Consensus Conference on North American Training in Hepatopancreaticobiliary Surgery: A Review of the Conference and Presentation of Consensus Statements.

The findings and recommendations of the North American consensus conference on training in hepatopancreaticobiliary (HPB) surgery held in October 2014 are presented. The conference was hosted by the Society for Surgical Oncology (SSO), the Americas Hepato-Pancreatico-Biliary Association (AHPBA), and the American Society of Transplant Surgeons (ASTS). The current state of training in HPB surgery in North America was defined through three pathways-HPB, surgical oncology, and solid organ transplant fellowships. Consensus regarding programmatic requirements included establishment of minimum case volumes and inclusion of quality metrics. Formative assessment, using milestones as a framework and inclusive of both operative and nonoperative skills, must be present. Specific core HPB cases should be defined and used for evaluation of operative skills. The conference concluded with a focus on the optimal means to perform summative assessment to evaluate the individual fellow completing a fellowship in HPB surgery. Presentations from the hospital perspective and the American Board of Surgery led to consensus that summative assessment was desired by the public and the hospital systems and should occur in a uniform but possibly modular manner for all HPB fellowship pathways. A task force composed of representatives of the SSO, AHPBA, and ASTS are charged with implementation of the consensus statements emanating from this consensus conference.

Dropped Gallstones Causing a Perihepatic Abscess and Empyema.

Iatrogenic perforation of the gallbladder during laparoscopic cholecystectomy is a well-known occurrence; however, the consequences of spillage of gallstones in the peritoneum and particularly intrathoracic complications are less defined. We describe the delayed development of a perihepatic abscess and empyema in a patient five years following laparoscopic cholecystectomy secondary to dropped gallstones. A 53-year-old man with medical history significant for a laparoscopic cholecystectomy five years prior to acute cholecystitis presented with purulent cough, hemoptysis, night sweats, and right-upper quadrant (RUQ) pain. Computed tomography (CT) scan revealed 5.4 cm right-sided subpulmonic and 5.9 cm perihepatic fluid collections with an 8 mm focal radiopaque density within the perihepatic fluid collection. Open intra-abdominal exploration resulted in retrieval of a 1 cm intraperitoneal gallstone. Laparoscopic cholecystectomy is a common surgical operation during which gallstone spillage can occur, causing both intra-abdominal and intrathoracic complications, presenting even years after surgery. This necessitates an attempt to retrieve all free intra-abdominal gallstones during the initial operation.

Long-term cognitive impairment after critical illness.

BACKGROUND: Survivors of critical illness often have a prolonged and disabling form of cognitive impairment that remains inadequately characterized. METHODS: We enrolled adults with respiratory failure or shock in the medical or surgical intensive care unit (ICU), evaluated them for in-hospital delirium, and assessed global cognition and executive function 3 and 12 months after discharge with the use of the Repeatable Battery for the Assessment of Neuropsychological Status (population age-adjusted mean [±SD] score, 100±15, with lower values indicating worse global cognition) and the Trail Making Test, Part B (population age-, sex-, and education-adjusted mean score, 50±10, with lower scores indicating worse executive function). Associations of the duration of delirium and the use of sedative or analgesic agents with the outcomes were assessed with the use of linear regression, with adjustment for potential confounders. RESULTS: Of the 821 patients enrolled, 6% had cognitive impairment at baseline, and delirium developed in 74% during the hospital stay. At 3 months, 40% of the patients had global cognition scores that were 1.5 SD below the population means (similar to scores for patients with moderate traumatic brain injury), and 26% had scores 2 SD below the population means (similar to scores for patients with mild Alzheimer's disease). Deficits occurred in both older and younger patients and persisted, with 34% and 24% of all patients with assessments at 12 months that were similar to scores for patients with moderate traumatic brain injury and scores for patients with mild Alzheimer's disease, respectively. A longer duration of delirium was independently associated with worse global cognition at 3 and 12 months (P=0.001 and P=0.04, respectively) and worse executive function at 3 and 12 months (P=0.004 and P=0.007, respectively). Use of sedative or analgesic medications was not consistently associated with cognitive impairment at 3 and 12 months. CONCLUSIONS: Patients in medical and surgical ICUs are at high risk for long-term cognitive impairment. A longer duration of delirium in the hospital was associated with worse global cognition and executive function scores at 3 and 12 months. (Funded by the National Institutes of Health and others; BRAIN-ICU ClinicalTrials.gov number, NCT00392795.).

Liver transplantation at Dumont-UCLA Transplant Center: an experience with over 3,000 cases.

Liver transplantation has seen extraordinary advances over the past 2 decades and now represents the only life-saving therapy for many patients with decompensated liver disease, regardless of etiology. As the indications for transplantation expand, the patient waiting list continues to grow, while the number of available donors each year remains relatively constant. As a result, there is a marked shortage of donor organs, prolonging the waiting time and thereby increasing the mortality of patients while waiting for OLT. At UCLA, we are actively pursuing novel approaches to increase retrieval of transplant organs. The use of in-vivo split-liver transplantation represents an effective technique to safely expand the number of organs and also provides a size-matched organ for pediatric patients. Living-donor liver transplantation represents a significant surgical achievement in an effort to expand the critical shortage of donor organs. However, the added risk imposed on a healthy individual by the use of this technique raises serious bio-ethical concerns. Although the results of OLT have improved substantially, most of the current recipient morbidity and mortality results from recurrence of disease, infectious complications, rejection, PNF, and technical complications. The development of effective pharmacological agents to prevent disease recurrence, as well as improvements in immunosuppression therapy will be important issues in the upcoming decade.

Surgical experience with hepatic colorectal metastasis.

The outcome of 134 patients undergoing hepatic resection for colorectal metastasis was studied. Current follow-up was available in 98 per cent of patients, for more than 5 years in 58 patients, and totaling 360 patient-years. Patients (52% male) had an average age of 62 +/- 1 years (standard error of the mean). Time lapse between the primary colon surgery and hepatic resection was a median of 16 months and a mean of 19 +/- 1 months. Thirty-two (24%) were operated on within 6 months for both their primary tumor and hepatic metastasis. Intensive care unit and total hospital length of stay were a median of 1 and 7 days, respectively. Pathology reports demonstrated that on average there were 2.0 +/- 0.1 lesions, with the largest lesion measuring 4.4 +/- 0.2 cm. In 72 per cent of patients, the lesions were found in one lobe only. CEA was elevated in 83 per cent of patients preoperatively and was 60 +/- 11 ng/mL before and 4.0 +/- 0.5 ng/mL after hepatic resection. Patient survival was 81 per cent at 1 year, 50 per cent at 3 years, 36 per cent at 5 years, and 23 per cent at 10 years. Actual 5- and 10-year survival was 22 of 58 (38%) patients and 4 of 21 (19%) patients respectively. Disease-free survival was 58 per cent at 1 year, 27 per cent at 3 years, 16 per cent at 5 years, and 12 per cent at 7 years. Survival was much better for one to four lesions than for five or more lesions (P < 0.01). Several other potential risk factors did not affect survival, including whether the patient received chemotherapy after hepatic resection. There were 36 (43%) patients who recurred with hepatic involvement only, 27 (32%) including hepatic involvement and 21 (25%) with nonhepatic involvement only. There were 15 patients who went on to receive repeat hepatic resections, with a 5-year survival of 74 per cent and disease-free survival of 58 per cent. Hepatic resection provides the best outcome of any form of therapy for selected patients with isolated hepatic metastasis.

Comparison of arcuate-legged clipped versus sutured hepatic artery, portal vein, and bile duct anastomoses.

Attempts at improving anastomoses have included the development of stapling techniques. Our purpose was to evaluate arcuate-legged clipped versus standard sutured anastomoses of the hepatic artery (HA), portal vein (PV), and bile duct in a porcine liver transplantation model. Two groups of pigs were studied intraoperatively and 1 day after liver transplantation. A control group underwent sutured anastomosis of PV and HA with polypropylene and of bile duct with polydioxanone (n = 8). An experimental group underwent anastomoses with arcuate-legged clips (n = 8). We analyzed the time to perform anastomosis and flows before and at various time points after anastomosis. In addition, patency and histology of the anastomoses were evaluated 1 day after operation, including a fibrin-thrombosis score, medial injury, and inflammation score. Times to complete HA and PV anastomoses were not different between clipped and sutured groups. However, the time was shorter to complete bile duct anastomosis with clips than with sutures (6.3 +/- 1.1 minutes and 13.3 +/- 2.0 minutes, respectively). Flows through HA anastomoses were not different between groups, but flow through the PV was higher in clipped compared with sutured anastomosis (P = 0.06). Patency was 100 per cent with no leaks for all three anastomoses in both groups. Histologic data were similar between vascular anastomotic groups. Sutured bile duct anastomoses revealed mild smooth muscle injury in 75 per cent whereas clipped bile duct anastomoses displayed no smooth muscle injury. We conclude that arcuate-legged clipped anastomosis represents a viable option to sutured anastomoses of the PV, HA, and bile duct anastomoses. Bile duct anastomoses were completed in less than half the time and with less tissue damage documented histologically.

The effect of nutritional and hormonal supplementation on protein synthesis immediately after liver transplantation.

We have previously shown that immediately after liver transplantation (LT) the porcine recipient exhibits elevated plasma glucagon, increased fractional synthetic rate (FSR) of fibrinogen, and decreased FSR of fixed or structural liver proteins. The purpose of this study was to evaluate the effect of nutritional and hormonal supplementation on these observations 24 h after LT. Two groups of nine pigs were studied 1 day after LT using radioisotopic and arteriovenous difference techniques. A control group underwent LT with saline infusion and a supplemented group underwent LT with infusion of glucose, amino acids (6 and 1.06 mg/kg. min, respectively), and intraportal insulin (0.6 mU/kg. min) and glucagon (1.3 ng/kg. min). Primed constant infusions of [3H]leucine were used to determine leucine flux, an estimate of whole body protein breakdown, and fractional synthetic rates (FSR). The following changes were noted with supplementation: elevated plasma insulin (6 +/- 1 versus 29 +/- 4 microU/ml, control versus supplemented, respectively, P < 0.05), decreased glucagon to normal levels (323 +/- 65 versus 102 +/- 12 pg/ml, P < 0.05), decreased fibrinogen FSR (108 +/- 15 versus 70 +/- 6%/day, P < 0.025), and increased fixed liver protein FSR (8 +/- 1 versus 13 +/- 2%/day, P < 0.05, respectively). Albumin FSR was unaltered by supplementation (8 +/- 2 versus 6 +/- 1%/day, respectively). Nutritional and hormonal supplementation immediately after LT restored the measured protein synthesis in the allograft to near normal levels 1 day after transplantation.

Screening for cerebral aneurysm in patients with polycystic liver disease.

BACKGROUND: Polycystic liver disease (PCLD) is an autosomal dominant disease characterized by multiple macrocystic lesions throughout the liver. The association between PCLD and cerebral aneurysm is well documented, and approximately 20% of patients with PCLD have demonstrable cerebral aneurysms at autopsy. The prevalence reported from autopsy series, however, may not reflect the true prevalence in patients with PCLD. We undertook this study to evaluate the prevalence and diagnosis of cerebral aneurysms in screening cerebral studies in patients with PCLD. METHODS: Patients were identified by searching the hepatobiliary surgical service data base and hospital medical records. Hospital charts were reviewed to confirm presence of PCLD and to identify screening studies for cerebral aneurysms. RESULTS: Ten patients with PCLD received screening studies of the cerebral vasculature during a 10 1/2-year period. One patient was found to have an asymptomatic cerebral aneurysm. A 45-year-old woman with no other significant medical history was referred for evaluation of PCLD. Screening magnetic resonance angiography (MRA) revealed a 5 mm aneurysm extending anteriorly near the origin of the right ophthalmic artery, without evidence of rupture. Cerebral angiography confirmed these findings, and the aneurysm was clipped. CONCLUSIONS: Because cerebral aneurysms can be an important source of morbidity and mortality in PCLD, we recommend screening by MRA or by computed tomographic angiography (CTA) of the cerebral vasculature in all patients who have PCLD.

Impact of Sandimmune, Neoral, and Prograf on rejection incidence and renal function in primary liver transplant recipients.

Following primary liver transplantation, immunosuppressive efficacy of Neoral and Prograf was similar and superior to that of Sandimmune. Rejection incidence was statistically increased with Sandimmune therapy. Incidence of hypertension, posttransplant diabetes mellitus, and infectious complications was not statistically different. Although early compromise in renal function was associated with Sandimmune, Neoral, and Prograf immunosuppression, no progressive renal dysfunction was identified.

Experience with neoral versus sandimmune in primary liver transplant recipients.

We compared results using Neoral versus Sandimmune, each in combination with steroid and azathioprine immunosuppression, in primary liver transplantation recipients. There were 15 patients in each group with similar demographic distributions. Intravenous cyclosporine was stopped at 4.3 +/- 1.9 days in the Neoral group vs 7.8 +/- 4.9 days in the Sandimmune group. (P < 0.025). Cyclosporine levels in the first 10 days were higher (mean 306 ng/ml vs 231 ng/ml) in the Neoral group than the Sandimmune group (P < 0.05). The Neoral dose was less than the Sandimmune dose (mean 5.5 ng/kg per day vs 7.9 ng/kg per day) to achieve these levels in that time period (P < 0.05). Two patients (13%) experienced three episodes of biopsy-proven rejection in the Neoral group compared to nine patients (60%) with 12 episodes of rejection in the Sandimmune group (P < 0.025). Incidences of neurological and renal complications were similar between the groups. Infections requiring treatment were also similar. Liver function, renal function, and marrow function, evaluated at days 7, 14, 21, 28, and 2, 4, 6, and 12 months post-transplant, were not different between the groups. In summary, shorter use of intravenous cyclosporine and quicker stabilization of trough cyclosporine levels was achieved with Neoral than with Sandimmune. In the early post-transplant period, higher levels with lower doses were achieved with Neoral than with Sandimmune. In our experience, the incidence of rejection was lower with Neoral than with Sandimmune. There were similar lengths of hospitalization, mortality, adverse events, retransplantation, and similar liver, renal, and marrow function up to 1 year post-transplantation. Because of this experience, we continued to use Neoral in a total of 59 primary liver transplant recipients. We have not used intravenous cyclosporine in the last 44 patients. Follow-up was a mean of 11.4 months, ranging from 1 to 27 months. The incidence of rejection was 24% in these 59 patients compared to our historical experience of 70% using Sandimmune.

Renal function in primary liver transplant recipients receiving neoral (cyclosporine) versus prograf (tacrolimus).

Immunosuppressive efficacy of Neoral and Prograf following primary hepatic transplantation was comparable. Incidence of rejection episodes, infectious complications, hypertension, and postoperative diabetes mellitus was comparable. Although clinical use of both immunosuppressants was associated with early compromise in renal function, no progressive renal dysfunction was observed.

Outcomes analysis in 100 liver transplantation patients.

BACKGROUND: There is an increasing demand for outcomes analysis, including quality of life and financial analysis, following medical interventions and surgical procedures. We analyzed outcomes for 100 consecutive patients undergoing liver transplantation during a period of case management revision. METHODS: Patient survival was calculated by Kaplan-Meier actuarial methods. The Karnofsky performance status was objectively assessed for surviving patients up to 6 years after transplantation and was evaluated by repeated measures analysis of variance and covariance. Subjective evaluation of quality of life over time was obtained using the Psychosocial Adjustment to Illness Scale. The correlations between time and scale were calculated. Financial data were accumulated from billing records. RESULTS: Six-month, 1-year, 2-year, and 3- through 5-year survival was 86%, 84%, 83%, and 78%, respectively. Karnofsky performance status confirmed poor functional status preoperatively with a mean of 53 +/- 2, but significantly improving to 72 +/- 2 at 3 months, 80 +/- 2 at 6 months, 90 +/- 1 at 1 year, 92 +/- 1 at 2 years, 94 +/- 1 at 3 years, 96 +/- 1 at 4 years, and 97 +/- 1 at 5 years (P <0.001). Psychosocial Adjustment to Illness Scale scores demonstrated significant improvement following transplantation overall (r = -0.33), improving most in sexual relationships (r = -0.41), and domestic environment (r = -0.35; P <0.001). Median length of stay for the first half of the patients was 19 days declining to 11 days for the second half. Median hospital charges declined from $105,000 to $90,000. CONCLUSIONS: Quality of life parameters assessed both by care givers (Karnofsky) and by patients (Psychosocial Adjustment to Illness Scale) improved dramatically following transplantation and over time, demonstrating that liver transplantation effectively restores a good quality of life. Outcomes can be improved while reducing length of stay and charges through modifications in case management.

Depletion of retinyl esters in the lungs coincides with lung prenatal morphological maturation.

Close to birth rat fetuses have lungs which are depleted in retinyl esters. Glucocorticoids administered to pregnant rats accelerate this process. We have investigated changes in fetal lung levels of retinol and retinyl palmitate and accompanying morphological changes after administration of dexamethasone to pregnant rats on day 18 of pregnancy. Here we show that this depletion temporarily coincides with prenatal morphological maturation of the lungs. The data presented support the idea that the maturational effect of glucocorticoids in the developing lungs is linked to vitamin A metabolism.