Intravenous lipomas of head and neck: an exceptional entity and its clinical implications.

Intravenous lipomas (IVLs) of the head and neck are uncommon benign tumors that develop within the venous walls, often detected incidentally during imaging for unrelated issues. While usually asymptomatic, these IVLs can cause congestive venous symptoms like swelling, paresthesia or pain in the head and neck and upper limbs, or even venous thromboembolism. The precise diagnosis of IVLs is predominantly achieved through computed tomography (CT) and magnetic resonance imaging (MRI), with CT being the most frequently used method. Symptomatic patients generally undergo open surgery with excision of the IVL followed by venous reconstruction, which has shown safe and effective outcomes. However, the management of asymptomatic IVLs remains controversial due to the limited number of reported cases. Despite this, there is a notable trend toward recommending surgical removal of IVLs to prevent complications and rule out malignancy, driven by the challenges of differentiating IVLs from malignant tumors using imaging alone. This review highlights the key differential imaging characteristics of IVLs and the main surgical techniques to remove the tumor and repair the vascular defect. Further research is necessary to establish a robust, evidence-based approach for treating asymptomatic IVLs, balancing the risks of surgery against the potential for future complications.

Psychological Factors Related to Treatment Outcomes in Head and Neck Cancer.

BACKGROUND: Patients with head and neck cancer (HNC) often demonstrate stress, distress, anxiety, depression, and are at risk for suicide. These affect their quality of life (QoL) but less attention has been given to psychological variables that may impact response to treatment. OBJECTIVES: This study aims to systematically review publications during 2013-2023 to collate evidence on the effects of psychological variables on HNC treatment outcomes. METHODS: We searched Ovid Medline, PubMed, Scopus, and Web of Science for articles that examined psychological factors related to treatment outcomes in patients with HNC. RESULTS: There were 29 studies (5 before treatment, 2 during, 17 after, and 5 covering the whole management trajectory) including 362,766 patients. The psychological factors were either behavioral (adjustment and coping strategy, unrealistic ideas, self-blame), cognitive (elevated risk of psychiatric co-comorbidity), or emotional (distress, depression, anxiety, nervousness, and fear of disfigurement and complications). It was found that there was a relationship between depression and decreased survival in patients with HNC. Pretreatment pain was an independent predictor of decreased survival in a large sample of patients. The distress level was approximately  54%, emotional problems ranged between 10 and 44%, while financial difficulties were identified in 54% of the patients. Sixty-nine percent of patients were reported to have used at least one cost-coping strategy within 6 months after treatment initiation. During post-treatment period, depression increased from 15% at the baseline to 29%, while the fear of recurrence was found among at least 35% of patients. DISCUSSION AND CONCLUSION: Several psychological factors predict QoL and survival among HNC survivors. Distress encompasses depression and anxiety, and physical burden from HNC diagnosis and treatment. Routine screening and early interventions that target distress could improve HNC survivors' QoL. A systematic and standardized measurement approach for QoL is warranted to homogenize these findings and to understand the underlying relationships.

Laryngeal cancer relative survival trends from 1972 to 2021 in the Nordic countries.

BACKGROUND AND PURPOSE: Changes in treatment approaches, characterised by the shift from laryngectomy to a focus on organ-preserving methods may have potentially resulted in lower survival. We aim to identify differences in survival trends for laryngeal cancer (LC) in the Nordic countries over a period of 50 years, and discuss the potential impact of factors such as changes in treatment protocols. MATERIALS AND METHODS: Five-year relative survival (RS) data from 1972 to 2021 were obtained from the NORDCAN database 2.0 which included 33,692 LC cases, of which 85% were diagnosed among men. In the NORDCAN database, the age-standardised RS is calculated using the Pohar Perme estimator with individual International Cancer Survival Standards weights. Joinpoint regression models were used to assess potential shifts in trend over the years in RS. RESULTS: While Denmark and Norway demonstrated an increasing trend in 5-year RS from 1972 to 2021, in Finland and Sweden, the 5-year RS among men remained static, without any discernible significant trend. Over the 30-year period from 1992-1996 to 2017-2021, RS improved by 9, 4, 13, and 2 percentage points in Denmark, Finland, Norway, and Sweden, respectively. Among women in Sweden, a linear negative trend was observed, noticeable as a 16 percentage-point decline in 5-year RS from the earliest to the latest period. INTERPRETATION: The underlying causes for the differences in survival trends remain unclear. Besides differences in treatment protocols, several other factors can affect RS making the interpretation of RS trends challenging.

Genome-wide association study indicates novel associations of annexin A13 to secretory and GAS2L2 with mucous otitis media.

To evaluate the genetics of chronic nonsuppurative otitis media (OM). We performed a genome-wide association study of 429,599 individuals included in the FinnGen study using three different case definitions: combined chronic nonsuppurative OM (7034 cases) (included serous and mucous chronic OM), mucous chronic OM (5953 cases), and secretory chronic OM (1689 cases). Individuals without otitis media were used as controls (417,745 controls). We used immunohistochemistry (IHC) of the murine middle ear to evaluate the expression of annexin A13. Four loci were significantly associated (p < 1.7 × 10-8) with nonsuppurative OM. Three out of the four association signals included missense variants in genes that may play a role in otitis media pathobiology. According to our subtype-specific analyses, one novel locus, located near ANXA13, was associated with secretory OM. Three loci (near TNFRSF13B, GAS2L2, and TBX1) were associated with mucous OM. Immunohistochemistry of murine middle ear samples revealed annexin A13 expression at the apical pole of the Eustachian tube epithelium as well as variable intensity of the secretory cells of the glandular structure in proximity to the Eustachian tube. We demonstrated that secretory and mucous OM have distinct and shared genetic associations. The association of GAS2L2 with ciliary epithelium function and the pathogenesis of dysfunctional mucosa in mucous OM is suggested. The abundant expression of annexin A13 in the Eustachian tube epithelium, along with its role in apical transport for the binding and transfer of phospholipids, indicates the role of annexin A13 and phospholipids in Eustachian tube dysfunction.

Socio-economic status and head and neck cancer incidence in the Nordic countries.

BACKGROUND: The impact of societal factors on the occurrence of head and neck cancers (HNCs) remains understudied, especially in the Nordic countries. METHODS: To quantify the association between socio-economic status (SES) and the occurrence of HNCs, this cohort study uses data from the Nordic Occupational Cancer project that combine occupational and cancer registry data from 1961 to 2005 of 14.9 million individuals aged between 30 and 64 years. Occupational categories were combined into seven socio-economic categories. Standardized incidence ratio (SIR) analyses were conducted with the cancer incidence rates for the entire national study populations used as reference rates. RESULTS: Altogether, 83 997 HNCs-72% in men and 28% in women-were recorded. Among men, a gradient of risk associated with SES was observed for cancers of the tongue, other oral cavity subsites, pharynx, oropharynx and larynx in groups with lower SES. Managers showed decreased SIRs of 0.50 to -0.90 also for cancers of the lip, tongue, other oral cavity subsites, oropharynx, nasopharynx, nose and larynx. In contrast, excess risks of tongue, other oral cavity subsites, pharyngeal, oropharyngeal and laryngeal cancers were observed among clerical (SIRs 1.05-1.16), skilled workers (1.04-1.14), unskilled workers (1.16-1.26) and economically inactive men (1.38-1.87). Among women, no risk gradient similar to that in men was revealed. CONCLUSIONS: The current study underscores the influence of SES on the incidence of HNCs and highlights the need for targeted interventions, including tobacco and alcohol control policies, and improved access to healthcare services, particularly for socio-economically disadvantaged populations.

Multiple DNA Viruses and HPV Integration in Inverted Papilloma and Associated Sinonasal Carcinoma.

OBJECTIVES: Sinonasal inverted papilloma (IP) has a locally destructive growth pattern, can relapse, and can undergo malignant transformation (IP-associated sinonasal squamous cell carcinoma (IP-SNSCC)). Human papillomaviruses (HPV)-6 and -16 are frequently detected in IPs. To clarify the possible roles of other DNA viruses in IPs, we explored viruses not studied in this context before. With the setting of pre- and post-malignant transformation samples, we investigated HPV genomes in depth to assess the integration of HPV into the human genome and the presence of minor intratypic variants. MATERIALS AND METHODS: We analyzed 35 IP samples representing 28 individuals, of which six had IP-SNSCC. For virus screening, we applied qPCR to detect 16 different DNA viruses in three virus families, comprising herpesviruses, parvoviruses, and polyomaviruses. In addition, targeted next generation sequencing (NGS) was used for detailed HPV analysis. RESULTS: We detected herpes-, parvo-, and polyomaviruses in 13/28 (46%) patients, with codetections of multiple viruses in six (21%) patients. NGS revealed HPV16 DNA in 2/6 IP-SNSCC and in their respective earlier benign IP samples, as well as in a plasma sample from one of these patients. HPV6 was detected in two IP samples without subsequent malignant transformation. We identified sequence reads containing junctions of HPV6 and HPV16 and host genome suggestive of viral integration. HPV6 and HPV16 minor intratypic variants were present across pre- and post-malignant transformation, with mostly nonsynonymous mutations. CONCLUSIONS: Multiple DNA viruses were present in IPs. HPV16 was detected only in IP-SNSCCs or in tumors that later underwent malignant transformation. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

Risk of Second Primary Cancer Among Patients with Cardio-Esophageal Cancer in Finland: A Nationwide Population-Based Study.

Purpose: The occurrence of a second primary cancer (SPC) after primary esophageal carcinoma (EC) or gastric cardia carcinoma(GCC) is well acknowledged. However, previous research on the risk of SPC among these patients has been predominantly conducted in Asian countries. Yet, notable population-dependent variation in histological types and risk profiles exists. This register-based study assesses the histology-specific risk of SPC among individuals initially diagnosed with a first primary EC or GCC. Patients and Methods: We obtained data on 7197 patients diagnosed with EC/GCC in Finland between 1980 and 2022 from the Finnish Cancer Registry. Standardized incidence ratios (SIR) of SPC were subsequently calculated relatively to the cancer risk of the general population. Results: The average and median follow-up times were 2.8 years and 10.5 months. Adenocarcinomas and squamous cell carcinomas comprised 57.8% (n = 4165) and 36.6% (n = 2631) of all cases, respectively. An increased SIR was noted among EC/GCC patients after 15-20 years of follow-up (SIR 1.49, 95% CI: 1.01-2.11). Among adenocarcinoma patients, an increased SIR for SPCs of the digestive organs was seen in the 40-54-year-old group (SIR 9.86, 95% CI: 3.62-21.45). Squamous cell carcinoma patients displayed increased SIRs for cancer of the mouth/pharynx (SIR 3.20, 95% CI: 1.17-6.95) and respiratory organs (1.77, 1.07-2.76). Conclusion: Healthcare professionals should be aware of the increased risk of SPCs occurring in the mouth/pharynx, respiratory and digestive organs in survivors of EC/GCC. Patients should be advised about this risk and remain alert for symptoms, even beyond the standard 5-year follow-up period.

Toll-like receptors 2 and 4, and bacterial proteins in IgG4-related sialadenitis, other types of chronic sialadenitis and sialolithiasis.

Background: The association of chronic sclerosing sialadenitis and IgG4-related disease (IgG4-RD) has resulted in the more frequent identification of IgG4-positivity in submandibular gland inflammations, also uncovering IgG4 overexpression in nonspecific inflammations. These findings lead us to hypothesise that IgG4-positive sialadenitis represents a continuous inflammatory process overlapping histologically with IgG4-RD, possibly differing in aetiology. However, the antigen underlying IgG4 overexpression in IgG4-positive sialadenitis and IgG4-RD remains unknown. Materials and methods: Here, we investigated toll-like receptor (TLR) - mediated bacterial inflammation in submandibular gland tissues of patients with IgG4-positive and IgG4-negative chronic inflammatory lesions of the submandibular gland (n = 61), with noninflamed submandibular glands serving as controls (n = 4). Utilising immunohistochemistry, we assessed the expression of TLR2 and TLR4, lipopolysaccharide (LPS) and the P. gingivalis-specific antigen gingipain R1. Results: We observed TLR2- and TLR4-immunopositivity in 64 (98%) samples. However, TLR2 and TLR4 staining intensity was significantly stronger in the IgG4-positive group. LPS- and gingipain R1 immunopositivity were observed in 56 (86%) and 58 (89%) samples, respectively. LPS-positivity localised exclusively in mast cell-like cells, while gingipain R1-positivity remained scarce. Conclusions: A stronger TLR2 or TLR4 expression in IgG4-positive sialadenitis may indicate a tissue-related factor underlying this form of chronic sialadenitis. LPS- and P. gingivalis immunopositivity remained weak throughout this series. Thus, gram-negative bacteria may not represent pathogens underlying these forms of chronic sialadenitis.

Psychosocial factors and patient and healthcare delays in large (class T3-T4) oral, oropharyngeal, and laryngeal carcinomas.

BACKGROUND: Psychosocial factors and socioeconomic status have been associated with incidence, survival, and quality of life among patients with head and neck cancer. We investigated the association between different psychosocial factors, socioeconomic status, and patient delays in T3-T4 oral, oropharyngeal, and laryngeal cancer. PATIENTS AND METHODS: We conducted a nationwide prospective questionnaire-based study (n = 203) over a 3-year period. RESULTS: We found no association between psychosocial factors (depression, social isolation, loneliness, and cynical hostility) and patient delay. Depression was three times more common among head and neck cancer patients compared with the general Finnish population. Head and neck cancer patients had lower educational levels and employment status, and were more often current smokers and heavy drinkers. CONCLUSIONS: Although we found no association between patient delay and psychosocial factors, patients diagnosed with a large head and neck cancer appeared to have a lower socioeconomic status and higher risk for developing depression, which should be considered in clinical practice.

LRG1 and SDR16C5 protein expressions differ according to HPV status in oropharyngeal squamous cell carcinoma.

The increasing incidence of oropharyngeal squamous cell carcinoma (OPSCC) is primarily due to human papillomavirus, and understanding the tumor biology caused by the virus is crucial. Our goal was to investigate the proteins present in the serum of patients with OPSCC, which were not previously studied in OPSCC tissue. We examined the difference in expression of these proteins between HPV-positive and -negative tumors and their correlation with clinicopathological parameters and patient survival. The study included 157 formalin-fixed, paraffin-embedded tissue samples and clinicopathological data. Based on the protein levels in the sera of OPSCC patients, we selected 12 proteins and studied their expression in HPV-negative and HPV-positive OPSCC cell lines. LRG1, SDR16C5, PIP4K2C and MVD proteins were selected for immunohistochemical analysis in HPV-positive and -negative OPSCC tissue samples. These protein´s expression levels were compared with clinicopathological parameters and patient survival to investigate their clinical relevance. LRG1 expression was strong in HPV-negative whereas SDR16C5 expression was strong in HPV-positive tumors. Correlation was observed between LRG1, SDR16C5, and PIP4K2C expression and patient survival. High expression of PIP4K2C was found to be an independent prognostic factor for overall survival and expression correlated with HPV-positive tumor status. The data suggest the possible role of LRG1, SDR16C5 and PIP4K2C in OPSCC biology.

Application of simultaneous uncertainty quantification and segmentation for oropharyngeal cancer use-case with Bayesian deep learning.

BACKGROUND: Radiotherapy is a core treatment modality for oropharyngeal cancer (OPC), where the primary gross tumor volume (GTVp) is manually segmented with high interobserver variability. This calls for reliable and trustworthy automated tools in clinician workflow. Therefore, accurate uncertainty quantification and its downstream utilization is critical. METHODS: Here we propose uncertainty-aware deep learning for OPC GTVp segmentation, and illustrate the utility of uncertainty in multiple applications. We examine two Bayesian deep learning (BDL) models and eight uncertainty measures, and utilize a large multi-institute dataset of 292 PET/CT scans to systematically analyze our approach. RESULTS: We show that our uncertainty-based approach accurately predicts the quality of the deep learning segmentation in 86.6% of cases, identifies low performance cases for semi-automated correction, and visualizes regions of the scans where the segmentations likely fail. CONCLUSIONS: Our BDL-based analysis provides a first-step towards more widespread implementation of uncertainty quantification in OPC GTVp segmentation.

Radiotherapy is used as a treatment for people with oropharyngeal cancer. It is important to distinguish the areas where cancer is present so the radiotherapy treatment can be targeted at the cancer. Computational methods based on artificial intelligence can automate this task but need to be able to distinguish areas where it is unclear whether cancer is present. In this study we compare these computational methods that are able to highlight areas where it is unclear whether or not cancer is present. Our approach accurately predicts how well these areas are distinguished by the models. Our results could be applied to improve the computational methods used during radiotherapy treatment. This could enable more targeted treatment to be used in the future, which could result in better outcomes for people with oropharyngeal cancer.

Core Legal Challenges for Medical 3D Printing in the EU.

3D printing has been adopted into routine use for certain medical applications, but more widespread usage has been hindered by, among other things, unclear legislation. We performed an analysis, using legal doctrinal study and legal informatics, of relevant EU legislation and case law in four issues relevant to medical 3D printing (excluding bioprinting or pharmacoprinting): pre-market approval, post-market liability, intellectual property rights, and data protection. Several gaps and uncertainties in the current legislation and interpretations were identified. In particular, we regard the current EU regulatory framework to be quite limiting and inflexible, exemplifying a cautionary approach common in EU law. Though the need to establish high safety standards in order to protect patients as a disadvantaged population is understood, both legal uncertainties and overregulation are seen as harmful to innovation. Hence, more adaptive legislation is called for to ensure continuous innovation efforts and enhanced patient outcomes.

Stereotactic Body Radiotherapy in Recurrent and Oligometastatic Head and Neck Tumours.

The treatment of head and neck cancers (HNCs) encompasses a complex paradigm involving a combination of surgery, radiotherapy, and systemic treatment. Locoregional recurrence is a common cause of treatment failure, and few patients are suitable for salvage surgery. Reirradiation with conventional radiation techniques is challenging due to normal tissue tolerance limits and the risk of significant toxicities. Stereotactic body radiotherapy (SBRT) has emerged as a highly conformal modality that offers the potential for cure while limiting the dose to surrounding tissue. There is also growing research that shows that those with oligometastatic disease can benefit from curative intent local ablative therapies such as SBRT. This review will look at published evidence regarding the use of SBRT in locoregional recurrent and oligometastatic HNCs.

Stereotactic Body Radiotherapy as a Curative Treatment for De Novo Mucosal Carcinoma of the Head and Neck: A Feasible Alternative Option for Fragile Patients with Small Lesion: A Systematic Review.

Stereotactic body radiotherapy (SBRT) is characterized by a high dose per fraction, well-defined small targets, superior dose conformity, and a steep off-target dose gradient. A literature search was conducted to examine the experience with SBRT as a curative treatment for newly diagnosed mucosal carcinoma of the head and neck (MCHN). Four retrospective case series and one prospective phase I clinical trial published between 2012 and 2020 described 124 patients. SBRT was mainly performed in older patients with different tumor sites. The median size of the planning target volumes ranged from 5.3 to 41 cm3. Different approaches were used to create margins. In two studies, limited elective nodal irradiation was performed. The equivalent doses used were 60-83.33 Gy delivered in five fractions. Considerable heterogeneity was observed in the radiation dose specification. The incidence of grade ≥3 late toxicity was 0-8.3%, with local and regional control ranging from 73% to 100%. Improved or stable quality of life after SBRT was reported in two studies. Curative-intent SBRT for de novo MCHN appears to be an effective and relatively safe treatment for small tumor targets, preferably without concomitant elective tissue irradiation. Standardization of SBRT practice and well-designed prospective clinical trials are needed to better define the role of SBRT in this setting.

Immunoexpression pattern of TLR3 and TLR7 in minor salivary gland adenoid cystic carcinoma and its role in prognosis.

OBJECTIVES: Adenoid cystic carcinoma (ACC) of the salivary glands has poor long-term prognosis and a high metastatic rate. Toll-like receptors (TLRs), first-line immune activators, have been associated with both tumor progression and suppression. We aimed to study TLR3 and TLR7 behavior in ACC. MATERIALS AND METHODS: We studied TLR3 and TLR7 immunoexpression of 46 minor salivary gland ACCs diagnosed at the Department of Otorhinolaryngology - Head and Neck Surgery, Helsinki University Hospital, Helsinki, Finland over the period 1974-2012. The associations of TLR3 and TLR7 immunoexpression with clinicopathological factors were evaluated by χ2-test and Fisher's exact test. RESULTS: In the majority of samples, both TLR3 and TLR7 were immunoexpressed in cytoplasm. The immunoexpression was heterogeneous between individual tumors. Stronger TLR7 immunoexpression associated with recurrence rate and poorer disease-specific survival (DSS). TLR3 did not associate significantly with survival although we found an inverse correlation between TLR3 and TLR7 immunopositivity. Hence, when TLR3 immunoexpression was negative or mild, TLR7 immunoexpression was moderate to strong, and vice versa. CONCLUSIONS: TLR3 and TLR7 are immunoexpressed in minor salivary gland ACC. TLR7 is potentially an independent prognostic marker for recurrence rate and DSS.

Treatment of the neck in residual/recurrent disease after chemoradiotherapy for advanced primary laryngeal cancer.

Concomitant chemoradiotherapy (CRT) is extensively used as primary organ preservation treatment for selected advanced laryngeal squamous cell carcinomas (LSCC). The oncologic outcomes of such regimens are comparable to those of total laryngectomy followed by adjuvant radiotherapy. However, the management of loco-regional recurrences after CRT remains a challenge, with salvage total laryngectomy being the only curative option. Furthermore, the decision whether to perform an elective neck dissection (END) in patients with rN0 necks, and the extent of the neck dissection in patients with rN + necks is still, a matter of debate. For rN0 patients, meta-analyses have reported occult metastasis rates ranging from 0 to 31 %, but no survival advantage for END. In addition, meta-analyses also showed a higher incidence of complications in patients who received an END. Therefore, END is not routinely recommended in addition to salvage laryngectomy. Although some evidence suggests a potential role of END for supraglottic and locally advanced cases, the decision to perform END should weigh benefits against potential complications. In rN + patients, several studies suggested that selective neck dissection (SND) is oncologically safe for patients with specific conditions: when lymph node metastases are not fixed and are absent at level IV or V. Super-selective neck dissection (SSND) may be an option when nodes are confined to one level. In conclusion, current evidence suggests that in rN0 necks routine END is not necessary and that in rN + necks with limited nodal recurrences SND or a SSND could be sufficient.

Presence of herpesviruses, parvoviruses, and polyomaviruses in sinonasal lymphoma.

PURPOSE: Sinonasal lymphoma (SL) is a rare lymphatic neoplasm of the nasal cavities, paranasal sinuses and nasopharynx. Whereas some risk factors for SL subtypes have been identified, their aetiology is unknown. Along with other predisposing factors, the viral association of lymphomas, such as Epstein-Barr virus (EBV) and Burkitt and Hodgkin lymphomas, is well-established. Modern molecular biology techniques have enabled the discovery of novel human viruses, exemplified by the protoparvovirus cutavirus (CuV), associated with cutaneous T-cell lymphoma. These findings, and the anatomical location of the sinonasal tract with its rich microbiome and infectious agents, justify in-depth studies among SL. METHODS: We analysed the presence of 20 viruses of Orthoherpesviridae, Parvoviridae, and Polyomaviridae by qPCR in 24 SL tumours. We performed RNAscope in situ hybridisation (RISH) to localize the viruses. Parvovirus-specific IgG was analysed by enzyme immunoassay and targeted next-generation sequencing (NGS) was applied to detect CuV in plasma. RESULTS: We detected viral DNA in 15/24 (63%) tumours; nine of EBV, six of human herpesvirus (HHV) -7, four each of HHV-6B and parvovirus B19, two of cytomegalovirus, and one each of CuV and Merkel-cell polyomavirus. We found tumours with up to four viruses per tumour, and localized CuV and EBV DNAs by RISH. Two of the ten plasma samples exhibited CuV IgG, and one plasma sample demonstrated CuV viremia by NGS. CONCLUSION: Viruses were frequent findings in SL. The EBV detection rate was high in diffuse large B-cell lymphoma, and co-detections with other viruses were prevalent.

Viral DNA in submandibular gland tissue with an inflammatory disorder.

Background: The etiology behind different types of chronic sialadenitis (CS), some of which exhibit IgG4 overexpression, is unknown. Further, IgG4-related disease (IgG4-RD) commonly affects the submandibular gland, but its relationship to IgG4-overexpressing CS, and the antigen triggering IgG4 overexpression, remain unknown. Materials and Methods: By qPCR, we assessed the presence of 21 DNA-viruses causing IgG4 overexpression in submandibular gland tissue from patients with IgG4-positive and IgG4-negative CS. Healthy submandibular glands and glands with sialolithiasis without CS were used as controls. We examined the distribution of HHV-7, HHV-6B and B19V DNA, within virus PCR-positive tissues with RNAscope in-situ hybridization (RISH). Results: We detected DNA from seven viruses in 48/61 samples. EBV DNA was more prevalent within the IgG4-positive samples (6/29; 21%) than the IgG4-negative ones (1/19; 5.3%). B19V DNA was more prevalent within the IgG4-negative samples (5/19; 26%) than the IgG4-positive ones (4/29; 14%). The differences in virus prevalence were not statistically significant. Of the IgG4-RD samples (n = 3) one contained HHV-6B DNA. RISH only showed signals of HHV-7. Conclusions: None of the studied viruses are implicated as triggering IgG4-overexpression in CS. Although our results do not confirm viral etiology in the examined conditions, they provide valuable information on the prevalence of viruses in both diseased and healthy submandibular gland tissue.

The impact of pre-, pro- and synbiotics supplementation in colorectal cancer treatment: a systematic review.

Introduction: The effectiveness of the supplementation of prebiotics, probiotics and synbiotics as a therapeutic approach in colorectal cancer (CRC) remains unclear. The aim of this systematic review is to critically examine the current scientific evidence on the impact of modulating the microbiota, through the use of prebiotics, probiotics and synbiotics, in patients diagnosed with CRC undergoing treatment, to determine the potential therapeutic use of this approach. Methods: This systematic review was made according to the PRISMA 2020 guidelines. Inclusion criteria were randomized controlled trials (RCT) comparing the impact of pre-, pro-, or synbiotic supplementation with placebo or standard care in patients with CRC undergoing treatment. Exclusion criteria were non-human studies, non-RCTs, and studies in languages other than English or Portuguese. Six databases were consulted, namely, Cochrane Library, Pubmed, Scopus, Cinahl, MedicLatina and Web of Science until May of 2023. RAYYAN software was used to manage the search results and risk of bias was assessed according to the guidelines of the Cochrane Collaboration using the Rob 2.0 tool. Results: Twenty-four RCTs met the inclusion criteria and were included in this review. Administration of pre-, pro-, or synbiotics improved surgical outcomes such as the incidence of infectious and non-infectious postoperative complications, return to normal gut function, hospital length of stay, and antibiotic usage. The supplementation of these microorganisms also alleviated some symptoms from chemotherapy and radiotherapy, mainly diarrhea. Evidence on the best approach in terms of types of strains, dosage and duration of intervention is still scarce. Conclusions: Pre-, pro-, and synbiotics supplementation appears to be a beneficial therapeutic approach in CRC treatment to improve surgical outcomes and to alleviate side-effects such as treatment toxicity. More RCTs with larger sample sizes and less heterogeneity are needed to confirm these potential benefits and to determine the best strains, dosage, and duration of administration in each situation. Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier CRD42023413958.