Reposition of the anti-inflammatory drug diacerein in an in-vivo colorectal cancer model.

Excessive interleukin (IL)-6 production is a driver for malignancy and drug resistance in colorectal cancer (CRC). Our study investigated a seven-week post-treatment with the anti-inflammatory drug, Diacerein (Diac), alone or in combination with 5-fluorouracil (5-FU), using a 1,2-dimethylhydrazine (DMH) rat model of CRC. Diac alone and 5-FU+Diac reduced serum levels of carcino-embryonic antigen (CEA), while all regimens decreased serum levels of colon cancer-specific antigen (CCSA), a more specific CRC biomarker. Additionally, Diac, 5-FU and their combination suppressed colonic content/gene expression of IL-6, its downstream oncogene, Kirsten rat sarcoma viral oncogene homolog (K-Ras), and consequently Notch intracellular domain and nuclear factor-kappa B (NF-κB) p65. In turn, NF-κB downstream factors, viz., matrix metalloproteinase-9 (MMP-9), vascular endothelial growth factor (VEGF), c-Myc, and B-cell lymphoma-2 (Bcl-2) were also downregulated, while E-cadherin was elevated. Additionally, the drugs reduced the immunoreactivity of CD31 to prove their anti-angiogenic effect, while the TUNEL assay confirmed the apoptotic effect. The apoptotic effect was confirmed by transferase dUTP nick-end labeling assay. Moreover, these drugs inhibited colon content of p-Akt, ß-catenin, and cyclin D1 immunoreactivity. The drugs also activated the tumor suppressor glycogen synthase kinase 3- ß (GSK3-ß) and upregulated the expression of the Nur77 gene, which represents the second arm of IL-6 signaling. However, only 5-FU upregulated miR-200a, another K-Ras downstream factor. The in-vitro cytotoxic and migration/invasion assays verified the molecular trajectories. Accordingly, we evaluated the antineoplastic effect of Diac alone and its possible chemosensitization effect when added to 5-FU. This combination may target critical oncogenic pathways, including the IL-6/K-Ras/Notch/NF-κB p65 axis, p-Akt/GSK3-ß/ß-catenin/cyclin D-1 hub, and Nur77.

Obstructing primary squamous cell carcinoma of caecum: A case report.

Squamous cell carcinoma (SCC) of the colon is a rare malignancy and usually a pathological surprise. Clinical presentation is usually very similar to adeno carcinoma variety. We report a case of a 56 year old male with primary SCC of caecum presenting as small bowel obstruction and managed with surgery and adjuvant chemotherapy. It was labelled as primary SCC after extensive search for other primary malignant SCC in body with possible metastasis to caecum. Due to rarity of the disease and lack of literature standardized protocols for neo-adjuvant and adjuvant therapy are not available.

Effect of camrelizumab plus transarterial chemoembolization on massive hepatocellular carcinoma.

OBJECTIVE: To investigate the efficacy of camrelizumab plus transarterial chemoembolization (TACE) on massive hepatocellular carcinoma (HCC) patients. METHODS: A total of 92 cases with massive HCC from October 2019 to January 2021 were prospectively enrolled and randomly divided into the study group (n = 46) and the control group (n = 46). The control group received TACE while the study group were treated with camrelizumab plus TACE. The primary end points were clinical efficacy and adverse events. And the secondary end points were liver function, and alpha fetoprotein (AFP), carcino-embryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9) levels before and after treatment. RESULTS: All participants were followed-up for 7 to 24 months, with a median of 12 months. Patients in the study group received TACE for 1-3 times, with an average of (2.01 ± 0.09) times, while patients in the control group receive TACE for 2-4 times, with an average of (3.78 ± 0.12) times, and the control group received significantly more TACEs (χ2 = 5.518, P = 0.019). During the follow-up, the response rate and disease control rate of the study group were significantly higher than those of the control group (χ2 = 5.518, P = 0.019; χ2 = 4.467, P = 0.041). Before treatment, the levels of total bilirubin (TBIL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alpha-fetoprotein (AFP), CEA, and CA19-9 were comparable between the groups (P > 0.05). After treatment, the levels of TBIL, ALT, AST, AFP, CEA, and CA19-9 decreased, and the above indicators in the study group were significantly lower than those in the control group (P < 0.05). All patients showed transient liver damage, vomiting, nausea, fever and abdominal pain after surgery, and their symptoms were relieved after symptomatic treatment. Adverse events occurred in 9 cases in the study group, and 3 cases in the control group (χ2 = 3.419, P = 0.064). CONCLUSION: Compared with TACE alone, camrelizumab plus TACE treatment can significantly improve the liver function of patients with massive HCC and enhance the treatment effect, which is worthy of clinical promotion.

Advance Rectal Cancer in a Young Patient: Should Screening Start Early?

Colorectal cancer is the third most common non-cutaneous malignancy in the United States, and the second most common cause of cancer-related deaths. Colorectal cancer is a broad term to include both colon and rectal cancer. Rectal cancer is commonly seen in age more the 50 years and often present with rectal bleeding. In this article, we will be discussing about a young female patient who presented with somatic pain as an initial symptom for metastatic rectal adenocarcinoma.

Primary Hepatic Burkitt Lymphoma: A Bizarre Site and Triumph Tale.

Primary hepatic Burkitt lymphoma (PHBL) is an extremely rare form extra nodal lymphoma and till now only 11 case reports have been found in the literature. We are reporting an adult female with primary hepatic Burkitt's lymphoma, who achieved complete remission after 5 months of combination chemotherapy containing vincristine, cyclophosphamide, doxorubicin, methotrexate, prednisolone and intrathecal chemotherapy. She is under regular follow up at our institute.

Nodule in Liver: Investigations, Differential Diagnosis and Follow-up.

Conventional ultrasonogram of the abdomen being noninvasive, inexpensive and ubiquitously available is the first imaging modality that raises suspicion of HCC in a patient with chronic liver disease with or without cirrhosis. The lesions in liver particularly nodule are being recognized with increased frequency with the wide spread use of ultrasonogram as the initial investigation and computerized tomography and magnetic resonance imaging subsequently. Any nodule in a cirrhotic liver should be considered as hepatocellular carcinoma until otherwise proved. This approach certainly is helpful in diagnosing HCC at its earliest possible stage to offer meaningful curative measures be it transplant, resection or ablative therapy. After a nodule is detected on ultrasonogram the next imaging modality can be a contrast enhanced study (dynamic CT scan or an MRI) to see if are present or not. Two vital clues for diagnosis of HCC by contrast enhanced imaging are presence of arterial hypervascularity and washout which are considered as "classical imaging features". This sequence of events of arterial uptake followed by washout is highly specific for diagnosis of HCC by imaging. If the features are typical showing classical imaging features (i.e hypervascular in the arterial phase with washout in portal venous or delayed phase) the lesion should be treated as HCC biopsy is not necessary. Nodular lesions showing an atypical imaging pattern, such as iso- or hypovascular in the arterial phase or arterial hypervascularity alone without portal venous washout, should undergo further examinations with another contrast enhanced imaging. Biopsy is advisable for those lesions which do not show classical features on the imaging.