Cytokines levels, Severity of acute mucositis and the need of PEG tube installation during chemo-radiation for head and neck cancer - a prospective pilot study

<p>Abstract</p> <p>Background</p> <p>The purpose of this pilot study was to detect a correlation between serum cytokine levels and severity of mucositis, necessitating installation of a percutaneous endoscopic gastrostomy tube (PEG) in head and neck (H&N) cancer patients receiving combined chemo-radiation therapy.</p> <p>Patients and Methods</p> <p>Fifteen patients with H&N epithelial cancer were recruited to this study. All patients received radiotherapy to the H&N region, with doses ranging from 50-70 Gy. Chemotherapy with cisplatin, carboplatin, 5-fluorouracil and taxanes was given to high-risk patients, using standard chemotherapy protocols. Patients were evaluated for mucositis according to WHO common toxicity criteria, and blood samples were drawn for inflammatory (IL-1, IL-6, IL-8, TNF-α) and anti-inflammatory (IL-10) cytokine levels before and during treatment.</p> <p>Results</p> <p>A positive correlation was found between IL-6 serum levels and severity of mucositis and dysphagia; specifically, high IL-6 levels at week 2 were correlated with a need for PEG tube installation. A seemingly contradictory correlation was found between low IL-8 serum levels and a need for a PEG tube.</p> <p>Conclusion</p> <p>These preliminary results, indicating a correlation between IL-6 and IL-8 serum levels and severity of mucositis and a need for a PEG tube installation, justify a large scale study.</p

Heparanase contributes to pancreatic carcinoma progression through insulin-dependent glucose uptake

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive tumor, which is highly resistant to existing therapies and characterized by one of the lowest survival rates known for solid cancers. Among the reasons for this poor prognosis are unique pathophysiological features of PDAC, such as dense extracellular matrix [ECM] creating barriers to drug delivery, as well as systemically-deregulated glucose metabolism manifested by diabetic conditions (i.e., hyperinsulinemia/hyperglycemia) occurring in the majority of PDAC patients. Moreover, in addition to systemically deregulated glucose homeostasis, intracellular metabolic pathways in PDAC are rewired toward increased glucose uptake/anabolic metabolism by the tumor cells. While the role of oncogene-driven programs in governing these processes is actively studied, mechanisms linking metabolic dysregulation and ECM enzymatic remodeling to PDAC progression/therapy resistance are less appreciated. The aim of the current study was to investigate the action of heparanase (the predominant mammalian enzyme that degrades heparan sulfate glycosaminoglycan in the ECM), as a molecular link between the diabetic state and the intracellular metabolic rewiring in PDAC pathogenesis. Here we show that in PDAC elevated levels of heparanase, coupled with diabetic conditions typical for PDAC patients, promote growth and chemotherapy resistance of pancreatic carcinoma by favoring insulin receptor signaling and GLUT4-mediated glucose uptake into tumor cells. Collectively, our findings underscore previously unknown mechanism through which heparanase acts at the interface of systemic and intracellular metabolic alterations in PDAC and attest the enzyme as an important and potentially modifiable contributor to the chemo-resistance of pancreatic tumors

The functional role of Nudt2 in human triple negative breast cancer

The main known function of Nudix hydrolase 2 (Nudt2) is to hydrolyze the secondary messenger diadenosine 5’, 5’’’-p1, p4-tetraphosphate (Ap4A). In this study we examined the role of Nudt2 in breast carcinoma through its expression in human invasive ductal carcinoma tissues, and its functions in human triple negative breast cancer (TNBC) cell lines. A significantly higher expression of Nudt2 was observed in human invasive ductal carcinoma tissues compared to that in normal breast tissue. Knockdown of Nudt2 in TNBC cell lines resulted in a significant reduction in cellular proliferation via the Ki67 marker, accompanied by G0/G1 phase cell cycle arrest, in the migration and invasion of these cells and in tumorigenicity and anchorage-independent growth. It can therefore be concluded that Nudt2 plays a significant role in promoting TNBC growth

A novel observation of pubic osteomyelitis due to Streptococcus viridans after dental extraction: a case report

<p>Abstract</p> <p>Introduction</p> <p>Pubic osteomyelitis should be suspected in athletic individuals with sudden groin pain, painful restriction of hip movements and fever. It is an infrequent and confusing disorder, which is often heralded by atypical gait disturbance and diffuse pain in the pelvic girdle. The most common pathogen is <it>Staphylococcus aureus </it>but, on occasions, efforts to identify infectious agents sometimes prove negative. Pubic osteomyelitis due to <it>Streptococcus viridans </it>has not been reported previously in the literature.</p> <p>Case presentation</p> <p>We describe the case of a fit 24-year-old athlete, who had a wisdom tooth extracted 2 weeks prior to the presentation, which could have served as a port of entry and predisposed the patient to transient bacteraemia.</p> <p>Conclusion</p> <p><it>S. viridans </it>is well known for causing infective endocarditis of native damaged heart valves, but to the best of the authors' knowledge it has not been reported previously as a cause of pubic osteomyelitis. We believe that this case should alert physicians to the association between dental procedures and osteomyelitis of the pubis secondary to <it>S. viridans</it>.</p

Peptide receptor radionuclide therapy in gastroenteropancreatic NEN G3:a multicenter cohort study

Peptide receptor radionuclide therapy (PRRT) is an established treatment of metastatic neuroendocrine tumors grade 1–2 (G1–G2). However, its possible benefit in high-grade gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN G3) is largely unknown. We therefore aimed to assess the benefits and side effects of PRRT in patients with GEP NEN G3. We performed a retrospective cohort study at 12 centers to assess the efficacy and toxicity of PRRT in patients with GEP NEN G3. Outcomes were response rate, disease control rate, progression-free survival (PFS), overall survival (OS) and toxicity. We included 149 patients (primary tumor: pancreatic n = 89, gastrointestinal n = 34, unknown n = 26). PRRT was first-line (n = 30), second-line (n = 62) or later-line treatment (n = 57). Of 114 patients evaluated, 1% had complete response, 41% partial response, 38% stable disease and 20% progressive disease. Of 104 patients with documented progressive disease before PRRT, disease control rate was 69%. The total cohort had median PFS of 14 months and OS of 29 months. Ki-67 21–54% (n = 125) vs Ki-67 ≥55% (n = 23): PFS 16 vs 6 months (P < 0.001) and OS 31 vs 9 months (P < 0.001). Well (n = 60) vs poorly differentiated NEN (n = 62): PFS 19 vs 8 months (P < 0.001) and OS 44 vs 19 months (P < 0.001). Grade 3–4 hematological or renal toxicity occurred in 17% of patients. This large multicenter cohort of patients with GEP NEN G3 treated with PRRT demonstrates promising response rates, disease control rates, PFS and OS as well as toxicity in patients with mainly progressive disease. Based on these results, PRRT may be considered for patients with GEP NEN G3.acceptedVersio

Reducing the number of CTs performed to monitor personalized dosimetry during peptide receptor radionuclide therapy (PRRT)

Abstract Background Peptide receptor radionuclide therapy (PRRT) with [177Lu]-DOTA-TATE is an effective treatment of neuroendocrine tumors (NETs). After each cycle of treatment, patient dosimetry evaluates the radiation dose to the risk organs, kidneys, and bone marrow, the most radiosensitive tissues. Absorbed doses are calculated from the radioactivity in the blood and from single photon emission computed tomography (SPECT) images corrected by computed tomography (CT) acquired after each course of treatment. The aim of this work is to assess whether the dosimetry along all treatment cycles can be calculated using a single CT. We hypothesize that the absorbed doses to the risk organs calculated with a single CT will be accurate enough to correctly manage the patients, i.e., whether or not to continue PRRT. Twenty-four patients diagnosed with metastatic NETs undergoing PRRT with [177Lu]-DOTA-TATE were retrospectively included in this study. We compared radiation doses to the kidneys and bone marrow using two protocols. In the “classical” one, dosimetry is calculated based on a SPECT and a CT after each treatment cycle. In the new protocol, dosimetry is calculated based on a SPECT study after each cycle but with the first acquired CT for all cycles. Results The decision whether or not to stop PRRT because of unsafe absorbed dose to the risk organs would have been the same had the classical or the new protocol been used. The agreement between the cumulative doses to the kidneys and bone marrow obtained from the two protocols was excellent with Pearson’s correlation coefficients r = 0.95 and r = 0.99 (P < 0.0001) and mean relative differences of 5.30 ± 6.20% and 0.48 ± 4.88%, respectively. Conclusions Dosimetry calculations for a given patient can be done using a single CT registered to serial SPECTs. This new protocol reduces the need for a hybrid camera in the follow-up of patients receiving [177Lu]-DOTA-TATE

Dermatomyositis Associated with Lung Cancer: A Brief Review of the Current Literature and Retrospective Single Institution Experience

Dermatomyositis is a rare inflammatory myopathy that is often related to lung cancer. In this retrospective observational study, we analyzed data from patients diagnosed with lung cancer at Soroka University Medical Center between January 2017 and July 2021. A total of 689 patients with lung cancer were included in this study, 97 of whom had small cell lung cancer and 592 had non-small cell lung cancer. We identified a single patient (60-year-old female) who presented with signs and symptoms of dermatomyositis, which was later confirmed to be associated with lung cancer as a paraneoplastic syndrome. Both our study and a recent review of the literature illustrate the temporal link between dermatomyositis and lung cancer, as well as reinforce the need for heightened cancer screenings in DM patients