Search Results (51)

Background/Objectives: Incidence of malnutrition varies greatly among gastrointestinal (GI) cancer patients and has a major impact on prognosis. We performed a meta-analysis to identify risk factors for malnutrition risk, malnutrition diagnosis, and cachexia in patients with GI cancer. Methods: A systematic search was performed on 31 October 2025 on the PubMed (Medline), Embase, and Cochrane Library databases. Eligible studies reported on risk factors for malnutrition risk, malnutrition diagnosis, malnutrition-related complication risk and cachexia in adult patients with GI cancer. Articles on neuroendocrine tumours, primary cancer outside the GI tract, and the paediatric population were excluded. The random-effects model yielded the pooled odds ratios (ORs) and 95% confidence intervals (CIs) for the investigated risk factors. Results: A total of 37,624 records were identified. Data from 262,525 patients from 578 articles were included in the analysis. Older age (≥65) was associated with higher odds for malnutrition risk across all GI cancers. In gastric cancer, males had a lower odds for malnutrition risk (OR 0.84; 95% CI 0.75–0.95); however, the sex difference across other cancer types was heterogeneous, and mostly not significant. Tumour location influenced the odds for malnutrition-related complication risk in pancreatic ductal adenocarcinoma (head vs. body/tail—OR 1.48; 95% CI 0.98–2.23) and colorectal cancer (colon vs. rectal—OR 1.39; 95% CI 1.07–1.81; right-sided vs. left-sided—OR 1.54; 95% CI 1.34–1.77). Increased C-reactive protein alone indicated higher odds for malnutrition risk at baseline. Conclusions: Inflammatory biomarkers and tumour characteristics may indicate malnutrition risk in GI cancer at baseline. There is a great need for standardised and harmonised approaches in nutritional status assessment in GI cancer. Full article

Background:Streptococcus pneumoniae is a well-known pathogen responsible for respiratory and invasive diseases; however, central nervous system (CNS) involvement in the form of bacterial myelitis is exceedingly rare, particularly in immunocompetent adults. Moreover, the association between pneumococcal infections and reactive arthritis is scarcely documented. We report an unusual case of pneumococcal myelitis complicated by reactive arthritis in an elderly patient with no evident immunosuppression. Case Presentation: A 68-year-old man with a medical history of hypertension, benign prostatic hyperplasia, multiple disc herniations, and a resected pancreatic neuroendocrine tumour presented to the emergency department with acute urinary retention and fever (38.5 °C). The neurological examination revealed lower limb weakness and decreased deep tendon reflexes. Spinal magnetic resonance demonstrated T2 hyperintense lesions suggestive of longitudinally transverse myelitis. Cerebrospinal fluid (CSF) analysis showed pleocytosis with elevated protein levels; the polymerase chain reaction (PCR) test resulted positive result for Streptococcus pneumoniae. The patient received intravenous antimicrobial and corticosteroid therapy with partial neurological improvement. Within days, he developed acute monoarthritis of the right ankle. Joint aspiration revealed sterile inflammatory fluid, negative for crystals and cultures, supporting a diagnosis of reactive arthritis. The articular symptoms resolved with the use of prednisone. An extensive immunological work-up was negative, and no other infectious or autoimmune triggers were identified. The patient underwent a structured rehabilitation program with gradual improvement in motor function over the following weeks. Conclusions: This case illustrates a rare clinical scenario of pneumococcal myelitis associated with reactive arthritis in a patient without overt immunosuppression. It highlights the importance of considering bacterial aetiologies in cases of acute transverse myelitis and the potential for unusual systemic immune responses such as reactive arthritis. Early recognition and the administration of appropriate antimicrobial and supportive therapies are crucial for improving neurological and systemic outcomes. To our knowledge, this is one of the first reported cases describing the co-occurrence of these two conditions in the context of S. pneumoniae infection. Full article

Background/Objectives: Insulinomas are rare insulin-secreting pancreatic neuroendocrine tumours (pNETs). Preoperative tumour localisation can usually be achieved by computed tomography (CT), magnetic resonance imaging, or positron emission tomography (PET)-CT. However, cross-sectional imaging can be negative, defining an insulinoma as occult and thus hampering surgical resection. Methods: All patients who underwent minimally invasive (MI) surgery for an insulinoma at the University Medical Center Hamburg-Eppendorf since 2017 were analysed. Clinicopathological parameters and diagnostic and operative approaches were assessed. A literature search of the MI resection of occult insulinomas was conducted. Results: Of eight patients with MI-resected insulinomas, two (25%) had negative preoperative imaging. Mean tumour size was 17.2 ± 13.3 mm. Patients underwent distal pancreatectomy (DP), enucleation, and pancreatic head resection (PHR) in 62.5% (5/8), 25.0% (2/8), and 12.5% (1/8) of cases, respectively. One patient had a major postoperative complication (Clavien–Dindo ≥ 3a). Twenty-four studies reporting on 140 occult insulinomas were identified. Occult insulinomas were more frequent in females, often located in the distal pancreas and G1-differentiated. Glucagon-Like Peptide-1 Receptor/PET-CT most frequently localised the conventionally non-visible insulinomas (positive in 67/76, 88.2%). Enucleation, DP, PHR and other resections were conducted in 47/94 (50.0%), 40/94 (42.6%), 4/94 (4.3%), and 3 (3.2%) of the reported cases. MI resection was reported in 10 of 19 (52.6%) specified resections. Conclusions: Insulinomas can be undetectable in cross-sectional and functional imaging. Surgical exploration with intraoperative ultrasound should be considered when clinical presentation and biochemical findings are highly suggestive for insulinoma. Minimally invasive and parenchyma sparing resection is feasible even for occult insulinomas and should always be considered. Full article

Aims: The purpose of this study was to evaluate survival outcomes and recurrence patterns following curative-intent resection of pancreatic neuroendocrine tumours (PNETs) at a UK tertiary centre. The secondary aims included identifying prognostic clinicopathological factors that influenced survival. Methods: Patients undergoing curative-intent surgical resection for PNETs between August 2010 and March 2024 were retrospectively reviewed. The data collated included demographics, histopathology, recurrence, and survival outcomes. Results: Eighty-six patients were included, with a median age of 61.5 years (IQR: 50–71) and an equal sex distribution. Most tumours were solitary (88.4%) and located in the pancreatic tail (57%), with distal pancreatectomy performed in 75% of cases. The median tumour size was 25 mm (IQR: 13–40). Lymph node metastases were observed in 23.3% of patients, and R0 resection was achieved in 67%. Most of the PNETs resected were WHO grade 1 tumours (65.1%), followed by grade 2 tumours (26.7%). Postoperative morbidity occurred in 37.2% of cases, while the 30-day postoperative mortality rate was 1.5%. Recurrence was observed in 13.95% of patients, with a median time to recurrence of 36.3 months. The 5-year overall survival (OS) was 83.0%, with a median OS and disease-free survival (DFS) of 143.3 months and 147.0 months, respectively. Multivariable analysis revealed that poorer DFS was associated with larger tumours (p = 0.009), higher tumour grade (p = 0.006), male sex (p = 0.039), vascular invasion (p = 0.003), perineural invasion (p = 0.042) and lymph node metastases (p = 0.015). OS was significantly influenced by the Charlson Comorbidity Index (p < 0.001) and tumour grade (p = 0.025). Conclusions: PNETs are associated with excellent long-term survival following curative-intent resection. However, adverse pathological features are linked to an increased risk of recurrence and a poorer prognosis. Full article

Cancer metabolism is a hallmark of cancer. However, the impact of systemic metabolism and diet on tumour evolution is less understood. This study delves into the role of glucagon, as a component of the pancreatic microenvironment, in regulating features of pancreatic neuroendocrine tumour (pNET) cells and the metabolic remodelling occurring in the presence and absence of glucose. pNET cell lines (BON-1 and QGP-1) and the non-malignant pancreatic α-TC1 cell line were used as models. Results showed that pNET cells responded differently to glucose deprivation than α-TC1 cells. Specifically, pNET cells upregulated the GCGR in the absence of glucose, while α-TC1 cells did so in high-glucose conditions, allowing the glucagon-related pERK1/2 activation under these conditions in pNET cells. Glucagon enhanced cancerous features in pNET BON-1 cells under glucose-deprived and hyperglucagonemia-compatible concentrations. In the α-TC1 cell line, glucagon modulated cell features under high-glucose and physiological glucagon levels. NMR exometabolome analysis revealed differences in metabolic processes based on glucose availability and glucagon stimulation across cell lines, highlighting amino acid metabolism, glycolysis, and gluconeogenesis. The expression of metabolic genes was consistent with these findings. Interestingly, QGP-1 and α-TC1 cells produced glucose in no-glucose conditions, and glucagon upregulated glucose production in α-TC1 cells. This suggests that gluconeogenesis may be beneficial for some pNET subsets, pointing out novel metabolism-based strategies to manage pNETs, as well as a step forward in endocrinology and systemic metabolism. The association between GCGR expression and malignancy and a negative correlation between glucagon receptor (GCGR) and glucagon-like peptide-1 receptor (GLP-1R) expression was observed, indicating a biological role of glucagon in pNETs that deserves to be explored. Full article

Belzutifan is a new HIF-α inhibitor mainly used in two different indications: von Hippel–Lindau syndrome-associated renal cell carcinoma, haemangioblastomas and pancreatic neuroendocrine tumours, as well as sporadic advanced pre-treated renal cell carcinoma. Although efficacy has been demonstrated in phase II and III studies, belzutifan is still not approved in many countries. In addition, von Hippel–Lindau syndrome is a rare disease. Therefore, there is virtually no real-world experience data of belzutifan efficacy available. We aim to determine the real-world efficacy and tolerability of belzutifan in patients with von Hippel–Lindau syndrome-associated tumours and in patients with sporadic advanced tyrosine kinase- and immune checkpoint inhibitors pre-treated for renal cell carcinoma. A retrospective analysis of five patients treated with belzutifan between 2023 and 2024 at a Swiss cancer centre was conducted. In this case series, all patients consistently benefitted from belzutifan with response to treatment. This case series provides real-world evidence that belzutifan is an effective and well-tolerated treatment option for patients with von Hippel–Lindau syndrome-associated renal cell carcinoma, haemangioblastomas and sporadic advanced pre-treated renal cell carcinoma. Full article

Background: Sarcopenia is a muscle disease that occur across a lifetime. It is commonly described in the aging population but can occur earlier in life in patients with cancer. Previous studies demonstrated sarcopenia is highly prevalent in patients with gastroenteropancreatic neuroendocrine tumours (GEP-NETs). In solid organ cancers, such as colorectal or pancreatic cancer, the presence of sarcopenia is associated with surgical complications. It is unknown if sarcopenia in patients with GEP-NETs is a risk factor for surgical complications. Methods: A multicentre retrospective study was performed in patients with a recently diagnosed GEP-NET and surgery to the primary tumour. CT scans were analysed for body composition analyses to assess for the presence of sarcopenia. Data regarding surgical procedures and complications were collected. Any major surgical complication was considered as Clavien–Dindo score ≥ 3. Results: This study included 180 patients, with 83 being male (46%) with a median age of 62 years (IQR 54–69). Most patients (n = 138, 77%) had a small intestinal NET, while 36 patients (20%) had pancreatic NETs. Sarcopenia was present in 109 patients (61%). In 43 patients (24%), surgical complications were recorded, and 21 complications (49%) were considered as major. Any type of surgical complication was not statistically different between patients without sarcopenia (n = 17, 24%) and with sarcopenia (n = 26, 24%)—a p-value of 0.36. This was the same for major complications; between patients without sarcopenia (n = 5, 24%) and with sarcopenia (n = 16, 76%)—a p-value of 0.18. Conclusions: Sarcopenia is highly prevalent in patients with a recently diagnosed GEP-NET, but this is not associated with major surgical complications. Future studies should include pathophysiological mechanisms that could be used to identify the causes of sarcopenia, its effect on quality of life and other oncological outcomes. Full article

Background: Given the rarity and heterogeneity of pancreatic neuroendocrine neoplasms (pNEN), treatment algorithms and sequencing are primarily guided by expert opinions with limited evidence. Aim: To investigate overall survival (OS), median progression-free survival (mPFS), and prognostic factors associated with the most common medical treatments for pNEN. Methods: Retrospective single-center study encompassing patients diagnosed and monitored between 2000 and 2020 (n = 192). Results: Median OS was 36 (95% CI: 26–46) months (99 months for grade (G) 1, 62 for G2, 14 for G3, and 10 for neuroendocrine carcinomas). Patients treated with somatostatin analogues (SSA) (n = 59, median Ki-67 9%) had an mPFS of 28 months. Treatment line (HR (first line as reference) 4.1, 95% CI: 1.9–9.1, p ≤ 0.001) emerged as an independent risk factor for time to progression. Patients with a Ki-67 index ≥10% (n = 28) had an mPFS of 27 months. Patients treated with streptozocin/5-fluorouracil (STZ/5FU) (n = 70, first-line treatment n = 68, median Ki-67 10%) had an mPFS of 20 months, with WHO grade serving as an independent risk factor (HR (G1 (n = 8) vs. G2 (n = 57)) 2.8, 95% CI: 1.1–7.2, p-value = 0.031). Median PFS was 21 months for peptide receptor radionuclide therapy (PRRT) (n = 41, first line n = 2, second line n = 29, median Ki-67 8%), 5 months for carboplatin and etoposide (n = 66, first-line treatment n = 60, median Ki-67 80%), and 3 months for temozolomide-based therapy (n = 56, first-line treatment n = 17, median Ki-67 30%). Conclusion: (1) Overall survival was, as expected, highly dependent on grade; (2) median PFS for SSA was around 2.5 years without difference between tumors with Ki-67 above or below 10%; (3) STZ/5FU as first-line treatment exhibited a superior mPFS of 20 months compared to what has historically been reported for targeted treatments; (4) PRRT in G2 pNEN achieved an mPFS similar to first-line chemotherapy; and (5) limited treatment efficacy was observed in high-grade tumors when treated with carboplatin and etoposide or temozolomide. Full article

A literature search of MEDLINE/PUBMED was conducted with the aim to highlight current endoscopic management of localised gastro-entero-pancreatic NETs. Relevant articles were identified through a manual search, and reference lists were reviewed for additional articles. The results of the research have been displayed in a narrative fashion to illustrate the actual state-of-the-art of endoscopic techniques in the treatment of NETs. Localised NETs of the stomach, duodenum and rectum can benefit from advanced endoscopic resection techniques (e.g., modified endoscopic mucosal resection, endoscopic full thickness resection, endoscopic submucosal dissection) according to centre expertise. Radiofrequency thermal ablation can be proposed as an alternative to surgery in selected patients with localised pancreatic NETs. Full article

Insulinomas are rare functional pancreatic neuroendocrine tumours, which metastasize in 10% of cases. As predicting the prognosis can be challenging, there is a need for the determination of clinicopathological factors associated with metastatic potential. The aim of this study is to evaluate the glucagon-like peptide-1 receptor (GLP-1R) expression in insulinomas and to analyse its association with clinicopathological features and patient outcome. This retrospective study involves pancreatic tumour tissue samples from fifty-two insulinoma patients. After histological re-evaluation, formalin-fixed paraffin-embedded tissue samples were processed into tissue microarrays and stained immunohistochemically with a monoclonal GLP-1R antibody. Forty-eight of the forty-nine (98%) non-metastatic tumours expressed GLP-1R, while one non-metastatic, multiple endocrine neoplasia type 1 (MEN1)-related tumour and all three of the metastatic tumours lacked GLP-1R expression. The lack of GLP-1R expression was associated with impaired overall survival, larger tumour diameter, higher Ki-67 PI and weaker insulin staining. Somatostatin receptor 1–5 expression did not differ between GLP-1R-positive and GLP-1R-negative insulinomas. In conclusion, the lack of GLP-1R expression is associated with metastatic disease and impaired survival in insulinoma patients. Thus, GLP-1R expression could be a useful biomarker in estimating the metastatic potential of the tumour and the prognosis of surgically treated patients. Full article

Several solid lesions can be found within the pancreas mainly arising from the exocrine and endocrine pancreatic tissue. Among all pancreatic malignancies, the most common subtype is pancreatic ductal adenocarcinoma (PDAC), to a point that pancreatic cancer and PDAC are used interchangeably. But, in addition to PDAC, and to the other most common and well-known solid lesions, either related to benign conditions, such as pancreatitis, or not so benign, such as pancreatic neuroendocrine neoplasms (pNENs), there are solid pancreatic lesions considered rare due to their low incidence. These lesions may originate from a cell line with a differentiation other than exocrine/endocrine, such as from the nerve sheath as for pancreatic schwannoma or from mesenchymal cells as for solitary fibrous tumour. These rare solid pancreatic lesions may show a behaviour that ranges in a benign to highly aggressive malignant spectrum. This review includes cases of an intrapancreatic accessory spleen, pancreatic tuberculosis, solid serous cystadenoma, solid pseudopapillary tumour, pancreatic schwannoma, purely intraductal neuroendocrine tumour, pancreatic fibrous solitary tumour, acinar cell carcinoma, undifferentiated carcinoma with osteoclastic-like giant cells, adenosquamous carcinoma, colloid carcinoma of the pancreas, primary leiomyosarcoma of the pancreas, primary and secondary pancreatic lymphoma and metastases within the pancreas. Therefore, it is important to determine the correct diagnosis to ensure optimal patient management. Because of their rarity, their existence is less well known and, when depicted, in most cases incidentally, the correct diagnosis remains challenging. However, there are some typical imaging features present on cross-sectional imaging modalities that, taken into account with the clinical and biological context, contribute substantially to achieve the correct diagnosis. Full article

Atrx loss was recently ascertained as insufficient to drive pancreatic neuroendocrine tumour (PanNET) formation in mice islets. We have identified a preponderant role of Atrx in the endocrine dysfunction in a Rip-Cre;Atrx^KO genetically engineered mouse model (GEMM). To validate the impact of a different Cre-driver line, we used similar methodologies and characterised the Pdx1-Cre;Atrx^KO (P.Atrx^KO) GEMM to search for PanNET formation and endocrine fitness disruption for a period of up to 24 months. Male and female mice presented different phenotypes. Compared to P.Atrx^WT, P.Atrx^HOM males were heavier during the entire study period, hyperglycaemic between 3 and 12 mo., and glucose intolerant only from 6 mo.; in contrast, P.Atrx^HOM females started exhibiting increased weight gains later (after 6 mo.), but diabetes or glucose intolerance was detected by 3 mo. Overall, all studied mice were overweight or obese from early ages, which challenged the histopathological evaluation of the pancreas and liver, especially after 12 mo. Noteworthily, losing Atrx predisposed mice to an increase in intrapancreatic fatty infiltration (FI), peripancreatic fat deposition, and macrovesicular steatosis. As expected, no animal developed PanNETs. An obese diabetic GEMM of disrupted Atrx is presented as potentially useful for metabolic studies and as a putative candidate for inserting additional tumourigenic genetic events. Full article

The most common tumour of the pancreas is ductal adenocarcinoma (PDAC). It remains one of the most lethal non-neuroendocrine solid tumours despite the use of a multi-approach strategy. Other, less-common neoplasms, which are responsible for 15% of pancreatic lesions, differ in treatment and prognosis. Due to the low incidence rate, there is a lack of information about the rarest pancreatic tumours. In this review, we described six rare pancreatic tumours: intraductal papillary mucinous neoplasm (IPMN), mucinous cystadenoma (MCN), serous cystic neoplasm (SCN), acinar cell carcinoma (ACC), solid pseudopapillary neoplasm (SPN) and pancreatoblastoma (PB). We distinguished their epidemiology, clinical and gross features, covered the newest reports about courses of treatment and systematised differential diagnoses. Although the most common pancreatic tumour, PDAC, has the highest malignant potential, it is still essential to properly classify and differentiate less-common lesions. It is vital to continue the search for new biomarkers, genetic mutations and the development of more specific biochemical tests for determining malignancy in rare pancreatic neoplasms. Full article

Somatostatin-analogues (SSAs) are a first-line treatment of unresectable neuroendocrine tumours (NETs). However, SSAs inhibit pancreatic secretions, which could lead to pancreatic exocrine insufficiency (PEI). PEI is known to be detrimental to patient quality of life and nutritional status. This study aimed to evaluate the effect of SSAs on pancreatic exocrine function in patients with NETs, using the ¹³C-mixed triglyceride breath test (¹³C-MTGT). Exocrine function was assessed using the ¹³C-MTGT at baseline and after a third SSA injection (two months). A quotient of ¹³CO₂/¹²CO₂ was measured by mass spectrometry, and the cumulative percent dose recovered at 6 h (cPDR) is reported. The secondary endpoints investigated were change in weight, HbA1C, and vitamin D levels. Ten patients completed the study. Exocrine function reduced in all patients (n = 10) following SSA therapy (median reduction from baseline: −23.4% (range: −42.1–0.5%, p = 0.005)). vitamin D levels decreased in all but one patient (median decrease from baseline: −26.5%, (−44.7–10%; p = 0.038)), and median HbA1C levels increased by 8.0% (0–59.3%; p = 0.008). Change in weight was not significant (median decrease from baseline: −0.21% (−4.5–3.5%, p = 1.000)). SSA therapy has a consistent impact on exocrine function from early in the treatment course, but the long-term clinical effects of this remain to be defined. Further studies are required to determine the clinical relevance of this observation and optimise the management of PEI in this cohort. Full article

Little information is available concerning protein expression of the calcitonin receptor-like receptor (CALCRL) at the protein level. Here, we developed a rabbit monoclonal antibody, 8H9L8, which is directed against human CALCRL but cross-reacts with the rat and mouse forms of the receptor. We confirmed antibody specificity via Western blot analyses and immunocytochemistry using the CALCRL-expressing neuroendocrine tumour cell line BON-1 and a CALCRL-specific small interfering RNA (siRNA). We then used the antibody for immunohistochemical analyses of various formalin-fixed, paraffin-embedded specimens of normal and neoplastic tissues. In nearly all tissue specimens examined, CALCRL expression was detected in the capillary endothelium, smooth muscles of the arterioles and arteries, and immune cells. Analyses of normal human, rat, and mouse tissues revealed that CALCRL was primarily present in distinct cell populations in the cerebral cortex; pituitary; dorsal root ganglia; epithelia, muscles, and glands of the larger bronchi; intestinal mucosa (particularly in enteroendocrine cells); intestinal ganglia; exocrine and endocrine pancreas; arteries, capillaries, and glomerular capillary loops in the kidneys; the adrenals; Leydig cells in the testicles; and syncytiotrophoblasts in the placenta. In the neoplastic tissues, CALCRL was predominantly expressed in thyroid carcinomas, parathyroid adenomas, small-cell lung cancers, large-cell neuroendocrine carcinomas of the lung, pancreatic neuroendocrine neoplasms, renal clear-cell carcinomas, pheochromocytomas, lymphomas, and melanomas. In these tumours with strong expression of CALCRL, the receptor may represent a useful target structure for future therapies. Full article