CD40-mediated immune cell activation enhances response to anti-PD-1 in murine intrahepatic cholangiocarcinoma

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Major Perioperative Morbidity Does Not Affect Long-Term Survival in Patients Undergoing Esophagectomy for Cancer of the Esophagus or Gastroesophageal Junction

Introduction

The incidence of cancer of the esophagus/GE junction is dramatically increasing but continues to have a dismal prognosis. Esophagectomy provides the best opportunity for long-term cure but is hampered by increased rates of perioperative morbidity. We reviewed our large institutional experience to evaluate the impact of postoperative complications on the long-term survival of patients undergoing resection for curative intent.

Methods

We identified 237 patients who underwent esophagogastrectomy, with curative intent, for cancer between 1994 and 2008. Complications were graded using the previously published Clavien scale. Survival was calculated using Kaplan–Meier methodology and survival curves were compared using log-rank tests. Multivariate analysis was performed with continuous and categorical variables as predictors of survival, and examined with logistic regression and odds ratio confidence intervals.

Results

There were 12 (5 %) perioperative deaths. The average age of all patients was 62 years, and the majority (82 %) was male. Complication grade did not significantly affect long-term survival, although patients with grade IV (serious) complications did have a decreased survival (p = 0.15). Predictors of survival showed that the minimally invasive type esophagectomy (p = 0.0004) and pathologic stage (p = 0.0007) were determining factors. There was a significant difference in overall survival among patients who experienced pneumonia (p = 0.00016) and respiratory complications (p = 0.0004), but this was not significant on multivariate analysis.

Conclusions

In this single-institution series, we found that major perioperative morbidity did not have a negative impact on long-term survival which is different than previous series. The impact of tumor characteristics at time of resection on long-term survival is of most importance.     

Defining Treatment and Outcomes of Hepaticojejunostomy Failure Following Pancreaticoduodenectomy

Background

The overall complication rate after pancreaticoduodenectomy (PD) approaches 50 %, with anastomotic failure being the most frequent cause of serious postoperative morbidity. Hepaticojejunostomy leaks (also called bile leaks) are the second most common type of leak, behind pancreaticojejunostomy leaks, yet have been the focus of only a single study as reported by Suzuki et al. (Hepatogastroenterology 50:254–257, 12).

Methods

We reviewed the recent experience with bile leaks at a single, high-volume pancreatic surgery center over a six-year time period.

Results

Bile leaks were identified in 16 out of 715 patients (2.2 %). Low preoperative albumin was associated with an increased risk. Bile leaks typically manifested within the first week after surgery as bilious drainage in a surgically placed drain. Associated warning signs included fever and leukocytosis. Patients with a bile leak frequently developed other complications, including a pancreatic fistula, wound infection, delayed gastric emptying, and sepsis. The impact on perioperative outcomes was comparable to patients with a pancreatic leak. A grading system is proposed based on the International Study Group on Pancreatic Fistula model. Grade A bile leaks were classified as those managed with prolonged drainage by operatively placed drains, grade B bile leaks with percutaneous abdominal drainage, and grade C bile leaks with insertion of a percutaneous transhepatic biliary drainage.

Conclusions

Hepaticojejunostomy leaks are rare after PD. The complication severity ranges from trivial to life threatening and is comparable overall to pancreaticojejunostomy leaks. Surgical intervention is rarely, if ever, required. With prompt and aggressive management, a full recovery can be expected.     

Preoperative Imaging for Resectable Periampullary Cancer: Clinicopathologic Implications of Reported Radiographic Findings

Background

High-resolution, multiphase, computed tomography (CT) is a standard preoperative test prior to pancreatectomy, yet the clinical significance of routinely reported findings remains unknown.

Methods

We identified patients who underwent a pancreaticoduodenectomy for a periampullary adenocarcinoma (PA) over the previous 5 years and had a pancreas protocol CT at our institution. Clinicopathologic implications of reported CT findings were evaluated.

Results

There were 155 pancreatic ductal adenocarcinomas (PDA) and 47 non-pancreatic PAs. No mass was visualized on CT in 6 % of PDAs and 23 % of non-pancreatic PA. A size discrepancy of ≥1 cm between radiographic and pathologic tumor diameters was observed in 40 % of PAs, with CT underestimating the size in most instances (75 %). Radiographically enlarged lymph nodes were not associated with true lymph node metastases in PDAs (70 % lymph node positive cases were enlarged on CT vs 74 % lymph node negative, p = 0.5), but were associated with a preoperatively placed biliary endoprosthesis (63 % with endoprosthesis were enlarged vs 37 % no endoprosthesis, p = 0.013). Major visceral vessel involvement on CT was not associated with a vascular resection (3 % with CT vessel involvement vs 2 % without, p = 0.8) or a positive uncinate resection margin (24 vs 20 %, respectively, p = 0.6).

Discussion

While dedicated pancreas protocol CT provides unprecedented detail, the test may lead to overinterpretation of the extent of disease in some instances. A radiographic suggestion of enlarged lymph nodes and vascular involvement does not necessarily preclude exploration with curative intent. CTs with local disease should be reported in an objective template and carefully reviewed by a multidisciplinary group of surgeons, radiologists, and oncologists to avoid missing an opportunity for neoadjuvant therapy or cure by resection.     

Elevated intracellular level of basic fibroblast growth factor correlates with stage of chronic lymphocytic leukemia and is associated with resistance to fludarabine

Chronic lymphocytic leukemia (CLL) is characterized by delayed senescence and slow accumulation of monoclonal, small lymphocytes. Basic fibroblast growth factor (bFGF) is a pleiotropic cytokine that plays a role in hematopoiesis and apoptosis. Elevated bFGF levels have been detected in urine from patients with a variety of neoplastic diseases including various leukemias; however, the cellular source of the bFGF has not been determined. In this study, the intracellular bFGF level in lymphocytes of 36 patients with B-CLL and 15 normal donors was determined using an enzyme-linked immunoassay. In cells derived from patients with high-risk disease, the median level of intracellular bFGF was 381.5 pg/2 x 10(5) cells, compared with a median of 90.5 pg/2 x 10(5) cells in patients with intermediate disease. In patients with low- risk disease, the median bFGF level was 4.9 pg/2 x 10(5) cells, and in normal controls, it was 6.0 pg/2 x 10(5) cells. The difference in the bFGF levels was significant for the comparison between low- and intermediate-risk (P = .00119), low- and high-risk (P < .0001), and intermediate- and high-risk disease (P = .0001). Immunofluorescent stains of peripheral blood mononuclear cells confirmed CLL lymphocytes as a cellular source of bFGF. To evaluate the potential contribution of elevated intracellular bFGF levels to the phenotype of CLL cells, leukemic cells were cultured in vitro with an apoptotic stimulus (fludarabine). CLL cells with high intracellular levels of bFGF appeared to be more resistant to fludarabine treatment. The addition of bFGF to fludarabine-treated CLL cells resulted in a delay of apoptosis and prolonged survival. These data suggest that bFGF may contribute to the resistance of CLL cells to an apoptotic stimulus.     

Mental health need: use of administrative data and record linkage to inform mental health policy and practice

Background

With mental ill-health on the rise globally, it is crucial to investigate whether the needs of individuals with mental ill-health are fully addressed. Attempts to measure negative consequences of unmet needs have been limited by the use of cross-sectional study designs or self-report measures. We aimed to investigate the interplay between perceived mental ill-health and unmet need in relation to mental health on a population level.