Pancreatic ductal adenocarcinoma complete regression after preoperative chemotherapy: Surgical results in a small series.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) becomes a systemic disease from an early stage. Complete surgical resection remains the only validated and potentially curative treatment; disappointingly only 20% of patients present with a resectable tumour. Although a complete pathological regression (pCR) after the preoperative chemotherapy could intuitively lead to better outcomes and prolonged survival some reports highlighted significant rates of recurrence. CASES PRESENTATION: We describe three cases of pCR following preoperative chemotherapy for PDAC. The first two cases received neoadjuvant mFOLFIRINOX and PAX-G scheme for borderline resectable PDAC. Recurrence appeared 9 and 12 months after surgery. Although both patients started adjuvant therapy straight after the diagnosis of recurrence, the disease rapidly progressed and led them to death 12 and 15 months after surgery. The third case was characterized by germline BRCA2 mutation. The patient presented with PDAC of the body, intrapancreatic biliary stenosis and suspected peritoneal metastasis. One year later, after first and second-line chemotherapy, she underwent explorative laparoscopy and total spleno-pancreatectomy without evidence of viable tumour cells in the surgical specimen. At six months she is recurrence-free. CONCLUSIONS: Very few reports describe a complete pathological response following preoperative chemotherapy in pancreatic cancer. We observed three cases in the last three years with disappointing oncological results. Further investigations are needed to predict PDAC prognosis in pCR after chemotherapy.

Extended criteria liver donation after circulatory death with prolonged warm ischemia: a pilot experience of normothermic regional perfusion and no subsequent ex-situ machine perfusion.

BACKGROUND: Livers from controlled donation after circulatory death (cDCD) with very prolonged warm ischemic time (WIT) are regularly transplanted after abdominal normothermic regional perfusion (aNRP) plus ex-situ machine perfusion (MP). Considering aNRP as in-situ MP, we investigated whether the results of a pilot experience of extended criteria cDCD liver transplantation (LT) with prolonged WIT, with aNRP alone, were comparable to the best possible outcomes in low-risk cDCD LT. METHODS: Prospectively collected data on 24 cDCD LT, with aNRP alone, were analyzed. RESULTS: The median total and asystolic WIT were 51 and 25 min. Measures within benchmark cut-offs were: median duration of surgery (5.9 h); median intraoperative transfusions (3 units of red blood cells); need for renal replacement therapy (2/24 patients); median intensive care stay (3 days); key complications; overall morbidity, graft loss, and retransplantation up to 12 months; 12-month mortality (2/21 patients). The median hospital stay (33 days, due to logistics) and mortality up to 6 months (2/24 patients, due to graft-unrelated causes) exceeded benchmark thresholds. CONCLUSIONS: This pilot experience suggests that livers from cDCD with very prolonged WIT that appear viable during adequate quality aNRP may be safely transplanted, with no need for ex-situ MP, with considerable resource savings.

Liver Transplantation in Patients with Portal Vein Thrombosis: Revisiting Outcomes According to Surgical Techniques.

Surgical strategies for graft portal vein flow restoration vary from termino-terminal portal vein anastomosis to more complex bypass reconstructions. Although the surgical strategy strongly influences the post-operative outcome, the Yerdel grading is still commonly used to determine the prognosis of patients with portal vein thrombosis (PVT) undergoing liver transplantation (LT). We retrospectively reviewed the cases of LT performed on recipients with complex PVT at two high-volume transplantation centres. We stratified the patients by the type of portal vein reconstruction, termino-terminal portal vein anastomosis (TTA) versus bypass reconstruction (bypass group), and assessed a multivariable survival analysis. The rate of mortality at 90 days was 21.4% for the bypass group compared to 9.8% in the TTA group (p = 0.05). In the multivariable correlation analysis, only a trend for greater risk of early mortality was confirmed in the bypass groups (HR 2.5; p = 0.059). Yerdel grade was uninfluential in the rate of early complications. A wide range of surgical options are available for different situations of PVT which yield an outcome unrelated to the Yerdel grading. An algorithm for PVT management should be based on the technical approach and should include a surgically oriented definition of PVT extension.

Physiological reno-portal bypass in liver transplantation with non-tumorous portal vein thrombosis.

Reno-portal anastomosis (RPA) in presence of spleno-renal shunts (SRS) is a physiological option to restore blood flow in liver transplantation with portal vein thrombosis (PVT). Diffuse splanchnic venous system thrombosis (complex PVT) is its main indication but RPA proved to be useful in selected cases of less extensive thrombosis (non-complex PVT). Up until now only two monocentric and one multicentric case series has been published on this topic in addition to few anecdotal reports. After 2014, we introduced RPA in our institution to manage some cases of complex PVT in presence of SRS. Here, we present the evolution of indication to RPA. From 2014 to 2020, we performed ten RPA: nine patients presented non-complex and one complex PVT. Overall early and late complication rates were 66.6% and 50%, respectively. Two patients developed RPA stenosis, treated by interventional radiology. Self-resolving acute kidney injury (AKI) was observed in three cases. No re-transplantation was necessary. RPA was patent in all patients, with a mean follow-up of 41.9 months. The overall patient survival was 70% at 1 year and 60% at 3 and 5 years. Four patients died at 1, 2, 3 and 20 months from LT. Causes of deaths were, respectively, stroke, cerebral infection, sepsis (MOF) and sudden variceal bleeding in sinusoidal obstruction syndrome. The relative simplicity and effectiveness of RPA in presence of SRS allowed us to rely more and more often on this technique in liver transplantation with challenging non-complex PVT.

Liver transplantation in patients with non-neoplastic portal vein thrombosis: 20 years of experience in a single center.

BACKGROUND: The Yerdel classification is widely used for describing the severity of portal vein thrombosis (PVT) in liver transplant (LT) candidates, but might not accurately predict transplant outcome. METHODS: We retrospectively analyzed data regarding 97 adult patients with PVT who underwent LT, investigating whether the complexity of portal reconstruction could better correlate with transplant outcome than the site and extent of the thrombosis. RESULTS: 79/97 (80%) patients underwent thrombectomy and anatomical anastomosis (TAA), 18/97 (20%) patients underwent non-anatomical physiological reconstructions (non-TAA). PVT Yerdel grade was 1-2 in 72/97 (74%) patients, and 3-4 in 25/97 (26%) patients. Univariate analysis revealed higher 30-day mortality, 90-day mortality, 1-year mortality, and a higher rate of severe early complications in the non-TAA group than in the TAA group (p = .018, .001, .014, .009, respectively). In the model adjusted for PVT Yerdel grade, non-TAA remained independently associated with higher 30-day, 90-day, and 1-year mortality (p = .021, .007, and .015, respectively). The portal vein re-thrombosis and overall patient and graft survival rates were similar. DISCUSSION: In our experience, the complexity of portal reconstruction better correlated with transplant outcome than the Yerdel classification, which did not even appear to be a reliable predictor of the surgical complexity and technique.

Long-Term Outcomes of Kidney Transplants from Older/Marginal Donors: A Cohort Study.

INTRODUCTION: To safely expand the donor pool, we introduced a strategy of biopsy-guided selection and allocation to single or dual transplantation of kidneys from donors >60 years old or with hypertension, diabetes, and/or proteinuria (older/marginal donors). Here, we evaluated the long-term performance of this approach in everyday clinical practice. METHODS: In this single-center cohort study, we compared outcomes of 98 patients who received one or two biopsy-evaluated grafts from older/marginal donors ("recipients") and 198 patients who received nonhistologically assessed single graft from ideal donors ("reference-recipients") from October 2004 to December 2015 at the Bergamo Transplant Center (Italy). RESULTS: Older/marginal donors and their recipients were 27.9 and 19.3 years older than ideal donors and their reference-recipients, respectively. KDPI/KDRI and donor serum creatinine were higher and cold ischemia time longer in the recipient group. During a median follow-up of 51.9 (interquartile range 23.1-88.6) months, 11.2% of recipients died, 7.1% lost their graft, and 16.3% had biopsy-proven acute rejection (BPAR) versus 3.5, 7.6, and 17.7%, respectively, of reference-recipients. Overall death-censored graft failure (rate ratio 0.78 [95% CI 0.33-2.08]), 5-year death-censored graft survival (94.3% [87.8-100.0] vs. 94.2% [90.5-98.0]), BPAR incidence (rate ratio 0.87 [0.49-1.62]), and yearly measured glomerular filtration rate decline (1.18 ± 3.27 vs. 0.68 ± 2.42 mL/min/1.73 m2, p = 0.37) were similar between recipients and reference-recipients, respectively. CONCLUSIONS: Biopsy-guided selection and allocation of kidneys from older/marginal donors can safely increase transplant activity in clinical practice without affecting long-term outcomes. This may help manage the growing gap between organ demand and supply without affecting long-term recipient and graft outcomes.

Preimplantation Histological Score Associates with 6-Month GFR in Recipients of Perfused, Older Kidney Grafts: Results from a Pilot Study.

BACKGROUND: Biopsy-guided selection of older kidneys safely expands the organ pool, and pretransplant perfusion improves the preservation of these fragile organs. Herein, we studied morphofunctional variables associated with graft outcomes in perfused, histologically evaluated older kidneys. METHODS: This single-center prospective cohort pilot study evaluated the relationships between preimplantation histologic scores and renal perfusion parameters during hypothermic, pulsatile, machine perfusion (MP) and assessed whether these morphofunctional parameters associated with GFR (iohexol plasma clearance) at 6 months after transplantation in 20 consecutive consenting recipients of a biopsy-guided single or dual kidney transplant from >60-year-old deceased donors. RESULTS: The donor and recipient age was 70.4 ± 6.5 and 63.6 ± 7.9 years (p = 0.005), respectively. The kidney donor profile index (KDPI) was 93.3 ± 8.4% (>80% in 19 cases), histologic score 4.4 ± 1.4, and median (IQR) cold ischemia time 19.8 (17.8-22.8 h; >24 h in 5 cases). The 6-month GFR was 41.2 (34.9-55.7) mL/min. Vascular resistances positively correlated with global histologic score (p = 0.018) at MP start and then decreased from 0.88 ± 0.43 to 0.36 ± 0.13 mm Hg/mL/min (p < 0.001) in parallel with a three-fold renal flow increase from 24.0 ± 14.7 to 74.7 ± 31.8 mL/min (p < 0.001). Consistently, vascular resistance reductions positively correlated with global histologic score (p = 0.009, r = -0.429). Unlike KDPI or vascular resistances, histologic score was independently associated with 6-month GFR (beta standardized coefficient: -0.894, p = 0.005). CONCLUSIONS: MP safely improves graft perfusion, particularly in kidneys with severe histologic changes that would not be considered for transplantation because of high KDPI. The preimplantation histologic score associates with the functional recovery of older kidneys even in the context of a standardized program of pulsatile perfusion.

Successful Dual Kidney Transplantation After Hypothermic Oxygenated Perfusion of Discarded Human Kidneys.

BACKGROUND The recovery of discarded human kidneys has increased in recent years and impels to use of unconventional organ preservation strategies that improve graft function. We report the first case of human kidneys histologically discarded and transplanted after hypothermic oxygenated perfusion (HOPE). CASE REPORT Marginal kidneys from a 78-year-old woman with brain death were declined by Italian transplant centers due to biopsy score (right kidney: 6; left kidney: 7). We recovered and preserved both kidneys through HOPE and we revaluated their use for transplantation by means of perfusion parameters. The right kidney was perfused for 1 h 20 min and the left kidney for 2 h 30 min. During organ perfusion, the renal flow increased progressively. We observed an increase of 34% for the left kidney (median flow 52 ml/min) and 50% for the right kidney (median flow 24 ml/min). Both kidneys had low perfusate's lactate levels. We used perfusion parameters as important determinants of the organ discard. Based on our previous organ perfusion experience, the increase of renal flow and the low level of lactate following 1 h of HOPE lead us to declare both kidneys as appropriate for dual kidney transplantation (DKT). No complications were reported during the transplant and in the post-transplant hospital stay. The recipient had immediate graft function and serum creatinine value of 0.95 mg/dL at 3 months post-transplant. CONCLUSIONS HOPE provides added information in the organ selection process and may improve graft quality of marginal kidneys.

Extensive cytoreductive surgery in a Jehovah's Witness patient. A case report.

Jehovah's Witnesses are a well-known patient demographic in medicine because of their religious-based refusal of blood transfusion. This case report outlines the treatment of a Jehovah's Witness patient in need of an extensive cytoreductive surgery due to a peritoneal carcinomatosis of ovarian origin. The surgeons carried out all the recommended surgical and anaesthetic measures concluding that extensive cytoreductive surgery on a Jehovah's Witness is possible and that a complete cytoreduction can be safely performed.

T.E.A. Study: three-day ertapenem versus three-day Ampicillin-Sulbactam.

BACKGROUND: Intra-abdominal infections are one of the most common infections encountered by a general surgeon. However, despite this prevalence, standardized guidelines outlining the proper use of antibiotic therapy are poorly defined due to a lack of clinical trials investigating the ideal duration of antibiotic treatment. The aim of this study is to compare the efficacy and safety of a three-day treatment regimen of Ampicillin-Sulbactam to that of a three-day regimen of Ertapenem in patients with localized peritonitis ranging from mild to moderate severity. METHODS: This study is a prospective, multi-center, randomized investigation performed in the Department of General, Emergency, and Transplant Surgery of St. Orsola-Malpighi University Hospital in Bologna, Italy. Discrete data were analyzed using the Chi-squared and Fisher exact tests. Differences between the two study groups were considered statistically significant for p-values less than 0.05. RESULTS: 71 patients were treated with Ertapenem and 71 patients were treated with Ampicillin-Sulbactam. The two groups were comparable in terms of age and gender as well as the site of abdominal infection. Post-operative infection was identified in 12 patients: 10 with wound infections and 2 with intra-abdominal infections. In the Ertapenem group, 69 of the 71 patients (97%) were treated successfully, while the therapy failed in 2 cases (3%). Therapy failures were more frequent in the Unasyn group, amounting to 10 of 71 cases (p = 0.03). CONCLUSION: According to these preliminary findings, the authors conclude that a three-day Ertapenem treatment regimen is the most effective antibiotic therapy for patients with localized intra-abdominal infections ranging from mild to moderate severity. TRIAL REGISTRATION: Trial registration: ClinicalTrials.gov: NCT00630513.

The ACTIVE (Acute Cholecystitis Trial Invasive Versus Endoscopic) Study: multicenter randomized, double-blind, controlled trial of laparoscopic versus open surgery for acute cholecystitis.

BACKGROUND/AIMS: In some randomized controlled trials laparoscopic cholecystectomy (LC) for acute cholecystitis was associated with a shorter hospital stay when compared with open cholecystectomy (OC). These studies were not double blinded and without intention to treat purpose. METHODOLOGY: The present study project was a prospective, randomized investigation. The study was performed in the Department of General, Emergency and Transplant Surgery St Orsola-Malpighi University Hospital (Bologna, Italy). Subjects were divided in two groups: in the first group the patient was submitted to LC while in the second group was submitted to OC. RESULTS: Of 164 consecutive patients, 20 were excluded from the study. The two groups were similar in demographic and clinical characteristics. Seven (9.7%) patients in the LC group required conversion to OC. There were no deaths or bile duct lesions in either group, and the postoperative complication rate was similar (p=n.s.). The mean postoperative hospital stay was also comparable. CONCLUSIONS: Even though LC for acute and gangrenous cholecystitis is technically demanding, in experienced hands it is safe and effective. It does not increase the mortality and the morbidity rate with a low conversion rate and no difference in hospital stay.