Surgeon\u27s perspective on short bowel syndrome: Where are we?

Short bowel syndrome (SBS) is due to a massive loss of small bowel: the reduction of gut function is below the minimum necessary to maintain health (in adults) and growth (in children) so intravenous supplementation is required. Parenteral nutrition represents the milestone of treatment and surgical attempts should be limited only when the residual bowel is sufficient to increase absorption, reducing diarrhea and slowing the transit time of nutrients, water and electrolytes. The surgical techniques lengthen the bowel (tapering it) or reverse a segment of it: developed in children, nowadays are popular also among adults. The issue is mainly represented by the residual length of the small bowel where ileum has shown increased adaptive function than jejunum, but colon should be considered because of its importance in the digestive process. These concepts have been translated also in intestinal transplantation, where a colonic graft is nowadays widely used and the terminal ileum is the selected segment for a living-related donation. The whole replacement by a bowel or multivisceral transplant is still affected by poor long term outcome and must be reserved to a select population of SBS patients, affected by intestinal failure associated with irreversible complications of parenteral nutrition

Surgeon's perspective on short bowel syndrome: Where are we?

Short bowel syndrome (SBS) is due to a massive loss of small bowel: the reduction of gut function is below the minimum necessary to maintain health (in adults) and growth (in children) so intravenous supplementation is required. Parenteral nutrition represents the milestone of treatment and surgical attempts should be limited only when the residual bowel is sufficient to increase absorption, reducing diarrhea and slowing the transit time of nutrients, water and electrolytes. The surgical techniques lengthen the bowel (tapering it) or reverse a segment of it: developed in children, nowadays are popular also among adults. The issue is mainly represented by the residual length of the small bowel where ileum has shown increased adaptive function than jejunum, but colon should be considered because of its importance in the digestive process. These concepts have been translated also in intestinal transplantation, where a colonic graft is nowadays widely used and the terminal ileum is the selected segment for a living-related donation. The whole replacement by a bowel or multivisceral transplant is still affected by poor long term outcome and must be reserved to a select population of SBS patients, affected by intestinal failure associated with irreversible complications of parenteral nutrition

LONG TERM RESULTS OF HEPATIC TRANSPLANTATION DURING THE CYCLOSPORINE ERA: THE PITTSBURGH EXPERIENCE.

We have reviewed the long term results of the first 500 liver transplant recipients performed by our group during the cyclosporine era. Three hundred and forty-nine recipients lived (69.8%) more than 1 year and the projected 5 year actuarial survival for this sub-group of patients is 88%. The two most common causes of graft dysfunction after the first year were recurrence of the original disease, usually malignancy, and chronic rejection. Most episodes of rejection can be controlled with medical treatment; however, 16 patients of 34 patients who experienced rejection episodes after the first year required retransplantation. Eleven of these 16 are currently alive and free of jaundice. Another common cause of late graft dysfunction is biliary strictures. The recognized side effects of cyclosporine such as nephrotoxicity and lymphoproliferative disease have been lesser problems as a result of the judicious use of the drug. The quality of life of long term survivors is excellent

Completely steroid-free immunosuppression in liver transplantation: a randomized study.

INTRODUCTION: Corticosteroids (CS) have been standard immunosuppression to prevent and treat rejection. However, CS are associated with increased risk of infection, obesity, hypertension, hyperlipidemia, diabetes, and accelerated hepatitis C virus (HCV) recurrence post-orthotopic liver transplantation (OLT). This study assesses the safety and efficacy of CS-free immunosuppressive regimen in adult OLT. METHODS: A two-yr, prospective, randomized study of CS with delayed withdrawal (CS) or CS-free regimen with basiliximab, tacrolimus, and enteric-coated mycophenolate sodium (EC-MPS) was performed in 39 patients (CS=20; CS-free=19). CS group received intra-operative methylprednisolone weaned by six months. HCV patients had HCV PCR pre-OLT and 0.5, one, three, and six months post-OLT. Protocol liver biopsies were performed at OLT, 2 and 24 wk post-OLT or when indicated. RESULTS: Rejection occurred in two patients. Patient survival at one yr (100% vs. 95%), three yr (85% vs. 63%), and five yr (80% vs. 63%) post-OLT were similar between CS and CS-free group, respectively. Death-censored graft survival at one yr (100% vs. 95%), three yr (85% vs. 63%), and five yr (75% vs. 63%) were also similar. The risk of new-onset DM, hypertension, hypercholesterolemia, and weight gain was similar between groups. CONCLUSION: CS avoidance with basiliximab, calcineurin inhibitor, and EC-MPS is safe and effective as CS- containing immunosuppression in adult OLT

A Hypothetical New Challenging Use for Indocyanine Green Fluorescence during Laparoscopic Appendectomy: A Mini-Series of Our Experience and Literary Review

Laparoscopic appendectomy (LA) is a well-standardized surgical procedure, but there are still controversies about the different devices to be used for the appendiceal stump closure and the related postoperative complications. Indocyanine green (ICG) fluorescence angiography (FA) has already been shown to be helpful in elective and emergency surgery, providing intraoperative information on tissue and organ perfusion, thus guiding the surgical decisions and the technical strategies. According to these two aspects, we report a mini-series of the first five patients affected by gangrenous and flegmonous acute appendicitis intraoperatively evaluated with ICG-FA during LA. The patients were admitted to the Emergency Department with an usual range of symptoms for acute appendicitis. The patients were successfully managed by fully LA with the help of a new hypothetical challenging use of ICG-FA

Weaning of immunosuppression in liver transplant recipients

Immunosuppression has been sporadically discontinued by noncompliant liver allograft recipients for whom an additional 4 1/2 years of follow-up is provided. These anecdotal observations prompted a previously reported prospective drug withdrawal program in 59 liver recipients. This prospective series has been increased to 95 patients whose weaning was begun between June 1992 and March 1996, 8.4±4.4 (SD) years after liver replacement. A further 4 1/2 years follow-up was obtained of the 5 self-weaned patients. The prospectively weaned recipients (93 livers; 2 liver/kidney) had undergone transplantation under immunosuppression based on azathioprine (AZA, through 1979), cyclosporine (CsA, 1980-1989), or tacrolimus (TAC, 1989-1994). In patients on CsA or TAC based cocktails, the adjunct drugs were weaned first in the early part of the trial. Since 1994, the T cell-directed drugs were weaned first. Three of the 5 original self-weaned recipients remain well after drug-free intervals of 14 to 17 years. A fourth patient died in a vehicular accident after 11 years off immunosuppression, and the fifth patient underwent retransplantation because of hepatitis C infection after 9 drug-free years; their allografts had no histopathologic evidence of rejection. Eighteen (19%) of the 95 patients in the prospective series have been drug free for from 10 months to 4.8 years. In the total group, 18 (19%) have had biopsy proved acute rejection; 7 (7%) had a presumed acute rejection without biopsy; 37 (39%) are still weaning; and 12 (13%, all well) were withdrawn from the protocol at reduced immunosuppression because of noncompliance (n=8), recurrent PBC (n=2), pregnancy (n=1), and renal failure necessitating kidney transplantation (n=1). No patients were formally diagnosed with chronic rejection, but 3 (3%) were placed back on preexisting immunosuppression or switched from cyclosporine (CsA) to tacrolimus (TAC) because of histopathologic evidence of duct injury. Two patients with normal liver function died during the trial, both from complications of prior chronic immunosuppression. No grafts suffered permanent functional impairment and only one patient developed temporary jaundice. Long surviving liver transplant recipients are systematically overimmunosuppressed. Consequently, drug weaning, whether incomplete or complete, is an important management strategy providing it is done slowly under careful physician surveillance. Complete weaning from CsA-based regimens has been difficult. Disease recurrence during drug withdrawal was documented in 2 of 13 patients with PBC and could be a risk with other autoimmune disorders

Initiation of a critical pathway for pancreaticoduodenectomy at an academic institution -- the first step in multi-disciplinary team building

Objective: This study was designed to identify quantifiable parameters to track performance improvements brought about by the implementation of a critical pathway for complex alimentary tract surgery. Background: Pancreaticoduodenectomy (PD) is a complex general surgical procedure performed in varying numbers at many academic institutions. Originally associated with significant perioperative morbidity and mortality, multiple studies have now shown that this operation can be performed quite safely at high volume institutions that develop a particular expertise. Critical pathways are one of the key tools used to achieve consistently excellent outcomes as these institutions. It remains to be determined if implementation of a critical pathway at an academic institution with prior moderate experience with PD will result in performance gains and improved outcomes. Methods: Between January 1, 2004 and October 15, 2006 135 patients underwent PD, 44 before the implementation of a critical pathway on October 15, 2005, and 91 after. Perioperative and postoperative parameters were analyzed retrospectively to identify those that could be used to track performance improvement and outcomes. Key aspects of the pathway include spending the night of surgery in the intensive care unit with careful attention to fluid balance, early mobilization on post-operative day one, aggressive early removal of encumbrances such as nasogastric tubes and urinary catheters, early post-operative feeding, and targeting discharge for postoperative day 6 or 7. Results: The pre- and post-pathway implementation groups were not statistically different with regards to age, sex, race, or pathology (malignant versus benign). Perioperative mortality, operative blood loss, and number of transfused units of packed red blood cells were also similar. As compared to the pre-pathway group, the post-pathway group had a significantly shorter postoperative length of stay (13 versus 7 days, P ≤ 0.0001), operative time (435 ± 14 minutes versus 379 ± 12 minutes, P ≤ 0.0001), and in room non-operative time (95 ± 4 minutes versus 76 ± 2 minutes, P ≤ 0.0001). Total hospital charges were significantly reduced from $240,242 ±$32,490 versus $126,566 ±$4883 (P ≤ 0.0001) after pathway implementation. Postoperative complication rates remained constant (44% pre-pathway versus 37% after, P = NS). Readmission rates were not negatively affected by the reduction in length of stay, with a 7% readmission rate prior to implementation and a 7.7% rate after implementation. Conclusion: Implementation of a critical pathway for a complex procedure can be demonstrated to improve short-term outcomes at an academic institution. This improvement can be quantified and tracked and has implications for better utilization of resources (greater OR and hospital bed availability) and overall cost containment. With a very conservative estimate of 75 pancreaticoduodenectomies per year by this group, this translates to a savings of 450 hospital days and over $8,550,000 in hospital charges on an annual basis. As we enter the pay for performance era, institutions will be required to generate such data in order to retain patient volumes, attract new patients, and receive incentive payments for high quality services rendered

Fulminant hepatic failure bridged to liver transplantation with molecular adsorbent recirculating system: a single center experience

Purpose: We herein describe the clinical course of a consecutive series of fulminant hepatic failure patients treated with molecular adsorbent recirculating system, a cell-free albumin dialysis technique. From November 2000 to September 2002, 7 adult patients age 22-61 (median 41), one male (14.2%), and 6 females (85.7%), affected by fulminant hepatic failure, underwent 7 courses (1 to 5 session each, six hours in duration) of extracorporeal support using the molecular adsorbent recirculating system technique. Pre and post treatment blood glucose, liver function tests, ammonia, arterial lactate, electrolytes, hemodynamic parameters, arterial blood gases, liver histology, Glasgow Coma Scale, and coagulation studies, were reviewed. No adverse side effects like generalized bleeding on non-cardiogenic pulmonary edema, often seen during MARS treatment, occurred in the patients included in this study. Results: Six patients (85.7%) are currently alive and well, and one (14.2%) died. Four patients (57%) were successfully bridged (two patients in 1 day and two other patients in 4 days) to liver transplantation, while 2 (28.5%) recovered fully without transplantation. All the measured variables stabilized after molecular adsorbent recirculating system commencement. No differences were noted between the pre and post molecular adsorbent recirculating system liver histology. Conclusions: Molecular adsorbent recirculating system is a safe, temporary life support mechanism for patients awaiting liver transplantation or recovering from fulminant hepatic failure

Autocrine IGF-II-Associated Cancers: From a Rare Paraneoplastic Event to a Hallmark in Malignancy

The paraneoplastic syndrome referred in the literature as non-islet-cell tumor hypoglycemia (NICTH) and extra-pancreatic tumor hypoglycemia (EPTH) was first reported almost a century ago, and the role of cancer-secreted IGF-II in causing this blood glucose-lowering condition has been widely established. The landscape emerging in the last few decades, based on molecular and cellular findings, supports a broader role for IGF-II in cancer biology beyond its involvement in the paraneoplastic syndrome. In particular, a few key findings are constantly observed during tumorigenesis, (a) a relative and absolute increase in fetal insulin receptor isoform (IRA) content, with (b) an increase in IGF-II high-molecular weight cancer-variants (big-IGF-II), and (c) a stage-progressive increase in the IGF-II autocrine signal in the cancer cell, mostly during the transition from benign to malignant growth. An increasing and still under-exploited combinatorial pattern of the IGF-II signal in cancer is shaping up in the literature with respect to its transducing receptorial system and effector intracellular network. Interestingly, while surgical and clinical reports have traditionally restricted IGF-II secretion to a small number of solid malignancies displaying paraneoplastic hypoglycemia, a retrospective literature analysis, along with publicly available expression data from patient-derived cancer cell lines conveyed in the present perspective, clearly suggests that IGF-II expression in cancer is a much more common event, especially in overt malignancy. These findings strengthen the view that (1) IGF-II expression/secretion in solid tumor-derived cancer cell lines and tissues is a broader and more common event compared to the reported IGF-II association to paraneoplastic hypoglycemia, and (2) IGF-II associates to the commonly observed autocrine loops in cancer cells while IGF-I cancer-promoting effects may be linked to its paracrine effects in the tumor microenvironment. Based on these evidence-centered considerations, making the autocrine IGF-II loop a hallmark for malignant cancer growth, we here propose the functional name of IGF-II secreting tumors (IGF-IIsT) to overcome the view that IGF-II secretion and pro-tumorigenic actions affect only a clinical sub-group of rare tumors with associated hypoglycemic symptoms. The proposed scenario provides an updated logical frame towards biologically sound therapeutic strategies and personalized therapeutic interventions for currently unaccounted IGF-II-producing cancers

A Hypothetical New Challenging Use for Indocyanine Green Fluorescence during Laparoscopic Appendectomy: A Mini-Series of Our Experience and Literary Review

Laparoscopic appendectomy (LA) is a well-standardized surgical procedure, but there are still controversies about the different devices to be used for the appendiceal stump closure and the related postoperative complications. Indocyanine green (ICG) fluorescence angiography (FA) has already been shown to be helpful in elective and emergency surgery, providing intraoperative information on tissue and organ perfusion, thus guiding the surgical decisions and the technical strategies. According to these two aspects, we report a mini-series of the first five patients affected by gangrenous and flegmonous acute appendicitis intraoperatively evaluated with ICG-FA during LA. The patients were admitted to the Emergency Department with an usual range of symptoms for acute appendicitis. The patients were successfully managed by fully LA with the help of a new hypothetical challenging use of ICG-FA