Preoperative profiles of plasma amino acids and derivatives distinguish periampullary cancer and benign disease.

Periampullary cancers, including pancreatic ductal adenocarcinoma, ampullary-, cholangio-, and duodenal carcinoma, are frequently diagnosed in an advanced stage and are associated with poor overall survival. They are difficult to differentiate from each other and challenging to distinguish from benign periampullary disease preoperatively. To improve the preoperative diagnostics of periampullary neoplasms, clinical or biological markers are warranted.In this study, 28 blood plasma amino acids and derivatives from preoperative patients with benign (N = 45) and malignant (N = 72) periampullary disease were analyzed by LC-MS/MS.Principal component analysis and consensus clustering both separated the patients with cancer and the patients with benign disease. Glutamic acid had significantly higher plasma expression and 15 other metabolites significantly lower plasma expression in patients with malignant disease compared with patients having benign disease. Phenylalanine was the only metabolite associated with improved overall survival (HR = 0.50, CI 0.30-0.83, P < 0.01).Taken together, plasma metabolite profiles from patients with malignant and benign periampullary disease were significantly different and have the potential to distinguish malignant from benign disease preoperatively.

Evaluation of tumor M2-pyruvate kinase (Tumor M2-PK) as a biomarker for pancreatic cancer.

BACKGROUND: Expression of the dimeric M2 isoenzyme of pyruvate kinase, termed Tumor M2-PK, is increased in some human cancers. This study evaluates the potential role of pre-operative Tumor M2-PK as a marker of prognosis in patients with pancreatic malignancy. METHODS: Seventy-three consecutive patients with a clinical diagnosis of pancreatic or peri-ampullary cancer were enrolled. Their median (range) age was 66 (23-83) years. Pre-operative samples of venous blood were taken for analysis of Tumor M2-PK. The full study protocol was approved by the North West Research Ethics Committee (protocol number 06/MRE08/69). RESULTS: The mean (standard deviation) plasma Tumor M2-PK in pancreatic/peri-ampullary malignancy was 60.3 (106.5) U/ml and 22 U/ml (SD: 12 U/ml) in benign disease (p < 0.001). Multivariate Cox regression analysis showed that Tumor M2-PK (> 27 U/mL), Ca19-9 (> 39 U/ml), resection status, and disease stage were associated with poorer survival. Tumor M2-PK values greater than 27 U/ml were associated with inferior survival compared to those with lower values (hazard ratio 2.049, significantly increased risk of death, p = 0.042). CONCLUSION: This preliminary study shows that an elevated level of Tumor M2-PK (with a cutoff threshold of 27 U/mL) measured pre-operatively is associated with poorer prognosis in patients with pancreatic and peri-ampullary cancer.

Preoperative platelet-to-lymphocyte ratio is a predictor of prognosis in patients with ampullary carcinoma.

AIM: To emphasize the significance of the platelet-to-lymphocyte ratio (PLR) in estimating the postoperative prognosis or survival measures in patients with carcinoma of the ampulla of Vater. METHODS: We retrospectively reviewed 82 patients, who underwent pancreaticoduodenectomy for ampullary carcinoma between July 2001 and April 2014. We investigated the predictive significance of the preoperative PLR for disease-free survival (DFS) or overall survival (OS). The possible correlations between the PLR and clinical or pathological features were also evaluated. RESULTS: The 5-year DFS and OS rates of the patients with carcinoma of the ampulla of Vater after pancreaticoduodenectomy were 51 % and 64 %, respectively. Multivariate analysis revealed a significantly worse OS in patients with a PLR ≥ 212 [hazard ratio (HR): 3.446; 95% confidence interval (CI): 1.4-8.43; p = 0.007], lymphovascular invasion (HR: 2.973; 95% CI: 1.25-7.03; p = 0.013), or pathological stage pT3/4 (HR: 2.761; 95% CI: 1-7.1; p = 0.035). Similarly, DFS was significantly worse in patients with lymphovascular invasion (HR: 2.24; 95% CI: 1.1-4.56; p = 0.025) or stage pT3/4 (HR: 2.243; 95% CI, 1.03-4.84; p = 0.04). CONCLUSION: The preoperative PLR shows a predictive significance for the prognosis of postoperative patients with carcinoma of the ampulla of Vater. We suggest that because of its predictive value, the PLR can be used in the development of further approaches to monitor and manage patients with poor prognosis Tab. 4, Fig. 1, Ref. 45).

Increased levels of sperm protein 17 mRNA and circulating antibodies in periampullary carcinoma patients.

BACKGROUND: Present-day diagnostic modalities for detecting periampullary carcinoma are suboptimal, and currently used proven markers lack specificity and sensitivity. METHODS: In order to assess the diagnostic potential of sperm protein 17, a cancer testis antigen, quantitative real-time PCR was performed to evaluate the expression of sperm protein 17 in tissue and sera specimens collected from periampullary carcinoma patients and normal subjects. Additionally, circulating levels of anti-sperm protein 17 antibodies were determined in sera of periampullary carcinoma patients and normal subjects using ELISA. RESULTS: Aberrant expression of sperm protein 17 was found in 14/15 (93 %) periampullary cancer tissues when compared with distant matched nonmalignant tissues (P = 0.006, Mann-Whitney U test). None of the distant matched nonmalignant tissues showed increased expression of sperm protein 17 mRNA. Area under the curve, sensitivity, and specificity were 0.791, 87, and 73 %, respectively. Increased levels of sperm protein 17 mRNA were demonstrated in sera of periampullary carcinoma patients (P = 0.020, Student's t test). Circulating levels of anti-sperm protein 17 antibody were found to be significantly elevated in 27/30 (90 %) periampullary carcinoma patients (P < 0.001, Student's t test). Area under the curve, sensitivity, and specificity were 0.954, 86.7, and 96.3 %, respectively. Only two of the normal subjects (7 %) showed elevated levels of anti-sperm protein 17 antibody. CONCLUSION: For the first time, our findings suggest that high levels of sperm protein 17 mRNA as well as increased circulating anti-sperm protein 17 antibodies can be used to distinguish periampullary cancer patients from healthy individuals, highlighting the diagnostic potential of sperm protein 17.

Prognostic factors of carcinoma of the ampulla of Vater after surgery.

The purpose of this study was to investigate the prognostic factors of carcinoma of the ampulla of Vater (CAV) after surgery. The clinicopathological factors related to the recurrence and prognosis of 162 CAV patients after surgical resection were retrospectively analyzed using univariate and multivariate methods. The in-hospital mortality rate was 4.32 % and the 5-year disease-free survival and overall survival of the 162 subjects were 55.1 and 51.7 %, respectively. Univariate analysis revealed that an advanced T stage (P = 0.002), lymph nodal metastasis (P = 0.002), poor differentiation (P = 0.006), tumor size (P = 0.033), tumor stage (P = 0.001), carbohydrate antigen (CA) 199 serum levels (P = 0.000), pancreatic invasion (P = 0.001), chemotherapy/radiation therapy (P = 0.006), and jaundice (P = 0.012) were factors that significantly affected the prognosis of CAV. Multivariate analysis showed that the pancreatic invasion (P = 0.009), lymph nodal metastasis (P = 0.009), and increased CA199 serum level (P = 0.001) were independent risk factors of recurrence. The pancreatic invasion, lymph nodal metastasis, and increased CA199 serum level are key prognostic factors of CAV after surgery.

Factors predicting survival and pathological subtype in patients with ampullary adenocarcinoma.

BACKGROUND: Carcinoma of the ampulla of Vater is uncommon. This study aimed to clarify predictors of survival for ampullary adenocarcinoma and to identify characteristics of its two major pathological subtypes. METHODS: Medical records were reviewed for 86 patients who underwent curative resection for ampullary adenocarcinoma between 2000 and 2012 at 12 principal hospitals in Kagawa, Japan. RESULTS: Resection was most common among 75-79-year-old patients. Actuarial 1-, 3-, and 5-year postoperative survival rates for ampullary adenocarcinoma were 90%, 72.3%, and 69.1%, respectively. Preoperative biliary drainage; serum CA19-9 and total bilirubin levels; pathological grade; perineural, vascular, pancreatic, and duodenal invasion; nodal metastasis; UICC-T stage; and pancreatobiliary subtype were predictors of poor survival. An elevated serum CA19-9 level; an elevated total bilirubin level; lymphatic, vascular, perineural, and pancreatic invasion; and advanced overall tumor stage were more common in patients with pancreatobiliary-type tumors than in patients with intestinal-type tumors. Additionally, pathologic subtype analysis showed that each subtype had distinct prognostic factors. CONCLUSIONS: Preoperative elevated serum CA19-9 and total bilirubin levels are prognostic factors for ampullary adenocarcinoma, and are both associated with pancreatobiliary-type tumors. Surgeons should be aware of these factors because pancreatobiliary-type adenocarcinoma is aggressively invasive and is associated with poor survival.

[Clinicopathological diagnosis of IgG4-related disease: report of eight cases].

OBJECTIVE: To evaluate the clinical and pathological features of IgG4-related disease (IgG4RD). METHODS: The clinical data, laboratory profiles, radiological, pathological and therapeutic features of eight cases of IgG4RD were analyzed. This cohort included two cases of common bile duct and partial hepatectomy specimens, two of submandibular gland excision specimens, one from lung biopsy specimen, one from open lung biopsy specimen, one from renal biopsy specimen, and one from renal excision specimen. In all cases, adequate lesion tissues were obtained. They were paraffin embedded, HE stained, and additional special stains and immunohistochemistry performed (MaxVision method). RESULTS: This series consisted of five males and three females, with a mean age of onset of 60 years. Five cases were suspected to be malignant pre-operatively, including two cases suspected of common bile duct carcinoma, two suspected of salivary gland tumor, and one suspected of renal pelvic carcinoma. Elevated serum levels of IgG4 and IgE were detected in five cases and eosinophilia in four cases. Multi-organ involvement was noted in four cases. The major histopathological features associated with IgG4-RD were: dense lymphoplasmacytic infiltrate, with lymphoid follicle formation. Extensive eosinophilic infiltrate (> 10/HPF) was seen in four cases; fibrosis that was arranged at least focally in a storiform pattern was also noted. The numbers of IgG4 positive plasma cells were > 20-50/HPF, while the IgG4 to IgG ratio was more than 40%. Obliterative phlebitis was present in four cases. Other pathological changes such as necrotizing vasculitis or lymphoma were not found. Five patients responded well to glucocorticoids. CONCLUSIONS: IgG4RD has relatively specific histopathological features; accurate evaluation of the absolute and relative number of IgG4 positive plasma cells in lesional tissue, combining with clinical examination and exclusion of other causes of elevated IgG4, allows the diagnosis of IgG4RD. IgG4RD has complicated clinical manifestation, and glucocorticoids therapy is efficacious.

Prediction of carcinoma after resection in subjects with ampullary adenomas on endoscopic biopsy.

BACKGROUND/GOALS: The endoscopic treatment of ampullary adenomas is established; however, the false-negative rate of endoscopic biopsy for carcinoma is 20% to 30%, and it remains uncertain whether identifiable features predict malignancy. Our aim in this study was to evaluate the predictable factors of malignancy in ampullary adenomas on endoscopic biopsy. STUDY: Ninety-one subjects diagnosed with ampullary adenoma on endoscopic biopsy were confirmed after endoscopic or surgical resection of ampullary lesions between 1995 and 2011 respectively. Clinical, laboratory, radiologic, and endoscopic findings were compared between patients with adenoma and carcinoma after resection. We examined the predictors of malignancy in ampullary adenoma on endoscopic biopsy. RESULTS: The malignancy rate in ampullary adenomas on endoscopic biopsy was 26.4%. Univariate analysis revealed that presence of symptoms, villous components, high-grade dysplasia (HGD), papilla enlargement on computed tomography, duct dilatation on radiologic imaging, bilirubin>2 mg/dL, aspartate aminotransferase>40 IU/L, alanine aminotransferase>40 IU/L, and alkaline phosphatase>90 U/L were associated with malignancy in patients over 65 years of age. HGD [odds ratio, 6.86 (95% confidence interval, 1.58-29.79)] and ductal dilatation [odds ratio, 11.12 (95% confidence interval, 2.27-54.37)] were independently associated with malignancy in multivariate analysis. The sensitivity and negative predictive value for ≥1 risk factors were 95.83% and 96.77%, respectively. The presence of 2 risk factors resulted in a high specificity (96%) and positive predictive value (84%) for malignancy. CONCLUSIONS: HGD and ductal dilatation are significant predictors of malignancy in ampullary adenomas. When these risk factors are present, precautions should be taken in the consideration of malignancy in patients with ampullary adenoma.

Clinical value of serum CA19-9 as a prognostic factor for the ampulla of Vater carcinoma.

BACKGROUND/AIMS: Ampulla of Vater carcinoma is a relatively rare digestive tract tumor; postoperative prognostic factors have been well studied. However, any indicator of preoperative prognosis remains poorly identified. This study aims to identify serum tumor markers as preoperative prognostic factors and other variables as postoperative prognostic factors for ampulla of Vater carcinoma. METHODOLOGY: This study retrospectively analyzed data from 26 patients undergoing pancreaticoduodenectomy (PD), including pylorus preserving PD for ampulla of Vater carcinoma between April 1993 and December 2006. The main outcome measures were survival rates of patients with and without high levels of CA19-9 and CEA. RESULTS: Patients with high levels of CA19-9 (n = 12) had significantly higher survival rates than those without (n = 14) (p = 0.0027). High levels of CEA did not influence cumulative survival rates (p = 0.4522). Histopathological classification was an independent predictor of poor survival rates; patients with well differentiated adenocarcinoma (n = 18) had significantly higher survival rates than those with moderate to poorly differentiated tumors (n = 12) (p = 0.0280). Other factors such as tumor size, lymph node metastasis (p = 0.4006), or invasion of pancreas (p = 0.1156), duodenum (p = 0.0.3723), vein (p = 0.4331), and lymph vessel (p = 0.8606), and perineural invasion (p = 0.0.8765) were not an independent indicators of poor survival rate. CONCLUSIONS: The results of our study indicated that high levels of CA19-9 and histopathological classification were significant independent predictors of poor survival rates for the ampulla of Vater carcinoma.

Can red cell distribution width help to discriminate benign from malignant biliary obstruction? A retrospective single center analysis.

BACKGROUND/AIMS: Differentiation of benign obstructive jaundice from malignant obstructive jaundice still remains difficult, despite improvements in diagnostic modalities. The aim of this study is to evaluate the usefulness of red cell distribution width (RDW) in differentiating benign and malignant causes of obstructive jaundice. METHODOLOGY: One hundred and ninety four consecutive patients (101 malignant, 93 benign) with a history of obstructive jaundice were reviewed in the period between January 2008 and August 2009. Definition of biliary strictures was suggested by cholangiographic features and supported by brush cytology, fine needle aspiration (FNA) and the presence of mass or metastases by imaging and/or clinical followup. Patients were divided into two groups, benign and malignant, based on the discharge diagnosis. RESULTS: The receiver operating characteristic analysis showed that a RDW of 14.8% was the best cut-off value for predicting a malignant biliary stricture with a sensitivity of 72% and a specificity of 69% (AUC=0.755, 95% CI=0.649-0.810). RDW was increased (>14.8%) in 31.6% of benign cases and 68.4% of malignancies. Depressed RDW levels (<14.8%) were found in 72.9% of benign cases and 27.1% of malignancies, which was statistically significant (p<0.001). CONCLUSIONS: Our results show that RDW is useful in the differentiation of benign from malignant causes of biliary obstruction when using an optimized cut-off value. In patients in whom biliary obstruction is suspected, an elevated RDW value may be a reliable additional predictor for differentiating the underlying etiology of biliary obstruction.

Clinical value of plasma hepatocyte growth factor measurement for the diagnosis of periampullary cancer and prognosis after pancreaticoduodenectomy.

BACKGROUND: Previous studies suggest that serum hepatocyte growth factor (HGF) level may be a useful diagnostic and prognostic biomarker for various tumors. We investigated the utility of plasma HGF level measurements in diagnosing periampullary cancer (PAC). METHODS: Of the patients enrolled in this pilot study (n = 118), 57 had PAC, 21 had benign pancreatic tumor (BPT), 20 had chronic pancreatitis (CP), and 20 were healthy controls. Plasma HGF was measured with ELISA kits. It was measured again at 10 days and 1, 2, 3, 6, and 12 months after pancreaticoduodenectomy (PD). RESULTS: Plasma HGF levels were significantly higher in PAC patients than in BPT patients, CP patients, or healthy controls. When a cutoff value of 1,120 pg/ml was used, 48/57 (84%) patients with PAC were positive for elevated HGF, but only 6/20 (30%) of patients with CP and none of the controls or patients with BPT were positive for elevated HGF. After PD, HGF levels were significantly elevated at day 10. CONCLUSIONS: Plasma HGF level discriminates well between PAC and other, benign diseases. Therefore, HGF measurement could be a useful addition to the existing array of diagnostic tools for PAC pancreatic cancer. The higher postoperative value may reflect the stress of surgery.

Adequate preoperative biliary drainage is determinative to decrease postoperative infectious complications after pancreaticoduodenectomy.

BACKGROUND AND PURPOSE: To assess the effectiveness of preoperative biliary drainage (PBD) by preoperative serum bilirubin level in patients with periampullary lesions receiving pancreaticoduodenectomy. PATIENTS AND METHODS: Between Jan. 1995 to May 2005, 240 consecutive cases received pancreaticoduodenectomy at the National Cheng Kung University Hospital, Taiwan and were included retrospectively. Factors possibly affecting postoperative morbidity and mortality were analyzed. RESULTS: One hundred and forty-three patients (59.6%) underwent preoperative biliary drainage (the PBD group) and 97 patients without drainage (the non-PBD group). The total postoperative morbidity rate was 49.6% and postoperative mortality was 2.9%. There was no difference in total postoperative morbidity and mortality between groups, but higher incidence of sepsis/bacteremia in the PBD patients (p = 0.03), and more cardiovascular events (p = 0.05) in the non-PBD patients. More bile leakage developed in the non-PBD patients, but only with marginal significance (p = 0.09). In the PBD group, patients with preoperative serum bilirubin level > or = 5 mg/dL had higher likelihood to acquire an infectious complication, (OR: 2.70; CI: 1.21-6.04), and surgical site infectious (OR: 2.70; CI: 1.21-6.04), intraabdominal abscess (OR: 2.74; CI: 0.94-8.03), and wound infection (OR: 2.44; CI: 0.97-6.16). CONCLUSION: Preoperative biliary drainage increased postoperative infectious complications but it also decreased cardiovascular events. However, adequate preoperative biliary drainage is the key to decrease infectious complications.

Effect of preoperative biliary drainage on surgical results after pancreaticoduodenectomy in patients with distal common bile duct cancer: focused on the rate of decrease in serum bilirubin.

AIM: To examine if the rate of decrease in serum bilirubin after preoperative biliary drainagecan be used as a predicting factor for surgical complications and postoperative recovery after pancreaticoduodenectomy in patients with distal common bile duct cancer. METHODS: A retrospective study was performed in 49 consecutive patients who underwent pancreaticoduodenectomy for distal common bile duct cancer. Potential risk factors were compared between the complicated and uncomplicated groups. Also, the rates of decrease in serum bilirubin were compared pre- and postoperatively. RESULTS: Preoperative biliary drainage (PBD) was performed in 40 patients (81.6%). Postoperative morbidity and mortality rates were 46.9% (23/49) and 6.1% (3/49), respectively. The presence or absence of PBD was not different between the complicated and uncomplicated groups. In patients with PBD, neither the absolute level nor the rate of decrease in serum bilirubin was significantly different. Patients with rapid decrease preoperatively showed faster decrease during the first postoperative week (5.5 +/- 4.4 micromol/L vs -1.7 +/- 9.9 micromol/L, P = 0.004). CONCLUSION: PBD does not affect the surgical outcome of pancreaticoduodenectomy in patients with distal common bile duct cancer. There is a certain group of patients with a compromised hepatic excretory function, which is represented by the slow rate of decrease in serum bilirubin after PBD.

Favorable glycemic response after pancreatoduodenectomy in both patients with pancreatic cancer and patients with non-pancreatic cancer.

Diabetes mellitus (DM) is prevalent in patients with pancreatic cancer and tends to improve after tumor resection. However, the glycemic response of non-pancreatic cancer patients after surgery has not been examined in detail. We aimed to investigate the changes in glucose metabolism in patients with pancreatic cancer or non-pancreatic cancer after pancreatoduodenectomy (PD).We prospectively enrolled 48 patients with pancreatic cancer and 56 patients with non-pancreatic cancer, who underwent PD. Glucose metabolism was assessed with fasting glucose, glycated hemoglobin (HbA1c), plasma C-peptide and insulin, quantitative insulin check index (QUICKI), and a homeostatic model assessment of insulin resistance (HOMA-IR) and ß cell (HOMA-ß) before surgery and 6 months after surgery. Patients were divided into 2 groups: "improved" and "worsened" postoperative glycemic response, according to the changes in HbA1c and anti-diabetic medication. New-onset DM was defined as diagnosis of DM ≤ 2 years before PD, and cases with DM diagnosis >2 years preceding PD were described as long-standing DM.After PD, insulin resistance (IR), as measured by insulin, HOMA-IR and QUICKI, improved significantly, although C-peptide and HOMA-ß decreased. At 6 months after PD, new-onset DM patients showed improved glycemic control in both pancreatic cancer patients (75%) and non-pancreatic cancer patients (63%). Multivariate analysis showed that long-standing DM was a significant predictor for worsening glucose control (odds ratio = 4.01, P = .017).Favorable glycemic control was frequently observed in both pancreatic cancer and non-pancreatic cancer after PD. PD seems to contribute improved glucose control through the decreased IR. New-onset DM showed better glycemic control than long-standing DM.

Prognostic Value of Preoperative Serum Carcinoembryonic Antigen and Carbohydrate Antigen 19-9 After Resection of Ampullary Cancer.

BACKGROUND: The purpose of this study is to investigate the prognostic value of pre-resection serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 after resection of ampullary cancer (AC) in consideration of intestinal (IT) and pancreatobiliary (PT) subtypes. METHODS: Overall survival (OS) analysis of patients undergoing curative resection of ampullary cancer. RESULTS: Elevated preoperative CEA (P = 0.013) and CA 19-9 levels (P = 0.030) were significant prognostic factors. Subgroup analysis, however, showed both markers having prognostic value only for the IT subgroup. Pre-resection CEA within normal range identified a subgroup of IT patients with an excellent median survival of 145 months. Compared to other AC patients, this low-risk ITCEA- subpopulation was characterized by less frequent advanced pT stages (pT3/pT4, 41 vs. 62%; P = 0.047) and lymph node involvement (pN+, 30 vs. 65%; P = 0.001). OS of this subgroup was significantly better compared to other AC patients (145 vs. 25 months; HR = 3.8; P < 0.001). By multivariate survival analysis, the patient age, the PT subtype, and an elevated pre-resection serum CEA value were identified as independent prognostic variables. CONCLUSIONS: In AC, the histomorphologic subclassification is highly relevant regarding the prognostic value of preoperative serum CEA and CA 19-9. IT-patients with normal preoperative CEA represent a favorable subgroup with excellent long-term survival.

Cytologic characteristics of circulating epithelioid cells in pancreatic disease.

BACKGROUND: Circulating epithelioid cells (CECs), also known as circulating tumor, circulating cancer, circulating epithelial, or circulating nonhematologic cells, are a prognostic factor in various malignancies that can be isolated via various protocols. In the current study, the authors analyzed the cytomorphologic characteristics of CECs isolated by size in a cohort of patients with benign and malignant pancreatic diseases to determine whether cytomorphological features could predict CEC origin. METHODS: Blood samples were collected from 9 healthy controls and 171 patients with pancreatic disease who were presenting for surgical evaluation before treatment. Blood was processed with the ScreenCell size-based filtration device. Evaluable CECs were analyzed in a blinded fashion for cytomorphologic characteristics, including cellularity; nucleoli; nuclear size, irregularity, variability, and hyperchromasia; and nuclear-to-cytoplasmic ratio. Statistical differences between variables were analyzed via the Fisher exact test. RESULTS: No CECs were identified among the 9 normal healthy controls. Of the 115 patients with CECs (positive or suspicious for), 25 had nonmalignant disease and 90 had malignancy. There were no significant differences in any of the cytologic criteria noted between groups divided by benign versus malignant, neoplastic versus nonneoplastic, or pancreatic ductal adenocarcinoma versus neuroendocrine tumor. CONCLUSIONS: CECs were observed in patients with malignant and nonmalignant pancreatic disease, but not in healthy controls. There were no morphologic differences observed between cells from different pancreatic diseases, suggesting that numerous conditions may be associated with CECs in the circulation and that care must be taken not to overinterpret cells identified by cytomorphology as indicative of circulating tumor cells of pancreatic cancer. Additional studies are required to determine the origin and clinical significance of these cells. Cancer Cytopathol 2017;125:332-340. © 2017 American Cancer Society.

18F-FDG activitiy PET/CT and CA-19.9 levels for the prediction of histopathological features and localization of peri- ampullary tumors.

BACKGROUND/AIMS: We sought to investigate the roles of maximum standardized uptake value (SUVmax) and serum carbohydrate antigen 19-9 (CA 19-9) in predicting the histopathological features of periampullary tumors. MATERIALS AND METHODS: Thirty-four patients with histologically confirmed periampullary tumors were classified into two groups, according to the localizations of their tumors (ampulla Vateri or pancreas). SUVmax was obtained from [(18)F]-fluorodeoxyglucose positron emission tomography computed tomography (18F-FDG PET/CT). SUVmax and CA 19-9 levels were measured and compared with histopathological features of the tumors. Logistic regression was used to assess the significance and independence of predictive factors. RESULTS: 18F-FDG PET/CT SUVmax (<2.5 vs. ≥2.5; p=0.031) and CA 19-9 level (normal vs. elevated; p=0.045) were significantly and independently predictive of the histopathological origin of the tumors (ampulla Vateri vs. pancreas). The ratio of CA 19-9 levels and SUVmax were found to be higher in cases of poorly differentiated tumors and tumors greater than 2 cm in diameter. CONCLUSION: A surgical approach to treatment may be considered for patients who have both i) an established or suspected diagnosis of periampullary tumors and ii) low SUVmax and CA 19-9 levels.

Double-Duct Sign in the Clinical Context.

OBJECTIVES: Double-duct sign (combined dilatation of the common bile duct and pancreatic duct) is an infrequently encountered finding in cross-sectional radiological imaging of the pancreatobiliary system. This sign is commonly deemed to signify on ominous pathology and suggests the presence of pancreatic or biliary malignancy. METHODS: We aim to correlate double-duct sign discovered on magnetic resonance cholangiopancreatogram (MRCP) in the clinical context. We retrospectively analyzed MRCP database over a period of 4 years, January 2010 to December 2013. Follow-up information was available for a median of 27 months (range, 12-42 months) RESULTS: The commonest cause of double-duct sign was choledocholithiasis followed closely by pancreatobiliary malignancy. Patients with jaundice in the context of double-duct sign had a higher incidence of malignancy (48%). None of the anicteric patients were found to have malignancy (P = 0.002). CONCLUSIONS: In patients with MRCP evidence of double-duct sign, the absence of jaundice makes a malignant etiology unlikely. Conversely, in jaundiced patients, a malignant cause is much more likely. Figures from larger series are needed to support this conclusion.

Intensified adjuvant therapy for pancreatic and periampullary adenocarcinoma: survival results and observations regarding patterns of failure, radiotherapy dose and CA19-9 levels.

PURPOSE: Primary endpoints were 1. To determine if, in the context of postoperative adjuvant therapy of pancreatic and nonpancreatic periampullary adenocarcinoma, continuous infusion (C.I.) 5-fluorouracil (5-FU) and leucovorin (Lv), combined with continuous-course external-beam radiotherapy (EBRT) to liver (23.4-27.0 Gy), regional lymph nodes (50.4-54.0 Gy) and tumor bed (50.4-57.6 Gy), followed by 4 months of C.I. 5-FU/Lv without EBRT could be given with acceptable toxicity. 2. To determine an estimate of disease-free and overall survival (DFS, OS) with this treatment in this context. Secondary endpoints were 1. To observe the effects of therapy at two different dose levels of irradiation, and 2. To observe for correlations among DFS, OS and CA 19-9 levels during therapy. METHODS: Patients received C.I. 5-FU 200 mg/m2 and Lv 5 mg/m2 Monday through Friday during EBRT, and 4 cycles of the same chemotherapy without EBRT were planned for each 2 weeks of 4, beginning 1 month following the completion of EBRT. Therapy was to begin within 10 weeks of surgery and patients were monitored for disease recurrence, toxicity, and CA 19-9 levels before the start of EBRT/5-FU/Lv, before each cycle of C.I. 5-FU/Lv, and periodically after the completion of therapy. There were two EBRT dosage groups: Low EBRT, 23.4 Gy to the whole liver, 50.4 Gy to regional nodes and 50.4 Gy to the tumor bed; High EBRT, 27.0 Gy to the whole liver, 54.0 Gy to regional nodes, and 57.6 Gy to the tumor bed. RESULTS: 29 patients were enrolled and treated (23 with pancreatic cancer, and 6 with nonpancreatic periampullary cancer). Of these, 18 had tumor sizes > or = 3 cm and 23 had at least one histologically involved lymph node; 6 had histologically positive resection margins. Mean time to start of EBRT/5-FU/Lv was 53 +/- 2 days following surgery. The first 18 patients were in the Low EBRT Group and the last 11 in the High EBRT Group. Toxicity was moderate and manageable, including a possible case of late radiation hepatitis. Median DFS was 8.3 months (pancreatic cancer patients 8.5 months) and OS was 14.1 months (pancreatic cancer patients 15.9 months). Among patients with pancreatic cancer, results were similar for the Low and High EBRT Groups (DFS: 8.3 vs. 8.6 months; OS: 14.4 vs. 16.9 months, respectively). With a mean follow up of 2.6 +/- 0.3 years for the surviving patients and a minimal follow-up of 2.5 years, 27 of 29 pts have relapsed and 25 pts have died. A rise in CA 19-9 levels preceded clinical relapse by 9.1 +/- 1.5 months. Time to first relapse by site showed inverse correlation with dose of radiotherapy to that site: peritoneal (5 +/- 1 month), hepatic (7 +/- 0.9 months), regional nodes/tumor bed (9.6 +/- 1.8 months). Mean postresection CA 19-9 level was 63.3 +/- 16.2 U/ml. Postresection CA 19-9 values did not correlate with survival, margin status, or with the identification of metastatic carcinoma in resected lymph nodes. However, among patients with histologically involved nodes in the resected specimen, postresection CA 19-9 values did correlate with the number of positive nodes identified (p = 0.05). CONCLUSIONS: Although toxicity was acceptable, survival results were not improved over those seen with standard adjuvant treatment. Most patients relapsed before the planned chemotherapy cycles were completed, or within 100 days thereof, suggesting disease resistance to C.I. 5-FU/Lv as used in this study. Although this regimen is not recommended for further study, the doses of EBRT utilized may be suitable for evaluation with other chemotherapy combinations. Postoperative CA 19-9 levels did not correlate with survival, but did correlate with the number of histologically involved lymph nodes found in the resected specimen among node-positive patients. Moreover, rising CA 19-9 levels anticipated ultimate clinical failure by 9 months.

Pancreaticoduodenectomy without homologous blood transfusion in an anemic Jehovah's Witness.

Whipple pancreaticoduodenectomy is an accepted procedure for management of periampullary and pancreatic carcinomas and has modern mortality rates of less than 10%. The procedure is associated with significant operative blood loss. Therefore, blood transfusion is an important supportive measure. We report the case of a bleeding ampullary carcinoma in a Jehovah's Witness who refused transfusion of all homologous blood products. Despite a preoperative hemoglobin level of 51 g/L, curative pancreaticoduodenectomy was successfully performed. The success of the procedure can be primarily attributed to careful surgical technique, intraoperative autotransfusion, avoidance of postoperative complications, minimization of perioperative phlebotomies, use of human recombinant erythropoietin, and, possibly, the use of the perfluorocarbon emulsion Fluosol DA-20%. The case illustrates several important principles for the surgical treatment of patients with severe anemia who refuse transfusion of homologous blood products.