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  • 1.
    Anlauf, Martin
    et al.
    Department of Pathology, University of Kiel, Germany.
    Garbrecht, Nele
    Department of Pathology, University of Kiel, Germany.
    Henopp, Tobias
    Department of Pathology, University of Kiel, Germany.
    Schmitt, Anja
    Department of Pathology, University of Zürich, Switzerland.
    Schlenger, Regina
    Department of Pathology and Department of Forensic Medicine, University of Kiel, Germany.
    Raffel, Andreas
    Department of General, Visceral and Pediatric Surgery, University of Düsseldorf, Germany.
    Krausch, Markus
    Department of General, Visceral and Pediatric Surgery, University of Düsseldorf, Germany.
    Gimm, Oliver
    Department of General and Visceral Surgery, University of Halle-Wittenberg, Germany.
    Eisenberger, Claus F
    Department of General, Visceral and Pediatric Surgery, University of Düsseldorf, Germany.
    Knoefel, Wolfram T
    Department of General, Visceral and Pediatric Surgery, University of Düsseldorf, Germany.
    Dralle, Henning
    Department of General and Visceral Surgery, University of Halle-Wittenberg, Germany.
    Komminoth, Paul
    Department of Pathology, University of Zürich, Switzerland / Department of Pathology, Kantonsspital Baden, Switzerland.
    Heitz, Philipp U
    Department of Pathology, University of Zürich, Switzerland.
    Perren, Aurel
    Department of Pathology, University of Zürich, Switzerland.
    Klöppel, Gunter
    Department of Pathology, University of Kiel, Germany.
    Sporadic versus hereditary gastrinomas of the duodenum and pancreas: distinct clinico-pathological and epidemiological features.2006In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 12, no 34, p. 5440-6Article in journal (Refereed)
    Abstract [en]

    Gastrinomas are defined as gastrin secreting tumors that are associated with Zollinger-Ellison syndrome (ZES). ZES is characterized by elevated fasting gastrin serum levels, positive secretin stimulation test and clinical symptoms such as recurrent peptic ulcer disease, gastroesophageal reflux disease and occasional diarrhea. Genetically, nonhereditary (sporadic) gastrinomas are distinguished from hereditary gastrinomas, which are associated with multiple endocrine neoplasia type 1 (MEN1) syndrome. In general, duodenal gastrinomas are small and solitary if they are sporadic and multiple as well as hereditary. The sporadic gastrinomas occur in the duodenum or in the pancreas while the hereditary gastrinomas almost all occur in the duodenum. Our series of 77 sporadic duodenal neuroendocrine tumors (NETs) includes 18 patients (23.4%) with gastrinomas and ZES. Of 535 sporadic NETs in the pancreas collected from the NET archives of the departments of pathology in Zurich, Switzerland, and Kiel, Germany, 24 patients (4.5%) suffered from sporadic pancreatic gastrinomas and ZES. These NETs have to be distinguished from tumors with immunohistochemical positivity for gastrin but without evidence of ZES. An additional 19 patients suffered from MEN1 and ZES. These patients showed exclusively duodenal gastrinomas, but not pancreatic gastrinomas. The prognosis of sporadic and MEN1-associated duodenal gastrinomas is better than that of pancreatic gastrinomas, since they progress slowly to liver metastasis. In summary, sporadic and MEN1-associated gastrinomas in the duodenum and pancreas show different clinico-pathological and genetic features. The incidence of sporadic duodenal gastrin-producing tumors is increasing, possibly due to optimized diagnostic procedures. In contrast, pancreatic MEN1-associated gastrinomas seem to be extremely rare. A considerable subset of tumors with immunohistochemical expression of gastrin but without evidence of ZES should be designated as functionally inactive NETs expressing gastrin, but not as gastrinomas.

  • 2.
    Björnsson, Bergthor
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Bojmar, Linda
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Olsson, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Sundqvist, Tommy
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Sandström, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Nitrite, a novel method to decrease ischemia/reperfusion injury in the rat liver2015In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 21, no 6, p. 1775-1783Article in journal (Refereed)
    Abstract [en]

    AIM: To investigate whether nitrite administered prior to ischemia/reperfusion (I/R) reduces liver injury.

    METHODS: Thirty-six male Sprague-Dawley rats were randomized to 3 groups, including sham operated (n = 8), 45-min segmental ischemia of the left liver lobe (IR, n = 14) and ischemia/reperfusion (I/R) preceded by the administration of 480 nmol of nitrite (n = 14). Serum transaminases were measured after 4 h of reperfusion. Liver microdialysate (MD) was sampled in 30-min intervals and analyzed for glucose, lactate, pyruvate and glycerol as well as the total nitrite and nitrate (NOx). The NOx was measured in serum.

    RESULTS: Aspartate aminotransferase (AST) at the end of reperfusion was higher in the IR group than in the nitrite group (40 ± 6.8 μkat/L vs 22 ± 2.6 μkat/L, P = 0.022). Similarly, alanine aminotransferase (ALT) was also higher in the I/R group than in the nitrite group (34 ± 6 μkat vs 14 ± 1.5 μkat, P = 0.0045). The NOx in MD was significantly higher in the nitrite group than in the I/R group (10.1 ± 2.9 μM vs 3.2 ± 0.9 μM, P = 0.031) after the administration of nitrite. During ischemia, the levels decreased in both groups and then increased again during reperfusion. At the end of reperfusion, there was a tendency towards a higher NOx in the I/R group than in the nitrite group (11.6 ± 0.7 μM vs 9.2 ± 1.1 μM, P = 0.067). Lactate in MD was significantly higher in the IR group than in the nitrite group (3.37 ± 0.18 mM vs 2.8 ± 0.12 mM, P = 0.01) during ischemia and the first 30 min of reperfusion. During the same period, glycerol was also higher in the IRI group than in the nitrite group (464 ± 38 μM vs 367 ± 31 μM, P = 0.049). With respect to histology, there were more signs of tissue damage in the I/R group than in the nitrite group, and 29% of the animals in the I/R group exhibited necrosis compared with none in the nitrite group. Inducible nitric oxide synthase (iNOS) transcription increased between early ischemia (t = 15) and the end of reperfusion in both groups.

    CONCLUSION: Nitrite administered before liver ischemia in the rat liver reduces anaerobic metabolism and cell necrosis, which could be important in the clinical setting.

  • 3.
    Björnsson, Bergthor
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Sandström, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Laparoscopic distal pancreatectomy for adenocarcinoma of the pancreas2014In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 20, no 37, p. 13402-13411Article in journal (Refereed)
    Abstract [en]

    Since the first report on laparoscopic distal pancreatectomy (LDP) appeared in the 1990s, the procedure has been performed increasingly frequently to treat both benign and malignant lesions of the pancreas. Many earlier publications have shown LDP to be a good alternative to open distal pancreatectomy for benign lesions, although this has never been studied in a prospective, randomized manner. The evidence for the use of LDP to treat adenocarcinoma of the pancreas is not as well established. The purpose of this review is to evaluate the current evidence for LDP in cases of pancreatic adenocarcinoma. We conducted a review of English language publications reporting LDP results between 1990 and 2013. All studies reporting results in patients with histologically proven pancreatic adenocarcinoma were included. Thirty-nine publications were found and included in the results for a total of 309 cases of pancreatic adenocarcinoma (potential double publications were not eliminated). Most LDP procedures are performed in selected cases and generally involve smaller tumors than open distal pancreatectomy (ODP) procedures. Some of the papers report unselected cases and include procedures on larger tumors. The number of lymph nodes harvested using LDP is comparable to the number obtained with ODP, as is the frequency of R0 resections. Current data suggest that similar short term oncological results can be obtained using LDP as those obtained using ODP.

  • 4.
    Björnsson, Bergthor
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Winbladh, Anders
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Bojmar, Linda
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Sundqvist, Tommy
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Gullstrand, Per
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Sandström, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Conventional, but not remote ischemic preconditioning, reduces iNOS transcription in liver ischemia/reperfusion2014In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 20, no 28, p. 9506-9512Article in journal (Refereed)
    Abstract [en]

    AIM: To study the effects of preconditioning on inducible nitric oxide synthase (iNOS) and interleukin 1 (IL-1) receptor transcription in rat liver ischemia/reperfusion injury (IRI). METHODS: Seventy-two male rats were randomized into 3 groups: the one-hour segmental ischemia (IRI, n = 24) group, the ischemic preconditioning (IPC, n = 24) group or the remote ischemic preconditioning (R-IPC, n = 24) group. The IPC and R-IPC were performed as 10 min of ischemia and 10 min of reperfusion. The iNOS and the IL-1 receptor mRNA in the liver tissue was analyzed with real time PCR. The total Nitrite and Nitrate (NOx) in continuously sampled microdialysate (MD) from the liver was analyzed. In addition, the NOx levels in the serum were analyzed. RESULTS: After 4 h of reperfusion, the iNOS mRNA was significantly higher in the R-IPC (Delta Ct: 3.44 +/- 0.57) group than in the IPC (Delta Ct: 5.86 +/- 0.82) group (P = 0.025). The IL-1 receptor transcription activity was reduced in the IPC group (Delta Ct: 1.88 +/- 0.53 to 4.81 +/- 0.21), but not in the R-IPC group, during reperfusion (P = 0.027). In the MD, a significant drop in the NOx levels was noted in the R-IPC group (12.3 +/- 2.2 to 4.7 +/- 1.2 mu mol/L) at the end of ischemia compared with the levels in early ischemia (P = 0.008). A similar trend was observed in the IPC group (11.8 +/- 2.1 to 6.4 +/- 1.5 mu mol/L), although this difference was not statistically significant. The levels of NOx rose quickly during reperfusion in both groups. CONCLUSION: IPC, but not R-IPC, reduces iNOS and IL-1 receptor transcription during early reperfusion, indicating a lower inflammatory reaction. NOx is consumed in the ischemic liver lobe.

  • 5.
    Daferera, Niki
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Kumar Kumawat, Ashok
    University of Örebro, Sweden.
    Hultgren-Hornquist, Elisabeth
    University of Örebro, Sweden.
    Ignatova, Simone
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Ström, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology. Linköping University, Faculty of Medicine and Health Sciences.
    Münch, Andreas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Fecal stream diversion and mucosal cytokine levels in collagenous colitis: A case report2015In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 21, no 19, p. 6065-6071Article in journal (Refereed)
    Abstract [en]

    In this case report, we examined the levels of cytokines expressed before and during fecal stream diversion and after intestinal continuity was restored in a patient with collagenous colitis. We report the case of a 46-year-old woman with chronic, active collagenous colitis who either failed to achieve clinical remission or experienced adverse effects with the following drugs: loperamide, cholestyramine, budesonide, methotrexate and adalimumab. Due to the intractable nature of the disease and because the patient was having up to 15 watery bowel movements per day, she underwent a temporary ileostomy. Colonic biopsies were analyzed for mucosal cytokine protein levels before and during fecal stream diversion and after intestinal continuity was restored. Mucosal protein levels of interleukin (IL)-1 beta, IL-2, IL-6, IL-12, IL-17 A, IL-23, TNF, IFN-gamma, IL-4, IL-5, IL-10 and IL-13 were all higher during active disease and decreased to non-detectable or considerably lower levels during fecal stream diversion. One month after the restoration of bowel continuity, when the patient experienced a relapse of symptoms, IL-2, IL-23 and IL-21 levels were again increased. Our results indicate that fecal stream diversion in this patient suppressed the levels of all cytokines analyzed in colonic biopsies. With the recurrence of clinical symptoms and histological changes after bowel reconstruction, the levels of primarily proinflammatory cytokines increased. Our findings support the hypothesis that a luminal factor triggers the inflammation observed in collagenous colitis.

  • 6.
    Franzen, Thomas
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping.
    Tibbling, Lita
    Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping.
    Is the severity of gastroesophageal reflux dependent on hiatus hernia size?2014In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 20, no 6, p. 1582-1584Article in journal (Refereed)
    Abstract [en]

    AIM:

    To determine if the severity of gastroesophageal reflux disease is dependent on the size of a hiatus hernia.

    METHODS:

    Seventy-five patients with either a small (n = 25), medium (n = 25) or large (n = 25) hiatus hernia (assessed by high resolution esophageal manometry) were investigated using 24-h esophageal monitoring and a self-assessed symptom questionnaire. The questionnaire comprised the following items, each graded from 0 to 3 according to severity: heartburn; pharyngeal burning sensation; acid regurgitation; and chest pain.

    RESULTS:

    The percentage total reflux time was significantly longer in the group with hernia of 5 cm or more compared with the group with a hernia of < 3 cm (P < 0.002), and the group with a hernia of 3 to < 5 cm (P < 0.04). Pharyngeal burning sensation, heartburn and acid regurgitation were more common with large hernias than small hernias, but the frequency of chest pain was similar in all three hernia groups.

    CONCLUSION:

    Patients with a large hiatus hernia are more prone to have pathological gastroesophageal reflux and to have more acid symptoms than patients with a small hiatus hernia. However, it is unlikely that patients with an absence of acid symptoms will have pathological reflux regardless of hernia size.

  • 7.
    Fägerstam, Patrik
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Pharmacology.
    Whiss, Per A
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Pharmacology.
    Higher platelet P-selectin in male patients with inflammatory bowel disease compared to healthy males2006In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 12, no 8, p. 1270-1272Article in journal (Refereed)
    Abstract [en]

    Aim: To observe if the total amount of platelet P-selectin (tP-selectin) in patients with inflammatory bowel disease (IBD) was related to disease entity or activity, 5-aminosalicylic acid (5-ASA) medication or gender. Methods: tP-selectin was measured by immunoassay in seventeen IBD patients and twelve healthy controls. Results: Compared to controls, there was no difference of tP-selectin in patients related to disease entity or activity and 5-ASA medication. When the groups were split according to gender the male patient group showed higher levels of tP-selectin compared to male controls (153 ng/mL vs 94 ng/mL, P<0.05). Conclusion: Increased tP-selectin levels may alter the inflammatory response and susceptibility to thromboembolic disease. As previously shown with soluble P-selectin, tP-selectin shows gender dependent differences important to consider in future studies. © 2006 The WJG Press. All rights reserved.

  • 8.
    Hagg, Mary
    et al.
    Hudiksvall Hospital, Sweden; Uppsala University, Sweden.
    Tibbling, Lita
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Franzen, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping.
    Esophageal dysphagia and reflux symptoms before and after oral IQoro(R) training2015In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 21, no 24, p. 7558-7562Article in journal (Refereed)
    Abstract [en]

    AIM: To examine whether muscle training with an oral IQoro(R) screen (IQS) improves esophageal dysphagia and reflux symptoms. METHODS: A total of 43 adult patients (21 women and 22 men) were consecutively referred to a swallowing center for the treatment and investigation of long-lasting nonstenotic esophageal dysphagia. Hiatal hernia was confirmed by radiologic examination in 21 patients before enrollment in the study (group A; median age 52 years, range: 19-85 years). No hiatal hernia was detected by radiologic examination in the remaining 22 patients (group B; median age 57 years, range: 22-85 years). Before and after training with an oral IQS for 6-8 mo, the patients were evaluated using a symptom questionnaire (esophageal dysphagia and acid chest symptoms; score 0-3), visual analogue scale (ability to swallow food: score 0-100), lip force test (greater than= 15 N), velopharyngeal closure test (greater than= 10 s), orofacial motor tests, and an oral sensory test. Another twelve patients (median age 53 years, range: 22-68 years) with hiatal hernia were evaluated using oral IQS traction maneuvers with pressure recordings of the upper esophageal sphincter and hiatus canal as assessed by high-resolution manometry. RESULTS: Esophageal dysphagia was present in all 43 patients at entry, and 98% of patients showed improvement after IQS training [mean score (range): 2.5 (1-3) vs 0.9 (0-2), P less than 0.001]. Symptoms of reflux were reported before training in 86% of the patients who showed improvement at follow-up [1.7 (0-3) vs 0.5 (0-2), P less than 0.001). The visual analogue scale scores were classified as pathologic in all 43 patients, and 100% showed improvement after IQS training [71 (30-100) vs 22 (0-50), P less than 0.001]. No significant difference in symptom frequency was found between groups A and B before or after IQS training. The lip force test [31 N (12-80 N) vs 54 N (27-116), P less than 0.001] and velopharyngeal closure test values [28 s (5-74 s) vs 34 s (13-80 s), P less than 0.001] were significantly higher after IQS training. The oral IQS traction results showed an increase in mean pressure in the diaphragmatic hiatus region from 0 mmHg at rest (range: 0-0 mmHG) to 65 mmHg (range: 20-100 mmHg). CONCLUSION: Oral IQS training can relieve/improve esophageal dysphagia and reflux symptoms in adults, likely due to improved hiatal competence.

  • 9.
    Hasselgren, Kristina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Sandström, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Björnsson, Bergthor
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Role of associating liver partition and portal vein ligation for staged hepatectomy in colorectal liver metastases: A review2015In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 21, no 15, p. 4491-4498Article, review/survey (Refereed)
    Abstract [en]

    Colorectal cancer is the third most common cancer in the Western world. Approximately half of patients will develop liver metastases, which is the most common cause of death. The only potentially curative treatment is surgical resection. However, many patients retain a to small future liver remnant (FLR) to allow for resection directly. There are therefore strategies to decrease the tumor with neoadjuvant chemotherapy and to increase the FLR. An accepted strategy to increase the FLR is portal vein occlusion (PVO). A concern with this strategy is that a large proportion of patients will never be operated because of progression during the interval between PVO and resection. ALPPS (associating liver partition and portal vein ligation for staged hepatectomy) is a new procedure with a high resection rate. A concern with this approach is the rather high frequency of complications and high mortality, compared to PVO. In this review, it is shown that with ALPPS the resection rate was 97.1% for CRLM and the mortality rate for all diagnoses was 9.6%. The mortality rate was likely lower for patients with CRLM, but some data were lacking in the reports. Due to the novelty of ALPPS, the indications and technique are not yet established but there are arguments for ALPPS in the context of CRLM and a small FLR.

  • 10.
    He, Lu-Jun
    et al.
    Hebei Medical University, Shijiazhuang, China..
    Yu, Yue-Ming
    Hospital of Hebei Medical University.
    Qiao, Fang
    Hebei Province Blood Center.
    Liu, Jing-Shan
    Hebei Province Blood Center.
    Sun, Xiao-Feng
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Jiang, Ling-Ling
    Hebei Medical University.
    Genetic polymorphisms of N-acetyltransferase 2 and colorectal cancer risk.2005In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 11, no 27, p. 4268-4271Article in journal (Refereed)
    Abstract [en]

    AIM: To identify the distribution of N-acetyltrasferase 2(NAT2) polymorphism in Hebei Han Chinese and the effects of the polymorphism on the development of colorectal cancer. METHODS: We performed a hospital-based case-control study of 237 healthy individuals and 83 colorectal cancer patients of Hebei Han Chinese. DNA was extracted from peripheral blood and cancer tissues. The genotypes of the polymorphisms were assessed by PCR-restriction fragment length polymorphism (RFLP). RESULTS: There were four NAT2 alleles of WT, M1, M2, and M3 both in the healthy subjects and in the patients, and 10 genotypes of WT/WT, WT/M1, WT/M2, WT/M3, M1/M1, M1/M2, M1/M3, M2/M2, M2/M3, M3/M3. M2 allele was present in 15.61% of healthy subjects and 29.52% of patients (chi(2) = 15.31, P<0.0001), and M3 allele was present in 30.59% of healthy subjects and 16.87% of patients (chi(2) = 25.33, P<0.0001). There were more WT/M2 (chi(2) = 34.42, P<0.0001, odd ratio = 4.99, 95%CI = 2.27-9.38) and less WT/M3 (chi(2) = 3.80, P = 0.03) in the patients than in the healthy subjects. In 70.3% of the patients, there was a difference in NAT2 genotype between their tumors and blood cells. Patients had more WT/M2 (chi(2) = 5.11, P = 0.02) and less M2/M3 (chi(2) = 4.27, P = 0.039) in their blood cells than in the tumors. Furthermore, 53.8% (7/13) of M2/M3 in tumors were from WT/M2 of blood cells. CONCLUSION: There is a possible relationship between the NAT2 polymorphisms and colorectal cancer in Hebei Han Chinese. The genotype WT/M2 may be a risk factor for colorectal cancer.

  • 11. Meng, Wen-Jian
    et al.
    Wang, Ling
    Tian, Chao
    Yu, Yong-Yang
    Zhou, Beng
    Gu, Yun
    Xia, Qing-Jie
    Sun, Xiao-Feng
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Li, Yuan
    Wang, Rong
    Zheng, Xue-Lian
    Zhou, Zong-Guang
    Novel mutations and sequence variants in exons 3-9 of human T Cell Factor-4 gene in sporadic rectal cancer patients stratified by microsatellite instability2007In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 13, no 27, p. 3747-3751Article in journal (Refereed)
    Abstract [en]

    Aim: To establish the role of human T Cell Factor-4 (hTCF-4) gene exons 3-9 mutation status in association with sporadic rectal cancer with microsatellite instability (MSI). Methods: Microsatellite markers were genotyped in 93 sporadic rectal cancer patients. Eleven cases were found to be high-frequency MSI (MSI-H). Sequence analysis of the coding region of the exons 3-9 of hTCF-4 gene was carried out for the 11 MSI-H cases and 10 controls (5 microsatellite stability (MSS) cases and 5 cases with normal mucosa). The sequencing and MSI identification were used. Results: Several novel mutations and variants were revealed. In exon 4, one is a 4-position continuous alteration which caused amino acid change from Q131T and S132I (391insA, 392 G > A, 393 A > G and 395delC) and another nucleotide deletion (395delC) is present in MSI-H cases (5/10 and 4/10, respectively) but completely absent in the controls. Conclusion: Novel mutations in exon 4 of hTCF-4 gene were revealed in this study, which might be of importance in the pathogenesis of sporadic rectal cancer patients with MSI-H. © 2007 WJG. All rights reserved.

  • 12.
    Monstein, Hans-Jurg
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Molecular Biological Techniques.
    Grahn, Niclas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Truedsson, Mikael
    Ohlsson, Bodil
    Progastrin-releasing peptide and gastrin-releasing peptide receptor mRNA expression in non-tumor tissues of the human gastrointestinal tract2006In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 12, no 16, p. 2574-2578Article in journal (Refereed)
    Abstract [en]

    Aim: To investigate the expression of gastrin-releasing peptide (GRP) and GRP-receptor mRNA in non-tumor tissues of the human esophagus, gastrointestinal tract, pancreas and gallbladder using molecular biology techniques. Methods: Poly A+ mRNA was isolated from total RNA extracts using an automated nucleic acid extractor and, subsequently, converted into single-stranded cDNA (ss-cDNA). PCR amplifications were carried out using gene-specific GRP and GRP-receptor primers. The specificity of the PCR amplicons was further confirmed by Southern blot analyses using gene-specific GRP and GRP-receptor hybridization probes. Results: Expre ssion of GRP and GRP-receptor mRNA was detected at various levels in nearly all segments of the non-tumor specimens analysed, except the gallbladder. In most of the biopsy specimens, co-expression of both GRP and GRP-receptor mRNA appeared to take place. However, expression of GRP mRNA was more prominent than was GRP-receptor mRNA. Conclusion: GRP and GRP-receptor mRNAs are expressed throughout the gastrointestinal tract and provides information for the future mapping and determination of its physiological importance in normal and tumor cells. © 2006 The WJG Press. All rights reserved.

  • 13.
    Rejler, Martin
    et al.
    Highland Hospital, Eksjö, Sweden.
    Tholstrup, Jörgen
    Highland Hospital, Eksjö, Sweden.
    Elg, Mattias
    Linköping University, Department of Management and Engineering, Quality Technology and Management. Linköping University, The Institute of Technology.
    Spångéus, Anna
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology.
    Andersson Gäre, Boel
    Jonköping University, Sweden.
    Framework for assessing quality of care for inflammatory bowel disease in Sweden2012In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 18, no 10, p. 1085-1092Article in journal (Refereed)
    Abstract [en]

    AIM: To create and apply a framework for quality assessment and improvement in care for inflammatory bowel disease (IBD) patients. less thanbrgreater than less thanbrgreater thanMETHODS A framework for quality assessment and improvement was created for IBD based on two generally acknowledged quality models. The model of Donabedian (Df) offers a logistical and productive perspective and the Clinical Value Compass (CVC) model adds a management and service perspective. The framework creates a pedagogical tool to understand the balance between the dimensions of clinical care (CVC) and the components of clinical outcome (Df). The merged models create a framework of the care process dimensions as a whole, reflecting important parts of the IBD care delivery system in a local setting. Clinical and organizational quality measures were adopted from clinical experience and the literature and were integrated into the framework. Data were collected at the yearly check-up for 481 IBD patients during 2008. The application of the quality assessment framework was tested and evaluated in a local clinical IBD care setting in Jonkoping County, Sweden. less thanbrgreater than less thanbrgreater thanRESULTS: The main outcome was the presentation of how locally-selected clinical quality measures, integrated into two complementary models to develop a framework, could be instrumental in assessing the quality of care delivered to patients with IBD. The selected quality measures of the framework noted less anemia in the population than previously reported, provided information about hospitalization rates and the few surgical procedures reported, and noted good access to the clinic. less thanbrgreater than less thanbrgreater thanCONCLUSION: The applied local quality framework was feasible and useful for assessing the quality of care delivered to IBD patients in a local setting.

  • 14.
    Rudholm, Tobias
    et al.
    Karolinska Institute.
    Hellstrom, Per Mikael
    Karolinska Institute.
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Campbell, Colin Allan
    GlaxoSmithKline Inc.
    McLean, Peter Geoffrey
    GlaxoSmithKline Inc.
    Naslund, Erik
    Danderyd Hospital.
    Bravo capsule system optimizes intragastric pH monitoring over prolonged time: Effects of ghrelin on gastric acid and hormone secretion in the rat2008In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 14, no 40, p. 6180-6187Article in journal (Refereed)
    Abstract [en]

    Aim: To evaluate measurements of intragastric pH with the Bravo capsule system over a prolonged time.

    Methods: A Bravo capsule was placed inside the rat gastric body and pH was studied for periods up to five consecutive. days. For comparison, a gastric fistula model was used. Effects of ghrelin and esomeprazole, with or without pentagastrin, on gastric pH were studied. In addition, effects of esomeprazole on plasma ghrelin, gastrin and somatostatin were analyzed.

    Results: All rats recovered after surgery. The average 24-h pH during free feeding was 2.3 +/- 0.1 (n = 20) with a variation of 18% +/- 6% over 5 d. Ghrelin, 2400 pmol/kg, t.i.d. increased pH from 1.7 +/- 0.1 to 3.1 +/- 0.3 (P < 0.01) as recorded with the Bravo system. After esomeprazole (1 mg/kg, 3 mg/kg and 5 mg/kg) there was a dose-dependent pH increase of maximally 3.4 +/- 0.1, with day-to-day variation over the entire period of 8% +/- 3%. The fistula and pH studies generated similar results. Acid inhibition with esomeprazole increased plasma ghrelin from 10 +/- 2 pmol/L to 65 +/- 26 pmol/L (P < 0.001), and somatostatin from 10 +/- 2 pmol/L to 67 +/- 18 pmol/L (P < 0.001).

    Conclusion: pH measurements with the Bravo capsule are reliable, and comparable to those of the gastric fistula model. The Bravo system optimizes accurate intragastric pH monitoring over prolonged periods and allows both short- and long-term evaluation of effects of drugs and hormones.

  • 15.
    Slind Olsen, Renate
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Department Lab Med, Sweden.
    Nijm, Johnny
    Division of Medical Diagnostics, Department of Clinical Physiology, Region Jönköping County, Jönköping, Sweden.
    Andersson, Roland
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Department of Surgery, Region Jönköping County, Sweden.
    Dimberg, Jan
    Jonköping University, Sweden.
    Wågsäter, Dick
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Circulating inflammatory factors associated with worse long-term prognosis in colorectal cancer2017In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 23, no 34, p. 6212-6219Article in journal (Refereed)
    Abstract [en]

    AIM To investigate association of circulating inflammatory factors at the time of colorectal cancer (CRC) surgery with survival. METHODS Plasma levels from 174 CRC patients (69 females and 105 men), with median age 70 years (range 29-90), localized in the colon (n = 105) or rectum (n = 69), with stage. (n = 24), stage. (n = 54), stage. (n = 67) and stage. (n = 29) were measured using commercially available Bio-Plex Pro (TM) Human Chemokine Panel 40-Plex, including 40 different chemokines, cytokines and interleukins. The prognostic association of each inflammatory factor was analysed as CRC-specific and total mortality. RESULTS Out of 174 patients, 66 died during the follow-up, 40 because of CRC specific mortality. High tertile levels of 8 factors were significantly associated with increased CRC-specific mortality, of which CCL1, CCL20, CCL24, CX3CL1, IL-4 and TNF-alpha remained significant in a multivariate Cox regression analysis. High tertile levels of 14 factors were associated with increased total mortality, of which CCL1, CCL15, CCL20, CX3CL1, CXCL13, IFN-gamma, IL-2, IL-4 and IL-10 remained significant after adjustment for clinical covariates. For most of the inflammatory factors the association between higher tertile levels and an increased mortality in general appeared two years after surgery. High tertile levels of TNF-alpha and CCL24 were exclusively associated with CRC-specific mortality. The distribution of these factors were not associated with TNM stage with exception for CCL20. CONCLUSION High plasma levels of inflammatory factors are associated with increased risk of mortality among CRC patients and could be potential biomarkers for revealing prognosis.

  • 16.
    Soderman, Jan
    et al.
    Ryhov County Hospital, Sweden .
    Noren, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Ryhov County Hospital, Sweden.
    Christiansson, Malin
    Ryhov County Hospital, Sweden .
    Bragde, Hanna
    Ryhov County Hospital, Sweden .
    Thiebaut, Raphaele
    University of Paris Diderot, France University of Paris Diderot Sorbonne Paris Cite, France .
    Hugot, Jean-Pierre
    University of Paris Diderot, France University of Paris Diderot Sorbonne Paris Cite, France Hop Robert Debre, France .
    Tysk, Curt
    Örebro University, Sweden Örebro Uni, Sweden .
    OMorain, Colm A.
    Adelaide and Meath Hospital, Ireland Trinity Coll Dublin, Ireland .
    Gassull, Miquel
    Health Science Research Institute, Spain .
    Finkel, Yigael
    Sachs Childrens Hospital, Sweden .
    Colombel, Jean-Frederic
    Hop Calmette, France Icahn School Medical Mt Sinai, NY 10029 USA .
    Lemann, Marc
    Hop St Louis, France .
    Almer, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Gastroentorology.
    Analysis of single nucleotide polymorphisms in the region of CLDN2-MORC4 in relation to inflammatory bowel disease2013In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 19, no 30, p. 4935-4943Article in journal (Refereed)
    Abstract [en]

    AIM: To investigate a possible genetic influence of claudin (CLDN) 1, CLDN2 and CLDN4 in the etiology of inflammatory bowel disease. METHODS: Allelic association between genetic regions of CLDN1, CLDN2 or CLDN4 and patients with inflammatory bowel disease, Crohns disease (CD) or ulcerative colitis were investigated using both a case-control study approach (one case randomly selected from each of 191 Swedish inflammatory bowel disease families and 333 controls) and a family-based study (463 non-Swedish European inflammatory bowel disease-families). A nonsynonymous coding single nucleotide polymorphism in MORC4, located on the same linkage block as CLDN2, was investigated for association, as were two novel CLDN2 single nucleotide polymorphism markers, identified by resequencing. RESULTS: A single nucleotide polymorphism marker (rs12014762) located in the genetic region of CLDN2 was significantly associated to CD (case-control allelic OR = 1.98, 95% CI: 1.17-3.35, P = 0.007). MORC4 was present on the same linkage block as this CD marker. Using the case-control approach, a significant association (case control allelic OR = 1.61, 95% CI: 1.08-2.41, P = 0.018) was found between CD and a nonsynonymous coding single nucleotide polymorphism (rs6622126) in MORC4. The association between the CLDN2 marker and CD was not replicated in the family-based study. Ulcerative colitis was not associated to any of the single nucleotide polymorphism markers. CONCLUSION: These findings suggest that a variant of the CLDN2-MORC4 region predisposes to CD in a Swedish population.

  • 17.
    Sun, Xiao-Feng
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Ahmadi, Ahmad
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Arbman, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Wallin, Åsa
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology.
    Asklid, Daniel
    Zhang, Hong
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of dermatology and venereology.
    Polymorphisms in sulfotransferase 1A1 and glutathione S-transferase P1 genes in relation to colorectal cancer risk and patients' survival2005In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 11, no 43, p. 6875-6879Article in journal (Refereed)
    Abstract [en]

    Aim: To examine whether polymorphisms in SULT1A1 and GSTP1 genes contribute to colorectal cancer development and whether they are associated with clinicopathological variables are not well identified. Methods: We examined the genotypes of 125 colorectal cancer patients and 666 healthy controls in a Swedish population by using PCR restriction fragment length polymorphism (RFLP). Results: SULT1A1 *2/*2 genotype (OR = 2.49, 95%CI = 1.48-4.19, P = 0.0002) and *2 allele (OR = 1.56, 95%CI = 1.16-2.10, P = 0.002) had an effect on colorectal cancer susceptibility, while GSTP1 genotype was without effect. However, GSTP1 G-type predicted a worse prognosis in the patients independently of gender, age, Dukes' stage, growth pattern, and differentiation (P = 0.03). Conclusion: Polymorphism in SULT1A1 may predispose to colorectal cancer and GSTP1 may be a biological indicator of prognosis in the patients. © 2005 The WJG Press and Elsevier Inc. All rights reserved.

  • 18. Tian, Chao
    et al.
    Zhou, Zong-Guang
    Meng, Wen-Jian
    Sun, Xiao-Feng
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Yu, Yong-Yang
    Li, Li
    Luo, Hong-Zhi
    Yang, Lie
    Zhou, Bin
    Gu, Jun
    Overexpression of connective tissue growth factor WISP-1 in Chinese primary rectal cancer patients2007In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 13, no 28, p. 3878-3882Article in journal (Refereed)
    Abstract [en]

    Aim: To clarify the expression change of Wnt-induced secreted protein-1 (WISP-1) in human rectal cancer and to determine whether it is correlated with invasion and metastasis of human rectal cancer. Methods: Eighty-six paired samples of rectal cancer and surgically resected distant normal rectal tissue were collected and allocated into cancer group and control group respectively. WISP-1 mRNA was detected by relative quantitative real-time RT-PCR and WISP-1 protein was examined by immunohistochemical staining. Results: WISP-1 gene overexpression was found in 65% (56/86) primary rectal cancers, 2-30 times that of the level in normal matched rectal tissues (P = 0.001). The mRNA expression level was correlated with Duke's staging, histological differentiation grade and lymph node status. The WISP-1 protein expression was in accordance with mRNA expression level. The positive degree of immunohistochemical staining in the cancer group (1.40 ± 0.35) was different from that in control group (1.04 ± 0.08, P < 0.001). Moreover, in cancer group the positive staining degree in high-level mRNA cancers (1.46 ± 0.37, n = 56) was higher than that in low-level mRNA (1.28 ± 0.28, n = 30, P = 0.018). Conclusion: Aberrant levels of WISP-1 expression may play a role in rectal tumorigenesis. WISP-1 may be used as a specific clinical diagnosis and prognosis marker in rectal cancer. © 2007 WJG. All rights reserved.

  • 19.
    Tibbling, Lita
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences.
    Gezelius, Per
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences.
    Franzen, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Östergötland.
    Factors influencing lower esophageal sphincter relaxation after deglutition2011In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 17, no 23, p. 2844-2847Article in journal (Refereed)
    Abstract [en]

    AIM: To study the relationship between upper esophageal sphincter (UES) relaxation, peristaltic pressure and lower esophageal sphincter (LES) relaxation following deglutition in non-dysphagic subjects. METHODS: Ten non-dysphagic adult subjects had a high-resolution manometry probe passed transnasally and positioned to cover the UES, the esophageal body and the LES. Ten water swallows in each subject were analyzed for time lag between UES relaxation and LES relaxation, LES pressure at time of UES relaxation, duration of LES relaxation, the distance between the transition level (TL) and the LES, time in seconds that the peristaltic wave was before (negative value) or after the TL when the LES became relaxed, and the maximal peristaltic pressure in the body of the esophagus. RESULTS:Relaxation of the LES occurred on average 3.5 s after the bolus had passed the UES and in most cases when the peristaltic wave front had reached the TL. The LES remained relaxed until the peristaltic wave faded away above the LES. CONCLUSION: LES relaxation seemed to be caused by the peristaltic wave pushing the bolus from behind against the LES gate.

  • 20.
    Tsolakis, Apostolos V.
    et al.
    Uppsala University, Sweden.
    Grimelius, Lars
    Uppsala University, Sweden.
    Granerus, Göran
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Stridsberg, Mats
    Uppsala University, Sweden.
    Falkmer, Sture E.
    Ryhov County Hospital, Sweden.
    Janson, Eva T.
    Uppsala University, Sweden.
    Histidine decarboxylase and urinary methylimidazoleacetic acid in gastric neuroendocrine cells and tumours2015In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 21, no 47, p. 13240-13249Article in journal (Refereed)
    Abstract [en]

    AIM: To study histidine decarboxylase (HDC) expression in normal and neoplastic gastric neuroendocrine cells in relationship to the main histamine metabolite. METHODS: Control tissues from fundus (n = 3) and corpus (n = 3) mucosa of six patients undergoing operations for gastric adenocarcinoma, biopsy and/or gastric surgical specimens from 64 patients with primary gastric neuroendocrine tumours (GNETs), as well as metastases from 22 of these patients, were investigated using conventional immunohistochemistry and double immunofluorescence with commercial antibodies vs vesicular monoamine transporter 2 (VMAT-2), HDC and ghrelin. The urinary excretion of the main histamine metabolite methylimidazoleacetic acid (U-MeImAA) was determined using high-performance liquid chromatography in 27 of the 64 patients. RESULTS: In the gastric mucosa of the control tissues, co-localization studies identified neuroendocrine cells that showed immunoreactivity only to VMAT-2 and others with reactivity only to HDC. A third cell population co-expressed both antigens. There was no co-expression of HDC and ghrelin. Similar results were obtained in the foci of neuroendocrine cell hyperplasia associated with chronic atrophic gastritis type A and also in the tumours. The relative incidence of the three aforementioned markers varied in the tumours that were examined using conventional immunohistochemistry. All of these GNETs revealed both VMAT-2 and HDC immunoreactivity, and their metastases showed an immunohistochemical pattern and frequency similar to that of their primary tumours. In four patients, increased U-MeImAA excretion was detected, but only two of the patients exhibited related endocrine symptoms. CONCLUSION: Human enterochromaffin-like cells appear to partially co-express VMAT-2 and HDC. Co-expression of VMAT-2 and HDC might be required for increased histamine production in patients with GNETs.

  • 21.
    Yeganeh, Behzad
    et al.
    University of Toronto, Toronto, Canada.
    Moghadam, Adel R
    Islamic Azad University, Ardabil, Iran.
    Alizadeh, Javad
    University of Manitoba, Winnipeg Canada.
    Wiechec, Emilia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Alavian, Seyed M
    Baqiyatallah Research Center for Gastroenterology and Liver Disease, Tehran, Iran.
    Hashemi, Mohammad
    Zahedan University of Medical Sciences, Zahedan, Iran.
    Geramizadeh, Bita
    Shiraz University of Medical Sciences, Shiraz, Iran.
    Samali, Afshin
    National University of Ireland Galway, Galway, Ireland.
    Lankarani, Kamran B
    Shiraz University of Medical Sciences, Shiraz, Iran.
    Post, Martin
    University of Toronto, Toronto, Canada.
    Peymani, Payam
    Shiraz University of Medical Sciences, Shiraz, Iran.
    Coombs, Kevin M
    University of Manitoba, Winnipeg, Canada.
    Ghavami, Saeid
    University of Manitoba, Winnipeg, Canada.
    Hepatitis B and C virus-induced hepatitis: apoptosis, autophagy and unfolded protein response.2015In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 21, no 47, p. 13225-13239Article in journal (Refereed)
    Abstract [en]

    AIM: To investigate the co-incidence of apoptosis, autophagy, and unfolded protein response (UPR) in hepatitis B (HBV) and C (HCV) infected hepatocytes.

    METHODS: We performed immunofluorescence confocal microscopy on 10 liver biopsies from HBV and HCV patients and tissue microarrays of HBV positive liver samples. We used specific antibodies for LC3β, cleaved caspase-3, BIP (GRP78), and XBP1 to detect autophagy, apoptosis and UPR, respectively. Anti-HCV NS3 and anti-HBs antibodies were also used to confirm infection. We performed triple blind counting of events to determine the co-incidence of autophagy (LC3β punctuate), apoptosis (cleaved caspase-3), and unfolded protein response (GRP78) with HBV and HCV infection in hepatocytes. All statistical analyses were performed using SPSS software for Windows (Version 16 SPSS Inc, Chicago, IL, United States). P-values < 0.05 were considered statistically significant. Statistical analyses were performed with Mann-Whitney test to compare incidence rates for autophagy, apoptosis, and UPR in HBV- and HCV-infected cells and adjacent non-infected cells.

    RESULTS: Our results showed that infection of hepatocytes with either HBV and HCV induces significant increase (P < 0.001) in apoptosis (cleavage of caspase-3), autophagy (LC3β punctate), and UPR (increase in GRP78 expression) in the HCV- and HBV-infected cells, as compared to non-infected cells of the same biopsy sections. Our tissue microarray immunohistochemical expression analysis of LC3β in HBVNeg and HBVPos revealed that majority of HBV-infected hepatocytes display strong positive staining for LC3β. Interestingly, although XBP splicing in HBV-infected cells was significantly higher (P < 0.05), our analyses show a slight increase of XBP splicing was in HCV-infected cells (P > 0.05). Furthermore, our evaluation of patients with HBV and HCV infection based on stage and grade of the liver diseases revealed no correlation between these pathological findings and induction of apoptosis, autophagy, and UPR.

    CONCLUSION: The results of this study indicate that HCV and HBV infection activates apoptosis, autophagy and UPR, but slightly differently by each virus. Further studies are warranted to elucidate the interconnections between these pathways in relation to pathology of HCV and HBV in the liver tissue.

  • 22. Zhao, Zeng-Ren
    et al.
    Zhang, Zhi-Yong
    Cui, Dong-Sheng
    Jiang, Li
    Zhang, Hui-Jun
    Wang, Ming-Wei
    Sun, Xiao-Feng
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Particularly interesting new cysteine-histidine rich protein expression in colorectal adenocarcinomas2006In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 12, no 2, p. 298-301Article in journal (Refereed)
    Abstract [en]

    Aim: To study the relationship between particularly interesting new cysteine-histidine rich protein (PINCH) expression and clinicopathological factors in Chinese colorectal cancer patients. Methods: The expression of PINCH was examined by immumohistochemistry in 141 samples of primary colorectal adenocarcinoma and 92 normal samples of colorectal mucosa. Eighty of the cases had both primary tumour and normal mucosa from the same patients. Results: PINCH was expressed in the stroma of normal mucosa and tumours. PINCH expression in tumourassociated stroma was increased compared to normal mucosa in both unmatched cases (n = 141, X2 = 85.79, df = 3, P<0.0001) and matched cases (n = 80, X2 = 45.86, df = 3, P<0.0001). Among 135 tumours with visible invasive margin, 86 (64%) showed stronger PINCH expression at the invasive margin than in the intratumoural stroma. The frequency of PINCH strong expression in mucinous and signet-ring cell carcinomas was higher (52%) compared to non-mucinous carcinomas (29%, X2= 5.13, P= 0.02). We did not find that PINCH expression was related to patient's gender, age, tumour location, tumour size, gross status, histological type, differentiation, invasion depth, lymph node status and Dukes' stage (P>0.05). Conclusion: The expression of PINCH was upregulated in colorectal cancers, and especially at the margin of tumours, and further was related to mucinous and signet-ring cell carcinomas. The results suggest that expression of PINCH may be involved in the tumourigenesis and aggressiveness of colorectal cancers. © 2006 The WJG Press. All rights reserved.

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