CURRICULUM VITAE Stephen L. Boehm II, PhD Associate Professor Psychobiology of Addictions Department of Psychology Indiana University – Purdue University Indianapolis Mailing Address: Phone/Email: Indianapolis, IN 46202 Educational Background: Postdoctoral, University of Texas at Austin, 2002-2005. Neuropharmacology. Ph.D., Oregon Health & Science Unive
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Drgramatica.com.arTreatment of Perforated Diverticulitis with GeneralizedPeritonitis: Past, Present, and Future Jefrey Vermeulen • Johan F. Lange Published online: 6 January 2010Ó The Author(s) 2010. This article is published with open access at Springerlink.com prevalence of perforated diverticulitis complicated by The supposed optimal treatment of perforated generalized peritonitis is low, its importance lies in the diverticulitis with generalized peritonitis has changed several significant postoperative mortality, ranging from 4–26% times during the last century, but at present is still unclear.
regardless of selected surgical strategy The first cases of complicated perforated Until today the optimal treatment for perforated diver- diverticulitis of the colon were reported in the beginning of ticulitis has been a matter of debate. During the last dec- the twentieth century. At that time the first therapeutic ades, the ‘‘gold standard’’ has changed several times.
guidelines were postulated in which an initial nonresec- Primary resection has become the standard practice, but tional procedure was provided to be the safest plan of fear of anastomotic leakage often deterred many surgeons management. After many years in which resection had from performing primary anastomosis. Therefore, for many become standard practice, today, one century later, again surgeons Hartmann’s procedure (HP) has remained the (laparoscopic) nonresectional surgery is presented as a safe favored option for these patients Nevertheless, and promising alternative in treatment of complicated improvements in surgical techniques, radiological inter- perforated diverticulitis. The question rises what had hap- vention techniques, anesthesia, advances in intensive care medicine, and progress in the management of peritoneal This paper includes a historic summary of sepsis have led to an increasing interest in resection with changing patterns in surgical strategies in perforated div- primary anastomosis (PA) with or without diverting stoma erticulitis complicated by generalized peritonitis.
Recently, laparoscopic lavage and drainage without resection has been successfully used for patients who have generalized peritonitis caused by perforated diverticulitis(PPD) ]. Because this nonresectional mini-invasive sur- Perforation with generalized peritonitis is the most com- gical strategy was associated with a reduction in morbidity mon life-threatening emergency requiring surgical inter- and mortality, it might be a promising alternative to the vention in diverticular disease of the colon . Whereas standard open resectional practice ].
most people with diverticular disease remain asymptom- This paper includes an overview of the development of atic, approximately 15% develop symptoms, and of these different surgical strategies in PPD through the years, and 15% will develop significant complications, such as per- based on this overview we present our personal opinion for foration . In most cases perforation is the first mani- the management of this surgical emergency.
festation of the disease Although the absolute J. Vermeulen (&) Á J. F. LangeDepartment of Colorectal Surgery, Erasmus Medical Center, Since the beginning of the previous century, a three-stage Dr Molewaterplein 40, 3015 GD Rotterdam, The Netherlandse-mail: email@example.com operation strategy was common practice for the treatment of diverticular disease. The first report of surgical treatment for a source of sepsis as bowel contractions continue evacu- complicated diverticulitis was by Mayo [in 1907. The ating infective material. Clinical observations and this new classic three-stage operation includes an initial diverting understanding of pathophysiology of diverticulitis led to colostomy and drainage followed by resection of the the conviction that the colonic perforation had to be involved colon and, finally, a colostomy closure as the third removed primarily , Nevertheless, controversy stage. This nonresectional surgery strategy was reaffirmed persisted because the ‘‘evidence’’ was only based on expert and advocated by the experiences at the Mayo Clinic, which opinion and some (small) noncomparative case series.
presented the results in 1924, to be the safest [ During the next two decades, indications for emergency surgery evolved toward complicated diverticulitis, such as Two-staged procedure with primary resection perforation, obstruction, and fistula formation, only. Apreliminary transverse colostomy was advised in all cases Since the 1980s and 1990s, the standard practice of PPD in which resection was contemplated, and the period of has definitively changed from nonresectional surgery delay before this resection should be from 3 to 6 months toward primary resection of the involved sigmoid. A two- . The rationale for this strategy was that primary stage operation with the initial operation being resection of resection is too difficult in the acute stage of the disease, the diseased segment with the construction of a colostomy often causing iatrogenic complications and hence mortal- proximally and suture closure of the distal rectal stump ity. After the fecal stream was diverged by performing a became the preferred surgical strategy in these category transverse colostomy during the first surgical stage, drain- patients ]. The second stage was represented by the age of the abdomen and pelvic cavity was initiated to colostomy closure. Among surgeons this operation has diminish sigmoid inflammation. After several months the been known since as Hartmann’s procedure (HP), although second stage—resection of the involved bowel—could be Hartmann ] himself only performed such a procedure performed to treat and prevent relapse of the disease.
for rectum carcinoma and had advocated that the patient Smithwick ] advocated this procedure in favor toward should not undergo restoration of bowel continuity.
resectional operations. He reported a postoperative mor- This change in strategy was mainly based on the results tality after a three-stage procedure of nearby 12% com- of two reviews published in 1980 and 1984 by Krukowski pared with 17% if the involved colon segment was resected and Matheson ] and Greif et al. ]. Mortality after during initial surgery ]. Considering that antibiotics primary resection was reported to be lower compared with were not discovered yet, these results can be regarded as those procedures in which the perforated segment could not be removed at initial operation , ]. Unfortunately both In 1945 Florey [was responsible for the development reviews were not systematic, containing a wide range of of penicillin for use as a medicine. Since then antibiotics different surgical techniques and covering more than were more frequently used during colonic surgery. Partly, 25 years during which substantial improvements in antibi- this led toward a shift in the continuing controversy otic and other perioperative supportive therapies has taken between three- and two-staged operations in favor of pri- place. Furthermore, it is not known whether the patients of mary resection of the involved colon. Although at that time both groups were comparable for a number of essential Smithwick ], amongst others, still recommended the variables, such as age, ASA classification, and Hinchey and three-stage and initially nonresectional operation , Mannheim Peritonitis Index (MPI) scores.
more publications advocating primary resection in case of Between 1993 and 2000, two randomized controlled PPD arose –Initial improvement after colostomy trials (RCT) assessing primary versus secondary resection and drainage, without resection, often was followed by were published [These RCTs drew opposite con- severe deterioration several days later when the involved clusions. Kronborg [concluded that three-stage nonre- sectional surgery (suture and transverse colostomy) in PPD Since the 1960s, combinations of antibiotics were used was still superior to primary resection because of a lower against gram-negative bacteria and anaerobic bacteria.
postoperative mortality rate. Mortality in Hinchey IV Combination antibacterial therapy had shown better sur- patients was not different in both groups. Unfortunately, vival in septic patients ]. Unfortunately, mortality rates the study was preliminary stopped because of low in patients with PPD remained high. The basic cause of this recruitment (an average of four patients each year) and high mortality was that the source of infection remained in hence underpowered. A total of 62 patients were included the peritoneal cavity [Painter and Burkitt [docu- and operated by 27 different surgeons during a period of mented the increased intraluminal pressures and muscle abnormalities as the cause for diverticula formation in the Zeitoun et al. ] concluded that primary resection was sigmoid. When left in situ, the perforated segment remains postoperative peritonitis and fewer reoperations. Never- diverting loop ileostomy seems not to diminish postoper- theless, postoperative mortality after primary resection was ative mortality . The use of perioperative colonic lavage higher compared with nonresectional surgery (24% vs.
appears to lower postoperative complications in case of 19%), but this difference was not significant. Although the PA, but the evidence in the present literature is limited evidence was weak, the American Society of Colon and Rectal Surgeons has published practice guidelines in which Postoperative morbidity and mortality rates of patients the three-stage operative approach strategy (nonresectional after emergency surgery for PPD are still high and mainly surgery) was no longer recommended for most patients caused by the poor general condition of the frequently aged because of high associated morbidity and mortality patients and the severity of disease –This suggests As a result of improvements in radiological intervention that further reduction in mortality will require improve- techniques, postoperative complications and ongoing ment in medical management of pre- and perioperative abdominal sepsis could be treated percutaneously, which sepsis and comorbid conditions. Type of surgery seems no made more radical resections during initial surgery possi- longer significantly related with postoperative mortality, ble [HP had become mandatory for emergency indi- although many recent studies favor PA, with or without cations in PPD. But skepticism about primary resection loop ileostomy, instead of HP in purulent of fecal PPD These statements were confirmed by a sys-tematic review by Salem and Flum in which mortalityrates after HP and PA of 19% and 10% respectively, were Improvements in surgical and radiological interventiontechniques and progress in the management of peritoneal sepsis led to an increasing interest in colonic resection withprimary anastomosis (PA) since the 1990s. Although not The role of laparoscopic resectional surgery in PPD is proven in randomized controlled trials, PA with or without limited. In acute complicated diverticulitis without perito- defunctioning loop ileostomy seemed not to be inferior to nitis, laparoscopic sigmoid resection with PA seemed to be HP in terms of severe postoperative complications and a safe procedure ]. Outcome after laparoscopic PA in mortality [, , Probably, even the presence of PPD is lacking in the present literature. Laparoscopic HP fecal peritonitis was no longer considered an absolute seems to be a technically feasible procedure with reason- contraindication to immediate bowel reconstruction able outcomes for patients in this category ]. In 1996, However, fear of anastomotic leakage often deters many Faranda et al. first described a nonresectional laparoscopic surgeons from performing a one-stage procedure (e.g., PA procedure that seemed to be a more promising alternative ]. In patients with peritonitis without gross fecal con- Although HP is considered a two-stage procedure, the tamination, laparoscopic peritoneal lavage, inspection of second stage (reversal of colostomy) will never be per- the colon, and the placement of abdominal drains appear to formed in a large number of patients , Restoration diminish morbidity and improve outcome . In a of bowel continuity after HP is a technically challenging series of 100 patients with PPD, Myers et al. [showed operation and is associated with significant morbidity and excellent results after laparoscopic lavage and drainage of mortality [These rates can be as high as 25% and 14%, the peritoneal cavity, with morbidity and mortality respectively, after colostomy reversal in patients who had undergone HP for PPD , Together with the debilitated Laparoscopic damage control surgery seems to decrease condition of many of these patients, this is one of the main the rate of more radical procedures, including HP [ reasons that HP often results in a permanent colostomy.
In patients who were found to have fecal peritonitis or who They face the physical (leakage, parastomal hernia) and fail to improve after lavage, acute resection should still be psychological (lifestyle alterations) challenges that are performed ]. A comparative study between laparoscopic associated with having a stoma , ]. The risk of per- peritoneal lavage and open PA with diverting loop ileos- manent ileostomy is recognizably less than that of HP and tomy for the management of PPD found no differences in postoperative morbidity and mortality [Laparoscopic The performance of a diverting loop ileostomy has been peritoneal lavage reduced the length of hospital stay and a reported to decrease the rate of symptomatic anastomotic stoma could be avoided in most patients.
leakage in patients operated for rectal cancer . The In a second elective stage definitive surgery can take same is found in case of diverticular peritonitis. However, place, e.g., laparoscopic resection and PA , although the quality of the present studies is poor. Besides, a subsequent elective resection is probably unnecessary [, Nevertheless, the number of studies are rather important [, Nevertheless, because the evidence is limited and mostly based on small groups of patients.
weak, until now primary resection remains the standard Besides, the rates of additional radiological interventions treatment for PPD, although the European Association for and conversion to an open procedure are high [Finally, Endoscopic Surgery Evidence-based Guidelines stated that for many hospitals it will not be possible to have a surgical laparoscopic nonresectional surgery may be considered in team with expertise in colorectal laparoscopic surgery present all the time. Therefore, laparoscopy is of unclear orlimited value in the emergency setting caused by PPD.
However, diagnostic laparoscopy may be useful if no diagnosis can be found by conventional diagnostics [ Some authors have expressed their concerns with lapa- Until the 1990s, all stages of perforated diverticulitis were roscopic nonresectional treatment of perforated diverticu- treated by surgery. The principles of primary treatment of litis. They state that the decision to perform nonresectional abdominal infections caused by perforation, as outlined by surgery is influenced by the surgical access to the abdomen, Polk in 1979 have not changed much during the years.
i.e., laparoscopy, rather than based on evidence in the lit- These principles include alimentary tract decompression, erature [Patients should undergo primary resection, fluid resuscitation, antibiotics to cover gram-negative aer- whether the surgical access to the abdomen is conventional obes and anaerobes, and so-called ‘‘source control.’’ Source or laparoscopic, because there is ‘‘evidence’’ in the litera- control consists of all measurements to eliminate the source ture that resectional surgery leads to lower postoperative of infection, to control ongoing contamination, and to peritonitis, and mortality rates, compared with nonresec- restore premorbid anatomy and its function , tional surgery [Unfortunately, the evidence to The progress of antibiotic development and interven- which they referred —resection favoring nonre- tional radiographic techniques has changed the manage- sectional surgery—is equivocal or to the contrary as stated ment of perforated diverticulitis. The high specificity of CT before. The major criticism of the nonresectional laparo- scan has allowed this modality to become a surrogate to the scopically lavage technique is the continued presence of perioperative assessment made by the Hinchey classifica- the perforated colon as a septic focus as well as the column tion [Furthermore, CT scan has become an important of feces remaining in the colon proximally to the perfora- therapeutic modality. It is now recognized that patients tion as a potential ongoing source of contamination. This with small, contained perforations, who are not systemi- also was the main criticism toward the three-stage proce- cally ill, can be treated initially with antibiotics alone or by dure that was used to treat PPD until the 1970s. Classen CT-guided percutaneous drainage [, Source control et al. had observed that postoperative mortality related to by percutaneous drainage has become the treatment of sepsis was lowered after addition of more effective anti- choice for most abscesses, provided that adequate drainage biotics to treat gram-negative and anaerobic bacteria since is possible and no debridement or repair of anatomical 1970 [Besides, PPD is accompanied by ileus, hence, it structures is necessary [The size of the drain used is is not likely that the fecal column is propelled toward the very important because complete evacuation of the abscess perforation. A patent communication between the colonic must be obtained. If the abscess cannot be drained suffi- lumen and the peritoneal cavity usually cannot be found ciently, source control will fail. Although mechanical during laparoscopy because the site of the original perfo- control of the source of infection remains important, sev- ration has become sealed by the inflammatory process and eral studies have found that abscesses up to 4 cm seem to omentum and seems efficient to control the source of respond better to antibiotics alone [Currently, the contamination. If the perforation site is too large to be only patients who require surgery (laparoscopically or sealed before peristalsis resumes, resection of the bowel open) for source control are those who fail conservative treatment and those who require emergency surgery, The suggestion that nonresectional surgery in combi- nation with more advanced antibiotics have never proven If nonresectional laparoscopic lavage and drainage to to be an inferior strategy could explain the excellent treat PPD is found to be a safe and better alternative for results after laparoscopic lavage in combination with resectional surgery in the future, why should this be dif- modern management of peritoneal sepsis with improved ferent from nonresectional nonsurgical, e.g., CT-guided, antibiotics and intensive care medicine. Naturally the percutaneous lavage and drainage? The present literature as latter technique has several advantages over the open yet does not report about this (hypothetical or future) three-stage procedure, of which less wound complications treatment strategy. Is it possible that this will be the next (such as infections and hernias), no stomal complications, step in the ever more conservative management of different and avoidance of a second operation are the most To answer this question, it is important to take into strategy in contained diverticular perforations, it is not account the main principles of abdominal infection treat- likely that nonresectional interventional radiographic ment when using percutaneous lavage and drainage. Fluid techniques will play a prominent role in the initial treat- resuscitation and modern antibiotic strategies will not be ment of PPD in the near future. Clearly, more (prospective different from laparoscopically lavage procedures. To gain randomized) research is warranted to confirm all of these source control in percutaneous techniques, it is important that large-size catheters will be used for adequate drainageof thick and viscous purulent contents ]. The main This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which per- problem is the inability for inspection of the abdominal mits any noncommercial use, distribution, and reproduction in any cavity to localize the site and size of the perforation. In medium, provided the original author(s) and source are credited.
laparoscopic procedures to treat PPD, careful removal ofadherent omentum or bowel is tried to locate the site ofperforation. If clearly adherent, the adhered omentum or small intestinal loops can be left in place and the abdominalcavity is irrigated with liters of warm saline At the end of 1. Vermeulen J, Gosselink MP, Hop WCJ, Lange JF, Coene PPLO, the procedure, one or more drains are inserted. Such a van der Harst E, Weidema WF, Mannaerts GHH (2009) Hospital careful adhesiolysis and inspection of the abdominal cavity, mortality after emergency surgery for perforated diverticulitis.
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Crackdown on 'off-label' pitches- national law journal- robert brady, meredith manning, and peter spivack
WHITE-COLLAR CRIME Pharmaceutical companies have been penalized for pushing their products for unapproved uses. approved off-label promotion. These cases furtherfor the treatment of osteoporosis in highlight the fact that the DOJ is stronglyand Peter Spivack SPECIAL TO THE NATIONAL LAW JOURNALscrutinizing practices in pharmaceutical,IN A MAJOR SHIFT OF enforcement strategy,“Main Justice