Persistence of severe liver fibrosis despite substantial weight loss with bariatric surgery.

BACKGROUND AND AIMS: It remains unclear to what extent and which components of advanced liver disease improve after bariatric surgery. We herein describe the histological outcome in patients with advanced NASH and its relationship with weight loss and metabolic improvement. APPROACH AND RESULTS: One hundred ninety-six patients with advanced NASH underwent bariatric surgery, 66 of whom agreed to a follow-up liver biopsy at 6 ± 3 years (36 with advanced fibrosis [AF] and 30 with high activity [HA] grade without AF). Liver biopsies LBs were centrally read and histological response was defined as the disappearance of AF or HA. Bariatric surgery induced major histological improvement: 29% of patients had normal histology at follow-up biopsy; 74% had NASH resolution without fibrosis progression; and 70% had ≥1 stage fibrosis regression. However, AF persisted in 47% of patients despite NASH resolution and some degree of fibrosis reversal, only evidenced by the EPoS seven-tier staging classification. These patients had lower weight loss and reduced hypertension or diabetes remission rates. Older age and sleeve gastrectomy were the only independent predictors for persistent AF after adjustment for duration of follow-up. All HA patients had major histological improvement: 50% normal histology, 80% NASH resolution, and 86% a ≥1 grade steatosis reduction. Patients with normal liver at follow-up had the largest weight loss and metabolic improvement. Independent predictors of normal liver were amount of weight loss, high histological activity, and the absence of AF before surgery. CONCLUSIONS: Although bariatric surgery successfully reverses active steatohepatitis, AF can persist for many years and is associated with lesser weight loss and metabolic improvement. Weight loss alone may not be sufficient to reverse AF.

Cholangiocarcinoma Following Bariatric Surgery: a Prospective Follow-Up Single-Center Audit.

BACKGROUND: Cholangiocarcinoma (CC) incidence is rising worldwide. Obesity and its related metabolic impairments are associated with primitive liver malignancies including CC. While bariatric surgery (BS) is associated with decreased risk of incident cancer, few data are available regarding CC incidence, presentation, and management issues after BS. METHODS: We retrospectively reviewed collected data on 1911 consecutive patients undergoing BS from 2010 to 2019. RESULTS: We recorded three cases (0.16%) of CC during the postoperative follow-up. All cases underwent a Roux-en-Y gastric bypass (RYGB) for class III obesity with metabolic diseases (i.e., type 2 diabetes mellitus, hypertension, dyslipidemia, and obstructive sleep apnea) without any personal or familial history of biliary disease. The patients presented with an inaugural jaundice or pruritus at 8, 12, and 13 months after RYBG, which enabled the diagnosis of metastatic CCs in all cases. In such palliative setting without access to the pancreato-biliary system, biliary drainage was ensured by a percutaneous trans-hepatic biliary drain. Chemotherapy was initiated in two patients. All the patients died within a delay of 2, 11, and 17 months after the diagnosis, respectively. CONCLUSION: The incidence of post-BS CC appears low, but the prognosis is poor because of advanced stages at diagnosis. These cases illustrate the difficulty to make both on-time diagnosis and optimal management of CC especially in patients operated of RYGB with limited access to the excluded anatomy.

Immunological environment in colorectal cancer: a computer-aided morphometric study of whole slide digital images derived from tissue microarray.

Cancer research has moved from investigating tumour cells to including analysis of the tumour microenvironment as well. The aim of this study was to assess the cellular infiltrate of colorectal cancer (CRC) using computer-aided analysis of whole slide digital image derived from tissue microarray (TMA). TMA slides from 31 CRC patients were immunostained for forkhead box protein 3 (FOXP3) and immunomodulatory enzyme indoleamine 2,3-dioxygenase (IDO) at four sites: centre (C) and invasive front (F) of the tumour, proximal non-metastatic draining lymph node (N-), tumour-draining lymph node with metastasis (N+) and healthy mucosa at 10 cm from the cancer (M). We analysed the proportion of IDO+ tissue areas in the lamina propria or in the non-epithelial area of the lymph node and in epithelial cells in each site. The normal mucosa of patients operated on for benign disease was also analysed. The proportion (%) of FOXP3+ tissue area in C, F, N-, N+ and M were 2.3 ± 1.8, 2.6 ± 2.9, 6.0 ± 2.9, 14.2 ± 5.8 and 1.2 ± 0.8 (p < 0.001). The proportion (%) of IDO+ tissue area in the lamina propria of C, F, N-, N+ and M were 1.6 ± 3.1, 1.1 ± 1.3, 3.4 ± 2.5, 9.1 ± 8.5 and 6.7 ± 5.4 (p < 0.001). IDO+ tissue area in the lamina propria was not significantly different between healthy mucosa of patients with cancer than without (1.8 ± 3 vs 1.1 ± 0.95). The proportion of IDO positive tissue area in the epithelium was significantly higher in healthy mucosa of patients with cancer than without (5.4 ± 13.8 vs 2.1 ± 2.4). The FOXP3+ tissue area was increased in healthy mucosa of CRC patients in comparison with healthy mucosa of patients with colorectal resection for disease other than cancer: 1.20 ± 1.81 versus 0.81 ± 0.51 (p < 0.05). The proportion of IDO+ tissue area in lymph node (N-) was correlated with the proportion of FOXP3+ tissue area in tumour area (r = 0.44, p < 0.01). TMA technique permits simultaneous analysis of FOXP3+ and IDO+ cells at different sites including tumour, draining non-metastatic lymph node, metastatic lymph node and normal mucosa.

Laparoscopic reversal of mini-gastric bypass to original anatomy for severe postoperative malnutrition.

PURPOSE: Malnutrition after mini-gastric bypass (MGB) is a rare and dreaded complication with few data available regarding its surgical management. We aim to report the feasibility, safety, and results of laparoscopic reversal of MGB to normal anatomy (RMGB) in case of severe and refractory malnutrition syndrome after intensive nutritional support (SRMS). METHODS: A 10-year retrospective chart review was performed on patients who underwent RMGB (video included) for SRMS following MGB. RESULTS: Twenty-six of 2934 patients underwent a RMGB at a mean delay of 20.9 ± 13.4 months post-MGB. At presentation, mean body mass index (BMI), excess weight loss (%EWL), and albumin serum level were 22 ± 4.4 kg/m2, 103.6 ± 22.5%, and 25.5 ± 3.6 gr/L, respectively. Seventeen (63.5%) patients had at least one severe malnutrition related complication including severe edema in 13 (50%), venous ulcers in 2 (7.7%), infectious complications in 7 (27%), deep venous thrombosis in 5 (19.2%), and motor deficit in 5 (19.2%) patients. At surgical exploration, 8 of 12 (66.5%) patients had a biliary limb longer than 200 cm and 9 (34.6%) had bile reflux symptoms. Overall morbidity was 30.8% but lower when resecting the entire previous gastrojejunostomy with creation of a new jejunojejunostomy (8.3 vs 50%, p = 0.03). After a mean follow-up of 8 ± 9.7 months, all patients experienced a complete clinical and biological regression of the SRMS after the RMGB despite a mean 13.9 kg weight regain in 16 (61.5%) patients. CONCLUSIONS: Post-MGB SRMS and its related comorbidities are rare but dreaded conditions. Although burdened by a significant postoperative morbidity and weight regain, RMGB remains an effective option to consider, when intensive nutritional support fails.

[The place of bariatric surgery in the management of obesity]. / Place de la chirurgie bariatrique dans la prise en charge de l'obésité.

Surgical treatment of obesity, also called "bariatric surgery", is the reference treatment for severe and morbid forms of obesity after proper multidisciplinary medical treatment has failed. However, it is only one step in the pathway of the obese patient and should only be envisaged in the framework of lifelong nutritional care.

[Management of failures and complications in weight loss surgery]. / Échecs et complications de la chirurgie de l'obésité.

The specific management of the surgical risks linked to obesity, as well as technological advances combined with the standardisation of techniques, have significantly reduced the morbidity and mortality associated with bariatric surgery over recent decades. However, as with all surgery, patients are exposed to medical and surgical failures and complications.

Laparoscopic Transgastric Enucleation of a Gastric Leiomyoma near the Esophagogastric Junction and Concomitant Sleeve Gastrectomy: Video Report.

BACKGROUND: Obesity and bariatric surgery (BS) are increasing worldwide and can potentially lead to incidental diagnosis of benign gastric tumor including gastric leiomyoma (GL). When indicated, local tumor enucleation, completed through laparoscopic minimal-invasive approaches, has proven to be safe and effective especially when located near the esophagogastric junction (EGJ) with limited morbidity as compared to partial or total gastrectomies. Little is known regarding the most appropriate strategy concerning the management of GL regardless of the location in patients' candidate for BS. METHODS: We present the case of a 67-year-old morbidly obese woman. She presented with an incidental 3-cm GL developed near the EGJ and antral histologic abnormalities mandating a gastric follow-up. Therefore, we performed both laparoscopic transgastric enucleation and sleeve gastrectomy simultaneously. RESULTS: After identification of the lesion, the gastrocolic ligament was divided and a gastrotomy was performed along the greater curvature to expose the tumor. Once the submucosal plan was identified, the lesion was enucleated from the submucosamuscle junction. After closure of the mucosal defect and ensuring the absence of gastric wall perforation, a conventional laparoscopic sleeve gastrectomy was performed. No adverse outcomes occurred during the post-operative period. The final pathologic diagnosis showed a completely resected and benign leiomyoma. CONCLUSION: Herein, we report the first laparoscopic transgastric enucleation of a GL localized close to the EGJ performed concomitant with a sleeve gastrectomy. This combined approach appeared feasible, safe, and do not compromise the access to the GI tract as well as potential future curative treatments on the gastric sleeve.

Minimal Invasive Internal Liver Retractor in Conventional and Trans-umbilical Single-Incision Laparoscopic Sleeve Gastrectomy: Video Report.

BACKGROUND: Sleeve gastrectomy (SG) is a safe and efficient procedure with comparable results between conventional and single-incision approach in selected patients. However, the critical point in both approaches is the retraction of the hypertrophic and fatty left lobe of the liver which increases technical difficulties and limit the exposure of the hiatus. Traditional liver retractors require an additional sub-xiphoid incision for insertion and cause post-operative pain as well as iatrogenic liver injuries. Various techniques have been described to allow adequate liver retraction through smaller incisions or fewer ports without compromising patient safety. However, some disadvantages of these methods are the need for incision of the liver ligament or diaphragmatic crura puncture rendering the device difficult to reposition. MATERIALS AND METHODS: Two morbidly obese patients underwent a SG by conventional laparoscopy and by trans-umbilical single-incision using a novel minimal invasive internal liver retractor: the Versa Lifter Band®. RESULTS: This soft and flexible internal retractor was fully repositionable and adjustable intraoperatively. The time required to complete the liver retraction was 4 min 12 s in conventional surgery and 5 min 23 s in single-incision approach. Liver retraction was always satisfying resulting in limited intra-operative difficulties without the need of additional retractors/ports or conversion in both patients. No adverse outcomes occurred during the intra and post-operative periods without rise in aspartate aminotransferase and alanine-aminotransferase serum levels. CONCLUSION: In our preliminary experience, this internal liver retractor was easy to handle and provided an effective and safe retraction with good exposure of the surgical field and improved ergonomy in single incision as well as reduced port laparoscopic SG.

Presentation and surgical management of leaks after mini-gastric bypass for morbid obesity.

BACKGROUND: Few data exist about the characteristics and management of enteric leaks after mini-gastric bypass (MGB). OBJECTIVES: We aimed to describe the incidence, presentation, and surgical management of enteric leaks in patients who underwent laparoscopic MGB for morbid obesity. SETTING: Private practice. METHODS: An 8-year, 9-month retrospective chart review was performed on patients who had enteric leak requiring reoperation after MGB at a single institution. RESULTS: Thirty-five of 2321 patients were included. Ninety-seven percent had symptoms. Arterial hypertension and heavy smoking were predicting factors of leaks occurrence post-MGB (P<.01). Enteric leak was diagnosed by systematic upper gastrointestinal series in 4 pts (11.4%) and by computed tomography with oral water soluble contrast in 4 of 31 pts (13%). In the other 27 patients, diagnosis of the leak was made intraoperatively. Eleven patients (32%) had leak arising from the gastric stapler line (type 1), 4 (11%) from the gastrojejunal anastomosis (type 2), and 20 (57%) from undetermined origin. The most common presentation was intra-abdominal abscess in type 1 and leaks of undetermined origin and generalized peritonitis in type 2. One third of the patients who underwent reoperation developed well-drained chronic fistula into the irrigation-drainage system, with complete healing in all patients without any further procedure. The mean hospital stay was 19 days with no mortality reported. CONCLUSION: Enteric leak leading to intra-abdominal sepsis post-MGB is rare (1.5%) An operative aggressive management based on clinical symptoms is the treatment of choice allowing no postoperative leak-related mortality and complete healing.

Nonalcoholic fatty liver disease increases the risk of hepatocellular carcinoma in patients with alcohol-associated cirrhosis awaiting liver transplants.

BACKGROUND & AIMS: Many patients with alcohol-associated cirrhosis also have diabetes, obesity, or insulin resistance-mediated steatosis, but little is known about how these disorders affect the severity of liver disease. We analyzed the prevalence and prognostic implications of metabolic risk factors (MRFs) such as overweight, diabetes, dyslipidemia, and hypertension in patients with alcohol-associated cirrhosis awaiting liver transplants. METHODS: We performed a retrospective study of 110 patients with alcohol-associated cirrhosis (77% male; mean age, 55 y; 71% with >6 mo of abstinence) who received liver transplants at a single center in Paris, France, from 2000 through 2013. We collected data on previous exposure to MRFs, steatosis (>10% in the explant), and histologically confirmed hepatocellular carcinoma (HCC). RESULTS: HCC was detected in explants from 29 patients (26%). Steatosis was detected in explants from 47 patients (70% were abstinent for ≥6 mo); 50% had a history of overweight or type 2 diabetes. Fifty-two patients (47%) had a history of MRFs and therefore were at risk for nonalcoholic fatty liver disease. A higher proportion of patients with MRF had HCC than those without MRF (46% vs 9%; P < .001). A previous history of overweight or type 2 diabetes significantly increased the risk for HCC (odds ratio, 6.23; 95% confidence interval [CI], 2.47-15.76, and odds ratio, 4.63; 95% CI, 1.87-11.47, respectively; P < .001). MRF, but not steatosis, was associated with the development of HCC (odds ratio, 11.76; 95% CI, 2.60-53; P = .001) independent of age, sex, amount of alcohol intake, or severity of liver disease. CONCLUSIONS: Patients with alcohol-associated cirrhosis who received transplants frequently also had nonalcoholic fatty liver disease. MRFs, particularly overweight, obesity, and type 2 diabetes, significantly increase the risk of HCC.

Right colon to rectal anastomosis (Deloyers procedure) as a salvage technique for low colorectal or coloanal anastomosis: postoperative and long-term outcomes.

BACKGROUND: After extended left colectomy, it may be difficult to take down a well-vascularized colon into the pelvis and perform a tension-free colorectal or coloanal anastomosis. The Deloyers procedure comprising complete mobilization and rotation of the right colon while maintaining the ileocolic artery may be used in this circumstance. OBJECTIVE: The aim of this study is to report postoperative and long-term outcomes after the Deloyers procedure as a salvage technique for colorectal anastomosis or coloanal anastomosis. DESIGN: From a prospective database, we retrospectively reviewed all patients who underwent a Deloyers procedure. SETTING: This study was conducted at the Colorectal Unit in a tertiary referral teaching hospital. PATIENTS: Between 1998 and 2011, 48 consecutive patients underwent a Deloyers procedure. Indications were as following: Hartmann reversal (n = 17), previous colorectal anastomosis-related complications (n = 11), diverticular disease (n = 6), left colon cancer (n = 6), ischemic colitis (n = 3), iterative colectomy for cancer (n = 3), rectal cancer local recurrence (n = 1), and synchronous colon cancer (n = 1). RESULTS: There were 38 men and 10 women (median age at surgery, 67 years). Colorectal anastomosis and coloanal anastomosis were performed in 38 and 10 patients. Thirty-one patients had defunctioning stoma. Mortality and early morbidity rate was 2% and 23%. Three patients (6%) had severe complications (Dindo ≥ 3). There was no anastomotic leakage. Reoperation was required in 2 patients for intra-abdominal hemorrhage. The median hospital stay was 12 days. The median follow-up was 26 months. All patients had their ileostomy closed. Twenty-three percent of patients developed late complications. The median number of bowel movements per day was 3 (range, 1-7), but 67% of patients had fewer than 3. One patient required an ileostomy refashioning because of poor functional results, and 23% of patients routinely take loperamide-based medication. LIMITATION: The retrospective nature of the study was a limitation. CONCLUSIONS: The Deloyers procedure is safe, associated with low morbidity and good long-term functional results. It represents a safe alternative to total colectomy and ileorectal anastomosis.

Thrombocytopenia, splenomegaly, and portal blood flow in patients who have undergone liver transplantation for cirrhosis.

The platelet count (PC), the spleen size (SS), and the portal blood flow (PBF) have been independently studied in the perioperative period after orthotopic liver transplantation (OLT) for cirrhosis, but these parameters have not been described and analyzed in combination. We analyzed PC data and Doppler sonography measurements of SS and PBF from 125 adult patients before OLT and 1, 3, 6, 9, and 12 months after transplantation. A linear mixed model with fixed subject random intercepts was used. PCs increased significantly from 101.5 ± 68.5 × 10(9) /L before OLT to 162.4 ± 86 × 10(9) /L 1 month after OLT and remained stable for 1 year after the operation. PBF increased significantly from 619 ± 239 mL/minute before OLT to 1379 ± 491 mL/minute after OLT and remained stable during the first year. SS slowly decreased after OLT, but the decrease became significant only 9 months after the operation (13.8 ± 4.2 cm before OLT versus 11.7 ± 3.7 cm at 9 months, P < 0.05). The cirrhosis etiology did not influence the evolution of the parameters. With or without replication or interferon treatment before OLT, the hepatitis C group viruses did not influence PCs postoperatively. The evolution of SS was correlated to the evolution of PCs in the year after transplantation. In conclusion, PCs and PBF increase rapidly after OLT, whereas SS slowly decreases. The cirrhosis etiology does not influence the evolution of PCs. Thrombocytopenia and splenomegaly are 2 results of portal hypertension, but the rapid normalization of PBF does not completely or rapidly reverse these 2 phenomena.

Inhibitory effect of TNF-α on malaria pre-erythrocytic stage development: influence of host hepatocyte/parasite combinations.

BACKGROUND: The liver stages of malaria parasites are inhibited by cytokines such as interferon-γ or Interleukin (IL)-6. Binding of these cytokines to their receptors at the surface of the infected hepatocytes leads to the production of nitric oxide (NO) and radical oxygen intermediates (ROI), which kill hepatic parasites. However, conflicting results were obtained with TNF-α possibly because of differences in the models used. We have reassessed the role of TNF-α in the different cellular systems used to study the Plasmodium pre-erythrocytic stages. METHODS AND FINDINGS: Human or mouse TNF-α were tested against human and rodent malaria parasites grown in vitro in human or rodent primary hepatocytes, or in hepatoma cell lines. Our data demonstrated that TNF-α treatment prevents the development of malaria pre-erythrocytic stages. This inhibitory effect however varies with the infecting parasite species and with the nature and origin of the cytokine and hepatocytes. Inhibition was only observed for all parasite species tested when hepatocytes were pre-incubated 24 or 48 hrs before infection and activity was directed only against early hepatic parasite. We further showed that TNF-α inhibition was mediated by a soluble factor present in the supernatant of TNF-α stimulated hepatocytes but it was not related to NO or ROI. Treatment TNF-α prevents the development of human and rodent malaria pre-erythrocytic stages through the activity of a mediator that remains to be identified. CONCLUSIONS: Treatment TNF-α prevents the development of human and rodent malaria pre-erythrocytic stages through the activity of a mediator that remains to be identified. However, the nature of the cytokine-host cell-parasite combination must be carefully considered for extrapolation to the human infection.

Variant on Manifestation of Duodenal Metastasis 26 Years after Initial Diagnosis of Primary Cutaneous Melanoma.

Malignant duodenal neoplasms are relatively rare, and the diagnosis is often delayed because of their vague and nonspecific symptoms. We report the case of a 79-year-old female who had a medical history of malignant melanoma of the cheek that had initially been diagnosed at 53 years of age. Work-up revealed severe stenosis of the duodenum caused by a large mass with ulceration at the tip of its mucosal surface. Tumor biopsy led to a histological diagnosis of extremely poorly differentiated carcinoma, but it was impossible to determine whether the lesion was a primary neoplasm or represented secondary involvement. Pancreatoduodenectomy was performed, and the surgical specimen showed a protuberant tumor in the nonampullary region of the second portion of the duodenum. Final diagnosis of metastatic duodenal melanoma was made by immunohistological examination. She is currently alive without recurrence 28 months after the surgical treatment.

Procalcitonin in liver transplantation: are high levels due to donors or recipients?

INTRODUCTION: To date, a specific marker to evaluate and predict the clinical course or complication of the liver-transplanted patient is not available in clinical practice. Increased procalcitonin (PCT) levels have been found in infectious inflammation; poor organ perfusion and high PCT levels in the cardiac donor appeared to predict early graft failure. We evaluated PCT as a predictor of early graft dysfunction and postoperative complications. METHODS: PCT serum concentrations were measured in samples collected before organ retrieval from 67 consecutive brain-dead donors and in corresponding recipients from day 0, before liver transplantation, up to day 7 after liver transplantation. The following parameters were recorded in donors: amount of vasopressive drug doses, cardiac arrest history 24 hours before retrieval, number of days in the intensive care unit, age of donor, and infection in donor, and the following parameters were recorded in recipients: cold and warm ischemia time, veno-venous bypass, transfusion amount during orthotopic liver transplantation (OLT), and occurrence of postoperative complication or hepatic dysfunction. RESULTS: In the donor, the preoperative level of PCT was associated with cardiac arrest and high doses of catecholamines before organ retrieval. In the recipient, elevated PCT levels were observed early after OLT, with a peak at day 1 or 2 after OLT, then a decrease until day 7. A postoperative peak of PCT levels was associated neither with preoperative PCT levels in the donor or the recipients nor with hepatic post-OLT dysfunction or other postoperative complications, but with two donor parameters: infection and cardiac arrest. CONCLUSION: PCT level in the donor and early PCT peak in the recipient are not predictive of post-OLT hepatic dysfunction or other complications. Cardiac arrest and infection in the donor, but not PCT level in the donor, are associated with high post-OLT PCT levels in the recipient.