A gene expression signature of epithelial tubulogenesis and a role for ASPM in pancreatic tumor progression.

BACKGROUND & AIMS: Many patients with pancreatic ductal adenocarcinoma (PDAC) develop recurrent or metastatic diseases after surgery, so it is important to identify those most likely to benefit from aggressive therapy. Disruption of tissue microarchitecture is an early step in pancreatic tumorigenesis and a parameter used in pathology grading of glandular tumors. We investigated whether changes in gene expression during pancreatic epithelial morphogenesis were associated with outcomes of patients with PDAC after surgery. METHODS: We generated architectures of human pancreatic duct epithelial cells in a 3-dimensional basement membrane matrix. We identified gene expression profiles of the cells during different stages of tubular morphogenesis (tubulogenesis) and of PANC-1 cells during spheroid formation. Differential expression of genes was confirmed by immunoblot analysis. We compared the gene expression profile associated with pancreatic epithelial tubulogenesis with that of PDAC samples from 27 patients, as well as with their outcomes after surgery. RESULTS: We identified a gene expression profile associated with tubulogenesis that resembled the profile of human pancreatic tissue with differentiated morphology and exocrine function. Patients with PDACs with this profile fared well after surgery. Based on this profile, we established a 6-28 gene tubulogenesis-specific signature that accurately determined the prognosis of independent cohorts of patients with PDAC (total n = 128; accuracy = 81.2%-95.0%). One gene, ASPM, was down-regulated during tubulogenesis but up-regulated in human PDAC cell lines and tumor samples; up-regulation correlated with patient outcomes (Cox regression P = .0028). Bioinformatic, genetic, biochemical, functional, and clinical correlative studies showed that ASPM promotes aggressiveness of PDAC by maintaining Wnt-ß-catenin signaling and stem cell features of PDAC cells. CONCLUSIONS: We identified a gene expression profile associated with pancreatic epithelial tubulogenesis and a tissue architecture-specific signature of PDAC cells that is associated with patient outcomes after surgery.

Anti-apoptotic effects of osteopontin through the up-regulation of Mcl-1 in gastrointestinal stromal tumors.

BACKGROUND: Osteopontin (OPN) is a secreted phosphoprotein expressed by neoplastic cells involved in the malignant potential and aggressive phenotypes of human malignancies, including gastrointestinal stromal tumors (GISTs). Our previous study showed that OPN can promote tumor cell proliferation in GISTs. In this series, we further aim to investigate the effect of OPN on apoptosis in GISTs. METHODS: The expression of apoptotic and anti-apoptotic proteins in response to OPN was evaluated. In vitro effects of OPN against apoptosis in GIST were also assessed. GIST specimens were also used for analyzing protein expression of specific apoptosis-related molecules and their clinicopathologic significance. RESULTS: Up-regulation of ß-catenin and anti-apoptotic proteins Mcl-1 with concomitant suppression of apoptotic proteins in response to OPN was noted. A significant anti-apoptotic effect of OPN on imatinib-induced apoptosis was identified. Furthermore, Mcl-1 overexpression was significantly associated with OPN and ß-catenin expression in tumor tissues, as well as worse survival clinically. CONCLUSIONS: Our study identifies anti-apoptotic effects of OPN that, through ß-catenin-mediated Mcl-1 up-regulation, significantly antagonized imatinib-induced apoptosis in GISTs. These results provide a potential rationale for therapeutic strategies targeting both OPN and Mcl-1 of the same anti-apoptotic signaling pathway, which may account for resistance to imatinib in GISTs.

Successfully seal pancreatic end after thermal distal pancreatectomy using needle arrays in alternating electromagnetic fields.

BACKGROUND: Pancreatic fistula is still the major postoperative morbidity after distal pancreatectomy (DP). An inductive heat technology via needle arrays in a system of alternating magnetic fields (AMFs) was designed to seal off the pancreatic end. METHODS: Twenty Lanyu pigs were divided into 2 groups for DP: the conventional group had hand-sewn closure of the pancreatic end (n = 10), and the AMF group received thermal DP by AMF (n = 10). Pathological examinations of the resected and remnant pancreas were studied immediately after resection and on the 14th postoperative day (POD), respectively. The severity and the incidence of pancreatic abscess were compared. RESULTS: The incidence and severity of pancreatic abscess were significantly decreased in the AMF group than those in the conventional group (P = .009). In the immediate postoperative period, microscopic examination of the pancreatic resected end showed prominent coagulative necrosis, loss of NADPH-diaphorase activity, and significant apoptosis at the resected pancreas in the AMF group compared with the control group. Fourteen days after AMF ablation, the pancreatic stump end was covered with thick fibrosis, and histological study of the remnant pancreas showed that the parenchyma had well recovered with positive NADPH-diaphorase activity, and the pancreatic duct was sealed off successfully by prominent periductal fibrosis and intraductal plug. The body weight gain on the 14th POD was significantly increased in the AMF group (from 23.8 ± 1.8 kg to 25.4 ± 5.5 kg) compared with the conventional group (from 25.3 ± 2.1 to 25.4 ± 6.0 kg; P = .003). CONCLUSIONS: Inductive heats by the AMF system via needle array can be performed easily and can seal the pancreatic cut surface well during DP.

A clustered ground-glass hepatocyte pattern represents a new prognostic marker for the recurrence of hepatocellular carcinoma after surgery.

BACKGROUND: The recurrence of hepatocellular carcinoma (HCC) after hepatectomy is a serious event. It has been demonstrated that different ground-glass hepatocyte (GGH) patterns harbor specific hepatitis B virus (HBV) pre-S deletion mutants and represent preneoplastic lesions in chronic HBV infection. In the current study, the authors investigated whether a specific GGH pattern in nontumorous liver tissues was associated with the recurrence of HBV-related HCC after surgery. METHODS: Clinicopathologic data from 82 patients with HBV-related HCC were reviewed. GGH patterns were assessed on hematoxylin and eosin-stained sections. Tissue hepatitis B surface antigen (HBsAg) expression was evaluated by immunohistochemical staining. Serum profiles of pre-S status, viral load, and HBV genotype were determined and correlated with clinical recurrence and survival after surgery. RESULTS: The results indicated that the clustered pattern of GGHs or HBsAg expression was associated significantly with decreased local recurrence-free survival (LRFS) during a mean follow-up of 46.4 months (P<.001). This biomarker was comparable to or better than the prognostic value of other parameters, such as multifocal tumors (P = .022), satellite nodules (P = .005), small cell dysplasia (P = .045), or elevated viral load (P = .027), to predict recurrent HCC. Multivariate analysis also revealed that type II GGHs, which expressed marginal HBsAg and consistently clustered in nodules, were independent variables associated with LRFS (P<.001) and overall survival (P = .003). CONCLUSIONS: The current results indicated that the assessment of GGH patterns or HBsAg expression in nontumorous liver tissues provides an easily recognized, new risk marker for the recurrence of HBV-related HCC after hepatic resection.

Establishment of an orthotopic transplantable gastric cancer animal model for studying the immunological effects of new cancer therapeutic modules.

Tumor cell growth is influenced by the cellular microenvironment including the presence of immune cells and blood vessels. Currently, no transplantable gastric cancer syngeneic animal models exist; therefore, we set out to establish a mouse gastric carcinoma cell line, which was named mouse gastric carcinoma cell line 3I (MGCC3I), from forestomach carcinoma developed in benzo[a]pyrene-treated ICR mice. MGCC3I cells showed epithelial-like morphology, multinuclear giant cell formation, and retained an intestinal phenotype, which are similar to human gastric cancer carcinoma cells. The expression of gastric cancer markers MUC1, MUC2, and MUC5AC, and oncogenes c-myc, c-met, cyclin E1, and cancer stem cell marker CD44 was determined in MGCC3I cells. MGCC3I cells formed poorly differentiated stomach tumors following orthotopic implantation into the stomachs of syngeneic ICR mice. Histone deacetylase inhibitors are recognized as a new class of anticancer drugs. The immunological therapeutic effects of the histone deacetylase inhibitors sodium butyrate and valproic acid were evaluated in this new animal tumor model. Sodium butyrate inhibited MGCC3I stomach tumor formation in animal models. Increased tumor infiltration by CD8 T cells and neutrophils was observed in mice treated with sodium butyrate or valproic acid. Depletion of CD8 T cells significantly attenuated tumor regression mediated by histone deacetylase inhibitors, which is correlated with enhancement of the MHC class I pathway in MGCC3I cells. Taken together, we have successfully established an orthotopic transplantable gastric tumor animal model and demonstrated its usefulness in revealing the role of CD8 T cells in the therapeutic effects of sodium butyrate.

Zinc deficiency in patients undergoing pancreatoduodenectomy for periampullary tumors is associated with pancreatic exocrine insufficiency.

BACKGROUND AND PURPOSE: The present study was done to investigate the prevalence of zinc deficiency after pancreatoduodenectomy (PD) and its correlation with pancreatic exocrine insufficiency. MATERIALS AND METHODS: Patients were included in this study if they had undergone PD for periampullary tumors without recurrence and had received follow-up for more than 6 months between February 2006 and June 2007. Serum levels of zinc, fasting glucose, albumin, and iron were obtained. The pancreatic exocrine function was evaluated by a fecal elastase-1 assay, stool fat assessment, and a pancreatic duct-parenchymal ratio (DPR) at the L1 level using abdominal computed tomography (CT). The quality of life was estimated with a questionnaire of EORTC QLQ-C30 and PAN26. All of these patients were then supplemented with oral pancreatic enzymes for 4 weeks to evaluate the effect of these enzymes on zinc deficiency. RESULTS: Forty-eight eligible patients, 27 men and 21 women, were included. The mean age was 61.3 ± 1.7 years. Thirty-three (68%) patients had a zinc deficiency with a mean zinc level of 72.3 ± 2.9 mcg/dl (normal range: 80-120 mcg/dl). Patients with lower serum zinc levels tended to have typical presentations of zinc deficiency (P = 0.039, χ(2)). The serum zinc level was significantly negatively correlated with pancreatic duct diameter, DPR, and positive stool fat during the late follow-up period. The most common presentations of patients with lower serum zinc levels were skin rash, photophobia, and glossitis. These gastrointestinal disorders, as well as symptoms of zinc deficiency, improved after pancreatic enzyme supplementation. CONCLUSIONS: Zinc deficiency after PD was a common phenomenon and correlated with pancreatic exocrine insufficiency.

Osteopontin expression is an independent adverse prognostic factor in resectable gastrointestinal stromal tumor and its interaction with CD44 promotes tumor proliferation.

BACKGROUND: Osteopontin (OPN) is a multifunctional secreted glycophosphoprotein involved in miscellaneous physiologic and pathologic processes and is functionally related to the transmembrane receptor CD44. Although OPN expression has been identified to be associated with poor prognosis in several gastrointestinal malignancies, its expression in gastrointestinal stromal tumor (GIST) has not been thoroughly investigated. This study was designed to evaluate the clinicopathologic significance of OPN expression in patients with resectable GIST. METHODS: OPN expression was analyzed for its clinicopathologic significance in surgical specimens from 99 patients with resectable GIST by immunohistochemistry. In situ Proximity Ligation Assay was used for examining OPN and CD44 interaction in tumor tissues and GIST cell lines. The in vitro effects of OPN and its interaction with CD44 also were assessed. RESULTS: Increased OPN expression was a significant poor prognostic factor that independently predicted recurrence and poor disease-free survival in patients with resectable GIST. The interaction of OPN and CD44 was confirmed by their significant correlation in both GIST tumor tissues and cell lines by in situ Proximity Ligation Assay analysis. OPN and its interaction with CD44 were related to increased mitosis and significantly enhanced GIST tumor cell proliferation in vitro. CONCLUSIONS: Our study identified the clinicopathologic significance and biologic effects of OPN expression in resectable GIST. Increased OPN expression was an independent poor prognostic factor and its interaction with CD44 significantly correlated with increased mitosis as well as in vitro proliferation-promoting effects.

Clinical implication and mitotic effect of CD44 cleavage in relation to osteopontin/CD44 interaction and dysregulated cell cycle protein in gastrointestinal stromal tumor.

BACKGROUND: CD44 and osteopontin (OPN) are functionally related molecules that, alone or in combination, play miscellaneous biological and pathophysiologic roles. CD44 cleavage, one unique feature of CD44, occurs in human cancers, but its function remains unclear. This study aimed to assess the clinicopathologic significance and mechanism of CD44 cleavage in gastrointestinal stromal tumor (GIST) with respect to OPN and OPN/CD44 interaction. MATERIALS AND METHODS: CD44 cleavage was evaluated by immunoblotting in 31 primary GIST tumor specimens with paired normal tissues. OPN/CD44 interaction was examined by in situ proximity ligation assay. The associations of CD44 cleavage activity with clinicopathologic parameters, cyclin D1 expression, beta-catenin expression, OPN expression, and OPN/CD44 interaction were analyzed. RESULTS: CD44 cleavage activity was demonstrated in 87.1% of GIST, in contrast to its absence in normal tissues. Increased CD44 cleavage activity was significantly associated with enhanced mitosis by multivariate analysis, in addition to being related to tumor size, recurrence, high-risk status, and poor survival by univariate analysis. Mitosis was significantly higher in GIST with increased CD44 cleavage activity, which also positively correlated with tumor-specific beta-catenin and cyclin D1 overexpression, indicating a mitotic effect through aberrant cell cycle. Both OPN and OPN/CD44 interactions were significantly associated with CD44 cleavage. CONCLUSION: Our study demonstrates the clinicopathological significance of CD44 cleavage in GIST. There is a significantly increased mitosis associated with CD44 cleavage in relation to OPN/CD44 interaction and dysregulated cell cycle in GIST.

Loss of E-cadherin and beta-catenin is correlated with poor prognosis of ampullary neoplasms.

BACKGROUND AND OBJECTIVES: Distant metastasis resulting from carcinoma cell detachment from the primary tumor involves modification of adhesion molecules. This study was conducted to examine the correlation of E-cadherin/beta-catenin expression with survival and recurrence in ampullary neoplasms. METHODS: Patients with diagnoses of ampullary neoplasms were enrolled in the study. Demographics, operative findings, and histopathological data were collected by retrospective chart review. Expression of E-cadherin and beta-catenin were detected by immunohistochemistry. RESULTS: A total of 110 patients were enrolled in the study. Preservation of membranous staining of E-cadherin was noted in 41 (37%) patients, aberrant cytoplasmic staining in 48 (44%) patients, and complete loss in 21 (19%) patients. Loss of E-cadherin was associated with pancreatic invasion, recurrence, and poor prognosis. Membranous staining of beta-catenin was noted in 65 (59%) patients, cytoplasmic or nuclear accumulation in 16 (15%) patients, and complete loss in 29 (26%) patients. Loss of beta-catenin expression was associated with tumor markers, ulcerative type, liver metastases, and poor prognosis. Pancreatic invasion, lymph node involvement, and loss of beta-catenin expression were predictors of disease recurrence. CONCLUSIONS: Loss of the E-cadherin/beta-catenin complex is related to poor prognosis in ampullary cancer. Loss of beta-catenin is predictor of recurrence in multivariate analysis.

Effect of pancreaticoduodenectomy on the course of hepatic steatosis.

BACKGROUND: The progression of hepatic steatosis after pancreaticoduodenectomy (PD) is controversial. This study was designed to determine whether PD would influence the course of hepatic steatosis. METHODS: Patients admitted for PD and distal pancreatectomy (DP) from January 2004 to January 2008 were enrolled. Exclusion criteria included liver metastasis, severe obesity (body mass index >30), diabetic mellitus, excessive alcohol consumption, and unavailable preoperative and 6-month postoperative unenhanced CT images. The pre-PD and post-PD liver attenuation, ratio, and difference of liver-to-spleen attenuation between liver and spleen attenuation were compared. RESULTS: Fifty patients who underwent PD and 20 patients who underwent DP were eligible. The mean follow-up period was 18.2 +/- 1.6 months for the PD group and 19.7 +/- 1.7 months for the DP group. Liver attenuation after PD was significantly decreased from 52.3 +/- 1.1 H. to 47.6 +/- 2 H. (p = 0.044), but no difference was observed in spleen attenuation. The liver-to-spleen attenuation ratio after PD also was significantly decreased: 1.12 +/- 0.02 versus 1.01 +/- 0.04 (p = 0.033). No difference in liver attenuation was found in the DP group. The female gender was a significant risk factor. CONCLUSIONS: The liver attenuation of CT images decreases in patients who receive PD, which implicates that hepatic steatosis can develop after PD; however, the mechanism needs to be elucidated.

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.

Bloodless liver resection using needle arrays under alternating electromagnetic fields.

BACKGROUND/AIM: Hemostasis is a major difficulty associated with hepatectomies. The authors designed a new thermal surgery system to reduce blood loss. METHODS: The newly designed system consists of an alternating magnetic field generator and stainless steel needle arrays with thermosensitive bands. Lanyu pigs were used: 4 for the Kelly crushing method and 4 for the newly designed method. The procedures used were S4-S5 segmentectomies or left lateral segmentectomies, after which the amount of blood loss and operation times were compared. The pigs were observed for 4 weeks, after which liver pathologies were studied. RESULTS: The blood loss in the method proposed by the authors was almost 0 mL, whereas with the Kelly crushing method it was 116 +/- 35 mL. The method proposed in this study can save 15 to 25 minutes of operation time. The resected liver margins exhibited prominent apoptosis and fibrotic change in the remnant livers. CONCLUSIONS: The method proposed is a novel new way of performing thermal surgery.

Cyanine-Based Polymer Dots with Long-Wavelength Excitation and Near-Infrared Fluorescence beyond 900 nm for In Vivo Biological Imaging.

Bioimaging in the near-infrared window is of great importance to study the dynamic processes in vivo with deep penetration, high spatiotemporal resolution, and minimal tissue absorption, scattering, and autofluorescence. In spite of the huge progress on the synthesis of small organic fluorophores and inorganic nanomaterials with emissions beyond 900 nm, it remains a tough challenge to synthesize semiconducting polymers with fluorescence over this region. Here, we synthesized a series of heptamethine cyanine-based polymers with both absorption and emission in the near-infrared region. We prepared these polymers as semiconducting polymer dots (Pdots) in pure water with great biocompatibility. The fluorescence quantum yield of the Pdots can be as high as 14% with a full width at half-maximum of 53 nm, and their single-particle brightness is more than 20 times higher than commercial quantum dots or ∼300 times brighter than Food and Drug Administration (FDA)-approved indocyanine green (ICG) dyes. We further demonstrated the use of cyanine-based Pdots for specific cellular labeling and long-term tumor targeting in mice. We anticipate that these cyanine-based ultrabright Pdots could open up an avenue for next generations of near-infrared fluorescent agents.

Heparanase inhibitor PI-88 as adjuvant therapy for hepatocellular carcinoma after curative resection: a randomized phase II trial for safety and optimal dosage.

BACKGROUND/AIMS: Hepatocellular carcinoma recurrence after curative treatment adversely influences clinical outcome. It is important to explore adjuvant therapies. This phase II/stage 1 multi-center, randomized trial investigated the safety, optimal dosage and preliminary efficacy of PI-88, a novel heparanase inhibitor, in the setting of post-operative recurrence of HCC according to a Simon's 2-stage design. METHODS: Three groups were included: one untreated arm (Group A) and two PI-88 arms (Group B: 160 mg/day; Group C: 250 mg/day). Treatment groups received PI-88 over nine 4-week treatment cycles, followed by a 12-week treatment-free period. Safety and optimal dosage were assessed. RESULTS: Overall, 172 patients were randomized and 168 were included in the intention-to-treat (ITT) population. Treatment-related adverse effects included cytopenia, injection site hemorrhage, PT prolongation, etc. Four serious adverse events were possibly related to PI-88 treatment. One (1.8%) group B patients and six (10.5%) group C had hepatotoxicity-related withdrawals. Among the ITT population, 29 patients (50%) in Group A, 35 (63%) in Group B, and 22 (41%) in Group C remained recurrence-free at completion. Calculated T(1) value suggested 160 mg/day treatment satisfied the criteria for the next stage of the trial. CONCLUSIONS: PI-88 at 160 mg/day is optimal and safe, and shows preliminary efficacy as an adjunct therapy for post-operative HCC.

Clinical and imaging characteristics relating to surgical outcomes of perforated appendicitis.

BACKGROUND/AIMS: To study the characteristics of clinical findings and CT imaging of perforated appendicitis for predicting the outcome of patients who received immediate appendectomy for perforated appendicitis. METHODOLOGY: Thirty-eight patients with perforated appendicitis who received immediate appendectomy were retrospectively reviewed. During a median follow-up period of 1091 days, 13 patients had to be re-hospitalized owing to occurrence of complications relating to the immediate appendectomy. Accordingly, the patients were divided into two groups as either complication or non-complication group. The clinical characteristics and CT imaging of these two groups were compared. RESULTS: Those patients who delayed seeking medical advice were more prone to develop surgical complications after immediate appendectomy. CT imaging showing either fat stranding with remarkable fluid content or abscess indicates the presence of severe inflammation and is related to adverse surgical outcomes. Moreover, extraluminal appendicolith was more frequently found in the CT imaging of complication group. CONCLUSIONS: Patients with perforated appendicitis differ in their severity. Patients who seek medical advice late or have signs of severe inflammation or extraluminal appendicolith on their CT imaging are associated with more severe diseases and are prone to develop complications of surgery at this time and should be better treated conservatively.

A phase I study of combination of intravenous gemcitabine, oxaliplatin, and 5-FU with daily oral thalidomide (GOFT) in metastatic/locally advanced pancreatic carcinoma patients.

BACKGROUND/AIMS: The phase I study was to determine the maximum tolerance dose and dose-limiting toxicity of gemcitabine/oxaliplatin/5-FU/thalidomide (GOFT) in patients with advanced pancreatic cancer. METHODOLOGY: Chemotherapy-naive patients with histologically proven locally advanced or metastatic pancreatic cancer were enrolled. Gemcitabine was given in a 1-hour infusion followed by oxaliplatin in a 2-hour infusion on day 1, and 5-FU in a 24-hour infusion on day 2, and oral thalidomide 100mg was given daily after intravenous chemotherapy. This regimen was given every 2 weeks. Dose levels of regimen were: level I: gemcitabine 1000mg/m2 + oxaliplatin 60mg/ m2 + 5-FU 1000mg/m2 + thalidomide 100mg/day, level II: gemcitabine 1000mg/m2 + oxaliplatin 70mg/m2 + 5-FU 1000mg/m2 + thalidomide 100mg/day, level III: gemcitabine 1250mg/m2 + oxaliplatin 60mg/m2 + 5-FU 1000mg/m2 + thalidomide 100mg/day. The NCI-CTC grade 3/4 toxicity was used for dose-limiting toxicity. Maximum tolerance dose was determined after the first two cycles in each patient. RESULTS: There were 6 patients in level I, 6 patients in level II, and 1 patient in level III. One of the 6 patients had DLT in level I (grade 3 infection and vomiting), 2 of 6 patients had DLT in level II (grade 3 leukopenia) and 1 patient in level III had DLT (grade 3 leukopenia and stomatitis). Other toxicities at level I/II were grade 1/2 leukopenia (7 episodes), grade 1/2 anemia (5), grade 1/2 nausea (5), grade 1 diarrhea (2), grade 1 alopecia (2), grade 1 skin (2), grade 1 allergy (1). CONCLUSIONS: The GOFT regimen was well tolerated and showed good treatment effect on the pancreatic cancer. We recommended the dose of level II GOFT regimen for further phase II trial.

Surgical decompression in the patients of pancreatic intraductal papillary mucinous neoplasm.

Intraductal papillary mucinous neoplasm (IPMN) is characterized by cystic dilatation of the main and/or branch pancreatic duct by intraductal growth of mucin-producing columnar epithelia. The malignancy is determined by the degree of epithelial dysplasia. Because most IPMNs are slow growing and the prognosis may be favorable even when the IPMN is malignant, aggressive surgical treatment is suggested after considering operative and postoperative risks. Palliative surgery should be considered in some circumstances, such as other synchronous malignancy or systemic comorbidity. Here, we report two patients with IPMN treated successfully by surgical decompression of pancreatic duct.

Zinc deficiency with acrodermatitis enteropathica-like eruption after pancreaticoduodenectomy.

Pancreaticoduodenectomy (PD) is the standard operation for periampullary lesions. Most reports have focused on the clinical outcome, complications and tumor recurrence after PD. Few studies have focused on the nutritional sequelae that result from the extended resection of the upper gastrointestinal tract and disruption of the normal physiologic process of digestion. Zinc is absorbed mainly in the duodenum and proximal jejunum, which are removed during PD. Herein, we report two patients who experienced zinc deficiency with acrodermatitis enteropathica-like eruption, alopecia, glossitis and nail dystrophy after PD. The lesions improved dramatically after supplementation with zinc sulfate, pancreatic enzyme and diet instructions. No symptoms related to zinc deficiency were noted on follow-up after nutritional instructions had been given to the patients.

Predictors of recurrence after pancreaticoduodenectomy in ampullary cancer: comparison between non-, early and late recurrence.

BACKGROUND/PURPOSE: Ampullary cancer is one of the periampullary cancers with a better prognosis, but relapse still occurs early in some patients. We sought to find predictors of recurrence to facilitate decisions about postoperative therapy. METHODS: Between January 1989 and March 2006, information was gathered on a total of 127 patients undergoing pancreaticoduodenectomy with regional lymphadenectomy for ampullary cancer at National Cheng Kung University Hospital and Tainan Municipal Hospital. Clinical information, histopathologic results and long-term outcomes were collected and predictors for recurrence were identified. RESULTS: Fifty-eight patients (46%) survived without evidence of recurrence (non-recurrence), while 32 patients (25%) suffered recurrent disease after 12 months (late recurrence) and 37 patients (29%) developed recurrent disease within 12 months (early recurrence). The median follow-up for non-recurrence was 65 months, 13 months for early recurrence, and 36 months for late recurrence. Patterns of recurrence were similar, without any significant difference between the early recurrence and late recurrence groups. The early and late recurrence patients had higher levels of microscopically (R1) or macroscopically (R2) positive margin of resection and more advanced disease (advanced tumor stage, numbers of lymph nodes involved, lymph node status, pancreatic invasion and TNM stage) than the non-recurrence group. After multivariate analysis, positive resection margin, pancreatic invasion and lymph node involvement were significant predictors for disease recurrence. Lymph node involvement was the main differentiating predictor between the late and early recurrence groups (odds ratio, 1.982; 95% confidence interval, 1.101-3.567; p = 0.022). CONCLUSION: Positive resection margin, pancreatic invasion, and lymph node involvement were found to be predictors for disease recurrence and indicators for postoperative treatment.

Clinical analysis of the predictive factors for recurrent appendicitis after initial nonoperative treatment of perforated appendicitis.

BACKGROUND: The purpose of this study was to study the clinical symptoms, laboratory data, and the characteristics of computed tomography (CT) imaging of nonoperated perforated appendicitis for predicting the recurrence of appendicitis. METHODS: Thirty-five patients with nonoperated perforated appendicitis were retrospectively reviewed for this study. During a median follow-up period of 1155 days, 7 patients had to receive an appendectomy owing to recurrent appendicitis. Accordingly, the patients were divided into 2 groups: the recurrence and the nonrecurrence group. The clinical characteristics between these 2 groups were compared. RESULTS: Both of the 2 patients who had a past history of appendicitis suffered recurrent appendicitis (the recurrence versus the nonrecurrence group, P<.05). The only CT imaging relating to the recurrence of appendicitis is the presence of calcified appendicolith (the recurrence versus the nonrecurrence group, P<.001). CONCLUSIONS: It is most likely that appendicitis will recur if a calcified appendicolith on CT imaging or a past history of appendicitis is presented. Interval appendectomy may be reserved only for those patients who possess one of these risk factors of recurrent appendicitis.