Richard Frothingham, MD

• Associate Professor of Medicine
• Assistant Professor in Molecular Genetics and Microbiology
• Member of the Duke Human Vaccine Institute

https://medicine.duke.edu/faculty/richard-frothingham-md

Although the first human pancreatic islet allografts were performed in 1977 medicine stone music festival residronate 35 mg with amex,12 it was not until 1990 that a pancreatic islet transplant recipient achieved sustained euglycemia off insulin (for 1 year) symptoms ectopic pregnancy purchase residronate 35 mg otc. Although they did not address the added issue of autoimmunity in type 1 diabetes (none of their patients were type 1 diabetics) medicine hat tigers 35 mg residronate buy overnight delivery, this study provided the first evidence of long-term reversal of diabetes after islet allotransplantation treatment 5cm ovarian cyst buy residronate 35 mg low price, with more than 50% of recipients having sustained insulin independence symptoms neuropathy generic residronate 35 mg online, lasting in one case up to 5 years. In 2000 the Edmonton group reported seven consecutive islet transplant recipients, all of whom achieved insulin independence at the end of 1 year without major complications. The remainder are from highly selected non­heart-beating donors or from living donors. Hyperglycemia or need for insulin therapy in the donor at the time of organ procurement is not a contraindication, but it is a minor risk factor for long-term graft loss. Some centers have exclusion criteria for the pancreas based on age (younger than 8 years), body weight (<30 kg), or diameter of the splenic artery (<2 mm). The main limiting factor regarding the effectiveness of the islet isolation is cold ischemia time (12 hours) but preferably less than 8 hours. Otherwise, the current organ allocation system promotes pancreas transplantation over islet transplantation. Therefore, other than in the United Kingdom, each pancreas is offered first to potential whole-organ recipients, and then if rejected, is considered for islet transplant patients. This allocation schema may be changed in the future, after islet transplantation achieves the same effectiveness and status as whole-organ pancreas transplantation, such as currently in the United Kingdom, where there is only one waiting list for islet/pancreas transplant. The next available organ is allocated for pancreas or islet transplantation, depending on the patient on the top of the common list. The gastrocolic ligament is divided to enter the lesser sac and expose the anterior aspect of the pancreas. At this point the pancreas is evaluated for signs of fat infiltration, edema, injury, hematoma, calcification, and tumor. If the organ is still suitable, a Kocher maneuver is performed to expose the inferior vena cava and aorta. If a replaced (accessory) right hepatic artery is present, it may be divided at its origin. Next, the spleen and tail of the pancreas are mobilized to allow for placement of the ice-slush posterior to the gland during perfusion. After the thoracic aorta is cross-clamped, cold preservation solution (most commonly University of Wisconsin or histidine-tryptophan-ketoglutarate) is introduced through cannulas in the inferior mesenteric vein and distal aorta. On completion of organ perfusion, the splenic artery is divided from the celiac trunk; the aorta is divided above and below the origin of the celiac trunk, and the portal vein is divided usually 2. The spleen remains attached to the pancreas to protect the tail during the procurement. Iliac venous and arterial grafts are obtained from the donor for the reconstruction of the pancreas vasculature. Next the pancreas with spleen and duodenum in continuity are placed in a container with preservation solution and placed on ice during transportation. As a result, the immunologic advantage of pancreas transplantation with living-donor transplants in the recent era is no longer as critical as it was before. Moreover, cadaver donors for pancreas transplantation are more available than for other organ transplants, and there is a substantial risk for donors developing diabetes after donation (26%). The splenic artery is divided just distal to its origin, and the splenic vein is divided proximal to its confluence with the superior mesenteric vein. The splenic arterial anastomosis is to the recipient common iliac artery, whereas venous drainage is to the common iliac vein. The pancreatic drainage is accomplished by pancreaticojejunostomy or pancreaticocystostomy. First, the pancreas for islet procurement is more sensitive to warm injury; therefore, the organ should be well flushed with the preservation solution to eliminate blood. Then the organ should be kept constantly surrounded by ice, even during dissection. Next, because no blood vessels are necessary for the isolation, the presence of a right hepatic artery does not preclude pancreas procurement. Instead, it is extremely important during the dissection not to cut or open the pancreas capsule because it compromises enzyme distention, organ digestion, and eventually the yield of the isolation. Because results of the islet isolation depend strongly on proper pancreas preservation, it is hard to overemphasize the importance of the pancreas procurement technique for the success of the islet isolation and then transplantation. During this important procedure, the pancreas vasculature is restored; excess surrounding fat, connective tissue, and the spleen are removed, followed by meticulous ligation of the surrounding blood vessels. This is all done to minimize unnecessary ischemic or bleeding injury, improving the results of pancreas transplantation. The portal vein is available for anastomosis and usually does not require elongation. The standard pancreas graft includes the entire pancreas and the second portion of the duodenum. In this situation, during the same procedure, the pancreas may be transplanted first because it has a shorter "shelf life" (optimal cold storage time is <12 hours vs. The pancreas is usually placed in the right pelvis, as in kidney transplantation, with the arterial anastomosis performed on the recipient common iliac artery. Venous drainage can be connected to the lower vena cava or the common iliac vein (systemic drainage) or superior mesenteric vein (portal drainage). The standard pancreas graft includes the entire pancreas and a portion of the duodenum. It also lowers the concentration of low-density lipoprotein and apolipoprotein B, and free cholesterol, as well as very-low-density lipoprotein. It was postulated based on experimental models that portal venous drainage decreases immunologic response to the graft; however, this was not confirmed clinically. However, clinically the advantages of the portal over systemic drainage in maintaining normal glucose homeostasis or lipid metabolism have never been shown. In cases of a leak from a bladder anastomosis, drainage with a Foley urinary catheter is usually sufficient. During the 1980s 25% of all pancreata were lost because of surgical technical failure. In the case of enteric drainage, intestinal contents leak and cause peritonitis and sepsis. This complication usually requires graft duodenal diversion with a Roux-en-Y limb. From this perspective, bladder drainage has a lower incidence of leakage but also, if it occurs, can be managed conservatively. Graft Pancreatitis Although only the endocrine part of the pancreas is needed to control normoglycemia, whole pancreas grafts have both islets and exocrine tissue. Postoperative pancreatitis may be treated conservatively, but severe cases may require relaparotomy with débridement or occasionally graft pancreatectomy. In addition, repetitive episodes of reflux pancreatitis in bladder-drained recipients are an indication for conversion from bladder to enteric drainage. Hemorrhage Significant intraabdominal bleeding after pancreas transplantation frequently requires relaparotomy; however, less than 0. After the failure of attempts at pancreatic duct ligation and obliteration, the urinary bladder with pancreas-duodenum anastomosis was developed. The advantage of this approach is that amylase concentration in urine allows for monitoring of graft function, enabling early detection of rejection. However, the major disadvantage is metabolic acidosis because of loss of bicarbonate with the relatively large amount of pancreas juice, frequent reflux pancreatitis (50%), cystitis, urinary tract infection, and perineal irritation. Therefore 90% of patients currently undergo enteric drainage for all three categories of pancreas transplantation. It is usually a side-to-side configuration with the loop (most common) or Roux-en-Y limb of the bowel (15% to 20%), either a handsewn double layer or a stapled anastomosis. It seems that enteric drainage has a slightly higher incidence of graft thrombosis than bladder anastomosis: 5. Even transplants between identical twins need immunosuppression to prevent autoimmune recurrence. Large trials tested a steroid-free regimen or minimization of calcineurin inhibitors, showing a slightly increased rejection rate of 20% to 30% without the hopedfor improvement in long-term results. The 1-year survival rate increased from 67% in 1980 to more than 95% in 2005­2009 and to greater than 97% currently. However, other authors reanalyzed the same United Network for Organ Sharing data and found several factors that could bias the previous results. Several patients were listed for many procedures at the same time, and the mortality rate of the patients on the waiting list was underestimated. Currently, we determine a presence of the pancreas graft function in those patients, who do not meet graft failure criteria (defined previously). In this way, those patients who require small amount of insulin support (often due to insulin resistance) are also included in the group of patients with present graft function. It is more often the case after early graft loss that extensive vascular disease and heart conditions may preclude that option. Islet transplantation after failed pancreas transplantation after failed pancreas may be still a very beneficial procedure with minimal risk and great benefit of restoring improved glucose control in long term. However, diabetic patients have also improved quality of life after they have a kidney transplant working, irrespective if they also received a pancreas graft. Abnormal glucose control may be caused also by complications (arterial or venous thrombosis of the graft, pancreatitis, or rejection). Therefore blood glucose levels and insulin requirements should be closely observed in the postoperative period. After the pancreas recovers from perioperative stress, patients typically experience normal fasting and postprandial blood glucose concentrations. Retinopathy Retinopathy can deteriorate in 10% to 35% of patients with unstable eye disease immediately after pancreas transplantation. Most of the patients have already developed advanced retinopathy or blindness at the time of transplantation. The long-term effects of pancreas transplantation on diabetic retinopathy have been conflicting. Despite the morphologic improvement and reduced urinary protein excretion, creatinine clearance usually gradually deteriorates. Early reports demonstrated that the motor and sensory nerve conduction indices increased significantly at all intervals after pancreas transplantation; however, the clinical examination and autonomic tests improved only slightly. In those with mild neuropathy before transplantation, some degree of improvement may be observed. Vascular Disease Macrovascular disease naturally progresses with age, and it is difficult to observe any beneficial influence following pancreas transplantation. However, coronary atherosclerosis can regress in nearly 40% of patients with functioning pancreas grafts. Peripheral vascular disease is usually too advanced to see substantive improvement after pancreas transplant. An intact capsule of the pancreas allows for full distention of the organ and effective digestion in the next step. During enzymatic digestion, the pancreas dissociates into acinar (exocrine tissue) and islets. The final product, purified islets, are tested for bacterial contamination, level of endotoxin, and mycoplasma. Quality tests include purity (>40%), viability (intracellular staining assessed under microscope instantly), and stimulation index (an in vitro functional test assessing the response of the islets to high and low glucose concentration). The final criterion is a sufficient amount of islets after the isolation, so as to benefit the patient. The interventional radiologist first inserts a small (7-French) catheter under ultrasound and fluoroscopy guidance into the main portal vein through a percutaneous, transhepatic approach. Islets (usually 2 to 5 mL; up to 10-mL tissue pellet) are suspended in 200 to 400 mL solution (transplant media) with heparin and human albumin contained in a plastic infusion bag. The procedure starts with portal pressure measurements to ensure absence of portal hypertension. Next, islets are dripped slowly through the intravenous line connecting the harvested islet bag with the portal catheter. Alternatively, it can be done under general anesthesia and in the operating room during a mini-laparotomy with infusion through the mesocolonic vein if percutaneous access via the portal vein fails. Postoperatively, subcutaneous heparin and insulin are administered for at least 2 weeks to promote islet engraftment. Because islets were used in "brittle" type 1 diabetics with preserved kidney function, the main rationale was to improve islet survival and function (thus a steroid-free approach) and protect kidney function (calcineurin inhibitors were minimized). After 5 years of disappointing experience with this approach, many different protocols were developed. Allosensitization Because pancreatic islet allotransplantation usually requires two or three islet infusions from the same number of different donors, there is theoretically an increased risk for allosensitization. With the current technology, we are able to retrieve only 30% to 50% of original islet mass, even from the best cadaveric pancreata. It is also estimated that an additional 50% of islets are being destroyed by the native immunity instant blood-mediated inflammatory response. After 1 to 2 months, after islet engraftment is accomplished, the patient is offered subsequent transplant with a chance of additional benefit-insulin independence (secondary endpoint). If required later, a patient may be offered supplemental islet infusions to maintain insulin independence. Of course, the ultimate goal of the current islet studies is to improve islet isolation and transplantation procedure to achieve insulin independence with only one infusion from a single donor routinely (currently 15% rate in Edmonton). Islet graft function (C-peptide positive) was preserved in 94% of patients with insulin independence rate of 51% at 1-year follow-up. As expected for a new and sophisticated procedure, there have been varied results among centers; therefore the average insulin independence rate might be seen as low. Those few, most experienced centers have reported much higher insulin independence rates, as high as 40% to 50% at 5-year follow-up.

As in the case of right paraduodenal hernias medicine woman residronate 35 mg cheap, it is common for these patients to have some element of malrotation treatment brown recluse bite purchase cheap residronate on line. A local mass effect can cause decreased gastric volume or even gastric outlet obstruction medicine pictures residronate 35 mg with mastercard. Given its association with the common bile duct symptoms of anemia purchase 35 mg residronate free shipping, patients may also present with jaundice medicine natural residronate 35 mg order otc. Because the bowel is isolated from the peritoneum in the lesser sac, frankly necrotic bowel may not present with peritonitis. Children may display a tendency to draw their knees to their chest in this condition, which theoretically reduces tension across the hepatoduodenal ligament. Loops of small bowel will be clustered posterior to the stomach with anterior displacement of the stomach. This can be confused with left paraduodenal hernia on imaging, but the herniated bowel is more superiorly located in the right upper quadrant with displacement of the stomach instead of the transverse colon. The vital surrounding structures afford little leeway with widening of the foramen, although the Kocher maneuver has been used. If a malrotated cecum is present in the hernia, resection is recommended, as it would be with cecal volvulus. Case reports exist that describe suturing of the open aperture to the retroperitoneum, or pexy of the omentum, hepatic flexure, or duodenum into the foramen to block the aperture. Because this aperture usually does not involve a peritoneal covering, or sac, significant lengths of small bowel may herniate, which can quickly lead to strangulation. Treatment involves reduction of the herniated contents, closure of the aperture, and resection of necrotic bowel, if necessary. Improper development can lead to varying degrees of defects in the sigmoid mesentery. Simply redundant sigmoid colon may also have redundant sigmoid mesentery, which can form a pseudo sac into which bowel may herniate and be trapped. A defect in one leaf of the mesocolon may create a true sac which bowel can fill, blocked by the other leaf of mesentery. Lastly, a through-and-through mesenteric defect can obviously allow sizeable lengths of bowel to herniate. Diagnosis on imaging is difficult, but loops of small bowel in the left lower quadrant that displace the sigmoid colon anteriorly or medially may be apparent. The increasing prevalence of patients with gastric bypass anatomy makes awareness more imperative. Diagnosis in a patient with acute abdominal pain requires prompt surgical response because bowel ischemia and necrosis can develop rapidly, as with other hernias. Although surgeons are well aware of the acquired type of transmesenteric hernia after bowel anastomosis, the congenital form is quite rare. It is most likely due to failure of proper mesenteric development secondary to ischemic insult in utero, similar to the pathogenesis of intestinal atresia. This is supported by the most common associated anomaly, intestinal atresia, which is found in 50% of infants presenting with transmesenteric hernia. Although this may occur anywhere along the length of the mesentery, the most commonly encountered locations involve the pericecal mesentery, the sigmoid mesentery, and the duodenojejunal junction. Congenital and acquired internal hernias: unusual causes of small bowel obstruction. Laparoscopic gastric bypass, Roux-en-Y- 500 patients: technique and results, with 3­60 month follow-up. As described earlier, failure of proper development of the pericecal mesentery, likely due to an ischemic event in utero, allows the presence of an aperture through which small bowel may herniate. Causes and timing of nonelective reoperations after bariatric surgery: a review of 1304 cases at a single institution. Laparoscopic Roux-en-Y gastric bypass patients have an increased lifetime risk of repeat operations when compared to laparoscopic sleeve gastrectomy patients. Modification of internal hernia classification system after laparoscopic Roux-en-Y bariatric surgery. Internal hernias after laparoscopic Roux-en-Y gastric bypass: incidence, treatment and prevention. Small bowel obstruction after laparoscopic Roux-en-Y gastric bypass: a review of 9,527 patients. Laparoscopic antecolic Roux-en-Y gastric bypass with closure of internal defects leads to fewer internal hernias than the retrocolic approach. Bowel obstruction rates in antecolic/antegastric versus retrocolic/retrogastric Roux limb gastric bypass: a meta-analysis. Pregnancy following gastric bypass for morbid obesity: effect of surgery-to-conception interval on maternal and neonatal outcomes. Intussusception complicating pregnancy following laparoscopic Roux-en-Y gastric bypass. Internal hernia in pregnant women after gastric bypass: a retrospective register-based cohort study. Acute intestinal obstruction secondary to left paraduodenal hernia: a case report and literature review. Congenital mesenteric defect: description of a rare cause of distal intestinal obstruction in a neonate. Gastric outlet obstruction from a caecal volvulus, herniated through epiploic foramen: a case report. Crohn disease is characterized by transmural inflammation that can involve any part of the gastrointestinal tract, from mouth to anus, and presentations of the disease vary widely. As such, a multidisciplinary team approach to care, including specialized experts in gastroenterology, surgery, and radiology is essential to ensure these patients receive current, appropriate, and high-quality care. An imbalance in this system is thought to play a role in the pathophysiology of Crohn disease. Specifically, a Western style diet including processed, fried, low-fiber, and sugary foods has been implicated in the development of Crohn disease. In addition to the overall risk of developing Crohn disease within families, there appears to be concordance in the location. A variety of genes affecting the adaptive and innate immune systems and epithelial function can all lead to colitis, and a single gene alteration can lead to variable clinical presentations depending on the mouse strain. There is an overall female predominance in Crohn disease; however, there is no current evidence that there is a hormonal effect on disease expression. Although there is no cure for Crohn disease at this time, great advances in medicine and surgery have aided in reducing the symptoms and suffering of these patients. In addition, complex alterations in local and systemic immune response lead to varying presentations of Crohn disease. Disease severity varies widely from asymptomatic, posttreatment remission to asymptomatic, mild, moderate, or severe active disease. Cohort studies have found that only 10% to 20% of patients with Crohn disease have prolonged remission after their initial presentation with active disease. Surgical care is reserved for patients who do not respond to medical therapy or those who develop complications. Less than 2% of patients have been reported to undergo an intestinal operation within the first year of diagnosis; however, this rate increases over time to up to 17% at 5 years and 28% at 10 years after diagnosis. The relapsing and remitting course of Crohn disease requires that patients understand the need to seek medical attention if they are having symptoms requiring urgent attention. Importantly, remission of the disease improves quality of life, whether it is achieved through medical or operative management. The cost of this chronic disease should also be understood by clinicians in an effort to understand the burden placed on patients. As a chronic disease, Crohn disease is very costly due to the direct expenses of medical and surgical treatments and hospitalizations. However, one should not overlook the indirect and opportunity costs from the disease due to days missed at work by the patient, as well as their caretakers. Similar to other chronic diseases, being aware of this cost is important because the financial hardship placed on patients and families can affect compliance with treatment or cause delays in presentation for medical care leading to poorer outcomes. This variability in disease presentation makes diagnosis difficult in some patients. The majority of patients (70%) are diagnosed within 1 year of symptom onset; however, 14% of patients have a delay in diagnosis of 5 years. This is especially true in older patients who are less likely to be referred to specialty clinics. Complications are common long term, with 94% of terminal ileal disease patients and 78% of colonic disease patients experiencing a complication at 20 years. Abdominal pain is usually mild and diffuse with inflammation but can be colicky with underlying obstruction of the small or large bowel. Patients with obstruction often also present with nausea, vomiting, and abdominal distention. Diarrhea is a common complaint in patients with Crohn disease and can have several etiologies. Impaired fluid absorption by inflamed bowel segments can lead to diarrhea from excessive intraluminal fluid content. Terminal ileal inflammation or resection can lead to bile salt malabsorption and subsequent diarrhea. Finally, patients who have lost a large portion of their small bowel through disease and/or surgical resection can exhibit steatorrhea due to bile salt deficiency, leading to fat malabsorption. Fistula formation is a common complaint in patients, with Crohn disease with one-third of patients developing a fistula within 10 years of disease presentation and half of patients developing a fistula within 20 years of disease presentation. The most common sites for fistulas in Crohn disease are enterovesical (intestine to bladder), enterocutaneous (intestine to skin), enteroenteric (intestine to intestine), and enterovaginal (intestine to vagina). Severe, acute hemorrhage in patients with Crohn disease is rare (<10% of patients). Bleeding most commonly occurs in patients with colon disease, but it can occur in patients with inflammation in any location of the gastrointestinal tract. This problem is addressed elsewhere in this book; however, it is important to note that perianal involvement occurs in 10% of patients as the initial symptom of disease and is the sole location of disease in approximately 5% of patients. Approximately 30% of Crohn patients will experience perianal disease at some point in their disease course. Weight loss can occur due to malnutrition from malabsorption of diseased bowel segments or due to anorexia from the systemic immune response. It is important to be mindful of this potential problem when considering resection of the small bowel in operative management of this disease. This is especially important in patients who present with Crohn disease requiring surgical interventions at a young age. Fatigue and malaise are also common complaints that are thought to occur due to an imbalance in inflammatory mediators and immune cells in the systemic circulation. Fever can occur due to ongoing inflammation and dysregulation of the immune system; however, it is important to note that high fevers could be due to active infections, such as uncontrolled abscesses. Extraintestinal manifestations of Crohn disease are reported with wide overall incidence (6% to 40%), depending on the study population. The most common extraintestinal manifestations are arthritis (20%), eye involvement. Standard tests that are routinely obtained for patients being considered for Crohn disease diagnosis include complete blood count, blood chemistry (including electrolytes, renal function tests, liver enzymes, and blood glucose), erythrocyte sedimentation rate, C-reactive protein, serum iron, and vitamin B12 levels. General laboratory findings in patients with active inflammation include an elevated white blood cell count, platelet count, erythrocyte sedimentation rate, and C-reactive protein. All of these studies lack specificity but can be helpful in monitoring patients for changes in the level of inflammation of the disease over time. For example, anti-Saccharomyces cerevisiae antibodies are found in 48% to 69% of patients with Crohn disease and 5% to 15% of patients with ulcerative colitis. Perinuclear antineutrophil cytoplasmic antibodies are found in only 5% to 20% of patients with Crohn disease and 48% to 82% of patients with ulcerative colitis. In addition, the anti-OmpC antibody has been identified in 46% of patients with Crohn disease. Mutations in this gene are infrequent in patients with Crohn disease, and the inheritance pattern of the gene is not strictly mendelian. These are increasingly being used in clinical practice, especially as an indication of acute inflammatory activity. There are endoscopic scoring systems that have been developed to describe the severity of Crohn disease as seen on endoscopy. These four characteristics are scored from 0 to 3 in each area of the large intestine (rectum, left colon, transverse colon, or right colon) and ileum. This scoring system has been found to be reproducible among providers; however, there is no agreement on a cutoff score to define disease remission. Another scoring system, the Rutgeerts score, is used to grade lesions recurring at the site of an anastomosis or neoterminal ileum. This score is meant to predict the likelihood of symptomatic recurrence of Crohn disease after curative resection. During the course of this 8-hour study, two images are acquired every second, yielding around 50,000 images in total. Patients are able to continue their normal daily activities while the images are being obtained. Movement of the capsule through the gastrointestinal tract relies upon peristalsis and complete evaluation of the small intestine is achieved in 65% to 80% of patients. Patients with suspected intestinal strictures are recommended not to undergo this study because the capsule may not be able to pass through the narrowing, necessitating surgical removal. Patency capsules to test for severe narrowing due to strictures can be used prior to use of this technology to ensure that it will not become lodged during the examination. Actual reported rates of surgical or endoscopic retrieval of wireless endoscopy capsules due to stricture are as low as 0% to 15% in studies of Crohn disease patients.

Cystoduodenostomy Cystoduodenostomy is rarely necessary daughter medicine buy discount residronate 35 mg on-line, except when the pseudocyst is located at the pancreatic head and immediately abutting the duodenal wall symptoms 12 dpo residronate 35 mg buy low cost. A longitudinal duodenotomy should be used to expose the medial wall of the duodenum treatment carpal tunnel 35 mg residronate order amex. An aspirating needle can be used to identify the area of nearest apposition of the pseudocyst to the duodenal wall medications parkinsons disease order 35 mg residronate. When creating the 2- to 3-cm-long cystoduodenostomy treatment vitiligo 35 mg residronate order with visa, caution must be taken to avoid injury to the gastroduodenal artery, as well as the common bile duct or the main pancreatic duct. If those structures impede clear access to the pseudocyst from the medial duodenal wall, a cystojejunostomy may be preferable. Interrupted hemostatic sutures can be placed along the cystoduodenostomy if there is any bleeding from intervening pancreatic parenchyma. The lateral duodenotomy is then closed in one or two layers and a closed-suction drain may be placed per surgeon preference. Historically, a lateral side-to-side cystoduodenostomy has a high rate of morbidity and mortality related to anastomotic dehiscence and abscess formation, and therefore it should rarely (if ever) be performed. Nealon and Walser studied 103 patients with pseudocyst and chronic pancreatitis with a main pancreatic duct diameter of greater than 7 mm who received longitudinal pancreaticojejunostomy (Puestow procedure) alone for duct drainage or surgical cystojejunostomy combined with duct drainage. The wall of the pseudocyst must be mature and thick enough to hold suture for anastomosis, which is typically true more than 6 weeks after the initial appearance of the pseudocyst. In chronic pancreatitis, surgery for a pseudocyst may proceed as soon as any acute inflammation has subsided. Given the usual significant inflammation from the antecedent pancreatitis, dissection around the pseudocyst should be minimized whenever possible. If there is any concern about the possibility of a cystic neoplasm, a full-thickness biopsy of the cyst wall can be excised where the anastomosis will be performed and sent for immediate frozen section evaluation. Residual debris or necrotic material within the pseudocyst cavity should also be gently suctioned or debrided prior to anastomosis. Cystogastrostomy, Roux-en-Y cystojejunostomy, or cystoduodenostomy are options for internal drainage depending on the anatomic location of the pseudocyst. Especially in cases of giant pseudocysts, the anastomosis should be located to optimize dependent drainage of the pseudocyst. External drainage can result in a prolonged pancreaticocutaneous fistula, but may be necessary in emergent septic situations when a more definitive or extensive intervention is not prudent. Cystogastrostomy When the anterior pseudocyst wall is seen to be directly opposed to the posterior stomach wall from its location in the lesser sac, generally cystogastrostomy is the internal drainage procedure of choice. This technique involves a longitudinal gastrotomy at the level of the anterior wall of the stomach, typically in the body. The bulge of a large pseudocyst can be visualized by pressing into the posterior stomach wall, or an aspirating needle can be used to localize a smaller lesion. The pseudocyst is entered by incision (or excisional biopsy) of the posterior stomach wall at least 3 cm long and the pseudocyst contents are suctioned out. There were no pseudocyst recurrences in the cohort with duct drainage alone over a mean follow-up of more than 5 years, and 89% of patients had complete resolution of their preoperative pain symptoms. Toward the end of this study, the index pseudocyst was addressed by a single intraoperative aspiration during the ductal drainage procedure. There are data that suggest surgical intervention in chronic pancreatitis may be more efficient and effective for pain relief than endoscopic interventions. Pancreatic Resection Partial pancreatic resection is generally not considered the first option in the treatment of pseudocysts because of the resultant decrease in pancreatic endocrine and exocrine function and the more extensive surgical dissection required in an area of chronic inflammation and fibrosis. Patients with a small pancreatic remnant less than 6 cm long and the presence of splenic vein thrombosis were most likely to have distal pancreatectomy and splenectomy. Other patients treated via resection of the left pancreatic remnant had a small pancreatic duct unsuitable for anastomosis. Pseudocysts in the pancreatic head of patients receiving surgery for symptoms of chronic pancreatitis may be removed along with a duodenum-preserving pancreatic head resection or Whipple procedure, to ensure postoperative pain relief. Disconnected pancreatic duct syndrome: disease classification and management strategies. As discussed earlier, if preoperative imaging and sampling of cyst fluid from a pancreatic lesion cannot exclude a cystic neoplasm and confirm the diagnosis of pseudocyst, then resection may be necessary. External Drainage Open external drainage of a pseudocyst often creates a controlled pancreaticocutaneous fistula and is associated with delayed closure of the fistula, depending on the degree of communication with the underlying pancreatic duct. When emergent surgery is undertaken to control hemorrhage or peritonitis from pseudocyst rupture, external drainage may be the most expedient temporizing action. If the pseudocyst wall is unexpectedly too thin and immature for anastomosis, external drainage can be performed. In operations when a planned internal drainage procedure is anatomically unachievable due to adhesions, then external drainage of the pseudocyst is a reasonable "bailout" option. If an infected pseudocyst is encountered at the time of necrosectomy for an acute necrotic collection, external drainage of the pseudocyst is also warranted. Once adequately drained, the pseudocyst cavity obliterates and fuses to the wall of the organ to which it was anastomosed. These modern series demonstrate the continued importance of surgical treatment for pancreatic pseudocysts. No Endoscopic or surgical internal drainage procedure Yes Surgery Duct wide enough for anastomosis Yes Endoscopic or surgical cystogastrostomy or cystoduodenostomy or cystojejunostomy No Yes Transpapillary pancreatic duct stent placement No Successful decompression of pseudocyst Additionally, prior catheter drainage from a percutaneous or surgical intervention for pancreatitis may lead to an external pancreatic fistula. Severe disruption of the pancreas from blunt or penetrating trauma can also cause an internal pancreatic fistula. Pseudocysts managed without intervention can progress to rupture less than 5% of the time and form an internal pancreatic fistula. Although this event can occasionally be detected through sudden symptoms of pain, hemorrhage, or chemical peritonitis requiring emergent intervention, more often the internal fistula develops silently and is detected as symptoms of abdominal discomfort, shortness of breath, or bowel obstruction slowly progress. These patients usually had a residual pseudocyst cavity suitable for cystojejunostomy, but 18% required fistula tract­jejunostomy due to prior collapse of the pseudocyst and 11% required distal pancreatectomy because the fistula emanated from a disconnected left pancreatic remnant. The external drain (D) is injected with contrast medium, which opacifies an area of walled-off pancreatic necrosis (N), the fistula (arrow), and descending colon (C). Pancreaticocolonic fistulas secondary to severe acute pancreatitis treated by percutaneous drainage: successful nonsurgical outcomes in a single-center case series. Although in some cases this can lead to fortuitous decompression and resolution of a pseudocyst or walled-off pancreatic necrosis, the inflammatory process of fistula formation more typically causes hemorrhage or sepsis from infected pancreatic necrosis. A pancreaticoenteric fistula may develop de novo or as a complication following manipulation by necrosectomy or closed drainage. In a recent study of 311 patients with acute pancreatitis and infected necrosis, 38% developed pancreaticoenteric fistulas and 61% of fistulas involved the colon. Fluid analysis is the key to the diagnosis of pancreatic ascites or pancreaticopleural fistula, because these types of internal pancreatic fistula are classically the sequelae of an indolent course of chronic pancreatitis and only a minority of these patients will present with abdominal pain or tenderness on physical exam to suggest pancreatic pathology. Note the large left pleural effusion with enhancing rim (thin red arrow in [A]), periaortic fistulous tract extending from abdomen into mediastinum (bold red arrows in [B] and [C]), and pancreatic pseudocyst deep to the dilated main pancreatic duct (green arrow in [D]). Diet restriction and parenteral nutrition are often employed to reduce fistula output, although nasojejunal feeding that minimizes pancreatic stimulation may be preferable as long as it does not increase fistula output. Octreotide and other antisecretory medications may decrease the volume of fistula output, but they have not shown a consistent benefit in shortening the time to fistula closure. Fistula Tract­Jejunostomy Roux-en-Y fistula tract­jejunostomy is recommended for treatment of recalcitrant nonhealing external pancreatic fistulas when pancreatic resection can be avoided, due to its associated decrease in morbidity and mortality (compared to resection). Peritoneal tap showed an amylase level of 20,000 U/L, consistent with pancreatic ascites. Although many authors report waiting at least 6 months prior to fistula tract­jejunostomy, Bassi et al. Distal Pancreatectomy For internal pancreatic fistulas, as with other cases of disconnected pancreatic duct syndrome, distal pancreatectomy can be performed if the pancreatic fistula originates close to the tail of the pancreas. Roux-en-Y cystojejunostomy is suitable if the fistula involves a mature pseudocyst. Roux-en-Y pancreaticojejunostomy is indicated if the proximal pancreatic duct requires decompression or if the fistula tract is too thin to support an anastomosis. After necrotizing pancreatitis, once a pancreaticoenteric fistula is controlled with external drainage, it may warrant a longer period of nonoperative and endoscopic management prior to surgery. One exception to this rule is a pancreaticocolonic fistula, in which case a temporary proximal stoma for fecal diversion or a segmental colon resection is often necessary to sufficiently control the fistula output and mitigate the development of worsening sepsis. Pseudocysts are often present in patients with chronic pancreatitis and splenic vein thrombosis, as seen in 89% of patients in a single-institution review of the natural history of pancreatitis-induced splenic vein thrombosis. Only 53% of splenic vein thrombosis patients had gastric or esophageal varices present and only 52% went on to manifest splenomegaly. Within this meta-analysis, four out of seven studies published since 1997 showed a 0% rate of spontaneous bleeding. Thus it seems that splenic vein thrombosis in the context of pancreatitis is less consequential than in patients with cirrhosis or cancer. Splenic vein thrombosis is usually an incidental finding on abdominal imaging for patients with chronic pancreatitis, and neither routine anticoagulation nor prophylactic splenectomy is recommended. If esophagogastric variceal bleeding from leftsided portal hypertension occurs, splenectomy is the definitive treatment. Splenic artery embolization is another option for symptomatic patients medically unfit for surgery. Some authors have argued that splenic vein thrombosis patients with asymptomatic gastric varices undergoing pancreatic surgery for another indication (chronic pain, pseudocyst, etc. Rarely in the setting of acute necrotizing pancreatitis there will be direct erosion by a pseudocyst or necrotic collection into a major vessel such as the portal vein or splenic artery. More commonly, pseudoaneurysms will form adjacent to a pseudocyst or an area of pancreatic necrosis due to enzymatic breakdown of a small arterial wall from contact with pancreatic secretions. Late hemorrhagic complications including pseudoaneurysm, diffuse bleeding from pancreatic necrosis, and pseudocyst bleeding appear to complicate 1% to 4% of pancreatitis cases. In a series by Balthazar and Fisher, these complications typically presented late, anywhere from 2 months to 8 years (mean 2. Coil embolization is the usual technique, but stent placement can be used if the target artery cannot be sacrificed, such as with a common hepatic or proper hepatic artery pseudoaneurysm. Pseudoaneurysm communication with the gastrointestinal tract or exposure to pancreatic juice over time may lead to infection and rebleeding. Emergent surgery has an important role for control of bleeding when a patient is hemodynamically unstable or when attempted angiographic embolization of the bleeding vessel is unsuccessful. Proximal and distal ligation of the bleeding vessel is usually the most expedient procedure, although limited pancreatic resection may also be performed. Obstruction due to pseudocyst compression can occur anywhere along the gastrointestinal tract from the stomach to the colon. After pseudocyst decompression, obstruction should resolve unless the pathophysiology of pancreatitis has caused adjacent ischemia and fibrosis. In rare cases, infarction of the mesentery or bowel wall has caused intestinal necrosis or perforation requiring emergent resection and proximal stoma. It is important to have a multidisciplinary approach to treatment including surgeons, endoscopists, radiologists, and interventional radiologists. Understanding the status of the main pancreatic duct is essential for selecting the optimal therapies. There are many scenarios in which surgery remains the most efficient and effective treatment strategy. Incidence, risk factors and clinical course of pancreatic fluid collections in acute pancreatitis. Incidental pancreatic cysts: clinicopathologic characteristics and comparison with symptomatic patients. Association between advances in high-resolution cross-section imaging technologies and increase in prevalence of pancreatic cysts from 2005 to 2014. Pancreatic pseudocysts: a proposed classification and its management implications. A unifying concept: pancreatic ductal anatomy both predicts and determines the major complications resulting from pancreatitis. Selected management of pancreatic pseudocysts: operative versus expectant management. Pancreatic pseudocysts following acute pancreatitis: risk factors influencing therapeutic outcomes. Equal efficacy of endoscopic and surgical cystogastrostomy for pancreatic pseudocyst drainage in a randomized trial. Endoscopic transmural drainage of peripancreatic fluid collections: outcomes and predictors of treatment success in 211 consecutive patients. Percutaneous drainage of pancreatic pseudocysts is associated with a higher failure rate than surgical treatment in unselected patients. A national comparison of surgical versus percutaneous drainage of pancreatic pseudocysts: 1997­2001. Surgical management of complications associated with percutaneous and/or endoscopic management of pseudocyst of the pancreas. The effect of size of giant pancreatic pseudocysts on the outcome of internal drainage procedures. Duct drainage alone is sufficient in the operative management of pancreatic pseudocyst in patients with chronic pancreatitis. Pancreatic pseudocysts complicated by splenic parenchymal involvement: results of operative and percutaneous management. Laparoscopic and endoscopic approaches for drainage of pancreatic pseudocysts: a systematic review of published series.

A Kocher maneuver is performed by elevating the duodenum and head of the pancreas out of the retroperitoneum symptoms strep throat cheap 35 mg residronate overnight delivery. The gallbladder is mobilized out of the gallbladder fossa and the cystic duct and artery are divided medications via g tube residronate 35 mg buy with mastercard. The portal structures should be assessed during these maneuvers to determine if a replaced right hepatic artery originating from the superior mesenteric artery is present medicine vials buy residronate us. The common hepatic duct is encircled and divided close to the level of the cyst duct entry site early in the operation symptoms quiz buy genuine residronate. The bile duct is retracted caudally medications qd buy 35 mg residronate overnight delivery, and a dissection plane is opened on the anterior surface of the portal vein. After the plane anterior to the portal vein and superior mesenteric vein is complete, a Penrose drain can be looped under the neck of the pancreas. The mesenteric vasculature to the third and fourth portions of the duodenum and divided jejunum is carefully divided. Once the distal duodenum and proximal jejunum are separated from their mesentery, it can be delivered dorsal beneath the superior mesenteric vessels from the left to the right side. Stay sutures are placed superiorly and inferiorly on the pancreatic remnant to reduce bleeding from the segmental pancreatic arteries. The Penrose drain placed previously under the neck of the pancreas is used to elevate the pancreatic tissue during division, thus protecting the underlying major veins. The main pancreatic duct should be identified so that it can be incorporated into the subsequent reconstruction. The portal vein and superior mesenteric veins are then rolled out of the vascular groove. The specimen is then removed by dividing the uncinate process of the pancreas from the superior mesenteric artery. This is accomplished by serially clamping, dividing, and tying the smaller vascular branches of the superior mesenteric artery and should result in skeletonization of the superior mesenteric artery for at least 180 degrees. The pancreatic neck margin, uncinate margin, and common hepatic duct margins are marked for pathologic examination. There are multiple options for reconstruction, with the most common involving creation of a pancreaticojejunostomy to the divided jejunum, followed by hepaticojejunostomy and then gastrojejunostomy. Controversy exists regarding the best type of pancreaticojejunostomy, the use of pancreatic duct stents, and the use of adjuncts such as fibrin glue or somatostatin analogues. The pancreatic anastomosis can be performed with an invagination technique or a duct-to-mucosa anastomosis. With either technique, the proximal jejunal stump is brought through a defect in the mesocolon to the right of the middle colic artery. The duct-to-mucosa anastomosis is constructed in an end-to-side fashion in which the outer row consists of interrupted 3-0 silk sutures that incorporate the capsule of the transected pancreas and seromuscular bites of the jejunum. A small defect is then made in the jejunum to which a duct-tomucosa anastomosis is performed that incorporates the pancreatic duct and the full thickness of the jejunum with interrupted 5-0 absorbable monofilament suture. Some surgeons prefer to stent this anastomosis with a 6-cm pediatric feeding tube. Three centimeters of the stent is placed in the pancreatic duct, and the other half is placed in the jejunum. This stent typically passes through the intestinal tract and into the stool within a couple of weeks. The invagination technique is performed with an endto-end or end-to-side pancreaticojejunostomy. The pancreatic remnant is circumferentially cleared and mobilized for 2 to 3 cm to allow for an optimal anastomosis. The pancreaticojejunostomy is performed in two layers, with the outer layer consisting of interrupted 3-0 silk sutures that incorporate the capsule of the pancreas and the seromuscular layers of the jejunum. The inner layer consists of running 3-0 absorbable suture that incorporates the capsule and a portion of the cut edge of the pancreas and the full thickness of the jejunum. An attempt should be made to incorporate the pancreatic duct into the inner layer for several bites to splay it open. When completed, this anastomosis invaginates the cut surface of the pancreatic neck into the jejunal lumen for several centimeters. The stomach can also be used to reconnect the pancreas with an invagination method similar to the one described for the jejunum. The biliary anastomosis is performed next with an end-to-side hepaticojejunostomy approximately 5 to 10 cm distal to the pancreaticojejunostomy. This anastomosis is performed with a single layer of interrupted absorbable suture. Finally, the last anastomosis, either a duodenojejunostomy or gastrojejunostomy, is performed depending on whether the pylorus has been preserved. This anastomosis can be performed 10 to 15 cm distal to the hepaticojejunostomy, proximal to the portion of jejunum traversing the defect in the mesocolon. Alternatively, it can be performed in antecolic fashion more distally on the jejunal limb, distal to where it traverses the mesocolic defect. At the end of the operation, closed suction drains are left in place near the pancreatic and biliary anastomoses. Some groups prefer not to drain and accept that if a fluid collection becomes clinically evident postoperatively, percutaneous drainage by interventional radiology may be required. The drains around the pancreatic anastomosis are typically removed once the patient has been on a regular diet without any significant output of amylase-rich or bilious fluid. However, given the technical demands of this operation, it is primarily limited to high-volume centers. The hepatic artery is identified and dissected with the hook cautery to find the takeoff of the gastroduodenal artery, which is a landmark for the portal vein below. At this point, the inferior portion of the pancreas is dissected looking for the superior mesenteric vein. Earlier identification of the portal vein helps with superior mesenteric vein identification. Once found, the tunnel is created under the neck of the pancreas with gentle blunt dissection and encircled with an umbilical tape. Once the tunnel under the pancreas neck is created, the gallbladder is mobilized and used to find the common bile duct, which is encircled with a vessel loop prior to transection. Following the resection of the common bile duct, the Kocher maneuver can be started by mobilizing the duodenum staying close to the bowel. After the extended kocherization is complete, the distal jejunum is identified 30 to 40 cm distal to the ligament of Treitz and transected with a stapler. The stapled ends of the jejunum are sewn to each other with a 25-cm silk stitch with a large gap to facilitate pulling the distal jejunum through the ligament of Treitz for future anastomosis. Next, the colon is lifted and the ligament of Treitz is freed with a hook cautery and the antrum is divided with a stapler. As the specimen is pulled to the right upper quadrant, the previously sewn jejunal limb will be pulled through the ligament of Treitz defect into proper place for pancreatic and biliary anastomosis. Reconstruction of the three anastomoses can now be done with the jejunum already in proper position. These anastomoses are done similar to the open technique requiring intracorporeal stitches. The pancreatic anastomosis can be done from the duct to the mucosa or using the invagination technique. The hepaticojejunostomy is done with interrupted suture with the assistant holding the bowel up to facilitate this step. The final gastroduodenojejunal anastomosis can be done in a two-layered intracorporeal sewn fashion or stapled. Staging laparoscopy is advocated for patients with distal pancreatic cancer because carcinomatosis is a more common finding in patients with cancers of the body and tail. Exposure is provided by a vertical midline incision from the xiphoid process to several centimeters below the umbilicus. The lesser sac is entered by elevating the greater omentum off the transverse colon. The splenic flexure of the colon is then mobilized caudally and away from the spleen by dividing the splenocolic ligament. Splenectomy is usually performed with distal pancreatectomy in patients suspected of having carcinoma to obtain better margins, and to remove the lymph nodes at the tip of the pancreas and the hilum of the spleen. However, for some limited benign pancreatic diseases, the spleen can be preserved. The spleen is mobilized toward the midline by dividing the splenorenal ligament with the electrocautery device. A plane is then developed behind the pancreatic tail and body to also mobilize and control the splenic vein. This dissection is continued until an adequate margin is reached beyond the tumor. The electrocautery device is next used to transect the pancreatic parenchyma distal to this suture line. A row of overlapping "U" stitches of absorbable suture should then be placed to control the transected remnant. If the main pancreatic duct can be identified, it should be suture ligated with an absorbable monofilament suture. A frozen section should be performed on the pancreatic margin to confirm clearance of the lesion prior to completion of the operation. If an operative drain is left in place, it is monitored for signs of a pancreatic leak. Removing the spleen does place the patient theoretically at increased risk for postsplenectomy sepsis, and vaccines are given preoperatively or after recovery for pneumococcus, Neisseria meningitidis, and Haemophilus influenzae. In recent years, the laparoscopic approach has become a standard method to perform a distal pancreatectomy with or without splenectomy. Laparoscopic distal pancreatectomy has been demonstrated to have similar outcomes without any increase in morbidity or mortality when compared to the open approach. However, several postoperative complications continue to be frequent after pancreatic resection. With these interventions, symptoms will typically resolve and the majority of patients are able to tolerate an oral diet. Grade B pancreatic fistulas occur in patients who generally appear well, but may require parenteral nutrition or fistula drainage for the fistula to heal. The most severe form are grade C fistulas, in which patients appear ill and require parenteral nutrition, interventional drainage, and potentially even reoperation for treatment. Conversely, severe hemorrhage involves large-volume blood loss evidenced by a hemoglobin drop of greater than 3 g/dL and requires urgent intervention to treat. Early hemorrhage occurs within 24 hours of surgery, whereas late hemorrhage is defined as occurring on or beyond 5 days after surgery. Late bleeding is usually caused by a pseudoaneurysm formed by a pancreatic fistula or nearby infection, leading to erosion of the vasculature by amylase-rich fluid. Surgical exploration and control is reserved for instances in which the patient is too unstable for interventional radiology or in whom embolization is unsuccessful. In addition, improved 5-year survival is seen for patients with well-differentiated tumors, negative lymph nodes, and negative (or R0) resection margins despite the tumor type. Median and overall survival at 5 years is higher for patients with right-sided lesions in the pancreatic head when compared to left-sided pancreatic cancers. It is estimated that as many as 80% of patients with pancreatic malignancies will present with unresectable or metastatic disease. As a result, a combination of operative and nonoperative management is usually required for symptom management. In the majority of patients, nonoperative palliation is the first choice in treatment, with surgery reserved for patients unable to be adequately managed by these methods. The three main symptoms necessitating palliation are obstructive jaundice, gastric outlet obstruction, and pain. Often, this obstruction will lead to symptoms such as jaundice, abdominal discomfort, pruritus, and nausea. Many patients will require endoscopic or surgical decompression of the biliary tract to relieve obstruction, mitigate symptoms, and improve quality of life. This is accomplished by surgical resection of the primary tumor in patients with early stage, resectable disease. However, for patients with metastatic or unresectable periampullary tumors, this requires biliary stenting or surgical bypass. Endoscopic stenting involves the placement of a metallic or plastic stent into the biliary tree to provide passage of bile through the area of obstruction. Plastic stents were historically used but required periodic replacement and were more prone to occlusion and migration. As a result, self-expanding metallic stents have been more commonly used in recent years. These have a larger diameter when compared to plastic stents and are less likely to occlude. However, these can fail due to tumor ingrowth, presenting a problem because they are not readily changeable and cannot be removed after placement. Alternatively, surgical bypass by hepaticojejunostomy, cholecystojejunostomy, or choledochojejunostomy can be performed providing a direct communication between the biliary tree and the small bowel to bypass the obstruction. The most effective operation is hepaticojejunostomy, which is performed by removing the gallbladder and circumferentially dissecting the common hepatic duct near the bifurcation. Hepaticojejunostomy has a lower rate of failure compared to other surgical methods. Cholecystojejunostomy has a higher chance of recurrent biliary obstruction and obstructive jaundice given that the insertion site of the cystic duct into the common bile duct is often close to the site of the original obstruction. However, surgical bypass tends to be reserved for patients who are fit for surgery and have failed endoscopic means to relieve obstruction. Most studies are retrospective and include only a small number of patients, although a limited number of early randomized controlled trials were performed to compare the two methods. These randomized trials of endoscopic biliary drainage and surgical bypass have demonstrated no differences in morbidity or overall survival between the two methods.

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References

• Shamoun JR, Barraza KR, Jurkovich GJ, et al: In extremis use of staples for cardiorrhaphy in penetrating cardiac trauma: case report. J Trauma 29:1589, 1989.
• Slamon D, Eiermann W, Robert N, Pienkowski T, Martin M, Press M, et al. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med 2011; 365(14):1273.
• ClinicalTrials.gov Identifier: NCT00911508 Catheter Ablation vs. Anti-arrhythmic Drug therapy for Atrial Fibrillation Trial (CABANA) is ongoing. 322.
• Drew BJ, Krucoff MW: Multilead ST-segment monitoring in patients with acute coronary syndromes: A consensus statement for healthcare professionals. ST- Segment Monitoring Practice Guideline International Working Group, Am J Crit Care 8:372-386, 1999 quiz 387-388.
• Starzl TE, Marchioro TL, Waddell WR. The reversal of rejectio- i- huma- re-al homografts with subseque-t developme-t of homograft tolera-ce. Surg Gy-ecol Obstet. 1963;117:385-395.