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Current concepts of pancreas and liver trauma management
488
SELECTED SUMMARIES
GASTROENTEROLOGY Vol. 91. No. 2
this study implicate neuropeptides in the control of the mucosal immune system. This may be of importance for future clinical studies in that neuropeptide regulation of immunity in the intestine could modulate inflammatory intestinal diseases or may influence mucosal defense mechanisms. Furthermore, the development of pharmacologic agents to modulate the effects of neuropeptides on the mucosal immune system will be of interest as the mechanisms whereby neuropeptides modulate intestinal immune or inflammatory processes are delineated. The work by Stanisz and coworkers, therefore, will provide added impetus for further studies of the effect of neuropeptides on the mucosal immune system. R. P. MAcDERMOTT. M.D.
Reply.
The existence of a neuroendocrine-immune axis with bidirectional interactions has been suggested for many years, but it was not until recently that several studies have provided evidence in support of this hypothesis. Innervation of lymphoid tissues by adrenergic and peptidergic nerves is now well documented (J Immunol 1985;136:755s-65s). It is almost certain that these nerves release neuropeptides locally in lymphoid organs. Other reports suggest the presence of neuropeptides within cells that are not neuroendocrine in type or origin. For example, vasoactive intestinal peptide has been found in mast cells (Nature 1978;275:661-2) and polymorphonuclear leukocytes (J Lab Clin Med 1980;96:666-721, whereas a somatostatinlike peptide was found recently in rat basophilic leukemia cells (J Immunol 1985;135:2707-12). Thus, the effect of neuropeptides is probably not limited to lymphocytes but must include other cells of the immune network such as mast cells and phagocytes. In previous reports from this laboratory, it was documented that vasoactive intestinal peptide, somatostatin, substance P, and other neuropeptides such as endorphins stimulate histamine release from peritoneal mast cells. As in the case of the lymphocyte responses this effect appears to be both neuropeptideand organ- or cell-specific. Rat intestinal mucosal mast cells can only be triggered to release histamine by substance P, as opposed to peritoneal mast cells, which are activated by the majority of the neuropeptides examined (J Immunol 1985;135:1331-37). The most likely mechanism underlying cell activation by neuropeptides is specific binding to cell membrane receptors. Receptors for vasoactive intestinal peptide (J Immunol 1984; 132:417-23) and substance P (J Clin Invest 1984;74:1532-9) have been identified on T cells and it has been suggested these are their main target cells. However, we recently obtained evidence showing the presence of specific receptors for somatostatin and substance P on both T and B mouse lymphocytes isolated from the Peyer’s patches and spleen (in preparation). Information regarding the effects of neuropeptides on the immune response comes mainly from in vitro experiments, but obviously the case for a role of the peptides in immunoregulation would be stronger if effects could be demonstrated in vivo. We have obtained such evidence recently. The effect of neuropeptides on in vitro immune responses is not artifactual. In preliminary in vivo studies, using a constant microdelivery system for substance P, we have shown enhanced cell proliferation and immunoglobulin synthesis by mouse lymphocytes. In a different experimental system Ottaway (J Exp Med 1984;160:1054-69) was able to demonstrate a modulatory effect of vasoactive intestinal peptide on migration of mouse lymphocytes in vivo. Different neuropeptides may act at different levels of the immune network. Their immunomodulatory effect is likely to be mediated by direct interaction with both T and B cells. The net effect may depend on the cell population present in a particular tissue and the local level of interaction between diverse cell populations (e.g., helper versus suppressor T cells). Therefore, it
could be anticipated that in some situations the same neuropeptide may inhibit and in other instances it may enhance immunity. The further study of the neuro-immune axis will undoubtedly provide interesting new data which will have to be taken into consideration in interpretation of results. It is no longer tenable to think of immunologic systems as discrete entities; rather, they must be viewed as part of a physiologic whole. A. M. STANISZ, M.D. J. BIENENSTOCK, M.D.
CURRENT CONCEPTS OF PANCREAS LIVER TRAUMA MANAGEMENT
AND
Jones RC (Department of Surgery, University of Texas Health Science Center at Dallas, Dallas, Tex.) Management and of pancreatic trauma. Am J Surg 1985;150:698-704; Moore FA, Moore EE, and Seagraves A (Departments of Surgery, Denver General Hospital and University of Colorado Health Sciences Center, Denver, Colo.) Nonresectional management of major hepatic trauma: an evolving concept. Am J Surg 1985;150:725-9. These reports, presented at the 1985 meeting of the Southwestern Surgical Congress, come from two busy trauma centers. They summarize recent experience dealing with pancreatic and hepatic trauma, and both come to the conclusion that less radical surgery may yield better results in these areas. In the first report, Jones reviews the Dallas experience, over 35 yr, with 500 patients who had sustained pancreatic trauma. Fifty patients died intraoperatively leaving 450 for evaluation. Simple drainage was the treatment for 342 patients (76%) with only 6 subsequent deaths attributable to the pancreatic injury. Distal pancreatectomy was perfomed in 71 cases (Zl%] with one subsequent death attributable to the pancreatic injury. Eighteen patients underwent Roux-Y anastomosis to the area of injury or to both ends of a divided pancreas with three subsequent deaths. Twelve patients underwent pancreaticoduodenectomy (only 5 ultimately survived) and 5 underwent duodenal diverticulization (4 survived). The author states that, over the most recent IO-yr period, only z patients have died as a result of pancreatic injury and he attributes the high degree of success achieved to the progressive use of more conservative and simple procedures. The vast majority of pancreatic injuries are now managed by drainage alone at his institution, and resection is performed only when required to deal with hemorrhage or fragmentation of the pancreas. Thus, the frequency with which resections or Roux-Y drainage procedures, or both, have been performed during the most recent lo-yr period has markedly decreased. This has been associated with an increased survival rate. Pancreaticoduodenectomy, Jones argues, should only be performed either when severe combined pancreatic and duodenal trauma is present and the duodenum cannot be repaired or when uncontrollable hemorrhage from the pancreas is encountered. Duodenal diverticulization should be considered as an alternative method of managing severe pancreaticoduodenal injuries. The second report, by Moore et al., summarizes the Denver General Hospital 6-yr experience with 319 patients
August 1986
who had sustained liver injury and who had undergone laparotomy. Simple operative techniques such as clot evacuation, temporary packing, and control of bleeding vessels by cautery, topical agents, or ligation, or a combination thereof, were sufficient for the management of 83% of the injuries, and none of the patients managed in this manner died. The remaining 17% of the patients (53 individuals) sustained major hepatic trauma and required complex operative procedures, including lobectomy (21 patients), segmentectomy (6 patients), selective hepatic artery ligation (3 patients), and temporary packing (7 patients). Throughout the study period, there was a progressive shift away from resectional procedures (lobectomy and segmentectomy) and increased utilization of nonresectional alternatives such as hepatotomy, selective hepatic artery ligation, and packing. This change in strategy was a response to the high mortality rate for lobectomy (-60%) when done for parenchymal injury, with death most often resulting from perioperative exsanguination. With the increased use of nonresectional procedures, mortality rates for major hepatic trauma were found to decrease. Moore et al. conclude that surgical restraint in the operative treatment of complex liver trauma is warranted and that, in this setting, hepatic lobectomy is rarely justified. Comment. These two papers were chosen for presentation because they summarize currently accepted concepts regarding the preferred methods of management of pancreatic and hepatic trauma. Each report is a retrospective summary of the clinical experience at a single institution, and the conclusions reached are in no way original or even controversial. For the most part, they are consistent with those advocated by many other traumatologists. Unfortunately, patients with severe pancreatic or hepatic injury have not been evaluated in randomized trials testing various surgical procedures. Thus, the conclusions reached in these, as well as in other, reports are entirely based on a subjective evaluation of past experiences: i.e., the shift away from complex resective or drainage procedures, or both, to more simple maneuvers was associated with enhanced survival, therefo!e the simpler maneuvers are advocated. Obviously, there may have been many factors underlying the recently noted enhanced survival in addition to the utilization of less complex procedures. For example, advances in the perioperative intensive care of critically injured patients, rather than changes in operative strategy could have led to improved survival rates. Similarly, improvement in the diagnosis and treatment of associated injury in these patients could have had a greater impact than the shift toward less radical hepatic and pancreatic procedures. In fact, one might argue that more radical procedures, if used in the current setting of better overall trauma care, could lead to even better survival rates. In spite of these reservations, the experiences of groups such as those presenting these reports must be seriously considered. They are, after all, “in the trenches.” Moreover, the observations presented in these reports have been previously made by many other groups-radical and complex operative procedures undertaken in seriously, frequently multiply, injured and unstable patients should be avoided. Any lesser procedure that can even temporarily control the problem should be seriously considered. Simple drainage for pancreatic injury or alternatively, distal resections should be attempted unless the duodenum and head of the pancreas are so severely injured that they are either nonviable or
SELECTED SUMMARIES 487
bleeding to a degree requiring resection for control. Similarly, drainage, debridement, or local maneuvers, or a combination thereof, to control bleeding from hepatic injury should be attempted and, if unsuccessful, packing rather than lobectomy should be used to stabilize the patient. The move to more conservative operative management of pancreatic and liver injuries in major trauma centers should also be translated into similar conservative management of these injuries in other hospitals. The key word should be stabilization. There is little to justify the performance of major hepatic resections or pancreaticoduodenectomy in the middle of the night with inadequate blood bank and surgical support in outlying hospitals. Rather, these patients should be managed by the less complex methods outlined in these reports and, once stabilized, transferred to major health care centers if they are in need of more complex procedures. M. L.STEER.M.D.
SALICYLATES AND REYE’S SYNDROME Hurwitz ES, Barrett MJ, Bregman D, et al. (Public Health Service Reye Syndrome Task Force, Atlanta, Georgia]. Public Health Service study on Reye’s syndrome and medications: report of the pilot phase. N Engl J Med 1985;313:849-57 (October). This case-control evaluate the role Reye’s syndrome. were identified at
study was planned as a pilot project to of medication in the pathogenesis of Thirty children with Reye’s syndrome
16 participating pediatric tertiary centers from 11 states between mid-February and May 1984. The diagnosis of Reye’s syndrome was established by standard clinical criteria, and confirmed by an independent expert panel at the conclusion of the study. All of the children had a prodromal respiratory or gastrointestinal illness, or varicella within 3 wk before hospitalization, and all had coma of stage II or greater. Four control groups (total n = 145) included children (a) in the emergency room or (b) inpatient service at the hospital treating the matched case, (c) attending the same school or day-care center, and (d) identified by random-digit dialing. They were selected randomly from among children matched to patients on the basis of age, race, and occurrence of a similar antecedent illness. The home-care provider for each child was interviewed in depth; other care providers were interviewed about medications only. Ten generic components of medications were identified to have been given to at least 20% of the members of the Reye’s syndrome group and of the control groups. Only two of these medications were used with significantly different frequency in cases and controls (evaluated by the odds ratio method]: salicylates (cases, 93% vs. controls, 46%) and acetaminophen (cases, 27% vs. controls, 67%). For salicylates, the odds ratios were significant for all four control groups as well. No difference in the brands of salicylate given to cases or controls was noted. The dose of salicylate taken was not excessive (mean = 34 mgikg body wt day). No dose relationship to stage of coma was noted. Comment. Although Reye’s syndrome often follows influenza B and varicella infections, other factors must determine which individuals with these illnesses are at risk for the syndrome. One
SELECTED SUMMARIES
GASTROENTEROLOGY Vol. 91. No. 2
this study implicate neuropeptides in the control of the mucosal immune system. This may be of importance for future clinical studies in that neuropeptide regulation of immunity in the intestine could modulate inflammatory intestinal diseases or may influence mucosal defense mechanisms. Furthermore, the development of pharmacologic agents to modulate the effects of neuropeptides on the mucosal immune system will be of interest as the mechanisms whereby neuropeptides modulate intestinal immune or inflammatory processes are delineated. The work by Stanisz and coworkers, therefore, will provide added impetus for further studies of the effect of neuropeptides on the mucosal immune system. R. P. MAcDERMOTT. M.D.
Reply.
The existence of a neuroendocrine-immune axis with bidirectional interactions has been suggested for many years, but it was not until recently that several studies have provided evidence in support of this hypothesis. Innervation of lymphoid tissues by adrenergic and peptidergic nerves is now well documented (J Immunol 1985;136:755s-65s). It is almost certain that these nerves release neuropeptides locally in lymphoid organs. Other reports suggest the presence of neuropeptides within cells that are not neuroendocrine in type or origin. For example, vasoactive intestinal peptide has been found in mast cells (Nature 1978;275:661-2) and polymorphonuclear leukocytes (J Lab Clin Med 1980;96:666-721, whereas a somatostatinlike peptide was found recently in rat basophilic leukemia cells (J Immunol 1985;135:2707-12). Thus, the effect of neuropeptides is probably not limited to lymphocytes but must include other cells of the immune network such as mast cells and phagocytes. In previous reports from this laboratory, it was documented that vasoactive intestinal peptide, somatostatin, substance P, and other neuropeptides such as endorphins stimulate histamine release from peritoneal mast cells. As in the case of the lymphocyte responses this effect appears to be both neuropeptideand organ- or cell-specific. Rat intestinal mucosal mast cells can only be triggered to release histamine by substance P, as opposed to peritoneal mast cells, which are activated by the majority of the neuropeptides examined (J Immunol 1985;135:1331-37). The most likely mechanism underlying cell activation by neuropeptides is specific binding to cell membrane receptors. Receptors for vasoactive intestinal peptide (J Immunol 1984; 132:417-23) and substance P (J Clin Invest 1984;74:1532-9) have been identified on T cells and it has been suggested these are their main target cells. However, we recently obtained evidence showing the presence of specific receptors for somatostatin and substance P on both T and B mouse lymphocytes isolated from the Peyer’s patches and spleen (in preparation). Information regarding the effects of neuropeptides on the immune response comes mainly from in vitro experiments, but obviously the case for a role of the peptides in immunoregulation would be stronger if effects could be demonstrated in vivo. We have obtained such evidence recently. The effect of neuropeptides on in vitro immune responses is not artifactual. In preliminary in vivo studies, using a constant microdelivery system for substance P, we have shown enhanced cell proliferation and immunoglobulin synthesis by mouse lymphocytes. In a different experimental system Ottaway (J Exp Med 1984;160:1054-69) was able to demonstrate a modulatory effect of vasoactive intestinal peptide on migration of mouse lymphocytes in vivo. Different neuropeptides may act at different levels of the immune network. Their immunomodulatory effect is likely to be mediated by direct interaction with both T and B cells. The net effect may depend on the cell population present in a particular tissue and the local level of interaction between diverse cell populations (e.g., helper versus suppressor T cells). Therefore, it
could be anticipated that in some situations the same neuropeptide may inhibit and in other instances it may enhance immunity. The further study of the neuro-immune axis will undoubtedly provide interesting new data which will have to be taken into consideration in interpretation of results. It is no longer tenable to think of immunologic systems as discrete entities; rather, they must be viewed as part of a physiologic whole. A. M. STANISZ, M.D. J. BIENENSTOCK, M.D.
CURRENT CONCEPTS OF PANCREAS LIVER TRAUMA MANAGEMENT
AND
Jones RC (Department of Surgery, University of Texas Health Science Center at Dallas, Dallas, Tex.) Management and of pancreatic trauma. Am J Surg 1985;150:698-704; Moore FA, Moore EE, and Seagraves A (Departments of Surgery, Denver General Hospital and University of Colorado Health Sciences Center, Denver, Colo.) Nonresectional management of major hepatic trauma: an evolving concept. Am J Surg 1985;150:725-9. These reports, presented at the 1985 meeting of the Southwestern Surgical Congress, come from two busy trauma centers. They summarize recent experience dealing with pancreatic and hepatic trauma, and both come to the conclusion that less radical surgery may yield better results in these areas. In the first report, Jones reviews the Dallas experience, over 35 yr, with 500 patients who had sustained pancreatic trauma. Fifty patients died intraoperatively leaving 450 for evaluation. Simple drainage was the treatment for 342 patients (76%) with only 6 subsequent deaths attributable to the pancreatic injury. Distal pancreatectomy was perfomed in 71 cases (Zl%] with one subsequent death attributable to the pancreatic injury. Eighteen patients underwent Roux-Y anastomosis to the area of injury or to both ends of a divided pancreas with three subsequent deaths. Twelve patients underwent pancreaticoduodenectomy (only 5 ultimately survived) and 5 underwent duodenal diverticulization (4 survived). The author states that, over the most recent IO-yr period, only z patients have died as a result of pancreatic injury and he attributes the high degree of success achieved to the progressive use of more conservative and simple procedures. The vast majority of pancreatic injuries are now managed by drainage alone at his institution, and resection is performed only when required to deal with hemorrhage or fragmentation of the pancreas. Thus, the frequency with which resections or Roux-Y drainage procedures, or both, have been performed during the most recent lo-yr period has markedly decreased. This has been associated with an increased survival rate. Pancreaticoduodenectomy, Jones argues, should only be performed either when severe combined pancreatic and duodenal trauma is present and the duodenum cannot be repaired or when uncontrollable hemorrhage from the pancreas is encountered. Duodenal diverticulization should be considered as an alternative method of managing severe pancreaticoduodenal injuries. The second report, by Moore et al., summarizes the Denver General Hospital 6-yr experience with 319 patients
August 1986
who had sustained liver injury and who had undergone laparotomy. Simple operative techniques such as clot evacuation, temporary packing, and control of bleeding vessels by cautery, topical agents, or ligation, or a combination thereof, were sufficient for the management of 83% of the injuries, and none of the patients managed in this manner died. The remaining 17% of the patients (53 individuals) sustained major hepatic trauma and required complex operative procedures, including lobectomy (21 patients), segmentectomy (6 patients), selective hepatic artery ligation (3 patients), and temporary packing (7 patients). Throughout the study period, there was a progressive shift away from resectional procedures (lobectomy and segmentectomy) and increased utilization of nonresectional alternatives such as hepatotomy, selective hepatic artery ligation, and packing. This change in strategy was a response to the high mortality rate for lobectomy (-60%) when done for parenchymal injury, with death most often resulting from perioperative exsanguination. With the increased use of nonresectional procedures, mortality rates for major hepatic trauma were found to decrease. Moore et al. conclude that surgical restraint in the operative treatment of complex liver trauma is warranted and that, in this setting, hepatic lobectomy is rarely justified. Comment. These two papers were chosen for presentation because they summarize currently accepted concepts regarding the preferred methods of management of pancreatic and hepatic trauma. Each report is a retrospective summary of the clinical experience at a single institution, and the conclusions reached are in no way original or even controversial. For the most part, they are consistent with those advocated by many other traumatologists. Unfortunately, patients with severe pancreatic or hepatic injury have not been evaluated in randomized trials testing various surgical procedures. Thus, the conclusions reached in these, as well as in other, reports are entirely based on a subjective evaluation of past experiences: i.e., the shift away from complex resective or drainage procedures, or both, to more simple maneuvers was associated with enhanced survival, therefo!e the simpler maneuvers are advocated. Obviously, there may have been many factors underlying the recently noted enhanced survival in addition to the utilization of less complex procedures. For example, advances in the perioperative intensive care of critically injured patients, rather than changes in operative strategy could have led to improved survival rates. Similarly, improvement in the diagnosis and treatment of associated injury in these patients could have had a greater impact than the shift toward less radical hepatic and pancreatic procedures. In fact, one might argue that more radical procedures, if used in the current setting of better overall trauma care, could lead to even better survival rates. In spite of these reservations, the experiences of groups such as those presenting these reports must be seriously considered. They are, after all, “in the trenches.” Moreover, the observations presented in these reports have been previously made by many other groups-radical and complex operative procedures undertaken in seriously, frequently multiply, injured and unstable patients should be avoided. Any lesser procedure that can even temporarily control the problem should be seriously considered. Simple drainage for pancreatic injury or alternatively, distal resections should be attempted unless the duodenum and head of the pancreas are so severely injured that they are either nonviable or
SELECTED SUMMARIES 487
bleeding to a degree requiring resection for control. Similarly, drainage, debridement, or local maneuvers, or a combination thereof, to control bleeding from hepatic injury should be attempted and, if unsuccessful, packing rather than lobectomy should be used to stabilize the patient. The move to more conservative operative management of pancreatic and liver injuries in major trauma centers should also be translated into similar conservative management of these injuries in other hospitals. The key word should be stabilization. There is little to justify the performance of major hepatic resections or pancreaticoduodenectomy in the middle of the night with inadequate blood bank and surgical support in outlying hospitals. Rather, these patients should be managed by the less complex methods outlined in these reports and, once stabilized, transferred to major health care centers if they are in need of more complex procedures. M. L.STEER.M.D.
SALICYLATES AND REYE’S SYNDROME Hurwitz ES, Barrett MJ, Bregman D, et al. (Public Health Service Reye Syndrome Task Force, Atlanta, Georgia]. Public Health Service study on Reye’s syndrome and medications: report of the pilot phase. N Engl J Med 1985;313:849-57 (October). This case-control evaluate the role Reye’s syndrome. were identified at
study was planned as a pilot project to of medication in the pathogenesis of Thirty children with Reye’s syndrome
16 participating pediatric tertiary centers from 11 states between mid-February and May 1984. The diagnosis of Reye’s syndrome was established by standard clinical criteria, and confirmed by an independent expert panel at the conclusion of the study. All of the children had a prodromal respiratory or gastrointestinal illness, or varicella within 3 wk before hospitalization, and all had coma of stage II or greater. Four control groups (total n = 145) included children (a) in the emergency room or (b) inpatient service at the hospital treating the matched case, (c) attending the same school or day-care center, and (d) identified by random-digit dialing. They were selected randomly from among children matched to patients on the basis of age, race, and occurrence of a similar antecedent illness. The home-care provider for each child was interviewed in depth; other care providers were interviewed about medications only. Ten generic components of medications were identified to have been given to at least 20% of the members of the Reye’s syndrome group and of the control groups. Only two of these medications were used with significantly different frequency in cases and controls (evaluated by the odds ratio method]: salicylates (cases, 93% vs. controls, 46%) and acetaminophen (cases, 27% vs. controls, 67%). For salicylates, the odds ratios were significant for all four control groups as well. No difference in the brands of salicylate given to cases or controls was noted. The dose of salicylate taken was not excessive (mean = 34 mgikg body wt day). No dose relationship to stage of coma was noted. Comment. Although Reye’s syndrome often follows influenza B and varicella infections, other factors must determine which individuals with these illnesses are at risk for the syndrome. One