Search Results (17)

Background: Whipple’s disease (WD) is a rare infection caused by Tropheryma whipplei. Diagnosis is challenging and requires a combination of several data sets, such as patient history, clinical and laboratory investigations, and endoscopy with histology analyses. While persistent diarrhea is a common symptom, WD can affect multiple organs. Case description: We present the case of a 66-year-old immunocompetent patient with WD and a history of Helicobacter pylori infection who developed chronic diarrhea. Colonoscopy and histopathological analysis revealed the presence of foamy macrophages with periodic acid-Schiff-positive particles. Subsequently, molecular methods confirmed the clinical WD diagnosis and metagenomic analyses further identified a co-infection with Giardia intestinalis. The patient fully recovered after 14 months of antibiotic therapy. During pharmacological treatment, clinical and laboratory follow-ups were conducted at 6 and 12 months, and microbiome profiles were also analyzed to identify the most abundant species in the samples. Conclusion: The metagenomic analyses showed the eradication of the two pathogens and a progressive restoration to a healthy/balanced status after antibiotic therapy. Full article

Background: Pancreatic ductal adenocarcinoma (PDAC) is the most common pancreatic malignancy and is characterized by a very unfavorable prognosis. Rarely, patients may develop synchronous PDAC and another distinct primary pancreatic tumor, such as a pancreatic neuroendocrine tumor. This systematic review consolidates published case reports describing the presentation, imaging characteristics, management, and outcomes of patients with synchronous PDAC and other pancreatic malignancies. Methods: A comprehensive search of PubMed and Scopus identified 26 relevant case reports, with inclusion criteria focused on histologically confirmed synchronous pancreatic tumors and exclusion of metastatic disease. Results: The majority of patients present with two pancreatic lesions, often located in both the body and tail of the pancreas. Diagnostic imaging modalities, such as computed tomography and endoscopic ultrasound, reveal common findings. Tumor markers, particularly CA 19-9, are often elevated and aid in the diagnosis. Surgical approaches also vary according to tumor location and staging, with procedures ranging from Whipple surgery to total pancreatectomy. Chemotherapy is frequently employed postoperatively. Notably, lymph node involvement and larger tumor size are associated with poorer prognoses. Conclusions: In conclusion, these patients may present with a common or non-common clinical picture as well as laboratory and imaging findings, constituting an important and unique diagnostic and therapeutic challenge. Full article

Background: Pancreatoduodenectomy with venous resection (PDVR) may be performed to achieve tumour clearance in patients with a pancreatic ductal adenocarcinoma (PDAC) with venous involvement. This study aimed to evaluate the impact of PDVR on PDAC outcomes. Methods: In total, 435 PDAC patients with either R0 status (n = 322) or R1 status within the superior mesenteric vein groove (n = 113) were extracted from the Recurrence After Whipple’s (RAW) study dataset. PDVR patients were matched in a 1:2 ratio with standard PD patients. Comparisons were then made between the two groups (surgical radicality and survival). Results: A total of 81 PDVRs were matched with 162 PDs. Neoadjuvant chemotherapy (5.7% vs. 13.6%, p = 0.032) and R1 resection rates (17.9% vs. 42%, p < 0.001) were higher in the PDVR group. Risk factors for R1 resection included venous resection (p < 0.001 for sleeve and p = 0.034 for segmental resection), pT3 (p = 0.007), and pN1 stage (p = 0.045). PDVR patients had lower median overall survival (OS, 21 vs. 30 months (m), p = 0.023) and disease-free survival (DFS, 17 m vs. 24 m, p = 0.043). Among PDVR patients, R status did not impact on OS (R0: 23 m, R1: 21 m, p = 0.928) or DFS (R0: 18 m, R1: 17 m, p = 0.558). Irrespective of R status, systemic recurrence was higher in the PDVR group (p = 0.034). Conclusions: Independent of R status, the PDVR group had lower overall survival and higher systemic recurrence rates. Full article

(1) Background: The modified Whipple procedure, or pylorus-preserving pancreaticoduodenectomy, is a complex surgical intervention used to treat pancreatic head tumors. While preserving digestive function, it is associated with significant perioperative risks. This study explores the clinical, immunological, and microbiome-related factors influencing postoperative complications, focusing on the interplay between patient comorbidities, systemic inflammation, and gut dysbiosis. (2) Methods: A retrospective analysis was conducted on 123 patients undergoing the modified Whipple procedure for pancreatic head tumors. Patients were categorized into two groups based on the occurrence of significant postoperative complications (Group A: with complications; Group B: without complications). Data on demographics, comorbidities, inflammatory markers (CRP, IL-6, procalcitonin), and gut microbiome composition were collected. Microbial diversity was evaluated using the Shannon Index, and logistic regression was performed to identify independent predictors of complications. (3) Results: Patients in Group A had a significantly higher prevalence of diabetes mellitus (43.1% vs. 20.8%; p = 0.02) and cardiovascular disease (35.3% vs. 13.9%; p = 0.01). Elevated inflammatory markers (CRP ≥ 40 mg/L, IL-6 ≥ 30 pg/mL, procalcitonin ≥ 0.5 ng/mL) were strongly associated with higher complication rates. Microbiome analysis indicated dysbiosis in Group A, with reduced Lactobacillus and Bifidobacterium levels, increased Enterobacteriaceae abundance, and a lower Shannon Index (<2). Patients exhibiting both dysbiosis and elevated inflammation had the highest complication rate (60%). Multivariate analysis identified diabetes, elevated IL-6, and dysbiosis as independent predictors of adverse outcomes. (4) Conclusions: Postoperative complications after the modified Whipple procedure are influenced by systemic inflammation and gut dysbiosis. A systematic preoperative assessment of microbiome health and inflammatory markers enables accurate risk stratification and personalized interventions, potentially reducing the incidence of complications and improving overall surgical outcomes. Full article

We conducted a prospective cohort study at the IRCCS Sacro Cuore Don Calabria Hospital in Negrar di Valpolicella from 2019 to 2021 to investigate the duration of T. whipplei colonization. In addition, the correlation between persistent colonization and the continent of origin, current treatment regimen, clinical manifestations, and parasite coinfection was evaluated. The cohort included subjects who were tested in a previous study (years 2014–2016) and found to be positive for T. whipplei DNA in fecal samples. Thirty-three subjects were enrolled in a prospective study between 2019 and 2021. Feces, saliva, urine, and blood were collected at baseline and after 12 months. Medical history, current treatment, and symptoms were recorded. Among them, 25% showed persistent intestinal or oral colonization, 50% had no colonization at both visits, and 25% had intermittent colonization. No association was found between persistent T. whipplei colonization and subjects’ continent of origin, current treatment regimen, initial clinical manifestations, and parasite coinfection. The longest duration of persistent T. whipplei intestinal colonization exceeded six years, with 11 subjects presenting persistent positivity for more than three years, including 1 minor. Our research was limited by the lack of a strain-specific identification of T. whipplei that made it impossible to distinguish between persistence of the same T. whipplei strain, reinfection from household exposure, or infection by a new strain. Larger prospective studies are needed to further explore the implications of this persistence and determine the key factors influencing the duration of colonization and its potential health impacts. Full article

We describe an atypical case of Whipple disease exclusively involving the spinal cord in an adolescent receiving immunosuppressive therapy for systemic lupus erythematosus. The diagnosis was particularly difficult since lupus and Whipple disease can present similar clinical features and the patient’s prolonged contact with sewage was initially not mentioned. A literature review of the clinical, imaging, diagnostic, and therapeutic challenges of Whipple disease is also performed. Full article

Background: Tropheryma whipplei (TW) can cause different pathologies, e.g., Whipple’s disease and transient gastroenteritis. The mechanism by which the bacteria pass the intestinal epithelial barrier, and the mechanism of TW-induced gastroenteritis are currently unknown. Methods: Using ex vivo disease models comprising human duodenal mucosa exposed to TW in Ussing chambers, various intestinal epithelial cell (IEC) cultures exposed to TW and a macrophage/IEC coculture model served to characterize endocytic uptake mechanisms and barrier function. Results: TW exposed ex vivo to human small intestinal mucosae is capable of autonomously entering IECs, thereby invading the mucosa. Using dominant-negative mutants, TW uptake was shown to be dynamin- and caveolin-dependent but independent of clathrin-mediated endocytosis. Complementary inhibitor experiments suggested a role for the activation of the Ras/Rac1 pathway and actin polymerization. TW-invaded IECs underwent apoptosis, thereby causing an epithelial barrier defect, and were subsequently subject to phagocytosis by macrophages. Conclusions: TW enters epithelia via an actin-, dynamin-, caveolin-, and Ras-Rac1-dependent endocytosis mechanism and consecutively causes IEC apoptosis primarily in IECs invaded by multiple TW bacteria. This results in a barrier leak. Moreover, we propose that TW-packed IECs can be subject to phagocytic uptake by macrophages, thereby opening a potential entry point of TW into intestinal macrophages. Full article

Whipple’s disease is caused by T. whipplei, a Gram-positive pathogenic bacterium. It is considered a persistent infection affecting various organs, more likely to infect males. There is currently no licensed vaccination available for Whipple’s disease; thus, the development of a chimeric peptide-based vaccine against T. whipplei has the potential to be tremendously beneficial in preventing Whipple’s disease in the future. The present study aimed to apply modern computational approaches to generate a multi-epitope-based vaccine that expresses antigenic determinants prioritized from the core proteome of two T. whipplei whole proteomes. Using an integrated computational approach, four immunodominant epitopes were found from two extracellular proteins. Combined, these epitopes covered 89.03% of the global population. The shortlisted epitopes exhibited a strong binding affinity for the B- and T-cell reference set of alleles, high antigenicity score, nonallergenic nature, high solubility, nontoxicity, and excellent binders of DRB1*0101. Through the use of appropriate linkers and adjuvation with a suitable adjuvant molecule, the epitopes were designed into a chimeric vaccine. An adjuvant was linked to the connected epitopes to boost immunogenicity and efficiently engage both innate and adaptive immunity. The physiochemical properties of the vaccine were observed favorable, leading toward the 3D modeling of the construct. Furthermore, the vaccine’s binding confirmation to the TLR-4 critical innate immune receptor was also determined using molecular docking and molecular dynamics (MD) simulations, which shows that the vaccine has a strong binding affinity for TLR4 (−29.4452 kcal/mol in MM-GBSA and −42.3229 kcal/mol in MM-PBSA). Overall, the vaccine described here has a promising potential for eliciting protective and targeted immunogenicity, subject to further experimental testing. Full article

Tropheryma whipplei (TW), Helicobacter pylori (HP), and intestinal protozoa (IP) are widespread pathogens with similar routes of transmission and epidemiological risk factors. Epidemiological data on co-infection between TW, HP, and IP are scarce. We aim to more deeply investigate the co-infection rate for these pathogens, evaluating the risk factors and symptoms. Methods: This is a cross-sectional study conducted at the IRCCS Sacro Cuore Don Calabria Hospital in Northern Italy, a referral center for tropical and Whipple’s disease (WD). Stored stool samples from 143 subjects previously tested for TW DNA by real-time PCR were explored for HP and IP DNA detection. The virulence factor cagA was investigated in HP-positive patients. Results: A history of migration was reported significantly more in TW-positive than in negative subjects (34.1% vs. 9.1%, p = 0.001) and in HP-infected than in those non-infected (59.1% vs. 9.1%, p < 0.001). The HP infection rate differed significantly between TW-infected and uninfected groups (31.8% vs. 8.1%, p = 0.001), while no difference was observed for IP infection. Significantly higher TW intestinal colonization was found in HP-infected patients than in non-infected (63.6% vs. 24.8%, p < 0.001). In addition, the proportion of Blastocysts positive finding was also significantly higher in HP-infected than in non-infected (40.9% vs. 17.4%, p = 0.018). Conclusions: The present study is the first to report a high TW and HP co-infection rate. To reduce the risk of morbidity from a chronic infection of either pathogen, clinicians may consider TW-HP molecular screening on the same stool sample for patients with suspected HP disease or WD, particularly in case of travel history. Full article

Whipple’s Disease is a rare systemic infectious disease caused by the ubiquitous actinomycetes Tropheryma whipplei (T. whipplei). We report herein a rare case of a cutaneous granulo matosis with hypercalcemia as an unusual presenting feature of Whipple’s disease. The diagnosis of the bacteria was obtained from skin and inguinal lymph node biopsy (16 rDNA PCR screening and histological examination using PAS staining). T. whipplei was also identified on saliva and stool specimens, using specific PCR and colonic biopsies. Treatment with hydroxychloroquine and doxycycline allowed a rapid resolution of symptoms with a complete recovery. Full article

Background: Recent studies demonstrated higher prevalence rates of Tropheryma whipplei (T. whipplei) in HIV positive than in HIV negative subjects. However, associations with the immune status in HIV positive participants were conflicting. Methods: For this cross-sectional study, stool samples of 906 HIV positive and 98 HIV negative individuals in Ghana were tested for T. whipplei. Additionally, sociodemographic parameters, clinical symptoms, medical drug intake, and laboratory parameters were assessed. Results: The prevalence of T. whipplei was 5.85% in HIV positive and 2.04% in HIV negative participants. Within the group of HIV positive participants, the prevalence reached 7.18% in patients without co-trimoxazole prophylaxis, 10.26% in subjects with ART intake, and 12.31% in obese participants. Frequencies of clinical symptoms were not found to be higher in HIV positive T. whipplei carriers compared to T. whipplei negative participants. Markers of immune activation were lower in patients colonized with T. whipplei. Multivariate regression models demonstrated an independent relationship of a high CD4+ T cell count, a low HIV-1 viral load, and an obese body weight with the presence of T. whipplei. Conclusions: Among HIV positive individuals, T. whipplei colonization was associated with a better immune status but not with clinical consequences. Our data suggest that the withdrawal of co-trimoxazole chemoprophylaxis among people living with HIV on stable cART regimen may inadvertently increase the propensity towards colonization with T. whipplei. Full article

Background: The human anti-IL-6 receptor antibody tocilizumab (TCZ) has been approved for the treatment of rheumatoid arthritis (RA) and giant cell arteritis (GCA). It is observed that CRP levels drop quickly after starting TCZ treatment. This may lead to misinterpretation of laboratory results when accessing the patient with infectious disease while on TCZ. We conducted this study to report cases treated with tocilizumab who developed serious infections with special reference to levels of CRP and to review the literature on the effect of tocilizumab on acute phase response (APR) during infections. Methods: The files of RA and GCA patients hospitalized in the Tel Aviv medical center between 2009–2019 were reviewed. Cases of patients with RA and GCA treated with tocilizumab who were hospitalized due to severe infections were reviewed with special emphasis on the duration of treatment, type of infection, and APR. Results: We identified nine admissions. Seven patients were treated with tocilizumab for RA, two for GCA. The diagnosis was pneumonia in three cases, osteomyelitis in one, cellulitis in one, endocarditis due to Whipple disease in one, abscess of cervix uteri in one, meningitis in one, and perforated diverticulitis in one. The mean CRP levels on admission were 4.75 mg/L (normal range, up to 5 mg/L). All cases were diagnosed correctly on admission. Conclusions: CRP levels may not correctly reflect the severity of infectious diseases during tocilizumab treatment. Increased awareness of the masking effect of tocilizumab on the APR during infection is needed in order to avoid a delay in the diagnosis. Full article

Whether gastric adenocarcinoma (GC) patients with adjacent organ invasion (T4b) benefit from aggressive surgery involving pancreatic resection (PR) remains unclear. This study aimed to clarify the impact of PR on survival in patients with locally advanced resectable GC. Between 1995 and 2017, patients with locally advanced GC undergoing radical-intent gastrectomy with and without PR were enrolled and stratified into four groups: group 1 (G1), pT4b without pancreatic resection (PR); group 2 (G2), pT4b with PR; group 3 (G3), positive duodenal margins without Whipple’s operation; and group 4 (G4), cT4b with Whipple’s operation. Demographics, clinicopathological features, and outcomes were compared between G1 and G2 and G3 and G4. G2 patients were more likely to have perineural invasion than G1 patients (80.6% vs. 50%, p < 0.001). G4 patients had higher lymph node yield (40.8 vs. 31.3, p = 0.002), lower nodal status (p = 0.029), lower lymph node ratios (0.20 vs. 0.48, p < 0.0001) and higher complication rates (45.2% vs. 26.3%, p = 0.047) than G3 patients. The 5-year disease-free survival (DFS) and overall survival (OS) rates were significantly longer in G1 than in G2 (28.1% vs. 9.3%, p = 0.003; 32% vs. 13%, p = 0.004, respectively). The 5-year survival rates did not differ between G4 and G3 (DFS: 14% vs. 14.4%, p = 0.384; OS: 12.6% vs. 16.4%, p = 0.321, respectively). In conclusion, patients with T4b lesion who underwent PR had poorer survival than those who underwent resection of other adjacent organs. Further Whipple’s operation did not improve survival in pT3–pT4 GC with positive duodenal margins. Full article

Background: Superior vena cava (SVC) syndrome may result from extravascular compression or intravascular obstruction such as thrombosis. Recurrent venous thrombosis is typically associated with a hypercoagulable state such as malignancy, and inheritable or acquired coagulopathy. Sarcoidosis is a derangement of the immune system, and it has been associated with malignant diseases and hypercoagulation. The association of pancreatic cancer and sarcoidosis with SVC syndrome has not been reported previously. Here, we present a case of recurrent venous thrombosis causing SVC syndrome in a patient with pancreatic ductal adenocarcinoma and underlying thoracic sarcoidosis. Methods: The patient’s electronic health record was retrospectively analyzed. Results: A 66-year-old woman with pancreatic adenocarcinoma was treated with neoadjuvant chemotherapy followed by Whipple procedure, before developing tumor recurrence in the liver. Her treatment course was complicated with repeated incidents of venous thrombosis in the presence of a central venous catheter leading to recurrent SVC syndrome, which resolved with anti-coagulation. Conclusions: This case raises a plausible inter-relationship between sarcoidosis, pancreatic cancer, and hypercoagulable state. We suggest that patients with multiple risk factors for developing venous thrombosis should be carefully monitored for any thrombotic event, and they may benefit from prophylactic anti-coagulation. Full article