Endoluminal vacuum-assisted therapy as treatment for anastomotic leak after ileal pouch-anal anastomosis: a pilot study.

BACKGROUND: Anastomotic leak after ileal pouch-anal anastomosis (IPAA) could lead to poor functional results and failure of the pouch. The aim of the present study was to analyze the outcomes of the vacuum-assisted closure therapy as the unique treatment for anastomotic leaks following IPAA without any additional surgical operations. METHODS: Consecutive patients with anastomotic leak after IPAA treated at our institution between March 2016 and March 2017 were prospectively enrolled. After diagnosis, the Endosponge® device was positioned in the gap and replaced until the cavity was reduced in size and covered by granulating tissue. A pouchoscopy was performed every week for the first month and monthly subsequently. No additional procedures were performed. RESULTS: Eight patients were included in the study. The leak was diagnosed at a median of 14 (6-35) days after surgery. At the time of diagnosis, seven patients had a defunctioning ileostomy performed as routine at the time of pouch formation, while one patient was diagnosed after ileostomy closure and underwent emergency diversion ileostomy. The Endosponge® treatment started after a median of 6.5 (1-158) days after the diagnosis of the leakage and was carried on for a median of 12 (3-42) days. The device was replaced a median of 3 (1-10) times. The median length of hospital stay after the first application of the treatment was 15.5 (6-48) days. The complete healing of the leak was documented in all patients, after a median of 60 (24-90) days from the first treatment. All patients but one had their ileostomy reversed at a median of 2.5 (1-6) months from the confirmation of the complete closure. CONCLUSIONS: Endosponge® is effective as the only treatment after IPAA leak. Based on the results of our prospective pilot study, application of Endosponge® should be the treatment of choice in selected pouch anastomotic leaks not requiring immediate surgery. These results will have to be confirmed by future prospective studies including a larger number of patients.

Multimodal Surgical Approach for Adult Patients With Chronic Intestinal Pseudo-Obstruction: Clinical and Psychosocial Long-term Outcomes.

BACKGROUND: Clinical and psychosocial outcomes of a multimodal surgical approach for chronic intestinal pseudo-obstruction were analyzed in 24 patients who were followed over a 2- to 12-year period in a single center after surgery or intestinal/multivisceral transplant (CTx). METHODS: The main reasons for surgery were sub-occlusion in surgery and parenteral nutrition-related irreversible complications with chronic intestinal failure in CTx. RESULTS: At the end of follow-up (February 2015), 45.5% of CTx patients were alive: after transplantation, improvement in intestinal function was observed including a tendency toward recovery of oral diet (81.8%) with reduced parenteral nutrition support (36.4%) in the face of significant mortality rates and financial costs (mean, 202.000 euros), frequent hospitalization (mean, 8.8/re-admissions/patient), as well as limited effects on pain or physical wellness. CONCLUSIONS: Through psychological tests, transplant recipients perceived a significant improvement of mental health and emotional state, showing that emotional factors were more affected than were functional/cognitive impairment and social interaction.

Alemtuzumab plus cyclosporine treatment of the autoimmune hemolytic anemia in an adult bowel transplant.

An adult male underwent a bowel transplant for tufting enteropathy, receiving alemtuzumab, tacrolimus, and steroids as immunosuppressants. Five years later, he developed an autoimmune hemolytic anemia (AIHA), anti-IgG positive, with reduced reticulocyte count, leukopenia, and thrombocytopenia with antiplatelet antibodies. After an unsuccessful initial treatment with high dose steroids, reduction in tacrolimus dose, and intravenous immunoglobulin (IVIG), a bone marrow biopsy revealed absence of erythroid maturation with precursor hyperplasia. The patient was switched to sirolimus and received four doses of rituximab plus two courses of plasmapheresis, which decreased his transfusion requirements. After a febrile episode one month later, the AIHA relapsed with corresponding decreases in platelet and leukocyte count: cyclosporine A (CsA) was started with a second course of rituximab and IVIG without response, even though repeat bone marrow biopsy did not reveal morphology correlated to an acquired pure red cell aplasia (APRCA). Considering the similarity in his clinical and laboratory findings to APRCA, alemtuzumab was added (three doses over a week) with CsA followed by steroids. The patient was eventually discharged transfusion-independent, with increasing hemoglobin (Hb) levels and normal platelet and leukocyte count. One year later he is still disease-free with functioning graft.

Long-term endoscopic follow-up in small bowel transplant recipients: single-center series.

BACKGROUND: The reliability of endoscopic findings after adult intestinal transplantation on short-term follow-up has been shown. The aim of this study was to evaluate in a long-term follow-up the diagnostic value of endoscopies compared with the biopsy value. METHODS: We evaluated 52 endoscopies over a period of 2 years (2 in each patient in 2010 and 1 in each patient in 2011, plus 1 endoscopy for suspected post-transplant lymphoproliferative disease [PTLD]) on 17 recipients transplanted between the years 2000 and 2006 (more than 5 years of follow-up). RESULTS: All the 52 endoscopic findings were comparable to biopsy definitive results: only 1 case of mild enteritis and 1 case of Epstein-Barr virus (EBV) chronic infection at biopsy were not diagnosed by endoscopy. One case of rectal PTLD and 1 of EBV-related enteritis were diagnosed by use of both procedures. Specificity was 98%: we did not calculate sensitivity because no episodes of rejection were diagnosed because recipients were stable in long-term follow-up. CONCLUSIONS: Endoscopy is a reliable procedure even on a long-term follow-up after intestinal transplantation, allowing a support to biopsy for diagnosis on adult recipients, especially for EBV infections and PTLD surveillance.

Disease-related intestinal transplant in adults: results from a single center.

Intestinal transplantation is gaining worldwide acceptance as the main option for patients with irreversible intestinal failure and complicated total parenteral nutrition course. In adults, the main cause is still represented by short bowel syndrome, but tumors (Gardner syndrome) and dismotility disorders (chronic intestinal pseudo-obstruction [CIPO]) have been treated increasingly by this kind of transplantation procedure. We reviewed our series from the disease point of view: although SBS confirmed results achieved in previous years, CIPO is nowadays demonstrating an excellent outcome similar to other transplantation series. Our results showed indeed that recipients affected by Gardner syndrome must be carefully selected before the disease is to advanced to take advantage of the transplantation procedure.

Operative endoscopy for treatment of native rectal post-transplantation lymphoproliferative disease after adult small bowel transplantation: a case report.

Post-transplantation lymphoproliferative disease (PTLD) of the gastrointestinal (GI) tract is often recognized in transplant recipients. Small bowel recipients are prone to develop GI disease due to the higher incidence of Epstein-Barr Virus (EBV) infection and enteritis as a consequence of heavy immunosuppressive regimens. So far treatment has been based on anti-CD20 therapy (Rituximab), modulation of immunosuppression, antiviral therapy (Gancyclovir), and surgery (up to allograft enterectomy if necessary), whereas endoscopy is usually used to perform the diagnosis via biopsy. We report a case of an adult small bowel recipient, who underwent transplantation due to Gardner's Syndrome 6 years earlier and was EBV positive. A native rectal PTLD was treated using opertive endoscopy combined with antiviral therapy using 4 courses of Rituximab for positive pelvic lymph nodes in addition to reduced immunosuppression. Two years after treatment the recipient is alive and disease-free with a functional graft.

Mortality after steroid-resistant acute cellular rejection and chronic rejection episodes in adult intestinal transplants: report from a single center in induction/preconditioning era.

Steroid-resistant acute cellular rejection (ACR) and chronic rejection (CR) are still major concerns after intestinal transplantation. We report our experience from a single center on 48 adults recipients using 49 grafts from 2001 to 2011, immunosuppressing them initially with daclizumab initially and later Alemtuzumab. Overall patient survival was 41.9% at 10 years while graft survival was 38.5%. The steroid-resistant ACR population of 14 recipients (28.5%) experienced 50% mortality mainly due to sepsis, while the five (8%) CR recipients, included two survivors. All but 1 graft was placed without a liver. CR was often preceded by ACR episodes. Mortality related to steroid-resistant ACR and CR still affects the intestinal transplant population despite induction/preconditioning, especially in the absence of a protective liver effect of the liver. New immunosuppressive strategies are needed.

Prevalence and clinical picture of gastroesophageal prolapse in gastroesophageal reflux disease.

The prevalence of gastroesophageal (GE) mucosal prolapse in patients with gastroesophageal reflux disease (GERD) was investigated as well as the clinical profile and treatment outcome of these patients. Of the patients who were referred to our service between 1980 and 2008, those patients who received a complete diagnostic work-up, and were successively treated and followed up at our center with interviews, radiology studies, endoscopy, and, when indicated, esophageal manometry and pH recording were selected. The prevalence of GE prolapse in GERD patients was 13.5% (70/516) (40 males and 30 females with a median age of 48, interquartile range 38-57). All patients had dysphagia and reflux symptoms, and 98% (69/70) had epigastric or retrosternal pain. Belching decreased the intensity or resolved the pain in 70% (49/70) of the cases, gross esophagitis was documented in 90% (63/70) of the cases, and hiatus hernias were observed in 62% (43/70) of the cases. GE prolapse in GERD patients was accompanied by more severe pain (P < 0.05) usually associated with belching, more severe esophagitis, and dysphagia (P < 0.05). A fundoplication was offered to 100% of the patients and was accepted by 56% (39/70) (median follow up 60 months, interquartile range 54-72), which included two Collis-Nissen techniques for true short esophagus. Patients who did not accept surgery were medically treated (median follow up 60 months, interquartile range 21-72). Persistent pain was reported in 98% (30/31) of medical cases, belching was reported in 45% (14/31), and GERD symptoms and esophagitis were reported in 81% (25/31). After surgery, pain was resolved in 98% (38/39) of the operative cases, and 79% (31/39) of them were free of GERD symptoms and esophagitis. GE prolapse has a relatively low prevalence in GERD patients. It is characterized by epigastric or retrosternal pain, and the need to belch to attenuate or resolve the pain. The pain is allegedly a result of the mechanical consequences of prolapse of the gastric mucosa into the esophagus.

Acute cellular rejection monitoring after intestinal transplant: utility of serologic markers and zoom videoendoscopy as support of conventional biopsy and clinical findings.

Acute cellular rejection (ACR) episodes in intestinal transplant recipients are diagnosed by histologic and clinical findings. We have applied zoom video endoscopy and the use of serologic markers granzyme B (GrB) and perforin (PrF) to monitor rejection together with conventional tools. Seven hundred eighty-two blood samples (obtained at the time of the biopsy) collected from 34 recipients for GrB/PrF upregulation were positive among 64.9% of ACRs during a 3-year follow-up. Considering only the first year results posttransplantation, it reached 73.1% of rejection events. Zoom videoendoscopy was used by our group in 29 recipients of isolated intestine (n = 24) or multivisceral transplantations (n = 5) to enable observation of villi and crypt areas. From more than 270 procedures, 84% of the zoom findings agreed with the histologic results, namely, a specificity of 95%. In fact, during ongoing ACR, villi were altered in 80% of cases. Both procedures were helpful to support conventional histologic findings and clinical symptoms of ACR in intestinal transplant recipients.

Rejection episodes and 3-year graft survival under sirolimus and tacrolimus treatment after adult intestinal transplantation.

PURPOSE: Mammalian target of rapamycin (mTOR) inhibitors have been recently introduced in clinical practice after intestinal transplantation. We focused on Sirolimus (Rapamycin) to examine effects on rejection and graft survival following intestinal transplantation. PATIENTS AND METHODS: Twenty isolated intestinal recipients and 5 multivisceral patients (2 with liver) in our series were divided into 3 groups: patients started on Sirolimus (because of nephrotoxicity or biopsy-proven rejection), who continued therapy longer than 3 months (n = 11); patients started on Sirolimus (because of nephrotoxicity or biopsy-proven rejection), who received therapy less than 3 months because of side effects (n = 4); and a control group, who never received rapamycin (n = 10). RESULTS: During prolonged treatment combined with Tacrolimus (Prograf), both Sirolimus groups showed a decreased number of acute cellular rejections (P < .01). Cumulative 3-year graft and patient survival rates were 81% in the Sirolimus greater than 3 months group, 100% in the Sirolimus less than 3 months group, and 80% and 90% in the control group, respectively (P = .63 and P = .62). CONCLUSION: In our experience, the use of mTOR-inhibitors in combination with calcineurin-inhibitors seemed to be more effective than monotherapy to reduce the number of rejections. Side effects can limit its use as maintenance therapy.

Steroids in intestinal transplantation.

BACKGROUND: Recently, new immunosuppressive protocols after intestinal transplantation have been proposed to avoid steroids use and their adverse effects. We evaluated the impact of steroids on survival and post-transplant complications in our experience. PATIENT AND METHODS: In our retrospective study we considered the mean daily dosage of steroids received by 25 patients after intestinal/multivisceral transplantation (minimal follow-up was six months). We analyzed graft and patient survival rates, correlation with rejection and infectious episodes and steroids side effects. RESULTS: After a mean follow-up of three yr, we did not find any significant difference in steroid doses between our immunosuppressive protocols. Patients with a mean dosage of prednisone higher than 20 mg/d experienced a lower graft (p = 0.009) and patient (p = 0.02) survival rate. The side effects of steroids after transplant were similar. Infections were more frequent during steroids administration (p = 0.04). DISCUSSION AND CONCLUSION: Steroids therapy may be useful to treat acute rejection, but in our experience high steroids regimen did not improve graft and patient survival, increasing infectious rate. We assumed that high dose of steroids can be avoided as maintenance therapy, except in selected cases.

Daclizumab and alemtuzumab as induction agents in adult intestinal and multivisceral transplantation: A comparison of two different regimens on 29 recipients during the early post-operative period.

INTRODUCTION: Induction therapy has been recently adopted for intestinal transplant. PATIENTS AND METHODS: We compared during first 30 days post-transplantation 29 recipients, allocated in two groups, treated with Daclizumab (Zenapax) or Alemtuzumab (Campath-1H). RESULTS: During first month, 45% of Daclizumab recipients experienced six acute cellular rejections (ACRs) of mild degree, while 63% of them developed an infection requiring treatment. We found three acute cellular rejections in 17.6% of Alemtuzumab recipients, two with moderate degree; 64.7% of them required treatment for infection. DISCUSSION AND CONCLUSIONS: Graft and patient 3-years cumulative survival rate were not significantly different between groups. Alemtuzumab seems to offer a better immunosuppression during first month.

Results of intestinal and multivisceral transplantation in adult patients: Italian experience.

PURPOSE: We report our experience with intestinal and multivisceral transplantation in Italy. METHODS: We performed 23 adult isolated intestinal transplants and seven multivisceral ones, three with liver, between December 2000 and June 2005. Indications for transplantation were loss of venous access (n = 14), recurrent sepsis (n = 10), and electrolyte-fluid imbalance (n = 6), 14 of whom also presented with total parenteral nutrition (TPN)-related liver dysfunction. Immunosuppression was based on induction agents like daclizumab (followed by tacrolimus and steroids) in the first period; alemtuzumab or thymoglobulin (with tacrolimus) in a second period after 2002. RESULTS: The mean follow-up was 742 +/- 550 days. Three-year patient actuarial survival rate was 88% for intestinal transplants and 42% for multivisceral (P = .015). Three-year graft actuarial survival rate was 73% for intestinal patients and 42.8% for multivisceral (P = .1). Graft loss was mainly due to rejection (57%). Complications were mainly represented by bacterial infections (92% of patients), relaparotomies (82%), and rejections (72%). Full bowel function without any parenteral nutrition or intravenous fluid support was achieved in 60% of recipients with functioning bowel including 95% on a regular diet. One patient underwent abdominal wall transplantation as well. DISCUSSION AND CONCLUSION: Intestinal transplantation has achieved high rates of patient and graft survival with even longer follow-up. Early referral of patients, especially in cases of TPN-liver disease, is mandatory to obtain good outcomes and avoid high mortality rates on the transplant waiting list. Immunosuppressive management remains the key factor to increase the success rate.

Comparison between subjective and objective assessment of the long-term results after the Heller-Dor operation in patients affected by oesophageal achalasia.

INTRODUCTION: Nowadays the subjective assessment of Health-Related Quality of Life after surgery for achalasia is often associated with the instrumental methods in order to evaluate long-term results of therapy. AIMS: To assess the long-term objective and subjective results of the surgical treatment of achalasia and to study the correlation between clinical-instrumental methods and those based on the patient's self-assessment and on Health-Related Quality of Life questionnaires. METHODS: One hundred and twenty-four patients consecutively submitted to trans-abdominal Heller-Dor operation were periodically followed up with clinical examination, endoscopy, barium swallow and manometry. The Health-Related Quality of Life was assessed using the 36 item short form (SF-36) and the Psychological General Well-Being Index questionnaire. The statistical comparison between the results of the self-assessment questionnaires and the long-term clinical-instrumental result was calculated by means of linear regression analysis. RESULTS: Over the years, 123 patients underwent at least one complete clinical-instrumental check-up and filled the self-assessment questionnaires. Mean follow-up was 105 months (range 12-288) with a median of 82.5 months. The result of the surgery was considered satisfactory in 93.5% of the patients, while the reflux oesophagitis observed in 6.5% of the cases was the main cause of failure. Clinical scores for dysphagia and for gastro-oesophageal reflux symptoms were significantly reduced after surgery. The results of the SF-36 and Psychological General Well-Being Index questionnaires were in our population very high and clinical correlation (p<0.05) emerged in physical function, in role physical, in mental health and in vitality domains of SF-36 questionnaire, and in self-control and general health scales of Psychological General Well-Being Index questionnaire. CONCLUSIONS: Health-Related Quality of Life questionnaires can be considered valid aids in evaluating surgical results, but the clinical-instrumental evaluation remains the cardinal point of every long-term assessment in order to diagnose complications, the disease-related conditions of the patient and to acquire reliable data on which scientific discussion can be based.

Twenty-seven consecutive intestinal and multivisceral transplants in adult patients: a 4-year clinical experience.

Adult isolated intestinal and multivisceral transplantation is gaining acceptance as the standard treatment for patients with intestinal failure with life-threatening parenteral nutrition-related complications. We report our 4-year experience with intestinal and multivisceral transplantation. We performed 20 isolated small bowel and seven multivisceral ones, including three with liver. The underlying diseases were mainly short bowel syndrome due to intestinal infarction, chronic intestinal pseudo-obstruction, and Gardner syndrome. Indications for transplant were loss of central venous access in 14 patients, recurrent sepsis in eight patients, and major electrolyte and fluid imbalance in five patients. One-year patient actuarial survival rate was 94% for isolated intestinal transplants and 42% for multivisceral recipients (P = .003), while 1-year graft actuarial survival rate was 88.4% for isolated small bowel patients and 42.8% for multivisceral ones (P = .01). The death rate was 18.5%. Our graftectomy rate was 14.8%. Our immunosuppressive protocols were based on induction agents such as alemtuzumab, daclizumab, and antithymocyte globulins. The majority of our complications were bacterial infections, followed by rejections and relaparotomies; most rejection episodes were treated with steroid boluses and tapering. We believe that our results were due to optimal candidate and donor selection, short ischemia time, and use of induction therapy. Multivisceral transplantation is a more complex procedure with less frequent clinical indications than isolated small bowel transplant, but our data concerning multivisceral transplants include only a small number of patients and require further evaluation.

Endoscopic finding of granular cell tumour associated with leiomyomas in the oesophagus.

Following a single report in the literature of granular cell tumour associated with diffuse leiomyomatosis in the oesophagus, we describe the case of a 39-year-old man in whom a granular cell tumour and two leiomyomas were endoscopically removed from this site. This previously unreported association of granular cell tumour with isolated leiomyomas suggests the need to bear in mind the possibility of other mesenchymal lesions, including leiomyomas or leiomyomatosis, when a granular cell tumour is found in the oesophagus.

Review article: indications for anti-reflux surgery in gastro-oesophageal reflux disease.

Gastro-oesophageal reflux disease (GERD) is a complex multifactorial disorder whose treatment is based on knowledge of its pathophysiology, natural history and evolution. Recently the relationship between the severest degrees of cardial incontinence and hiatus hernia has been emphasized, which causes the impairment of the mechanical properties of the gastro-oesophageal barrier and of oesophageal acid clearing. Among different types of hiatus hernia, those characterized by the permanent axial orad migration of the oesophago-gastric (EG) junction (nonreducible hiatus hernia) are correlated with severe GERD. Barium swallow may adequately differentiate hiatal insufficiency, concentric hiatus hernia and short oesophagus which are the steps of migration across or above the diaphragm. When associated with panmural oesophagitis and fibrosis of the oesophageal wall, these conditions may be the cause of recurrence of hiatus hernia and reflux after laparoscopic standard anti-reflux surgical procedures; in the presence of nonreducibility of the EG junction below the diaphragm without tension, dedicated surgical procedures are necessary. It is currently agreed that surgical therapy is indicated for patients affected by severe GERD who are not compliant with long-term medical therapy, require high dosages of drugs and are too young for lifetime medical treatment. While the existence of severe GERD correlated with an irreversible anatomical disorder represents an elective indication for surgery, warrants further investigation. Accurate identification of the functional and anatomical abnormalities underlying GERD is mandatory in order to decide whether medical or surgical therapy should be implemented, and to tailor the surgical technique, laparoscopic or open, to each patient.

Three-dimensional CT imaging and virtual endoscopy for the placement of self-expandable stents in oesophageal and tracheobronchial neoplastic stenoses.

We examined the value of multislice computed tomography (CT) with three-dimensional (3D) reconstruction of the images as a pre-treatment examination in order to plan endoluminal stenting in 14 patients with large tumours involving the oesophagus and/or the tracheobronchial tree. The measurement of the stenosis obtained during 3D reconstruction of the CT images corresponded to that obtained by endoscopy and to the prosthesis chosen in all cases, with the exception of one patient undergoing double stenting due to inadequate gaseous distension of the oesophageal lumen. 3D CT may add information with respect to axial imaging, and be helpful to better plan and perform stenting of the oesophagus and airways without burdening the preoperative work-up.

Surgical therapy for adenocarcinoma of the cardia: modalities of recurrence and extension of resection.

In order to define the optimal extent of resection for cancer of the cardia, we considered 116 patients operated upon with five different surgical techniques. The procedures were: transabdominal total gastrectomy associated with distal esophagectomy in 38 patients; transabdominal total gastrectomy and left thoracotomic esophageal resection at the inferior pulmonary vein level in 26 patients; transabdominal total gastrectomy and right thoracotomic esophageal resection at the azygos vein level in 27 patients; transabdominal total gastrectomy and transhiatal lower third esophagectomy in 18 patients; transhiatal total esophagectomy and upper third gastrectomy with cervical esophago-gastroplasty in seven patients. Grading, staging, neoplastic lymphangitis, satellite intramural metastases, infiltration of the resection margin, site of recurrence, and survival were analyzed. N+ was the single independent prognostic factor for survival. A poorly differentiated grading was related to T (P = 0.0009), N (P = 0.001), satellite growth (P = 0.05), and infiltration of the resection margin (P = 0.0001). Recurrence was local in 26% and distant in 74% of patients. The modalities of recurrence were not related to the aggressiveness parameters and the surgical technique. Infiltration of the esophageal resection margin was related to the type of operation (P = 0.005) and survival (P = 0.02), but it was not related to the site of recurrence. Transabdominal total gastrectomy and the right thoracotomic esophageal resection procedure achieved free margins and control of the lymph nodal metastatic spread. Transabdominal total gastrectomy and right thoracotomic esophageal resection at the azygos vein level provides a radical oncologic resection, particularly in poorly differentiated tumors. However, surgery alone cannot cure the majority of adenocarcinomas of the cardia.

Efficacy and safety of Nd:YAG laser for the treatment of bleeding from radiation proctocolitis.

BACKGROUND: Bleeding due to radiation proctocolitis is a frequent and severe complication of radiotherapy in cancers of the pelvis. AIM: The aim of this study was to evaluate the efficacy and safety of endoscopic treatment with Nd:YAG laser in this condition. PATIENTS AND METHODS: A series of 9 patients with radiation-induced damage in the rectum and sigma were treated with endoscopic Nd:YAG laser until significant bleeding stopped and endoscopic features of proctocolitis improved. They received a median of 3 laser treatments (range 1-10) over a maximum time period of 11 months. RESULTS: In 4 cases, bleeding ceased and, in 4, it was reduced to occasional spotting. In the remaining patient, laser therapy led to only a transient improvement, but did not modify the requirement of blood transfusion. In the 5 patients also suffering from urgency, incontinence and/or rectal mucoid discharge, the laser therapy course also relieved these symptoms. No significant treatment-related complications were observed. CONCLUSIONS: Endoscopic Nd: YAG laser is a useful and safe treatment for patients with bleeding due to radiation proctocolitis.