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336. EFFICACY AND SAFETY OF PHOTODYNAMIC THERAPY FOR SECONDARY PRIMARY ESOPHAGEAL SQUAMOUS CELL CARCINOMA AFTER CHEMORADIOTHERAPY OR RADIOTHERAPY FOR ANOTHER MALIGNANCY

Abstract Background Photodynamic therapy (PDT) using talaporfin sodium is known as the effective, safe, and less invasive treatment for local failure after chemoradiotherapy (CRT) or radiotherapy (RT) for esophageal squamous cell carcinoma (ESCC). The secondary primary ESCC sometimes occur at different site after CRT/RT for ESCC or other cancer, and PDT may be considered for such lesion if endoscopic resection and surgery are not suitable for patients. However, the actual therapeutic efficacy remains unclear. This study aims to evaluate the efficacy and safety of PDT using talaporfin sodium for untreated secondary primary ESCC with a history of CRT/RT for another malignancy. Methods This retrospective study enrolled the patients underwent PDT using talaporfin sodium for untreated secondary primary ESCC in the treatment field of prior CRT/RT for another malignancy at the National Cancer Center Hospital East from September 2016 to October 2021. The inclusion criteria of PDT in this study were as follow; 1) invasion depth limited within T2, 2) <3/4 of the esophageal circumference, 3) absence of lymph node or distant metastasis, and 4) patient’s refusal or unsuitable physical condition for surgery. We evaluated the rate of local complete response (L-CR), incidence of adverse events, and clinical outcomes. Results Ten patients were enrolled in this study. Previous malignancy organ was hypopharynx (n=1), lung (n=2), and esophagus (n=7). All secondary primary ESCC were diagnosed as T1b. Finally, L-CR was achieved in 6 patients (L-CR rate: 60.0%). Among 6 patients with L-CR, one had local recurrence, one had lymph node recurrence, and the remaining four had no recurrence. During the median follow-up of 27.5 months, one patient with L-CR died from other diseases. Adverse events included grade ≤2 esophageal pain in 2 patients, photosensitivity and esophageal stricture in each one, and no esophageal perforation or treatment-related death. Conclusion As retreatment with RT is not available, PDT may be the treatment options for the secondary primary ESCC after CRT/RT for another malignancy.

Feasibility of Regional Lymphadenectomy for Stomach-Preserving Surgery in Early Gastric Cancer Omitting Sentinel Node Navigation: A Post Hoc Analysis of the SENORITA Trial.

Sentinel node navigation (SNN) has been known as the effective treatment for stomach-preserving surgery in early gastric cancer; however, SNN presents several technical difficulties in real practice. This study aimed to evaluate the feasibility of regional lymphadenectomy omitting SNN, using the post hoc analysis of a randomized controlled trial. Using data from the SENORITA trial that compared laparoscopic standard gastrectomy with lymphadenectomy and laparoscopic SNN, 237 patients who underwent SNN were included in this study. Tumor location was divided into longitudinal and circumferential directions. According to the location of the tumor, the presence or absence of lymph node (LN) metastases between sentinel and non-sentinel basins were analyzed. Proposed regional LN stations were defined as the closest area to the primary tumor. Sensitivities, specificities, positive predictive values, and negative predictive values (NPV) of SNN and regional lymphadenectomy were compared. Metastasis to non-sentinel basins with tumor-free in sentinel basins was observed in one patient (0.4%). The rate of LN metastasis to non-regional LN stations without regional LN metastasis was 2.5% (6/237). The sensitivity and NPV of SNN were found to be significantly higher than those of regional lymphadenectomy (96.8% vs. 80.6% [p=0.016] and 99.5% vs. 97.2% [p=0.021], respectively). This study showed that regional lymphadenectomy for stomach-preserving surgery, omitting SNN, was insufficient; therefore, SNN is required in stomach-preserving surgery.

Expression and clinical significance of PD-L1 and infiltrated immune cells in the gastric adenocarcinoma microenvironment.

Programmed death-ligand 1 (PD-L1) is a crucial negative costimulatory molecule expressed on both tumor and immune cells. It binds to programmed death-1, facilitating tumor escape. Tumor-infiltrating immune cells play a vital role in this process. However, the clinical relationship between PD-L1 expression and tumor-infiltrating immune cells remains uncertain. Immunohistochemistry (IHC) was utilized to assess PD-L1 expression and TIIC markers (CD3, CD4, CD8, CD19, CD31, CD68, CD11c, CD56, and α-smooth muscle actin) in gastric adenocarcinoma tissues from 268 patients. The aim was to explore the prognostic significance of PD-L1 and the infiltration of different immune cell types. The study analyzed overall survival and the correlations between PD-L1 expression, immune cell infiltration, and clinicopathological characteristics. Among the 268 patients, 52 (19.40%) exhibited high PD-L1 expression on tumor cells (TPD-L1), while 167 (62.31%) displayed high PD-L1 expression on immune cells (IPD-L1). Patients with high IPD-L1 expression showed improved survival compared to those with low IPD-L1 expression (P = .028). High TPD-L1 expression associated with various clinicopathological features, such as larger tumor size, poorer differentiation, deeper invasion depth, and higher tumor stage. Conversely, patients with high IPD-L1 expression exhibited shallower tumor invasion and lower mortality rates. Univariate analysis indicated that superficial tumor infiltration, absence of lymph node and distant metastasis, low tumor stage, high IPD-L1 expression, and elevated CD8 and CD19 expression were associated with a reduced risk of tumor progression. Multivariate analysis revealed that patients with high IPD-L1 and CD8 expression or high TPD-L1 and low CD31 expression experienced significantly better overall survival than patients with other combinations. The findings indicate that patients with high PD-L1 expression in immune cells have a substantially improved prognosis. Additionally, the combination of PD-L1 with CD8 or CD31 expression status can serve as an indicator of prognosis in patients with gastric adenocarcinoma.

HER-3 surface expression increases in advanced colorectal cancer representing a potential therapeutic target

HER-3 (also known as ErbB-3) is a human epidermal growth factor receptor tyrosine kinases family member, and its expression in CRC (colorectal cancer) tissues was previously associated with poor prognosis. In this study, HER-3 expression was analyzed by immunohistochemistry in two cohorts of early and advanced metastatic CRC patients. The first cohort included 180 patients diagnosed with CRC in absence of lymph nodes or distant metastases (Stage I and Stage II), while the second was obtained from 53 advanced metastatic CRC patients who developed synchronous (SM) and metachronous (MM) liver metastases. In the first early-stage CRC cohort, 86 out of 180 (47.8%) tumors showed membranous expression of HER-3, with a mean percentage of positive tumor cells of 25.7%; conversely, in advanced metastatic CRC primary tumors, HER-3 was detected in all specimens, with a mean percentage of positive tumor cells of 76.1%. Kaplan–Meier curves showed that in the advanced metastatic CRC group, patients with HER-3high tumors had a significantly lower Cancer-Specific Survival (CSS) rate compared to patients with HER-3low tumors (p = 0.021). Importantly, this worse CSS rate was observed only in the MM subgroup of patients with HER-3high tumors (p = 0.002). Multivariate analysis confirmed that high HER-3 expression represents a significant and strong risk factor for death in patients developing MM liver metastases (Hazard Ratio = 64.9; 95% Confidence Interval, 4.7–886.6; p = 0.002). In addition, using a specific anti-HER-3 antibody-drug conjugate, named EV20/MMAF, we showed that HER-3 + CRC cells can be efficiently targeted in vitro and in vivo. Overall, this study confirms that surface HER-3 is highly expressed in CRC and reveals that HER-3 expression increases in metastatic CRC patients compared to early stage. Importantly, the results suggest that HER-3 has a prognostic and therapeutic value in patients developing MM liver metastases.

Delivery of costimulatory blockade to lymph nodes promotes transplant acceptance in mice.

The lymph node (LN) is the primary site of alloimmunity activation and regulation during transplantation. Here, we investigated how fibroblastic reticular cells (FRCs) facilitate the tolerance induced by anti-CD40L in a murine model of heart transplantation. We found that both the absence of LNs and FRC depletion abrogated the effect of anti-CD40L in prolonging murine heart allograft survival. Depletion of FRCs impaired homing of T cells across the high endothelial venules (HEVs) and promoted formation of alloreactive T cells in the LNs in heart-transplanted mice treated with anti-CD40L. Single-cell RNA sequencing of the LNs showed that anti-CD40L promotes a Madcam1+ FRC subset. FRCs also promoted the formation of regulatory T cells (Tregs) in vitro. Nanoparticles (NPs) containing anti-CD40L were selectively delivered to the LNs by coating them with MECA-79, which binds to peripheral node addressin (PNAd) glycoproteins expressed exclusively by HEVs. Treatment with these MECA-79-anti-CD40L-NPs markedly delayed the onset of heart allograft rejection and increased the presence of Tregs. Finally, combined MECA-79-anti-CD40L-NPs and rapamycin treatment resulted in markedly longer allograft survival than soluble anti-CD40L and rapamycin. These data demonstrate that FRCs are critical to facilitating costimulatory blockade. LN-targeted nanodelivery of anti-CD40L could effectively promote heart allograft acceptance.

Free time evolution of the quantum wave function and optimal transportation

It is shown that, in the absence of nodes and under regularity assumptions, a solution in a finite interval of time of the free Schrodinger equation solves a minimization problem, which is a stochastic generalization of the classical optimal transportation problem with quadratic cost.

Determination of the extent of dissection in early gastric cancer based on lymph node station power index.

BackgroundThe relative prognostic value of each lymph node (LN) station remains undefined in the treatment of gastric cancer. This study aimed to develop a new method to evaluate LN station ranking and define the optimal extent of lymphadenectomy for early gastric cancer.MethodsClinical and histopathological information from patients who underwent curative gastrectomy with lymphadenectomy between 1989 and 2018 was reviewed. The LN station power index (LNPI) of each station was estimated using a LN retrieval frequency and the 5-year overall survival of patients with absence of LN at each station. External validation was conducted to evaluate the relevance of the LNPI.ResultsA training set was developed from examination of 7009 patient records. For most nodal stations, the absence of LN was significantly associated with a poor prognosis. For the perigastric stations, the prognostic value assessed using the LNPI was in the following order: LN 4 (LNPI = 19.68), LN 3 (LNPI = 17.58), LN 6 (LNPI = 15.16), LN 1 (LNPI = 6.71), LN 2 (LNPI = 4.64) and LN 5 (LNPI = 2.86). The value rank of the extra-gastric stations was in the following order: LN 8a (LNPI = 12.93), LN 7 (LNPI = 10.51) and LN 9 (LNPI = 9.70), but the index of LN 12a (LNPI = 4.79) was higher than that of LN 11 (LNPI = 4.78). These trends in the LNPI were similar in the validation patient cohort.ConclusionsThe LNPI is a simple tool to rank the priority of each LN station dissection. The optimal extent of D1 + lymphadenectomy using LNPI was determined to be D1 with LNs 7, 8a and 9.

Study of Podoplanin Expression in Head and Neck Squamous Cell Carcinoma.

Background & Objective:Head and Neck Squamous cell carcinoma (HNSCC) is one of the leading cancers worldwide. Cervical lymph node metastasis is the most adverse prognostic factor for patients with HNSCC. As there are no reliable factors in predicting lymph node metastasis, recent researchers focus on identifying various metastasis markers that will aid treatment selection. Podoplanin is a recent marker strongly associated with lymph node metastasis, aggressive tumor behavior, and poor prognosis. The expression of podoplanin in human squamous cell cancers and its association with cancer cell motility suggest a possibility that it could be used as a biomarker to predict lymph node metastasis. To study the expression of podoplanin in head and neck squamous cell carcinoma, determine its association with clinicopathological variables, and predict its use as a biomarker in predicting lymph node metastasis. Methods:The present study was conducted in a tertiary care hospital. Podoplanin expression was studied in 45 cases of HNSCC and its association with clinicopathological variables. The predictive power of podoplanin was further analyzed using univariate and multivariate logistic regression analysis. The positive and negative predictive values of podoplanin were determined concerning the presence or absence of lymph node metastasis.Results:Podoplanin expression is significantly associated with histological grade (P=0.03) and lymph node metastasis (P=0.01). In logistic regression analysis, podoplanin expression (Odds Ratio: 5.66, Confidence Interval: 1.23 -25.87, P=0.02) was a significant independent predictor of lymph node metastasis. Conclusion: Our study demonstrates that podoplanin provides prognostic information and predicts lymph node metastasis which was consistent with our studies in the literature. Thus, podoplanin may help better stratify patients selected for elective neck node dissection in early tumor stages and clinically negative regional disease.

Concurrent Weekly Cisplatin and Simultaneous Integrated Boost-IMRT in Locally Advanced Head and Neck Squamous Cell Carcinoma-An Institutional Experience.

Introduction Concurrent chemoradiation with weekly cisplatin in locally advanced head and neck squamous cell carcinoma (LA-HNSCC) is widely practiced in India. Radiation with simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) has the advantage of executing IMRT in single phase with better dose distribution. Material and Methods 150 patients with LA-HNSCC treated between April 2015 and December 2019 were retrospectively evaluated. All patients received 70Gy in 33 to 35 fractions with SIB-IMRT and concurrent weekly cisplatin at a dose of 40 mg/m 2 . Treatment compliance and toxicities were assessed. Overall survival (OS) was evaluated using Kaplan-Meier estimates; univariate and multivariate analysis of prognostic factors were also evaluated. Results Median age was 58.5 years. Forty-five percent had primary oropharyngeal cancer. Sixty-two percent had T3 disease, 41% had N2 disease, and 51% had stage IV disease. All patients received 70Gy dose of RT. Median chemotherapy cycles were six, 84.7% received 200 mg/m 2 . Acute grade 2 xerostomia was seen in 79%, grade 3 neutropenia, mucositis and pharyngitis were seen in 11, 15, and 21%, respectively. Complete response was seen in 66.6%. At median follow-up of 21.4 months (3-71) OS was 60% and median OS was 33.2 months. Estimated 2 and 3 year OS was 56 and 48%. On univariate analysis, absence of node, N0-N1, stage III, cisplatin use, dose per fraction 2.12Gy ,and complete response showed good OS ( p <0.05). On multivariate analysis dose per fraction 2.12Gy and complete response showed good OS ( p <0.05). Conclusion Definitive chemoradiation with weekly cisplatin and SIB-IMRT in LA-HNSCC is well tolerated with good clinical outcomes.

Novel intragraft regulatory lymphoid structures in kidney allograft tolerance

Intragraft events thought to be relevant to the development of tolerance are here subjected to a comprehensive mechanistic study during long-term spontaneous tolerance that occurs in C57BL/6mice that receive life sustaining DBA/2kidneys. These allografts rapidly develop periarterial Treg-rich organized lymphoid structures (TOLS) that form in response to class II but not to class I MHC disparity and form independently of lymphotoxin α and lymphotoxin β receptor pathways. TOLS form in situ in the absence of lymph nodes, spleen, and thymus. Distinctive transcript patterns are maintained over time in TOLS including transcripts associated with Treg differentiation, T cell checkpoint signaling, and Th2 differentiation. Pathway transcripts related to inflammation are expressed in early stages of accepted grafts but diminish with time, while B cell transcripts increase. Intragraft transcript patterns at one week posttransplant distinguish those from kidneys destined to be rejected, that is, C57BL/6 allografts into DBA/2 recipients, from those that will be accepted. In contrast to inflammatory tertiary lymphoid organs (iTLOs) that form in response to chronic viral infection and transgenic Lta expression, TOLS lack high endothelial venules and germinal centers. TOLS represent a novel, pathogenetically important type of TLO that are in situ markers of regulatory tolerance.

MECHANICAL PROPERTIES OF BAMBOO (BAMBUSA VULGARIS)

This research project investigated the tensile, bending and compressive strength of a species of bamboo called Bambusa vulgaris. The density of the B. vulgaris was found to be 500kg/m3 (oven dry). The tensile strength was 94.3MPa with nodes and 117.8MPa without nodes. The compressive strength was 49.9MPa with nodes and 56.7MPa without nodes, bending strength was 107.0MPa with nodes and 137.7MPa without nodes and Modulus of Elasticity in tension was 3002.2MPa with nodes and 3594.0MPa without nodes. Modulus of Elasticity in compression was 10,405.3MPa without nodes and 7,268.1MPa with nodes. The nodes were found to have a significant effect in lowering the tensile and bending strength of bamboo. The compressive strength was not affected by the presence or absence of nodes.

Histopathological evaluation of estrogen receptors, progesterone receptors, and human epidermal growth factor Receptor-2/Neu expressions in breast carcinoma and their correlations with other prognostic factors: A hospital-based study

Background: Breast carcinoma is a leading cause of death among women. Factors such as estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER-2/neu) have important prognostic and predictive value. Aim: The aim of the study is to demonstrate ER, PR, and HER-2/neu expression in breast cancer specimens and to correlate these expressions with other prognostic factors such as tumor size, type, grade, and lymph node status. Methods: This prospective study included 70 cases of female breast carcinoma. Histopathological evaluation of all cases done and tumor size, site, presence, or absence of lymph node was recorded. Typing of tumor, grade, and lymph node status were determined. Immunohistochemical staining for ER, PR, and HER-2/neu of breast lesions was done, and the data were analyzed to find out any correlation of expression of ER, PR, HER-2/neu with the above prognostic factors. Results: The majority of patients were in 41–50 years (44.29%). Most of tumors were 2–5 cm in size and the infiltrating duct carcinoma-not otherwise specified was the commonest type. ER and PR expression decreases (P = 0.02340 and P = 0.02413 respectively), while HER-2/neu expression increases with increase tumor size (P = 0.02289). ER and PR expression were low while Her-2/neu expression was more in higher tumor grade (P = 0.022472, P = 0.04149 and P = 0.03339 respectively). No significant association was identified between ER, PR, HER-2/neu and number of metastatic lymph node. Conclusion: ER, PR, and HER-2/neu status correlates well with histopathological grading and tumor size. However, no significant association is seen with cancer type and lymph node status.

TERT promoter mutations in penile squamous cell carcinoma: high frequency in non-HPV-related type and association with favorable clinicopathologic features

PurposePenile carcinoma is a rare malignant neoplasm with a largely unknown molecular pathogenesis. Telomerase reverse transcriptase promoter (TERT-p) mutations have been detected in several types of human malignancies. The aim of this study was to investigate the presence of TERT-p mutations in penile squamous cell carcinomas (SCCs) and their associations with clinicopathologic features.MethodsIn this retrospective study, Sanger sequencing was performed to detect TERT-p mutations in formalin-fixed paraffin-embedded tissue samples from 37 patients with penile SCC, 16 patients with cutaneous SCC, and 4 patients with non-neoplastic penile/skin tissue. The expression of p16INK4a and Ki-67 was investigated via immunohistochemistry. Associations of TERT-p mutation with clinicopathological factors, immunohistochemical results, and clinical outcome were statistically analyzed.ResultsRecurrent TERT-p mutations were identified in 18 out of 37 (48.6%) penile SCCs, including all 3 carcinoma in situ cases. TERT-p mutations were significantly more frequent in non-human papilloma virus (HPV)-related penile SCC types than in non-HPV-related penile SCC based on both histologic classification and p16INK4a immunoreactivity. Furthermore, TERT-p mutation was associated with a low histologic grade, low mitotic count, absence of necrosis, low Ki-67/MIB-1 labeling index, and absence of lymph node or distant metastasis.ConclusionOur study shows TERT-p mutations are the most frequent somatic mutations in penile SCC. In addition, TERT-p mutations are far more frequent in non-HPV-related penile SCC than in HPV-related penile SCC, indicating TERT-p mutations may have a role in tumorigenesis distinct from HPV-related penile SCC.

Vascularized composite allotransplants as a mechanistic model for allograft rejection - an experimental study.

Vascularized composite allotransplants (VCAs) seem to have several unique features of clinical and experimental importance, including uniquely definable lymphatic drainage that can be easily accessed at the level of ipsilateral regional node beds. Thus, VCA offers a unique opportunity to assess the relative contribution of peripheral and secondary lymphoid tissue to the process of rejection. We transplanted hind limb grafts from C3H donors to six different groups of C57BL/6 recipients: Spleen+ Map3k14-/- ; Spleen- Map3k14-/- ; Spleen+ Node- Map3k14-/- ; and Spleen- Node- Map3k14-/- . As positive controls, we used Map3k14+/- with or without spleen. Map3k14+/- mice demonstrated an average graft survival of 9.6 and 9.2days for Spleen- and Spleen+ Map3k14+/- , respectively. Rejection in the Map3k14-/- group was considerably delayed (28.4days, P=0.002) in all recipients. The Spleen- Map3k14-/- mice rejected their hind limb allografts in an even more delayed fashion compared to Spleen+ Map3k14-/- (54.4days, P=0.02). Histological analysis of skin showed that acute rejection in both Map3k14+/- mice groups was graded as Banff III or Banff IV. In the Map3k14-/- groups, rejection was graded as Banff III. We demonstrated that in the absence of lymph nodes, grafts reject in a delayed fashion. Also, splenectomy in alymphoplastic mice further extends graft survival, but does not eliminate rejection all together.

Prognostic and clinicopathological implications of expression of Beclin-1 and hypoxia-inducible factor 1α in serous ovarian carcinoma: an immunohistochemical study.

Serous ovarian carcinoma (SOC) is anovarian cancer with ahigh fatality rate. Therefore, alot ofresearchers have tried to identify novel prognostic biomarkers which might improve thepatient prognosis. The aims ofthestudy were to detect thetissue protein expression ofBeclin-1 in addition to HIF-1α in SOC patients, to evaluate therelationship between their expression, theclinicopathological parameters, patients' prognosis, and therelation to chemotherapy resistance in SOC. We evaluated theexpression ofBeclin-1 in addition to HIF-1α in 60 patients with SOC using immunohistochemistry, followed all patients for about 36 months, analyzed associations between both markers' expression, clinicopathological data, and patients' prognosis. Beclin-1 expression was related to low grade (p=0.002), early SOC stage, absence ofperitoneal spread (p=0.006), and absence oflymph nodes, and distant metastases (p=0.004 and<0.001 respectively), while HIF-1α expression was associated with higher grade and stage (p=0.007), and presence ofnodal and distant metastases (p<0.001 and=0.012 respectively). High Beclin-1 expression and low HIF-1α expression were positively associated with good response to chemotherapy (p=0.047 and p=0.022 respectively), alower recurrence rate after successful therapy (p=0.006 and<0.001 respectively), and increased three-year recurrence-free and overall survival rates (p<0.001). In SOC patients; Beclin-1 is agood prognostic marker, while HIF-1α is apoor prognostic marker.

Physico-mechanical Properties of Two Philippine Bamboos Thermally Modified in a Steam Environment

Two commercial bamboo species – namely, “kauayan tinik” (Bambusa blumeana J.A. and J.H. Schultes) and giant bamboo [Dendrocalamus asper (Schultes et.) Backer ex Heyne] – were treated by thermal modification (TM) or heat treatment in a steam environment using temperature and duration settings of 175 °C – 30 min and 200 °C – 30 min. The effect of TM and the presence and absence of node on the physical and mechanical properties of bamboo were studied. Physical [moisture content (MC), thickness swelling (TSw), water absorption (WA), and specific gravity] and mechanical (flexural, compression, and tensile strength) properties were determined. A factorial experiment in a completely randomized design (CRD) was used to analyze the data. Results showed that TM improved the dimensional stability of bamboo as evidenced by lower MC, TSw, and WA compared to control samples. Except for tensile strength, the flexural and compressive strength of heat-treated bamboo did not significantly change at 175 °C – 30 min compared to the control. The presence of nodes, on the other hand, significantly reduced the bamboo samples’ flexural and tensile strength. Generally, TM improved the dimensional stability of bamboo without significantly affecting the mechanical properties at 175 °C – 30 min. At 200 °C – 30 min, a slight reduction in strength was observed, especially for D. asper.

Early Diagnosis of Low-Risk Papillary Thyroid Cancer Results Rather in Overtreatment Than a Better Survival.

We are witnessing a rapid worldwide increase in the incidence of papillary thyroid carcinoma (PTC) in the last thirty years. Extensive implementation of cancer screening and wide availability of neck ultrasound or other imaging studies is the main reason responsible for this phenomenon. It resulted in a detection of a growing number of clinically asymptomatic PTCs, mainly low-risk tumors, without any beneficial impact on survival. An indolent nature of low-risk PTC, particularly papillary thyroid microcarcinoma (PTMC), and the excellent outcomes raise an ongoing discussion regarding the adequacy of treatment applied. The question of whether PTMC is overtreated or not is currently completed by another, whether PTMC requires any treatment. Current ATA guidelines propose less extensive preoperative diagnostics and, if differentiated thyroid cancer is diagnosed, less aggressive surgical approach and limit indications for postoperative radioiodine therapy. However, in intrathyroidal PTMCs in the absence of lymph node or distant metastases, active surveillance may constitute alternative management with a low progression rate of 1%–5% and without any increase in the risk of poorer outcomes related to delayed surgery in patients, in whom it was necessary. This review summarizes the current knowledge and future perspectives of active surveillance in low-risk PTC.

Cervical cancer recurrence - can we predict the type of recurrence?

We aimed to identify if there is an association between the severity of cervical cancer at diagnosis and the pattern of recurrence. We conducted a retrospective study of recurrent cervical cancers diagnosed between 2016 and 2018. We characterized the cases according to histology, size, FIGO stage (according to 2009 and 2018 FIGO classifications) and nodal involvement at diagnosis, symptoms at the time of recurrence, interval between the end of treatment and recurrence, imaging methods used, and location of the recurrence. Statistical analysis was performed between histology, size, FIGO stage and nodal involvement at diagnosis and time to recurrence and type of recurrence (locoregional versus lymph node, distant or multiple site involvement). We included 48 patients with recurrent cervical cancer. At diagnosis, mean tumor size was 5 cm and 83% of the patients had squamous cell carcinoma. The FIGO stage changed in 43.8% of patients between the 2009 and the 2018 classifications. A mean of 26 months elapsed between the end of treatment and recurrence. Recurrence was symptomatic in 64.6% of patients. Imaging identified recurrence in 97.9% of patients. The most frequent recurrence sites were locoregional and lymph node metastases. We found a statistically significant association between 2009 FIGO stage and time to recurrence (P = 0.030) and lymph node involvement at diagnosis and type of recurrence (P = 0.022). As expected patients with more advanced disease recurred sooner, though this was only observed for the 2009 FIGO classification. Absence of lymph nodes at initial diagnosis was associated with locoregional recurrence, while presence of lymph node involvement was associated with lymph node, distant or multiple site involvement of recurrence. No other significant associations were found. In our cohort of recurrent cervical cancer, we found an association between patients without lymph node metastases at initial diagnosis and locoregional recurrence. Further studies are needed in order to evaluate whether this association has predictive value.

High Expression of Nuclear Transcription Factor-κB is Associated with Cisplatin Resistance and Prognosis for Ovarian Cancer.

BackgroundAbnormal activation of the nuclear transcription factor-κB (NF-κB) signaling pathway plays a crucial role in the chemoresistance of tumor cells. This study aimed to explore the significance of NF-κB in the chemoresistance of ovarian cancer.MaterialsWe performed immunohistochemical staining for evaluating the expression of NF-κB in cancer tissues. The MTT assay was performed for analyzing cell proliferation, Western blotting was performed to quantify NF-κB p65, and flow cytometry was used to determine the apoptosis rate.ResultsNuclear NF-κB p65 over-expression was closely associated with ovarian cancer with advanced FIGO stage, residual disease ≥1 cm, low histologic grade, platinum resistance and refractory, chemotherapy resistance (P< 0.05). FIGO stage I–II and residual disease <1 cm were associated with complete response (CR) to chemotherapy, while FIGO stage I–II, residual disease <1cm and absence of lymph node (LN) metastasis were associated with platinum sensitivity. In multivariate logistic regression, residual disease ≥1 cm was a risk factor for response to chemotherapy, while the over-expression of nuclear NF-κB p65 was a risk factor for sensitivity to chemotherapy. In the ROC curves, nuclear NF-κB p65 expression had the discriminative ability for sensitivity to chemotherapy (AUC = 0.637, P = 0.021). Furthermore, nuclear NF-κB p65 expression was an independent prognostic factor. Western blotting showed that NF-κB p65 level in cisplatin-resistant cells (C13* and A2780cp) was significantly higher than that in cisplatin-sensitive cells (OV2008 and A2780s) (P < 0.05), and this increased expression could be suppressed by NF-κB inhibitor-PDTC treatment. The proliferation inhibitory rates of cisplatin in C13* and A2780cp cells increased after PDTC treatment in a concentration-dependent manner. PDTC treatment could also enhance cisplatin-induced apoptosis.ConclusionNF-κB was associated with the clinicopathological features, chemoresistance, and prognosis of ovarian cancer. The NF-κB inhibitor PDTC can enhance cisplatin sensitivity of platinum-resistant C13* and A2780cp ovarian cancer cells.

A pooled analysis of the prognostic value of PD-L1 in melanoma: evidence from 1062 patients.

BackgroundProgrammed death-ligand 1 (PD-L1) was the first identified ligand of programmed death-1 (PD-1). PD-1/PD-L1 interactions inhibit T cell-mediated immune responses, limit cytokine production, and promote tumor immune escape. Recently, many studies have investigated the prognostic value of PD-L1 expression in patients with melanoma. However, the results of these analyses remain a subject of debate. We have therefore carried out a meta-analysis to identify the prognostic role of PD-L1 in melanoma.MethodsA thorough medical literature search was performed in the databases PubMed, Web of Science, and Embase until October 2019. The pooled hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated to evaluate the correlation between PD-L1 overexpression and prognosis. Publication bias was evaluated using Begg’s test and Egger’s test.ResultsThirteen articles with 1062 enrolled patients were included in this meta-analysis. High PD-L1 expression did not correlate with overall survival (OS) (HR = 0.93, 95% CI 0.57–1.52, P = 0.781) or progression-free survival (PFS) (HR = 0.82, 95% CI 0.43–1.54, P = 0.535). However, PD-L1 overexpression correlated with the absence of lymph node (LN) metastasis (OR = 0.46, 95% CI 0.22–0.95, P = 0.036). Further, there was no significant relationship between PD-L1 expression and sex (OR = 1.29, 95% CI 0.90–1.84, P = 0.159), age (OR = 0.90, 95% CI 0.51–1.57, P = 0.708), or Eastern Cooperative Oncology Group Performance Status (OR = 0.55, 95% CI 0.06–4.83, P = 0.592).ConclusionsThis meta-analysis suggested that PD-L1 expression did not predict an inferior prognosis in patients with melanoma. However, high PD-L1 expression was associated with absence of LN metastasis in such patients.