30% of patients with pancreatic cancer have localized tumors that are unresectable due to major vessel involvement (Stage III). Historically, these patients were treated with systemic therapy but the majority never made it to surgical resection. In part, this was due to the notoriously ineffective nature of the systemic therapy in terms controlling systemic disease and lack of response of the primary tumor. Recently, several more effective chemotherapy regimens such as FOLFIRINOX have shown improved efficacy in Stage IV disease. This has prompted the use of FOLFIRINOX in stage III patients in an attempt to better control micrometastatic disease, “sterilize” margins or downstage the tumor. Currently very little is known about selection of patients for surgical resection and the surgery-related outcomes of Stage III patients who underwent induction or neoadjuvant FOLFIRNOX treatment. This is the impetus for the manuscript in this month's journal club.

About the Author

Christopher L. Wolfgang, MD, PhD is the Chief of Hepatobiliary and Pancreatic Surgery at the Johns Hopkins Hospital and Professor of Surgery, Pathology and Oncology at Johns Hopkins University School of Medicine. He also is the Paul K. Neumann Professor of Pancreatic Cancer Research and a member of the Miller-Coulson Academy of Clinical Excellence. He obtained his medical degree from Temple University School of Medicine and residency training in General Surgery at Penn State Milton S. Hershey Medical Center. In addition, Dr. Wolfgang obtained a Ph.D. degree in Biochemistry, also from Temple University School of Medicine. Dr. Wolfgang has completed a research fellowship in surgical oncology from Penn State and a clinical fellowship in gastrointestinal surgery at Johns Hopkins.

Of the several interesting findings in this study I would like to focus on the two that I think are the most important. In the study 47 Stage III patients underwent exploration after receiving FOLFIRINOX. Among this cohort, 40 were able to undergo an oncological resection despite the fact that 62% were initially locally advanced and unresectable based on AHPBA/SSO/SSAT criteria. Moreover, the margin-negativity rate in this group was 92%. The FOLFIRNOX resulted in downstaging of 9 patients in this group but the post treatment CT continued to demonstrate unresectablity in the majority of patients. To confirm the staging determined by the tumor board, the study also had Andrew Warshaw, a senior experienced pancreatic surgeon, assess resectability in a blinded fashion. His observations were nearly identical to the tumor board. Taken together, these observations lead to the first major finding of the study and, that is, following FOLFIRINOX treatment a CT scan becomes less useful in determining resectability. The second important finding of this paper is an assessment of the biological activity of FOLFIRINOX. Only 35% of patients had regional lymph node metastases compared to 79% in the cohort not undergoing neoadjuvant therapy. In fact, all negative pathological features were less prevalent in the FOLFIRONOX group.
Others have confirmed many of the findings of this study in more recent manuscripts as outlined in a recent meta-analysis by Petrelli et al., 2015.1
Although the study is nicely done there are some limitations inherent to a retrospective analysis. This is not an intention to treat analysis, so it is not known how many Stage III patients were initially treated with FOLFIRNOX and never made it to exploration. In addition, the initial AHPBA/SSO/SSAT stage is reported for the cohort, but the post-treatment stage is not - only the extent of response. Finally we have no follow-up on disease specific survival to know if the pathological features in the FOLFIRINOX group translate into improved survival.


  1. If the CT scan does not accurately predict resectability follow FOLFIRINOX (and likely other aggressive regimens), what should be the criteria to explore a Stage III patient following treatment? Based on the findings of this paper, should the new criteria be anatomic? Extent of response? Performance status alone?
  2. Since a significant proportion of the FOLFIRINOX cohort also received external beam radiation, do you think that some of the effect may be more related to the radiation than the systemic therapy? Is chemoradiation possibly synergistic with FOLFIRINOX?
  3. Based on the biological activity of FOLFIRINOX in terms of nodal status, margin status and CT response rate, should we consider moving toward neoadjuvant therapy in all patients including Stage I/II resectable?
  4. What do you predict will be the correlation of pathological features with survival after neoadjuvant? Will the same pathological feature apply post-treatment? Put in another way, does a negative nodal status mean the same following treatment as it does in a chemo-naive patient?

1. Petrelli F, Coinu A, Borgonovo K, et al. FOLFIRINOX-based neoadjuvant therapy in borderline resectable or unresectable pancreatic cancer: a meta-analytical review of published studies. Pancreas. 2015;44:515-521.

Monday, September 07, 2015

Moderator: Julie A. Margenthaler, MD

Prospective Study of Surgical Decision-making Processes for Contralateral Prophylactic Mastectomy in Women With Breast Cancer. Ann Surg. 2015 March 27 [epub ahead of print].

Parker et al. tackle the controversial topic of contralateral prophylactic mastectomy in this month's journal club article "Prospective Study of Surgical Decision-making Processes for Contralateral Prophylactic Mastectomy in Women with Breast Cancer." In 1991, the National Institute of Health Consensus Conference endorsed breast conserving therapy (BCT) as the preferred treatment of early-stage breast cancer. This endorsement was based on evidence demonstrating that women undergoing BCT for early stage breast cancer have equivalent survival outcomes compared to mastectomy. These findings led to the widespread use of BCT as the treatment for early stage breast cancer at major centers across the United States during the past two decades. More recently, however, physicians have noted, and studies have confirmed, increased rates of mastectomy and contralateral prophylactic mastectomy (CPM) for the treatment of breast cancer. The underlying reasons for this shift have been hotly debated in the past few years and have generated many retrospective reports.

About the Author

Julie A. Margenthaler, MD is the Director of Breast Surgical Services at Siteman Cancer Center and Associate Professor of Surgery and Director of the Breast Fellowship Program at Washington University School of Medicine in St. Louis, MO. She is a graduate of Southern Illinois University School of Medicine and completed her general surgery residency and breast fellowship at Washington University School of Medicine. Dr. Margenthaler is on the Board of the American Society of Breast Surgeons and a Councilor at Large for the Society of Surgical Oncology. Her research interests include breast cancer clinical outcomes and the development of novel imaging devices.

This paper is unique from other recent publications in that it is a prospective study examining the women's interest in contralateral prophylactic mastectomy (CPM) before and after their visit with the breast surgeon, and the perception of the appropriateness of CPM by the surgeon. The authors studied 117 women who were of average risk for breast cancer prior to their diagnoses. Prior to their first visit, 50% of women reported that they were moderately to extremely interested in CPM. However, only 10% of the women ultimately had CPM. Interestingly, only 43% of women reported that CPM had been discussed moderately to extensively with their surgeon, while surgeons reported this number to be 33%. In fact, surgeons reported that CPM was not discussed at all in 45% of visits. Cancer worry was the strongest factor associated with having a CPM.

There are some limitations to this study despite its prospective nature. The sample size is relatively small and it is difficult to determine whether the results are generalizable to other practice settings. There are likely factors not captured by the study that impact the final decision. For instance, 23% of women reported that they were likely to have a CPM following the visit with the surgeon, but only 10% actually did.

The importance of this study is that it provides a glimpse into the real-time decision-making of a patient who is considering CPM. It is clear from this study that the patient's perception of risk and the surgeon's ability to communicate that risk and the options for treatment are paramount in driving the rate of CPM for average-risk women. It also illustrates the need for systematic communication tools to guide these discussions.


  1. For average risk women with breast cancer, what is an acceptable CPM rate? Are there certain patient and/or tumor factors where this rate would be acceptably higher (young age at diagnosis, need for unilateral mastectomy for known disease, lobular histology, reconstructive symmetry)?
  2. Do you think that the individual surgeon's beliefs and practices impact the rate of CPM? Does surgeon sex, age, or level of training play a role?
  3. Cancer worry is a strong factor in the decision for CPM in this study and in previous retrospective studies. Do you think cancer worry decreases with CPM? What tools might we use to counsel women about cancer worry?

Thursday, August 06, 2015

Moderator: Karen Brasel, MD, MPH

Cooper Z, Courthwright A, Karlage A, et al. Pitfalls in Communication That Lead to Nonbeneficial Emergency Surgery in Elderly Patients With Serious Illness: Description of the Problem and Elements of a Solution. Ann Surg. 2014;260:949-957.

In this month's journal club article, “Pitfalls in Communication That Lead to Nonbeneficial Emergency Surgery in Elderly Patients With Serious Illness: Description of the Problem and Elements of a Solution”, Cooper et al provide a structure describing elements that lead to nonbeneficial emergency surgery in elderly patients with serious illness. This well-written manuscript provides a framework with which to conceptualize and potentially address the problem of nonbeneficial surgery. However, it is not a rigorous methodological review, but rather a well-referenced opinion piece. The lack of rigorous methodology leaves the assessment of the underlying factors open to bias; this is important as it has direct impact on whether the proposed solutions can be expected to be successful.

About the Author

Karen Brasel, MD, MPH, Professor of Surgery, is the General Surgery Residency Program Director at Oregon Health & Science University in Portland, Oregon.  Dr. Brasel received her medical degree from the University of Iowa, completed her surgical residency and master's degree in Public Health at the University of Minnesota, and her surgical critical care fellowship at the University of North Carolina. She serves on the Executive Committee of the American College of Surgeons Board of Governors, the American College of Surgeons Task Force on Surgical Palliative Care, and is a Director of the American Board of Surgery. Her research interests, funded by the Centers for Disease Control, include post-injury quality of life and functional outcomes, surgical palliative care, ethics and education.
The problem being addressed is the increased use of resources, particularly surgery unlikely to alter an elderly patient's clinical course, that occurs in elderly patients with serious illness. The authors identify surgeon, patient, surrogate, and systemic or structural factors as potential areas of communication pitfalls. Surgeon factors include inadequate time for conversation, inadequate training, and a belief that patients do not want to talk about death and dying. The authors provide evidence that training improves surgeon confidence and competence in these discussions, suggesting that one strategy to address the primary underlying problem would be to increase education for all surgeons, beginning with surgeons in training. This effort is being helped through efforts of SCORE, the ACS Task Force on Surgical Palliative Care, and the American Board of Surgery. Another difficulty that is common to both surgeon and patient is the difficulty in prognostication. Data that show patients who understand their prognosis, and have had prior discussions with healthcare providers about prognosis, seem to be supportive of the fact that lack of a long-term relationship between surgeon and patient may be part of the prognostication problem. However, providers who have a long-term relationship with a patient may actually be less able to accurately prognosticate due to their emotional investment with the patient. Use of standardized prognostic tools, such as the NSQIP risk calculator, provides much more accurate prognostic information. In at least one center, use of a threshold prognostic value for mortality in the elective setting triggers a palliative care consult, mandatory discussion about risks and benefits. This has reduced both mortality and nonbeneficial surgery; such an approach could potentially be modified for the urgent/emergent setting.

The biggest benefit of this review is the logical organization and the extensive reference list. It not only outlines potentially beneficial approaches to improve communication, but importantly outlines areas in which we have very little if any evidence on the outcomes that are of primary importance to our patients and their families.


  1. What evidence do the authors cite that surgeon education and training improves patient outcomes? What evidence would convince you to participate in an educational intervention?
  2. What information leads to inaccurate prognostication? How strong is the evidence supporting this information?
  3. Does an appropriately completed informed consent discussion lead to a decrease in nonbeneficial emergent surgery in elderly patients?

Wednesday, July 01, 2015

Moderator: Thomas H. Cogbill, M.D.

Paquette IM, Zuckerman R, Finlayson SRG: Perforated appendicitis among rural and urban patients: implications of access to care. Ann Surg. 2011;253:534-538.

In this retrospective cohort study, the authors used the 2003-2004 National Inpatient Sample to collect data on 122,990 patients with acute appendicitis. Using urban influence codes provided by the United States Department of Agriculture, 7597 patients were classified as rural and 103,801 patients as urban. These two groups were compared by univariate and multivariate analysis.

The overall rate of perforated appendicitis was 32%. Patients with perforation had mean hospital lengths of stay 3.6 days longer and incurred mean charges of $5714 more per patient than those without perforation. The rate of perforation was 35.8% in rural patients and 31.5% in urban patients (p 40 years, male gender, transfer from another facility, black race, poorest 25 percentiles, Charlson comorbidity score >= 3, and rural residence. Logistic regression was used to demonstrate that the difference in perforation rates between rural and urban patients persisted when other factors associated with perforation were controlled.

Nearly 98% of urban patients were discharged from an urban hospital and 30% of rural patients were discharged from an urban hospital. Rural patients discharged from urban hospitals were more likely than rural patients discharged from rural hospitals to have a diagnosis of perforation (OR = 1.23).

The authors concluded that patients from rural areas have higher rates of perforation associated with acute appendicitis than their urban counterparts. They opined that this difference suggests a disparity in access to timely surgical care and is the result of geographic, provider, and/or patient factors.

About the Author

Dr. Thomas H. Cogbill  received his MD from the University of Colorado in 1977 and completed surgical residency at the University of Colorado Medical Center in 1982.  He has practiced general surgery at Gundersen Health System in La Crosse WI from 1982 to present.   He was the Program Director of the general surgery residency at Gundersen Medical Foundation from 1990-2010..  He is a Clinical Professor of Surgery at the University of Wisconsin School of Medicine and Public Health.  Dr. Cogbill was the Chair of the American Board of Surgery in 2012-2013.  His research interests include general surgery workforce, general surgery education, trauma, and rural surgery.


  1. Could selection bias have accounted for some of the difference in the rates of perforated appendicitis in rural patients treated at urban versus rural hospitals? Is it possible that rural patients with perforated appendicitis and abscess might have been transferred to urban hospitals for percutaneous drainage by interventional radiologists? Is it likely that rural patients with sepsis and multiple system organ failure due to perforated appendicitis required transfer to urban hospitals for critical care management? How could the authors have investigated the magnitude of these effects?
  2. Many rural U.S. counties have Critical Access Hospitals (CAH). One of the stipulations for CAH designation is adherence to the 96 hour rule. This rule states a) the CAH is required to assure that acute inpatient care does not exceed 96 hours on average per patient and b) the CAH will only receive payment if a physician certifies that a patient being admitted is expected to be discharged or transferred to another institution within 96 hours. Could application of this rule have caused more rural patients with perforated appendicitis ( with longer expected length of stay ) to be transferred to urban hospitals?
  3. There are three common situations in rural U.S. counties : a) No hospital and no general surgeon(s) are in the county, b) A hospital but no general surgeon(s) are in the county, and c) Both a hospital and a general surgeon(s)are in the county. Are there possible differences in the rates of perforation in residents of these county classifications? Are the barriers to access of health care different in each of the three different settings above? How might these differences influence potential solutions in each of these three settings? Does the presence of a general surgeon in a rural county result in lower rates of perforated appendicitis in that county's residents?
  4. Several authors have recently proposed that early appendicitis can be safely managed with antibiotics alone. If this trend were to expand, how might the disparity in rates of perforated appendicitis between rural and urban areas be affected? Who would follow rural patients treated nonoperatively?
  5. The authors concluded that the increased rate of perforated appendicitis in residents of the rural U.S. was due to geographic, patient, and/or provider factors. What strategies might be used to alleviate obstacles in each of these three categories?
  6. Currently, the most serious surgical workforce shortage in the U.S. concerns general surgeons in rural areas. The shortage is forecast to worsen over the next 20 years. What strategies might be used to provide incentive for general surgeons to practice in rural areas?

Monday, June 01, 2015

Moderator: Paul E. Wise, M.D.

Vather R, Josephson R, Jaung R, et al. Gastrografin in Prolonged Postoperative Ileus--A Double-blinded Randomized Controlled Trial. Ann Surg. 2015 Jan 8. [Epub ahead of print].

In this trial from New Zealand conducted between September 2012 and June 2014, the authors performed a double-blinded, randomized, placebo-controlled study in 80 patients comparing a one-time dose of Gastrografin (an orally administered, water-soluble, hyperosmolar agent) versus a control agent (an anise oil, ethanol, glycerol mixture) to resolve prolonged post-operative ileus (PPOI) after elective colorectal operations. Well-defined criteria were used to determine the presence of PPOI and resolution of PPOI, and they followed the patients prospectively to assess the primary endpoint of duration of PPOI (time from diagnosis to resolution of PPOI) and the secondary endpoints of time until discharge criteria were met, length of stay (LOS), and readmission. The authors found that the mean duration of PPOI did not differ between the groups (83.7 vs 101.3 hours; P=0.191) despite an "accelerated time to flatus or stool (18.9 vs 32.7 hours; P = 0.047) and time to resolution of abdominal distension (52.8 vs 77.7 hours; P = 0.013)." There were no differences in complications, readmission, or LOS (10 days vs 13 days; p=0.262). The authors concluded that "Gastrografin is not clinically useful in shortening an episode of PPOI characterized by upper and lower gastrointestinal symptoms."

About the Author

Dr. Paul E. Wise is an Associate Professor of Surgery at Washington University in St. Louis School of Medicine where he serves as Program Director of the General Surgery Residency and Director of the Inherited Colorectal Cancer and Polyposis Registry. He completed his General Surgery residency at Vanderbilt University Medical Center in Nashville and his colon and rectal surgery fellowship at Washington University in St, Louis/Barnes Jewish Hospital after completing medical school at Johns Hopkins University School of Medicine in 1996. He has been a Council member as well as President of the Collaborative Group of the Americas on Inherited Colorectal Cancer and is a member of multiple committees in the American Society of Colon and Rectal Surgeons and the Society of Surgeons of the Alimentary Tract. His research interests include hereditary colorectal cancer syndromes, improving outcomes after colorectal surgery, and surgical education.


  1. The sample size for the study of 80 patients was determined based on a PPOI incidence at their institution of almost 20% and lasting 4.5 days (Vather R, Bissett IP. Int J Colorectal Dis. 2013;28(10):1385-91). To calculate their sample size, the authors anticipated a 33% shorter duration of PPOI with Gastrografin. Does this seem like a reasonable means to determine the number of patients needed to avoid a type II error (failure to reject the null hypothesis)?
  2. The authors point out in the Discussion that defining the types of ileus may impact the possible therapeutic measures employed to help the PPOI resolve, if any. With less than 50% of the patients in this study showing "hard" signs of ileus (cessation of bowel function/flatus and/or radiographic findings), did the authors select a patient group less likely to benefit from the intervention? If so, would their numbers likely allow a subgroup analysis of the effectiveness of Gastrografin for those patients with "hard" signs/"lower GI symptoms"?
  3. Should the authors have included patients with ostomies in the cohort? If not, why not?
  4. The authors have noted factors that impact development of PPOI (Vather R, et al. Surgery. 2015;157(4):764-73). Should the authors have used any of these criteria for the randomization?
  5. Should the authors ensure (or at least report) their protocol for post-operative care in terms of early ambulation or other interventions known to impact development, and potentially duration, of PPOI? Would the randomization necessarily negate the need to report these factors?
  6. Does the increased use of opiates in the Gastrografin group impact the results, and if so, how?
  7. How are the author's endpoints potentially impacted by the clinicians' rounding and ordering habits? Might this impact time to consumption of oral diet and/or discharge timing/LOS, for example?