• Clinical Endoscopy
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• v.56 no.2
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• pp.183-184
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• 2023

• Journal of Digestive Cancer Research
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• v.3 no.2
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• pp.61-69
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• 2015

About 80% of all pancreatic cancer patients suffer from a wasting syndrome defined as the cancer cachexia characterized by abnormally low weight, weakness, and loss of skeletal muscle mass, which directly impacts physical activity, quality of life and overall survival. Over the past decades, we have gained new insights into the underlying mechanism of cachexia associated with pancreatic cancer. The aim of this review was to explore recent findings about cancer cachexia pathophysiology and describe the current pharmacologic approach. Pancreatic cancer cachexia is a multifactorial syndrome mediated by mechanical factors, inflammatory cytokines, neuropeptides, hormones and tumor-derived factors. The treatment of cancer cachexia remains controversial but is currently an active area of research. Several new targeted drugs are under investigation, and we hope to open a new prospect in the management of cancer cachexia in the future.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.10
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• pp.4349-4352
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• 2014

Background: Pancreatic cancer has a high mortality rate because it is usually diagnosed late. Since little is known about this cancer in Iran, with the aim of improving this knowledge deficiency, we evaluated clinical, laboratory biomarkers, imaging findings and treatment modalities in Iranian patients with pancreatic adenocarcinoma. Materials and Methods: 131 cases of pancreatic adenocarcinoma in 2010-2013 were obtained from the Taleghani Hospital Record Department. Cases confirmed by histopathology from CT-guided biopsy, EUS-FNA and surgery examination were included. We excluded those with incomplete medical records. Results: The study included 131 subjects between 24 and 97 years of age and a mean age of $63{\pm}13.4$ years. Eighty (61.1%) were male and 51 (38.9%) female. Previous history included diabetes mellitus in 36 (27.5%), alcohol drinking in 5 (3.9%), smoker in 28 (21.4%) and opium addiction in 13 (10%). The common presenting history included weight loss in 79 (60.3%), abdominal pain in 77 (58.8%), fever in 11 (8.4%), nausea in 30 (22.9%), jaundice in 72 (55%), pruritus in 52 (39.7) and anemia in 33 (25.2%). CA19-9 levels with cut offs of 50, 100 and 200 U/ml were increased in 81%, 72% and 66% of patients, respectively. Tumor staging was: stage I, 3 (2.3%); stage II, 10 (7.6%); stage III, 58 (44.3%); and stage IV, 60 (45.8%). From 45 patients, 17 received ERCP inserted metallic stents and 22 plastic stents, the remaining 6 failed that PTC was done. Whipple surgery and chemotherapy were conducted for 10 and 29 patients, respectively. Conclusions: This disease affected older people and there was a male preponderance. The commonest risk factors were diabetes mellitus, smoking and cholelithiasis. The majority of patients presented with loss of appetite, loss of weight, jaundice, abdominal pain and discomfort. Almost all presented at late stages of the disease so that curative surgery was impossible. Also chemotherapy was only performed in a few patients as a neoadjuant treatment.

• Korean Journal of Radiology
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• v.22 no.1
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• pp.23-40
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• 2021

In pancreatic cancer, imaging plays an essential role in surveillance, diagnosis, resectability evaluation, and treatment response evaluation. Pancreatic cancer surveillance in high-risk individuals has been attempted using endoscopic ultrasound (EUS) or magnetic resonance imaging (MRI). Imaging diagnosis and resectability evaluation are the most important factors influencing treatment decisions, where computed tomography (CT) is the preferred modality. EUS, MRI, and positron emission tomography play a complementary role to CT. Treatment response evaluation is of increasing clinical importance, especially in patients undergoing neoadjuvant therapy. This review aimed to comprehensively review the role of imaging in relation to the current treatment strategy for pancreatic cancer, including surveillance, diagnosis, evaluation of resectability and treatment response, and prediction of prognosis.

• Biomolecules & Therapeutics
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• v.32 no.3
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• pp.281-290
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• 2024

Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis owing to its desmoplastic stroma. Therefore, therapeutic strategies targeting this tumor stroma should be developed. In this study, we describe the heterogeneity of cancer-associated fibroblasts (CAFs) and their diverse roles in the progression, immune evasion, and resistance to treatment of PDAC. We subclassified the spatial distribution and functional activity of CAFs to highlight their effects on prognosis and drug delivery. Extracellular matrix components such as collagen and hyaluronan are described for their roles in tumor behavior and treatment outcomes, implying their potential as therapeutic targets. We also discussed the roles of extracellular matrix (ECM) including matrix metalloproteinases and tissue inhibitors in PDAC progression. Finally, we explored the role of the adaptive and innate immune systems in shaping the PDAC microenvironment and potential therapeutic strategies, with a focus on immune cell subsets, cytokines, and immunosuppressive mechanisms. These insights provide a comprehensive understanding of PDAC and pave the way for the development of prognostic markers and therapeutic interventions.

• Annals of Hepato-Biliary-Pancreatic Surgery
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• v.27 no.1
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• pp.114-119
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• 2023

A 51-year-old male patient had four times of massive hematochezia episode three days before arrival. Carbohydrate antigen (CA) 19-9 level was extremely elevated. Computed tomography, magnetic resonance imaging, and positron emission tomography-computed tomography identified 5.7 cm sized periampullary duodenal cancer with regional metastatic lymph nodes and vascular invasion to aberrant right hepatic artery, main portal vein, and superior mesenteric vein. Diagnosed as duodenal adenocarcinoma through endoscopic biopsy, 16 times of FOLFIRI (5-fluorouracil, leucovorin, irinotecan) was conducted. The regimen changed to XELOX (capecitabine, oxaliplatine), four times of administration was done, and the CA19-9 level dramatically decreased. The tumor decreased to 2.1 cm. After R0 laparoscopic pylorus preserving pancreatoduodenectomy, no adjuvant therapy was given. No sign of recurrence or metastasis was reported, and the patient reached complete remission after five years. We reported a case where neoadjuvant chemotherapy for locally advanced duodenal adenocarcinoma was shown to be effective.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.22
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• pp.9667-9672
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• 2014

Background: Pancreatic adenocarcinoma is a malignant gastrointestinal cancer with significant morbidity and mortality. Despite severe side effects of chemotherapy, the use of immunotherapy combined with chemotherapy has emerged as a common clinical treatment. In this study, we investigated the efficacy of the combined doxorubicin and interferon-${\alpha}$ (IFN-${\alpha}$) therapy on murine pancreatic cancer Panc02 cells in vitro and in vivo and underlying mechanisms. Materials and Methods: A Panc02-bearing mouse model was established to determine whether doxorubicin and interferon-${\alpha}$ (IFN-${\alpha}$) could effectively inhibit tumor growth in vivo. Cytotoxicity of natural killer (NK) cells and cytotoxic T lymphocytes (CTLs) was evaluated using a standard LDH release assay. To evaluate the relevance of NK cells and CD8 T cells to the combination therapy-mediated anti-tumor effects, they were depleted in tumor-bearing mice by injecting anti-asialo-GM-1 antibodies or anti-CD8 antibodies, respectively. Finally, the influence of doxorubicin+interferon-${\alpha}$ (IFN-${\alpha}$) on the ligands of NK and T cells was assessed by flow cytometry. Results: The combination therapy group demonstrated a significant inhibition of growth of Panc02 in vivo, resulting from activated cytotoxicity of NK cells and CTLs. Depleting CD8 T cells or NK cells reduced the anticancer effects mediated by immunochemotherapy. Furthermore, the doxorubicin+IFN-a treatment increased the expression of major histocompatibility complex class I (MHC I) and NKG2D ligands on Panc02 cells, suggesting that the combined therapy may be a potential strategy for enhancing immunogenicity of tumors. All these data indicate that the combination therapy using doxorubicin and interferon-${\alpha}$ (IFN-${\alpha}$) may be a potential strategy for treating pancreatic adenocarcinoma.

• Journal of Gastric Cancer
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• v.21 no.1
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• pp.16-29
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• 2021

Purpose: Incidence, risk factors, and clinical consequences of pancreatic fistula (POPF) after D1+/D2 radical gastrectomy have not been well investigated in Western patients, particularly those from Eastern Europe. Materials and Methods: A total of 358 D1+/D2 radical gastrectomies were performed by surgeons with high caseloads in a single surgical center from 2002 to 2017. A retrospective analysis of data that were prospectively gathered in an electronic database was performed. POPF was defined and graded according to the International Study Group for Pancreatic Surgery (ISGPS) criteria. Uni- and multivariate analyses were performed to identify potential predictors of POPF. Additionally, the impact of POPF on early complications and long-term outcomes were investigated. Results: POPF was observed in 20 patients (5.6%), according to the updated ISGPS grading system. Cardiovascular comorbidities emerged as the single independent predictor of POPF formation (risk ratio, 3.051; 95% confidence interval, 1.161-8.019; P=0.024). POPF occurrence was associated with statistically significant increased rates of postoperative hemorrhage requiring re-laparotomy (P=0.029), anastomotic leak (P=0.002), 90-day mortality (P=0.036), and prolonged hospital stay (P<0.001). The long-term survival of patients with gastric adenocarcinoma was not affected by POPF (P=0.661). Conclusions: In this large series of Eastern European patients, the clinically relevant rate of POPF after D1+/D2 radical gastrectomy was low. The presence of co-existing cardiovascular disease favored the occurrence of POPF and was associated with an increased risk of postoperative bleeding, anastomotic leak, 90-day mortality, and prolonged hospital stay. POPF was not found to affect the long-term survival of patients with gastric adenocarcinoma.

• Annals of Hepato-Biliary-Pancreatic Surgery
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• v.27 no.1
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• pp.76-86
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• 2023

Backgrounds/Aims: The aim of this study was to describe short- and long-term outcomes of patients who underwent pancreatoduodenectomy (PD) at a typical United Kingdom hepatopancreatobiliary unit. Methods: A retrospective analysis of all PD patients with histologically-confirmed pancreatic ductal adenocarcinoma (PDAC), ampullary adenocarcinoma (AA), or distal cholangiocarcinoma (CC) from September 1st, 2006 to May 31st, 2015 was carried out. The following information was obtained: demographics, comorbidities, preoperative investigations, neoadjuvant treatment, operative details, postoperative management, complications, adjuvant treatment, five-year recurrence, and five-year survival. Effects of selected preoperative variables on short- and long-term outcomes were investigated. Results: Of 271 included patients, 57.9% had PDAC, 25.8% had AA, and 16.2% had CC. In total, 67.9% experienced morbidity and 17.3% developed a Clavien-Dindo grade ≥ III complication. The 90-day mortality was 3.3%. Clinically-relevant postoperative pancreatic fistula, bile leak, gastrojejunal leak, postpancreatectomy haemorrhage and delayed gastric emptying affected 8.1%, 4.1%, 0.0%, 9.2%, and 19.9% of patients, respectively. American Society of Anesthesiologists grade III-VI correlated with overall morbidity (p = 0.002) and major morbidity (p = 0.009), but not 90-day mortality or five-year survival. The same pattern was observed in patients with a preoperative serum bilirubin > 29 µmol/L and/or a neutrophil/lymphocyte ratio > 3.1. Five-year cancer recurrence and five-year survival were 68.3% and 22.5%, respectively. PDAC patients had higher five-year recurrence but lower five-year survival rates (both p = 0.001). Conclusions: In our series, the majority of patients experienced a complication. However, few patients experienced major morbidity. Surgical risk factors did not affect five-year survival.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.7
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• pp.2719-2724
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• 2015

Objective: The aim of this study was to investigate the clinical significance of annexin a1 (ANXA1) and provide molecular evidence to support that decreased ANXA1 expression could enhance cancer migration and invasion in pancreatic ductal adenocarcinoma (PDAC). Materials and Methods: Immunohistochemistry of a tissue microarray with 162 surgically resected PDAC specimens was performed to examine the expression of ANXA1. We also investigated the relationship between ANXA1 expression and clinicopathological factors and prognosis of PDAC patients. We further studied the role of ANXA1 in PDAC cell proliferation, migration and invasion by cell proliferation assay, migration assay and matrigel invasion assay with reduced ANXA1 expression by RNAi. Western blotting was used to detect matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinase-1 (TIMP-1) expression. We also detected MMP-9 enzyme activity by gelatin zymography. Results: Decreased expression of ANXA1 was significantly associated with poor differentiation, lymph node metastasis and advanced TNM stage of PDAC patients (p<0.05). Moreover, decreased expression of ANXA1 was correlated with poor survival (p<0.05). Furthermore, we found that ANXA1 knockdown inhibited cell proliferation, induced G1 phase cell cycle arrest, increased PDAC cell migration and invasion capacity compared with controls. In addition, Western blotting showed that ANXA1 knockdown increased the MMP-9 protein level and decreased TIMP-1 expression. Gelatin zymography showed that MMP-9 enzyme activity was also elevated. Conclusions: Negative ANXA1 expression is a most unfavorable prognostic factor for PDAC patients. ANXA1 knockdown inhibits cell proliferation by inducing G1 phase cell cycle arrest and increases migration and invasion of PDAC cells through up-regulating MMP-9 expression and activity, implying that ANXA1 may serve as a promising prognostic biomarker and therapeutic target for PDAC.