Conversion of one-anastomosis gastric bypass (OAGB) to Roux-en-Y gastric bypass (RYGB) for gastroesophageal reflux disease (GERD): who is more at risk? A multicenter study.

BACKGROUND: Although gastroesophageal reflux disease (GERD) affects 0.6% to 10% of patients operated on for one-anastomosis gastric bypass (OAGB), only about 1% require surgery to convert to Roux-en-Y gastric bypass (RYGB) [3-5]. The aim of the present study was to analyze the characteristics of OAGB patients converted to RYGB for GERD not responding to medical treatment. METHODS: This retrospective multicenter study included patients who underwent conversion from OAGB to RYGB for severe GERD. The conversion was performed with resection of the previous gastro-jejunal anastomosis and the use of the afferent loop as a new biliary loop. RESULTS: A total of 126 patients were included in the study. Of these patients, 66 (52.6%) had a past medical history of bariatric restrictive surgery (gastric banding, sleeve gastrectomy). A hiatal hernia (HH) was present in 56 patients (44.7%). The association between previous restrictive surgery and HH was recorded in 33 (26.2%) patients. Three-dimensional gastric computed tomography showed an average gastric pouch volume of 242.4 ± 55.1 cm3. Conversion to RYGB was performed on average 60 ± 35.6 months after OAGB. Seven patients (5.5%) experienced an early postoperative complication (4 patients grade IIIb and 3 grade IIb), and 3 (2.4%) a late complication. Patients showed further weight loss after RYGB conversion and an average of 24.8 ± 21.7 months after surgery, with a mean % of total weight loss (%TWL) of 6.9 ± 13.6 kg. From a clinical point of view, the problem of GERD was definitively solved in more than 90% of patients. CONCLUSIONS: Situations that weaken the esogastric junction appear to be highly frequent in patients operated on for OAGB and converted to RYGB for severe reflux. Similarly, the correct creation of the gastric pouch could play an important role in reducing the risk of conversion to RYGB for GERD.

Resizing of the Gastric Pouch for Weight Regain after Laparoscopic Roux-en-Y Gastric Bypass and One-Anastomosis Gastric Bypass: Is It a Valid Option?

Introduction: The laparoscopic resizing of the gastric pouch (LPR) has recently been proposed as a revisional technique in the case of weight regain (WR) after gastric bypass procedures. The aim of this study was to report our experience with LPR for WR. Materials and Methods: All patients with WR ≥ 25% after gastric bypass and with a dilated gastric pouch and/or gastrojejunal anastomosis who underwent LPR between January 2017 and January 2022 were retrospectively reviewed. From a radiological point of view, a gastric pouch was considered dilated when its volume was calculated at >80 cm3 for LRYGB and >200 cm3 for OAGB upon a 3D-CT scan. The endoscopic criterion considered both the diameter of the gastrojejunal anastomosis and the gastric pouch volume. All anastomoses > 20 mm for LRYGB and >40 mm for OAGB were considered dilated, while a gastric pouch was considered endoscopically dilated when the retrovision maneuver with the gastroscope was easily performed. These selection criteria were arbitrarily established on the basis of both our personal experience and literature data. Results: Twenty-three patients had LPR after a Roux-en-Y gastric bypass or one-anastomosis gastric bypass. The mean BMI at LPR was 36.3 ± 4.7 kg/m2. All patients underwent LPR, while the resizing of the GJA was also performed in 3/23 (13%) cases, and hiatoplasty was associated with the resizing of the pouch in 6/23 cases (26.1%). The mean BMI at the last follow-up was 29.3 ± 5.8 kg/m2. The difference between the BMI before resizing and the BMI at the last follow-up visit was statistically significant (p = 0.00005). The mean %TWL at 24.2 ± 16.1 months was 19.6 ± 9%. Comorbidities had an overall resolution and/or improvement rate of 47%. The mean operative time was 71.7 ± 21.9 min. The conversion rate was nil. Postoperative complications occurred in two cases (8.7%). Conclusions: In our series, LPR for WR showed good results in weight loss and in improvement/resolution of comorbidities, with an acceptable complication rate and operative time. Only further studies with a greater cohort of patients and a longer postoperative follow-up will be able to highlight the long-term benefits of this technique.

Influence of gene polymorphisms in ulcer healing process after superficial venous surgery.

OBJECTIVE: Role of superficial venous surgery in reducing the time it takes for ulcers to heal is still controversial, although all studies confirm a significant reduction in ulcer recurrences. Recently, the HFE-C282Y and FXIII-V34L gene variants demonstrated a role in the risk of venous ulceration in primary chronic venous disorder (CVD) and in modulating lesion size in chronic venous ulcer (CVU), respectively. This study was conducted to investigate the role of HFE-C282Y and FXIII (V34L and P564L) gene variants in ulcer healing time after superficial venous surgery, by assessing the outcome of a cohort of homogeneous CVU patients. METHODS: The study selected 91 patients affected by primary CVU (CEAP C6, Ep, Asp, Pr), with the exclusion of any other comorbidity factor involved in delayed healing process, who underwent surgery. We assessed the ulcer area and the healing time. Patients were genotyped by polymerase chain reaction for FXIII (V34L and P564L) and for HFE-C282Y substitutions. RESULTS: Globally, CVU cases had a postoperative mean healing time of 8.5 +/- 5.7 weeks. For the subset of cases above and below the median value (M = 8.0 weeks), FXIII-V34L genotype distribution significantly differed (P < .0001). In addition, Kaplan-Meier analysis yielded specific healing time profiles for the different FXIII-V34L classes of genotype (P = .00001), with an increased risk of delayed healing for the FXIII-VV genotype (hazard ratio, 4.14; 95% confidence interval, 2.1 to 8.2; P = .00005). Although FXIII-P54L genotype distributions did not differ, homozygous 564LL cases (P = .005) and double carriers for both FXIII variants (P < .0001), had a significantly reduced healing time vs wild types. No differences in healing time were observed between carriers and noncarriers of the HFE-C282Y variant, whereas when these cases were stratified by FXIII-V34L genotypes, the L34 carriers had a significantly shorter healing time, irrespective of the HFE genotype. CONCLUSION: The FXIII-34L variant was significantly associated with shorter healing time after superficial venous surgery, suggesting a role in the healing and tissue regeneration phases. Conversely, HFE-C282Y, despite its role in ulcer establishment, did not affect the postoperative healing time. In perspective, the identification of patients with a poor prognosis may give clinicians the opportunity to modify management and to target tailored therapies in the view of a new and alternative concept of treatment based on pharmacogenomics.

The overlapping of local iron overload and HFE mutation in venous leg ulcer pathogenesis.

Chronic venous stasis determines red blood cell extravasation and either dermal hemosiderin deposits or iron-laden phagocytes. Several authors have suspected that iron could play a role in the pathogenesis of venous leg ulcers. They hypothesized that local iron overload could generate free radicals or activate a proteolytic hyperactivity on the part of metalloproteinases (MMPs) or else down-regulate tissue inhibitors of MMPs. However, they were unable to explain why iron deposits, visible in the legs of patients with chronic venous disease (CVD), cause lesions in only some individuals, whereas in others they do not. We hypothesized that such individual differences could be genetically determined and investigated the role of the C282Y and H63D mutations of the HFE gene. C282Y mutation significantly increases the risk of ulcer in primary CVD more than six times (OR = 6.69; 1.45-30.8; p = 0.01). Patients carrying the H63D variant have an earlier age of ulcer onset, by almost 10 years (p > 0.004). The increased risk of skin lesion and the early age of onset of the disease in HFE carriers confirm in a clinical setting that intracellular iron deposits of mutated macrophages have less stability than those of the wild type. We hypothesize that the physiologic iron protective mechanisms are affected by the HFE mutations and should be investigated in all diseases characterized by the combination of iron overload and inflammation.

Factor XIII contrasts the effects of metalloproteinases in human dermal fibroblast cultured cells.

Matrix metalloproteinases (MMPs) are overexpressed in venous leg ulcers, determining a breakdown of the main extracellular matrix (ECM) components owing mainly to collagenase activities, and so playing a crucial role in ulcer pathogenesis. The authors studied the effects of coagulation factor XIII (FXIII), which cross-links collagen and other ECM components, in human fibroblast cultured cells in the presence and in the absence of matrix metalloproteinases from Clostridium histolyticum collagenase. Clostridium collagenase at concentrations of 2.0, 1.0, and 0.5 mg/mL was added to normal human dermal fibroblasts cultured in the presence of 0.0, 1.0, and 5.0 U/mL of FXIII concentrate (Fibrogammin P, Aventis Behring). Cell counting and metabolically active fibroblast evaluation in the cultures were monitored for 72 hours, by means of trypan-blue dye and MTT test, respectively. The MTT test showed that at the highest collagenase concentration (2.0 mg/mL), the cell number decreased more than 95% in 72 hours of treatment and no significant differences were observed regardless of the FXIII concentrations utilized. At lower collagenase concentration (1.0 mg/mL), in absence or in presence of FXIII (1.0 U/mL), the cell number decreased by about 80% in 72 hours. In contrast, in the presence of higher FXIII levels (5.0 U/mL), cells suffered globally significantly less collagenase effects (p = 0.011) and the gain was appreciable at each time tested. Finally, at 0.5 mg/mL of collagenase concentration, in the absence of FXIII, the cell number decreased by about 60% in 72 hours, whereas in presence of FXIII 1.0 U/mL and 5.0 U/mL, cells decreased significantly less, by about 35% and 20%, respectively (p < 0.025 and p < 0.01, respectively). These data were also confirmed by direct cell counting utilizing the trypan-blue test. Factor XIII contrasts effectively the detrimental action of Clostridium collagenases in human fibroblast cultured cells. These results support several in vivo reports about the effectiveness of its topical application in order to enhance the venous ulcer healing processes.

Factor XIII V34L polymorphism modulates the risk of chronic venous leg ulcer progression and extension.

Low Factor XIII (FXIII) activity has been reported in the blood of patients with chronic venous leg ulcer (CVU). In vivo studies have described increased wound healing in CVU patients treated with FXIII concentrate, and in vitro studies have shown increased regenerative capacity in FXIII-treated fibroblasts. In addition, a common G-to-T polymorphism in the FXIIIA-subunit gene (V34L) significantly increases the activity and modifies the cross-linking properties of the FXIII molecule and this variant has been investigated as a protective factor against thrombosis, a recognized risk factor for CVU establishment. Therefore, the role of FXIII levels, FXIII V34L, FVR506Q, and FIIG20210A, common gene polymorphisms in the pathogenesis of CVU was investigated. Ninety-one patients with CVU and 195 healthy controls (91 of them sex- and age-matched) were PCR-genotyped for the FXIIIV34L, FVR506Q, and FIIG20210A substitutions and FXIIIA-subunit levels were determined by immuno-electrophoresis. The extent of the venous ulcer surface in patients was measured by computer software. The allele frequency and the genotype distribution of the FXIII polymorphism did not show significant differences between the whole group of cases and controls as well as prothrombin variants did. On the contrary, the FVR506Q variant (FV Leiden) allele was more frequent in patients, yielding a significant OR value of 5.93 (95 percent CI, 1.83-19.17; p= 0.003). Considering only CVU cases secondary to a post-thrombotic syndrome (n= 24), FV Leiden yielded a greater OR value of 16.08 (95 percent CI, 4.33-59.6; p < 0.0001). When the CVU cases were stratified by the three possible FXIII genotypes, a significant trend toward a lower mean value of the ulcerated area was clearly evident as the number of the polymorphic alleles (L34) increased in the genotype of patients (VV = 11.9 cm(2,)+/- 23.6; VL = 6.1 cm(2,)+/- 6.9; LL = 4.1 cm(2,)+/- 2.8; p= 0.01). On the other hand, FXIIIA antigen levels were similar between CVU cases and matched controls, but 11 percent of cases had FXIII deficiency (FXIIIA