Background:Aberrant mitogen/extracellular signal-regulated kinase 5 (MEK5)–extracellular signal-regulated protein kinase 5 (ERK5)-mediated signalling has been implicated in a number of tumour types including prostate cancer (PCa). The molecular basis of ERK5-driven carcinogenesis and its clinical relevance remain to be fully characterised.Methods:Modulation of ERK5 expression or function in human PCa PC3 and PC3–ERK5 (stably transfected with ERK5) cells was performed using siRNA-mediated knockdown or the MEK inhibitor PD18435 respectively. In vitro significance of ERK5 signalling was assessed by assays for proliferation, motility, invasion and invadopodia. Expression of matrix metalloproteinases/tissue inhibitors of metalloproteases was determined by Q-RT–PCR. Extracellular signal-regulated protein kinase 5 expression in primary and metastatic PCa was examined using immunohistochemistry.Results:Reduction of ERK5 expression or signalling significantly inhibited the motility and invasive capability of PC3 cells. Extracellular signal-regulated protein kinase 5-mediated signalling significantly promoted formation of in vivo metastasis in an orthotopic PCa model (P<0.05). Invadopodia formation was also enhanced by forced ERK5 expression in PC3 cells. Furthermore, in metastatic PCa, nuclear ERK5 immunoreactivity was significantly upregulated when compared with benign prostatic hyperplasia and primary PCa (P=0.013 and P<0.0001, respectively).Conclusion:Our in vitro, in vivo and clinical data support an important role for the MEK5–ERK5 signalling pathway in invasive PCa, which represents a potential target for therapy in primary and metastatic PCa.

Some simple pretreatment blood parameters and NIFS showed high accuracy for predicting development of SLRE post treatment. Application of these simple scores can improve assessment of long-term liver prognosis for CHC.

King's score for significant and advanced fibrosis and the APRI or FIB-4 score for cirrhosis could be the best simple indirect noninvasive scores.

Key Clinical MessagePrimary apocrine sweat gland carcinoma is a rare neoplasm. It is usually slow growing and is often suspected to be a benign disease at initial assessment. A thorough clinical and histological workup is required for diagnosis. Treatment of choice is wide local excision with clear margins.

T cell immunoglobulin mucin-3 (TIM-3) is an immune checkpoint identified as one of the key players in regulating T-cell responses. Studies have shown that TIM-3 is upregulated in the tumor microenvironment (TME). However, the precise role of TIM-3 in colorectal cancer (CRC) TME is yet to be elucidated. We performed phenotypic and molecular characterization of TIM-3+ T cells in the TME and circulation of CRC patients by analyzing tumor tissues (TT, TILs), normal tissues (NT, NILs), and peripheral blood mononuclear cells (PBMC). TIM-3 was upregulated on both CD4+ and CD3+CD4− (CD8+) TILs. CD4+TIM-3+ TILs expressed higher levels of T regulatory cell (Tregs)-signature genes, including FoxP3 and Helios, compared with their TIM-3− counterparts. Transcriptomic and ingenuity pathway analyses showed that TIM-3 potentially activates inflammatory and tumor metastatic pathways. Moreover, NF-κB-mediated transcription factors were upregulated in CD4+TIM-3+ TILs, which could favor proliferation/invasion and induce inflammatory and T-cell exhaustion pathways. In addition, we found that CD4+TIM-3+ TILs potentially support tumor invasion and metastasis, compared with conventional CD4+CD25+ Tregs in the CRC TME. However, functional studies are warranted to support these findings. In conclusion, this study discloses some of the functional pathways of TIM-3+ TILs, which could improve their targeting in more specific therapeutic approaches in CRC patients.

Background The pure large cell type is a rare variant of primary neuroendocrine carcinoma of the gallbladder. Few reports have mentioned extended survival. Although a multimodal treatment has been described in the treatment of such rare disease, redo liver resection has not yet been mentioned. Case report A 67-year-old lady was found to have poorly differentiated, high grade, pure large cell neuroendocrine tumor of the gallbladder after cholecystectomy for gallstones. After the diagnosis, staging workup showed a lesion in segment IVB/V of the liver, and chromogranin was elevated (982 mcg/L). The patient underwent central inferior hepatectomy and wedge excision of a lesion in segment III (discovered intra-operatively), with hilar lymphadenectomy. Three months after the first liver resection, she developed a new liver lesion II/III and underwent left lateral liver resection. The patient remained disease-free for 4 months following the second liver resection but then developed recurrent liver disease and was started on chemotherapy. Further progression led to multi-organ failure and death at 26 months from initial diagnosis. Conclusion This is the first reported repeat liver resection in such a rare disease that has led to extended overall survival. We suggest that a group of selected patients with this rare malignancy, and liver-limited disease, may benefit from repeated liver resection.

Myofibroma tumors are uncommon benign neoplasms, affecting mainly the early pediatric age group. Infantile myofibromas consist of benign nodules in the skin, muscle, or bone .Less often, they can occur in the lung, heart, gastrointestinal tract, or orbit. Infantile myofibromas exhibit growth in the immediate perinatal period that may continue for the first few months of life, reaching a size approaching several centimeters in diameter. Because this tumor grows rapidly during infancy, capillary hemangioma of the scalp or malignant neoplasia is often suspected. We examine a case of solitary infantile myofibroma in a newborn's scalp, which presented a diagnostic challenge.

Liver biopsy even today remains the standard of care for grading and staging chronic hepatitis despite advances in noninvasive markers of liver fibrosis. Literature suggests an expanding role for real-time image guided liver biopsy and declining trend for blind liver biopsies. In our center, where we perform around 400 liver biopsies per year, we performed a prospective clinical audit of our practice of blind outpatient percutaneous liver biopsies. Patients requiring histological grading and staging of chronic hepatitis routinely undergo blind outpatient percutaneous liver biopsies in our endoscopy unit unless there is a definite indication for real-time image guidance. All procedures were assessed for safety, and all specimens were evaluated by a specimen quality grading score for adequacy for grading and staging of chronic hepatitis. Of the 446 patients referred for histological grading and staging of chronic hepatitis C by liver biopsy, only 42 patients (9.5 %) required real-time ultrasound for liver biopsy. The remaining 404 patients underwent blind outpatient percutaneous liver biopsies which were found to be extremely safe with no major complications, yielding adequate liver tissue with high specimen quality score allowing optimal grading and staging of chronic hepatitis.