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Background and aims: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a precursor of pancreatic cancer. While earlier research has shown a high prevalence of synchronous/metachronous extrapancreatic tumors in IPMN patients, these studies have often been small with retrospective data collection. The aim of the study was to examine absolute and relative risks of non-pancreatic gastrointestinal (GI) cancer precursors and mortality in histologically confirmed IPMN. Methods: Through the nationwide ESPRESSO histopathology cohort, we retrieved data on IPMN between 1965 and 2016. Each index case was matched to <= 5 general population controls. Through Cox regression, we estimated hazard ratios (HRs) for future GI cancer precursors and death. Results: A total of 117 patients with IPMN and 539 age- and sex-matched controls were included. Over a median of 2.1 years of follow up, we confirmed two (1.7%) incident GI cancer precursors in IPMN vs. four (0.7%) in controls, corresponding to an HR of 1.89 (95%CI = 0.34-10.55). By contrast, IPMN patients were at increased risk of death (HR 3.61 (95%CI = 1.79-7.27)). The most common cause of death in IPMN was pancreatic cancer (n = 14; 45.2% of all deaths). Conclusions: We found no association between IPMN and other GI cancer precursors. This argues against comprehensive routine surveillance for other GI cancer precursors in IPMN patients. Mortality was increased in IPMN with pancreatic cancer being the most common cause of death, indicating the need for lifelong follow up in all resected and non-resected patients with IPMN. However, results should be confirmed in larger cohorts.

Introduction: Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated condition associated with fibroinflammatory lesions that can occur at almost any anatomical site. It often presents as a multiorgan disease that may mimic malignancy, infection, or other immune-mediated conditions. Autoimmune pancreatitis (AIP) type 1 is the most prominent manifestation of IgG4-RD in the digestive tract, with common extra-pancreatic inflammation. We present the first patient with AIP and involvement of the testicles and nasal cavity. Patient and methods: A case of a patient with AIP type 1 and other organ involvement (bile ducts, testicles, nasal polyps, and lungs) is described. Additionally, a systematic review of AIP type 1 with testicular and nasal involvement was conducted. Results: The systematic review found two cases of AIP type 1 with testicular involvement and 143 cases with AIP type 1 with nasal cavity involvement. None of them had both testicular and nasal involvement. Conclusions: This is the first case of AIP type 1 with other organ involvement, including testicular and nasal involvement, to be described. The number of patients with nasal and testicular involvement described in the literature is low. Creating awareness of this rare clinical condition is necessary, especially due to the very effective available treatment with corticosteroids and rituximab., Funding Agencies|We thank the Swedish Society for Development of Pancreatology (SveSuP) for their continuing support, promotion, and raising awareness of pancreatic diseases in Swedish society.

Background: Studies of colorectal cancer (CRC) have suggested different mechanisms of carcinogenesis in men and women, young and old patients, right- and left sided tumors, and sporadic and familial tumors. These differences might be reflected in morphology. Methods: CRCs from 1613 patients operated on in 2004–2006 in Sweden were histologically reviewed. Morphology was examined in relation to sex, age groups, location, and family history. Results: Tumors in the right colon were larger, of higher stage, more often poorly differentiated, more mucin-producing, more often had a peritumoral lymphocytic infiltrate and a high level of tumor-infiltrating lymphocytes (TILs), and more seldom had an infiltrating margin than tumors in the left colon and rectum (p < 0.0001 for most features). Young patients (<60 years) more seldom had multiple tumors but more often had perineural invasion, an infiltrative tumor margin, and high-stage tumors. Three features, TILs, medullary tumors, and invasive tumor margin, were related to sex. Only vascular invasion was related to familiality. Conclusion: Location is the factor that has the most influence on tumor morphology. The results support the idea that different carcinogenic mechanisms may be involved in the right and left colon. Age is the most important determinant for the presence of multiple tumors and is a crucial factor for the aggressiveness of the disease.

Colorectal cancer (CRC) is the third most common form of cancer in Sweden. The etiology of CRC is considered to be influenced by environmental risk factors on a background of constitutional and acquired genetic variations. It is estimated that inherited susceptibility accounts for approximately 35% of all CRC cases. The well-known high-risk syndromes familial adenomatous polyposis and Lynch syndrome, however, explain less than 5%. The remaining part of the “genetic” group is contributed by risk factors of much smaller magnitude, such as mutations in several low-risk alleles. Genome-wide association studies have identified multiple genetic loci and single nucleotide polymorphisms (SNPs) associated with an increased or decreased risk of CRC. Also, the histopathological profile of CRC shows considerable variation in relation to sex, age, tumor location, family history and mode of presentation, which could speak for different mechanisms of tumor development in different groups of patients. The aim of paper I was to determine whether 11 newly identified genetic susceptibility loci were associated with tumor morphology, to confirm them as distinct and etiologically different risk factors in colorectal carcinogenesis. To that end, we analyzed 15 histological features in 1572 cases of consecutively operated CRCs during the years 2004-2006. Of the tested loci, five SNPs were significantly associated with morphological parameters such as poor differentiation, mucin production and decreased frequency of Crohn-like peritumoral reaction and desmoplastic response (p=0.004). The results are consistent with pathogenic variants in several loci acting in distinct CRC morphogenic pathways. The aim of paper II was to provide a systematic histopathological characterization of CRC in the patient material above by comparing the morphology of tumors in men and women, in different age groups, in different anatomical locations, and in sporadic and familial cases, in order to isolate the effe

Objective: To correlate placental histopathology, in particular ischemic changes, with the clinical severity of preeclampsia. Design: A blinded retrospective study. Setting: One Swedish hospital. Sample: One hundred and fifty-seven women with severe (n= 116) or mild (n= 41) preeclampsia and 157 normotensive women matched according to gestational-age. Methods: One senior pathologist, blinded to clinical data and group, examined all histological slides. In the statistical analyses, adjustment for gestational week was done when appropriate. Main outcome measures: Placental histopathological findings. Results: Amount of infarction increased with the severity of preeclampsia (p < 0.001). Infarction involving ≥5% of the placental tissue was seen in 39.7% of severe preeclampsia, 17.1% of mild preeclampsia and 5.1% of non-preeclampsia. When comparing placentas in severe preeclampsia, mild preeclampsia and non-preeclampsia, there was an increase in the presence of any infarction (80.2%, 61.0%, vs. 20.4%). Also, there was a difference in the presence of decidual arteriopathy (35.3%, 22.0%, vs. 3.8%) and accelerated villous maturation (71.6%, 53.3%, vs. 12.6%). We found no difference in intervillous thrombosis, abruption placenta or placental weight in relation to gestational week. Conclusions: In pregnancies with mild or severe preeclampsia, a large proportion of the placentas had histological signs of pathology, in particular signs of ischemia. The pathology was similar, but more pronounced in severe compared to mild preeclampsia, suggesting mild and severe preeclampsia to have similar underlying etiology.

Hofbauer cells are placental macrophages found in chorionic villous stroma; they express classic monocyte/macrophage markers, such as CD68. Little is known about their participation in placental disease and immunologic interactions at the placental interface. The aim of this study was to quantify the amount of Hofbauer cells in placentas complicated, or not, by chorioamnionitis and in placentas from different gestational ages. Fifty-eight 2nd-and 3rd-trimester placentas with the histologic diagnosis of acute chorioamnionitis were compared with 42 control placentas matched according to gestational age. Immunohistochemistry evaluation was performed with a monoclonal anti-CD68 antibody. Five areas of each placenta were photographed and 5 investigators, with the help of a computerized image analysis program, independently evaluated the number of CD68+ cells. Our results showed that there are significantly fewer CD68+ cells per villous area in placentas diagnosed with chorioamnionitis than in those of controls (P < 0.001). Moreover, there was a significant overall decrease in the number of these cells in 3rd as compared with 2nd trimester placentas (P = 0.02), as well as in placentas from term as compared to preterm pregnancies (P = 0.004). Our data indicate that CD68+ Hofbauer cells may be involved in placental infection and possibly associated with the developmental maturation of the fetoplacental unit.

In-hospital observation with repeated clinical examinations is commonly used in patients with an equivocal diagnosis of appendicitis. It is not known if repeated measurements of temperature and laboratory examinations have any diagnostic importance in this situation. The importance of repeated measurements of the body temperature, white blood cell (WBC) and differential cell counts, C-reactive protein concentration (CRP) and of the surgeon's repeated assessments was prospectively analyzed in 420 patients with an equivocal diagnosis of appendicitis at admission who were reexamined after a median of 6 hours of observation. The final diagnosis was appendicitis in 137 patients. After observation the inflammatory response was increasing among patients with appendicitis and decreasing among patients without appendicitis. The variables discriminating power for appendicitis consequently increased, from an area under the receiver operating characteristic (ROC) curve of 0.56 to 0.77 at admission, to 0.75 to 0.85 after observation. The ROC area of the surgeons' clinical assessment increased from 0.69 to 0.89. The WBC and differential cell counts were the best discriminators at the repeat examination. The change in the variables between the observations had weak discriminating power and had no additional importance in addition to the actual level at the repeat examination. To conclude, the diagnostic information of the temperature and laboratory examinations increased after observation. Repeated controls of the body temperature and laboratory examinations are therefore useful in the management of patients with equivocal signs of appendicitis, but the result of the examinations must be integrated with the clinical assessment.