Duilio Pagano

The STROCSS statement: Strengthening the Reporting of Cohort Studies in Surgery

INTRODUCTION The development of reporting guidelines over the past 20 years represents a major advance in scholarly publishing with recent evidence showing positive impacts. Whilst over 350 reporting guidelines exist, there are few that are specific to surgery. Here we describe the development of the STROCSS guideline (Strengthening the Reporting of Cohort Studies in Surgery). METHODS AND ANALYSIS We published our protocol apriori. Current guidelines for case series (PROCESS), cohort studies (STROBE) and randomised controlled trials (CONSORT) were analysed to compile a list of items which were used as baseline material for developing a suitable checklist for surgical cohort guidelines. These were then put forward in a Delphi consensus exercise to an expert panel of 74 surgeons and academics via Google Forms. RESULTS The Delphi exercise was completed by 62% (46/74) of the participants. All the items were passed in a single round to create a STROCSS guideline consisting of 17 items. CONCLUSION We present the STROCSS guideline for surgical cohort, cross-sectional and case-control studies consisting of a 17-item checklist. We hope its use will increase the transparency and reporting quality of such studies. This guideline is also suitable for cross-sectional and case control studies. We encourage authors, reviewers, journal editors and publishers to adopt these guidelines.

Surgical predictors of recurrence of Crohn’s disease after ileocolonic resection

Background/aimsAnastomotic recurrence after bowel resection is a major problem in Crohn’s disease (CD) surgery. The aims of this retrospective study are to assess the role of anastomotic configuration, the type of suture and the type of surgical approach (laparoscopy-assisted vs laparotomy) in CD recurrence. Secondary end points were to identify any possible predictor that would help the selection of patients for medical prophylaxis.Materials and methodsIn this retrospective study, we enrolled 141 consecutive patients who had undergone ileocolonic resection for CD. Univariate actuarial analysis was performed according to demographic, clinical and surgical predictors. Variables that resulted to be significant at the univariate analysis were included in two multivariate Cox proportional hazards models that analyzed symptomatic and surgical recurrence, respectively.ResultsIn the long-term, handsewn side-to-side anastomosis reported a significantly lower surgical recurrence rate than stapled end-to-side (p < 0.05). At multivariate analysis, anastomosis type, surgical and intestinal complications (p < 0.01) and age at CD onset (p < 0.05) resulted to be significant predictors for re-operation for CD recurrence. Multivariate analysis showed that surgical complication was also a significant predictor of symptomatic recurrence.ConclusionsSide-to-side anastomosis configuration seems to delay re-operation and can be assumed as the standard configuration in ileocolonic anastomosis in CD. Post-operative complications and young age at disease onset might be a signal of aggressive CD that may warrant prophylactic pharmacological therapy.

Lamivudine monoprophylaxis for de novo HBV infection in HBsAg-negative recipients with HBcAb-positive liver grafts.

Vizzini G, Gruttadauria S, Volpes R, D’Antoni A, Pietrosi G, Filì D, Petridis I, Pagano D, Tuzzolino F, Maria Santonocito M, Gridelli B. Lamivudine monoprophylaxis for de novo HBV infection in HBsAg‐negative recipients with HBcAb‐positive liver grafts.
Clin Transplant 2011: 25: E77–E81.

Minimally invasive management of Crohn's disease complicated by ureteral stenosis

Ureteral involvement due to Crohns disease occurs in 3% to 6% of cases. Herein, we present a case of a 22-year-old woman with ileocolic Crohns disease with right hydronephrosis due to compression of the ureter that was resolved with a 3-stage, minimally invasive procedure (preoperative percutaneous nephrostomy, ureteral stent placement, and sequential laparoscopically assisted ileocolectomy). Percutaneous right nephrostomy drainage permitted us to prevent renal damage before surgery, and successive ureteral double-J catheter placement minimized the risk of ureteral damage during the laparoscopic procedure. The safety and feasibility of sequential minimally invasive management of ileocolonic Crohns disease involving the right ureter was assessed, and a good cosmetic result was achieved.

Characterization of Liver-Specific Functions of Human Fetal Hepatocytes in Culture.

This study was designed to assess liver-specific functions of human fetal liver cells proposed as a potential source for hepatocyte transplantation. Fetal liver cells were isolated from livers of different gestational ages (16-22 weeks), and the functions of cell preparations were evaluated by establishing primary cultures. We observed that 20- to 22-week-gestation fetal liver cell cultures contained a predominance of cells with hepatocytic traits that did not divide in vitro but were functionally competent. Fetal hepatocytes performed liver-specific functions at levels comparable to those of their adult counterpart. Moreover, exposure to dexamethasone in combination with oncostatin M promptly induced further maturation of the cells through the acquisition of additional functions (i.e., ability to store glycogen and uptake of indocyanine green). In some cases, particularly in cultures obtained from fetuses of earlier gestational ages (16-18 weeks gestation), cells with mature hepatocytic traits proved to be sporadic, and the primary cultures were mainly populated by clusters of proliferating cells. Consequently, the values of liver-specific functions detected in these cultures were low. We observed that a low cell density culture system rapidly prompted loss of the mature hepatocytic phenotype with downregulations of all the liver-specific functions. We found that human fetal liver cells can be cryopreserved without significant loss of viability and function and evaluated up to 1 year in storage in liquid nitrogen. They might, therefore, be suitable for cell banking and allow for the transplantation of large numbers of cells, thus improving clinical outcomes. Overall, our results indicate that fetal hepatocytes could be used as a cell source for hepatocyte transplantation. Fetal liver cells have been used so far to treat end-stage liver disease. Additional studies are needed to include these cells in cell-based therapies aimed to treat liver failure and inborn errors of metabolism.

A gastrocolic fistula in Crohn's disease.

To the Editor: Gastrocolic fistulas are rare in Crohn’s disease. Only 37 cases have been described in the literature (1, 2). Typical features include diarrhea, abdominal pain, and weight loss but these alone are not sufficient to distinguish a fistula from active disease (3). Fecal vomiting is considered pathognomic but it is only present in one third of gastrocolic fistulas (4, 5). Case Report. A 26-year-old woman was referred to our institute with a 15-year history of Crohn’s disease for incoercible alimentary vomiting, crampiform abdominal pain, and weight loss. One year prior to admission a colonoscopy had shown a Crohn’s disease stenosis of the descending colon, while an upper endoscopy with biopsies had detected chronic gastritis and ruled out Crohn’s disease activity. One month prior to admission to our clinic an upper gastrointestinal (GI) series had revealed a fistulous tract between the inferior gastric margin and the transverse colon. This picture was definitely confirmed by a barium enema (Figure 1); the left colon showed Crohn’s disease as demonstrated by its cobblestone appearance and the segmental distribution of stenosis and dilatations. Unexpectedly, red blood cells, white blood cells, erythrocyte sedimentation rate, and C-reactive protein were normal, while albuminemia was slightly decreased. After initial medical therapy with mesalazine with no relief of symptoms and worsening of general conditions, the patient underwent left hemicolectomy and wedge resection of the stomach wall, followed by primary closure of the gastric defect. Histologic evidence demonstrated active Crohn’s disease of the whole colonic specimen, while the stomach was not primarily involved. The patient was discharged on the ninth postoperative day. Twenty months later she is asymptomatic, taking 5-aminosalicylate, 2.4 g orally daily. Discussion. Albrecht von Haller was the first to describe a gastrocolic fistula in 1775. Gastrocolic fistulas are usually due to colic or gastric tumors and gastric resections but are very rare in Crohn’s disease. Crohn’s disease is frequently complicated by internal or external fistulas. The most common types of internal fistulas in Crohn’s disease are enteroenteric, ileosigmoid, enterovaginal, or enterovesical. Fecal vomiting is considered pathognomonic of gastrocolic fistulas and is rarely present in patients with duodenal fistulas (6). Most gastric fistulas complicating Crohn’s disease arise from the transverse colon and extend by means of the gastrocolic ligament to involve the greater curvature of the stomach secondarily (7). The most reliable examination for the detection of fistulas is a barium enema, since it increases the intraluminal pressure within the bowel and leads to a better filling of the fistulous tracts (8). Initial medical therapy is recommended but when symptoms are uncontrollable, surgery is mandatory. Gastrocolic fistulas are treated successfully by resection of the diseased segment and primary closure of the gastric defect if the stomach is not involved by Crohn’s disease (2). In our case, because endoscopic biopsies 11 months earlier had shown only chronic gastritis, a barium meal was performed to investigate symptoms, exclude any functional disorder, and eventually localize Crohn’s disease in the upper GI tract. When the gastrocolic fistula was revealed the execution of a barium enema was then indispensable to define the lower GI tract involvement. An interesting point in our case was the low Crohn’s disease activity demonstrated by the normal inflammatory parameters, in contrast to the severe symptomatic picture, which was not typical. Since relevant diarrhea was absent, weight

A matched pair analysis of multicenter longterm follow-up after split-liver transplantation with extended right grafts.

Split‐liver transplantation has been proposed as an alternative to whole liver (WL) transplantation to expand the donor pool, but studies comparing adult longterm outcomes between the 2 methods are conflicting and limited. This is the first Italian multicenter study that retrospectively analyzed 119 matched‐pair recipients of whole and extended right grafts (ERGs) for longterm survival outcomes. In the overall population, WL recipients showed higher patient survival at 1 (93% versus 73%), 5 (87% versus 65%), and 10 years (83% versus 60%) after transplantation compared with split‐liver recipients (P < 0.001); graft survivals of WL recipients were also superior at 1 (90% versus 76%), 5 (84% versus 57%), and 10 years (81% versus 52%) posttransplant (P < 0.001). However, among the 81 matched pairs that survived the first posttransplant year, 5‐ and 10‐year patient survivals were 90% and 81% for split recipients and 99% and 96% for whole recipients, respectively (P = 0.34). The 5‐ and 10‐year graft survivals were also comparable: 87% and 77% for split recipients, and 86% and 82% for whole recipients (P = 0.86). Cox regression analysis identified donor age >50, donor‐to‐recipient weight ratio < 1, retransplantation status, and United Network for Organ Sharing I‐IIA status as risk factors for partial graft use. There were no significant differences in 5‐year outcomes based on center volume. In conclusion, we demonstrate that adult liver transplantation with ERGs can achieve longterm success comparable with that of whole grafts in appropriate patients but should be selectively used in patients with risk factors. Liver Transplantation 23 1384–1395 2017 AASLD.

Mini-Invasive Approach Contributes to Expand the Indication for Liver Resection for Hepatocellular Carcinoma Without Increasing the Incidence of Posthepatectomy Liver Failure and Other Perioperative Complications: A Single-Center Analysis.

BACKGROUND Liver resection (LR) for hepatocellular carcinoma (HCC) is the best alternative option for increasing the survival of many patients with intermediate or advanced stages of the Barcelona Clinic Liver Cancer staging classification. Mini-invasive approach may play a positive role in treating a tumor rising almost exclusively in a diseased liver. METHODS A prospectively collected database was retrospectively reviewed for 167 consecutive patients who underwent LR between 1999 and 2015. RESULTS A total of 38 LRs were performed from 1999 to 2009 (Period I), and 129 between 2010 and 2015 (Period II). Laparoscopic procedures increased from 5.3% to 38.1%. Not undergoing laparoscopic LR increased length of stay, and Clavien Grade II or worse complications. Ninety-day mortality decreased from 5.2% to 0%, and morbidity did not differ significantly, despite the fact that the most complex patients were in Period II. CONCLUSIONS Mini-invasive approaches allow to safely expand limits of LR for HCC; in particular, laparoscopic approach favors surgical option even in more complex patients without increase the risk of posthepatic liver failure or other postsurgical complications.

Liver Volume Restoration and Hepatic Microarchitecture in Small-for-Size Syndrome.

BACKGROUND We investigated preoperative parameters that could work as markers of liver regeneration (LR), and tried to create an algorithm for therapeutic decision-making, looking at the clinical setting of post-hepatectomy liver failure (PHLF) after major liver resection for malignancies (LRM) and of the small-for-size syndrome (SFSS) after adult-to-adult living related liver transplantation (LRLT), considering PHLF and SFSS a single clinical entity. MATERIAL AND METHODS The clinical data of 2 series of 10 consecutive patients who experienced liver-specific complications after LRLT or LRM between 2008 and 2013 were analyzed. LR was evaluated by multidetector computed tomography (MDCT) and hepatic parenchymal findings with specific re-examinations of liver biopsies. The analysis was done according to demographics, tumor characteristics, and postoperative complications occurring within 90 days of surgery and codified within the Clavien classification. RESULTS A total of 13 cases of SFSS occurred in 8 LRLT recipients (61.5%) and in 5 patients after LRM (38.5%). The incidence of SFSS was significantly associated with a greater spleen volume/future remnant liver volume ratio (1.08±0.5; P=0.02) and a reduced number of hepatic tumors (0.58±0.6; P=0.04). A greater degree of LR was not associated with a lesser likelihood of developing SFSS (P=0.31). SFSS incidence and re-examination of post-operative liver biopsies differed according to the evidence of focal endothelial denudation in the portal vein and centrilobular hepatocanalicular cholestasis. We found an association between SFSS incidence and the immunohistochemical overexpression of cytological proliferation marker Ki-67 (29.3±29.8%; P=0.007), which was a significant predictor of poor post-operative survival (OR=1.12, C.I.: 1.013; 1.242). CONCLUSIONS SFSS is a rare but dangerous clinical entity characterized by anarchic hepatic regeneration. We suggest focusing on early diagnosis in order to establish non-surgical modulation of the portal inflow, in conjunction with optimization of medical management.

Liver regeneration after liver resection: Clinical aspects and correlation with infective complications

AIM To investigate whether early liver regeneration after resection in patients with hepatic tumors might be influenced by post-operative infective complications. METHODS A retrospective analysis of 27 liver resections for tumors performed in a single referral center from November 2004 to January 2010. Regeneration was evaluated by multidetector computed tomography at a mean follow-up of 43.85 d. The Clavien-Dindo classification was used to evaluate postoperative events in the first 6 mo after transplantation, and Centers for Disease Control and Prevention definitions were used for healthcare associated infections data. Generalized linear regression models with Gaussian family distribution and log link function were used to reveal the principal promoters of early liver regeneration. RESULTS Ten of the 27 patients (37%) underwent chemotherapy prior to surgery, with a statistically significant prevalence of patients with metastasis (P = 0.007). Eight patients (30%) underwent embolization, 3 with primary tumors, and 5 with secondary tumors. Twenty patients (74%) experienced complications, with 12 (60%) experiencing Clavien-Dindo Grade 3a to 5 complications. Regeneration ≥ 100% occurred in 10 (37%) patients. The predictors were smaller future remnant liver volume (-0.002; P < 0.001), and a greater spleen volume/future remnant liver volume ratio (0.499; P = 0.01). Patients with a resection of ≥ 5 Couinaud segments experienced greater early regeneration (P = 0.04). Nine patients experienced surgical site infections, and in 7 cases Clavien-Dindo Grade 3a to 4 complications were detected (P = 0.016). There were no significant differences between patients with primary or secondary tumors, and either onset or infections or severity of surgical complications. CONCLUSION Regardless of the onset of infective complications, future remnant liver and spleen volumes may be reliable predictors of early liver regeneration after hepatic resection on an otherwise healthy liver.