Endoscopic detection and diagnostic strategies for minute gastric cancer: A real-world observational study.

BACKGROUND: Minute gastric cancers (MGCs) have a favorable prognosis, but they are too small to be detected by endoscopy, with a maximum diameter ≤ 5 mm. AIM: To explore endoscopic detection and diagnostic strategies for MGCs. METHODS: This was a real-world observational study. The endoscopic and clinicopathological parameters of 191 MGCs between January 2015 and December 2022 were retrospectively analyzed. Endoscopic discoverable opportunity and typical neoplastic features were emphatically reviewed. RESULTS: All MGCs in our study were of a single pathological type, 97.38% (186/191) of which were differentiated-type tumors. White light endoscopy (WLE) detected 84.29% (161/191) of MGCs, and the most common morphology of MGCs found by WLE was protruding. Narrow-band imaging (NBI) secondary observation detected 14.14% (27/191) of MGCs, and the most common morphology of MGCs found by NBI was flat. Another three MGCs were detected by indigo carmine third observation. If a well-demarcated border lesion exhibited a typical neoplastic color, such as yellowish-red or whitish under WLE and brownish under NBI, MGCs should be diagnosed. The proportion with high diagnostic confidence by magnifying endoscopy with NBI (ME-NBI) was significantly higher than the proportion with low diagnostic confidence and the only visible groups (94.19% > 56.92% > 32.50%, P < 0.001). CONCLUSION: WLE combined with NBI and indigo carmine are helpful for detection of MGCs. A clear demarcation line combined with a typical neoplastic color using nonmagnifying observation is sufficient for diagnosis of MGCs. ME-NBI improves the endoscopic diagnostic confidence of MGCs.

Clinical, Morphological, and Molecular Study on Grade 2 and 3 Pleomorphic Xanthoastrocytoma.

PURPOSE: Pleomorphic xanthoastrocytoma (PXA) is an uncommon astrocytoma that tends to occur in children and young adults and has a relatively favorable prognosis. The 2021 WHO classification of tumors of the central nervous system (CNS WHO), 5th edition, rates PXAs as grade 2 and grade 3. The histological grading was based on mitotic activity (≥2.5 mitoses/mm2). This study specifically evaluates the clinical, morphological, and, especially, the molecular characteristics of grade 2 and 3 PXAs. METHODS: Between 2003 and 2021, we characterized 53 tumors with histologically defined grade 2 PXA (n = 36, 68%) and grade 3 PXA (n = 17, 32%). RESULTS: Compared with grade 2 PXA, grade 3 PXA has a deeper location and no superiority in the temporal lobe and is more likely to be accompanied by peritumoral edema. In histomorphology, epithelioid cells and necrosis were more likely to occur in grade 3 PXA. Molecular analysis found that the TERT promoter mutation was more prevalent in grade 3 PXA than in grade 2 PXA (35% vs. 3%; p = 0.0005) and all mutation sites were C228T. The cases without BRAF V600E mutation or with necrosis in grade 3 PXA had a poor prognosis (p = 0.01). CONCLUSION: These data define PXA as a heterogeneous astrocytoma. Grade 2 and grade 3 PXAs have different clinical and histological characteristics as well as distinct molecular profiles. TERT promoter mutations may be a significant genetic event associated with anaplastic progression. Necrosis and BRAF V600E mutation play an important role in the prognosis of grade 3 PXA.

c(RGDyk)-modified nanoparticles encapsulating quantum dots as a stable fluorescence probe for imaging-guided surgical resection of glioma under the auxiliary UTMD.

Surgical resection remains the preferred approach for some patients with glioblastoma (GBM), and eradication of the residual tumour niche after surgical resection is very helpful for prolonging patient survival. However, complete surgical resection of invasive GBM is difficult because of its ambiguous boundary. Herein, a novel targeting material, c(RGDyk)-poloxamer-188, was synthesized by modifying carboxyl-terminated poloxamer-188 with a glioma-targeting cyclopeptide, c(RGDyk). Quantum dots (QDs) as fluorescent probe were encapsulated into the self-assembled c(RGDyk)-poloxamer-188 polymer nanoparticles (NPs) to construct glioma-targeted QDs-c(RGDyk)NP for imaging-guided surgical resection of GBM. QDs-c(RGDyk)NP exhibited a moderate hydrodynamic diameter of 212.4 nm, a negative zeta potential of -10.1 mV and good stability. QDs-c(RGDyk)NP exhibited significantly lower toxicity against PC12 and C6 cells and HUVECs than free QDs. Moreover, in vitro cellular uptake experiments demonstrated that QDs-c(RGDyk)NP specifically targeted C6 cells, making them display strong fluorescence. Combined with ultrasound-targeted microbubble destruction (UTMD), QDs-c(RGDyk)NP specifically accumulated in glioma tissue in orthotropic tumour rats after intravenous administration, evidenced by ex vivo NIR fluorescence imaging of bulk brain and glioma tissue sections. Furthermore, fluorescence imaging with QDs-c(RGDyk)NP guided accurate surgical resection of glioma. Finally, the safety of QDs-c(RGDyk)NP was verified using pathological HE staining. In conclusion, QDs-c(RGDyk)NP may be a potential imaging probe for imaging-guided surgery.

Inflammatory bowel disease- and Barrett's esophagus-associated neoplasia: the old, the new, and the persistent struggles.

Early diagnosis of and adequate therapy for premalignant lesions in patients with inflammatory bowel disease (IBD) and Barrett's esophagus (BE) has been shown to decrease mortality. Endoscopic examination with histologic evaluation of random and targeted biopsies remains the gold standard for early detection and adequate treatment of neoplasia in both these diseases. Although eventual patient management (including surveillance and treatment) depends upon a precise histologic assessment of the initial biopsy, accurately diagnosing and grading IBD- and BE-associated dysplasia is still considered challenging by many general as well as subspecialized pathologists. Additionally, there are continuing updates in the literature regarding the diagnosis, surveillance, and treatment of these disease entities. This comprehensive review discusses the cancer risk, detailed histopathological features, diagnostic challenges, and updates as well as the latest surveillance and treatment recommendations in IBD- and BE-associated dysplasia.

BMP-2 plasmid DNA-loaded chitosan films - A new strategy for bone engineering.

OBJECTIVES: Bone defects are common in every area of medicine and remain a clinical challenge. Tissue engineering has led to promising new strategies in accelerating bone repair. Bone morphogenetic proteins (BMPs) play crucial roles in bone regeneration, but are required in supra-physiological doses, which are expensive and produce severe side effects. METHODS: To address these issues, we prepared BMP-2 plasmid DNA-loaded chitosan films, and examined their effects on mouse osteoblast-like MC3T3-E1 cell morphology, proliferation, and runt-related transcription factor 2 (RUNX2) expression. In vivo testing was performed using calvarial critical-sized defects and histomorphometry in 36 Sprague-Dawley rats. Unloaded chitosan films and empty defects served as controls. RESULTS: In contrast to the controls, cells grown on BMP-2 plasmid DNA-loaded chitosan films had well established filopodia and lamellipodia, significantly higher proliferation 2, 4, and 6 days post-seeding (P ≤ 0.05), and higher nuclear RUNX2 expression. In vivo, new bone growth was significantly greater in the BMP-2 group than in the control groups at 4, 8, and 12 weeks (P ≤ 0.01). CONCLUSIONS: Based on our study findings, BMP-2 plasmid DNA-loaded chitosan films provide an effective strategy for GBR, combining cellular compatibility with biocapability in vivo.

Three-dimensional virtual planning in precise chimeric fibula free flap for metacarpal defects: A case report.

RATIONALE: Metacarpal and phalanx defects with soft tissue loss were suggested to be reconstructed by vascularized bone flap. The fibular osteocutaneous flap is a preferred method. Three-dimensional virtual planning has successfully applied in mandibular reconstruction with fibular free flap. We applied three-dimensional virtual planning in precise fibula flap harvest to maintain the continuity of the fibula and to achieve accurate metacarpal and phalanx reconstruction. PATIENT CONCERNS: A 35-year-old male presented with extensive soft tissue defects and first metacarpal defect involving the first metacarpophalangeal joint. DIAGNOSES: There were 4 cm of first metacarpal defect involving the first metacarpophalangeal joint and soft tissue defects of 5cm × 3cm + 3cm × 2cm. INTERVENTIONS: By combining three-dimensional virtual planning, we harvested a chimeric fibular flap. The precise fibula partial osteotomies were performed with cutting guides designed in virtual planning. OUTCOMES: All the chimeric flaps survived and no significant donor-site morbidity was noted. Michigan Hand Outcome Questionnaire scores indicated acceptable functional results. LESSONS: Our preliminary experience with the approach of three-dimensional virtual planning in precise chimeric fibula free flap is practical and efficient. Although more cases and follow-up are needed to evaluate it, this approach is expected to benefit patients.

Pharyngoesophageal Reconstruction With the Medial Sural Artery Perforator Flap After Total Laryngopharyngectomy: A New Method.

BACKGROUND: The medial sural artery perforator (MSAP) flap has become a popular target in head and neck reconstruction. This flap has many advantages compared with other free flaps but has not yet been used in the reconstruction of circumferential haryngoesophageal defects. METHODS: Reconstruction of pharyngoesophageal circumferential defects using the MSAP flap was performed in 4 patients. The design of the flap was based on the perforators, which were confirmed by endoscopy. The MSAP flap was tubed and anastomosed end to end to the esophagus. The artery was anastomosed to the superior thyroid arteries, whereas the vein was anastomosed to the internal jugular vein. RESULTS: All the flaps survived. All 4 patients gained acceptable speech and swallow function. One patient developed an infection at the donor site, a second developed fistulas, and a third experienced stricture. All complications were successfully treated. CONCLUSIONS: Here, we demonstrated the use of the MSAP flap in reconstruction of circumferential pharyngoesophageal defects. Further application and follow-up studies should be performed.

Treatment of Tear Trough Deformity: Fat Repositioning versus Autologous Fat Grafting.

BACKGROUND: Fat-preserving lower blepharoplasty techniques and filling techniques using autologous or non-autologous materials are increasingly used to treat tear trough deformity. However, there has been no definitive comparison of the results of fat repositioning versus autologous fat grafting for this condition. The authors used statistical analysis to compare the results of the two methods. METHODS: From October 2013 to September 2015, a total of 101 patients, aged 20-43 years, underwent fat repositioning or autologous fat grafting in our department. Group 1 (51 patients, 102 eyes) underwent intraorbital fat repositioning with septal reset by transconjunctival lower blepharoplasty. Group 2 (50 patients, 100 eyes) underwent autologous fat grafting by lipoinjection. RESULTS: No significant complications occurred in any patient postoperatively. Four of 102 eyes in Group 1 and seven of 100 eyes in Group 2 had no improvement; the rest had different degrees of improvement. In Grade II and III deformities, fat repositioning resulted in significantly greater improvement of grade compared with autologous fat grafting. The surgical method of Group 1 resulted in better curative effects than that of Group 2. CONCLUSION: In patients with tear trough deformity and without obvious skin or orbicularis oculi muscle laxity, both fat repositioning and autologous fat grafting are acceptable for mild deformity. In patients with higher-grade deformities, fat repositioning produced superior results than autologous fat grafting. LEVEL OF EVIDENCE IV: This journal requires that the authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://www.springer.com/00266 .

Expression of hepatocyte growth factor and c-Met is characteristic of α-fetoprotein-producing colorectal adenocarcinoma: A report of three cases.

α-fetoprotein (AFP)-producing colorectal adenocarcinoma is rare and typically not well recognized. In the present study, 3 cases of AFP-producing colorectal cancer are described. All 3 of these cases demonstrated increased levels of blood AFP associated with disease progression. Only case 2 exhibited classical histological hepatoid features. Following immunohistochemical tissue staining, all 3 cases were observed to be positive for AFP expression. In addition, the expression of hepatocyte growth factor (HGF), c-Met receptor and the transcription factor c-Myc were identified to be associated with the expression of AFP. The 3 cases demonstrated resistance to multiple drugs, including epidermal growth factor receptor inhibitors, despite the presence of wild-type Kirsten rat sarcoma viral oncogene homolog (K-RAS; codons 12 and 13), neuroblastoma-RAS (codons 12 and 13) and B-Raf proto-oncogene, serine/threonine kinase (V600E). We propose that hepatoid histological features or a positive AFP finding by immunohistochemistry are sufficient for a diagnosis of AFP-producing colorectal adenocarcinoma. Furthermore, we speculates that autocrine HGF/c-Met activation may be capable of inducing the dedifferentiation of common adenocarcinoma cells, reverting them to a cancer stem cell state and producing AFP or hepatoid differentiation. Consequently, therapy targeted to the HGF/c-Met signaling pathway may potentially be effective for the treatment of AFP-producing colorectal adenocarcinoma.

A Case Report of Gastrointestinal Hemorrhage and Perforation During Apatinib Treatment of Gastric Cancer.

Apatinib is a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2, which shows good efficacy and safety in clinical trials for chemotherapy-refractory gastric cancer patients. Till now, there is no case report after apatinib came in the market. We presented a 55-year-old Chinese woman with advanced gastric cancer, who received apatinib after failure of second-line chemotherapy. On the 19th day of apatinib administration, she suffered from gastrointestinal hemorrhage. Then, her condition rapidly deteriorated to gastrointestinal perforation. Although the patient received timely medical and surgical treatment, she finally died of septic shock. Although apatinib shows exciting efficacy and good tolerance in phase II and III clinical trials, this novel targeted drug should be prescribed carefully and close clinical monitoring is needed when using it.

Metachronous Primary Adenocarcinoma of Lung During Adjuvant Imatinib Mesylate Therapy for Gastrointestinal Stromal Tumor of Stomach: A Case Report.

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor in gastrointestinal tracts; however, the synchronous or metachronous coexistence of GIST with additional primary malignancy is not common.Here, we present an unusual case of gastric GIST with metachronous primary lung adenocarcinoma diagnosed during his adjuvant treatment with oral receptor tyrosine kinase inhibitor imatinib mesylate (400 mg daily). After 6-month use of imatinib, the patient suffered from dry cough and dyspnea. Subsequent lung biopsy demonstrated adenocarcinoma with diffuse interstitial changes.Our research emphasizes the possibility of an additional primary tumor with GIST, and reminds the clinicians to strengthen the surveillance of the additional cancer during the follow-up of GIST patients.

Afatinib circumvents multidrug resistance via dually inhibiting ATP binding cassette subfamily G member 2 in vitro and in vivo.

Multidrug resistance (MDR) to chemotherapeutic drugs is a formidable barrier to the success of cancer chemotherapy. Expressions of ATP-binding cassette (ABC) transporters contribute to clinical MDR phenotype. In this study, we found that afatinib, a small molecule tyrosine kinase inhibitor (TKI) targeting EGFR, HER-2 and HER-4, reversed the chemoresistance mediated by ABCG2 in vitro, but had no effect on that mediated by multidrug resistance protein ABCB1 and ABCC1. In addition, afatinib, in combination with topotecan, significantly inhibited the growth of ABCG2- overexpressing cell xenograft tumors in vivo. Mechanistic investigations exhibited that afatinib significantly inhibited ATPase activity of ABCG2 and downregulated expression level of ABCG2, which resulted in the suppression of efflux activity of ABCG2 in parallel to the increase of intracellular accumulation of ABCG2 substrate anticancer agents. Taken together, our findings may provide a new and useful combinational therapeutic strategy of afatinib with chemotherapeutical drug for the patients with ABCG2 overexpressing cancer cells.

Transsacral excision with pre-operative imatinib mesylate treatment and approach for gastrointestinal stromal tumors in the rectum: A report of two cases.

Gastrointestinal stromal tumors (GISTs) are rare in the rectum. Radical surgery, such as an abdominoperineal resection, is necessary for large rectal GISTs, which can result in the loss of function of involved organs. Imatinib mesylate can be used as perioperative therapy and may reduce tumor size, and it is now approved for use in the adjuvant therapy of locally resected anorectal GISTs. The present study describes two cases of large rectal GISTs, for which abdominoperineal resections were initially planned. The two patients received pre-operative imatinib mesylate treatment, and the therapeutic response was assessed by magnetic resonance imaging. Finally, transsacral local resection was successfully performed for these two GISTs. A macroscopically complete resection was achieved, and microscopically, the resection margin was negative. One patient experienced the complication of rectal leakage, which was successfully managed by drainage. No recurrence occurred in the two patients after more than two years. Pre-operative imatinib mesylate therapy with subsequent transsacral local resection for selected rectal GISTs is a feasible treatment modality and can prevent extended surgery.

Afatinib enhances the efficacy of conventional chemotherapeutic agents by eradicating cancer stem-like cells.

Cancer stem cells (CSC) have garnered significant attention as a therapeutic focus, based on evidence that they may represent an etiologic root of treatment-resistant cells. Indeed, expression of the multidrug resistance protein ATP-binding cassette subfamily G member 2 (ABCG2) confers chemoresistance to CSCs, where it serves as a potential biomarker and therapeutic target. Here, we show that afatinib, a small-molecule inhibitor of the tyrosine kinases EGFR, HER2, and HER4, preferentially eliminated side population cells with CSC character, in both cell lines and patient-derived leukemia cells, by decreasing ABCG2 expression. In these cells, afatinib also acted in parallel to suppress self-renewal capacity and tumorigenicity. Combining afatinib with the DNA-damaging drug topotecan enhanced the antitumor effect of topotecan in vitro and in vivo. Mechanistic investigations suggested that ABCG2 suppression by afatinib did not proceed by proteolysis through the ubiquitin-dependent proteosome, lysosome, or calpain. Instead, we found that afatinib increased DNA methyltransferase activity, thereby leading to methylation of the ABCG2 promoter and to a decrease in ABCG2 message level. Taken together, our results advocate the use of afatinib in combination with conventional chemotherapeutic drugs to improve efficacy by improving CSC eradication.

Reconstruction after complete avulsion of the nipple caused by a human bite using an amputated tissue graft in situ.

Integrated avulsion of the nipple by human bite is not common. We treated a patient whose left nipple had been completely avulsed by modifing the nipple as a free skin graft and reconstructing a pillar-like fascia flap as the core to reshape the configuration of the nipple.

Adenosquamous carcinoma of the uncinate process of the pancreas with synchronous gastrointestinal stromal tumor of the stomach: Case report and review of the literature.

Recently, the coexistence of gastrointestinal stromal tumors (GISTs) with other neoplasms has been studied with increasing frequency. Coexistence of pancreatic cancer with GISTs remains a rarity; however, here, we report a very rare case of adenosquamous carcinoma (ASC) of the uncinate process of the pancreas with synchronous GISTs of the stomach in a 62-year-old female. The patient presented with epigastric discomfort and vomiting. Radiographic imaging revealed two masses; one located at the body of the stomach and the other located at the uncinate process of the pancreas. Intraoperatively, a fine needle aspiration biopsy was conducted in the uncinate process of the pancreas, which revealed the malignancy of the masses. A pancreaticoduodenectomy and partial gastrectomy were then conducted, and subsequent pathological examinations identified an ASC of the pancreas and a GIST of the stomach. In our case, contrary to the majority of previous cases of synchronous GISTs and other malignancies, GIST was not an incidental finding. The initial suspicion on the GIST as the underlying cause of clinical symptoms led to the discovery of the ASC of the uncinate process of the pancreas.

Complications after polyacrylamide hydrogel injection for facial soft-tissue augmentation in China: twenty-four cases and their surgical management.

BACKGROUND: Polyacrylamide hydrogel has been used for soft-tissue augmentation for more than 10 years. Although it is considered a nontoxic, nonimmunogenic material, complications after polyacrylamide hydrogel injections during facial soft-tissue augmentation have been reported. METHODS: Between 2003 and 2009, 24 patients underwent surgical management of complications after facial soft-tissue augmentation. Histories, preoperative imaging, and photographs of operations were recorded. RESULTS: Complications included hematomas, infection, nodule formation, and migration. Ultimately, 23 of 24 cases underwent surgery to remove the gel; the remaining case underwent surgical drainage to remove it. CONCLUSIONS: As more complications have been reported, especially ones that are difficult to treat, the safety of polyacrylamide hydrogel needs to be reconsidered. The authors' experiences provide methods to remove polyacrylamide hydrogel if complications occur. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

Intrahepatic biliary cystadenoma presenting with pleural effusion.

Hepatobiliary cystadenomas are rare cystic neoplasms that often occur in middle aged women. The exact etiology of these tumors is unknown. Diagnosis is often delayed in these cases. However, misdiagnosis and inappropriate treatment may result in unfavorable outcome. We report a case of hepatobiliary cystadenoma with pleural effusion. We also review the literature and discuss the current diagnostic and treatment modalities.

Endoscopic ultrasound features of gastric schwannomas with radiological correlation: a case series report.

Gastric schwannomas are rare mesenchymal tumors of the gastrointestinal tract. They are usually misdiagnosed as other submucosal tumors preoperatively. Experience of the imaging features of gastric schwannomas is extremely limited. In this report, we summarize the features of a series of endoscopic ultrasound (EUS) images of gastric schwannomas in an effort to improve the diagnosis and differential diagnosis rate. We retrospectively reviewed the endosonographic features of four patients with gastric schwannomas and their computed tomography imaging results. Gastric schwannomas had heterogeneous hypoechogenicity or isoechogenicity, and a well-demarcated margin. The tumors originated from the fourth layer. Cystic changes and calcification were uncommon. Marginal hypoechoic haloes were observed in two patients. The results described here were different from those of previous studies. In the EUS evaluation, the internal echogenicity of gastric schwannomas was heterogeneous and low, but slightly higher than that of muscularis propria. These features might help us differentiate gastric schwannomas from other submucosal tumors. Further investigation is needed to differentiate these mesenchymal tumors.