Hepatocellular carcinoma (HCC) is the most common liver cancer and is highly malignant. Current diagnostic tests are blood, imaging and biopsy, with no useful predictive biomarker. Additionally, targeted therapies are unavailable, which hinders the potential for personalized therapy in HCC patients. Here, we discuss the limited studies conducted thus far to identify molecular targets for early detection and treatment of HCC, their limitations and future directions in this field. However, the integration of multi-omics analyses, such as genomics, proteomics, and phosphoproteomics, has provided valuable insights into the mechanisms and pathways underlying the disease.
Objective: To identify and compare current modifiable and non-modifiable risk factors for pancreatic cancer (PaCa) that may have potential application in PaCa risk stratification, prevention, and early detection. Material: All articles in this literature review were identified through systematic searches of PubMed, Medline
Understanding the currently available evidence regarding multimodal approaches is critically important.The Southwest Oncology Group INT-0116 trial demonstrated improved overall survival and disease-free survival using adjuvant therapy-specifically CRT-compared to surgery alone [16].Subsequently, several other studies have supported the use of postoperative chemotherapy and/or CRT in addition to surgery with improved outcomes [17][18][19][20][21].This was followed by the MAGIC trial, which demonstrated a survival advantage for the use of perioperative combination chemotherapy (epirubicin, cisplatin,) as compared to resection alone and
Introduction: Pancreatic metastases from soft tissue sarcomas is rare.Case presentation: A woman known for high grade intimal sarcoma presented during her follow a solitary metastatic relapse of the head of pancreas.The MRI evidenced a 3.5 cm mass of the head of pancreas, hyper-intense on T1, T2 and diffusion weighted images.A new 18 F-FDG PET/CT confirmed the presence of a solitary hypermetabolic mass of the head of the pancreas (SUVmax 11.4), highly suspicious of an isolated pancreatic relapse.Results: Following multidisciplinary discussion, a pancreaticoduodenectomy with resection of whole gallbladder and locoregional lymph nodes dissection was performed.The patient had survived > 6 years after the pancreatectomy.Conclusions: Pancreatic metastases from STS are quite rare and no standard approach has been established yet.Multidisciplinary approach and evaluation of a surgical resection of isolated metastases can achieve long disease-free survival interval and be of curative intent.
Providing the many beneficial effects of RFs which are reviewed as follows, denying to oncology patients at any stage of the disease the possibility of using them, would be a discriminatory act in comparison with other patients in areas such as rehabilitation, aesthetic and sports medicine.We envision the use of RFs based technologies in a complementary medicine approach, recommending that their use would not induce AbstractIn this paper, we review the scientific literature dealing with many potentially interesting applications of non-ionizing electromagnetic radiations, in the radiofrequencies range, in oncology.Despite their mechanisms of action are still largely unrecognised and clinical trials haven't still been carried out to support their efficacy with respect to the natural course of the disease, these technologies are usually characterized by very favorable safety profiles both for patients and operators.We reason that denying their use to oncology patients at any stage of the disease appears a discriminatory act in comparison with patients in other areas of medicine, such as rehabilitation, aesthetic and sports medicine, where these technologies are routinely applied, instead.We envision their application in a complementary approach, in order not to compromise compliance with currently validated and proven therapeutic protocols.
While adverse gastrointestinal events related to chemotherapy are known to occur, delayed anastomotic leakage during chemotherapy with concurrent ramucirumab treatment has never been reported.We describe the clinical course of a patient who experienced delayed anastomotic leakage during 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) and ramucirumab treatments, which was ultimately fatal.The patient was a 78-year-old man who underwent laparoscopic right hemicolectomy with regional lymphadenectomy for advanced ascending colon cancer that was symptomatic and accompanied by unresectable and multiple liver metastases.Anastomosis was performed using a stapler (a functional end-to-end anastomosis technique); the postoperative course was uneventful.One-month post-surgery, the patient received five courses of chemotherapy, which included 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) with bevacizumab as the first-line treatment and FOLFIRI with ramucirumab as the second-line treatment due to the progression of liver metastases observed on contrast-enhanced computed tomography.During the sixth course of ramucirumab and FOLFIRI, the patient reported right lower abdominal pain.Butylscopolamine was administered because the abdominal pain was considered a side effect of irinotecan, and his symptoms slightly improved.That night, he presented to our emergency room with sustained abdominal pain.Abdominal computed tomography showed intra-abdominal free air and anastomotic leakage at the ileo-colonic anastomosis from his previous surgery, without any peritoneal dissemination or local recurrence.Emergency surgery including resection of the leaked anastomosis and ileostomy was performed.Postoperative ileus was observed, and leucopenia (neutropenia) occurred from postoperative day 7. Severe pneumonia and respiratory failure also occurred.The patient died on postoperative day 11.We believe that our patient's delayed anastomotic leakage (6 months post-initial surgery) was a novel adverse event related to ramucirumab use.Although abdominal pain may occur after irinotecan administration, clinicians should be aware of this potentially fatal side effect of ramucirumab to facilitate rapid treatment.
Many experimental models are applied to expand the arsenal of molecules that can inhibit or stimulate angiogenesis.Walker 256 carcinosarcoma was discovered when analyzing mammary gland adenocarcinomas in female rats and has been maintained in the laboratory since then.It has fast and aggressive growth, enabling experimental evaluation of the response to antiangiogenics.We analyzed the use of gum arabic, a natural substance obtained from the sap of the trunks and branches of Acacia senegal trees, and eugenol, one of the main components of clove essential oil, against Walker tumors in rats.Both substances alone have been experimentally found to have antioxidant activity, as well as anticancerogenic and cytotoxic effects, but no study has yet tested the effect of both substances simultaneously.Specifically, we evaluated the effect of gum arabic and eugenol on the progression and angiogenesis of Walker tumor cells implanted in the subcutaneous tissue of Wistar rats.Sixty female rats, with average weight of 150 grams, were distributed in 10 groups of 6 animals each, with five control groups and five treatment groups.The treatment groups received Walker tumor implants on the first day of the experiment, followed by administration of the test substances by gavage for 5 days.The control groups received the same substances, except the inoculum was distilled water.The substances administered were distilled water, celecoxib, gum arabic and eugenol, the last of which was used in pure form.We evaluated the tumor dimensions and macroscopic and microscopic appearance (hematoxylin-eosin staining).The study of angiogenesis was performed by immunohistochemistry (CD-31), and the quantification was achieved by evaluation of the microvascular density by the SAMM software applied to images of the areas with greatest microvascular density.The animals that received only distilled water suffered from greater invasion of the dorsal subcutaneous tissue and musculature by the tumor in relation to the other groups.The tumor volume was smaller in the groups that received gum arabic or eugenol alone and those receiving gum arabic together with eugenol and celecoxib, but the microvascular density was smaller only in the group that received celecoxib alone.Thus, only celecoxib inhibited angiogenesis.Gum arabic and eugenol, in the doses administered, reduced the tumor growth, but did not inhibit angiogenesis of the Walker tumor cell implants.
A correlation exists between the number of lymph nodes (LNs) detected in radical cystectomy specimens and the accuracy of pathologic nodal (pN) staging.In this context, correct handling of pathology specimens is crucial, but there is currently no consensus on the optimal methodology.The objective of the present study was to compare two main methods: palpation and complete embedding of all fat tissue.Palpation of LNs and complete embedding of remaining fat tissue were performed in 42 patients.In 33.3% of the patients, no LNs were observed in the remaining fat tissue.The mean number and size of LNs detected were, respectively, 14 and 9 mm with palpation and 2.9 and 5 mm with complete embedding of remaining fat tissue.All positive LNs (30.9%) were detected by palpation.The mean pN density was 12.9% with palpation and 10.7% with complete embedding.All patients with a LN density higher than 20% were already observed by manual palpation.In conclusion, the complete embedding of fat tissue does not have a crucial impact on evaluation of the pN category.
Introduction: Familial Adenomatous Polyposis (FAP) is a genetic disorder that predisposes to colorectal cancer and many other extracolonic manifestations.Among them, desmoid disease is considered a great challenge and a major source of morbidity in these patients.The aim of the present manuscript is to evaluate the role of many clinical and surgical variables potentially involved in desmoid risk after prophylactic colectomy.Methods: we have searched case series, observational studies, retrospective studies, meta-analyses and systematic reviews (1990 to 2020) dealing with incidence and risk factors for desmoid disease after FAP surgical treatment.Results: desmoid disease may develop in approximately 10-20% of FAP patients leading to complications and mortality.Frequency and risk of desmoid risk have been associated with clinical and surgical variables not always dependent on surgeon control.Female sex, family history of desmoid disease, surgical trauma (reoperations and complications), specific genotypes and timing of surgery have demonstrated some influence on desmoid rates.Otherwise, type of surgery and surgical approach (open or laparoscopic) are not uniformly correlated with this risk.Conclusions: the information extracted from the literature suggests that our ability to influence desmoid disease development is limited.Integration of clinical and genetic data may help to define a higher risk subgroup of patients who may eventually benefit from specific preventive recommendations and postponed surgical intervention.
Dendropanax morbiferus H.Lév. has been used in traditional medicine for the treatment of skin diseases, migraine, dysmenorrhea and other maladies.Recent studies have reported that extract of Dendropanax morbiferus H.Lév. has an anti-tumor effect on several types of cancer cells in vitro.In this study, we investigated the anticancer effects and molecular mechanisms of extracts of Dendropanax morbiferus H. Lév.(DPL) in human lung carcinoma.In vitro studies were performed using the MTT assay, DAPI staining, flow cytometry and western blot.In vivo studies were performed on four-week-old female BALB/c nude mice using xenografts and oral administration, terminal deoxynucleotidyl transferase dUTP nick end labeling, immunohistochemistry, hematoxylin and eosin.The viability of A549 lung carcinoma cells assessed by MTT assay decreased in a concentration-dependent manner from 300 μg/mL.DAPI staining revealed that DNA fragmentation significantly increased in a concentration-dependent manner, indicating apoptosis.Flow cytometry revealed that apoptosis was increased in a dose-dependent manner following treatment with DPL.Western blotting revealed that the protein levels of Bax, cleaved-poly (ADP-ribose) polymerase, and phospho-p38 increased while those of B-cell lymphoma 2 decreased.In addition, levels of phosphorylated ERK1/2 and p-c-Jun N-terminal kinases were significantly different from the control.We also investigated the in vivo effects of DPL on tumor growth.Tumor size decreased in cells treated with 500 mg/kg DPL compared with the control group in vivo.Apoptosis, assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling, was significantly increased, and the inhibitory effect on tumors was confirmed.Immunohistochemistry staining showed increased expression of phospho-p38 in the 500 mg/kg-treated group.The results indicate that DPL induced apoptosis through the p38 mitogen-activated protein kinase signaling pathway in A549 cells.
For many years, now, the acridine orange dye has been successfully detecting acidity in isolated lysosomes and this has made it easy to evidence the existence of an ATP-ase responsible for the acidification of the organelles.The dye could also, as expected, detect the pH gradient between cytoplasm and organelles (ΔpHi) in intact cells.The detection of acidic organelles in cells can then be reasonably considered, in the absence of other specific causes of intracellular acidity deterioration, such as inhibitors of the above enzyme or ΔpHi collapsing agents, as a probe qualitatively reflecting the bioenergetic status of the cells.In the present study glutamine was tested as a feed for the oxidative phosphorylation in Ehrlich ascites tumor cells, using acridine orange just as a probe for the bioenergetic status (ATP levels) of cells.In line with a previous [1], less articulated suggestion [1], of a low involvement of suitable substrates available in cancer mitochondria at the basis of the Warburg/ Crabtree effects, the present findings support a specific role of glutamine supply in this respect.The results presented here and others taken from the scientific literature on this topic, as well as a few disposable, less conclusive in our opinion, in vivo studies, appear consistent with idea that the Warburg/Crabtree effects simply reflect the fact that the low glutamine content in cancer tissues often found in vivo, mainly supplies precursors for macromolecular synthesis rather than foraging, via a normal Krebs cycle, reducing power for the respiratory chain, and resulting in a inefficient oxidative phosphorylation pathway.Instead, a very important sustenance for oxidative phosphorylation is represented by high glutamine.Taking into account the low glutamine found in in vivo studies on cancer cells, it is argued that the Warburg effect would reflect the energy metabolism of cancer in a "milieu" with a low glutamine supply.
Purpose: To report late oncological outcomes in men with localized T1-T3 prostate cancer following single-session HIFU performed under the conception of wholegland therapy. Material and methods:This retrospective single-center study enrolled patients, who were uniformly treated by whole-gland ablation between December 2002 and September 2012.Treatment involved two generations of Ablatherm devices, the Maxis ® (A1) and the Integrated Imaging ® (A2).Outcome measures were overall survival, cancer-specific, metastasis-free, biochemical-free, and disease-free survival.Biochemical failure was assessed using PSA nadir+2 and nadir+1.2failure definitions.Disease failure was defined as positive control biopsy and/or PSA failure (nadir+2 ng/ml).Kaplan-Meier analyses were performed for survival estimates.Multivariate analysis was performed using Cox models.Results: Of 357 study patients, 146 (40.9%), 124 (34.7%) and 87 (24.4%) exhibited low-, intermediate-and high-risk disease (D´Amico), respectively.Median patient age was 70 yrs.Median follow-up was 6.5 yrs.(interquartile range, 4.3-8.9).The 10-year overall, cancer-specific and metastasis-free survival rates were 68%, 95% and 91%, respectively.The 8-year biochemical-free survival rates according to risk grouping were 93%, 76% and 48%, or 81%, 62% and 45% for nadir+2 and nadir+1.2failure definitions.The 8-year disease-free survival (DFS) rates were 76%, 49% and 42%, respectively.8-year estimates of DFS differed between the HIFU-devices A1 and A2 (54% vs. 74%, p<.001).The device generation predicted disease failure (hazard ratio .51,p= .001)independent from risk group, pre-treatment PSA level and Gleason sum.Conclusions: Success with single-session HIFU does not depend solely on tumor determinants.Ablation is more efficacious with the technically advanced A2 HIFU device.
