Prognostic factors in gastric cancer patients: a 10-year mono-institutional experience.

Introduction: Gastric cancer (GC) is one of the main causes of death from cancer globally. Long-term survival, especially in Western countries, remains dismal, with no significant improvements in recent years. Therefore, precise identification of clinical and pathological risk factors is crucial for prognosis, as it allows a better selection of patients suitable for oncologically radical treatments and contributes to longer survivals. Methods: We devised a retrospective observational longitudinal study over 10 years of experience with GC patients operated with curative intent. Results: Several factors were thoroughly investigated in a multivariate analysis to look for significance as independent risk factors for disease-free survival. Our results showed that only BMI, pTNM, and lymph node ratio expressed hazard ratios with implications for survival in our series of patients. Discussion: Although limited by the retrospective nature of the study, this is one of the few cancer reports from Northern Italy showing results over 10 years, which may in our view, have an impact on decision-making processes for multidisciplinary teams dedicated to the care of gastric cancer patients.

Strong impact of sarcopenia as a risk factor of survival in resected gastric cancer patients: first Italian report of a Bicentric study.

Gastric cancer (GC) accounts for 4% of all cancers in Europe. Sarcopenia is a complex syndrome characterized by a loss of muscle mass and function associated with age, often present in neoplastic patients. Recently, several studies have shown a significant association between sarcopenia and poor prognosis in various pathological conditions. The current observational retrospective study investigates the association between sarcopenia and overall survival (OS) and recurrence-free survival (RFS) in patients with GC undergoing up-front surgery with curative intent. Resected GC patients' clinical records and CT images were retrospectively assessed. The preoperative CT calculation of the skeletal muscle index (SMI) at L3 level allowed us to categorize patients as sarcopenic or not. Kaplan-Meyer and univariate and multivariate Cox regression analyses were performed to determine the difference in survival and presence of independent prognostic factors. Fifty-five patients, 28 male and 27 female, out of 298 studied for gastric cancer were enrolled in the current study from two cancer referral centers in Italy. The preoperative CT calculation of the SMI at L3 level allowed us to identify 39 patients with and 16 without sarcopenia. A statistically significant difference between the sarcopenic and non-sarcopenic groups was observed in both OS and RFS (p < 0.023; p < 0.006). Moreover, sarcopenia was strongly correlated to a higher risk of recurrence in univariate and multivariate analysis (p < 0.02). Sarcopenia can be considered a critical risk factor for survival in patients with resectable GC treated with up-front surgery. Identifying sarcopenic patients at the time of diagnosis would direct selection of patients who could benefit from early nutritional and/or physical treatments able to increase their muscle mass and possibly improve the prognosis. More extensive multicenter studies are needed to address this issue.

Multimodal Surgical Approach for Adult Patients With Chronic Intestinal Pseudo-Obstruction: Clinical and Psychosocial Long-term Outcomes.

BACKGROUND: Clinical and psychosocial outcomes of a multimodal surgical approach for chronic intestinal pseudo-obstruction were analyzed in 24 patients who were followed over a 2- to 12-year period in a single center after surgery or intestinal/multivisceral transplant (CTx). METHODS: The main reasons for surgery were sub-occlusion in surgery and parenteral nutrition-related irreversible complications with chronic intestinal failure in CTx. RESULTS: At the end of follow-up (February 2015), 45.5% of CTx patients were alive: after transplantation, improvement in intestinal function was observed including a tendency toward recovery of oral diet (81.8%) with reduced parenteral nutrition support (36.4%) in the face of significant mortality rates and financial costs (mean, 202.000 euros), frequent hospitalization (mean, 8.8/re-admissions/patient), as well as limited effects on pain or physical wellness. CONCLUSIONS: Through psychological tests, transplant recipients perceived a significant improvement of mental health and emotional state, showing that emotional factors were more affected than were functional/cognitive impairment and social interaction.

Reconnection surgery in adult post-operative short bowel syndrome < 100 cm: is colonic continuity sufficient to achieve enteral autonomy without autologous gastrointestinal reconstruction? Report from a single center and systematic review of literature.

A systematic bibliographic research concerning patients operated on for SBS was performed: inclusion criteria were adult age, reconnection surgery and SBS < 100 cm. Autologous gastrointestinal reconstruction represented an exclusion criteria. The outcomes of interest were the rate of total parenteral nutrition (TPN) independence and the length of follow-up (minimum 1 year) after surgery. We reviewed our experience from 2003 to 2013 with minimum 1-year follow-up, dealing with reconnection surgery in 13 adults affected by < 100 cm SBS after massive small bowel resection: autologous gastrointestinal reconstruction was not feasible. Three (out of 5168 screened papers) non randomized controlled trials with 116 adult patients were analysed showing weaning from TPN (40%, 50% and 90% respectively) after reconnection surgery without autologous gastrointestinal reconstruction. Among our 13 adults, mean age was 54.1 years (53.8 % ASA III): 69.2 % had a high stomal output (> 500 cc/day) and TPN dependence was 100%. We performed a jejuno-colonic anastomosis (SBS type II) in 53.8%, in 46.1% of cases without ileo-cecal valve, leaving a mean residual small bowel length of 75.7 cm. In-hospital mortality was 0%. After a minimum period of 1 year of intestinal rehabilitation, all our patients (100%) went back to oral intake and 69.2% were off TPN (9 patients). No one was listed for transplantation. A residual small bowel length of minimum 75 cm, even if reconnected to part of the colon, seems able to produce a TPN independence without autologous gastrointestinal reconstruction after a minimum period of 1 year of intestinal rehabilitation.

Surgery for post-operative entero-cutaneous fistulas: is bowel resection plus primary anastomosis without stoma a safe option to avoid early recurrence? Report on 20 cases by a single center and systematic review of the literature.

BACKGROUND: A review was performed on entero-cutaneous fistula (ECF) repair and early recurrence, adding our twenty adult patients (65% had multiple fistulas). METHODS: The search yielded 4.098 articles but only 15 were relevant: 1.217 patients underwent surgery. The interval time between fistula's diagnosis and operative repair was between 3 months and 1 year. A bowel resection with primary anastomosis was performed in 1.048 patients, 192 (18.3%) underwent a covering stoma: 856 patients (81.7%) had a fistula takedown in one procedure. RESULTS: The patients had 14.3% recurrence and 13.1% mortality rate. In our experience 75% were surgically treated after a period equal or above one year from fistula occurrence: surgery was very demolitive (in 40% remnant small bowel was less than 100 cm). We performed a bowel resection with a hand-sewn anastomosis (95%) without temporary stoma. In-hospital mortality was 0% and at discharge all were back to oral intake with 0% early re-fistulisation. CONCLUSIONS: Literature supports our experience: ECF takedown could be safely performed after an adequate period of recovery from 3 months to one year from fistula occurrence. In our series primary repair (bowel resection plus reconnection surgery without temporary stoma) avoided an early recurrence without mortality.

University of Modena experience in HIV-positive patients undergoing liver transplantation.

INTRODUCTION: Highly effective antiretroviral therapy in the last decade has increased the survival rates of HIV-positive patients, yielding a greater number of HIV patients suffering from liver-related disease. Liver transplantation (LT) is the only curative treatment for end-stage liver disease (ESLD) associated or not with hepatocellular carcinoma (HCC). PATIENTS AND METHODS: From June 2003 to September 2010, 23 patients underwent cadaveric donor LT for ESLD at our institution. Inclusion criteria followed the Italian Protocol for LT in HIV-positive patients. Immunosuppressive regimens were based on cyclosporine or tacrolimus, eventually switched to Rapamycin. RESULTS: The median CD4 T-cell count was 275/mmc (range=119-924). All patients were affected by ESLD, which was associated with HCC in 14 cases. Ten patients were within the Milan criteria and four patients exceeded them but were within the San Francisco criteria. Conversion from calcineurin inhibitors (CNI) to rapamycin occurred in ten cases. Hepatitis C virus (HCV) recurrence occurred in 13/21 HCV-positive patients. Acute cellular rejection occurred in eight patients with one developing chronic cellular rejection. Overall patient and graft survivals at 80 months were 50% and 45% respectively. DISCUSSION: LT in HIV-positive patients is a feasible procedure, even if in our experience was burdened by a greater incidence of complications including HCV recurrence and infection compared with HIV-negative patients.

Novel genetic mutation in apolipoprotein E2 homozygosis and its implication in organ donation: a case report.

Disorders in lipoprotein metabolism do not contraindicate liver procurement and transplantation (LT). In this circumstance, LT provides an intriguing opportunity to assess the in vivo contribution of the liver to the synthesis and degradation of genetically polymorphic plasma proteins. Apolipoprotein (APO) E exists with several common phenotypic differences due to gene polymorphism. Some authors have shown that the APOE phenotype of the recipient was virtually completely converted to that of the donor, providing evidence that >90% of plasma APOE arises from the liver. Homozygosis for APOE2 (E2-E2) is related to an increased incidence of type III hyperlipoproteinemia (HLP). Recently, some authors have identified 4 new APOE mutations that are strongly linked to a unique entity of renal lipidosis called lipoprotein glomerulopathy (LPG). At present, 65 cases of LPG have been reported worldwide, although most patients have been discovered in Japan and other East Asian countries. We have herein reported a case of LT in a patient with advanced hepatocarcinoma who received a liver from a caucasian donor affected by type III HLP due to homozygous E2-E2. The LPG was due to a novel genetic mutation in APOE. After the LT, the recipient, developed de novo severe lipid abnormalities despite good graft function. To our knowledge this is the first report of an LT using a graft from a non Asian donor with homozygous E2-E2 with the presence of a novel APOE mutation.

Liver transplantation due to iatrogenic injuries: two case reports.

The transjugular intrahepatic portosystemic shunt (TIPS) is an acceptable procedure that has proven benefits in the treatment of patients who have complications from portal hypertension due to liver cirrhosis. In the literature few reports have described complications after TIPS placement. Initial surgery and local hemostasis have been needed to manage abdominal bleeding: if this treatment is insufficient, it may be necessary to perform a liver transplantation. This report describes the role of liver transplantation to manage dangerous complications in 2 patients after TIPS placement, when surgical procedures and hemostasis were unable to stop the bleeding.

[Is there an age limit for radical surgery in case of tumors infiltrating the duodenum?]. / Per le neoplasie infiltranti il duodeno esiste un limite di età per una chirurgia radicale?

AIM: Radical resection is the only potential cure for pancreatic malignancies and a useful treatment for other benign diseases, such as pancreatitis. Over the last two decades, medical and surgical improvements have drastically changed the postoperative outcome of elderly patients undergoing pancreatic resection, and appropriate treatment for elderly potential candidates for pancreatic resection has become an important issue. METHODS: A hundred and five consecutive patients undergoing radical pancreatic resection between 2003 and 2007 at the Surgery Unit of the University of Modena, Italy, were considered and divided into two groups according to their age, i.e., over 75-year olds (group 1, 25 patients) and under 75-year-olds (group 2, 80 patients). The two groups were compared as regards to demographic features, American Society of Anesthesiologists scores, comorbidities, previous major surgery, surgical procedure, postoperative mortality, and morbidity. RESULTS: There were no significant differences between the two groups concerning postoperative mortality, and the duration of hospital stay and days in the postoperative Intensive Care Unit were also similar. Complications such as pancreatic fistulas, wound infections, and pneumonia were more frequent in the older group, but the differences were not statistically significant. CONCLUSION: In the light of these findings and as reported for other series, old age is probably not directly related with any increase in the rate of postoperative complications, but comorbidities (which are naturally related to the patients' previous life) may have a key role in the postoperative course.

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.

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.

Peritoneal leiomyosarcoma in a kidney transplant patient: a case report.

Sarcomas are rare neoplasms, accounting for a 1.7% incidence among all transplanted patients presenting with de novo malignancies. Our present report focused on a 46-year-old woman who received immunosuppressive therapy based on cyclosporine and steroids for renal transplantation. Eight years after transplantations, she suffered lower abdominal pain and a mass involving peritoneal soft tissues was located near the right iliac vessels. Upon radical tumor excision, the histological examination revealed a high-grade leiomyosarcoma. Immunosuppression was reduced and cyclosporine switched to rapamycin. After 30 days, a computed tomography scan revealed two small pulmonary metastases, so the patient received adriamycin. Six months after the diagnosis, there was no intra-abdominal relapse and the pulmonary metastasis remain stable. The function of the transplanted kidney was normal and the patient was listed for laparoscopic pulmonary resection. Sarcomas in solid organ transplant patients appear to have aggressive features with 62% being high grade and 40% metastatic at the time of primary diagnosis with a recurrence rate of 30% and a 5-year survival rate of 25%. Patients diagnosed with sarcoma should be treated with multimodality therapy. After aggressive surgery whenever possible, a combination of a traditional cytotoxic drug and a "signal" blocking agent like rapamycin may increase selectivity toward tumor cells.

Outcome in right living related liver transplantation with branch-patch arterial reconstruction.

cRight lobe living liver transplantation is being performed worldwide with increased frequency. Difficult arterial reconstructions are often encountered because of small diameter or discrepancy between arterial stumps. The risk of arterial thrombosis is reported as high as 26%: microsurgical techniques have reduced this rate below 2%, increasing warm ischemia time. We have developed a new branch patch technique in living related liver transplantation using the donor cystic artery to create an enlarged patch anastomosis that enables increase in the vessel's diameter and therefore greater inflow to the liver. We have followed 8 patients treated with this technique. After more than 1 year (mean follow-up: 636 days) we did not observe any arterial thrombosis by Doppler ultrasound performed every 3 months. The mean resistance index was 0.68 (0.57-0.83-). Three patients died with functional graft without signs of thrombosis. We believe that the cystic artery branch patch technique is feasible in all cases. It is fast (mean time: 6.2 min), it allows a shorter warm ischemia time, and there is no increased risk of thrombosis.

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.

Role of therapeutic drug monitoring in a patient with human immunodeficiency virus infection and end-stage liver disease undergoing orthotopic liver transplantation.

Pharmacological interactions between protease inhibitors and tacrolimus require careful monitoring to prevent toxicity in the posttransplantation period. A 42-year-old man with human immunodeficiency virus (HIV) infection and end-stage liver disease due to hepatitis C virus (HCV) received an orthotopic liver transplant. At the time of surgery the patient was on triple antiretroviral therapy (tenofovir, lamivudine, and lopinavir/ritonavir) with a stable CD4(+) count (>500 cells/mm(3)) and HIV-1 RNA (<50 copies/mL). Immunosuppression was maintained with tacrolimus (0.5 mg at a single dose once per week). One month after surgery HCV recurrence was documented. Pharmacokinetic evaluation of lopinavir/ritonavir showed a rapid increase in the area under the curve. Drug concentrations returned to normal levels, with reduction in liver enzymes. At the same time, tacrolimus dosages were reduced to a maintenance dose of 0.5 mg every 2 weeks. The patient, at 17 months postoperatively, is alive in good health with normal liver function and HCV RNA load levels. This is the first case in which a profound change in the pharmacokinetics of a protease inhibitor caused by a drug-drug interaction was observed during transient liver damage. Because this clinical event is particularly common in HIV-infected patients, our findings suggest that therapeutic drug monitoring should be performed to determine the impact of potential drug interactions in the early posttransplantation period, at the time of resumption of therapy or introduction of new anti-retroviral therapy and during HCV recurrence in order to optimize both tacrolimus and protease inhibitor treatment.

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.

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.