Paraconduit Hiatal Hernia Following Esophagectomy: Incidence, Risk Factors, Outcomes and Repair.

BACKGROUND: Paraconduit hiatal hernia (PCHH) is a known complication of esophagectomy with significant morbidity. PCHH may be more common with the transition to a minimally invasive approach and improved survival. We studied the PCHH occurrence following minimally invasive esophagectomy to determine the incidence, treatment, and associated risk factors. METHODS: We retrospectively reviewed records of patients who underwent esophagectomy at an academic tertiary care center between 2013-2020. We divided the cohort into those who did and did not develop PCHH, identifying differences in demographics, perioperative characteristics and outcomes. We present video of our laparoscopic repair with mesh. RESULTS: Of 49 patients who underwent esophagectomy, seven (14%) developed PCHH at a median of 186 d (60-350 d) postoperatively. They were younger (57 versus 64 y, P< 0.01), and in cases of resection for cancer, more likely to develop tumor recurrence (71% versus 23%, P= 0.02). There was a significant difference in 2-y cancer free survival of patients with a PCHH (PCHH 19% versus no hernia 73%, P< 0.01), but no significant difference in 5-y overall survival (PCHH 36% versus no hernia 68%, P= 0.18). Five of seven PCHH were symptomatic and addressed surgically. Four PCHH repairs recurred at a median of 409 d. CONCLUSIONS: PCHH is associated with younger age and tumor recurrence, but not mortality. Safe repair of PCHH can be performed laparoscopically with or without mesh. Further studies, including systematic video review, are needed to address modifiable risk factors and identify optimal techniques for durable repair of post-esophagectomy PCHH.

Activated Kupffer cells inhibit insulin sensitivity in obese mice.

Obesity promotes insulin resistance associated with liver inflammation, elevated glucose production, and type 2 diabetes. Although insulin resistance is attenuated in genetic mouse models that suppress systemic inflammation, it is not clear whether local resident macrophages in liver, denoted Kupffer cells (KCs), directly contribute to this syndrome. We addressed this question by selectively silencing the expression of the master regulator of inflammation, NF-κB, in KCs in obese mice. We used glucan-encapsulated small interfering RNA particles (GeRPs) that selectively silence gene expression in macrophages in vivo. Following intravenous injections, GeRPs containing siRNA against p65 of the NF-κB complex caused loss of NF-κB p65 expression in KCs without disrupting NF-κB in hepatocytes or macrophages in other tissues. Silencing of NF-κB expression in KCs in obese mice decreased cytokine secretion and improved insulin sensitivity and glucose tolerance without affecting hepatic lipid accumulation. Importantly, GeRPs had no detectable toxic effect. Thus, KCs are key contributors to hepatic insulin resistance in obesity and a potential therapeutic target for metabolic disease.

The presence of Helicobacter pylori is not associated with long-term anastomotic complications in gastric bypass patients.

BACKGROUND: Eradication of Helicobacter pylori prior to Roux-en-Y gastric bypass (RYGB) has been advocated as a measure to reduce the complications of anastomotic ulceration. However, evidence to support a causal relationship between preoperative H. pylori status and postoperative anastomotic ulceration is weak. METHODS: Intraoperative gastric biopsies were obtained on consecutive patients who underwent laparoscopic RYGB at our institution from December 2007 to June 2010. These samples were analyzed by Warthin-Starry stain for H. Pylori organisms. Retrospective chart review was conducted to determine the preoperative presence of acid dyspepsia and acid suppression therapy and to determine postoperative ulcer symptoms, smoking, NSAID or steroid use, and compliance with ulcer prophylaxis. The incidence of ulcer visualization, perforation, and stricture were obtained from a prospectively collected database. Fisher's exact test was used for analyzing associations between discrete groups. Multiple logistic regression was used to assess associations between anastomotic ulcer complications and potential predictors. RESULTS: Histologic evaluation for H. pylori was available in 708 of the 728 patients who underwent RYGB. Fourteen patients were lost to follow up leaving 694 patients available for review. H. pylori was positive in 66 (9.5 %) patients who did not go on to receive definitive treatment for eradication. Marginal ulcers or related late complications were seen in a total of 113 (16.3 %) patients. In the H. pylori positive group, five patients (7.6 %) developed ulcer complications compared to 108 (17.1 %) in the H. pylori negative group (p = 0.05). Groups were not different in terms of preoperative demographics, postoperative ulcer prophylaxis compliance, steroid, NSAIDs, and cigarette use. CONCLUSION: The presence of H. pylori infection at the time of RYGB was found to be associated with a significantly lower incidence of anastomotic ulcer complications postoperatively. This study brings into question efforts and expense allocated to identify and eradicate H. pylori prior to RYGB.

Remission of type 2 diabetes mellitus following bariatric surgery: review of mechanisms and presentation of the concept of 'reversibility'.

PURPOSE OF REVIEW: Roux-en-Y gastric bypass (RYGB) leads to remission of type 2 diabetes mellitus (T2DM) in a majority of patients. This is prompting investigation of RYGB, and other bariatric operations as interventional therapies for T2DM. RECENT FINDINGS: The impact of RYGB is due to an increase in the release of gastrointestinal hormones in response to a meal [glucagon-like peptide, peptide YY, oxyntomodulin]. This effect involves the parasympathetic nervous system. These same hormones are responsible for an early increase in ß-cell secretion of insulin, leading to early remission of T2DM following RYGB. Progressive weight loss leads to a later improvement in peripheral insulin sensitivity, which is required for later remissions, and is responsible for re-emergence of T2DM in individuals who regain weight in long-term follow-up. As the success of bariatric surgery has prompted the emergence of the concept that T2DM is reversible, we offer a theory to predict reversibility of diabetes after bariatric surgery that is based on baseline beta cell function. SUMMARY: This review will improve the understanding of the physiology of bariatric surgery and its impact on T2DM, stimulate investigations into new avenues to treat T2DM, and allow better selection of nonobese individuals for interventional therapy of T2DM.

Depot-specific differences and insufficient subcutaneous adipose tissue angiogenesis in human obesity.

BACKGROUND: Adipose tissue expands in response to excess caloric intake, but individuals prone to deposit visceral instead of subcutaneous adipose tissue have higher risk of metabolic disease. The role of angiogenesis in the expandability of human adipose tissue depots is unknown. The objective of this study was to measure angiogenesis in visceral and subcutaneous adipose tissue and to establish whether there is a relationship between obesity, metabolic status, and the angiogenic properties of these depots. METHODS AND RESULTS: Angiogenic capacity was determined by quantifying capillary branch formation from human adipose tissue explants embedded in Matrigel, and capillary density was assessed by immunohistochemistry. Subcutaneous adipose tissue had a greater angiogenic capacity than visceral tissue, even after normalization to its higher initial capillary density. Gene array analyses revealed significant differences in expression of angiogenic genes between depots, including an increased subcutaneous expression of angiopoietin-like protein 4, which is proangiogenic in an adipose tissue context. Subcutaneous capillary density and angiogenic capacity decreased with morbid obesity, and subcutaneous, but not visceral, adipose tissue angiogenic capacity correlated negatively with insulin sensitivity. CONCLUSIONS: These data imply that subcutaneous adipose tissue has a higher capacity to expand its capillary network than visceral tissue, but this capacity decreases with morbid obesity. The decrease correlates with insulin resistance, suggesting that impairment of subcutaneous adipose tissue angiogenesis may contribute to metabolic disease pathogenesis.

Body mass index-independent inflammation in omental adipose tissue associated with insulin resistance in morbid obesity.

BACKGROUND: Obesity is a strong risk factor for resistance to insulin-mediated glucose disposal, a precursor of type 2 diabetes and other disorders. However, not all obese individuals are insulin resistant. We sought to identify the molecular pathways that might cause obesity-associated insulin resistance in humans by studying the morbidly obese who were insulin sensitive versus insulin resistant, thereby eliminating obesity as a variable. METHODS: Combining gene expression profiling with computational approaches, we determined the global gene expression signatures of omental and subcutaneous adipose tissue samples obtained from similarly obese patients undergoing gastric bypass surgery. RESULTS: Gene sets related to chemokine activity and chemokine receptor binding were identified as most highly expressed in the omental tissue from insulin-resistant compared with insulin-sensitive subjects, independent of the body mass index. These upregulated genes included chemokines (C-C motif) ligand 2, 3, 4, and 18 and interleukin-8/(CC-X motif) ligand 8 and were not differentially expressed in the subcutaneous adipose tissues between the 2 groups of subjects. Insulin resistance, but not the body mass index, was associated with increased macrophage infiltration in the omental adipose tissue, as was adipocyte size, in these morbidly obese subjects. CONCLUSION: Our findings have demonstrated that inflammation of the omental adipose tissue is strongly associated with insulin resistance in human obesity even in subjects with similar body mass index values.

Reduced heart rate variability correlates with insulin resistance but not with measures of obesity in population undergoing laparoscopic Roux-en-Y gastric bypass.

BACKGROUND: Obesity is associated with a pathologic predominance of sympathetic over parasympathetic tone. With respect to the heart, this autonomic dysfunction presents as a decreased heart rate variability (HRV), which has been associated with increased cardiovascular morbidity. Gastric bypass (GB) reduces cardiovascular mortality, and, thus, could beneficially affect the HRV. We sought to identify the factors predictive of HRV in a severely obese population of undergoing GB at a university hospital in the United States. METHODS: The data of all patients presenting for GB were included in a prospective database. The homeostatic model of assessment (HOMA) was used to calculate the insulin resistance and glucose disposition index. A 24-hour Holter monitor was used to assess the HRV. Measurements were repeated at 2 weeks and 6 months postoperatively. The correlations between variables were determined using linear mixed models. RESULTS: We studied 30 patients undergoing GB. All exhibited some degree of reduced HRV that improved postoperatively. The HOMA-insulin resistance inversely correlated with the HRV, and the HOMA-glucose disposition index directly correlated with the parameters of HRV in our longitudinal models. Weight, body mass index, excess body weight, gender, and age did not correlate with HRV. Improvements in HRV correlated with reductions in the average heart rate, underscoring a postoperative increase in relative vagal tone. CONCLUSION: HRV in the severely obese is better predicted by the degree of insulin resistance, than by the degree of obesity, age, or gender. GB led to an improvement in HRV, the magnitude of which correlated with the change in insulin resistance and glucose disposition index, but not with weight loss.

Small-bowel obstruction after laparoscopic Roux-en-Y gastric bypass surgery.

PURPOSE: The purpose of this study was to review the etiology and computed tomography (CT) findings of small-bowel obstruction (SBO) in patients who have undergone bariatric laparoscopic Roux-en-Y gastric bypass (LGBP) surgery. MATERIALS AND METHODS: Prospectively entered data from a surgical database of 835 consecutive patients who underwent antecolic-antegastric LGBP for morbid obesity from June 1999 to April 2005 in a single institution were retrospectively reviewed. A total of 42 cases of bowel obstruction were observed in 41 patients. Surgical proof was available in 38 cases, and 4 cases had characteristic imaging features and/or clinical follow-up. Seventeen CT scans were reviewed to determine cause and level of obstruction, and this was correlated with surgical findings and clinical follow-up. RESULTS: Internal hernia was the most common (13 cases) and also the most frequently missed etiology of SBO on CT scans, with the diagnosis being made prospectively in only 2 of 6 cases, in which CT was done. Adhesions, ventral hernia, postoperative ileus, and jejunojejunal (JJ) anastomotic strictures, in that order, were the other commonly observed etiologies for SBO, with 11, 7, 5, and 4 cases, respectively. Some causes of SBO post-LGBP (JJ anastomotic stricture and postoperative ileus) developed relatively early, whereas others (internal hernia) tended to develop later or had a bimodal distribution (adhesions and ventral hernia). Fifteen (36%) of 42 cases had SBO at or near the level of jejunojejunostomy site; causes included internal hernia (5 cases), adhesions/kinking of small bowel (5 cases), JJ anastomotic stricture (4 cases), and JJ intussusception (1 case). CONCLUSION: The time interval between LGBP and development of SBO might provide a useful clinical clue to its etiology. The JJ level is an important location for SBO post-LGBP because of a variety of causes, and special attention must be paid to this site at imaging of post-LGBP patients.

Cidea is associated with lipid droplets and insulin sensitivity in humans.

Storage of energy as triglyceride in large adipose-specific lipid droplets is a fundamental need in all mammals. Efficient sequestration of fat in adipocytes also prevents fatty acid overload in skeletal muscle and liver, which can impair insulin signaling. Here we report that the Cide domain-containing protein Cidea, previously thought to be a mitochondrial protein, colocalizes around lipid droplets with perilipin, a regulator of lipolysis. Cidea-GFP greatly enhances lipid droplet size when ectopically expressed in preadipocytes or COS cells. These results explain previous findings showing that depletion of Cidea with RNAi markedly elevates lipolysis in human adipocytes. Like perilipin, Cidea and the related lipid droplet protein Cidec/FSP27 are controlled by peroxisome proliferator-activated receptor gamma (PPARgamma). Treatment of lean or obese mice with the PPARgamma agonist rosiglitazone markedly up-regulates Cidea expression in white adipose tissue (WAT), increasing lipid deposition. Strikingly, in both omental and s.c. WAT from BMI-matched obese humans, expression of Cidea, Cidec/FSP27, and perilipin correlates positively with insulin sensitivity (HOMA-IR index). Thus, Cidea and other lipid droplet proteins define a novel, highly regulated pathway of triglyceride deposition in human WAT. The data support a model whereby failure of this pathway results in ectopic lipid accumulation, insulin resistance, and its associated comorbidities in humans.

Use of laparoscopy in evaluation and treatment of penetrating and blunt abdominal injuries.

Use of laparoscopy in penetrating trauma has been well established; however, its application in blunt trauma is evolving. The authors hypothesized that laparoscopy is safe and feasible as a diagnostic and therapeutic modality in both the patients with penetrating and blunt trauma. Trauma registry data and medical records of consecutive patients who underwent laparoscopy for abdominal trauma were reviewed. Over a 4-year period, 43 patients (18 blunt trauma / 25 penetrating trauma) underwent a diagnostic laparoscopy. Conversion to laparotomy occurred in 9 (50%) blunt trauma and 9 (36%) penetrating trauma patients. Diagnostic laparoscopy was negative in 33% of blunt trauma and 52% of penetrating trauma patients. Sensitivity/specificity of laparoscopy in patients with blunt and penetrating trauma was 92%/100% and 90%/100%, respectively. Overall, laparotomy was avoided in 25 (58%) patients. Use of laparoscopy in selected patients with blunt and penetrating abdominal trauma is safe, minimizes nontherapeutic laparotomies, and allows for minimal invasive management of selected intra-abdominal injuries.

Metabolic characterization of nondiabetic severely obese patients undergoing Roux-en-Y gastric bypass: preoperative classification predicts the effects of gastric bypass on insulin-glucose homeostasis.

INTRODUCTION: Obese individuals may have normal insulin-glucose homeostasis, insulin resistance, or diabetes mellitus. Whereas gastric bypass cures insulin resistance and diabetes mellitus, its effects on normal physiology have not been described. We studied insulin resistance and beta-cell function for patients undergoing gastric bypass. METHODS: One hundred thirty-eight patients undergoing gastric bypass had fasting insulin and glucose levels drawn on days 0, 12, 40, 180, and 365. Thirty-one (22%) patients with diabetes mellitus were excluded from this analysis. Homeostatic model of assessment was used to estimate insulin resistance, insulin sensitivity, and beta-cell function. Based on this model, patients were categorized as high insulin resistance if their insulin resistance was >2.3. RESULTS: Body mass index did not correlate with insulin resistance. Forty-seven (34%) patients were categorized as high insulin resistance. Correction of insulin resistance for this group occurred by 12 days postoperatively. Sixty (43%) patients were categorized as low insulin resistance. They demonstrated an increase of beta-cell function by 12 days postoperatively, which returned to baseline by 6 months. At 1 year postoperatively, the low insulin resistance group had significantly higher beta-cell function per degree of insulin sensitivity. CONCLUSIONS: Adipose mass alone cannot explain insulin resistance. Severely obese individuals can be categorized by degree of insulin resistance, and the effect of gastric bypass depends upon this preoperative physiology.

Predictors of weight status following laparoscopic gastric bypass.

BACKGROUND: Weight loss after bariatric surgery varies and depends on many factors, such as time elapsed since surgery, baseline weight, and co-morbidities. METHODS: We analyzed weight data from 494 patients who underwent laparoscopic Roux-en-Y gastric bypass (RYGBP) by one surgeon at an academic institution between June 1999 and December 2004. Linear regression was used to identify factors in predicting % excess weight loss (%EWL) at 1 year. RESULTS: Mean patient age at time of surgery was 44 +/- 9.6 (SD), and the majority were female (83.8%). The baseline prevalence of co-morbidities included 24% for diabetes, 42% for hypertension, and 15% for hypercholesterolemia. Baseline BMI was 51.5 +/- 8.5 kg/m(2). Mean length of hospital stay was 3.8 +/- 4.6 days. Mortality rate was 0.6%. Follow-up weight data were available for 90% of patients at 6 months after RYGBP, 90% at 1 year, and 51% at 2 years. Mean %EWL at 1 year was 65 +/- 15.2%. The success rate (> or = 50 %EWL) at 1 year was 85%. Younger age and lower baseline weight predicted greater weight loss. Males lost more weight than females. Diabetes was associated with a lower %EWL. Depression did not significantly predict %EWL. CONCLUSION: The study demonstrated a 65 %EWL and 85% success rate at 1 year in our bariatric surgery program. Our finding that most pre-surgery co-morbidities and depression did not predict weight loss may have implications for pre-surgery screening.

Immunologic effects of hand-assisted surgery on peritoneal macrophages: comparison to open and standard laparoscopic approaches.

BACKGROUND: Exaggerated activation of peritoneal immunity after major abdominal surgery activates peritoneal macrophages (PMs), which may lead to a relative local immunosuppression. Although laparoscopy (L) is known to elicit a smaller attenuation of peritoneal host defenses, compared with open (O) surgery, effects of the hand-assisted (HA) approach have not been investigated to date. METHODS: Eighteen pigs underwent a transabdominal nephrectomy via O, HA, or L approach. PMs were harvested at 4, 12, and 24 hours through an intraperitoneal drain and stimulated in vitro with lipopolysaccharide. The production of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) by the purified macrophage cultures was measured with the use of a standard enzyme-linked immunosorbent assay technique. Statistical comparison was performed by using analysis of variance and Student t test. RESULTS: In vitro lipopolysaccharide-induced IL-6 and TNF-alpha production by PMs increased over the 24-hour period in all 3 groups. Stimulated PMs harvested at 12 and 24 hours postoperatively secreted higher levels of IL-6 in the O group, compared with both the HA group (P = .02, P = .01) and L group (P = .04, P = .001). PMs harvested at 4, 12 and 24 hours postoperatively also produced more TNF-alpha in O group, compared with both the HA group (P = .03, P = .03, and P = .01) and L group (P = .01, P = .05 and P = .03). There was no significant difference between H and L groups in production of either cytokine. CONCLUSIONS: Abdominal surgery attenuates peritoneal host defenses regardless of the surgical approach employed. However, for the first time, we demonstrated that the HA approach, similar to laparoscopy, is superior to open surgery in the degree of PM activation. Overall, in addition to clinical benefits of minimal access, HA surgery may confer an immunologic advantage over laparotomy.

Predictors of complication and suboptimal weight loss after laparoscopic Roux-en-Y gastric bypass: a series of 188 patients.

HYPOTHESIS: An analysis of patients undergoing laparoscopic Roux-en-Y gastric bypass (RYGB) may identify factors predictive of complication and of suboptimal weight loss. DESIGN: Inception cohort. SETTING: Metropolitan university hospital. PATIENTS: One hundred eighty-eight consecutive patients with severe obesity who met National Institutes of Health consensus guidelines for bariatric surgery. INTERVENTIONS: Laparoscopic RYGB. MAIN OUTCOME MEASURES: Complications requiring therapeutic intervention and percentage of excess body weight lost at 1 year after surgery. RESULTS: Of the 188 patients who underwent laparoscopic RYGB, 50 (26.6%) developed complications that required an invasive therapeutic intervention, including 2 deaths. The average follow-up was 351 days (range, 89-1019 days). Multivariate analysis by stepwise logistic regression identified surgeon experience, sleep apnea (P =.003; odds ratio, 3.0; 95% confidence interval, 1.3-7.1), and hypertension (P =.07; odds ratio, 2.0; 95% confidence interval, 1.0-4.0) as predictors of complications. The most common complication requiring therapeutic intervention was stricture at the gastrojejunal anastomosis, occurring in 27 patients (14.4%). Of the 115 patients who underwent surgery more than 1 year previously, 1-year follow-up data were available for 93 (81%). The body mass index (weight in kilograms divided by the square of height in meters) decreased from 53 +/- 8 preoperatively to 35 +/- 6 at 1 year. The mean +/- SD percentage of excess body weight lost at 1 year was 61% +/- 14%. Diabetes mellitus was negatively correlated with percentage of excess body weight lost at 1 year (P =.06). CONCLUSIONS: Surgeon experience, sleep apnea, and hypertension are associated with complications after laparoscopic RYGB. Diabetes mellitus may be associated with poorer postoperative weight loss.

Feasibility of laparoscopic adrenalectomy for large adrenal masses.

Laparoscopic adrenalectomy (LA) is a preferred method for the removal of small adrenal masses. However, the role of LA for surgical treatment of large adrenal masses is less established. We evaluated the outcomes of LA for large (>/=5 cm) adrenal masses. We retrospectively reviewed 24 consecutive patients who underwent LA for large adrenal masses at a tertiary care university hospital. The average age of the 24 patients was 49 years, and each underwent laparoscopic resection of a large adrenal mass. All LAs were performed via a lateral transperitoneal approach. The average (+/- standard deviation) size of the masses was 6.8 +/- 1.5 cm (range, 5-11). Pathologic diagnoses included adrenal cortical adenoma (10 cases), pheochromocytoma ( 7), cyst/pseudocyst ( 3), myolipoma ( 2), and adrenal cortical hyperplasia ( 2). Statistical analysis was performed with a two-sample t test. The average operating time was 178 +/- 55 minutes (range, 120-300), and average blood loss was 87 +/- 69 mL (range, 20-300); the averages were nonsignificantly greater in the right LA group than in the left LA group (203 vs. 166 minutes, P = 0.89; 124 vs. 77 mL, P = 0.14). The average duration of nothing-by-mouth (NPO) status was 0.7 days (range, 0-4), and the average time until return to a regular diet was 1.74 +/- 0.9 days (range, 1-5). The average length of stay was 2.5 +/- 1.9 days (range, 1-10). One patient had a transient episode of pseudomembranous colitis. There were no conversions to open adrenalectomy and no major morbidities or mortalities. LA is safe and effective for surgical treatment of large adrenal masses. Both right and left large adrenal masses can be approached laparoscopically with equal success. The role of minimally invasive approaches to adrenal malignancies necessitates further investigation.