Presence of cancer cells in gastric lavage of gastric cancer patients as an indicator of advanced disease, predictor of tumour aggressive phenotype and independent prognostic factor for poor survival: The endoluminal metastatic pathway of gastric cancer and GL0/GL1 classification.

OBJECTIVE: As of 2017, the pathobiology of gastric cancer (GC) is far from fully understood; consequently, new methods of basic and advanced research have been proposed and tested. The presence (GL1) vs absence (GL0) of malignant cells exfoliated in gastric lavage (GL) of GC patients was formerly evaluated with diagnostic intent but not for staging or prognostic assessment. We investigated this hitherto unreported application of cytopathology. METHODS: GL was preoperatively and prospectively collected from 80 GC patients and cytologically analysed. The results were compared with the classic clinicopathological features of GC and related to survival. The prognostic value of GL1 was assessed through univariate and multivariate analyses. RESULTS: GL1 was detected in 36 samples (45%) and correlated with advanced tumour depth (T3-T4), lymphatic metastasis (N+), distant metastasis (M1) and lymphovascular invasion (LVI1; P=.0317, .0024, .003 and .0028, respectively). Overall survival (OS) was significantly shorter for GL1 (23 months) vs GL0 patients (42 months; P=.005) and GL1 vs GL0 T1 subjects (12.6 vs 47.8 months, P=.0029). Univariate analysis revealed that GL1, N+, M1, LVI1 and advanced stage were significantly associated with OS. Multivariate analysis assessed GL1 as the only independent prognostic factor for worse OS and progression-free survival (P=.0013 and .0107). CONCLUSIONS: In the present study, GL1 was correlated with advanced disease, aggressive tumour behaviour and poor prognosis. Although additional studies are needed to confirm these findings, the GL0/GL1 classification can be applied to GC patients to achieve higher accuracy in staging, prognostic stratification and treatment selection.

Mortality after steroid-resistant acute cellular rejection and chronic rejection episodes in adult intestinal transplants: report from a single center in induction/preconditioning era.

Steroid-resistant acute cellular rejection (ACR) and chronic rejection (CR) are still major concerns after intestinal transplantation. We report our experience from a single center on 48 adults recipients using 49 grafts from 2001 to 2011, immunosuppressing them initially with daclizumab initially and later Alemtuzumab. Overall patient survival was 41.9% at 10 years while graft survival was 38.5%. The steroid-resistant ACR population of 14 recipients (28.5%) experienced 50% mortality mainly due to sepsis, while the five (8%) CR recipients, included two survivors. All but 1 graft was placed without a liver. CR was often preceded by ACR episodes. Mortality related to steroid-resistant ACR and CR still affects the intestinal transplant population despite induction/preconditioning, especially in the absence of a protective liver effect of the liver. New immunosuppressive strategies are needed.

Duodenal carcinoma at ligament of Treitz. Case report and review of the literature.

We report a case of adenocarcinoma of the duodenojejunal angle and remark the rarity of this pathology, the difficulty of diagnosis and treatment peculiar to tumours of the duodenum. This rare tumour is characterized by polymorphic and non specific symptomatology. The possible therapy is surgery. Radio and chemotherapy don't significantly improve survival.

[Pancreatic carcinoma presenting with invasion of the vena porta or the superior mesenteric vein: our experience and review of the literature]. / Carcinoma del pancreas con infiltrazione della vena porta o della vena mesenterica superiore: nostra esperienza e revisione della letteratura.

AIM: Adenocarcinoma of the pancreas can present with invasion of the vena porta or the superior mesenteric vein (SMV). Pancreatectomy with resection of the vena porta and/or the SMV remains controversial although the procedure is potentially curative. The aim of this study was to validate the indication for resection on the basis of our experience and evidence from recently published studies. METHODS: Studies published in the last 10 years on pancreatectomy (duodenocephalopancreatectomy, total and distal pancreatectomy) with resection of the vena porta and/or the SMV were retrieved from the Medline database and reviewed. A total of 18 studies meeting the inclusion criteria were analyzed for information about indications, type of intervention, use of adjuvant therapies, histopathology, perioperative results and survival in 620 patients with adenocarcinoma of the pancreas undergoing pancreatectomy with resection of the vena porta and the SMV. This data set was then compared with our experience with this procedure from the last 3 years. RESULTS: The mortality and postoperative complication rates varied between 0% and 7.7% and 12.5% and 54%, respectively. The median survival varied from 12 to 22 months; the 1 year survival rate was between 31% and 83%; the 5-year survival rate was between 9 and 18% according to the studies reviewed. CONCLUSION: On the basis of evidence from the literature and our experience, en bloc resection of the vena porta and/or the SMV during pancreatectomy appears to be a safe procedure with acceptable outcomes, and should be considered in patients with pancreatic cancer presenting with venous invasion. Venous resection increases the surgical cure rate, prolonging survival in patients selected according to correct indications.

Model for End-Stage Liver Disease (MELD) system to allocate and to share livers: experience of two Italian centers.

BACKGROUND: The use of the Model for End-stage Liver Disease (MELD) score to prioritize patients on liver waiting lists and to share organs among centers was effective according to US data, but few reports are available in Europe. MATERIALS AND METHODS: We evaluated the outcome of 887 patients listed between April 2004 and July 2006 in a common list by two transplant centers (University of Bologna [BO] and University of Modena [MO] ordered according to the MELD system. Patients with hepatocellular carcinoma had a score calculated according to their real MELD, tumor stage, and waiting time. RESULTS: Five hundred eighty-six (67%) patients were listed from BO and 291 (33%) from MO. The clinical features of recipients (sex, age, blood group, and real MELD) were comparable between centers. The number of liver transplantations performed was 307, and 273 (89%) recipients had a calculated MELD >or=20. Liver transplantations were equally distributed according to the number of patients listed: 215 out of 586 (36.7%) for BO and 92 out of 291 (31.6%) for MO. The median real MELD of patients transplanted was 20, and 246 out of 307 (80.1%) grafts transplanted were functioning. The dropouts from the list were 124 (14%), and 87 (70%) of these patients had a calculated MELD >or=20. CONCLUSION: The MELD system was effective to share livers among the two Italian centers. According to this policy, livers were allocated to the recipients with the highest probability of dropout and who had a satisfactory survival after liver transplantation.

Acute cellular rejection monitoring after intestinal transplant: utility of serologic markers and zoom videoendoscopy as support of conventional biopsy and clinical findings.

Acute cellular rejection (ACR) episodes in intestinal transplant recipients are diagnosed by histologic and clinical findings. We have applied zoom video endoscopy and the use of serologic markers granzyme B (GrB) and perforin (PrF) to monitor rejection together with conventional tools. Seven hundred eighty-two blood samples (obtained at the time of the biopsy) collected from 34 recipients for GrB/PrF upregulation were positive among 64.9% of ACRs during a 3-year follow-up. Considering only the first year results posttransplantation, it reached 73.1% of rejection events. Zoom videoendoscopy was used by our group in 29 recipients of isolated intestine (n = 24) or multivisceral transplantations (n = 5) to enable observation of villi and crypt areas. From more than 270 procedures, 84% of the zoom findings agreed with the histologic results, namely, a specificity of 95%. In fact, during ongoing ACR, villi were altered in 80% of cases. Both procedures were helpful to support conventional histologic findings and clinical symptoms of ACR in intestinal transplant recipients.

Liver transplantation for recurrent hepatocellular carcinoma on cirrhosis after liver resection: University of Bologna experience.

Liver resection (LR) for patients with small hepatocellular carcinoma (HCC) with preserved liver function, employing liver transplantation (LT) as a salvage procedure (SLT) in the event of HCC recurrence, is a debated strategy. From 1996 to 2005, we treated 227 cirrhotic patients with HCC transplantable: 80 LRs and 147 LTs of 293 listed for transplantation. Among 80 patients eligible for transplantation who underwent LR, 39 (49%) developed HCC recurrence and 12/39 (31%) of these patients presented HCC recurrence outside Milan criteria. Only 10 of the 39 patients underwent LT, a transplantation rate of 26% of patients with HCC recurrence. According to intention-to-treat analysis of transplantable HCC patients who underwent LR (n = 80), compared to all those listed for transplantation (n = 293), 5-year overall survival was 66% in the LR group versus 58% in patients listed for LT, respectively (p = NS); 5-year disease-free survival was 41% in the LR group versus 54% in patients listed for LT (p = NS). Comparable 5-year overall (62% vs. 73%, p = NS) and disease-free (48% vs. 71%, p = NS) survival rates were obtained for SLT and primary LT for HCC, respectively. LR is a valid treatment for small HCC and in the event of recurrence, SLT is a safe and effective procedure.

[Hepatic resections for hepatocarcinoma in the XXI century]. / Le resezioni epatiche per epatocarcinoma nel XXI secolo.

Hepatic resection is today the treatment of choice for cirrhotic patients affected by hepatocellular carcinoma (HCC). Short term results are now definitely satisfactory, with a mortality rate in the referral centers lower than 5%. However, long term results are affected by a high recurrence rate, between 50% and 100%, due to the underlying cirrhosis. Notwithstanding the high recurrence rate, the hepatic resection guarantees a five years survival between 40% and 60%, comparable to the one offered by liver transplantation. The aim of this paper is to review the results of studies on resected cirrhotic patients affected by HCC.

Adult-to-adult living donor liver transplantation using left lobes: the importance of surgical modulations on portal graft inflow.

BACKGROUND: Due to the shortage of available cadaveric organs, living donor liver transplantation (LDLT) has been recently applied extensively in adults. The use of the left lobe should be encouraged because of donor safety, but frequently the metabolic requirements of severely cirrhotic patients are great and subsequent graft dysfunction is encountered after transplantation. The importance of increased portal inflow to the graft in previously severely cirrhotic patients and other hemodynamic changes in LDLT using left lobes are still under debate, as are the surgical modulations to correct them. In this study, we have reported an initial series of adult-to-adult LDLT using left lobes, underlining the hemodynamic changes encountered during the transplant and the surgical modulations we applied to correct them. METHODS: Eight adult recipients underwent left lobe liver transplantation from living donors. Portal vein pressure and central venous pressure were measured before and after surgical modulation. RESULTS: We encountered four cases of small-for-size syndrome. Two patients were retransplanted; the other two died. Seventy-five percent of our recipients survived and 50% did not require further surgery. CONCLUSION: Surgical portal inflow modulation should be considered in cases of left lobe liver transplantation between adults.

Italian experience in adult clinical intestinal and multivisceral transplantation: 6 years later.

PATIENTS AND METHODS: Between December 2000 and November 2006, 28 isolated intestinal transplants and nine multivisceral transplants (five with liver) from cadaveric donors have been performed for short gut syndrome (n = 15), chronic intestinal pseudo-obstruction (n = 10), Gardner's syndrome (n = 9), radiation enteritis (n = 1), intestinal atresia (n = 1), and massive intestinal angiomatosis (n = 1). Indications for transplantations were: loss of venous access, recurrent sepsis due to central line infection, and/or major electrolyte and fluid imbalance. Liver dysfunction was present in 19 cases. All patients were adults of median age at transplant of 34.7 years and mean weight 59.6 kg. All recipients were on total parenteral nutrition for a mean time of 38.8 months. Mean donor/recipient body weight ratio was 1.1. RESULTS: The mean follow-up was 892 +/- 699 days. Twenty-five patients were alive (67.5%) with 3-year patient survivals of 70% for isolated intestinal transplantations and 41% for the multivisceral transplantations (P = .01). The mortality rate was 32.5% with losses due to sepsis (63%) or rejection. Our 3-year graft survival rates were 70% for isolated intestinal transplantations and 41% for multivisceral transplantations (P = .02); graftectomy rate was 16%. These were 88% of grafts working properly with patients on regular diet with no need for parenteral nutrition. DISCUSSION AND CONCLUSIONS: Induction therapy has reduced the doses of postoperative immunosuppressive agents, especially in the first period, lowering the risk of renal failure and sepsis, mucosal surveillance protocol for early detection of rejection dramatically reduced the number of severe acute chronic rejections.

Incidence, clinical significance, and outcome of vascular alterations in intestinal biopsies after isolated small bowel transplantation: a single-center experience.

BACKGROUND: Mild and moderate vascular alterations in intestinal biopsies after isolated small bowel transplantation (SBT) have uncertain clinical significance. METHODS: We retrospectively investigated the incidence, association with acute cellular rejection (ACR), treatment, and outcome of mild and moderate vascular changes in 15 adult SBTs performed between December 2000 and October 2003. The semiquantitative Ruiz score for vascular changes in intestinal mucosa was used. RESULTS: A total of 332 biopsies were analyzed. All patients had at least one sample showing mild or moderate vascular injury, which was globally found in 117 biopsies (35% of the total; 29% mild and 6% moderate). No cases of severe vascular injury were observed. First appearance of vascular alterations occurred 2 to 36 days after SBT (median: 6). Patients with vascular injury had a higher incidence of associated ACR than patients without this feature (16% vs 5%, P = .001). Patients with moderate vascular injury were also more likely to have moderate-to-severe ACR than patients showing no or mild vascular changes (14% vs 2%; P = .015). Treatment of rejection was more frequently administered with simultaneous diagnosis of ACR than in cases of isolated vascular alterations (84% vs 26%; P < .0001). Only one graft (7%) was lost due to severe ACR. DISCUSSION: Mild and moderate vascular changes are common findings in early post-SBT biopsies. They are frequently associated with ACR and parallel its severity. The clinical impact of mild or moderate vascular injury appears to be of little relevance.

[Prognostic factors after surgical resection for hilar cholangiocarcinoma]. / Facteurs pronostiques après résection pour cholangiocarcinome hilaire.

AIMS: To evaluate short and long-term results in 23 patients resected for hilar cholangiocarcinoma. METHODS: Between January 2001 and December 2003, 23 patients with hilar cholangiocarcinoma were resected and considered for retrospective analysis. Univariate and multivariate analysis were performed on several clinicopathological variables in order to evaluate the short-term results. Median follow-up was 11 months (interquartile range 2-20 months). RESULTS: A major liver resection was performed in 19 out of 23 patients (82%): a right hepatectomy extended to segment 4 in 5 patients and a left hepatectomy in 14 patients. Resection of the caudate lobe was performed in 7 patients (30%). No hospital mortality occurred. Overall morbidity rate was 43%. The 1-year survival rate was 63.2% with a median survival of 19 months. Tumor recurrence appeared in 12 patients (52%). Low preoperative albumin level (P=0.006), presence of positive resection margin (P=0.03) and T-stage (P=0.02) were found to be related to a worse median survival. On multivariate analysis, only the preoperative albumin level and the presence of positive margin were confirmed as independent prognostic factors. CONCLUSION: Aggressive surgical approach remains the only potentially curative therapy for the hilar cholangiocarcinoma. Low preoperative albumin level, presence of positive resection margin and T-stage resulted as factors influencing the prognosis after resection.

Living donor liver transplantation in adult patients: our experience.

INTRODUCTION: Living donation in adult liver transplantation (LDLTx) is an important resource because of the waiting list growth. We started a living donor program to overcome the shortage of cadaveric sources. PATIENTS: From May 2001 to May 2003, 36 patients underwent LDLTx: 27 received a right lobe, 8 received a left lobe, and 1 received segments II and III. RESULTS: The 1-year actuarial survival rate was 77.7%, with a mean follow-up, in survivors, of 754 +/- 248 days. Eleven of 27 (40.7%) right lobe recipients died. Among left graft recipients, 3 patients died (33%). We undertook retransplantation in 4 cases, because of 2 "small for size" syndrome, 1 late hepatic artery thrombosis, and 1 early portal vein thrombosis. After a period of 797 days, all 36 donors returned to a normal social and working life. Two donors, who underwent right lobe donation, experienced major complications: 1 case of biliary stenosis, treated by stenting, and 1 case of biliary leak from the cut surface of the liver, requiring laparotomy and abscess drainage. Left lobe donors developed no complications. CONCLUSIONS: LDLTx has a learning curve for experienced liver transplantation surgeons. Our last 18 cases showed better survivals than the first 18 (9 deaths vs 5), even if, in the latter group, we transplanted 8 left livers. In our experience, LDLTx of a left liver graft has an increased risk of "small for size syndrome," but patients, both donors and recipients, report improved outcomes.

Preliminary results of immunosuppression with thymoglobuline pretreatment and hepatitis C virus recurrence in liver transplantation.

Induction with thymoglobulin, a potent anti-thymocyte polyclonal antibody, has been recently reported to allow minimization of postoperative immunosuppression in organ transplantation. The relationship with recurrence of hepatitis C virus (HCV) after liver transplantation (LT) has never been investigated. We report herein on the outcome of 22 HCV+ patients receiving thymoglobulin pretreatment and minimal immunosuppression after liver transplantation. Patient survival and acute rejection rates were good, with remarkably low dosages and levels of immunosuppression achieved with thymoglobulin, and without exposing patients to an elevated risk of rejection. A progressive weaning of the primary immunosuppressant was also possible in the majority of patients without complications. The HCV recurrence rate was similar to that reported in the literature, although lower HCV RNA viral loads were obtained with thymoglobulin and a mild histologic course. Although our results need to be validated in large cohort studies, our experience shows that minimization of immunosuppression with thymoglobulin is effective to protect against rejection and demonstrated a positive impact on HCV recurrence that deserves further investigation.

Twenty-seven consecutive intestinal and multivisceral transplants in adult patients: a 4-year clinical experience.

Adult isolated intestinal and multivisceral transplantation is gaining acceptance as the standard treatment for patients with intestinal failure with life-threatening parenteral nutrition-related complications. We report our 4-year experience with intestinal and multivisceral transplantation. We performed 20 isolated small bowel and seven multivisceral ones, including three with liver. The underlying diseases were mainly short bowel syndrome due to intestinal infarction, chronic intestinal pseudo-obstruction, and Gardner syndrome. Indications for transplant were loss of central venous access in 14 patients, recurrent sepsis in eight patients, and major electrolyte and fluid imbalance in five patients. One-year patient actuarial survival rate was 94% for isolated intestinal transplants and 42% for multivisceral recipients (P = .003), while 1-year graft actuarial survival rate was 88.4% for isolated small bowel patients and 42.8% for multivisceral ones (P = .01). The death rate was 18.5%. Our graftectomy rate was 14.8%. Our immunosuppressive protocols were based on induction agents such as alemtuzumab, daclizumab, and antithymocyte globulins. The majority of our complications were bacterial infections, followed by rejections and relaparotomies; most rejection episodes were treated with steroid boluses and tapering. We believe that our results were due to optimal candidate and donor selection, short ischemia time, and use of induction therapy. Multivisceral transplantation is a more complex procedure with less frequent clinical indications than isolated small bowel transplant, but our data concerning multivisceral transplants include only a small number of patients and require further evaluation.

Comparison between the fifth and sixth editions of the AJCC/UICC TNM staging systems for hepatocellular carcinoma: multicentric study on 393 cirrhotic resected patients.

AIMS: To compare the prognostic efficacy of the 5th and 6th edition of the TNM staging system for HCC. METHODS: We retrospectively applied the old and the new systems to 393 resected patients, comparing the efficacy of both in prognostic evaluation. RESULTS: The 1-, 3- and 5-year overall survival rates were 89.7, 71.1 and 56.3%, respectively. The 1-, 3- and 5-year disease-free survival rates were 79.4, 54.6 and 39.4%, respectively. Among the factors evaluated, Child's grade B and C (p=0.001) and presence of multiple nodules (p=0.01) were found to be related either to a worse long-term survival or to a worse disease-free survival. Stratifying patient survivals according to the old TNM system, we found significant differences only between stages II and IIIA (p=0.001); otherwise stages I and II (p=0.9) as well as stages IIIA and IVA (p=0.9) showed similar survival rates. Analysing the new TNM system, we found a more homogeneous staging stratification, with significant differences both between stage I and II (p=0.02) and between stage II and IIIA (p=0.05). CONCLUSIONS: In the present multicentric study, long term overall and disease-free survival after liver resection for HCC was strongly affected by the number of tumours and the underlying liver disease. Our results suggest that the new classification appears to achieve an accurate stratification of patients, simpler than the previous edition, as well as a more reliable comparative analysis of outcome after hepatic resection for HCC.

Liver transplantation for familial amyloid polyneuropathy non-VAL30MET variants: are cardiac complications influenced by prophylactic pacing and immunosuppressive weaning?

BACKGROUND: Cardiac complications represent a cause of morbidity and mortality after liver transplantation among patients with familial amyloid polyneuropathy (FAP), especially for the non-VAL30MET variant types. METHODS: We retrospectively evaluated 11 recipients from a nonendemic area including 90.9% affected by FAP variants. Preoperative cardiovascular symptoms were present in 81% of patients. An intraoperative pacemaker was placed prophylactically in 90.9% of all recipients. Since tacrolimus has been reported in the international literature to display cardiac toxicity, we evaluated the influence of intraoperative prophylactic pacing and rapid postoperative weaning from tacrolimus, mainly allowed by thymoglobulin on the occurrence of posttransplantation cardiac complications. RESULTS: One patient received a combined heart-liver transplant, another, living donor liver transplantation. We did not observe any significant intraoperative cardiac complications. Postoperatively, the pacemaker was removed from all patients but 1. Five patients received tacrolimus and steroids; a subsequent, second group of 6 patients (54.5%) was treated with thymoglobulin followed by tacrolimus. At discharge the mean tacrolimus level was 10.6 ng/mL, whereas after 1 month it was 7.5 ng/mL. We observed a case of acute cellular rejection before discharge, which was successfully treated with intravenous steroids and OKT3. After a mean follow-up of 17.4 months (range, 1-31), 2 patients had died (18.1%): 1 due to sepsis and another, to MI. Two recipients experienced cardiac complications (18.1%), namely, the patient who died due to an myocardial infarction and a second one with a tachyarrhythmia, which was treated successfully with beta-blockers and amiodarone. CONCLUSION: Prophylactic pacing and rapid weaning from immunosuppression are still associated with a significant rate of postoperative cardiac complications.

[Outcome of isolated small bowel transplantation in adults: experience from a single Italian center]. / Risultati del trapianto di intestino isolato nell'adulto: esperienza di un singolo centro italiano.

AIM: Isolated small bowel transplantation is becoming the treatment of choice for adult patients with serious parenteral nutrition (PN) related complications: we report our three-year experience (December 2000-December 2003) from a single Italian center (Modena-Italy), with one of the larger European series. METHODS: We transplanted 14 patients, with a previous mean PN course of 27 months and a mean 21-month post-transplantation follow-up (range 3-36 months), obtaining a one-year actuarial survival rate of 92.3% with no intraoperative deaths. RESULTS: We lost 1 patient (7.2%), died for post-transplantation overwhelming sepsis following Cytomegalovirus (CMV) enteritis. Thirteen patients are alive, with one-year actuarial graft survival rate of 85.1%: 1 patient underwent graft removal (7.2%) for intractable severe acute rejection. Our immunosuppressive regimen was based on tacrolimus and 3 induction protocols: daclizumab (8 patients) with steroids, alemtuzumab (4 patients) and thymoglobulin (2 patients) without steroids. In 9 cases, we added sirolimus. Nine recipients experienced 22 episodes of acute cellular rejection (ACR), treated successfully in all cases but one. One patient (7.2%) was treated successfully for Post Transplant Lymphoproliferative Disease (PTLD) and is disease-free after 8 months. CONCLUSIONS: Small bowel transplantation can achieve optimal results depending on appropriate immunosuppressive management and candidate selection, added to shorter ischemia time and careful donor and graft selection.