Dysfunctional immune-privilege in morbid obesity: implications and effect of gastric bypass surgery.

BACKGROUND: Despite the epidemiological evidence linking obesity and cancer, there has never been a causal link. We believe the chronic inflammation present in obesity may predispose the obese to cancer through Fas-receptor over-expression and L-selectin under-expression in leukocytes, and elevated Fas ligand secretion in tumors affecting the morbidly obese. METHODS: Leukocytes from 25 patients having gastric bypass surgery were compared to 15 normal controls preoperatively and at 1, 3, 6, and 12 months postoperatively using flow cytometry to measure CD3, CD4, CD8, CD56, CD62 (L-selectin), CD69, and CD95 (Fas antigen) expression on T lymphocytes, B lymphocytes, natural killer cells, and neutrophils. RESULTS: The percentage of CD95 + T cells was significantly elevated from controls (69.4% vs 56%, P = 0.005). This difference persisted through 1 month postoperatively. Furthermore, expression of CD95 per cell, was significantly greater in these patients than that of the controls (80.2 vs 62.6 gmf, P = 0.018) preoperatively, and this continued to 1 month. Polymorphonuclear cells also displayed a similar elevation in CD95 gmf expression preoperatively (54.1 vs 40.7 gmf, P = 0.023) which normalized by 3 months. Natural killer cells did not display elevated numbers of CD95 gmf preoperatively, but they did experience a significant decline by 12 months. Additionally, there was significant reduction in the number of naiveT cells [(T cells without L-selectin (CD62L)], when compared to normals preoperatively (41.8% vs 51.3%, P = 0.001). There was no statistical difference between the postoperative patients and the controls by 3 months. CD69 was not different at baseline from controls in T or B cells, but there was a significant decrease by 12 months. CONCLUSION: The reduced expression of L-selectin combined with the elevated levels of CD95 suggests that morbid obesity predisposes patients to sites of immune privilege. This could be the mechanism for increased rates of cancer and wound infections seen in obesity. Surgically-induced weight loss eliminates these risk factors.

Effect of surgically-induced weight loss on leukocyte indicators of chronic inflammation in morbid obesity.

BACKGROUND: Recent evidence suggests that morbid obesity is a chronic inflammatory condition that may be associated with immune dysfunction. To test this hypothesis, we investigated several leukocyte cell surface markers of chronic inflammation and followed their response to surgically-induced weight loss. METHODS: 26 patients having Roux-en-Y gastric bypass (RYGBP) for morbid obesity (BMI > 40) were compared to 10 normal controls (BMI < 25). Relative monocyte and neutrophil frequencies and expression of the activation antigens CD11b (adhesion molecule), CD16 (Fc receptor), and CD62L (L-selectin), were evaluated by flow cytometry preoperatively and at 1, 3, 6 and 12 months after RYGBP. Cases served as their own controls but were also compared to non-obese controls. The results were statistically analyzed using Student's t-test and ANOVA for parametric values and Mann-Whitney along with Kruskal-Wallis ANOVA for nonparametric values. RESULTS: The control group had mean age 37 +/- 7.6 with mean 23 +/- 2.5 and no comorbidities. The mean age of the sample group was 40.36 +/- 13.7 with mean BMI 52 +/- 8.2. The neutrophil and monocyte relative frequencies of CD11b (monocytes and neutrophils), and CD16 (neutrophils only) were comparable to controls at baseline and did not change significantly with weight loss throughout the study period. However, a significant reduction of CD62L (L-selectin) expression was noted in monocytes and neutrophils at baseline (neutrophils 103 vs 240 gmf, p < 0.001) (monocytes 104 vs 246 gmf, P < 0.001) when compared to normal controls. Levels of L-selectin normalized by 6 months in both monocytes and neutrophils, and by 12 months had become abnormally elevated in monocytes (monocytes 391 gmf, P = 0.007); in neutrophils, there was an upward trend that did not reach significance. The expression of the LPS receptor CD14 in the study group was elevated significantly compared to controls at baseline (1129 vs 719 gmf, P = 0.004); this marker appeared to return to normal by 3 months. Monocyte CD14+/CD16+ subset percentage were also elevated significantly at baseline (14.3% vs 5.25%, P < 0.001), declined throughout the time period but was still significant at 1 year (8.8%, P < 0.001). Eosinophil percentages were elevated at baseline (3.3% obese vs 1.8% controls, P = 0.003) and remained so throughout the time period. CONCLUSION: Deficiencies in the immune system of morbidly obese individuals include elevated levels of eosinophils, monocyte CD14, and monocyte CD14+/CD16+ subsets, with depression of monocyte and neutrophil CD62L. These abnormal levels reverse rapidly with surgically-induced weight loss. RYGBP is not only a weight loss operation but also appears to be an immune restorative procedure.

The effect of obesity on neutrophil Fc receptors and adhesion molecules (CD16, CD11b, CD62L).

BACKGROUND: There is a large body of epidemiological data associating obesity with a wide variety of clinical disease processes, including cancer and wound infections. However, defining the specific defects of neutrophils has proved difficult and often contradictory. METHODS: 27 patients having gastric bypass surgery for obesity (BMI > 40) were compared with 10 normal controls (BMI < 26). Relative neutrophil frequencies and expression of the activation antigens CD11b (integrin adhesion molecule), CD16 (Fc receptor), and CD62L (L-selectin), were evaluated by flow cytometry. RESULTS: The study control group had a mean age of 37 +/- 7.6 yrs (range 30 to 57) with no significant health problems. Their mean BMI was 23 +/- 2.5 kg/m2 (range 21-26). The mean age of the sample group was 40.36 +/- 13.7 yrs (range 18 to 60) with a mean BMI of 52 +/- 8.2 kg/m2 (range 41 to 72). These patients had a large spectrum of diseases that afflict the morbidly obese, including hypertension (14), arthritis (10), exertional dyspnea (13), venous stasis (7), hypothyroidism (2), NIDDM (3), heart murmur (1), along with 8 smokers. The neutrophil frequency in the obese patients was comparable to the controls (control 49% vs obese 51%). Additionally, there was no apparent difference between obese and controls regarding CD11b or CD16 expression (424 vs 498 gmf) (267 vs 262 gmf). However, there was a significant reduction of CD62L (L-selectin) expression noted in the morbidly obese with respect to controls (102 vs 303 gmf, p < 0.001). An increased percentage of eosinophils when compared to controls (6.7% vs 1.73%, p < 0.001) was also observed. CONCLUSION: Discordant CD11b/CD62L levels, depressed levels of CD62L, and elevated eosinophil percentages support the hypothesis that a chronic inflammatory state exists in morbid obesity. Decreased levels of CD62L in the morbidly obese neutrophil pool possibly affect the neutrophil's ability to activate and migrate to sites of inflammation. This may play a role in the higher incidence of infectious complications seen in morbidly obese individuals.

Preoperative radiographic staging for ureteral injuries is not warranted in patients undergoing celiotomy for trauma.

Preoperative radiographic staging of the urinary tract has been shown to be inaccurate with regard to the ureter. The purpose of this study was to assess the need for radiographic staging of the injured patient for the diagnosis of ureteral injury before operative exploration. We conducted a retrospective review of all patients who sustained injury of the ureter as the result of external trauma over an 8 Y2-year period at an urban and suburban Level I trauma center. All patients were injured through penetrating mechanisms and underwent laparotomy. Only three patients had preoperative radiographic staging of the urinary tract. No ureteral injuries were missed. We conclude that surgical exploration of the ureter is sufficiently accurate to obviate the need for preoperative radiographic staging of the ureters in patients who have sustained penetrating injury and warrant laparotomy.

Laparoscopic repair of traumatic perforation of the urinary bladder.

Laparoscopy as a diagnostic modality in trauma has been reported. However, therapeutic laparoscopy for trauma remains a controversial subject. We present a case of laparoscopic repair of a traumatic bladder rupture. A 25-year-old man was brought to the emergency room after a head-on collision. Physical examination was unremarkable with the exception of gross hematuria upon insertion of a urinary catheter. Computed tomography scan of the abdomen demonstrated a small amount of free intraperitoneal fluid. An anteroposterior cystogram was obtained which showed no intraperitoneal or extraperitoneal leak. Repeat examinations of the abdomen revealed a mild tenderness in the lower abdomen. Because of the presence of unexplained free intraperitoneal fluid and equivocal signs of peritoneal irritation, exploratory laparoscopy was performed. Three 5-mm ports and a 5-mm laparoscope were used. Laparoscopic examination of the abdomen revealed a 4-cm rupture at the dome of the bladder. The laceration was sutured in two layers using an intracorporeal technique. The patient was discharged on the second postoperative day with indwelling urinary catheter. Eight days after the operation, a repeated cystogram revealed no evidence of leak. We believe that laparoscopic exploration for trauma in hemodynamically stable patients is feasible. The repair of simple intraabdominal injuries such as bladder rupture can be safely performed.

Main pulmonary artery laceration after blunt trauma: accurate preoperative diagnosis.

Blunt chest trauma is associated with a variety of lethal injuries, many of which are responsible for prehospital mortality. Major intrathoracic vascular injury accounts for a vast majority of these fatal injuries. Patients surviving after main pulmonary artery injury are rare. We present the case of a patient who sustained a main pulmonary artery laceration as a result of a blunt motor vehicle crash. He was diagnosed accurately by computed tomography and underwent successful repair.

Blocking prostaglandin E2 after trauma attenuates pro-inflammatory cytokines and improves survival.

Major injury leads to impaired immune responses and increases the risk of infectious complications. Following trauma, increased prostaglandin E2 (PGE2) levels may be important in immunodysregulation. We hypothesized that blocking PGE2 with NS-398, a selective COX-2 inhibitor, during the first 24 h after injury may modify the immune response and protect the host from a subsequent septic challenge. BALB/c mice were given NS-398 (10 mg/kg) immediately after injury, at 12, and at 24 h after sham injury or trauma (femur fracture and 40% hemorrhage). On day 7 after injury, splenic macrophages were evaluated for cytokine production and COX-2 mRNA. In a separate study mice were injured, then given 3 doses of NS-398. After 7 days, cecal ligation and puncture was performed and mice were followed for survival. Traumatized mice given NS-398 had a significant survival advantage compared with trauma mice alone (P < 0.001). Macrophages from traumatized mice showed increased COX-2 mRNA and proinflammatory cytokines compared with controls (P < 0.05), whereas treatment of injured mice with NS-398 significantly decreased proinflammatory cytokine production (P < 0.05) and COX-2 mRNA. Therefore NS-398 given within 24 h of injury suppressed PGE2 through inhibition of cyclooxygenase, in addition to decreasing proinflammatory cytokines, and providing a survival advantage to the host.

Effects of traditional versus delayed resuscitation on serum lactate and base deficit.

OBJECTIVE: To test the hypothesis that delayed resuscitation of hemorrhagic shock produces a less severe shock insult than traditional resuscitation, characterized by repeated episodes of alternating hypotension and normotension. METHODS: Female pigs were divided into three groups. Sham operated controls (C) (n = 4), sustained hypotension (SS) (n = 6), and hypotension with multiple cycles of shock and resuscitation (SR) (n = 6). SS and SR animals were bled to a mean arterial pressure (MAP) of 50 mmHg. SS animals were maintained at an MAP of 50 mmHg for 65 min and then resuscitated to baseline blood pressure with normal saline and shed blood. SR animals were initially bled and maintained at an MAP of 50 mmHg for 35 min, resuscitated to baseline BP, and subsequently bled and resuscitated twice more. The total period of shock was the same in both SS and SR. RESULTS: Following hemorrhage, there was a significant increase in lactate and base deficit in SS as compared to C and SR. CONCLUSION: Delayed resuscitation produces a more profound shock insult than traditional resuscitation.

A laparoscopic approach to posterior gastric wall leiomyomectomy.

Leiomyomas represent 2% of gastric tumors. Commonly, gastric leiomyomas are clinically silent. Most often they become clinically apparent due to bleeding from ulceration of the overlying gastric mucosa. Surgical extirpation of the tumor is the standard treatment. Gastric leiomyomectomy was done routinely through open laparotomy until availability of laparoscopic equipment and techniques. Recently, there have been a few published reports regarding laparoscopic or laparoscopic-assisted removal of smooth muscle gastric tumors. There is little data, however, describing or discussing a laparoscopic approach to gastric leiomyomas located on the posterior gastric wall. We describe two different laparoscopic approaches to posterior wall gastric leiomyomas that we used in two patients. The postoperative recovery of both patients was remarkably quick and uneventful.

A new approach in the management of incarcerated hernia. Emergency laparoscopic hernia repair.

The authors describe the case of a 74-year-old male presenting with an incarcerated epigastric hernia. An algorithm for successful management of such a case is proposed.

Ligation: an alternative for control of exsanguination in major vascular injuries.

BACKGROUND: Temporization in the management of patients in extremis has gained acceptance in trauma surgery. Resection, without anastomosis, in major visceral injuries followed by delayed reconstruction has been successful. METHODS: To evaluate this approach in patients with substantial vascular trauma, we reviewed our experience of five patients with major vascular injuries that were ligated as a temporizing procedure during a 58-month period. If the patient was hypothermic, acidotic, and potentially or actually coagulopathic with significant blood loss, achieving expeditious hemostasis was the primary consideration. After hemodynamic resuscitation, warming, and correction of the coagulation profile, if necessary the patients were returned to the operating room for definitive reconstruction. RESULTS: All patients survived; only two required subsequent vascular reconstruction. CONCLUSIONS: The prompt control of hemorrhage must be the first objective of treatment in critically injured patients. Ligation of major vessel injury is a therapeutic alternative as part of the "damage control" philosophy.

Nonoperative salvage of computed tomography-diagnosed splenic injuries: utilization of angiography for triage and embolization for hemostasis.

OBJECTIVES: The aims of this study were to determine if angiographic findings can be used to predict successful nonoperative therapy of splenic injury and to determine if coil embolization of the proximal splenic artery provides effective hemostasis. METHODS: Splenic injuries detected by diagnostic imaging between 1981 and 1993 at a level I trauma center were prospectively collected and retrospectively reviewed after management by protocol that used diagnostic peritoneal lavage, computed tomography (CT), angiography, transcatheter embolization, and laparotomy. Computed tomography was performed initially or after positive diagnostic peritoneal lavage. Angiography was performed urgently in stabilized patients with CT-diagnosed splenic injuries. Patients without angiographic extravasation were treated by bed rest alone; those with angiographic extravasation underwent coil embolization of the proximal splenic artery followed by bed rest. RESULTS: Patients (172) with blunt splenic injury are the subject of this study. Twenty-two patients were initially managed operatively because of associated injuries or disease (11 patients) or because the surgeon was unwilling to attempt nonoperative therapy (11 patients) and underwent splenectomy (17 patients) or splenorrhaphy (5 patients). One hundred fifty of 172 consecutive patients (87%) with CT-diagnosed splenic injury were stable enough to be considered for nonoperative management. Eighty-seven of the 90 patients managed by bed rest alone, and 56 of 60 patients treated by splenic artery occlusion and bed rest had a successful outcome. Overall splenic salvage was 88%. It was 97% among those managed nonoperatively, including 61 grade III and grade IV splenic injuries. Sixty percent of patients received no blood transfusions. Three of 150 patients treated nonoperatively underwent delayed splenectomy for infarction (one patient) or splenic infection (two patients). CONCLUSIONS: (1) Hemodynamically stable patients with splenic injuries of all grades and no other indications for laparotomy can often be managed nonoperatively, especially when the injury is further characterized by arteriography. (2) The absence of contrast extravasation on splenic arteriography seems to be a reliable predictor of successful nonoperative management. We suggest its use to triage CT-diagnosed splenic injuries to bed rest or intervention. (3) Coil embolization of the proximal splenic artery is an effective method of hemostasis in stabilized patients with splenic injury. It expands the number of patients who can be managed nonoperatively.

Surgical management of pediatric renal trauma: an urban experience.

This study was undertaken to review our operative experience in the management of pediatric renal trauma. Over a 2-year period (August 1988 to August 1990) 25 of 60 children undergoing celiotomy sustained renal injuries. There were 22 boys and three girls ranging in age from 5 to 18 years. Eighty-four per cent were victims of gunshot wounds, 12 per cent were stabbed, and 4 per cent sustained blunt trauma. The 25 injured children sustained a total of 45 individual organ injuries. Only 16 per cent required a nephrectomy, while the great majority (84%) were managed with renal sparing procedures. When we compared survivors to nonsurvivors, there was more thoracic and vascular injury along with more blood transfusion requirements in nonsurvivors. There was no statistical difference in Pediatric Trauma Score (PTS) between survivors and nonsurvivors (9.8 +/- 0.26 vs 9.5 +/- 1.5). Preoperative intravenous pyelographies (IVPs) performed in 52 per cent of all patients demonstrated the site of injury, presence of contralateral function as well as the anatomic position of the kidneys. We conclude that renal injury is common following penetrating abdominal trauma in childhood, however, these injuries can be managed by early operation with renal sparing procedures. There is a high incidence of associated intra-abdominal injury in those who have sustained penetrating renal trauma, but mortality is more common in patients sustaining associated thoracic and vascular injuries. An IVP should be performed, even in the absence of hematuria, when trauma trajectory strongly suggests urologic injury. This study also illustrates the sharp rise in drug-related urban violence with an associated increase in pediatric renal trauma.

Delayed gastrointestinal reconstruction following massive abdominal trauma.

Routine use of the concepts of expeditious hemostasis including the use of packing and temporizing surgical resection without anastomosis followed by delayed reexploration and reconstruction in victims of major pancreaticoduodenal trauma encouraged us to manage other devastating abdominal injuries in a similar fashion. A variety of multiple organ injuries accompanied by massive blood loss, hypothermia, and acidosis also have been managed with the philosophy that hemostasis and control of continued gastrointestinal soiling were the only necessary initial surgical procedures. Following recovery room or surgical intensive care unit stabilization with full hemodynamic resuscitation and restoration of coagulation variables to normal, delayed definitive reconstruction was done. A summary of our experience and principles of management are presented.

The effect of cocaine on gastric mucosal PGE(2), LTC(4) and ulcerations.

The association between cocaine use and acute gastroduodenal perforation is known. The effect of cocaine and stress on gastric mucosal ulceration and the levels of prostaglandin E(2) (PGE(2)) and leukotriene C(4) (LTC(4)) was studied in 40 Sprague-Dawley rats. Controls received intraperitoneal (i.p.) saline, ten received i.p. cocaine (35 mg/kg), ten were stressed by the cold restraint method, and ten had i.p. cocaine and stress. Cocaine alone did not induce ulceration, but decreased PGE(2) levels. Stress alone caused ulceration, but was not associated with a change in either PGE(2) or LTC(4) levels. When combined with stress, however, cocaine caused a three-fold increase in ulceration and a significant increase in PGE(2) and LTC(4) levels. Stress may predispose the cocaine addict to loss of gastroduodenal mucosal integrity, which is related to an imbalance of PGE(2) and LTC(4) synthesis.