Delayed gastric emptying after classical Whipple or pylorus-preserving pancreatoduodenectomy: a randomized clinical trial (QUANUPAD).

PURPOSE: Pylorus-preserving pancreatoduodenectomy (PPPD) has been the gold standard for pancreatic head lesion resection for several years. Some studies have noted that it involves more delayed gastric emptying (DGE) than classical Whipple (i.e., pancreatoduodenectomy with antrectomy). Our working hypothesis was that the classical Whipple has a lower incidence of DGE. We aimed to compare the incidence of DGE among pancreatoduodenectomy techniques. METHODS: This pragmatic, randomized, open-label, single-center clinical trial involved patients who underwent classical Whipple (study group) or PPPD (control group). Gastric emptying was clinically evaluated using scintigraphy. DGE was defined according to the International Study Group of Pancreatic Surgery (ISGPS) criteria. The secondary endpoints were postoperative morbidity, length of hospital stay, anthropometric measurements, and nutritional status. RESULTS: A total of 84 patients were randomized (42 per group). DGE incidence was 50% (20/40, 95% confidence interval (95% CI): 35-65%) in the study group and 62% (24/39, 95% CI: 46-75%) in the control group (p = 0.260). No differences were observed between both groups regarding postoperative morbidity or length of hospital stay. Anthropometric measurements at 6 months post-surgery: triceps fold measurements were 12 mm and 16 mm (p = 0.021). At 5 weeks post-surgery, triceps fold measurements were 13 mm and 16 mm (p = 0.020) and upper arm circumferences were 26 cm and 28 cm (p = 0.030). No significant differences were observed in nutritional status. CONCLUSION: DGE incidence and severity did not differ between classical Whipple and PPPD. Some anthropometric measurements may indicate a better recovery with PPPD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03984734.

Applicability and results of liver transplant combined with neoadjuvant chemo-radiotherapy in the treatment of unresectable hilar cholangiocarcinoma. / Aplicabilidad y resultados del trasplante hepático combinado con quimiorradioterapia neoadyuvante en el tratamiento del colangiocarcinoma perihiliar irresecable.

BACKGROUND: In 2007, a multicenter protocol was developed in Catalonia, Spain, combining neoadjuvant chemoradiotherapy and liver transplantation (LT) for those patients with unresectable hilar cholangiocarcinoma (hCCA). AIM: To analyse the effectiveness of the neoadjuvant chemoradiotherapy and LT for those patients enrolled in the protocol based on intention-to-treat. METHODS: Observational multicenter study which includes patients ≤ 68 years-old diagnosed with unresectable, solitary tumors ≤ 3 cm in radial diameter, without evidence of lymph node metastases. The protocol was based on a strategy of neoadjuvant therapy with high-dose radiation (45 Gy in total) plus intravenous fluorouracil (5-FU) given as a daily bolus for the first 3 days of radiation follow by oral capecitabine until transplantation. The patient was included in waiting list for LT if no evidence of disseminated disease was found. RESULTS: Between 2007 and 2018, 13 patients were enrolled in the transplant protocol. Of those, 61% (8/13) of the patients were transplanted. The average time spent on the waiting list was 122 days (range 5-192). Intent-to-treat survival was 69% and 39% at one and 5 years. Post-transplantation overall survival was 87% and 62% and 29% recurrence rate at 5 years. CONCLUSION: The suitability of the neoadjuvant chemoradiotherapy and LT protocol was 61% in our series with long-term overall survival and should be considered as an alternative to resection for patients with localized node-negative hCCA.

Randomized trial of two types of gastrojejunostomy after pancreatoduodenectomy and risk of delayed gastric emptying (PAUDA trial).

BACKGROUND: Delayed gastric emptying (DGE) is the most important cause of an extended hospital stay after pancreatoduodenectomy. Reports suggest that a Roux-en-Y gastroenteric anastomosis may have lower incidence of DGE than a Billroth II reconstruction. The primary aim of this RCT was to compare Billroth II (single loop) and Roux-en-Y (double loop) after pancreatoduodenectomy to determine whether Roux-en-Y reconstruction is associated with a lower incidence of DGE. Secondary endpoints were postoperative complications. METHODS: This was a randomized unblinded single-centre trial without masked evaluation of the main outcome. Patients undergoing pancreatoduodenectomy between 2013 and 2015 were randomized to undergo one of two types of gastroenteric anastomosis for reconstruction. RESULTS: A total of 80 patients were randomized, 40 in each group. The incidence of DGE was the same in patients undergoing Billroth II or Roux-en-Y gastroenteric anastomosis (both 18 of 40 patients; P = 1·000). The grade of DGE was also similar in the Billroth II and Roux-en-Y groups (grade A, both 10 of 40; grade B, 5 of 40 versus 6 of 40; grade C, 3 of 40 versus 2 of 40; P = 0·962). The mortality rate was 3 per cent, with no significant difference between the two groups. There were no differences in the overall rate of postoperative morbidity, relaparotomy rate or duration of hospital stay. CONCLUSION: The incidence and severity of DGE does not differ between single- or double-loop gastroenteric anastomosis performed after pancreatoduodenectomy. Registration number: NCT00915863 (http://www.clinicaltrials.gov).

Identifying Improved and Non-improved Aspects of Health-related Quality of Life After Liver Transplantation Based on the Assessment of the Specific Questionnaire Liver Disease Quality of Life.

INTRODUCTION: The specific questionnaire Liver Disease Quality of Life (LDQOL) is a valid tool for measuring quality of life (QOL) and has been used to show that liver transplantation (LT), which is an effective treatment for end-stage liver disease, may improve QOL. OBJECTIVES: This study aims to identify aspects of QOL that improve after LT and those that do not. PATIENTS AND METHODS: Patients accepted for LT were invited to answer the LDQOL at baseline and after transplantation at 6 and 12 months. LDQOL contains the 36-item Short Form Health Survey (SF-36) and 12 specific dimensions. Responsiveness was assessed using the paired Student t test. RESULTS: The study included a cohort of 156 patients, 73% males, of an average age of 53 (26-67) years, with the following common indications: tumor (35%), hepatitis C (23%), and alcohol-related (21%) liver disease. Mean scores showed a statistically significant (P < .05) improvement after 1 year in 6 of 8 SF-36 dimensions, in the physical component summary score, and in 7 of 12 disease-specific dimensions. The two dimensions that showed no improvement in the SF-36 dimensions were "social functioning" and "vitality," whereas the specific dimensions to not improve were "sleep problems," "social interaction," "activities of daily living," and "concerns about the future." CONCLUSION: Findings suggest that perceived QOL after LT improves but could be further enhanced with the use of specific programs for amending sleep disorders and physical aspects.

The anterior hanging-approach improves postoperative course after right hepatectomy in patients with colorectal liver metastases. Results of a prospective study with propensity-score matching comparison.

PURPOSE: To establish the role of the anterior approach with liver hanging maneuver for right hepatectomy in patients with colorectal liver metastases (CRLM). SUMMARY BACKGROUND DATA: The indications for hepatectomy in patients with CRLM are expanding. The liver remnant must be protected to avoid morbidity. METHODS: We prospectively enrolled all patients with the diagnosis of CRLM requiring right hepatectomy from 2009 to 2012. In all cases right hepatectomy with an anterior-hanging maneuver approach was attempted. We compared the group of patients who underwent this procedure with a group of patients who had previously undergone a conventional right hepatectomy. To minimize selection bias, propensity score matching was performed, based on baseline patient characteristics. RESULTS: A right hepatectomy was planned in 57 cases. The anterior-hanging approach was feasible in 85% of cases. Overall morbidity was similar. In-hospital mortality due to hepatic insufficiency was 2.3% in anterior-hanging group compared to 9% in the conventional group (p = 0.30). The incidence of ascites was significantly greater in the conventional group (AH: 18% vs Conv: 54%; p = 0.002), and hospital stay was longer (AH: 10.9 ± 5.7 vs Conv: 14.4 ± 8.1 days; p = 0.05). Bilirubin levels were significantly lower in anterior-hanging group in day 1 and 3. There were no differences on recurrence nor survival. CONCLUSIONS: The anterior-hanging approach for right hepatectomy in patients with CRLM can be used safely with a high feasibility rate. Its use contributes to improve postoperative course.

"Very early" intrahepatic cholangiocarcinoma in cirrhotic patients: should liver transplantation be reconsidered in these patients?

A retrospective cohort multicenter study was conducted to analyze the risk factors for tumor recurrence after liver transplantation (LT) in cirrhotic patients found to have an intrahepatic cholangiocarcinoma (iCCA) on pathology examination. We also aimed to ascertain whether there existed a subgroup of patients with single tumors ≤2 cm ("very early") in which results after LT can be acceptable. Twenty-nine patients comprised the study group, eight of whom had a "very early" iCCA (four of them incidentals). The risk of tumor recurrence was significantly associated with larger tumor size as well as larger tumor volume, microscopic vascular invasion and poor degree of differentiation. None of the patients in the "very early" iCCA subgroup presented tumor recurrence compared to 36.4% of those with single tumors >2 cm or multinodular tumors, p = 0.02. The 1-, 3- and 5-year actuarial survival of those in the "very early" iCCA subgroup was 100%, 73% and 73%, respectively. The present is the first multicenter attempt to ascertain the risk factors for tumor recurrence in cirrhotic patients found to have an iCCA on pathology examination. Cirrhotic patients with iCCA ≤2 cm achieved excellent 5-year survival, and validation of these findings by other groups may change the current exclusion of such patients from transplant programs.

Intrahepatic cholangiocarcinoma or mixed hepatocellular-cholangiocarcinoma in patients undergoing liver transplantation: a Spanish matched cohort multicenter study.

OBJECTIVE: To evaluate the outcome of patients with hepatocellular-cholangiocarcinoma (HCC-CC) or intrahepatic cholangiocarcinoma (I-CC) on pathological examination after liver transplantation for HCC. BACKGROUND: Information on the outcome of cirrhotic patients undergoing a transplant for HCC and with a diagnosis of HCC-CC or I-CC by pathological study is limited. METHODS: Multicenter, retrospective, matched cohort 1:2 study. STUDY GROUP: 42 patients undergoing a transplant for HCC and with a diagnosis of HCC-CC or I-CC by pathological study; and control group: 84 patients with a diagnosis of HCC. I-CC subgroup: 27 patients compared with 54 controls; HCC-CC subgroup: 15 patients compared with 30 controls. Patients were also divided according to the preoperative tumor size and number: uninodular tumors 2 cm or smaller and multinodular or uninodular tumors 2 cm or larger. Median follow-up: 51 (range, 3-142) months. RESULTS: The 1-, 3-, and 5-year actuarial survival rate differed between the study and control groups (83%, 70%, and 60% vs 99%, 94%, and 89%, respectively; P < 0.001). Differences were found in 1-, 3-, and 5-year actuarial survival rates between the I-CC subgroup and their controls (78%, 66%, and 51% vs 100%, 98%, and 93%; P < 0.001), but no differences were observed between the HCC-CC subgroup and their controls (93%, 78%, and 78% vs 97%, 86%, and 86%; P = 0.9). Patients with uninodular tumors 2 cm or smaller in the study and control groups had similar 1-, 3-, and 5-year survival rate (92%, 83%, 62% vs 100%, 80%, 80%; P = 0.4). In contrast, patients in the study group with multinodular or uninodular tumors larger than 2 cm had worse 1-, 3-, and 5-year survival rates than their controls (80%, 66%, and 61% vs 99%, 96%, and 90%; P < 0.001). CONCLUSIONS: Patients with HCC-CC have similar survival to patients undergoing a transplant for HCC. Preoperative diagnosis of HCC-CC should not prompt the exclusion of these patients from transplant option.

Surgical treatment of biliary tract complications after liver transplantation.

OBJECTIVE: Biliary strictures are the most common biliary tract complication after liver transplantation. There are scarce data on the results of hepaticojejunostomy (HJ) in the management of biliary complications after orthotopic liver transplantation (OLT). Thus, the role of surgery in this setting remains to be established. The aim of this study was to evaluate the results of surgical treatment of patients with biliary complications at our institution. PATIENTS AND METHODS: We reviewed 1000 consecutive liver transplantations performed at our institution from 1984 to 2007. We used a prospectively recorded database to identify patients who underwent HJ to treat any biliary tract complication. RESULTS: Overall, 62 patients (6.2%) underwent HJ, 40 for an anastomotic and 7 for a non-anastomotic stricture as well as 15 for biliary leaks. Postoperative morbidity was 16%, and postoperative mortality 1.6%. There were 7 cases of anastomotic stenosis (11.3%). Four patients (5%) required retransplantation. CONCLUSIONS: HJ is a safe procedure to manage biliary complications after OLT. It may be the first treatment choice especially for cases with anastomotic strictures.

Enlarged lymph nodes in the upper abdomen after liver transplantation: imaging features and clinical significance.

PURPOSE: Our aim was to review our single-centre experience regarding imaging features and pathological conditions arising from enlarged lymph nodes following orthotopic liver transplantation (OLD) and identify imaging features that may allow narrowing the differential diagnosis. MATERIALS AND METHODS: Between January 1997 and September 2008, 715 OLTs were performed at our Institution in 585 patients. In 19 patients (2.6 %) ultrasound (US) showed enlarged lymph nodes in the upper abdomen, and abdominal computed tomography (CT) was performed RESULTS: Histological results showed posttransplantation lymphoproliferative disorder (PTLD) in six patients (31.5 %), hepatic tumoral disease in six (31.5 %), disseminated systemic tuberculosis in one (5.2%) and sarcoidosis in one (5.2%). Histological results showed nonspecific reactive lymph node hyperplasia in five patients (26%). CONCLUSIONS: Detecting enlarged lymph nodes in the upper abdomen after liver transplantation is and infrequent occurrence; however, thorough imaging is required to detect and characterise a wide variety of disorders. Most of the time, enlarged lymph nodes will be related to posttransplantation lymphoproliferative disorder or tumoral recurrence.

A prospective, multicenter study of once-daily extended-release tacrolimus in de novo liver transplant recipients.

To minimize noncompliance in organ transplantation, a new formulation was developed of once-daily extended-release (EXTD) tacrolimus. To analyze the efficacy and safety of this new drug formulation in de novo liver transplant recipients, a prospective, multicenter study was performed in six centers in Spain. The primary objective of the study was to evaluate the incidence of biopsy-proven acute rejection episodes (BPAR) according to the BANFF criteria during the first 3 months of immunosuppression with the EXTD formulation of tacrolimus. Fifty-two patients received a mean initial dose of 10.0 ± 3.8 mg that was gradually reduced to 7.1 ± 4.0 mg, achieving stable mean blood levels of 8.6 ± 3.7 ng/mL at 3 months. BPAR was reported in seven (13%) patients, but patient and graft survivals were 100%. After transplantation liver function improved and was stably maintained throughout the study. At 3 months, mean bilirubin levels were 2.1 ± 5.5 mg/dL and mean alanine aminotransferase and aspartate aminotransferase were 61.6 ± 75.2 U/L and 55.2 ± 76.9 U/L, respectively. Mean serum creatinine of 0.8 ± 0.3 mg/dL pretransplant increased to 1.1 ± 0.4 mg/dL after 3 months (P < .0001). There was no significant increase in the rate of hypertension from pretransplant levels: 30% at baseline versus 31% at 3 months. Mean glucose levels did not change significantly throughout the study. There were no cases of hepatitis C virus relapse. EXTD tacrolimus demonstrated excellent stability in blood trough levels with a good efficacy and safety profile in de novo liver transplant recipients that was similar to the well-described properties of standard-release twice-daily formulation of tacrolimus.

Definitive diagnosis of neuroendocrine tumors using fine-needle aspiration-puncture guided by endoscopic ultrasonography.

BACKGROUND: The detection and diagnosis of neuroendocrine tumors (NETs) is challenging. Endoscopic ultrasonography (EUS) has a significant role in the detection of NETs suspected from clinical manifestations or imaging techniques, as well as in their precise localization and cytological confirmation using EUS-Fine-needle aspiration-puncture (FNA). OBJECTIVE: To assess the usefulness and precision of EUS-FNAP in the differential diagnosis and confirmation of NETs, in a retrospective review of our experience. PATIENTS AND METHODS: in a total of 55 patients with suspected NETs who underwent radial or sectorial EUS, 42 tumors were detected in 40 cases. EUS-FNA using a 22G needle was performed for 16 cases with suspected functional (hormonal disorders: 6 cases) and non-functional NETs (10 cases). Ki 67 or immunocytochemistry (ICC) testing was performed for all.There was confirmation in 9 cases (5 female and 4 male) with a mean age of 51 years (range: 41-81 years).All tumors were located in the pancreas except for one in the mediastinum and one in the rectum, with a mean size of 19 mm (range: 10-40 mm). RESULTS: There were no complications attributable to FNA. Sensitivity was 100% and both precision and PPV were 89%, as a false positive result suggested a diagnosis with NET during cytology that surgery finally revealed to be a pancreatic pseudopapillary solid tumor. CONCLUSIONS: EUS-FNA with a 22G needle for NETs has high sensitivity and PPV at cytological confirmation with few complications.

A double-blind, placebo-controlled trial of ciprofloxacin prophylaxis in patients with acute necrotizing pancreatitis.

BACKGROUND: The use of prophylactic antibiotics in acute severe necrotizing pancreatitis is controversial. METHODS: Prospective, randomized, placebo-controlled, double-blind study was carried out at Bellvitge Hospital, in Barcelona, Spain. Among 229 diagnosed with severe acute pancreatitis, 80 had evidence of necrotizing pancreatitis (34/80 patients were excluded of the protocol). Forty-six patients without previous antibiotic treatment with pancreatic necrosis in a contrast-enhanced CT scan were randomly assigned to receive either intravenous ciprofloxacin or placebo. Five patients were secondarily excluded, and the remaining 41 patients were finally included in the study (22 patients received intravenous ciprofloxacin and 19 patients placebo). RESULTS: Comparing the 22 with intravenous ciprofloxacin and 19 with placebo, infected pancreatic necrosis was detected in 36% and 42% respectively (p = 0.7). The mortality rate was 18% and 11%, respectively (p = 0.6). No significant differences between both treatment groups were observed with respect to variables such as: non-pancreatic infections, surgical treatment, timing and the re-operation rate, organ failure, length of hospital and ICU stays. CONCLUSION: The prophylactic use of ciprofloxacin in patients with severe necrotizing pancreatitis did not significantly reduce the risk of developing pancreatic infection or decrease the mortality rate. The small number of patients included in this study should be considered.

Antral mass due to cytomegalovirus infection requiring gastrectomy in a liver transplant recipient.

The incidence of cytomegalovirus (CMV) infection after liver transplantation (LT) has decreased in recent years. Advances in immunosuppression and CMV prophylaxis have improved the management of CMV disease. Organ involvement is infrequent and gastrointestinal CMV disease is quite rare. Few cases of an antral mass due to CMV infection have been described; those reported to date have mostly been in patients with acquired immunodeficiency syndrome. We describe a case of a CMV-seronegative liver transplant patient who received a seropositive liver graft. Owing to gastrointestinal complaints, CMV prophylaxis was stopped one month after LT. The patient developed an antral mass due to CMV infection and an anastomotic biliary stricture. Antigenemia became negative with ganciclovir, but this treatment did not eliminate the mass. Ganciclovir resistance was ruled out as well as other causes of antral mass, especially malignancy. The patient finally required gastrectomy and hepaticojejunostomy. We conclude that CMV disease is less common today but should be included in the diagnosis of gastrointestinal mass after transplantation.

Solid pseudopapillary tumors of the pancreas: diagnosis and curative treatment.

OBJECTIVES: To highlight an infrequent occurrence using a series of clinical cases with symptoms and signs, and specific radiological findings allowing its diagnosis and treatment, which is in most cases successful. PATIENTS AND METHODS: A descriptive and retrospective study of patients diagnosed by computed tomography scanning and then treated with surgery in the Pancreas and Biliary Unit of a University Hospital from March 1999 to September 2005. RESULTS: There were 6 female patients with a mean age of 33.5 years (range 11-72). Most common signs included pain and a palpable mass in the abdomen. Three patients were diagnosed by computed tomography scanning, and a differential diagnosis with a neuroendocrine tumor was performed for the remaining three subjects. Surgical treatment was adapted to each patient according to the findings and images seen in their computed tomography scans. Biopsy results confirmed the presumed diagnoses, and showed one case of solid pseudopapillary carcinoma of the pancreas. Average hospital stay was of 18.16 days (range 8-30). Mortality rate was 0%. No recurrences occurred during follow-up for 46.3 months on average (range 12-76). CONCLUSIONS: The presence of a huge mass in the pancreas of a young female should prompt suspicion for a solid pseudopapillary tumor. Given its low malignant potential, and the presence of specific radiographic patterns, its diagnosis should be accurate, as radical surgical treatment is effective.

[Factors related to renal dysfunction after liver transplantation in patients with normal preoperative function]. / Factores relacionados con la disfunción renal postoperatoria en pacientes trasplantados hepáticos con función preoperatoria normal.

OBJECTIVE: To determine perioperative factors related to postoperative renal dysfunction in patients receiving liver transplants who had normal renal function before surgery. PATIENTS AND METHODS: We analyzed the cases of 189 consecutive patients. Patients with hepatorenal syndrome and previously diagnosed renal insufficiency were excluded, as were patients undergoing a second transplant operation. Postoperative renal dysfunction was diagnosed when creatinine levels exceeded 1.5 mg x dL(-1) in the first postoperative week. Multivariate analysis of preoperative variables (patient characteristics; Child-Pugh score; status with the United Network for Organ Sharing; and sodium, coagulation, hemoglobin, and creatinine levels); intraoperative variables (blood product units required, duration of surgery, reperfusion syndrome, surgical technique, and crystalloids required); and postoperative variables (hemodialysis or filtration, reoperation, mortality, creatinine levels at 6 and 12 months). RESULTS: One hundred fifty patients with normal kidney function were included. Postoperative renal dysfunction developed in 45 (30%). Differences between patients with and without postoperative renal dysfunction were found for weight; sex; Child-Pugh score; blood transfusion requirements (mean [SD] of 2.36 [2.4] units of packed red cells in the group of patients with renal dysfunction vs 1.3 [1.8] in the patients with normal function); and reperfusion syndrome (26 [66.7%] patients with renal dysfunction and 35 [21.5%] without). The last 2 variables continued to be significantly correlated with renal dysfunction in the multivariate analysis with a relative risk of 1.25, (95% confidence interval [CI], 1.01-1.55) for units of blood transfusion and 2.41 (95% CI, 1.04-5.57) for reperfusion syndrome. Renal replacement therapy was used in 4 patients (2.7%). Mortality rates were similar. At 6 and 12 months, 26 (17.3%) and 18 (12%) patients had renal dysfunction. CONCLUSIONS: Acute renal dysfunction is a frequent complication following a liver transplant and it is associated with transfusion of more units of blood products even when the average transfusion amount is not large.

[Domino or sequential liver transplantation. Is it a feasible technique?]. / El trasplante hepático dominó o secuencial, es una técnica factible?

BACKGROUND: In domino liver transplantation (LT), the explanted liver of a patient with familial amyloidotic polyneuropathy (FAP) is donated to another patient. PATIENTS AND METHOD: Between February 1999 and March 2001 we performed 131 LT with 121 cadaveric donors in our unit. Ten domino LTs were performed. RESULTS: Patients with FAP were younger (37 years) than recipients of the second LT (64 years). The evolution of patients undergoing transplantation for FAP was excellent and all are currently alive and without complications. Among recipients of the second LT, one patient died in the postoperative period. A further two patients died from tumoral recurrence and hepatitis C virus recurrence 18 months and 9 months after transplantation, respectively. The remaining patients have shown no symptoms of FAP during the follow-up. CONCLUSION: The results of this study show that domino LT is technically feasible. The technique increases the number of grafts without apparent risk either to the recipient with FAP or to the recipient of the latter's explanted liver.