Superficial Cancer Research Articles

Endoscopic submucosal dissection using an ultrathin endoscope for superficial pharyngeal cancer: a prospective feasibility study (with video).

Background and study aims Endoscopic submucosal dissection (ESD) of pharyngeal cancers with conventional endoscopes often is difficult, not only because of the narrow working space, but also because endoscope maneuverability in the pharynx is poor due to interference from the endotracheal tube and/or hyoid bone. However, we hypothesized that those problems could possibly be resolved by use of an ultrathin endoscope for ESD of superficial pharyngeal cancer. The aim of this prospective interventional study was to investigate the feasibility of ESD for superficial pharyngeal cancer using an ultrathin endoscope. Patients and methods This feasibility study was conducted at NTT Medical Center Tokyo between June 2020 and September 2021, and data from a total of 20 consecutively superficial pharyngeal cancers were analyzed. The primary outcome measure was the R0 resection rate. The ESD completion rate, en bloc resection rate, procedure time, and frequency of intraoperative and postoperative adverse events (AEs) were also evaluated as secondary outcome measures. Results Data from 16 patients with 20 lesions were included in the analysis. All of the lesions were successfully resected by ultrathin endoscope ESD, and the en bloc and R0 resection rates were 100 % and 85.0 % (17/20), respectively; the procedure time was 37.8 ± 28.2 minutes. No intraoperative or postoperative AEs were encountered in any cases. Conclusions ESD using an ultrathin endoscope is feasible for superficial pharyngeal cancers and has potential to be a safe and effective treatment option for these cancers.

Paraffin gauze bolus as tissue compensator in photon irradiation for mycosis fungoides – regarding a case study

Abstract Introduction: Total skin electron beam therapy is a treatment option in patients with mycosis fungoides (MF) affecting a significant amount of the body surface. For patients with involvement of soles and interdigital folds, however, this approach is ineffective, requiring alternatives such as localised radiotherapy (RT). Although electron beams are well suited for superficial lesions, on irregular surfaces it provides inadequate tumour coverage and excess dose variance, requiring photon irradiation with tissue compensation. Methods: We present the case of a patient with extensive cutaneous MF with skin lesions spread over both lower limbs and treated on these affected areas with photon beam RT. Long sheets of paraffin gauze dressings were used to create a 0·5-cm-thick bolus. The patient received a single fraction of 8 Gy. In vivo dosimetry using Gafchromic films was performed. Results: After 3 months, a complete response was achieved. In this case, paraffin gauze bolus proved to be an inexpensive, convenient, effective and flexible method for irregular superficial cancer irradiations. Conclusion: Paraffin gauze bolus is a suitable option for irregular contours.

Monocationic Chlorin as a Promising Photosensitizer for Antitumor and Antimicrobial Photodynamic Therapy.

Cancer is one of the leading causes of death worldwide. Despite substantial progress in the understanding of tumor biology, and the appearance of new generations of targeted drugs and treatment techniques, the success achieved in this battle, with some notable exceptions, is still only moderate. Photodynamic therapy (PDT) is a successful but still underestimated therapeutic modality for treating many superficial cancers. In this paper, we focus on the extensive investigation of the monocationic chlorin photosensitizer (PS), considered here as a new photosensitizing agent for both antitumor and antimicrobial PDT. This monocationic chlorin PS (McChl) obtained from methylpheophorbide a (MPh) via a two-step procedure is well soluble in water in the physiological temperature range and forms stable complexes with passive carriers. McChl generates singlet oxygen with a good quantum yield in a lipid-like environment and binds mainly to low- and high-density lipoproteins in a vascular system. A comparison of the photodynamic activity of this agent with the activity of the well-established photosensitizer chlorin e6 (Chl e6) clearly indicates that McChl provides a much more efficient photoinactivation of malignant and microbial cells. The pilot PDT treatment of M1 sarcoma-bearing rats with this PS demonstrates its good potential for further preclinical investigations.

Photodynamic Therapy as an Effective Treatment for Cutaneous Lymphomas.

Topical photodynamic therapy (PDT) is a non-invasive treatment modality frequently used in dermatology to treat superficial skin cancers but also some inflammatory or infectious dermatoses. PDT appears a more and more promising therapeutic option also for cutaneous lymphomas, either of T- or B-cell origin. It is a well-tolerated treatment and has excellent cosmetic outcomes, less side effects compared to other therapies (steroids, surgery, radiotherapy, and so on), no particular contraindications, and is easily repeatable in case of relapses. However, how PDT works in the treatment of cutaneous lymphoproliferative diseases is poorly understood and the literature data are still controversial. Further randomized, controlled clinical trials involving a greater number of patients and centers with a long follow-up are necessary to assess the efficacy of PDT and establish a unique standardized treatment protocol in relation to the lymphomatous disease and the type, thickness, and location of the lesions.

Nanotherapeutic Intervention in Photodynamic Therapy for Cancer.

The clinical need for photodynamic therapy (PDT) has been growing for several decades. Notably, PDT is often used in oncology to treat a variety of tumors since it is a low-risk therapy with excellent selectivity, does not conflict with other therapies, and may be repeated as necessary. The mechanism of action of PDT is the photoactivation of a particular photosensitizer (PS) in a tumor microenvironment in the presence of oxygen. During PDT, cancer cells produce singlet oxygen (1O2) and reactive oxygen species (ROS) upon activation of PSs by irradiation, which efficiently kills the tumor. However, PDT's effectiveness in curing a deep-seated malignancy is constrained by three key reasons: a tumor's inadequate PS accumulation in tumor tissues, a hypoxic core with low oxygen content in solid tumors, and limited depth of light penetration. PDTs are therefore restricted to the management of thin and superficial cancers. With the development of nanotechnology, PDT's ability to penetrate deep tumor tissues and exert desired therapeutic effects has become a reality. However, further advancement in this field of research is necessary to address the challenges with PDT and ameliorate the therapeutic outcome. This review presents an overview of PSs, the mechanism of loading of PSs, nanomedicine-based solutions for enhancing PDT, and their biological applications including chemodynamic therapy, chemo-photodynamic therapy, PDT-electroporation, photodynamic-photothermal (PDT-PTT) therapy, and PDT-immunotherapy. Furthermore, the review discusses the mechanism of ROS generation in PDT advantages and challenges of PSs in PDT.

Myeloid-derived suppressor cells and plasmacytoid dendritic cells are associated with oncogenesis of oral squamous cell carcinoma.

Myeloid-derived suppressor cells (MDSCs) help establish the tumor microenvironment by suppressing T-cell response in tumor-bearing hosts. Plasmacytoid dendritic cells (pDCs) activate antigen-specific T cells, thereby, maximizing their antitumor effects. IDO1 is associated with both MDSCs and pDCs and plays a major role in the formation of the tumor-mediated immunosuppressive environment. We utilized immunohistochemistry to examine the involvement of IDO1 in oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMDs, precancerous lesions). We examined the expression of MDSC markers, CD11b and CD33, as well as pDC markers, CD303 and IDO1, in 60 OSCC and 45 precancerous lesion specimens and analyzed their association with clinicopathological parameters. Expression of these biomarkers identifying MDSCs and pDCs was high in precancerous lesions in patients with severe dysplasia and OSCC. While detecting pDCs, high CD303 and IDO1 expression levels were frequently observed in moderately or poorly differentiated OSCCs. CD11b, CD33, and CD303 levels were significantly correlated with the mode of invasion; CD33 was correlated with OSCC invasion depth while the other three markers tended to be highly expressed in superficial cancer cases showing microinvasion. Expression levels of all four biomarkers were significantly associated with the cancerization of OPMDs to OSCCs. We show, for the first time, that the infiltration of MDSCs and pDCs is significantly associated with progression of premalignant lesions to OSCC. This suggests that these cells may act as prognostic biomarkers for premalignant lesion progression and that immunotherapeutic approaches that control each of these immunosuppressive cells may protect against progression to malignancy.

Usefulness of third-generation narrow band imaging and texture and color enhancement imaging in improving visibility of superficial early gastric cancer: A study using color difference.

Overlooking early gastric cancer (EGC) during endoscopy is an issue to be resolved. Image-enhanced endoscopy is expected to improve EGC detection. This study investigated the usefulness of third-generation narrow band imaging (3G-NBI) and texture and color enhancement imaging (TXI) in improving the visibility of EGC using the color difference between EGC and its surrounding gastric mucosa. In this retrospective observational study, we examined 51 superficial EGCs that underwent endoscopic submucosal dissection and were observed by all three methods: 3G-NBI, TXI, and white light imaging (WLI). The primary endpoint was to compare the color difference of each method. For each EGC, we prepared one non-magnifying image for each method so that the location and size of the lesion in each image were the same. The L*a*b* color space was used to evaluate the color values. When the color values of the cancerous lesion and its surrounding mucosa were (L*c, a*c, b*c) and (L*s, a*s, b*s), respectively, the color difference was defined to be [(L*c-L*s)2+(a*c-a*s)2+(b*c-b*s)2]1/2. The median color difference was 9.2 (interquartile range, 5.3-15.7) in WLI, 13.5 (interquartile range, 9.4-19.5) in 3G-NBI, and 15.3 (interquartile range, 9.1-22.1) in TXI. Statistically, the color difference was significantly larger in 3G-NBI than in WLI (p < 0.001) and TXI compared with WLI (p < 0.001). However, there was no significant difference between 3G-NBI and TXI (p = 0.330). Regarding color difference, both 3G-NBI and TXI were estimated to be more useful than WLI in improving the visibility of superficial EGC.

Recent Progress and Trends in X-ray-Induced Photodynamic Therapy with Low Radiation Doses.

The prominence of photodynamic therapy (PDT) in treating superficial skin cancer inspires innovative solutions for its congenitally deficient shadow penetration of the visible-light excitation. X-ray-induced photodynamic therapy (X-PDT) has been proven to be a successful technique in reforming the conventional PDT for deep-seated tumors by creatively utilizing penetrating X-rays as external excitation sources and has witnessed rapid developments over the past several years. Beyond the proof-of-concept demonstration, recent advances in X-PDT have exhibited a trend of minimizing X-ray radiation doses to quite low values. As such, scintillating materials used to bridge X-rays and photosensitizers play a significant role, as do diverse well-designed irradiation modes and smart strategies for improving the tumor microenvironment. Here in this review, we provide a comprehensive summary of recent achievements in X-PDT and highlight trending efforts using low doses of X-ray radiation. We first describe the concept of X-PDT and its relationships with radiodynamic therapy and radiotherapy and then dissect the mechanism of X-ray absorption and conversion by scintillating materials, reactive oxygen species evaluation for X-PDT, and radiation side effects and clinical concerns on X-ray radiation. Finally, we discuss a detailed overview of recent progress regarding low-dose X-PDT and present perspectives on possible clinical translation. It is expected that the pursuit of low-dose X-PDT will facilitate significant breakthroughs, both fundamentally and clinically, for effective deep-seated cancer treatment in the near future.

S1125 Utility and Role of Endoscopic Ultrasound for Suspected Early Esophageal Cancer

Introduction: Accurate clinical staging of esophageal cancer is vital in selecting appropriate treatment options. Endoscopic ultrasound (EUS) has been determined to be an accurate imaging modality for esophageal cancer staging, differentiating superficial lesions from deep lesions. Despite being accurate, utilization of EUS in apparent early-stage cancer remains controversial. The current study aims to assess the utility of EUS for early-stage esophageal cancer and whether endoscopic features of esophageal malignancy can help direct the optimal management of the cancer. Methods: This was a retrospective study of patients who underwent pre-resection EUS after a diagnosis of esophageal cancer at a tertiary medical center. 50 patients met inclusion criteria for this study. Patient clinical data, initial EGD/biopsy, EUS, and final resection pathology reports were extracted from chart review and statistical analysis was performed to determine the accuracy of EUS and associations of endoscopic findings with deeper invasion. Results: EUS T stage was concordant with histological T stage in 74% of patients (37/50). In determining sub-mucosal involvement (T1a vs T1b), EUS had a specificity of 85% and sensitivity of 53.8%. EUS had an overall accuracy of 72.7% in identifying sub-mucosal invasion in T1 cancers. Prominent lymph nodes on EUS and tumor size >2 cm on visual inspection were significantly associated with deeper invasion of cancer on histology with p-values < 0.01. Barrett’s morphology was significantly associated with superficial cancers with a p-value < 0.01. EUS affected management from EMR/ESD to esophagectomy in 9.4% of patient with Barrett’s morphology and 6.7% of patients with tumor size < 2cm. In patients without any endoscopic findings suggestive of deep invasion, EUS identified deeper cancer and changed management in < 7% of cases. Conclusion: For assessing deeper invasion (T2, T3 and T4), EUS has been substantiated as a significantly effective tool. In staging T1b lesions, EUS was reasonably specific in ruling out sub-mucosal invasion; however, it had relatively poor sensitivity in identifying sub-mucosal invasion. Additionally, data validated endoscopic features suggesting superficial cancers including a tumor size < 2cm and the presence of Barrett’s morphology. In patients with these findings suggesting superficial cancer, EUS rarely identified a deep cancer that warranted a change in management.

Super Light-Sensitive Photosensitizer Nanoparticles for Improved Photodynamic Therapy against Solid Tumors.

Photodynamic therapy (PDT) is an effective method for superficial cancer treatment. However, the limited light intensity in tissues, tumor hypoxia, and the low accumulation efficiency of photosensitizers (PSs) in tumors are still major challenges. Herein, we introduce super light-sensitive PS nanoparticles (designated HR NPs) that can increase singlet oxygen (1 O2 ) production and improve PS accumulation in tumors. HR NPs have the ability to produce a large amount of 1 O2 under ultralow power density light (0.05 mW cm-2 ) irradiation. More significantly, HR NPs have a long circulating time in tumor-bearing mice and can accumulate in tumors with high efficiency. When irradiated by light with a suitable wavelength, the nanoparticles exhibit excellent antitumor efficacy. This work will make it possible to cure solid tumors by PDT by enhancing the therapeutic effects.

Super Light‐Sensitive Photosensitizer Nanoparticles for Improved Photodynamic Therapy against Solid Tumors

AbstractPhotodynamic therapy (PDT) is an effective method for superficial cancer treatment. However, the limited light intensity in tissues, tumor hypoxia, and the low accumulation efficiency of photosensitizers (PSs) in tumors are still major challenges. Herein, we introduce super light‐sensitive PS nanoparticles (designated HR NPs) that can increase singlet oxygen (1O2) production and improve PS accumulation in tumors. HR NPs have the ability to produce a large amount of 1O2 under ultralow power density light (0.05 mW cm−2) irradiation. More significantly, HR NPs have a long circulating time in tumor‐bearing mice and can accumulate in tumors with high efficiency. When irradiated by light with a suitable wavelength, the nanoparticles exhibit excellent antitumor efficacy. This work will make it possible to cure solid tumors by PDT by enhancing the therapeutic effects.

Degradation strategy of cyclin D1 in cancer cells and the potential clinical application.

Cyclin D1 has been reported to be upregulated in several solid and hematologic tumors, promoting cancer progression. Thus, decreasing cyclin D1 by degradation could be a promising target strategy for cancer therapy. This mini review summarizes the roles of cyclin D1 in tumorigenesis and progression and its degradation strategies. Besides, we proposed an exploration of the degradation of cyclin D1 by FBX4, an F box protein belonging to the E3 ligase SKP-CUL-F-box (SCF) complex, which mediates substrate ubiquitination, as well as a postulate about the concrete combination mode of FBX4 and cyclin D1. Furthermore, we proposed a possible photodynamic therapy strategythat is based on the above concrete combination mode for treating superficial cancer.

Dual-source powered nanomotor with integrated functions for cancer photo-theranostics

While the miniaturization and motility of artificial nanomotors made them popular tools for exploring novel and innovative biomedical cancer treatment strategies, the integration of multiple functions on the small motor bodies is key to achieve further progress but remains unresolved. Here, we propose a dual-source powered Janus nanomotor whose composition integrates multiple photo-theranostic functions such as surface-enhanced Raman scattering (SERS) sensing, fluorescence imaging/photoacoustic imaging (PAI), photodynamic therapy (PDT), and photothermal therapy (PTT). This nanomotor can be fabricated by sputtering a thin gold layer onto one side of mesoporous silica (mSiO2) combined with surface modification by photo-sensitizer, Raman reporter, and catalase. Upon illumination with 808 nm near-infrared light, the half-coated gold nanoshell serves as PAI/PTT agent, and by upconverting NIR to visible light, the pre-loaded photosensitizer can be excited by the upconverted light of UCNPs to convert the dissolved oxygen (O2) into reactive oxygen species for efficient PDT. Furthermore, ratiometric SERS signal can be captured to quantitatively detect the tumor marker, H2O2, in cellular microenvironments. The immobilized catalase as a nano-engine can catalyze endogenous H2O2 to O2. This function not only improves the hypoxic tumor microenvironment and therefore enhances PDT efficiency, but also provides a thrust force for deep penetration. As a proof of concept for the in vivo trial we performed cancer photo-theranostics where our nanomotors successfully treated a mouse breast tumor in a subcutaneous tumor model. The results are promising and encourage the use of an integrated nanomotor platform that could be further developed into a photo-theranostic agent for superficial cancer treatment.

Prediction of depth of invasion and lymph node metastasis in superficial pharyngeal cancer by magnifying endoscopy using the Japan Esophageal Society classification.

BackgroundsThe pharynx has no muscularis mucosae, so it is unclear whether diagnostic techniques used for the esophagus can be applied to the pharynx. This study investigated the usefulness of magnifying endoscopy with narrowband imaging using the Japan Esophageal Society (JES) classification for predicting the depth of invasion and lymph node metastasis (LNM) in pharyngeal cancer.MethodsA total of 123 superficial pharyngeal carcinoma lesions that had been observed preoperatively with magnifying endoscopy with narrowband imaging between January 2014 and June 2021 were analyzed. Predictors of subepithelial invasion (SEP) and LNM were sought based on endoscopic findings, including microvascular morphology, using the JES classification.ResultsThe lesions were divided into carcinoma in situ (n = 41) and SEP (n = 82). Multivariate analysis identified B2–B3 vessels (odds ratio [OR] 6.54, 95% confidence interval [CI] 1.74–24.61, p = 0.005) and a middle/large avascular area (OR 4.15, 95% CI 1.18–14.62, p = 0.027) as independent predictors of SEP. Significant predictors of LNM were protruding type, B2–B3 vessels, middle/large avascular area, SEP, venous invasion, lymphatic invasion, and tumor thickness > 1000 μm. Median tumor thickness increased significantly in the order of B1 < B2 < B3 vessels (B1, 305 μm; B2, 1045 μm; B3, 4043 μm; p < 0.001). The LNM rates for B1, B2, and B3 vessels were 1.6% (1/63), 4.8% (2/42), and 55.6% (10/18), respectively (p < 0.001).ConclusionsMagnifying endoscopy with narrowband imaging using the JES classification could predict the depth of invasion in superficial pharyngeal carcinoma. The JES classification may contribute to the prediction of LNM, suggesting that it could serve as an alternative to tumor thickness.

Endoscopic Treatment of Superficial Gastric Cancer: Present Status and Future.

Although the mortality rates of gastric cancer (GC) are gradually declining, gastric cancer is still the fourth leading cause of cancer-related death worldwide. This may be due to the high rate of patients who are diagnosed with GC at advanced stages. However, in countries such as Japan with endoscopic screening systems, more than half of GCs are discovered at an early stage, enabling endoscopic resection (ER). Especially after the introduction of endoscopic submucosal dissection (ESD) in Japan around 2000, a high en bloc resection rate allowing pathological assessment of margin and depth has become possible. While ER is a diagnostic method of treatment and may not always be curative, it is widely accepted as standard treatment because it is less invasive than surgery and can provide an accurate diagnosis for deciding whether additional surgery is necessary. The curability of ER is currently assessed by the completeness of primary tumor removal and the possibility of lymph node metastasis. This review introduces methods, indications, and curability criteria for ER of EGC. Despite recent advances, several problems remain unsolved. This review will also outline the latest evidence concerning future issues.

Clinicopathological features of Epstein-Barr virus-associated superficial early stage gastric cancer treated with endoscopic submucosal dissection.

Epstein-Barr virus (EBV) is known to be involved in gastric carcinogenesis. EBV-associated early gastric carcinoma (EBVEGC) has a lower incidence of lymph node involvement and could be an expanded indication for endoscopic submucosal dissection (ESD) treatment. To clarify the prevalence and clinicopathological features of EBVEGC. This study reviewed 618 lesions in 519 patients treated with ESD between 2014 and 2016. Tissue microarray sections were subjected to in situ hybridization staining for EBV-encoded small RNA transcripts (EBER). Lesions positive for EBER were compared with control lesions and were retrospectively analyzed. 12 (1.9%) of the 618 lesions were EBVEGC. EBVEGCs were more frequently located near the atrophic border than control lesions in the middle or upper stomach and were reddish. EBVEGC invasion was deeper and more often histologically undifferentiated. On narrow-band imaging magnifying endoscopy, the EBVEGC group significantly more often showed an endoscopic lace pattern, defined as an absent or obscure microsurface pattern and a microvascular pattern of a tiny, dense, and irregular subepithelial capillary network. The rate of curative resection was significantly lower in the EBVEGC group. Only 1.9% of the ESD specimens were EBV-positive. Endoscopic features could raise clinical suspicion of EBV infection.

Efficacy of endoscopic submucosal dissection under nasal intubation for superficial pharyngeal cancer

Efficacy of endoscopic submucosal dissection under nasal intubation for superficial pharyngeal cancer

Intratumoral immunotherapy using a TLR2/3 agonist, L-pampo, induces robust antitumor immune responses and enhances immune checkpoint blockade

BackgroundToll-like receptors (TLRs) are critical innate immune sensors that elicit antitumor immune responses in cancer immunotherapy. Although a few TLR agonists have been approved for the treatment of patients with...

Anatomical Sites OF Superficial Basal Cell Cancers Demonstrate Higher Rates of Mixed Histology

Historically, "aggressive" histologic subsets (HSs) of basal cell carcinoma (BCC) seem to be more likely to statistically exhibit Subclinical extension and require more phases during Mohs micrographic surgery (MMS) and consequently larger margins upon excision. The "Mohs Suitable Use Criteria (MAUC)" for the most appropriate therapy of superficial basal cell carcinoma. Objective: To evaluate if aggressive subtypes of superficial Basal Cell Carcinoma are common among healthy, immunocompromised patients and high-risk anatomical sites. Methods: The study was carried out in Khyber Teaching Hospital Peshawar, from November 2021-march to 2022, A total of 100 Mohs surgeries on superficial basal cell carcinoma were performed. Under light microscope slides were examined for any pattern of histology besides superficial basal cell carcinoma for statistical analysis MAU anatomical site healthy individuals and immunocompromised patients were grouped accordingly Results: Among health and immunocompromised individuals’ zone H and zone L were significantly increased in mixed histology. While in healthy individuals’ the association between L Zone and M zone was incredibly significant but in immunocompromised was not significant Conclusions: The mixed histology of SBCC was higher in the head and neck region. Researchers say that the MAUC scoring technique for SBCC is supported by a high incidence in SBCC of the head and neck.

Use of fly larva (Maggots) in Cancer Treatment: A systematic review

Introduction: Superficial cancers are one of the most common cancers in humans and animals. The use of maggot therapy as an alternative treatment is expanding and has achieved great success in treating superficial. Maggot extracts and secretions have been also demonstrated to have beneficial biological effects. The present study aimed to perform the first systematic review of the use of maggot, as well as its secretions and extracts, in neoplasms. Methods: In the current review study, online databases, such as Pub Med, Web of Science, Scopus, and Embase, were searched to retrieve the published studies from 1985-2021. The used keywords were Maggot therapy, Larval therapy, Larval extract, Larval secretions, Cancer, Neoplasm, and Tumor. Only research on the larvae of the order Diptera was included in the present study. Results: Out of 387 screened papers, 9 articles met the proposed inclusion criteria. There were three articles on the use of maggot debridement therapy in tumor lesions and six articles on the effect of maggot secretions and extract on neoplastic cells. Maggot debridement therapy has been able to control the complications of skin tumors and breast cancer. Several studies have also reported anti-tumor effects on larval extracts and secretions. Conclusions: Maggots were able to improve the appearance of lesions and prevent further tumor growth that was progressing before larval therapy. It seems that maggot therapy can be used to treat necrotic tumors; moreover, its extract and secretions can be used to treat a wider range of cancers in humans and animals. Nonetheless, more studies are needed in non-progressive cancers to determine the true effects of this method.