Risk factors for cancer of unknown primary: a literature review.

Cancer of Unknown Primary (CUP) is metastatic cancer with an unidentifiable primary tumour origin during life. It remains difficult to study the occurrence and aetiology of CUP. Hitherto, it is unclear whether risk factors are associated with CUP, yet identifying these factors could reveal whether CUP is a specific entity or a cluster of metastasised cancers from various primary tumour origins. Epidemiological studies on possible CUP risk factors were systematically searched in PubMed and Web of Science on February 1st, 2022. Studies, published before 2022, were included if they were observational human-based, provided relative risk estimates, and investigated possible CUP risk factors. A total of 5 case-control and 14 cohort studies were included. There appears to be an increased risk for smoking in relation to CUP. However, limited suggestive evidence was found to link alcohol consumption, diabetes mellitus, and family history of cancer as increased risks for CUP. No conclusive associations could be made for anthropometry, food intake (animal or plant-based), immunity disorders, lifestyle (overall), physical activity, or socioeconomic status and CUP risk. No other CUP risk factors have been studied. This review highlights smoking, alcohol consumption, diabetes mellitus and family history of cancer as CUP risk factors. Yet, there remains insufficient epidemiological evidence to conclude that CUP has its own specific risk factor profile.

Association of metastatic pattern in breast cancer with tumor and patient-specific factors: a nationwide autopsy study using artificial intelligence.

BACKGROUND: Metastatic spread is characterized by considerable heterogeneity in most cancers. With increasing treatment options for patients with metastatic disease, there is a need for insight into metastatic patterns of spread in breast cancer patients using large-scale studies. METHODS: Records of 2622 metastatic breast cancer patients who underwent autopsy (1974-2010) were retrieved from the nationwide Dutch pathology databank (PALGA). Natural language processing (NLP) and manual information extraction (IE) were applied to identify the tumors, patient characteristics, and locations of metastases. RESULTS: The accuracy (0.90) and recall (0.94) of the NLP model outperformed manual IE (on 132 randomly selected patients). Adenocarcinoma no special type more frequently metastasizes to the lung (55.7%) and liver (51.8%), whereas, invasive lobular carcinoma mostly spread to the bone (54.4%) and liver (43.8%), respectively. Patients with tumor grade III had a higher chance of developing bone metastases (61.6%). In a subgroup of patients, we found that ER+/HER2+ patients were more likely to metastasize to the liver and bone, compared to ER-/HER2+ patients. CONCLUSION: This is the first large-scale study that demonstrates that artificial intelligence methods are efficient for IE from Dutch databanks. Different histological subtypes show different frequencies and combinations of metastatic sites which may reflect the underlying biology of metastatic breast cancer.

International consensus on the initial diagnostic workup of cancer of unknown primary.

BACKGROUND: Although the incidence of Cancer of Unknown Primary (CUP) is estimated to be 1-2 % of all cancers worldwide, no international standards for diagnostic workup are yet established. Such an international guideline would facilitate international comparison, provide adequate incidence and survival rates, and ultimately improve care of patients with CUP. METHODS: Participants for a four round modified Delphi study were selected via a CUP literature search in PubMed and an international network of cancer researchers. A total of 90 CUP experts were invited, and 34 experts from 15 countries over four continents completed all Delphi survey rounds. FINDINGS: The Delphi procedure resulted in a multi-layer CUP classification for the diagnostic workup. Initial diagnostic workup should at least consist of history and physical examination, full blood count, analysis of serum markers, a biopsy of the most accessible lesion, a CT scan of chest/abdomen/pelvis, and immunohistochemical testing. Additionally, the expert panel agreed on the need of an ideal diagnostic lead time for CUP patients. There was no full consensus on the place in diagnostic workup of symptom-guided MRI or ultrasound, a PET/CT scan, targeted gene panels, immunohistochemical markers, and whole genome sequencing. INTERPRETATION: Consensus was reached on the contents of the first diagnostic layer of a multi-layer CUP classification. This is a first step towards full consensus on CUP diagnostics, that should also include supplementary and advanced diagnostics.

Using Bilateral tDCS to Modulate EEG Amplitude and Coherence of Men With Opioid Use Disorder Under Methadone Therapy: A Sham-controlled Clinical Trial.

Objective. This study aimed to investigate the effect of bilateral transcranial direct current stimulation (tDCS) on the electroencephalography (EEG) amplitude and coherence in male patients with opioid use disorder (OUD), who were under methadone therapy. It compares the effects of active versus sham tDCS. Methods. This is a double-blind sham-controlled clinical trial. Participants were 30 male patients with OUD; they were divided into 3 groups of left anode/right cathode tDCS, right anode/left cathode tDCS, and sham tDCS. Their brainwave activity was measured by quantitative EEG before study and then active groups underwent tDCS (2 mA, 20 min) applied over their right/left dorsolateral prefrontal cortex (DLPFC) for 10 consecutive days. After stimulation, they were re-assessed. The collected data were analyzed in SPSS, MATLAB, and NeuroGuide v.2 applications. Results. After active tDCS, a significant decrease in amplitude of slow brain waves (delta, theta, and alpha) in prefrontal, frontal, occipital, and parietal areas, and an increase in the coherence of beta, delta, and theta frequency bands in the parietal, central, and temporal regions of addicts were reported. In the sham group, there was a significant decrease in the amplitude of the alpha wave and in the coherence of delta and theta waves. Conclusion. The active tDCS over the right/left DLPFC, as a noninvasive and complementary treatment, can modulate the amplitude and coherence of brainwaves in patients with OUD.