Prosanto Chaudhury

The International Position on Laparoscopic Liver Surgery: The Louisville Statement, 2008

Objective:To summarize the current world position on laparoscopic liver surgery. Summary Background Data:Multiple series have reported on the safety and efficacy of laparoscopic liver surgery. Small and medium sized procedures have become commonplace in many centers, while major laparoscopic liver resections have been performed with efficacy and safety equaling open surgery in highly specialized centers. Although the field has begun to expand rapidly, no consensus meeting has been convened to discuss the evolving field of laparoscopic liver surgery. Methods:On November 7 to 8, 2008, 45 experts in hepatobiliary surgery were invited to participate in a consensus conference convened in Louisville, KY, US. In addition, over 300 attendees were present from 5 continents. The conference was divided into sessions, with 2 moderators assigned to each, so as to stimulate discussion and highlight controversies. The format of the meeting varied from formal presentation of experiential data to expert opinion debates. Written and video records of the presentations were produced. Specific areas of discussion included indications for surgery, patient selection, surgical techniques, complications, patient safety, and surgeon training. Results:The consensus conference used the terms pure laparoscopy, hand-assisted laparoscopy, and the hybrid technique to define laparoscopic liver procedures. Currently acceptable indications for laparoscopic liver resection are patients with solitary lesions, 5 cm or less, located in liver segments 2 to 6. The laparoscopic approach to left lateral sectionectomy should be considered standard practice. Although all types of liver resection can be performed laparoscopically, major liver resections (eg, right or left hepatectomies) should be reserved for experienced surgeons facile with more advanced laparoscopic hepatic resections. Conversion should be performed for difficult resections requiring extended operating times, and for patient safety, and should be considered prudent surgical practice rather than failure. In emergent situations, efforts should be made to control bleeding before converting to a formal open approach. Utilization of a hand assist or hybrid technique may be faster, safer, and more efficacious. Indications for surgery for benign hepatic lesions should not be widened simply because the surgery can be done laparoscopically. Although data presented on colorectal metastases did not reveal an adverse effect of the laparoscopic approach on oncological outcomes in terms of margins or survival, adequacy of margins and ability to detect occult lesions are concerns. The pure laparoscopic technique of left lateral sectionectomy was used for adult to child donation while the hybrid approach has been the only one reported to date in the case of adult to adult right lobe donation. Laparoscopic liver surgery has not been tested by controlled trials for efficacy or safety. A prospective randomized trial appears to be logistically prohibitive; however, an international registry should be initiated to document the role and safety of laparoscopic liver resection. Conclusions:Laparoscopic liver surgery is a safe and effective approach to the management of surgical liver disease in the hands of trained surgeons with experience in hepatobiliary and laparoscopic surgery. National and international societies, as well as governing boards, should become involved in the goal of establishing training standards and credentialing, to ensure consistent standards and clinical outcomes.

Clostridium difficile colitis: Increasing incidence, risk factors, and outcomes in solid organ transplant recipients

Background Clostridium difficile-associated diarrhea (CDAD) is an increasingly important diagnosis in solid organ transplant recipients, with rising incidence and mortality. We describe the incidence, risk factors, and outcomes of colectomy for CDAD after solid organ transplantation. Methods Patients with CDAD were identified from a prospective transplant database. Complicated Clostridium difficile colitis (CCDC) was defined as CDAD associated with graft loss, total colectomy, or death. Results From 1999 to 2010, we performed solid organ transplants for 1331 recipients at our institution. The incidence of CDAD was 12.4% (165 patients); it increased from 4.5% (1999) to 21.1% (2005) and finally 9.5% (2010). The peak frequency of CDAD was between 6 and 10 days posttransplantation. Age more than 55 years (hazard ratio [HR]: 1.47, 95% confidence interval [CI]=1.16–1.81), induction with antithymocyte globulin (HR: 1.43, 95% CI=1.075–1.94), and transplant other than kidney alone (liver, heart, pancreas, or combined kidney organ) (HR: 1.41, 95% CI=1.05–1.92) were significant independent risk factors for CDAD. CCDC occurred in 15.8% of CDAD cases. Independent predictors of CCDC were white blood cell count more than 25,000/&mgr;L (HR: 1.08, 95% CI=1.025–1.15) and evidence of pancolitis on computed tomography scan (HR: 2.52, 95% CI=1.195–5.35). Six patients with CCDC underwent colectomy with 83% patient survival and 20% graft loss. Of the medically treated patients with CCDC (n=20), the patient survival was 35% with 100% graft loss. Conclusions We have identified significant risk factors for CDAD and predictors of progression to CCDC. Furthermore, we found that colectomy can be performed with excellent survival in selected patients.

Hypertonic saline and the microcirculation.

The systemic inflammation that occurs in shock states is believed to promote overexuberant microcirculatory activation, the release of toxic proteases and oxygen radicals causing microvascular damage, and subsequent tissue and organ injury. Although shock-associated microvascular failure is often unresolved after standard resuscitation, hypertonic saline (HTS) appears to reduce microvascular collapse, restoring vital nutritional blood flow. In addition, hypertonic fluids tend to blunt the up-regulation of leukocyte and endothelial adhesion molecules that occurs with isotonic resuscitation of shock. Recently, direct evaluation by intravital microscopy has shown that HTS resuscitation dampens the interactions between leukocytes, platelets, and endothelium found with Ringers lactate resuscitation. Furthermore, fewer cellular interactions have been correlated with attenuation in microvascular wall permeability after resuscitation with HTS. Better characterization of microcirculatory effects by hypertonic saline may provide mechanisms for improved morbidity and mortality associated with hypertonic resuscitation.

Evaluating intraoperative laparoscopic skill: direct observation versus blinded videotaped performances.

The Global Operative Assessment of Laparoscopic Skill (GOALS) has been shown to meet high standards for direct observation. The purpose of this study was to investigate the reliability and validity of GOALS when applied to blinded, videotaped performances. Five novice surgeons and 5 experienced surgeons were each evaluated by 2 observers during a laparoscopic cholecystectomy. Subsequently, 4 laparoscopists (V1 to V4) evaluated the videotaped procedures using GOALS. Two of the raters (V1 and V3) had prior experience using GOALS. The interrater reliabilities between video raters (VRs) and between VRs and direct raters (DRs) were calculated using the intraclass correlation coefficient. Construct validity was assessed using 2-way analysis of variance. Interrater reliability between the 4 VRs and the 2 DRs was 0.72. The intraclass correlation coefficient for the 4 VRs was 0.68 and for each VR compared with the mean DR was 0.86, 0.39, 0.94, and 0.76, respectively. All raters, except V2, differentiated between novice and experienced groups (P values ranged from .01 to .05). These data suggest that GOALS can be used to assess laparoscopic skill based on videotaped performances but that rater training may play an important role in ensuring the reliability and validity of the instrument. Experience with the tool in the operating room may improve the reliability of video rating and could be of value in training evaluators.

Liver transplant outcomes in HIV-infected patients: a systematic review and meta-analysis with synthetic cohort.

Objectives:The relative success of liver transplantation in those with HIV compared to HIV-uninfected individuals remains a point of intense debate. We aimed to evaluate the effectiveness of liver transplantation in HIV-hepatitis co-infected patients using a meta-analysis and individual patient data meta-analysis as a synthetic cohort. Methods:We searched MEDLINE via PubMed, EMBASE, Cochrane CENTRAL, AIDSLINE (inception to 2010), AMED, CINAHL, TOXNET, Development and Reproductive Toxicology, Hazardous Substances Databank, Psych-info and relevant conferences. We included cohort studies and individual case-reports evaluating survival of co-infected transplant patients. We abstracted data on cohort and case demographics and outcomes. We pooled cohorts using a random-effects analysis and created a synthetic cohort of cases using individual patient data. We confirmed this with the pooled cohort analysis. Results:We included 15 cohort studies and 49 case series with individual patient data. At 12 months, 84.4% [95% confidence interval (CI) 81.1–87.8%] of patients had survived. Within the HIV-infected population evaluated, HIV–hepatitis B virus (HBV) co-infection was associated with optimal survival. In an adjusted model, individuals positive for HBV were 8.28 (95% CI 2.26–30.33) times more likely to survive when compared to those without HBV. Further, individuals with an undetectable HIV viral load at the time of transplantation were 2.89 (95% CI 1.41–5.91) times more likely to survive when compared to those with detectable HIV viremia. Hepatitis C virus was not a predictor of patient survival when adjusted for by other key predictors [0.54 (95% CI 0.17–1.80)].

Portal vein embolization stimulates tumour growth in patients with colorectal cancer liver metastases

OBJECTIVES Portal vein embolization (PVE) can facilitate the resection of previously unresectable colorectal cancer (CRC) liver metastases. Bevacizumab is being used increasingly in the treatment of metastatic CRC, although data regarding its effect on post-embolization liver regeneration and tumour growth are conflicting. The objective of this observational study was to assess the impact of pre-embolization bevacizumab on liver hypertrophy and tumour growth. METHODS Computed tomography scans before and 4 weeks after PVE were evaluated in patients who received perioperative chemotherapy with or without bevacizumab. Scans were compared with scans obtained in a control group in which no PVE was administered. Future liver remnant (FLR), total liver volume (TLV) and total tumour volume (TTV) were measured. Bevacizumab was discontinued ≥ 4 weeks before PVE. RESULTS A total of 109 patients and 11 control patients were included. Portal vein embolization induced a significant increase in TTV: the right lobe increased by 33.4% in PVE subjects but decreased by 34.8% in control subjects (P < 0.001), and the left lobe increased by 49.9% in PVE subjects and decreased by 33.2% in controls (P= 0.022). A total of 52.8% of the study group received bevacizumab and 47.2% did not. There was no statistical difference between the two chemotherapy groups in terms of tumour growth. Median FLR after PVE was similar in both groups (28.8% vs. 28.7%; P= 0.825). CONCLUSIONS Adequate liver regeneration was achieved in patients who underwent PVE. However, significant tumour progression was also observed post-embolization.

Management of Chronic Allograft Nephropathy: A Systematic Review

Despite improving immunosuppressive protocols in renal transplantation, chronic allograft nephropathy (CAN) remains a major impediment to long-term graft survival. The optimal immunosuppressive regimen for a patient with CAN is unknown. The aim of this study is to evaluate the various immunosuppressive management strategies of biopsy-proven CAN and of chronic allograft dysfunction (CAD) (no biopsy). A systematic review of randomized trials (n = 12 trials with 635 patients) was conducted. Studies included patients who were >6 mo post-transplant. All patients were on a calcineurin inhibitor (CNI), most often cyclosporine, and were randomized to convert to mycophenolate mofetil (MMF), tacrolimus, or sirolimus (Rapa) or to add azathioprine, MMF or Rapa to their current regimen. Follow-up time was 6 to 36 mo. The outcome measures evaluated were renal function in 11 of 12 studies and repeat renal biopsy results in one study. The methodological quality scores of the trials were generally low, using the Jadad scale (median value 2/5). Results varied between studies but suggested that CNI withdrawal is safe and that conversion to MMF or Rapa may be beneficial. The incidence of adverse effects ranged from 0% to 68% between the studies, and medication withdrawal occurred in 0% to 24% of patients. The review did not result in a consensus regarding the management of CAN and CAD. Further studies are required to determine the best therapeutic option for patients with CAD and CAN.

Pretransplantation α-fetoprotein slope and milan criteria: strong predictors of hepatocellular carcinoma recurrence after transplantation.

Background Hepatocellular carcinoma (HCC) is a major cause of orthotropic liver transplantations (OLT). However, tumor recurrence remains a concern. Our group has shown that a rising natural &agr;-fetoprotein (AFP) slope (NAS) correlates with tumor characteristics. We want to assess if a rising NAS predicts tumor recurrence. Methods We reviewed first OLT for HCC (n=144) at our center from 1992 to 2010. Patients with less than two AFP values before treatment were excluded (n=52). A rising NAS (>0.1 &mgr;g/L/day) was found in 28 patients whereas 64 presented a stable or dropping NAS. Demographics, pre-OLT therapy, and tumor characteristics were collected. Statistical analysis was performed using ANOVA, chi-square or Fisher’s test, and logistic regression for recurrence after OLT. Results Demographics were similar among the recurrence (n=12) and nonrecurrence (n=80) groups. Patients who recurred received more treatment (P=0.017), had a higher number of lesions (P=0.025), a greater total tumor size (P=0.001), and a higher incidence of microvascular invasion (P=0.013). More patients exceeded the Milan criteria (75.0% vs. 31.3%, odds ratio [OR] 6.60, 95% confidence interval [CI] 1.45–4.05, P=0.008) and had a rising NAS (58.3% vs. 26.3%, OR 3.20, 95% CI 1.11–9.22, P=0.024) among the recurrence group. NAS was also a strong predictor of microvascular invasion (P=0.040). After correcting for age and sex, both a rising NAS (OR 3.98, 95% CI 1.01–15.81, P=0.039) and nonadherence to Milan criteria (OR 5.69, 95% CI 1.14–28.38, P=0.034) were strong predictors of recurrence after OLT. Conclusion The NAS is a predictor of microvascular invasion, a finding exclusive to pathology and in itself a predictor of HCC recurrence after OLT. The NAS and Milan criteria are good predictors of recurrence. These results encourage a frequent monitoring of AFP variations before OLT.

Male hypogonadism associated with advanced cancer: a systematic review

Male hypogonadism is commonly diagnosed on the basis of subphysiological concentrations of androgen hormones, and is associated with many symptoms present in advanced cancer. Androgen deficiency might be an important cause of muscle wasting in both cancer cachexia and sarcopenia. We did a systematic review of the clinical association of male hypogonadism in advanced cancer. We searched PubMed, Medline, and Embase for publications on the relation between male hypogonadism and functional status, nutritional status, body composition, symptoms, and quality of life in patients with advanced cancer. Of 381 publications identified, six original articles were included. We found no definitive association between nutritional, functional, or quality-of-life characteristics and male hypogonadism. Possible associations between male hypogonadism and weight loss, low albumin, low-body cell mass index, low-peripheral fat and muscle mass, higher inflammation, higher pain, higher opioid consumption, worse scores for anxiety, depression, and emotional and functional well-being need to be confirmed by better designed studies. There is no clear epidemiological data to indicate whether male hypogonadism is independently associated with clinical and biological sequelae of cancer cachexia, such as higher inflammation, fatigue, and body wasting. Standardised kits sensitive to low concentrations of free-testosterone or bioavailable testosterone are needed to diagnose androgen deficiency in women. A clearer epidemiology of androgen deficiencies in advanced cancer will help determine which patients should receive testosterone-replacement therapy for alleviating cancer cachexia symptoms and improving quality of life.

Liver transplantation in the critically ill: a multicenter Canadian retrospective cohort study

IntroductionCritically ill cirrhosis patients awaiting liver transplantation (LT) often receive prioritization for organ allocation. Identification of patients most likely to benefit is essential. The purpose of this study was to examine whether the Sequential Organ Failure Assessment (SOFA) score can predict 90-day mortality in critically ill recipients of LT and whether it can predict receipt of LT among critically ill cirrhosis listed awaiting LT.MethodsWe performed a multicenter retrospective cohort study consisting of two datasets: (a) all critically-ill cirrhosis patients requiring intensive care unit (ICU) admission before LT at five transplant centers in Canada from 2000 through 2009 (one site, 1990 through 2009), and (b) critically ill cirrhosis patients receiving LT from ICU (n = 115) and those listed but not receiving LT before death (n = 106) from two centers where complete data were available.ResultsIn the first dataset, 198 critically ill cirrhosis patients receiving LT (mean (SD) age 53 (10) years, 66% male, median (IQR) model for end-stage liver disease (MELD) 34 (26-39)) were included. Mean (SD) SOFA scores at ICU admission, at 48 hours, and at LT were 12.5 (4), 13.0 (5), and 14.0 (4). Survival at 90 days was 84% (n = 166). In multivariable analysis, only older age was independently associated with reduced 90-day survival (odds ratio (OR), 1.07; 95% CI, 1.01 to 1.14; P = 0.013). SOFA score did not predict 90-day mortality at any time. In the second dataset, 47.9% (n = 106) of cirrhosis patients listed for LT died in the ICU waiting for LT. In multivariable analysis, higher SOFA at 48 hours after admission was independently associated with lower probability of receiving LT (OR, 0.89; 95% CI, 0.82 to 0.97; P = 0.006). When including serum lactate and SOFA at 48 hours in the final model, elevated lactate (at 48 hours) was also significantly associated with lower likelihood of receiving LT (0.32; 0.17 to 0.61; P = 0.001).ConclusionsSOFA appears poor at predicting 90-day survival in critically ill cirrhosis patients after LT, but higher SOFA score and elevated lactate 48 hours after ICU admission are associated with a lower probability receiving LT. Older critically ill cirrhosis patients (older than 60) receiving LT have worse 90-day survival and should be considered for LT with caution.