The Role of Local Angiotensin II/Angiotensin Type 1-receptor Mechanisms in Adipose Tissue Dysfunction to Promote Pancreatic Cancer.

Obesity and adipose tissue dysfunction are important risk factors for pancreatic cancer. Pancreatic cancer is one of the most lethal cancers globally. The renin-angiotensin system (RAS) is expressed in many tissues, including adipose tissue. Dysregulation of angiotensin II and angiotensin II receptors in adipose tissue through the activation of different signaling pathways leads to adipose tissue dysfunction, including insulin resistance, adipose tissue inflammation, adipocytokines secretion, and metabolic alterations. The pathogenesis of pancreatic cancer remains uncertain. However, there is evidence that dysregulation of local angiotensin II in adipose tissue that occurs in association with obesity is, in part, responsible for the initiation and progression of pancreatic cancer. Due to the role of local angiotensin II in the dysfunction of adipose tissue, angiotensin receptor blockers may be considered a new therapeutic strategy in the amelioration of the complications related to adipose tissue dysfunction and prevention of pancreatic cancer. This review aims to consider the biological roles of local angiotensin II and angiotensin II receptors in adipose tissue dysfunction to promote pancreatic cancer progression with a focus on adipose tissue inflammation and metabolic reprogramming.

Elucidating the Role of Pro-renin Receptors in Pancreatic Ductal Adenocarcinoma Progression: A Novel Therapeutic Target in Cancer Therapy.

Pancreatic cancer is a highly aggressive malignancy with a very poor prognosis. The 5- year survival in these patients is very low, and most patients develop drug resistance to current therapies, so additional studies are needed to identify the potential role of new drug targets for the treatment of pancreatic cancer. Recent investigations have been performed regarding the roles of pro-renin receptors (PRR) in the initiation and development of cancers. PRR is a component of the local renin-angiotensin system (RAS). Local tissue RAS has been known in diverse organ systems, including the pancreas. Various investigations have implicated that PRRs are associated with the upregulation of various signaling pathways, like the renin-angiotensin system pathway, PI3K/Akt/mTOR, and the Wnt-signaling pathways, to contribute to pathological conditions, including cancer. In this review, we presented an overview of the role of PRR in the progression of pancreatic adenocarcinoma.

Evaluation of the diagnostic value of Sentinel Lymph Node in patients with gastric adenocarcinoma.

Objectives: Sentinel lymph node biopsy (SLNB) has been proven as a safe and efficient procedure in some cancers like breast cancer and melanoma with a reduction of complications and side effects of unnecessary lymphadenectomy in many patients. However, the diagnostic value of SLNB in gastric cancer is a point of debate. This study evaluated the diagnostic value of SLNB using radiotracer and isosulphan blue dye injection in patients with Gastric Adenocarcinomas (GA). Methods: This descriptive study was performed at Imam-Reza HOSPITAL on 39 patients diagnosed with GA with no lymphatic metastasis using two methods: the combination of radionuclide with isosulphan together (R&I) method compared with the isosulphan alone method. Lymphatic dissection was performed in all patients. The pathological results were compared between the sentinel lymph nodes (SLN) and other lymph nodes and their accordance rate was calculated. Results: In the T1 group, the sentinel lymph node biopsy detection rate was 100% for the combination of the R&I method and 60% for the isosulphan method and the false negative rate was zero. These values respectively were 88.8% and 88.8% in the T2 group with a false negative rate of 75%. In the T3 group, the values were 100% for the combination of the R&I method and 93.7% for the isosulphan method with a false negative rate of 40%. In the combination of the R&I method, the sensitivity, specificity, and positive and negative predictive values were 57.9, 100, 100, and 69.2 percent respectively. Conclusion: Based on the false negative rate (47.4%), SLNB by injection of isosulphan blue dye alone is not a diagnostic enough value for predicting lymph node metastasis in GA. Although, SLNB by combination of the R&I had better accuracy compared to the isosulphan alone, more studies with larger samples are needed to prove this result.

Targeting Lysyl Oxidase as a Potential Therapeutic Approach to Reducing Fibrotic Scars Post-operatively: Its Biological Role in Post-Surgical Scar Development.

Abdominal and pelvic surgery, or any surgical injury of the peritoneum, often leads to chronic abdominal adhesions that may lead to bowel obstruction, infertility, and pain. Current therapeutic strategies are usually ineffective, and the pathological mechanisms of the disease are unclear. Excess collagen cross-linking is a key mediator for extra-cellular matrix deposition and fibrogenesis. Lysyl oxidase is a key enzyme that catalyzes the formation of stabilizing cross-links in collagen. Dysregulation of Lysyl oxidase (Lox) expressing upregulates collagen cross-linking, leading ECM deposition. Tissue hypoxia during surgery induces molecular mechanisms and active transcription factors to promote the expression of several genes related to inflammation, oxidative stress, and fibrosis, such as transforming growth factor beta, and Lox. Studies have shown that targeting Lox improves clinical outcomes and fibrotic parameters in liver, lung, and myocardial fibrosis, therefore, Lox may be a potential drug target in the prevention of postsurgical adhesion.

Review the Role of Metabolism Reprogramming in the Pathogenesis of Post-surgical Adhesion: A New Therapeutic Strategy.

Metabolic reprogramming is defined as the skill of cells to change their metabolism to support the induced energy demand due to continuous growth. Metabolic reprogramming is a well- known occurrence in the progression of neoplastic cells, although, evidence has shown that it is present in fibrotic disorders. Post-surgical adhesion as a fibrotic disorder is a medical challenge and is defined by fibrotic bands connected between organs with the abdominal wall. Despite many investigations carried out about the pathogenesis of the disorder but there are many unknowns, therefore, targeting special pathways may have the potential to prevent the formation of fibrotic bands post-operative. Glycolysis is a necessary metabolic pathway in living cells. In hypoxic conditions, it is the dominant pathway in the production of energy for different types of cells such as fibroblasts, immune cells, and endothelial cells. Also, glycolysis is a main downstream target for transforming growth factor ß (TGF-ß) and upregulates during fibrotic conditions. Furthermore, this is noteworthy that hypoxia induces factor 1 alpha (HIF-1α) as a transcription factor, elevated during the hypoxia condition stimulates different signaling pathways such as TGF-ß/SMAD, nuclear factor kappa B (NF-kB), and mTOR pathway to control glycolytic metabolism and T-cell trafficking for immune cell migration. Different evidence has indicated that the administration of glycolytic inhibitors has the potential to prevent the development of fibrotic markers. In this review, we pointed out the role of the glycolysis pathway and its connection to profibrotic cytokines to promote inflammatory and fibrotic pathways. Based on the results of studies related to fibrotic disorders we hypothesized that targeting glycolysis may have therapeutic potential in the prevention of postoperative adhesions.

The Association between Circulating Adipocytokine Omentin Levels and Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-analysis.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver condition worldwide. NAFLD is often associated with features of Metabolic Syndrome such as obesity and insulin resistance. METHOD: The current comprehensive meta-analysis was performed to evaluate the association between circulating Omentin levels and NAFLD. A systematic search in Scopus, Web of Science, PubMed, and Google Scholar databases was conducted to identify relevant studies up until 5th May 2022. The standard mean difference (SMD) values and 95% confidence intervals (CIs) were computed for the association of Omentin levels with NAFLD risk in a random effect model. RESULT: The meta-analysis involved 6 case-control studies with a total of 371 cases and 269 controls. Pooled SMD showed no significant difference in serum Omentin between NAFLD and healthy groups (SMD= -0.047 and 95% CI -0.957_0.862 P=0.91). Subgroup analysis based on sample size showed that the average Omentin levels were significantly higher in NAFLD patients in studies with sample size ≥70 (SMD=0.356 CI 0.056_0.655 P=0.02). CONCLUSION: Additional well-designed studies with more sample sizes are essential to clarify the potential role of Omentin as a risk marker of NAFLD.

Leiomyosarcoma, a rare smooth muscle cancer in the pancreas: An adjuvant radiotherapy treatment approach.

BACKGROUND: Leiomyosarcoma of visceral organs is uncommon, and pancreatic primary occurrence is even rarer. In terms of curative treatment, patients are generally managed with surgery alone, without significant data on the role or efficacy of adjuvant chemotherapy. CASE PRESENTATION: This manuscript presents a case of a 22-year-old female with advanced primary leiomyosarcoma of the pancreas, treated with radical surgery and adjuvant radiation therapy. CONCLUSION: With a low-survival rate, consideration of radiation therapy in some advanced and unresectable cases could be potentially beneficial.

Assessment of the nutritional status of patients before, one, and three months after liver transplantation: A multi-center longitudinal study.

BACKGROUND: Nutrition management is an important pre-operative and post-operative challenge in liver transplantation. Preoperative malnutrition is associated with increased length of intensive care unit (ICU) stay, mortality, and length of hospital stay in liver transplant patients. This study aimed to evaluate the nutritional status of patients before and after liver transplantation and post-transplant complications. METHOD: This longitudinal study was conducted on liver transplant patients in Montaserieh Hospital, Mashhad and Firoozgar Hospital, Tehran from May 2021 to January 2022. Demographic characteristics, Subjective Global Assessment (SGA) standard questionnaire, anthropometric indices, laboratory analyses, and 3-day food records were collected before, one, and three months after transplantation. RESULTS: Thirty-nine patients with a mean age of 48.4 ± 14.2 were evaluated. Prevalence of severe malnutrition was 43.6% (56.3% women and 34.8% men) before transplantation. Body mass index (BMI), body weight, lean mass, total body water, and total serum protein significantly decreased after transplantation compared to before transplantation (P < 0.001). One month after transplantation, 54% of the patients lost more than 10% of their weight. Energy intake increased significantly after transplantation (P < 0.001). A significant relationship was observed between BMI (P = 0.005) and metabolic complications and between Arm Muscle Circumference and renal complications (P = 0.003) after transplantation. A cut-off point of 4.6 was determined for the phase angle in terms of SGA three months after transplantation. CONCLUSION: Malnutrition, weight loss, and nutritional problems were common in liver transplantation patients. Screening for nutritional status is necessary in these patients to treat or prevent malnutrition-related complications.

Complications and Efficacy of Sinopharm Vaccine among Liver and Kidney Transplantation.

BACKGROUND: There are various vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, vaccination may lead to some complications. OBJECTIVE: This study aimed to investigate the complications of transplant recipients who received the Sinopharm COVID-19 vaccine. METHODS: This was a retrospective cross-sectional study conducted among 667 transplant recipients (211 liver transplant recipients and 456 kidney transplant recipients) who received the Sinopharm COVID-19 vaccine from March to August 2021 and had medical records in Montaserieh Hospital, affiliated to Mashhad University of Medical Sciences, Mashhad, Iran. The demographic and clinical information, as well as patient's symptoms after each dose of the vaccine, were recorded. RESULTS: Only 16.8% and 13.7% of the patients experienced some symptoms following the first and second doses of the Sinopharm vaccine, respectively. No significant difference was observed between patients younger than 50 years and those aged 50 years and over in terms of the complication rate of the Sinopharm vaccine (P>0.005). Vaccine failure was reported in 10% of the cases; however, the mortality rate due to infection with the Delta variant of COVID-19 in this population was reported to be 0.7%. CONCLUSION: Based on the obtained results, adverse reactions of the Sinopharm COVID-19 vaccine are generally mild, predictable, and non-life-threatening both in the first and second doses. Vaccine failure was reported in 10% of the cases; however, mortality due to infection with the Delta variant of COVID-19 was reported in less than 1% of the cases.

Oncogenic fusion transcript analysis identified ADAP1-NOC4L, potentially associated with metastatic colorectal cancer.

PURPOSE: Fusion transcripts are transcriptome-mediated alterations involved in tumorigenesis and are considered as diagnostic, prognostic, and therapeutic biomarkers. In metastatic colorectal carcinoma (mCRC), fusion transcripts are rarely reported. The main challenge is to identify driver chimeras with a significant role in cancer progression. METHODS: In the present study, 86 RNA sequencing data samples were analyzed to discover driver fusion transcripts. Functional assays included clonogenic cell survival, wound-healing, and transwell cell invasion. Quantitative expression analysis of epithelial-mesenchymal transition (EMT), apoptotic regulators, and metastatic markers were examined for the candidate fusion genes. Kaplan-Meier survival analysis was performed using patient overall survival (OS). RESULTS: A variety of driver fusions were identified. Fourteen fusion genes (51% of mCRC), each at least found in two mCRC samples, were determined as oncogenic fusion transcripts by in silico analysis of their functions. Among them, two recurrent chimeric transcripts confirmed by Sanger sequencing were selected. Positive expression of ADAP1-NOC4L was significantly associated with an increased risk of poor OS in mCRC patients. In vitro transforming potential for the chimera, resulting from the fusion of ADAP1 and NOC4L was assessed. Overexpression of this fusion gene increased cell proliferation and enhanced migration and invasion of CRC cells. In addition, it significantly upregulated EMT and anti-apoptotic markers. CONCLUSIONS: ADAP1-NOC4L transcript chimera, a driver chimera identified in this study, provides new insight into the underlying mechanisms involved in the development and spread of mCRC. It suggests the potential of RNA-based alterations as novel targets for personalized medicine in clinical practice.

Minimally invasive and invasive liver surgery based on augmented reality training: a review of the literature.

A liver surgeon's knowledge of anatomy is critical. Due to the patient's small field of vision, patient specific, complex nerve system, and other factors, even a minor loss can result in irreversible damage. Surgeons could benefit from the use of augmented reality (AR) technology, which would bring three-dimensional image data into the operating room. AR visualization can improve surgical procedures, facilitate intraoperative planning, and enhance surgical guidance for the anatomy of interest, all of which contribute to the application's minimal invasiveness. This literature review on image guidance in liver surgery provides the reader with information about AR techniques. To ascertain the current state of Augmented reality technology's application in liver surgery, a PubMed and Embase search were conducted using the following keywords: < (Augmented reality) AND (liver surgery) > and < 'Augmented reality' AND 'liver surgery' > (publication date from January 1991 until Jun 2022). The query yielded a total of 205 publications-excluded papers in other languages, virtual reality (VR), and reviews leaving 135 studies for review. After removing duplication, the titles and abstracts of those studies were manually reviewed. Finally, 31 pertinent studies were determined to be pertinent to the subject. Generally, augmented reality technology includes preoperative planning and three-dimensional reconstruction, intraoperative three-dimensional navigation, and registration. Visualization may be aided by virtual three-dimensional reconstruction models of the liver from Computed Tomography/Magnetic Resonance Imaging scans. The results demonstrate that by utilizing augmented reality technology, blood vessels and tumor structures in the liver can be visualized during surgery, allowing for precise navigation during complicated surgical procedures. Augmented reality has been demonstrated to be safe and effective in both minimally invasive and invasive liver surgery. With recent advancements and significant effort by liver surgeons, augmented reality technologies have the potential to increase hepatobiliary surgical procedures dramatically. However, further clinical trials will be necessary to evaluate augmented reality as a tool for reducing post-operative morbidity and mortality. The impact of these cutting-edge computerized image guidance techniques on clinically relevant outcome parameters should be assessed in the future.

Efficacy of Sinopharm Vaccine Among Stem Cell Transplant Recipients During Two Peaks of Delta and Omicron variants of COVID-19.

BACKGROUND: Considering the dearth of research on the complications of Sinopharm coronavirus disease 2019 (COVID-19) vaccine in immunocompromised individuals and the lack of available data on COVID-19 vaccination from Iran. OBJECTIVE: This study aimed to investigate the efficacy of vaccine of Sinopharm COVID-19 vaccine and its complications in bone marrow transplant (BMT) recipients. METHODS: This was a retrospective cross-sectional study conducted on 250 patients with BMT who were referred to Montaserieh Hospital, Mashhad, Iran. Among them, 53 cases who received at least two doses of Sinopharm COVID-19 vaccine from March to January 2021 were entered in this study. The data were extracted from a student dissertation (Code:4000370). RESULTS: Sinopharm vaccine side effects were reported only in 7.7% of the patients, and shingles was the only serious side effect of the Sinopharm vaccine, which was observed only in one case. The results also revealed that Sinopharm COVID-19 vaccine side effects were not related to age or gender. Infection with the Delta variant of COVID-19 was reported in 7.5% (n=4) and no mortality was reported among them. Vaccine failure was reported in 39.6% of the cases; however, no mortality was reported among patients infected with the Omicron variant of COVID-19. CONCLUSION: In summary, it seems that Sinopharm COVID-19 vaccine adverse effects were not serious among stem cell transplant recipients. However, it may lead to some severe complications in the population. Vaccine failure against the Delta and Omicron variants of COVID-19 has been reported among more than one-third of BMT patients; however, no mortality was observed among BMT patients infected with the new variants of COVID-19.

Iranian Hydatid Disease Registry: Establishment and Implementation of a Neglected Tropical Disease Registry.

BACKGROUND: Cystic echinococcosis (CE) or hydatid disease is a global public health concern which imposes considerable economic costs on the communities in endemic regions. CE surveillance data are not adequately reliable. The present study reports the development and outcomes of a CE registry in Iran. METHODS: Hydatid Registry (HydatidReg) was initially established as a single-center registry in 2014 after the ethical approval of KMU. Following a call from MoHME to promote registry of different diseases and health outcomes, a call for participation was announced and all the Iranian Universities of Medical Sciences were requested to contribute to the registry. Subsequently, a nation-wide registry of hydatid disease was established in 2016. With a global perspective, HydatidReg joined the European Register of Cystic Echinococcosis (ERCE). A data collection form based on minimum dataset was designed and standard operating procedures (SOPs) were prepared to ensure standardized patient enrolment in the registry. A biobank system with two-dimensional barcoding was established along with HydatidReg for management and organization of biological specimens. RESULTS: As of March 2021, a total of 690 patients were enrolled in the registry. HydatidReg registered 362 (17.3%) out of the total 2097 patients enrolled in ERCE. Quality control (QC) of the data demonstrated 91.2% completeness and 80% timeliness. In the biobank, 322 biological specimens from 184 CE patients have been deposited including 70 blood, 96 sera and 156 parasite materials. CONCLUSION: High-quality data in the HydatidReg registry provided opportunities for health professionals to improve quality of care and organize meaningful research.

A meta-analysis of prognostic factors in patients with left-sided pancreatic cancer.

Background: Patients with ductal adenocarcinoma of the body and tail of the pancreas usually remain asymptomatic until late in the course of the disease, and the survival of such patients depends on multiple factors, which may affect the therapeutic approach and patient survival. Hence, the aim of this study was to investigate such risk factors by pooling various available studies. Methods: A systematic review was conducted according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines between January 1, 2007, and December 31, 2016, using the following databases: Medline, Scopus, the Cochrane Library, and Google Scholar. Studies were selected according to the predesigned eligibility criteria, and information was extracted for demographics, clinical features, and survival outcomes. Data were pooled using fixed- or random-effects models. Results: Sixteen studies were included (5,660 patients) with a median age of 64.8 years and a median survival of 28.5 (range 13-38) months. Identified significant factors for overall survival were higher age (hazard ratio [HR] = 1.211), men (HR = 1.182), presence of lymph node metastasis (HR = 1.964), multivisceral resection (HR = 1.947), N stage (1 versus 0; HR = 1.601), surgical margin (R0 versus No R0; HR = 0.519) and tumor size (>3 cm; HR = 1.890). Conclusion: The pooled results of this study revealed several risk factors for overall survival in patients with left-sided pancreatic cancer.

Association of a Genetic Variant in the Cyclin-Dependent Kinase Inhibitor 2B with Risk of Pancreatic Cancer.

Background: Pancreatic cancer (PC) is among the most aggressive tumors with a poor prognosis, indicating the need for the identification of a novel prognostic biomarker for risk stratifications. Recent genome-wide association studies have demonstrated common genetic variants in a region on chromosome 9p21 associated with an increased risk of different malignancies. Methods: In the present study, we explore the possible relationship between genetic variant, rs10811661, and gene expression of CDKN2B in 75 pancreatic cancer patients, and 188 healthy individuals. DNAs were extracted and genotyping and gene expression were performed by TaqMan real-time PCR and RT-PCR, respectively. Logistic regression was used to assess the association between risk and genotypes, while the significant prognostic variables in the univariate analysis were included in multivariate analyses. Results: The patients with PDAC had a higher frequency of a TT genotype for rs10811661 than the control group. Also, PDAC patients with dominant genetic model, (TT + TC), was associated with increased risk of developing PDAC (OR= 14.71, 95% CI [1.96-110.35], p= 0.009). Moreover, patients with CC genotype had a higher expression of CDKN2B, in comparison with TT genotype. Conclusion: Our findings demonstrated that CDKN2A/B was associated with the risk of developing PDAC, supporting further investigations in the larger and multicenter setting to validate the potential value of this gene as an emerging marker for PDAC.

The Therapeutic Potential of Targeting Key Signaling Pathways as a Novel Approach to Ameliorating Post-Surgical Adhesions.

BACKGROUND: Peritoneal adhesions (PA) are a common complication of abdominal operations. A growing body of evidence shows that inhibition of inflammation and fibrosis at sites of peritoneal damaging could prevent the development of intra-abdominal adhesions. METHODS: A search of PubMed, Medline, CINAHL and Embase databases was performed using the keywords 'postsurgical adhesion', 'post-operative adhesion', 'peritoneal adhesion', 'surgery-induced adhesion' and 'abdominal adhesion'. Studies detailing the use of pharmacological and non-pharmacological agents for peritoneal adhesion prevention were identified, and their bibliographies were thoroughly reviewed to identify further related articles. RESULTS: Several signaling pathways, such as tumor necrosis factor-alpha, tissue plasminogen activator, and type 1 plasminogen activator inhibitor, macrophages, fibroblasts, and mesothelial cells play a key part in the development of plasminogen activator. Several therapeutic approaches based on anti-PA drug barriers and traditional herbal medicines have been developed to prevent and treat adhesion formation. In recent years, the most promising method to prevent PA is treatment using biomaterial-based barriers. CONCLUSION: In this review, we provide an overview of the pathophysiology of adhesion formation and various agents targeting different pathways, including chemical agents, herbal agents, physical barriers, and clinical trials concerning this matter.

The Therapeutic Potential of Targeting the Angiotensin Pathway as a Novel Therapeutic Approach to Ameliorating Post-surgical Adhesions.

BACKGROUND: Post-surgical adhesion is a common complication after abdominal or pelvic surgeries. Despite improvements in surgical techniques or the application of physical barriers, few improvements have been achieved. It causes bowel obstruction, pelvic pain, and infertility in women and has an adverse effect on the quality of life. Renin-Angiotensin System (RAS) is traditionally considered a blood pressure regulator. However, recent studies have indicated that the RAS plays a vital role in other processes, including oxidative stress, fibrosis, proliferation, inflammation, and wound healing. Angiotensin II (Ang II) is the main upstream effector of the RAS that can bind to the AT1 receptor (ATIR). A growing body of evidence has revealed that targeting Angiotensin-Converting Enzyme Inhibitors (ACEIs), Angiotensin II type 1 Receptor Blockers (ARBs), and Direct Renin Inhibitors (DRIs) can prevent post-surgical adhesions. Here we provide an overview of the therapeutic effect of RAS antagonists for adhesion. METHODS: PubMed, EMBASE, and the Cochrane library were reviewed to identify potential agents targeting the RAS system as a potential approach for post-surgical adhesion. RESULTS: Available evidence suggests the involvement of the RAS signaling pathway in inflammation, proliferation, and fibrosis pathways as well as in post-surgical adhesions. Several FDA-approved drugs are used for targeting the RAS system, and some of them are being tested in different models to reduce fibrosis and improve adhesion after surgery, including telmisartan, valsartan, and enalapril. CONCLUSION: Identification of the pathological causes of post-surgical adhesion and the potential role of targeting the Renin-Angiotensin System may help to prevent this problem. Based on the pathological function of RAS signaling after surgeries, the administration of ARBs may be considered a novel and efficient approach to prevent postsurgical adhesions. Pre-clinical and clinical studies should be carried out to have better information on the clinical significance of this therapy against post-surgical adhesion formation.

Allogeneic tumor cell line-based vaccines: A good alternative to autologous and cancer stem cell vaccines in colorectal cancer.

OBJECTIVES: Besides the uncertainty about colorectal cancer stem cell (CCSC) markers, isolating, purifying, and enriching CCSCs to produce CCSC vaccines is highly challenging. However, allogeneic vaccines developed from CRC cell lines can provide universal, comprehensive, inexpensive, simple, and fast approach to cancer treatment. MATERIALS AND METHODS: CCSCs were isolated from human CRC tissue using the in vitro sphere formation assay and then characterized through gene expression analysis, in vivo and in vitro tumor formation assay, karyotyping, and surface marker detection. Subsequently, CCSCs and two CRC cell lines (HT-29 and SW-480) were inactivated with cisplatin (CDDP) and administrated as vaccines to the three groups of athymic C57BL/6 nude mice. Afterward, tumorigenesis was challenged with HT-29 cells. The antitumor effect of vaccines was evaluated by tumor and spleen examination and immune response analysis. The cytotoxic activity of splenocytes and serum levels of TGF-ß and IFN-γ were measured by Calcein-AM cytotoxicity assay and enzyme-linked immunosorbent assay (ELISA), respectively. RESULTS: The results of gene expression analysis showed that CCSCs are CD44+CD133-LGR5-. All vaccinations resulted in decreased tumor growth, spleen enlargement, enhanced serum level of IFN-γ and TGF-ß, and increased cytotoxic activity of natural killer (NK) cells. The antitumor efficacy of the CCSC vaccine was not more than CRC cell line-based vaccines. Interestingly, the allogeneic SW-480 vaccine could effectively inhibit tumorigenesis. CONCLUSION: Despite the great challenge in developing CCSC vaccines, allogeneic vaccines based on CRC cell lines can efficiently induce antitumor immunity in CRC.

Solid Pseudopapillary Neoplasms Are Rare, Indolent Pancreatic Tumors in Young Women.

Introduction. Solid pseudopapillary neoplasm (SPN) is a rare and indolent pancreatic tumor with low malignant potential which frequently occurs in reproductive-age females. Complete resection is almost always the curative option. Case Presentation. We present a 20-year-old woman with acute epigastric pain and vomiting in multiple episodes. Abdominal ultrasound showed a hypoechoic lesion with the probable source in the pancreas. Following that, CT scans and Endoscopic Ultrasound (EUS) manifested a 9 × 7.5 cm-sized hypodense mass with heterogeneous well-defined margins in the pancreas suggesting the diagnosis of SPN. Whipple's procedure was performed. Histopathological examination and immunohistochemistry confirmed SPN without evidence of malignancy. Discussion. SPN is known as a tumor with a favorable prognosis and a long survival rate after complete resection. However, some literature focused on minimally invasive surgery as an alternative surgical approach.

The accuracy of sentinel node biopsy by 99mTc-sodium phytate in patients with pancreatic cancer.

BACKGROUNDS/AIMS: Pancreaticoduodenectomy is the only potentially curative treatment for pancreatic cancer. The identification of the first nodal drainage site (sentinel node) may improve the detection of metastatic nodes and can contribute to a less invasive surgery. We aimed to determine the accuracy of sentinel node mapping in patients with pancreatic cancer using intraoperative radiotracer injection technique. METHODS: At surgical exposure, peritumoral injection of 0.4-0.5 mci/0.5 ml of 99mTc- sodium phytate was performed. After tumor resection, sentinel nodes were investigated in the most common areas using a hand-held gamma probe. Any lymph node with in vivo count twice the background was considered as sentinel node, thus, it was removed and sent for pathological assessment. Then a standard lymph node dissection was performed for all patients. RESULTS: Fourteen patients with cancer in the head of the pancreas were included in this study. Overall, 180 lymph nodes were harvested with a mean of 11.6±4.7 lymph nodes per patient. In eight patients, at least one sentinel node could be identified (detection rate about 64%). False negative rate of the study was 3/5 (60%). CONCLUSIONS: Our study revealed insufficient diagnostic accuracy and high false negative rate for sentinel lymph node mapping with 99mTc- sodium phytate in pancreatic cancer.