Gerald W. Shaftan

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 (Lselectin), 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 Students 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 (Lselectin) expression was noted in monocytes and neutrophils at baseline (neutrophils 103 vs 240 gmf, p<0.001) (monocytes104 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.

Preperitoneal Herniation Into a Laparoscopic Port Site Without a Fascial Defect

Background: Port site herniation is an uncommon event that usually occurs as a result of incomplete fascial closure. This allows the omentum or viscera to herniate through the incompletely closed defect. However, in laparoscopic surgery for morbid obesity, the omentum and viscera can herniate through the thick preperitoneal space even with a complete closure of the fascia. Case Report: A 19-year-old female with BMI 55 underwent uneventful long limb laparoscopic Roux-en-Y gastric bypass. On postoperative day 1 the patient had limited pain, was ambulating well, and was tolerating sips of liquids. A limited upper GI series performed on postoperative day 2 revealed no leak or obstruction. Several hours later the patient developed abdominal pain associated with nausea, which progressed to vomiting. CT of the abdomen suggested a port site herniation into the left subcostal port. The cause of the obstruction appeared to be herniation through the left subcostal port site. At laparotomy, a segment of bowel just distal to the anastomosis was found herniated through the port site. The Richters hernia was reduced. Careful inspection of the fascia revealed a complete fascial closure, with the strangulated portion of the bowel incarcerated in the preperitoneal space. Following repair of the preperitoneal defect, her subsequent recovery was unremarkable. Conclusion: Laparoscopic surgery for morbid obesity presents the possibility for preperitoneal herniation. Closure, using a fascial closure device, under laparoscopic control, may offer a solution by closing both the fascia and peritoneum all at once.

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), CD 69, 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.

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 neutrophils 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.

The effect of diabetes on endothelin, interleukin-8 and vascular endothelial growth factor-mediated angiogenesis in rats.

In diabetes mellitus, there is a problem of both premature atherosclerosis as well as impaired collateralization. Studies were performed using the rat corneal angiogenesis model as a surrogate for collateralization to determine the effect of diabetes mellitus on endothelin (ET)-1, ET-3, vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8)-mediated angiogenesis. In an initial group of experiments, streptozotocin-induced diabetes resulted in impairment of ET-1-mediated angiogenesis from 69% to 32%, but was only impaired from 74% to 59% for ET-3. When rats were fluid-resuscitated, mortality fell, and the incidence of inhibition of angiogenesis decreased for ET-1, but was still at 47%. Inhibition of ET-3-mediated angiogenesis in fluid-resuscitated rats was essentially unaffected from 74% to 75%. Studies of VEGF and IL-8 in fluid-resuscitated rats demonstrated that VEGF-mediated angiogenesis was only inhibited from 49% to 45%, but there was inhibition of IL-8-mediated angiogenesis from 62% to 31%. We concluded that there may be two mechanisms by which ET-1-mediated corneal angiogenesis is inhibited: a decrease in intravascular volume and dynamic forces affecting angiogenesis, and a direct effect of diabetes on some aspect of cell growth or angiogenic process. Diabetes also appeared to inhibit IL-8-mediated angiogenesis, but had very little or no effect on ET-3- or VEGF-mediated angiogenesis.

Lower Extremity Compartment Syndrome Following a Laparoscopic Roux-en-Y Gastric Bypass.

Background: Bariatric surgery has the potential for serious complications. A case is presented of unilateral lower extremity compartment syndrome after a laparoscopic Roux-en-Y gastric bypass performed in the modified lithotomy position. Case report: A 38-year-old female (weight 134.5 kg, BMI 49.6) underwent a laparoscopic Roux-en-Y gastric bypass (operating time 375 min). Postoperatively, she complained of bilateral lower extremity pain that gradually subsided over the course of the day. However, on the 1st postoperative day she developed numbness on the dorsum of the foot and compartment syndrome was diagnosed (anterior compartment pressure 71 mmHg). She underwent emergency fasciotomy,which resulted in a reduction of the pain and numbness on the dorsum of the foot. The next day she ambulated without difficulty and was discharged home on the 5th postoperative day. 12 days after her operation, delayed primary closure of the fasciotomy wound was done with the assistance of a novel device (Proxiderm) that applies constant tension to the wound edges. Subsequent recovery was uneventful, and at 4- month follow-up the patient had a weight loss of 28 kg without any right leg motor or sensory deficits. Conclusion: Bariatric surgeons should be aware of compartment syndrome as a rare but serious complication. Prevention, early recognition, and prompt fasciotomy are crucial for a favorable outcome.

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.