Neutrophils expressing lysyl oxidase-like 4 protein are present in colorectal cancer liver metastases resistant to anti-angiogenic therapy.

Colorectal cancer liver metastases (CRCLM) that present with a replacement histopathological growth pattern (HGP) are resistant to neoadjuvant anti-angiogenic therapy. Surrogate biomarkers are not available to preoperatively identify patients with these tumors. Here we identify differentially expressed genes between CRCLM with a replacement HGP and those with a desmoplastic HGP using RNA sequencing. We demonstrate that LOXL4 is transcriptionally upregulated in replacement HGP CRCLM compared with desmoplastic HGP CRCLM and the adjacent normal liver. Interestingly, lysyl oxidase-like 4 (LOXL4) protein was expressed by neutrophils present in the tumor microenvironment in replacement HGP CRCLM. We further demonstrate that LOXL4 expression is higher in circulating neutrophils of cancer patients compared with healthy control patients and its expression can be induced by stimulation with lipopolysaccharide and TNF-α. Our study is the first to show the expression of LOXL4 in neutrophils and reveals the potential for LOXL4-expressing neutrophils to support the replacement HGP phenotype and to serve as a surrogate biomarker for this subtype of CRCLM. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Short-term outcomes of revisional surgery after sleeve gastrectomy: a comparative analysis of re-sleeve, Roux en-Y gastric bypass, duodenal switch (Roux en-Y and single-anastomosis).

BACKGROUND: Sleeve gastrectomy (SG) is the most common primary bariatric surgery. Long-term, up to 20% of patients may need revisional surgery. We aimed to evaluate the short-term outcomes of various revisional bariatric surgeries after a failed primary SG. METHODS: This is a single-center retrospective study of a prospectively collected database of obese patients who underwent revisional bariatric surgery during 2010-2018 for a failed previous SG. Failure was defined as inadequate weight loss (< 50% excess weight loss), ≥ 20% weight regain of the weight lost, and presence of refractory non-reflux obesity-related comorbidities ≥ 1 year after SG. Revisions included were re-sleeve, Roux en-Y gastric bypass (RYGB), biliopancreatic diversion with duodenal switch (BPD/DS), and single-anastomosis duodenal switch (SADS). The primary outcome was weight loss after revision. Secondary outcomes included postoperative complications. Due to varying follow-up rates, short-term outcomes (≥ 6 and ≤ 18 months) were assessed. Descriptive statistics are expressed as count(percentage) or median(interquartile range). RESULTS: Ninety-four patients met inclusion criteria. Forty-one underwent conversion to RYGB, 33 had BPD/DS, 7 had SADS, and 13 underwent re-sleeve surgery. Median interval between SG and revision was 31(27) months. At a median of 14(18) months, follow-up rate was 76% for the study cohort. Prior to revision, median BMI was 41.9(11.7) kg/m2 and 1 year after decreased by 6.3(5.1) kg/m2. BPD/DS resulted in the largest total weight loss of 21.8(10.9) kg followed by RYGB 13.2(11.3), SADS 12.2(6.1), and re-sleeve 12.0(11.9) kg; p = 0.023. Major 90-day and long-term complications occurred only after RYGB and BPD/DS and were similar (7.3% vs. 3.0%; p = 0.769 and 9.8% vs. 24.2%; p = 0.173, respectively). CONCLUSIONS: At 1 year, revisional procedures offer further weight loss after a failed primary SG. Bypass-type revisions are preferred over re-sleeve surgery. In the absence of refractory reflux symptoms, duodenal switch-type procedures are safe and effective options especially in patients with severe obesity before SG.

Mapping the triglyceride distribution in NAFLD human liver by MALDI imaging mass spectrometry reveals molecular differences in micro and macro steatosis.

Hepatic lipid accumulation, mainly in the form of triglycerides (TGs), is the hallmark of non-alcoholic fatty liver disease (NAFLD). To date, the spatial distribution of individual lipids in NAFLD-affected livers is not well characterized. This study aims to map the triglyceride distribution in normal human liver samples and livers with NAFLD and cirrhosis with imaging mass spectrometry (MALDI IMS). Specifically, whether individual triglyceride species differing by fatty acid chain length and degree of saturation correlate with the histopathological features of NAFLD as identified with classical H&E. Using a recently reported sodium-doped gold-assisted laser desorption/ionization IMS sample preparation, 20 human liver samples (five normal livers, five samples with simple steatosis, five samples with steatohepatitis, and five samples with cirrhosis) were analyzed at 10-µm lateral resolution. A total of 24 individual lipid species, primarily neutral lipids, were identified (22 TGs and two phospholipids). In samples with a low level of steatosis, TGs accumulated around the pericentral zone. In all samples, TGs with different degrees of side-chain saturation and side-chain length demonstrated differential distribution. Furthermore, hepatocytes containing macro lipid droplets were highly enriched in fully saturated triglycerides. This enrichment was also observed in areas of hepatocyte ballooning in samples with steatohepatitis and cirrhosis. In conclusion, macro lipid droplets in NAFLD are enriched in fully saturated triglycerides, indicating a possible increase in de novo lipogenesis that leads to steatohepatitis and cirrhosis.

An incidental intra-operative finding of sclerosing encapsulating peritonitis, "abdominal cocoon" in an emergency presentation of small bowel obstruction, a case report.

INTRODUCTION AND IMPORTANCE: Sclerosing encapsulating peritonitis (SEP) is a disease characterized by a chronic inflammatory process in which the small intestines are encased by a dense fibrocollagenous membrane. In this article, we report a 57 year old male who presented with bowel obstruction secondary to sclerosing encapsulating peritonitis with an initial imaging suggesting internal hernia. CASE PRESENTATION: A 57-year-old male, who presented to the emergency department at our center with a chronic persistent nausea and vomiting, associated with anorexia, constipation and weight loss, CT scan showed a transition zone seen at the duodeno-jejunal (DJ) junction and findings suggesting internal hernia, he was treated conservatively initially followed by a diagnostic laparoscopy that was converted to open with intraoperative findings of intra-abdominal cocoon rather than an internal hernia, managed with adhesolysis and discharged home in stable good condition. CLINICAL DISCUSSION: There are multiple factors that could attribute to PSEP including cytokines, fibroblasts, and angiogenic factors, such patients might be asymptomatic or presenting with GI obstruction symptoms. The diagnosis of PSEP varying from abdominal x rays to contrast enhanced CT scan. CONCLUSION: The management of PSEP depends on the presentation and should be individualized, weather conservative medical or surgical approach can be used.

Laparoscopic sleeve gastrectomy in 108 obese children and adolescents aged 5 to 21 years.

OBJECTIVE: To report experience with laparoscopic sleeve gastrectomy (LSG) in 108 severely obese children and adolescents. BACKGROUND: Obesity during childhood and adolescence can be accompanied by serious long-term adverse health and longevity outcomes. With increased use of bariatric surgery to treat obesity in these patients, diverse guidelines have been published, most of which exclude children aged younger than 14 years. Few reports describe LSG in children and adolescents, delaying determining its safety and effectiveness and developing guidance regarding its use. METHODS: A retrospective review of LSG performed from March 2008 through February 2011 by a single surgeon at King Saud University Hospitals, Riyadh, Saudi Arabia, included 108 patients aged 5 through 21 years. RESULTS: Patients attending follow-up visits at 3 (n = 88), 6 (n = 76), 12 (n = 41), and 24 (n = 8) months postoperatively experienced median excess weight loss (EWL) of 28.9%, 48.1%, 61.3%, and 62.3%, respectively. At 6 and 12 months follow-up, 42.1% (n = 32) and 73.2% (n = 30) of patients achieved at least 50% EWL, whereas 7.9% (n = 6) and 4.9% (n = 2) had 25% or less EWL, respectively. There were no serious postoperative complications and no adverse sequelae developed during the current follow-up. Available comorbidity data indicate resolution of dyslipidemia, 21 of 30 (70.0%); hypertension, 27 of 36 (75.0%); prehypertension, 15 of 18 (83.3%); symptoms of obstructive sleep apnea, 20 of 22 (90.9%); diabetes, 15 of 16 (93.8%); and prediabetes, 11 of 11 (100.0%). CONCLUSIONS: LSG resulted in successful short-term weight loss in more than 90% of pediatric patients and 70% or more comorbidity resolution during up to 24 months of follow-up. Long-term data are necessary to evaluate persistence of weight loss and maturation to adulthood.

Laparoscopic sleeve gastrectomy in adult and pediatric obese patients: a comparative study.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is a recent bariatric procedure that has gained widespread popularity in morbidly obese adults. However, pediatric bariatric surgery is controversial, and the type(s) of bariatric surgery that are suitable for children and adolescents is under debate. No studies exit that compare LSG outcomes in adult and pediatric patients. We reviewed our experience to assess the safety, efficacy, and complications of LSG in adult and pediatric morbidly obese patients. METHODS: A retrospective review of all patients who underwent LSG by a single surgeon between March 2008 and February 2011 was performed. The 222 patients included 108 pediatric patients aged 21 years or younger and 114 adult patients older than 21 years. Baseline, operative, perioperative, and available follow-up data were abstracted. RESULTS: Pediatric patients had a mean age of 13.9 ± 4.3 years and a mean baseline body mass index (BMI) of 49.6 kg/m(2), whereas adults had a mean age of 32.2 ± 9.4 years and a mean baseline BMI of 48.3 kg/m(2). Our pediatric group achieved a mean percent of excess weight loss (%EWL) of 32.4, 52.1, 65.8, and 64.9 % at 3, 6, 12, and 24 months postoperative, respectively, compared with a mean %EWL of 30.9, 55.2, 68.5, and 69.7 %, respectively, in our adult group (p > 0.05). During the 24-month follow-up period, pediatric patients attended 71.7 % of follow-up visits, whereas adults attended 61.2 % of follow-up visits (p = 0.01). Postoperative complications occurred in six (5.6 %) and eight (7 %) pediatric and adult patients, respectively. CONCLUSIONS: Laparoscopic sleeve gastrectomy in the pediatric age group is of similar safety and effectiveness compared with adults. Pediatric patients had fewer major complications and were more compliant with follow-up than adults. Nevertheless, long-term results are required to further clarify the safety and effectiveness of LSG in pediatric patients.

Blood Group and Response to Bariatric Surgery in Morbidly Obese Patients: A Retrospective Study in Saudi Arabia.

OBJECTIVES: To explore the relationship between the blood group of patients and their response to bariatric surgery and to identify predictors of better outcomes. METHODS: This was a retrospective cross-sectional analysis of patients who underwent laparoscopic sleeve gastrectomy for morbid obesity between 2014 and 2020 at King Saud University Medical City in Riyadh, Saudi Arabia. RESULTS: This study included 1434 individuals. The mean change in BMI (pre- versus post-BMI) differed statistically significantly between blood groups (p ≤ 0.01). The greatest drop in body weight was seen in individuals with the AB-negative blood type (56.0 (21.4) kg), which corresponds to the greatest percentage of reduction from baseline (47.7% (14.8)). The mean BMI of the patients decreased by 34.7% (9.2) from a mean pre-operation BMI of 45.5 (8.4) kg/m2 to 29.7 (6.1) kg/m2 (p ≤ 0.001). After laparoscopic sleeve gastrectomy, male patients and those with the B-negative blood type are more likely to see a greater BMI reduction (pre-operation compared to post-operation) (p ≤ 0.05). CONCLUSIONS: For morbidly obese patients, laparoscopic sleeve gastrectomy demonstrated promising weight loss outcomes. Blood groups may be able to predict the success rate of bariatric surgery in morbidly obese patients.

Laparoscopic Ventral Hernia Repair with Poly-4-Hydroxybutyrate Absorbable Barrier Composite Mesh.

BACKGROUND: Repair of ventral and incisional hernias (VIHR) is a common procedure, newly introduced resorbable mesh biomaterials provide an attractive option to reduce the use of permanent synthetic mesh in hernia surgery and reduce its complications. However, data on the use of slowly resorbable mesh materials remains scarce, this study aims to evaluate the use of poly-4-hydroxybutyrate/absorbable barrier composite mesh (P4HB/ABCM) in laparoscopic repair of VIHR. METHODS: This is a retrospective study of a sequential cohort of patients undergoing laparoscopic VIHR utilizing a P4HB/ABCM mesh. Perioperative characteristics and clinical outcomes were collected. RESULTS: In total, 26 patients including 10 females and 7 males underwent laparoscopic VIHR using P4HB/ABCM. All surgeries were performed in a single institution by the same surgeon. The average patient age was 52.6, and the mean BMI was 35.5. All patients had a clean wound classification. The average defect size was 136.4 cm2. All patients were seen in clinic with a median follow-up of 28 months. We observed 4 wound seromas, and no wound infections or recurrences during the follow-up period. CONCLUSION: Results of laparoscopic VIHR with P4HB/ABCM are favorable and encourages further studies on the role of absorbable biosynthetic mesh materials in hernia surgery.

Single anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S): short-term outcomes from a prospective cohort study.

BACKGROUND: Single anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) is a modification of the classic duodenal switch (DS). These modifications are intended to address concerns about DS, including malnutrition, longer operative times, and technical challenges, while preserving the benefits. OBJECTIVES: To evaluate safety and outcomes of SADI-S as it compares to classic DS procedure. SETTING: Bariatric Surgery Center of Excellence, University Hospital, Montreal, Canada. METHODS: In a single-institution prospective cohort study, we compared safety and outcomes of the SADI-S versus DS procedures (ClinicalTrials.gov: NCT02792166; registered: 06/2016). Data is depicted as count (percentage) or median (interquartile range). RESULTS: There were 42 patients who underwent SADI-S, of whom 11 had it as a second-stage procedure (26%). There were 20 patients who underwent DS, of whom 12 had it as second-stage procedures (60%). Both groups were similar at baseline. The median age was 45 (14) years, 39 (63%) were female, the median body mass index (BMI) was 48.2 (7.7) kg/m2, and 29 (47%) patients had diabetes. The operative time was shorter for 1-stage SADI-S versus DS surgery (211 [70] versus 250 [60] min, respectively; P = .05) but was similar for second-stage procedures (P = .06). The 90-day complication rates were 11.9% (N = 5/42) after SADI-S and 5.0% (N = 1/20) after DS surgery (P = .64). There were no mortalities. Median follow-ups for 1-stage SADI-S and DS were 17 (11) and 12 (24) months, respectively (P = .65). Similar BMI changes were observed after 1-stage SADI-S (17.9 kg/m2 [8.7]) and DS (17.5 kg/m2 [16]; P = .65). At median follow-ups of 10 (20) and 14 (16) months after second-stage SADI-S and DS, respectively (P = .53), surgical procedures yielded added 5.0 kg/m2 (5.8) and 6.5 kg/m2 (7.1) changes in BMI, respectively (P = .26). Complete remission rates for diabetes were 91% after SADI-S (n = 21/23) and 50% after DS (n = 3/6). Compared with the SADI-S procedure, DS surgery was associated with higher frequencies of deficiencies in some fat-soluble vitamins, especially vitamin D. CONCLUSIONS: The SADI-S procedure is safe, and its short-term outcomes, including weight loss and the resolution of co-morbidities, are similar to those of DS. SADI-S surgery also has promising potential as a second-stage procedure after sleeve gastrectomy.

Laparoscopic Transgastric Resection of a Gastric Submucosal Tumor near Esophagogastric Junction with Concomitant Sleeve Gastrectomy: a Video Case Report.

BACKGROUND: Over the past two decades, there has been a significant rise in bariatric surgery. As a consequence, the prevalence of obese patients with a combined gastric pathology such as a submucosal tumor (SMT) requiring excision at the same time as bariatric surgery is higher but the management remains controversial. We report the safety and effectiveness of a simultaneous laparoscopic transgastric resection of a large gastric SMT near the esophagogastric junction (EGJ) with sleeve gastrectomy (SG). METHODS: We present a video report of a 52-year-old male (BMI = 49 kg/m2) referred for bariatric surgery, who was found to have a large SMT 2 cm from the EGJ on the lesser curvature on previous gastroscopy. RESULTS: Using five ports placed for laparoscopic SG, the gastric SMT was localized through an anterior gastrotomy and fully excised using a linear stapler and the gastrotomy site was closed. SG was then performed over a 54Fr bougie, including the gastrotomy suture closure. CONCLUSIONS: Several factors play important roles in deciding the best surgical approach for patients who are candidates for bariatric surgery and have concomitant gastric SMTs. This video report describes a safe and effective technique of simultaneous transgastric resection of a lesser curvature gastric SMT near the EGJ in a patient undergoing SG.

Pigment Epithelium-Derived Factor Declines in Response to an Oral Glucose Load and Is Correlated with Vitamin D and BMI but Not Diabetes Status in Children and Young Adults.

BACKGROUND: Pigment epithelium-derived factor (PEDF) is associated with obesity and diabetes complications in adults, yet little is known about PEDF in younger individuals. We investigated the relationship between PEDF and various metabolic biomarkers in young healthy volunteers (HV) and similar-aged patients with diabetes (type 1 and type 2). METHODS: A fasting blood sample was collected in 48 HV, 11 patients with type 1 diabetes (T1D), and 11 patients with type 2 diabetes (T2D) 12-25 years of age. In 9 healthy subjects, PEDF was also serially measured during a frequently sampled oral glucose tolerance test (OGTT). RESULTS: PEDF was positively correlated with BMI and systolic blood pressure and negatively correlated with vitamin D. Upon multivariable analysis, BMI and vitamin D were independent predictors of PEDF. Prior to adjustment, PEDF was highest in T2D patients (7,168.9 ± 4417.4 ng/mL) and lowest in individuals with T1D (2,967.7 ± 947.1 ng/mL) but did not differ by diagnosis when adjusted for BMI and vitamin D. Among volunteers who underwent an OGTT, PEDF declined by ∼20% in response to an oral glucose load. CONCLUSION: PEDF was acutely regulated by a glucose load and was correlated with BMI but not with diabetes. The negative correlation with vitamin D, independent of BMI, raises the question whether PEDF plays a compensatory role in bone matrix mineralization.

Novel blood test to predict neoplastic activity in healthy patients and metastatic recurrence after primary tumor resection.

We reported that single oncosuppressor-mutated (SOM) cells turn malignant when exposed to cancer patients' sera. We tested the possibility to incorporate this discovery into a biological platform able to detect cancer in healthy individuals and to predict metastases after tumor resection. Blood was drawn prior to tumor resection and within a year after surgery. Blood samples from healthy individuals or metastatic patients were used as negative and positive controls, respectively. Patients at risk for cancer were included in the screening cohort. Once treated, cells were injected into nonobese diabetic/severe combined immunodeficiency mice to monitor tumor growth. All samples of sera coming from metastatic patients transformed SOM cells into malignant cells. Four samples from screened patients transformed SOM cells. Further clinical tests done on these patients showed the presence of early cancerous lesions despite normal tumor markers. Based on the xenotransplants size, we were able to predict metastasis in three patients before diagnostic tests confirmed the presence of the metastatic lesions. These data show that this serum-based platform has potentials to be used for cancer screening and for identification of patients at risks to develop metastases regardless of the Tumor Node Metastasis (TNM) stage or tumor markers level.

ARFGAP1 is dynamically associated with lipid droplets in hepatocytes.

The ARF GTPase Activating Protein 1 (ARFGAP1) associates mainly with the cytosolic side of Golgi cisternal membranes where it participates in the formation of both COPI and clathrin-coated vesicles. In this study, we show that ARFGAP1 associates transiently with lipid droplets upon addition of oleate in cultured cells. Also, that addition of cyclic AMP shifts ARFGAP1 from lipid droplets to the Golgi apparatus and that overexpression and knockdown of ARFGAP1 affect lipid droplet formation. Examination of human liver tissue reveals that ARFGAP1 is found associated with lipid droplets at steady state in some but not all hepatocytes.

Laparoscopic removal of poor outcome gastric banding with concomitant sleeve gastrectomy.

BACKGROUND: Laparoscopic adjustable gastric banding (LAGB) has a significant incidence of long-term failure, which may require an alternative revisional bariatric procedure to remediate. Unfortunately, there is few data pinpointing which specific revisional procedure most effectively addresses failed gastric banding. Recently, it has been observed that laparoscopic sleeve gastrectomy (LSG) is a promising primary bariatric procedure; however, its use as a revisional procedure has been limited. This study aims to evaluate the safety and efficacy of LSG performed concomitantly with removal of a poor-outcome LAGB. METHODS: A retrospective review was performed on patients who underwent LAGB removal with concomitant LSG at King Saud University in Saudi Arabia between September 2007 and April 2012. Patient body mass index (BMI), percentage of excess weight loss (%EWL), duration of operation, length of hospital stay, complications after LSG, and indications for revisional surgery were all reviewed and compared to those of patients who underwent LSG as a primary procedure. RESULTS: Fifty-six patients (70 % female) underwent conversion of LAGB to LSG concomitantly, and 128 (66 % female) patients underwent primary LSG surgery. The revisional and primary LSG patients had similar preoperative ages (mean age 33.5 ± 10.7 vs. 33.6 ± 9.0 years, respectively; p = 0.43). However, revisional patients had a significantly lower BMI at the time of surgery (44.4 ± 7.0 kg/m(2) vs. 47.9 ± 8.2; p < 0.01). Absolute BMI postoperative reduction at 24 months was 14.33 points in the revision group and 18.98 points in the primary LSG group; similar %EWL was achieved by both groups at 24 months postoperatively (80.1 vs. 84.6 %). Complications appeared in two (5.5 %) revisional patients and in nine (7.0 %) primary LSG patients. No mortalities occurred in either group. CONCLUSIONS: Conversion of LAGB by means of concomitant LSG is a safe and efficient procedure and achieves similar outcomes as primary LSG surgery alone.