Floodmcdowell2266
isms. Our data support (neoadjuvant) TDLN-targeted therapeutic interventions based on CTLA-4 and PD-1 blockade, to reinvigorate memory T cells and curb early metastatic spread and growth.
Combination therapy has been explored for advanced head and neck squamous cell carcinoma (HNSCC) owing to the limited efficacy of anti-epidermal growth factor receptor (EGFR) therapy. Increased expression and glycosylation of immune checkpoint molecules in tumors are responsible for cetuximab therapy refractoriness. The role of programmed death ligand 2 (PD-L2), a ligand of PD-1, in the immune function is unclear. Here, we examined the regulatory mechanism of PD-L2 glycosylation and its role in antitumor immunity and cetuximab therapy.
Single-cell RNA sequencing and immunohistochemical staining were used to investigate PD-L2 expression in cetuximab-resistant/sensitive HNSCC tissues. The mechanism of PD-L2 glycosylation regulation was explored in vitro. The effects of PD-L2 glycosylation on immune evasion and cetuximab efficacy were verified in vitro and using mice bearing orthotopic SCC7 tumors.
The PD-L2 levels were elevated and
-glycosylated in patients with cetuximab-resistant HNSCC. Glycosylated Pechanism for cetuximab therapy refractoriness. Thus, the combination of PD-L2 glycosylation inhibition and cetuximab is a potential therapeutic strategy for cancer.Fanconi anaemia due to biallelic loss of BRCA2 (Fanconi anaemia subtype D1) is traditionally diagnosed during childhood with cancer rates historically reported as 97% by 5.2 years. This report describes an adult woman with a history of primary ovarian failure, who was diagnosed with gastrointestinal adenocarcinoma and BRCA2-associated Fanconi anaemia at 23 years of age, only after she suffered severe chemotherapy toxicity. The diagnostic challenges include atypical presentation, initial false-negative chromosome fragility testing and variant classification. It highlights gastrointestinal adenocarcinoma as a consideration for adults with biallelic BRCA2 pathogenic variants with implications for surveillance. find more After over 4 years, the patient has no evidence of gastrointestinal cancer recurrence although the tumour was initially considered only borderline resectable. The use of platinum-based chemotherapy, to which heterozygous BRCA2 carriers are known to respond, may have had a beneficial anticancer effect, but caution is advised given its extreme immediate toxicity at standard dosing. Fanconi anaemia should be considered as a cause for women with primary ovarian failure of unknown cause and referral to cancer genetic services recommended when there is a family history of cancer in the hereditary breast/ovarian cancer spectrum.
Placenta percreta is a rare event, but it poses serious problems due to potential hemorrhagic events. We report a particular case of placenta percreta with massive hematuria due to maternal bladder invasion, and describe the surgical protocol performed that resulted in an excellent outcome.
A 33-year-old patient, at 27
weeks gestational age, presented in the emergency room of the Urology Department with urinary blood clot acute retention, because of massive hematuria from a placenta percreta with bladder invasion. After extracting the clots from the bladder, and coagulation of an area of venous ectasies of the posterior wall, hematuria ceased, but appeared after two days, necessitating again the bladder clots removal and coagulation. A surgical team with gynecologists, urologists, anesthesiologists and a neonatologist was composed, and after bilateral ureteral double J insertion, cesarean section was performed followed by hemostatic hysterectomy and partial cystectomy, bilateral internal iliac artery ligature and repair of the bladder wall. The postoperative evolution was without incidents; the Foley catheter was removed in the 14
postoperative day.
In the context of a massive hematuria of a pregnant woman, the urologist must always consider a diagnosis of complicated placenta percreta.
In the context of a massive hematuria of a pregnant woman, the urologist must always consider a diagnosis of complicated placenta percreta.
Locally advanced pancreatic cancer invading the surrounding vascular structures has long been considered as unresectable and, therefore, patients were usually submitted to palliative chemotherapy.
We present the case of a 44-year-old male investigated for weight loss and abdominal pain and diagnosed with a locally advanced pancreatic tumor invading the celiac axis. An endoscopic ultrasound was performed and a biopsy was retrieved demonstrating the presence of a moderately differentiated pancreatic adenocarcinoma. After discussing with the patient the risks and the benefits of performing an extended surgical procedure, the patient consented to distal pancreatectomy en bloc with celiac axis resection. Postoperatively, the patient was submitted to low-molecular-weight heparin therapy for 3 weeks followed by oral anticoagulant for 2 months. Histopathological studies confirmed the presence of a moderately differentiated pancreatic adenocarcinoma invading the celiac axis and described negative resection margins.
Although celiac axis invasion has been considered for a long period of time as a sign of unresectable disease due to the high rates of perioperative complications, it seems that in selected cases, surgery can be safely performed with curative intent, especially if negative resection margins are achieved.
Although celiac axis invasion has been considered for a long period of time as a sign of unresectable disease due to the high rates of perioperative complications, it seems that in selected cases, surgery can be safely performed with curative intent, especially if negative resection margins are achieved.
Thymic lipofibroadenoma is a benign growth of unknown etiology extremely rarely described in the literature, morphologically resembling lipofibroadenoma of the breast. The diagnosis is usually a postoperative surprise and is made by the anatomopathologist. Surgical resection is curative.
The presented case is the first reported in a woman, to date. The patient was successfully submitted to surgery and complete resection of the giant intrathoracic tumor was performed. The histopathological and immunohistochemical studies came to demonstrated the presence of a thymic lipofibroadenoma while the postoperative outcomes were favorable.
In cases presenting large intrathoracic tumors complete resection is able to provide a significant improvement of the general condition of the patient, as well as a chance for cure.
In cases presenting large intrathoracic tumors complete resection is able to provide a significant improvement of the general condition of the patient, as well as a chance for cure.
We describe a rare case of ovarian mesonephric-like adenocarcinoma (MLA) involving the fimbria and mimicking serous tubal intraepithelial carcinoma (STIC).
A 47-year-old woman presented with a 4.4-cm left ovarian mass. Histologically, the ovarian tumor showed papillary and solid architecture, severe nuclear pleomorphism, and increased mitotic activity. Some microscopic foci where the tumor cells spread horizontally along the fimbrial surface epithelium were noted, compatible with STIC. We initially considered the ovarian tumor to be high-grade serous carcinoma accompanied by a fimbrial STIC. However, immunostaining revealed nuclear immunoreactivity for paired box 2 and GATA-binding protein 3, but lacked expression of Wilms tumor 1. A thorough slide review and additional immunostaining revealed architectural diversity, densely eosinophilic intraluminal secretions, and lack of hormone receptor expression, supporting the diagnosis of MLA.
Microscopic intraepithelial metastases of the MLA to the fimbria mimic STIC. We recommend ancillary tests, such as immunostaining, in patients with ovarian tumors whenever possible, particularly for those with differential diagnosis of MLA and high-grade serous carcinoma.
Microscopic intraepithelial metastases of the MLA to the fimbria mimic STIC. We recommend ancillary tests, such as immunostaining, in patients with ovarian tumors whenever possible, particularly for those with differential diagnosis of MLA and high-grade serous carcinoma.
Conjunctival malignant melanoma (CMM) is a rare, but very aggressive tumor with a high metastasis rate. Not much is known about the CMM metastasis mechanisms. So far, epidermal growth factor (EGF) and its receptor (EGF-R) as well as macrophages and matrix metalloproteinase 9 (MMP-9) have been reported to lead to metastasis by epithelial-mesenchymal-transition and tumor migration in different solid tumors. Therefore, we evaluated whether EGF and EGF-R, CD68 and MMP-9 are altered in CMM samples in comparison to conjunctival nevi and healthy conjunctiva.
EGF, EGF-R, the macrophage marker CD68 and MMP-9 expression were analyzed in human conjunctival melanoma (CMM, n=16), human conjunctival nevi (n=13) and disease-free human conjunctiva (controls, n=14) by immunohistology. Staining of each sample was evaluated using a standardized score ranging from negative (0) to triple positive (3). The groups were then compared by ANOVA, followed by Tukey's post-hoc test.
A statistically significant increase of EGF was seen in CMM samples in comparison to conjunctival nevi (p=0.03). In contrast, no statistically significant differences in EGF-R expression were noted between the three groups. A statistically significant increase of CD68 was only seen in conjunctival nevi compared to controls (p=0.04). MMP-9 expression was similar in all groups.
In CMM, the study data demonstrated an up-regulation of EGF in comparison to conjunctival nevi. Hence, EGF might promote proliferation of CMM cells and induce the epithelial-mesenchymal transition. Therefore, our data suggest that an interplay between EGF and CMM might have a critical role in the developing CMM tumors and metastasis.
In CMM, the study data demonstrated an up-regulation of EGF in comparison to conjunctival nevi. Hence, EGF might promote proliferation of CMM cells and induce the epithelial-mesenchymal transition. Therefore, our data suggest that an interplay between EGF and CMM might have a critical role in the developing CMM tumors and metastasis.
During the coronavirus disease 2019 (COVID19) pandemic, pedicle flaps (instead of free flaps) were recommended for reconstruction following wide resection for patients with head and neck cancer, in order to reduce the use of medical resources. Currently, there are no established treatment guidelines for patients with head and neck cancer with synchronous esophageal cancer.
We present a 68-year-old male with cT4aN2cM0 oral floor and synchronous cT1bN1M0 esophageal cancers who had defective reconstruction following oral tumor resection before esophagectomy during the pandemic. At the initial surgery, the oral resected defect was reconstructed using supraclavicular artery flap. The subsequent esophagectomy was reconstructed by gastric tube reconstruction. Both postoperative courses were successful, without the need for postoperative ventilator use. The days from initial or second surgery to discharge were 14 or 16 days, respectively.
This case had achieved negative surgical margins and recovered oral intake with tracheostomy decannulation.
