Persistent correlation of ghrelin plasma levels with body mass index both in stable weight conditions and during gastric-bypass-induced weight loss.

BACKGROUND: Studies done on serial changes in plasma ghrelin levels after gastric bypass (GBP) have yielded contrasting results since decreased, unchanged, or increased levels have been reported in the literature. This study investigates whether or not GBP has an inhibitory effect on fasting ghrelin levels independently of weight loss. METHODS: Fasting ghrelin levels were measured in 115 stable body weight females, classified as normal body weight (NW; body mass index (BMI)<25 kg/m2), overweight (OW; BMI 25-30 kg/m2), and obese subjects, divided in three subgroups with increasing BMI (BMI 30-40 kg/m2; BMI 40-50 kg/m2; BMI>50 kg/m2). RESULTS: Each obese subgroup showed significantly lower ghrelin levels as compared to both NW (p<0.0001) and OW subjects (p<0.05 or 0.005); however, no significant differences were observed within the three obese subgroups. Forty-nine obese patients underwent a GBP. Plasma ghrelin, measured at 3, 6, and 12 months after GBP, significantly increased from the sixth month on (p<0.0001). When patients were classified, at each postoperative time point, according to their actual BMI, ghrelin was significantly (p=0.0002) related to postoperative BMI and not significantly different from ghrelin measured in stable body weight conditions. CONCLUSIONS: Fasting ghrelin displays an inversely significant correlation with BMI in both stable body weight conditions and after GBP. No evidence was found that GBP had an effect on fasting ghrelin levels, independent of weight loss.

Treatment strategies for the management of advanced colorectal liver metastases detected synchronously with the primary tumour.

The review summarises the contributions of chemotherapy, interventional radiology and surgery to the improved survival observed in patients with colorectal liver metastases. The rationale in favour of modern neoadjuvant chemotherapy regimens, of pro-generative manoeuvres to increase the volume of the future remnant liver, and of resection techniques that preserve its function is discussed. For advanced synchronous colorectal metastases, the arguments in favour of a reversed approach with systemic chemotherapy, liver surgery and colon surgery in that order, as opposed to the traditional approach of colon surgery first, or to a simultaneous liver and large bowel resection, are presented.

[Vacuum-assisted abdominal closure: its role in the treatment of complex abdominal and perineal wounds. Experience in 48 patients]. / Le Vacuum Assisted Closure: utilité dans le traitement des plaies abdomino-périnéales complexes. Expérience sur 48 patients.

INTRODUCTION: Vacuum-assisted closure (VAC) is a promising approach for the management of complex abdominal and perineal wounds. This paper summarizes our experience with this therapeutic modality and demonstrates its efficacity in difficult situations. PATIENTS AND METHODS: From January 2003 until December 2005, 48 patients (age 30-89) were treated with VAC therapy for open abdomen, infected laparotomy wounds, or tissue loss due to debridement of Fournier's gangrene. Wound dressings were changed every 2-3 days. RESULTS: Thirty-eight patients (79%) had major co-morbid conditions liable to impact negatively on wound healing. The treatment duration with VAC varied from 20-30 days with an average of eleven dressing changes (minimum 3-maximum 18). Treatment was effective in all patients. Spontaneous closure was achieved in 36 cases (75%); nine patients (19%) required a split-thickness skin graft, and three (6%) underwent delayed secondary closure. CONCLUSION: In our institution, VAC has become the treatment of choice for complex abdominal and perineal wounds. It is a safe, simple, and effective technique to speed wound healing and it has reduced the duration of hospital treatment in difficult clinical situations and in patients whose general condition is often severely compromised.

Percutaneous CT scan-guided drainage vs. antibiotherapy alone for Hinchey II diverticulitis: a case-control study.

PURPOSE: CT-scan-guided percutaneous abscess drainage of Hinchey Stage II diverticulitis is considered the best initial approach to treat conservatively the abscess and to subsequently perform an elective sigmoidectomy. However, drainage is not always technically feasible, may expose the patient to additional morbidity, and has not been critically evaluated in this indication. This study was undertaken to compare the results of percutaneous drainage vs. antibiotic therapy alone in patients with Hinchey II diverticulitis. METHODS: This was a case-control study of all patients who presented in our institution with Hinchey Stage II diverticulitis between 1993 and 2005. Thirty-four patients underwent abscess drainage under CT-scan guidance (Group 1), and 32 patients were treated with antibiotic therapy alone (Group 2), in most cases because CT-scan-guided abscess drainage was considered technically unfeasible by the interventional radiology team. Initial conservative treatment was considered a failure when: 1) emergency surgery had to be performed, 2) signs of worsening sepsis developed, and 3) abscess recurred within four weeks of drainage. RESULTS: The median size of abscess was 6 (range, 3-18) cm in Group 1 and 4 (range, 3-10) cm in Group 2 (P = 0.002). Median duration of drainage was 8 (range, 1-18) days. Conservative treatment failed in 11 patients (33 percent) of Group 1, and in 6 patients (19 percent) of Group 2 (P = 0.26). Ten patients (29 percent) in Group 1 and five patients (16 percent) in Group 2 underwent emergency surgery (P = 0.24); there were four postoperative deaths (26.6 percent) in this subgroup. Twelve patients (35 percent) in Group 1 and 16 patients (50 percent) in Group 2 subsequently underwent an elective sigmoid resection (P = 0.31). In this subgroup of patients, there was neither anastomotic leakage nor postoperative death. CONCLUSIONS: Emergency surgery for Hinchey Stage II diverticulitis carries a high mortality rate and should be avoided. To achieve this, antibiotic therapy alone seems to be a safe alternative, whenever percutaneous drainage is technically difficult or hazardous. Actually, our data did not demonstrate any benefit of CT scan-guided percutaneous abscess drainage, suggesting that the role of interventional radiology techniques in this indication deserves further critical evaluation.

An audit of surgical management of gastrointestinal stromal tumours (GIST).

AIM: To analyze GIST outcome after primary resection and to determine if a new grading system could adequately predict there prognosis. METHODS: A retrospective review (1993-2002) identified 80 patients who underwent primary surgical resection for, c-KIT positive, GIST. Follow-up was complete for all patients (median follow-up 42, range 1-132, months). GIST were classified as low or high grade according to the following parameters: size, mitotic rate, mitotic index (MiB1), presence of necrosis, invasion of adjacent structure and presence of metastasis. RESULTS: GIST originated from the stomach (46), small bowel (30), colon and rectum two and mesentery two. At surgery, 94% of cases presented with localized disease and 6% blood born metastasis with or without lymph node invasion. Resections were complete (R0) in 72 cases. R0 resection correlated with prognosis (p<0.01). Sixty GIST were classified as low grade (median follow-up 60 months) and 20 as high grade (median follow-up 27 months). Five-year actuarial survival of patients with low or high grade GIST were of 95 and 21%, respectively, (p<0.001). CONCLUSION: Prognosis of GIST after surgical treatment is influenced by completeness of primary resection and tumour malignant potential. Low grade GIST have an excellent prognosis after surgery alone, while high grade GIST have a high rate of recurrence after primary resection. Adjuvant treatment should be advocated for patient with either high grade GIST or after incomplete primary resection. The presented grading system can reliably predict GIST outcome after primary surgical treatment. Complete surgical resection offers good chance of cure for low grade GIST, while for high grade GIST surgery alone is not sufficient. The presented grading system could be used to identify patients who may benefit of adjuvant treatment with imatinib mesylate after GIST resection.

A comparison of cold storage solutions for pancreas preservation prior to islet isolation.

BACKGROUND: Several solutions are used to preserve the pancreas prior to islet isolation. This study sought to assess whether the type of solution had an impact on the isolation outcome. METHODS: We reviewed data from 125 islet isolation procedures performed from January 2002 to January 2005. Pancreata were preserved in University of Wisconsin (UW) (n = 101), Celsior (CS) (n = 19), or IGL-1 (n = 5) solutions. Islet isolation results and transplantation rates were compared between groups. RESULTS: UW, CS, and IGL-1 groups were similar according to donor's age, weight, and body mass index. Weight of undigested pancreas was 20 +/- 13.1, 21.4 +/- 15.7, and 17.4 +/- 8.7 g for UW, CS, and IGL-1, respectively (P > .2). Final total number of IEQ was 267,000 +/- 132,000, 277,000 +/- 155,000, and 311,000 +/- 163,000, respectively (P > .4). Success rate (defined as >250,000 IEQ) was 55.5%, 52.9%, and 60% for UW, Celsior, and IGL-1 (P > .9); the transplantation rate was 42.2% for UW, 36.8% for Celsior, and 80% for IGL-1 preservation (P > .2). CONCLUSIONS: In this preliminary study, UW, Celsior, and IGL-1 solutions demonstrated similar islet isolation results. The new IGL-1 solution appears promising.

Treatment of hepatocellular carcinoma at the dawn of the third millennium: liver transplantation and its alternatives.

Hepatocellular carcinoma is one of the most frequent tumors worldwide, and its frequency is increasing. The management of hepatocellular carcinoma has changed in recent years, this because screening allows to discover tumors at an earlier stage, and because of effective treatments are available, such as liver transplantation, liver resection, percutaneous ablation and transarterial chemoembolization. Each one of these treatments has its own advantages and drawbacks, and range of application according to the stage of the tumor and of the underlying liver disease. This review summarizes the recent progress in the management of HCC and the practice in our unit.

Morbidity associated with intraportal islet transplantation.

INTRODUCTION: Complications associated with intraportal islet infusion have been reported. In this study, we analyzed the relationship between occurrence of complications and islet preparation characteristics/infusion technique. METHODS: We reviewed all intraportal islet infusions from 1992 to 2003. RESULTS: Sixteen islet autotransplantations were performed without infusion-related complications. The tissue volume injected was 13 +/- 11 mL with basal and peak portal pressures of 13 +/- 6 and 21 +/- 6 mm Hg. Seventy-seven intraportal islet allotransplantations were performed in 51 patients. Fifteen islet infusions were done by laparotomy during simultaneous islet/kidney transplantation without complication. Among 62 percutaneous transhepatic injections, nine complications (two portal branch thrombosis and seven intra-abdominal hemorrhages) were recorded. Rise in portal pressure was related to tissue volume injected (P <.05). Basal and peak portal pressures were 14 +/- 5 and 18 +/- 6 mm Hg in uncomplicated infusions, 14 +/- 9 and 18 +/- 9 mm Hg in the thrombosis group, and 13 +/- 7 and 18 +/- 5 mm Hg in the hemorrhage group (P >.05). Complications occurred only after percutaneous islet infusion (P <.03). CONCLUSIONS: Procedure-related morbidity of intraportal islet infusion is low. Changes in portal pressure are related to volume of tissue injected but do not seem to be associated with the occurrence of complications. Percutaneous infusion is a minimally invasive procedure, but this advantage must be balanced by the higher rate of complications.

Serva collagenase NB1: a new enzyme preparation for human islet isolation.

INTRODUCTION: Advances in the rate of success of human islet isolation are due in part to the availability of new purified enzyme blends. In this study we evaluated a new enzyme preparation composed of a highly purified collagenase that can be reproducibly blended with predetermined amounts of separately packaged neutral protease. METHODS: Nine human islet isolations were performed with collagenase NB1 supplemented with neutral protease (Serva Electrophoresis GMbH, group I). Yields, purity, morphology, in vitro function and islet cell apoptosis were assessed. The results were compared to those of nine human islet isolations performed with Liberase (Roche, group II) and matched for donor age, BMI, and circumstances of death. RESULTS: Islet yields were similar in both groups. However, islet equivalents (IE) per gram of pancreas and IE number to islet number were higher in group I (P <.05). Stimulation indices after insulin response to glucose (static incubation) were similar in both groups. Islet cell apoptosis rate was statistically significantly lower in group I. Islet morphology was significantly improved in group I with a higher proportion of intact islets. CONCLUSION: This new enzyme preparation (collagenase NB1 with neutral protease adjunct) was as effective as Liberase in terms of islet yields and function. Islet morphology was improved and rate of islet cell apoptosis was lower with this new collagenase. The absence of lot-to-lot variability in terms of neutral protease to collagenase ratio makes collagenase NB1 a promising enzyme for human islet isolation.

Retransplantation of discordant xenogeneic islets with costimulatory blockade.

BACKGROUND: The aim of the study was to analyze the possibility of xenogeneic islet retransplantation using costimulatory blockade. METHODS: Streptozotocin-induced diabetic mice were transplanted under the kidney capsule with human islets. Mice were nephrectomized and retransplanted with 1000 human islets under the contralateral kidney capsule 14 days later. Four groups were performed group I, first and second Tx without MR1; group II, first Tx without MR1, second Tx with MR1; group III, first Tx with MR1, second Tx without MR1; group IV, first and second Tx with MR1. A control group was transplanted only once without MR1 with human islets. After second Tx, cross-matches between recipient, serum and human lymphocyte were done for detection of antidonor antibodies. RESULTS: In the control group, mean graft survival was 13 (+/-7) days. In group I, mean graft survival was 5 +/- 3 days. In group II, mean graft survival was 16 +/- 13 days. In group III, mean graft survival was 81 +/- 22 days. In group IV, no rejection were recorded and all graft survived more than 120 days. Pretransplant cross-matches were negative. In groups I and II all cross-matches were positive, while none were positive in group IV. CONCLUSION: Retransplantation of xenogeneic islets was associated with accelerated rejection. After presensitization, MR1 was unable to induce tolerance to a second Tx. MR1 given at the first Tx only allowed prolonged survival of the second Tx, but rejection still occurred. MR1 given at first and second Tx allowed long-term survival of retransplanted xenoislets and prevented occurrence of antidonor antibodies.

Appendix tumors in the era of laparoscopic appendectomy.

BACKGROUND: The safety of laparoscopic appendectomy for the management of incidentally discovered appendiceal tumors has not yet been established. METHODS: Appendiceal tumor cases managed by laparoscopy or laparotomy over a 10-year period were reviewed. RESULTS: The pathological diagnoses were 23 carcinoid and 20 cancerous lesions. The median patient ages were 36 and 69 years, respectively, for carcinoid and other tumors (p < 0.05). Acute appendicitis was present in 70% of carcinoid cases and 35% of other tumors (p < 0.05). Eight patients with carcinoid tumors were operated on by laparoscopy, whereas 15 underwent laparotomy. Laparoscopic and open procedures were performed in three and 17 patients with cancerous lesions, respectively. Invaded surgical margins were seen after laparoscopy in 20% of patients and open surgery in 6%. Synchronous colon carcinoma was detected in 14% of the patients with an appendix neoplasm. The 5-year survival rates were similar after both laparoscopic and open appendectomy for either carcinoid or other tumors. CONCLUSION: Laparoscopic appendectomy for appendiceal tumors seems to have a slightly higher rate of inadequate resection. However, it is not associated with a significantly worse patient prognosis than open appendectomy.

Paraganglioma of the ampulla of Vater: a potentially malignant neoplasm.

Paragangliomas are rare tumours originating from neuroectodermic remnants and are usually considered as benign. We present two cases of paraganglioma of the ampulla of Vater that were treated surgically by pancreaticoduodenectomy. In one case, histopathology revealed malignant characteristics of the tumour with invasion of the pancreas and simultaneous duodenal lymph-node metastases. Both patients had a favourable outcome without disease recurrence at 40 and 44 months postoperatively. Only 21 cases of ampullary paraganglioma have been reported in the literature, 7 of them with malignant characteristics. In conclusion, paragangliomas of the ampulla of Vater have malignant potential. Surgical therapy of these tumours should not be limited to local resection, as disease recurrence and lymph node involvement have been reported. We propose that paragangliomas of the ampulla of Vater should be operated by cephalic pancreaticoduodenectomy, which allows long-term and disease-free survival.

Bioartificial organ grafts: a view at the beginning of the third millennium.

An immunoisolated collection of cells, which communicate and exchange essential factors, co-stimulatory hormones, as well as providing immunoprotection and immunomodulation, can be prepared, given existing scientific and medical know-how, within two decades. These "Bioartificial Organ Grafts" have advantages relative to isolated cell therapies, including beta-cell encapsulation for diabetes treatment, and xenotransplantation, which has a de facto moratorium. This paper documents that the majority of the research for the bioartificial organ grafts has been concluded, with the remaining hurdles minimum in comparison. The use of co-encapsulation and the induction of local immune-privilege will provide a more sensitive humoral hormonal response and graft survival, without systemic immunosuppression. A call for the staged implementation of bioartificial organ grafts, based on the best available medical practice, materials, tissue and technology available, is advocated. The implementation of bioartificial organ grafts can begin within the next two years, based on allografts succeeded by genetically modified human tissue, without the need to pass through a xenograft stage.

Adult-to-adult living-donor liver transplantation. A summary of current status and an outline of the program in Geneva.

Living donor liver transplantation is a relatively new procedure in which the right side of the liver is harvested in a healthy donor and transplanted into a recipient. After the first case in 1994, over 3000 cases have been done worldwide. This review summarizes the reasons why the procedure is needed, describes its main technical aspects, highlights the boundaries in which it can be done safely, summarizes the current experience worldwide and describes the main points of the program in our unit. We argue that living-donor transplantation is a viable alternative to a long time on the waiting list for several patients, and it can be performed safely and successfully provided that all precautions are undertaken to minimize the risks in the donor and to increase the chances of a good outcome in the recipients. If these prerequisites are met, and within the framework of a structured multidisciplinary program, we believe that living-donor liver transplantation should be funded by health insurances as a recognized therapeutic option.

Islet of Langerhans transplantation for the treatment of type 1 diabetes.

Islet of Langerhans transplantation is gaining recognition as a therapy for type 1 diabetes. The procedure involves enzymatic digestion of the pancreatic tissue, purification of the islets from the exocrine tissue, infusion of the islets into the portal vein and implantation in the liver. Until 1999, and overall rate of insulin independence of 14% at one year was reported in the International Islet Transplant Registry. The results of the "Edmonton protocol" since 2000 were a breakthrough in the field, with reports of 80% insulin independence at 1-year after solitary islet transplantation in non uremic patients with brittle type 1 diabetes. A rapamycin-based, steroid-free, islet-sparing immunosuppressive regimen was designed and the problem of the insufficient islet mass was tackled by sequential infusions of islets isolated from at least two pancreatic. The University of Geneva has been involved in clinical islet transplantation since 1992, and has performed 51 allogeneic and 17 autologous. Twenty-one patients have been transplanted in Geneva since 2002. They were five solitary islet transplants, 14 islet after kidney transplants and two simultaneous islet-kidney (SIK) recipients. Insulin independence was achieved in 67%.

Medical problems occurring during the long-term follow-up after liver transplantation.

Liver transplantation is a standardized therapy for end-stage liver disease. With current immunosuppressive protocols and patient care, ten-year patient survival rate has reached 60%. Several medical complications may develop during this period, including renal dysfunction, hypertension, diabetes mellitus, hyperlipidemia, and metabolic bone disease. The aim of this article is to analyze long-term results of several clinical trials reporting common medical dysfunctions after liver transplantation and to discuss their management.

Long-term expression of fibrogenic cytokines in radiation-induced damage to the internal anal sphincter.

BACKGROUND: There is accumulating evidence, both quantitative and qualitative, that pelvic irradiation affects anorectal function. However, the molecular mechanisms responsible for radiation-induced damage to the anal sphincter remain unclear. AIM: To determine the expression of transforming growth factor-beta 1 (TGF-beta 1) and its downstream effector connective tissue growth factor (CTGF) in the anal sphincter of a patient irradiated for prostate cancer. PATIENT: A 82 year-old patient developed a rectal adenocarcinoma and underwent an abdomino-perineal resection (APR), four years after receiving pelvic irradiation for prostate carcinoma. METHODS: Tissue sections of the anal sphincter were processed for histology. Immunostaining for TGF-beta 1 and CTGF were performed. RESULTS: CTGF and TGF-beta 1 immunoreactivity was detected in the irradiated anal sphincter, and was absent in controls. Immunoreactivity for both cytokines predominated in the internal sphincter. CTGF and TGF-beta 1 were preferentially detected in endothelial cells, myofibroblasts and fibroblasts; in addition, there was strong immunoreactivity for TGF-beta 1, but not for CTGF in smooth muscle cells of the anal canal. CONCLUSION: Four years after pelvic irradiation, radiation-induced damage appeared to affect predominantly the smooth muscle layer of the anal canal. The molecular mechanisms responsible for radiation-induced fibrosis to these tissues involve prolonged activation of TGF-beta 1 and its downstream effector CTGF.

[Perspectives for diabetes treatment through pancreas transplantation or islet transplantation]. / Perspectives dans le traitement du diabete par transplantation de pancreas ou greffe d'ilots de langerhans.

Replacement of beta-cell function by transplantation of endocrine tissue is an alternative treatment for patients with complicated type 1 diabetes. Pancreas transplantation is presently the only treatment allowing to normalise glycemia without increasing the risk of hypoglycemia and to stop exogenous insulin-therapy. In spite of postoperative morbidity and mortality, pancreas transplantation improves quality of life, reduces cardiovascular risk factors and prolongs the life expectancy of diabetic patients with end-stage kidney failure. Islet transplantation is still an experimental procedure. However, the results obtained recently are a proof of principle that a cellular transplant can induce normoglycemia and insulin-independence in diabetic patients. In this review, the results and perspectives of pancreas and islet transplantation are discussed.

[Bilateral adrenal gland hemorrhage after anterior deep rectum resection. Case report with review of the literature]. / Bilaterale Nebennierenhämorrhagie nach vorderer tiefer Rektumresektion. Fallbericht mit Literaturübersicht.

UNLABELLED: Adrenal insufficiency due to bilateral adrenal hemorrhage is a rare but potentially life-threatening postoperative complication. The difficulty lies in making a timely diagnosis, as the symptoms are often unspecific and similar to those presented by other, more common postoperative complications. We report the case of a 71-year-old patient presenting bilateral adrenal hemorrhage following an otherwise uncomplicated low anterior rectum resection for a villous adenoma of the middle rectum. CONCLUSION: In cases of unexplained postoperative deterioration, surgeons should be aware of acute adrenal insufficiency due to bilateral adrenal hemorrhage. With a high index of suspicion the diagnosis is made easily by CT scan and serum-cortisol measurements and prompt steroid replacement can help to avoid a deleterious outcome.

Long-term follow-up after first acute episode of sigmoid diverticulitis: is surgery mandatory?: a prospective study of 118 patients.

PURPOSE: This study was designed to evaluate the long-term natural history of sigmoid diverticulitis in patients treated nonoperatively after a first acute episode and to assess the role of elective colectomy. METHODS: Between 1986 and 1991, 144 patients were admitted for acute diverticulitis diagnosed by abdominal computed tomography and had a successful nonoperative treatment. Remote complications (persisting or recurring diverticulitis) were also diagnosed by computed tomography. Patients had a poor outcome if they had one of these complications. Diverticulitis was graded mild or severe on computed tomography according to Ambrosetti's criteria. We determined statistically whether young age (< or =50 years old) and severe diverticulitis were risk factors for a poor outcome. RESULTS: One hundred eighteen patients with a contributive computed tomographic scan at admission were followed up. Median age was 63 (range, 23-93) years, with a median follow-up of 9.5 (range, 0.2-13.8) years. Eighty patients had no complications, and 38 had remote complications. The incidence of remote complications was the highest (54 percent at 5 years) for young patients with severe diverticulitis on computed tomography and the lowest (19 percent at 5 years) for older patients with mild disease. Young age and severe diverticulitis taken separately were both statistically significant factors of poor outcome (P = 0.007 and P = 0.003, respectively), although age was no longer significant after stratification for disease severity on computed tomography (P = 0.07). Twenty-four patients died. The cause of death was unrelated to diverticulitis in 21 cases and unknown in the remaining 3. CONCLUSIONS: We propose that after a first acute episode of diverticulitis treated nonoperatively, elective colectomy should be offered to young patients (< or =50 years old) with severe diverticulitis on computed tomography.