Treatment outcome for systemic chemotherapy for recurrent pancreatic cancer after postoperative adjuvant chemotherapy

ObjectivesA global consensus on how to treat recurrent pancreatic cancer after adjuvant chemotherapy with gemcitabine (ADJ-GEM) does not exist.MethodsWe retrospectively reviewed the clinical data of 41 patients with recurrences who were subsequently treated with chemotherapy.ResultsThe patients were divided into two groups according to the time until recurrence after the completion of ADJ-GEM (ADJ-Rec): patients with an ADJ-Rec < 6 months (n = 25) and those with an ADJ-Rec ≥ 6 months (n = 16). The disease control rate, the progression-free survival after treatment for recurrence and the overall survival after recurrence for these two groups were 68 and 94% (P = 0.066), 5.5 and 8.2 months (P = 0.186), and 13.7 and 19.8 months (P = 0.009), respectively. Furthermore, we divided the patients with an ADJ-Rec < 6 months into two groups: patients treated with gemcitabine (n = 6) and those treated with alternative regimens including fluoropyrimidine-containing regimens (n = 19) for recurrent disease. Patients treated with the alternative regimens had a better outcome than those treated with gemcitabine.ConclusionsFluoropyrimidine-containing regimens may be a reasonable strategy for recurrent disease after ADJ-GEM and an ADJ-Rec < 6 months.     

Perioperative and long-term outcomes after pancreaticoduodenectomy in elderly patients 80 years of age and older

Purpose

Although a pancreaticoduodenectomy (PD) has been recently regarded as a safe surgical procedure at high-volume centers, the efficacy of PD for patients 80 years of age and older is controversial. The aim of this study was to evaluate the perioperative and long-term outcomes following PD in patients 80 years of age and older.

Methods

Elderly patients 80 years of age and older who underwent PD between 2001 and 2009 were identified. The perioperative and long-term outcomes were compared with patients younger than 80 years of age.

Results

Of 561 total patients, 22 patients (3.9 %) were 80 years of age or older. Mortality occurred in one patient (4.5 %). Postoperative major complications (Clavien–Dindo classification ≥grade III) occurred in six patients (27.3 %) in this group, which was significantly higher than in patients younger than 80 years of age (P?=?0.008). The survival of the elderly patients undergoing PD for pancreatic cancer was significantly shorter than that for the same patient group with other diseases (median survival, 13 versus 82 months; P?=?0.014). Only one elderly patient with pancreatic cancer survived more than 3 years.

Conclusions

PD for pancreatic cancer in patients aged 80 and older should be carefully selected, because it is associated with a higher incidence of severe postoperative complications and a small change of long-term survival.     

Delayed Gastric Emptying After Stapled Versus Hand-Sewn Anastomosis of Duodenojejunostomy in Pylorus-Preserving Pancreaticoduodenectomy: a Randomized Controlled trial

Background

A retrospective analysis indicated that the incidence of delayed gastric emptying (DGE) was less after using a circular stapler (CS) for duodenojejunostomy than that after hand-sewn (HS) anastomosis in pylorus-preserving pancreaticoduodenectomy (PpPD). This randomized clinical trial compared the incidence of DGE postoperative after CS duodenojejunostomy with that of conventional HS anastomosis in PpPD.

Methods

We randomly assigned 101 patients (age 20–80) undergoing PpPD to receive CS duodenojejunostomy (group CS, n?=?50) or HS duodenojejunostomy (group HS, n?=?51) in two Japanese cancer center hospitals between 2011 and 2013. The patients were stratified by institution and size of the main pancreatic duct (<3 or ≥3 mm). The primary endpoint was the incidence of grade B or C DGE according to the international definition with a non-inferiority margin of 5 %. This trial is registered with University hospital Medical Information Network (UMIN) Center: UMIN000005463.

Results

Per-protocol analysis of data on 95 patients showed that grade B or C DGE was found in 4 (8.9 %) of 45 patients who underwent CS anastomosis and in 8 (16 %) of 50 patients who underwent HS anastomosis (P?=?0.015). There were no differences in the overall incidence of DGE (P?=?0.98), passage of the contrast medium through the anastomosis (P?=?0.55), or hospital stays (P?=?0.22).

Conclusions

CS duodenojejunostomy is not inferior to HS anastomosis with respect to the incidence of clinically significant DGE, justifying its use as treatment option.

     

A comprehensive gene expression analysis of human hepatocellular carcinoma cell lines as components of a bioartificial liver using a radial flow bioreactor.

BACKGROUND/AIMS: The cells constituting a bioartificial liver are crucial for an effective liver support system. We compared global gene expression profiles in a radial flow bioreactor or a monolayer culture of three functional liver cell lines previously established from human hepatocellular carcinoma. METHODS: The expressions of 60,000 genes of the FLC-4, FLC-5, and FLC-7 cell lines were analyzed by the microarray technique with the Affymetrix GeneChip system. Global gene expression profiles were compared with two-way cluster analysis. Several liver function-related genes were compared between the bioreactor and culture conditions. RESULTS: Cluster analysis revealed that gene expression profiles of bioreactor-grown cells resembled those of the normal liver. Genes related to cellular structure were highly expressed in the bioreactor-grown cells, while genes involved in proliferation or carcinogenesis were suppressed. In the bioreactor-grown cells, some genes for liver functions were expressed at a level similar to that in normal liver, although none of the cell lines expressed the complete set of genes encoding ammonium metabolism or cytochrome P450 species. CONCLUSION: The high-density three-dimensional culture in the radial flow bioreactor prompted differentiation of the cells. These data may be useful for improving the cells by genetic or pharmacological reinforcement and for monitoring bioartificial livers.     

Reconstruction of hepatic venous tributaries using a Y-shaped left portal vein graft harvested from a resected left liver

Hepatic vein resection and reconstruction after major hepatectomy is a technically feasible but controversial procedure. Reported autologous vein grafts include the great saphenous, external iliac vein, superficial femoral, gonadal, left renal and inferior mesenteric veins. The procedures required to obtain these grafts, however, are associated with a risk of postoperative morbidity such as edema of the lower leg. We performed the reconstruction of two middle hepatic vein (MHV) branches by using an autologous left portal vein graft that was harvested with its tributaries from the left hepatectomy specimen in a 57-year-old man who had undergone a sigmoidectomy for colon cancer and a partial resection of the right lateral sector of the liver for a metastasis. In conclusion, this is the first report on the reconstruction of MHV tributaries using a single autologous Y-shaped portal vein graft during a hepatectomy. This method produces no complications related to the harvesting of the graft.     

Oxygen metabolism of the liver during an HA clamp: HV saturation and free radicals

BACKGROUND/AIMS: To clarify changes in the hepatic oxygen metabolism and tissue damage resulting from oxygen-derived free radical generation from polymorphonuclear cells during a hepatic arterial clamp. METHODOLOGY: Subjects were 32 male Wistar rats. Hepatic tissue blood flow, and hepatic venous chemiluminescence, indicating oxygen-derived free radicals from polymorphonuclear cells, and liver lipid peroxide were measured, and hepatic and portal venous blood gas analysis were performed before and after 130 minutes of hepatic arterial clamping. RESULTS: Hepatic tissue blood flow decreased by hepatic arterial clamp. The values of hepatic arterial oxygen pressure (HTBF), hepatic venous oxygen saturation (ShvO2), and O2 contents after hepatic arterial clamp were lower than those before hepatic arterial clamp (P = 0.035, 0.024, and 0.028, respectively). Hepatic venous chemiluminescence decreased and the lipid peroxide level of the liver increased by hepatic arterial clamp (P = 0.001). CONCLUSIONS: ShvO2 is useful for the evaluation of hepatic oxygen metabolism and hepatic tissue blood flow during acute hepatic arterial clamp. This condition should prepare the following tissue damage due to oxygen-derived free radicals from polymorphonuclear cells.     

Intraductal dissemination of papillary adenocarcinoma of the ampulla of Vater in the pancreatic duct

It has been speculated that intraductal dissemination, via the pancreatic duct, bile duct, or mammary duct, is a unique form of cancer cell spread. However, clinical evidence to confirm this form of dissemination has been lacking. Here we report a case of papillary adenocarcinoma of the ampulla of Vater in which retrograde dissemination to the pancreatic duct was strongly suggested. A 79‐year‐old woman underwent pancreatoduodenectomy for a 22 mm microinvasive papillary adenocarcinoma of the ampulla. Multiple carcinomas in situ were found in the pancreatic duct distant from the ampulla. Seven months later, she underwent a second operation for a recurrent papillary adenocarcinoma at the pancreato‐jejunal anastomosis showing exophytic and expansive growth into the jejunal lumen that connected to an intraductal adenocarcinoma in the pancreatic body. None of these tumors showed invasive growth, or vascular or neural invasion, being separate from each other but sharing identical histological, immunohistochemical, and molecular features; papillary growth, a pancreatobiliary phenotype, the same pattern of genomic loss of heterozygosity, and no mutation of the KRAS, TP53, and GNAS genes. These results imply that this papillary adenocarcinoma of the ampulla of Vater had disseminated to the pancreatic duct in a retrograde manner and recurred in the remnant pancreas.     

Preoperative identification of intraoperative blood loss of more than 1,500?mL during elective hepatectomy

Background

Despite recent advances in surgical techniques, hepatectomies remain one of the most hemorrhagic procedures in abdominal surgery. It is important to identify preoperatively patients who are at high risk of suffering massive intraoperative blood loss.

Methods

The clinical records of 251 patients who underwent an elective hepatectomy for liver tumors between September 2007 and December 2009 were reviewed retrospectively. A multivariate logistic regression analysis of preoperative factors potentially influencing intraoperative blood loss was performed. We set the cut-off value of the amount of blood loss for safe hepatectomy as less than 1,500?mL because no patients with blood loss of less than 1,500?mL received blood transfusion in this study. A scoring system to predict blood loss of more than 1,500?mL was constructed and validated in a cohort of 59 subsequent patients.

Results

Intraoperative blood loss of more than 1,500?mL was recognized in 35 of 251 patients (13.9%). Prothrombin activity?<?70%, non-peripheral location of the tumor, involvement of hepatic veins, body mass index????23.0, and major hepatectomy were independently associated with intraoperative blood loss of more than 1,500?mL. The score was calculated by assigning 1 point for each of the 5 risk factors. The area under the receiver operating characteristic curve (AUC) was 0.814 (95% CI 0.731?C0.898). This scoring system was highly predictive in the subsequent validation group of 59 patients (AUC?=?0.839, 95% CI 0.710?C0.969).

Conclusion

This predictive scoring system is considered to be useful for identifying before hepatectomy those patients with a high risk of intraoperative blood loss of more than 1,500?mL.