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World Journal of Surgical Oncology Jul 2023Tumors of the abdominal wall are uncommon but diverse. The surgical challenge is double. The tumor must be completely removed and the abdominal wall repaired. Our aim... (Review)
Review
BACKGROUND AND OBJECTIVES
Tumors of the abdominal wall are uncommon but diverse. The surgical challenge is double. The tumor must be completely removed and the abdominal wall repaired. Our aim was to describe the indications, techniques, and results of surgery on these tumors in an African context.
METHODS
Retrospective, multicentric and descriptive study conducted in three West African surgical oncology units. We included all abdominal wall tumors followed up between January 2010 and October 2022. Histological type, size, surgical procedure, and method of abdominal wall repair were considered. Survival was calculated using the Kaplan-Meier method and comparisons of proportions were made using the Student t test.
RESULTS
We registered 62 tumors of the abdominal wall and we operated on 41 (66.1%). The mean size of the tumors was 14.3 ± 26 cm. Dermatofibrosarcoma and desmoid tumor were present in 33 and 3 cases respectively. In 31.7% of cases in addition to the tumour, the resections carried away the muscular aponeurotic plane. Parietal resections required the use of a two-sided prosthesis in 6 cases. In 13 cases, we used skin flaps. The resections margins were invaded in 5 cases and revision surgery was performed in all of them. Incisional hernia was noticed in 2 cases. The tumor recurrence rate was 12.2% with an average time of 13 months until occurrence. Overall survival at 3 years was 80%.
CONCLUSIONS
Surgery is the mainstay of treatment for abdominal wall tumors. It must combine tumor resections and parietal repair. Cancer surgeons need to be trained in abdominal wall repair.
Topics: Humans; Abdominal Wall; Retrospective Studies; Surgical Oncology; Neoplasm Recurrence, Local; Peritoneal Neoplasms; Surgical Mesh; Hernia, Ventral; Recurrence
PubMed: 37525223
DOI: 10.1186/s12957-023-03125-3 -
BMC Pediatrics Aug 2023Hepatocellular adenomas (HCAs) are rare benign tumors of the liver that occur predominantly in women taking oral contraceptives. In children, HCAs comprise < 5% of... (Review)
Review
BACKGROUND
Hepatocellular adenomas (HCAs) are rare benign tumors of the liver that occur predominantly in women taking oral contraceptives. In children, HCAs comprise < 5% of hepatic tumors. We report a case of HCAs in a 7-year-old girl with estrogen and glucose imbalance.
CASE PRESENTATION
A 7-year-old girl was presented to our hospital with bilateral breast enlargement for 2 months, polydipsia, polyuria, polyphagia, hyperglycemia, and significant weight gain. Computed tomography (CT) showed a 7.2 cm×6.9 cm×5.3 cm round-shaped mass in the left inner lobe of the liver, ovarian ultrasound showed multiple follicles in the ovaries bilaterally, and cranial magnetic resonance imaging (MRI) showed an enlarged superior pituitary. Hematological and biochemical results were as follows: fasting glucose was 19.7 mmol/L, estradiol was 122.9 pmol/L, follicle-stimulating hormone 10.81 IU/L, luteinizing hormone 10.99 IU/L, insulin-like growth factor 1,513 ng/mL, glutamine aminotransferase 86 U/L, and alkaline phosphatase 362 U/L. Thyroid functions, methemoglobin, fetal protein, carcinoembryonic antigen, and chorionic gonadotropin were normal. The patient had a complete surgical resection of the liver tumor, and the postoperative histopathological diagnosis was HCAs. After the surgery, insulin was injected and the glucose levels were stable. During the 36-month follow-up period, neither tumor recurrence nor significant abnormalities were detected using color Doppler ultrasound of the liver. The child's precocious puberty is currently under control.
CONCLUSIONS
HCAs are particularly rare in children with liver tumors, and risk factors for the development of HCAs in children include sex hormone imbalance, obesity, Fanconi anemia (FA), glycogen storage diseases (GSDs) type I, III, and IV, galactosemia, immunodeficiency, congenital portosystemic shunts (CPSS), cardiac hepatopathy status-post Fontan procedure, Hurler syndrome, familial adenomatous polyposis, germline HNF1A mutations, and maturity-onset diabetes of the young type 3. Most HCAs are detected during a physical examination without clinical symptoms, and some patients may present with symptoms such as abdominal pain, abdominal distension, and abdominal masse. Serum liver function tests can show increased alkaline phosphatase (ALP) and γ- glutamyl transferase (GT), whereas α-Fetoprofein (AFP) levels are normal. The definitive diagnosis relies mainly on histopathological examination. Because HCAs can rupture and bleed and become malignant. Early surgical treatment is recommended after detection.
Topics: Child; Humans; Female; Adenoma, Liver Cell; Alkaline Phosphatase; Neoplasm Recurrence, Local; Liver Neoplasms
PubMed: 37620840
DOI: 10.1186/s12887-023-04209-5 -
Cellular and Molecular Life Sciences :... Apr 2024Peritoneal metastasis, the third most common metastasis in colorectal cancer (CRC), has a poor prognosis for the rapid progression and limited therapeutic strategy....
Peritoneal metastasis, the third most common metastasis in colorectal cancer (CRC), has a poor prognosis for the rapid progression and limited therapeutic strategy. However, the molecular characteristics and pathogenesis of CRC peritoneal metastasis are poorly understood. Here, we aimed to elucidate the action and mechanism of adipose-derived stem cells (ADSCs), a prominent component of the peritoneal microenvironment, in CRC peritoneal metastasis formation. Database analysis indicated that ADSCs infiltration was increased in CRC peritoneal metastases, and high expression levels of ADSCs marker genes predicted a poor prognosis. Then we investigated the effect of ADSCs on CRC cells in vitro and in vivo. The results revealed that CRC cells co-cultured with ADSCs exhibited stronger metastatic property and anoikis resistance, and ADSCs boosted the intraperitoneal seeding of CRC cells. Furthermore, RNA sequencing was carried out to identify the key target gene, angiopoietin like 4 (ANGPTL4), which was upregulated in CRC specimens, especially in peritoneal metastases. Mechanistically, TGF-β1 secreted by ADSCs activated SMAD3 in CRC cells, and chromatin immunoprecipitation assay showed that SMAD3 facilitated ANGPTL4 transcription by directly binding to ANGPTL4 promoter. The ANGPTL4 upregulation was essential for ADSCs to promote glycolysis and anoikis resistance in CRC. Importantly, simultaneously targeting TGF-β signaling and ANGPTL4 efficiently reduced intraperitoneal seeding in vivo. In conclusion, this study indicates that tumor-infiltrating ADSCs promote glycolysis and anoikis resistance in CRC cells and ultimately facilitate peritoneal metastasis via the TGF-β1/SMAD3/ANGPTL4 axis. The dual-targeting of TGF-β signaling and ANGPTL4 may be a feasible therapeutic strategy for CRC peritoneal metastasis.
Topics: Humans; Peritoneal Neoplasms; Transforming Growth Factor beta1; Glycolysis; Colorectal Neoplasms; Stem Cells; Tumor Microenvironment; Smad3 Protein; Angiopoietin-Like Protein 4
PubMed: 38643448
DOI: 10.1007/s00018-024-05215-1 -
Cancer Letters Apr 2024Gastric cancer (GC) is a common malignant tumor of the digestive tract, and chemoresistance significantly impacts GC patients' prognosis. PANoptosis has been associated...
Gastric cancer (GC) is a common malignant tumor of the digestive tract, and chemoresistance significantly impacts GC patients' prognosis. PANoptosis has been associated with oxaliplatin-induced cell death. However, the direct regulatory role of YBX1 in cellular chemoresistance through PANoptosis remains unclear. In this study, we investigated the impact of YBX1 on regulating PANoptosis and its influence on the resistance of gastric cancer cells to oxaliplatin. Through overexpression and silencing experiments, we assessed YBX1's effect on proliferation and PANoptosis regulation in gastric cancer cells. Additionally, we identified PPM1B and USP10 as interacting proteins with YBX1 and confirmed their influence on YBX1 molecular function and protein expression levels. Our results demonstrate that YBX1 suppresses PANoptosis, leading to enhanced resistance of gastric cancer cells to oxaliplatin. Furthermore, we found that PPM1B and USP10 play critical roles in regulating YBX1-mediated PANoptosis inhibition. PPM1B directly interacts with YBX1, causing dephosphorylation of YBX1 at serine 314 residue. This dephosphorylation process affects the deubiquitination of YBX1 mediated by USP10, resulting in decreased YBX1 protein expression levels and impacting PANoptosis and oxaliplatin resistance in gastric cancer cells. Additionally, we discovered that the 314th amino acid of YBX1 has a profound impact on its own protein expression abundance, thereby affecting the functionality of YBX1. In conclusion, our study reveals the significance of PPM1B-mediated dephosphorylation of YBX1 and USP10-mediated deubiquitination in regulating PANoptosis and sensitivity to oxaliplatin in gastric cancer cells. These findings offer a potential therapeutic strategy for patients with oxaliplatin-resistant gastric cancer.
Topics: Humans; Oxaliplatin; Stomach Neoplasms; Drug Resistance, Neoplasm; Cell Proliferation; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Ubiquitin Thiolesterase; Y-Box-Binding Protein 1; Protein Phosphatase 2C
PubMed: 38364962
DOI: 10.1016/j.canlet.2024.216712 -
Nature Communications Apr 2024Notable-HCC (NCT05185531) is a phase 1b trial, aiming to evaluate the safety and preliminary effectiveness of neoadjuvant PD-1 blockade plus stereotactic body...
Notable-HCC (NCT05185531) is a phase 1b trial, aiming to evaluate the safety and preliminary effectiveness of neoadjuvant PD-1 blockade plus stereotactic body radiotherapy (SBRT) in early-stage resectable hepatocellular carcinoma (HCC). Twenty patients with HCC of BCLC stage 0-A received 3 Gy SBRT and two cycles of tislelizumab, an anti-PD-1 monoclonal antibody before the curative HCC resection. Primary endpoints were the surgery delay, radiographic and pathological tumor response after the neoadjuvant therapy, safety and tolerability. During the neoadjuvant therapy, treatment-related adverse events (TRAEs) of grade 1-2 occurred in all 20 patients (100%), eight patients (40%) had grade 3 TRAEs, no grade 4 to 5 TRAE occurred, and all resolved without corticosteroids treatment. Per mRECIST, the objective response rate was 63.2% (12/19), with 3 complete response; the disease control rate was 100%. Two (10.5%) patients achieved complete pathological response. No surgery delay occurred. The neoadjuvant therapy did not increase the surgical difficulty or the incidence of complications. Secondary endpoints of disease-free survival and overall survival were not mature at the time of the analysis. Our pilot trial shows that neoadjuvant therapy with anti-PD-1 + SBRT is safe and promotes tumor responses in early-stage resectable HCC.
Topics: Humans; Neoadjuvant Therapy; Carcinoma, Hepatocellular; Radiosurgery; Antineoplastic Combined Chemotherapy Protocols; Liver Neoplasms; Neoplasm Staging; Adjuvants, Immunologic; Antibodies, Monoclonal, Humanized
PubMed: 38627377
DOI: 10.1038/s41467-024-47420-3 -
International Journal of Gynecological... Nov 2023Progression-free survival is an established clinically meaningful endpoint in ovarian cancer trials, but it may be susceptible to bias; therefore, blinded independent... (Review)
Review
Optimizing disease progression assessment using blinded central independent review and comparing it with investigator assessment in the PRIMA/ENGOT-ov26/GOG-3012 trial: challenges and solutions.
OBJECTIVE
Progression-free survival is an established clinically meaningful endpoint in ovarian cancer trials, but it may be susceptible to bias; therefore, blinded independent centralized radiological review is often included in trial designs. We compared blinded independent centralized review and investigator-assessed progressive disease performance in the PRIMA/ENGOT-ov26/GOG-3012 trial examining niraparib monotherapy.
METHODS
PRIMA/ENGOT-ov26/GOG-3012 was a randomized, double-blind phase 3 trial; patients with newly diagnosed stage III/IV ovarian cancer received niraparib or placebo. The primary endpoint was progression-free survival (per Response Evaluation Criteria in Solid Tumors [RECIST] v1.1), determined by two independent radiologists, an arbiter if required, and by blinded central clinician review. Discordance rates between blinded independent centralized review and investigator assessment of progressive disease and non-progressive disease were routinely assessed. To optimize disease assessment, a training intervention was developed for blinded independent centralized radiological reviewers, and RECIST refresher training was provided for investigators. Discordance rates were determined post-intervention.
RESULTS
There was a 39% discordance rate between blinded independent centralized review and investigator-assessed progressive disease/non-progressive disease in an initial patient subset (n=80); peritoneal carcinomatosis was the most common source of discordance. All reviewers underwent training, and as a result, changes were implemented, including removal of two original reviewers and identification of 10 best practices for reading imaging data. Post-hoc analysis indicated final discordance rates between blinded independent centralized review and investigator improved to 12% in the overall population. Median progression-free survival and hazard ratios were similar between blinded independent centralized review and investigators in the overall population and across subgroups.
CONCLUSION
PRIMA/ENGOT-ov26/GOG-3012 highlights the need to optimize blinded independent centralized review and investigator concordance using early, specialized, ovarian-cancer-specific radiology training to maximize validity of outcome data.
Topics: Female; Humans; Carcinoma, Ovarian Epithelial; Disease Progression; Ovarian Neoplasms; Peritoneal Neoplasms; Progression-Free Survival; Randomized Controlled Trials as Topic; Clinical Trials, Phase III as Topic
PubMed: 37931976
DOI: 10.1136/ijgc-2023-004605 -
Clinical Breast Cancer Jul 2024Trastuzumab emtansine (T-DM1), sacituzumab govitecan (SG), and trastuzumab deruxtecan (T-DXd) are three ADCs approved for the treatment of metastatic breast cancer... (Review)
Review
Trastuzumab emtansine (T-DM1), sacituzumab govitecan (SG), and trastuzumab deruxtecan (T-DXd) are three ADCs approved for the treatment of metastatic breast cancer (MBC). Since gastrointestinal toxicities have been commonly observed with these drugs in clinical trials, a pooled analysis evaluating gastrointestinal adverse events (AEs) in patients with MBC treated with ADCs in clinical trials was performed. PubMed, Embase, and the Cochrane Library were searched from inception until May 2023 for phase II and III clinical trials reporting frequency and severity of gastrointestinal AEs during treatment with ADCs. Data were retrieved for nausea, vomiting, diarrhea, constipation, and abdominal pain: overall and grade 3-4 toxicity rates according to NCI-CTCAE were collected and expressed as proportions. A pre-specified subgroup analysis according to the agent was also carried out. Fourteen studies, comprising 5608 patients, were included in the analysis. Gastrointestinal AEs were frequently registered with SG and T-DXd. A significantly higher frequency of nausea (65.6% with SG, 75% with T-DXd), vomiting (43.7% with SG, 45% with T-DXd), and diarrhea (59.7% with SG, 29% with T-DXd) was noticed with these ADCs compared to TDM-1. Furthermore, diarrhea was more frequently associated with SG (grade 3 in 7.5% of patients), while constipation and abdominal pain were less common. Gastrointestinal AEs, notably nausea and diarrhea, were frequently reported by MBC patients treated with SG and T-DXd in clinical trials. Since these ADCs are administered continuously until disease progression or occurrence of unbearable AEs, gastrointestinal toxicity may have a negative impact on patient quality of life. Therefore, appropriate management of gastrointestinal AEs is mandatory to ensure treatment efficacy and adherence.
Topics: Humans; Female; Breast Neoplasms; Immunoconjugates; Gastrointestinal Diseases; Ado-Trastuzumab Emtansine; Antibodies, Monoclonal, Humanized; Trastuzumab; Camptothecin; Nausea; Neoplasm Metastasis; Antineoplastic Agents, Immunological
PubMed: 38734491
DOI: 10.1016/j.clbc.2024.04.003 -
Urology Annals 2024Perivascular epithelioid cell neoplasm (PEComa) is a rare mesenchymal tumor composed of histologically and immunohistochemically distinctive perivascular epithelioid... (Review)
Review
Perivascular epithelioid cell neoplasm (PEComa) is a rare mesenchymal tumor composed of histologically and immunohistochemically distinctive perivascular epithelioid cells. They can arise in various localizations such as the bladder. A total of 36 case reports regarding bladder PEComa have been described in the literature. Eleven reviews regarding this tumor have been published in literature so far primarily focusing on anatomic pathology. Through these reviews, it is known that in bladder PEComa, the melanocytic marker Human Melanoma Black-45 is expressed in 100% of cases whereas variable expression can be seen in multiple other melanocytic and myoid markers such as smooth muscle actin, , and CD34. Since current reviews mainly emphasize anatomic pathology, we perform a review focusing on the clinical aspects of PEComa at the level of the clinician. A manual electronic search of the PubMed/Medline and Web of Science Core Collection databases was conducted. Search was done on (perivascular epithelioid cell neoplasms [MeSH terms]) AND (Bladder). All case reports and reviews were encompassed until March 15, 2023, to identify studies that assessed bladder PEComa. The age of presentation is relatively low with a median age of 37 years. There is a female predominance with a female/male ratio of 1.5. The tumor shows no preference in anatomical localization within the bladder. Even involvement of the bladder neck, proximal urethra, and distal ureter has been described. The clinical presentation consists in the majority of patients of symptoms related to the urinary tract such as hematuria, dysuria, passage of urine sediment, frequency, and urgency. Other symptoms include abdominal discomfort and dysmenorrhea. In clinical examination, an abdominal mass can be found based on the size and location of the tumor. Further examination usually encompasses cystoscopy due to the hematuria and radiological investigations such as ultrasound (US), computed tomography, and magnetic resonance imaging. These radiological investigations reveal a heterogeneous solid mass with clear borders. In our center, we performed a transvaginal US additionally in a patient with bladder PEComa, which was the only investigation in our patient that concluded the mass was located in the Retzius space. For treatment, transurethral resection of the bladder tumor and partial cystectomy were both described in equal numbers. The choice of treatment depends on the localization and size of the tumor. Follow-up consists of imaging, but clear guidelines on this matter are lacking. Bladder PEComa is a rare condition and usually presents itself with nonspecific symptoms. Radiological investigations will reveal the tumor, but the final diagnosis is based on cytological and immunohistochemical features. Since bladder PEComa is an entity with uncertain malignant potential, it is important to include this entity in the differential diagnosis when a patient presents with lower abdominal discomfort and lower urinary tract symptoms in combination with a mass in the pelvic region.
PubMed: 38415228
DOI: 10.4103/ua.ua_40_23 -
Cancer Medicine Sep 2023Liver metastasis is one of the most important factors affecting the prognosis of patients with neuroendocrine neoplasms (NENs). Transhepatic artery embolization (TAE) is...
PURPOSE
Liver metastasis is one of the most important factors affecting the prognosis of patients with neuroendocrine neoplasms (NENs). Transhepatic artery embolization (TAE) is the main local treatment of NENs with liver metastasis (NENLM). This study aimed to elucidate the differences between pancreatic and rectal NENLM with a discrepancy in blood supply.
METHODS
A total of 32 patients with NENLM of different primary sites received 102 TAE treatments at our hospital. Clinical features, such as age, sex, World Health Organization (WHO) tumour grade and progression-free survival (PFS), were compared between patients with pancreatic and rectal NENLM with different blood supplies. The total follow-up time is 1-5 years.
RESULTS
There were 12 cases with tumours originating from the rectum or pancreas, respectively. Other tumour-originated sites included the duodenum (two cases, 6.25%), the thymus and lung (four cases, 12.5%), and the unknown (two cases, 6.25%). The average age of patients was 51.59 years, and 17 (53.1%) were men. WHO grade 1, 2 or 3 tumours occurred in three (9.4%), 23 (71.9%) and six (18.7%) patients, respectively. Hepatic tumour burdens of low (<25%), middle (25%-50%) and high (>50%) levels were found in 13 (40.6%), eight (25%) and 11 (34.4%) patients, respectively. There were more patients with hypervascular pancreatic NENLM than with hypovascular rectal NENLM (p = 0.005). Tumour shrinkage in all cases with NENLM was 50% with an objective response rate of 37.5%, disease control rate of 75% and PFS of 12 months. Disease progression (p = 0.09), tumour shrinkage (p = 0.07) and death (p = 0.19) were more prominent in the pancreatic NENLM group than in the rectal NENLM group. Progression-free survival was not reached in the pancreatic NENLM group, which was more prominent than in the rectal NENLM group (7 months; hazard ration, 0.22; 95% confidence interval, 0.07-0.76; p = 0.016). The main adverse events were abdominal pain (71.9%) and transaminase elevation (50%), which were more common in pancreatic NENLM than in rectal NENLM.
CONCLUSIONS
Transhepatic artery embolization treatment is markedly effective and safe for treating NENLM, especially pancreatic NENLM.
PubMed: 37587855
DOI: 10.1002/cam4.6464 -
Scientific Reports Jul 2023Peritoneal metastases (PM) are common routes of dissemination for colorectal cancer (CRC) and remain a lethal disease with a poor prognosis. The properties of the...
Peritoneal metastases (PM) are common routes of dissemination for colorectal cancer (CRC) and remain a lethal disease with a poor prognosis. The properties of the extracellular matrix (ECM) are important in cancer development; studying their changes is crucial to understand CRC-PM development. We studied the elastic properties of ECMs derived from human samples of normal and neoplastic PM by atomic force microscopy (AFM); results were correlated with patient clinical data and expression of ECM components related to metastatic spread. We show that PM progression is accompanied by stiffening of the ECM, increased cancer associated fibroblasts (CAF) activity and increased deposition and crosslinking in neoplastic matrices; on the other hand, softer regions are also found in neoplastic ECMs on the same scales. Our results support the hypothesis that local changes in the normal ECM can create the ground for growth and spread from the tumour of invading metastatic cells. We have found correlations between the mechanical properties (relative stiffening between normal and neoplastic ECM) of the ECM and patients' clinical data, like age, sex, presence of protein activating mutations in BRAF and KRAS genes and tumour grade. Our findings suggest that the mechanical phenotyping of PM-ECM has the potential to predict tumour development.
Topics: Humans; Peritoneal Neoplasms; Extracellular Matrix; Colorectal Neoplasms
PubMed: 37500685
DOI: 10.1038/s41598-023-38763-w