Jerome M. Laurence

A Systematic Review of Clinical Response and Survival Outcomes of Downsizing Systemic Chemotherapy and Rescue Liver Surgery in Patients with Initially Unresectable Colorectal Liver Metastases

BackgroundSelected patients with unresectable colorectal liver metastases (CLM) may be rendered resectable after systemic chemotherapy. We reviewed the evidence of downsizing systemic chemotherapy followed by rescue liver surgery in patients with initially unresectable CLM.MethodsLiterature search of databases (Medline and PubMed) to identify published studies of neoadjuvant chemotherapy followed by liver resection in patients with initially unresectable CLM was undertaken and focused on response rate of chemotherapy and survival outcomes.ResultsTen observational studies were reviewed. A total of 1,886 patients with initially unresectable CLM underwent systemic chemotherapy. An objective response was observed in 64% (range, 43–79%) of patients after systemic chemotherapy. Of these, 22.5% underwent macroscopically curative liver resection. Median overall survival was 45 (range, 36–60) months with 19% of patients alive and recurrence-free.ConclusionsCurrent evidence suggests that downsizing systematic chemotherapy followed by rescue liver resection is safe and effective for selected patients with initially unresectable CLM. Further studies are required to examine response rates and secondary resectability using new targeted molecular therapy-based regimens.Selected patients with unresectable colorectal liver metastases (CLM) may be rendered resectable after systemic chemotherapy. We reviewed the evidence of downsizing systemic chemotherapy followed by rescue liver surgery in patients with initially unresectable CLM. Literature search of databases (Medline and PubMed) to identify published studies of neoadjuvant chemotherapy followed by liver resection in patients with initially unresectable CLM was undertaken and focused on response rate of chemotherapy and survival outcomes. Ten observational studies were reviewed. A total of 1,886 patients with initially unresectable CLM underwent systemic chemotherapy. An objective response was observed in 64% (range, 43–79%) of patients after systemic chemotherapy. Of these, 22.5% underwent macroscopically curative liver resection. Median overall survival was 45 (range, 36–60) months with 19% of patients alive and recurrence-free. Current evidence suggests that downsizing systematic chemotherapy followed by rescue liver resection is safe and effective for selected patients with initially unresectable CLM. Further studies are required to examine response rates and secondary resectability using new targeted molecular therapy-based regimens.

Endoscopic necrosectomy of pancreatic necrosis: a systematic review

AimTo review the current status of the novel technique of endoscopic necrosectomy in the management of pancreatic necrosis after acute pancreatitis.MethodsStudies were identified by searching Medline, PubMed and Embase databases for articles from January 1990 to December 2009 using the keywords “acute pancreatitis”, “pancreatic necrosis” and “endoscopy”. Additional papers were identified by a manual search of the references from the key articles. Case series of fewer than five patients and case reports were excluded.ResultsIndications, techniques and outcomes of endoscopic necrosectomy were analysed. There were no randomised controlled trials identified. Ten case series were included in this analysis. There were a total of more than 1,100 endoscopic necrosectomy procedures in 260 patients with pancreatic necrosis. One hundred fifty-five were proven to be infected necrosis on culture. The overall mortality rate was 5%. The mean procedure-related morbidity rate was 27%. The rate of complete resolution of pancreatic necrosis with the endoscopic method alone was 76%.ConclusionsEndoscopic necrosectomy is a safe and effective treatment option in selected patients with pancreatic necrosis after acute pancreatitis. Future studies will be required to further define the selection criteria and the techniques for the endoscopic procedure.

A Systematic Review and Meta-analysis of Survival and Surgical Outcomes Following Neoadjuvant Chemoradiotherapy for Pancreatic Cancer

IntroductionThis systematic review and meta-analysis aims to characterize the surgically important benefits and complications associated with the use of neoadjuvant chemoradiotherapy for the treatment of both resectable and initially unresectable pancreatic cancer. Studies were identified through a systematic literature search and analyzed by two independent reviewers. Survival, peri-operative complications, death rate, pancreatic fistula rate, and the incidence of involved surgical margins were analyzed and subject to meta-analysis.MethodsNineteen studies, involving 2,148 patients were identified. Only cohort studies were included.ResultsThe meta-analysis found that patients with unresectable pancreatic cancer who underwent neoadjuvant chemoradiotherapy achieved similar survival outcomes to patients with resectable disease, even though only 40% were ultimately resected. Neoadjuvant chemoradiotherapy was not associated with a statistically significant increase in the rate of pancreatic fistula formation or total complications.ConclusionPatients receiving neoadjuvant chemoradiotherapy were less likely to have a positive resection margin, although there was an increase in the risk of peri-operative death.

Systematic review of actual 10‐year survival following resection for hepatocellular carcinoma

BACKGROUND Hepatic resection is a potentially curative therapy for hepatocellular carcinoma (HCC), but recurrence of disease is very common. Few studies have reported 10-year actual survival rates following hepatic resection; instead, most have used actuarial measures based on the Kaplan-Meier method. This systematic review aims to document 10-year actual survival rates and to identify factors significant in determining prognosis. METHODS A comprehensive search was undertaken of MEDLINE and EMBASE. Only studies reporting the absolute number of patients alive at 10 years after first resection for HCC were included; these figures were used to calculate the actual 10-year survival rate. A qualitative review and analysis of the prognostic factors identified in the included studies were performed. RESULTS Fourteen studies, all of which were retrospective case series, including data on 4197 patients with HCC were analysed. Ten years following resection, 303 of these patients were alive. The 10-year actual survival rate was 7.2%, whereas the actuarial survival quoted from the same studies was 26.8%. Positive prognostic factors included better hepatic function, a wider surgical margin and the absence of satellite lesions. CONCLUSIONS The actual long-term survival rate after resection of HCC is significantly inferior to reported actuarial survival rates. The Kaplan-Meier method of actuarial survival analysis tends to overestimate survival outcomes as a result of censorship of data and subgroup analysis.

Transarterial Chemoembolization with Irinotecan Beads in the Treatment of Colorectal Liver Metastases: Systematic Review

PURPOSE For patients with unresectable colorectal liver metastasis (CRLM), transarterial embolization with the use of drug-eluting beads with irinotecan (DEBIRI) represents a novel alternative to systemic chemotherapy or local treatments alone. The present systematic review evaluates available data on the efficacy and safety of DEBIRI embolization. MATERIALS AND METHODS A comprehensive search of medical literature identified studies describing the use of DEBIRI in the treatment of CRLM. Data describing adverse events, pharmacokinetics, tumor response, and overall survival were collected. RESULTS Five observational studies and one randomized controlled trial (RCT) were reviewed. A total of 235 patients were included in the descriptive analysis of observational studies. Postembolization syndrome was the most common adverse event. Peak plasma levels of irinotecan were observed at 1-2 hours after administration. Wide variations in tumor response were observed. The median survival time ranged from 15.2 months to 25 months. In the RCT, treatment with DEBIRI was superior to systemic chemotherapy with 5-fluorouracil/leucovorin/irinotecan in terms of quality of life and progression-free survival. CONCLUSIONS For patients with unresectable CRLM, particularly after failure to respond to first-line regimens, DEBIRI represents a novel alternative to systemic chemotherapy alone, transarterial embolization with other agents, or other local treatments (eg, microwave or radiofrequency ablation). In these reports, DEBIRI was safe and effective in the in the treatment of unresectable CRLM. Further RCTs comparing DEBIRI with alternative management strategies are required to define the optimal role for this treatment.

Laparoscopic hepatectomy, a systematic review.

This systematic review was undertaken to assess the published evidence for the safety, feasibility and reproducibility of laparoscopic liver resection. A computerized search of the Medline and Embase databases identified 28 non‐duplicated studies including 703 patients in whom laparoscopic hepatectomy was attempted. Pooled data were examined for information on the patients, lesions, complications and outcome. The most common procedures were wedge resection (35.1%), segmentectomy (21.7%) and left lateral segmentectomy (20.9%). Formal right hepatectomy constituted less than 4% of the reported resections. The conversion and complication rates were 8.1% and 17.6%, respectively. The mortality rate over all these studies was 0.8% and the median (range) hospital stay 7.8 days (2–15.3 days). Eight case–control studies were analysed and although some identified significant reductions in‐hospital stay, time to first ambulation after surgery and blood loss, none showed a reduction in complication or mortality rate for laparoscopically carried out resections. It is clear that certain types of laparoscopic resection are feasible and safe when carried out by appropriately skilled surgeons. Further work is needed to determine whether these conclusions can be generalized to include formal right hepatectomy.

The extended Toronto criteria for liver transplantation in patients with hepatocellular carcinoma: A prospective validation study

The selection of liver transplant candidates with hepatocellular carcinoma (HCC) relies mostly on tumor size and number. Instead of relying on these factors, we used poor tumor differentiation and cancer‐related symptoms to exclude patients likely to have advanced HCC with aggressive biology. We initially reported similar 5‐year survival for patients whose tumors exceeded (M+ group) and were within (M group) the Milan criteria. Herein, we validate our original data with a new prospective cohort and report the long‐term follow‐up (10‐years) using an intention‐to‐treat analysis. The previously published study (cohort 1) included 362 listed (294 transplanted) patients from January 1996 to August 2008. The validation cohort (cohort 2) includes 243 listed (105 M+ group, 76 beyond University of California San Francisco criteria; 210 transplanted) patients from September 2008 to December 2012. Median follow‐up from listing was 59.7 (26.8‐103) months. For the validation cohort 2, the actuarial survival from transplant for the M+ group was similar to that of the M group at 1 year, 3 years, and 5 years: 94%, 76%, and 69% versus 95%, 82%, and 78% (P = 0.3). For the combined cohorts 1 and 2, there were no significant differences in the 10‐year actuarial survival from transplant between groups. On an intention‐to‐treat basis, the dropout rate was higher in the M+ group and the 5‐year and 10‐year survival rates from listing were decreased in the M+ group. An alpha‐fetoprotein level >500 ng/mL predicted poorer outcomes for both the M and M+ groups. Conclusion: Tumor differentiation and cancer‐related symptoms of HCC can be used to select patients with advanced HCC who are appropriate candidates for liver transplantation; alpha‐fetoprotein level limitations should be incorporated in the listing criteria for patients within or beyond the Milan criteria. (Hepatology 2016;64:2077‐2088)

Laparoscopic or open cholecystectomy in cirrhosis: a systematic review of outcomes and meta-analysis of randomized trials

BACKGROUND Cholecystectomy is associated with increased risks in patients with cirrhosis. The well-established advantages of laparoscopic surgery may be offset by the increased risk for complications relating particularly to portal hypertension and coagulopathy. METHODS A systematic search was undertaken to identify studies comparing open cholecystectomy (OC) and laparoscopic cholecystectomy (LC) in patients with cirrhosis. A meta-analysis was performed of the available randomized controlled trials (RCTs). RESULTS Forty-four studies were analysed. These included a total of 2005 patients with cirrhosis who underwent laparoscopic (n= 1756) or open (n= 249) cholecystectomy, with mortality rates of 0.74% and 2.00%, respectively. A meta-analysis of three RCTs involving a total of 220 patients was conducted. There was a reduction in the overall incidences of postoperative complications and infectious complications and a shorter length of hospital stay in LC. However, frequencies of postoperative hepatic insufficiency did not differ significantly. CONCLUSIONS There are few RCTs comparing OC and LC in patients with cirrhosis. These studies are small, heterogeneous in design and include almost exclusively patients with Child-Pugh class A and B disease. However, LC appears to be associated with shorter operative time, reduced complication rates and reduced length of hospital stay.

Blocking indoleamine dioxygenase activity early after rat liver transplantation prevents long-term survival but does not cause acute rejection.

In a well-characterized rat model of liver transplantation, Piebald Virol Glaxo strain livers are accepted long term in fully mismatched Dark Agouti recipients (tolerance; TOL), but rejected in Lewis recipients (rejection; REJ). Spontaneous tolerance induction is associated with increased interferon-&ggr; expression, and we examined the role of the interferon-&ggr;-inducible immunomodulatory enzyme indoleamine dioxygenase (IDO) in this model. On day 3 after transplantation, IDO expression in the spleen of TOL recipients was significantly greater than in REJ. The B-cell population accounted for this early IDO increase. Intragraft expression of IDO increased to the same extent in both TOL and REJ. IDO inhibition for 7 days after transplantation reduced survival, but did not cause acute rejection of the liver in the TOL model. In conclusion, the differential IDO expression by B lymphocytes in the spleen of TOL recipients is not critical for preventing acute rejection.

Utilization of small pediatric donor kidneys: a decision analysis.

Background. Given the disparity between static supply and increasing demand for organs, the greatest challenge is broadening access to the benefits of kidney transplantation. Organs from small deceased pediatric donors are a potentially underused resource. These may be transplanted as en bloc kidney transplants (EBKTs) to one recipient or as single kidney transplants (SKTs) to two recipients, albeit with an increased risk of graft failure. Methods. A systematic literature search identified data on transplant outcomes for recipients of organs from small pediatric deceased donors. A decision analysis model was constructed to allow the outcome in life years (LY) to be predicted for patients with end-stage kidney disease on the transplant waiting list depending on whether they received EBKT or SKT. Results. At all recipient ages, the projected LY of both recipients of an SKT was greater than the projected LY of an EBKT recipient. The net estimated gain in LY associated with the SKT technique was greatest for recipients aged 20 to 39 years (14.3 years) and lowest for recipients aged 60 to 74 years (3.36 years). Only for recipients of organs from donors weighing less than 10 kg, there was an estimated net loss of LY associated with the SKT technique across all recipient age groups. Conclusions. There is a greater gain in overall life expectancy using SKTs, because this technique yields two recipients per donor, which more than compensates for the increased risk of graft failure.