Unveiling the mechanism of source-sink rebalancing in cucumber-pumpkin heterografts: the buffering roles of rootstock cotyledon.

Grafting onto pumpkin rootstock is widely applied in cucumber production to improve growth and yield, as well as to overcome soil-borne diseases and enhance resistance to abiotic stresses. In this study, we constructed the cucumber-pumpkin heterografts with the one-cotyledon grafting method, and examined the effects of heterografting on biomass allocation and sugar partitioning, with cucumber and pumpkin self-grafts used as control. Compared with cucumber self-grafts, heterografting onto pumpkin rootstock promoted photosynthesis in cucumber scion, and led to higher sucrose contents in the 1st true leaf (source) and newly emerged leaf (sink). Thereby, the scion part of heterografts accumulated more biomass than cucumber self-grafts. In contrast, when compared to pumpkin self-grafts, grafting with cucumber scion reduced root vigor and biomass but promoted cotyledon growth in pumpkin rootstock. The roots (sink) of heterografts contained less sucrose and hexoses, and showed reduced sucrose synthase (SuSy) and hexokinase (HXK) activities. However, the rootstock cotyledon (source) contained more sucrose and starch, and showed higher activities of HXK, cell-wall invertase (CWIN), and enzymes for starch synthesis and degradation. Furthermore, removal or shade of rootstock cotyledon led to reduced growth of root and scion. Silencing of CmoMEX1a gene in rootstock cotyledon inhibited maltose export and reduced root growth of heterografts. These results indicated that rootstock cotyledon, especially its starch content, played a buffering role in the growth regulation of cucumber-pumpkin heterografts. Taken together, our results provided a major contribution to our understanding of source-sink sugar partitioning and scion-rootstock growth balancing in cucumber-pumpkin heterografts.

ABA-responsive AREB1/ABI3-1/ABI5 cascade regulates IAA oxidase gene SlDAO2 to inhibit hypocotyl elongation in tomato.

Hypocotyl elongation is dramatically influenced by environmental factors and phytohormones. Indole-3-acetic acid (IAA) plays a prominent role in hypocotyl elongation, whereas abscisic acid (ABA) is regarded as an inhibitor through repressing IAA synthesis and signalling. However, the regulatory role of ABA in local IAA deactivation remains largely uncharacterized. In this study, we confirmed the antagonistic interplay of ABA and IAA during the hypocotyl elongation of tomato (Solanum lycopersicum) seedlings. We identified an IAA oxidase enzyme DIOXYGENASE FOR AUXIN OXIDATION2 (SlDAO2), and its expression was induced by both external and internal ABA signals in tomato hypocotyls. Moreover, the overexpression of SlDAO2 led to a reduced sensitivity to IAA, and the knockout of SlDAO2 alleviated the inhibitory effect of ABA on hypocotyl elongation. Furthermore, an ABA-responsive regulatory SlAREB1/SlABI3-1/SlABI5 cascade was identified to act upstream of SlDAO2 and to precisely control its expression. SlAREB1 directly bound to the ABRE present in the SlDAO2 promoter to activate SlDAO2 expression, and SlABI3-1 enhanced while SlABI5 inhibited the activation ability of SlAREB1 by directly interacting with SlAREB1. Our findings revealed that ABA might induce local IAA oxidation and deactivation via SlDAO2 to modulate IAA homoeostasis and thereby repress hypocotyl elongation in tomato.

Transcriptional repression specifies the central cell for double fertilization.

Double fertilization is a key innovation for the evolutionary success of angiosperms by which the two fertilized female gametes, the egg cell and central cell, generate the embryo and endosperm, respectively. The female gametophyte (embryo sac) enclosed in the sporophyte is derived from a one-celled haploid cell lineage. It undergoes successive events of mitotic divisions, cellularization, and cell specification to give rise to the mature embryo sac, which contains the two female gametes accompanied by two types of accessory cells, namely synergids and antipodals. How the cell fate of the central cell is specified has long been equivocal and is further complicated by the structural diversity of female gametophyte across plant taxa. Here, MADS-box protein AGL80 was verified as a transcriptional repressor that directly suppresses the expression of accessory cell-specific genes to specify the central cell. Further genetic rescue and phylogenetic assay of the AGL80 orthologs revealed a possible conserved mechanism in the Brassicaceae family. Results from this study provide insight into the molecular determination of the second female gamete cell in Brassicaceae.

A receptor heteromer mediates the male perception of female attractants in plants.

Sexual reproduction requires recognition between the male and female gametes. In flowering plants, the immobile sperms are delivered to the ovule-enclosed female gametophyte by guided pollen tube growth. Although the female gametophyte-secreted peptides have been identified to be the chemotactic attractant to the pollen tube, the male receptor(s) is still unknown. Here we identify a cell-surface receptor heteromer, MDIS1-MIK, on the pollen tube that perceives female attractant LURE1 in Arabidopsis thaliana. MDIS1, MIK1 and MIK2 are plasma-membrane-localized receptor-like kinases with extracellular leucine-rich repeats and an intracellular kinase domain. LURE1 specifically binds the extracellular domains of MDIS1, MIK1 and MIK2, whereas mdis1 and mik1 mik2 mutant pollen tubes respond less sensitively to LURE1. Furthermore, LURE1 triggers dimerization of the receptors and activates the kinase activity of MIK1. Importantly, transformation of AtMDIS1 to the sister species Capsella rubella can partially break down the reproductive isolation barrier. Our findings reveal a new mechanism of the male perception of the female attracting signals.

ZBTB7A functioned as an oncogene in colorectal cancer.

BACKGROUND: Despite zinc finger and BTB domain-containing 7A (ZBTB7A) documented importance in multiple tumors, the function and clinical value in Colorectal cancer (CRC) remain elusive. The aim of this study was to evaluate the functional roles and the clinical value of ZBTB7A in CRC progression. METHODS: The level of ZBTB7A was detected in a large cohort of CRC patients (n = 189) by immunohistochemistry (IHC), and we analyzed the diagnostic and prognostic value of the protein. In addition, the functional roles of ZBTB7A on CRC were explored in vitro and in vivo. RESULTS: Survival analyses indicated that patients with high ZBTB7A expression made the prognosis worse (P = 0.024). Functionally, knockdown of ZBTB7A could markedly inhibit tumor proliferation in vitro and in vivo, whereas ZBTB7A overexpression displayed the opposite results. CONCLUSIONS: ZBTB7A was associated with poor survival outcomes and functioned as an oncogene in CRC patients, indicating that it is a potential prognostic biomarker and therapeutic target for CRC patients.

Arabidopsis CBP1 Is a Novel Regulator of Transcription Initiation in Central Cell-Mediated Pollen Tube Guidance.

In flowering plants, sperm cells are delivered to the embryo sac by a pollen tube guided by female signals. Both the gametic and synergid cells contribute to pollen tube attraction. Synergids secrete peptide signals that lure the tube, while the role of the gametic cells is unknown. Previously, we showed that CENTRAL CELL GUIDANCE (CCG) is essential for pollen tube attraction in Arabidopsis thaliana, but the molecular mechanism is unclear. Here, we identified CCG BINDING PROTEIN1 (CBP1) and demonstrated that it interacts with CCG, Mediator subunits, RNA polymerase II (Pol II), and central cell-specific AGAMOUS-like transcription factors. In addition, CCG interacts with TATA-box Binding Protein 1 and Pol II as a TFIIB-like transcription factor. CBP1-knockdown ovules are defective in pollen tube attraction. Expression profiling revealed that cysteine-rich peptide (CRP) transcripts were downregulated in ccg ovules. CCG and CBP1 coregulate a subset of CRPs in the central cell and the synergids, including the attractant LURE1. CBP1 is extensively expressed in multiple vegetative tissues and specifically in the central cell in reproductive growth. We propose that CBP1, via interaction with CCG and the Mediator complex, connects transcription factors and the Pol II machinery to regulate pollen tube attraction.

Cetuximab or nimotuzumab plus intensity-modulated radiotherapy versus cisplatin plus intensity-modulated radiotherapy for stage II-IVb nasopharyngeal carcinoma.

To compare intensity-modulated radiotherapy (IMRT) with cisplatin (CDDP) versus cetuximab (CTX) and nimotuzumab (NTZ) for Stage II-IVb Nasopharyngeal Carcinoma (NPC). A total of 1,837 patients with stage II-IVb NPC who received IMRT plus CTX or NTZ, or CDDP between January 2009 and December 2013 were included in the current analysis. Using propensity scores to adjust for potential prognostic factors, a well-balanced cohort of 715 patients was created by matching each patient who underwent IMRT plus concomitant NTZ/CTX with four patients who underwent IMRT plus concomitant CDDP (1:4). Efficacy and safety were compared between the CTX/NTZ and CDDP groups of this well-balanced cohort. Furthermore, we conducted multivariate analysis and subgroup analysis based on all the 1,837 eligible cases. There was no significant difference between CTX/NTZ group and CDDP group in terms of DFS (3-year, 86.7% vs. 86.2%, p > 0.05), LRRFS (96.2% vs. 96.3%, p > 0.05), DMFS (91.1% vs. 92.3%, p > 0.05) and OS (91.7% vs. 91.9%, p > 0.05). Subgroup analysis demonstrated a significant interaction effect between patients with IMRT plus CTX/NTZ and N3 node stage on LRRFS with the highest risk of loco-regional relapse (HR 8.85, p = 0.001). Significantly increased hematologic toxicities, gastrointestinal reactions were observed in the CDDP group (p < 0.05). Patients of 3.4-4.7% experienced severe hematologic toxicities during the treatment with concomitant CTX and NTZ. Increased rate of CTX related-skin reaction and mucositis was observed in the CTX group. CTX/NTZ used concurrently with IMRT may be comparable to those of the standard CDDP-IMRT combination for maximizing survival for patients with stage II-IVb NPC.

Establishment of an innovative staging system for extramedullary plasmacytoma.

BACKGROUND: Extramedullary plasmacytoma (EMP) is a rare malignant disease that lacks a unique clinical staging system to predict the survival of EMP patients and to design individualized treatment. Instead, clinicians have chosen to use the multiple myeloma (MM) staging system. METHODS: Forty-eight EMP patients treated between 1996 and 2014 were included in this study. The new clinical stages were established according to independent survival factors using Cox regression model. RESULTS: Lymph node metastasis and a larger primary tumor (≥5 cm) were the only two independent poor prognostic factors for overall survival (OS) and disease-free survival (P < 0.05). Stage I was defined as the disease without those two poor prognostic factors. Stage II was defined as the presence of either factor, and Stage III was defined as the presence of both factors. OS was significantly different in each stage of the new staging system (P < 0.001), with a median follow-up time for Stage I, Stage II and Stage III of 68, 23 and 14 months. The new staging system had enhanced prognostic value compared to the MM staging system (the area under ROC 0.763 versus 0.520, P = 0.044). Although no difference was observed between treatments in Stage I, the combination treatment was associated with a significantly beneficial OS in the late stages (5-year OS: 15.3 % versus 79.5 %; P = 0.032). CONCLUSIONS: The new staging system exhibited a promising prognostic value for survival and could aid clinicians in choosing the most suitable treatment for EMP patients.

The elevated pretreatment platelet-to-lymphocyte ratio predicts poor outcome in nasopharyngeal carcinoma patients.

The aim of this study was to evaluate whether the platelet-to-lymphocyte ratio (PLR) could be used to predict the prognosis of patients with nasopharyngeal carcinoma (NPC). Patients (n = 1261) who were diagnosed with nonmetastatic NPC between January 2008 and December 2010 were recruited. The peripheral platelet and lymphocyte counts were retrieved, and the PLR was calculated. Univariate and multivariate Cox proportional hazards analyses were used to assess their association with PLR: overall survival (OS), cancer-specific survival (CSS), and distant metastasis-free survival (DMFS). The elevated PLR, using the third quartile values (153.64) as the optimal cutoff values, was found to be associated with the significant decline in CSS (hazard ratio [HR] 1.83, 95 % confidence interval [CI] 1.27-2.63, P < 0.001), OS (HR 1.81, 95 % CI 1.28-2.56, P < 0.001), and DMFS (HR 1.60, 95 % CI 1.15-2.23, P = 0.005) that remained significant during the multivariable analyses (CCS HR 1.84, 95 % CI 1.26-2.67, P < 0.001; OS HR 1.83, 95 % CI 1.28-2.61, P < 0.001; DMFS HR 1.56, 95 % CI 1.11-2.19, P = 0.011). Subgroup analyses indicated that the PLR could be used to stratify prognosis effectively for patients with early- or advanced-stage NPC, and Epstein-Barr virus DNA levels of ≥1500 copies/mL. In conclusions, elevated PLR values were associated with poor CSS, OS, and DMFS for patients with NPC; this easily accessed variable based on a large amount of cases multivariate analysis is valuable for predicting prognosis in patients with NPC.

Targeting GPR65 alleviates hepatic inflammation and fibrosis by suppressing the JNK and NF-κB pathways.

BACKGROUND: G-protein coupled receptors (GPCRs) are recognized as attractive targets for drug therapy. However, it remains poorly understood how GPCRs, except for a few chemokine receptors, regulate the progression of liver fibrosis. Here, we aimed to reveal the role of GPR65, a proton-sensing receptor, in liver fibrosis and to elucidate the underlying mechanism. METHODS: The expression level of GPR65 was evaluated in both human and mouse fibrotic livers. Furthermore, Gpr65-deficient mice were treated with either bile duct ligation (BDL) for 21 d or carbon tetrachloride (CCl4) for 8 weeks to investigate the role of GPR65 in liver fibrosis. A combination of experimental approaches, including Western blotting, quantitative real-time reverse transcription­polymerase chain reaction (qRT-PCR), and enzyme-linked immunosorbent assay (ELISA), confocal microscopy and rescue studies, were used to explore the underlying mechanisms of GPR65's action in liver fibrosis. Additionally, the therapeutic potential of GPR65 inhibitor in the development of liver fibrosis was investigated. RESULTS: We found that hepatic macrophages (HMs)-enriched GPR65 was upregulated in both human and mouse fibrotic livers. Moreover, knockout of Gpr65 significantly alleviated BDL- and CCl4-induced liver inflammation, injury and fibrosis in vivo, and mouse bone marrow transplantation (BMT) experiments further demonstrated that the protective effect of Gpr65 knockout is primarily mediated by bone marrow-derived macrophages (BMMs). Additionally, in vitro data demonstrated that Gpr65 silencing and GPR65 antagonist inhibited, while GPR65 overexpression and application of GPR65 endogenous and exogenous agonists enhanced the expression and release of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and transforming growth factor-ß (TGF-ß), all of which subsequently promoted the activation of hepatic stellate cells (HSCs) and the damage of hepatocytes (HCs). Mechanistically, GPR65 overexpression, the acidic pH and GPR65 exogenous agonist induced up-regulation of TNF-α and IL-6 via the Gαq-Ca2+-JNK/NF-κB pathways, while promoted the expression of TGF-ß through the Gαq-Ca2+-MLK3-MKK7-JNK pathway. Notably, pharmacological GPR65 inhibition retarded the development of inflammation, HCs injury and fibrosis in vivo. CONCLUSIONS: GPR65 is a major regulator that modulates the progression of liver fibrosis. Thus, targeting GPR65 could be an effective therapeutic strategy for the prevention of liver fibrosis.

Efficacy of sequential chemoradiotherapy combined with toripalimab in de novo metastatic nasopharyngeal carcinoma: A phase II trial.

Locoregional radiotherapy added to chemotherapy has significantly improved survival in de novo metastatic nasopharyngeal carcinoma (mNPC). However, only 54% of de novo mNPC patients who received sequential chemoradiotherapy have complete or partial response 3 months after radiotherapy. This Simon's optimal two-stage design phase II study (NCT04398056) investigates whether PD-1 inhibitor could improve tumor control in combination with chemoradiation. The primary endpoint is objective response rate (ORR) at 3 months after radiotherapy. Twenty-two patients with primary mNPC are enrolled. The ORR at 3 months after radiotherapy is 81.8% (22.7% complete response, n = 5; 59.1% partial response, n = 13), and the disease control rate is 81.8%. The 3-year progression-free survival (PFS) rate is 44.9% (95% confidence interval 26.4%-76.3%). Fifteen patients (68.2%) experienced grade 3-4 adverse events. Patients with high baseline plasma Epstein-Barr virus DNA copy number (>104 cps/mL) show worse PFS. Addition of toripalimab to sequential chemoradiotherapy suggests promising tumor response in patients with primary mNPC.

Gemcitabine combined with apatinib and toripalimab in recurrent or metastatic nasopharyngeal carcinoma.

BACKGROUND: The role of a triple combination of gemcitabine (chemotherapy) plus apatinib (anti-vascular endothelial growth factor [VEGFR]) and toripalimab (anti-PD-1) (GAT) in recurrent/metastatic nasopharyngeal carcinoma (RM-NPC) is unclear. METHODS: Between August 2019 and April 2020, 41 patients with RM-NPC were enrolled and received GAT for up to 6 cycles followed by apatinib and toripalimab. The primary endpoint was the safety. The secondary endpoints included the objective response rate (ORR) and progression-free survival (PFS). Integrated genomic and transcriptional analyses were conducted to identify the patients who benefited in response to this novel combination therapy. FINDINGS: As of April 1, 2022, treatment-related grade 3 or 4 adverse events (AEs) occurred in 23 of 41 patients (56.1%, 95% confidence interval [CI] 41%-70.1%). G3-4 nasopharyngeal necrosis was observed in 9 (9/41, 21.9%) patients. High-risk factors for necrosis included repeated radiotherapy and an interval of less than 12 months from the last radiotherapy. The ORR was 90.2% (95% CI: 76.9%-97.2%). The median PFS was 25.8 months (95% CI: not reached (NR)-NR), and the 24-month PFS rate was 50.7% (95% CI: 34.0%-67.4%). MAS-related GPR family member F (MRGPRF) high expression in tumors correlated with poor PFS from the GAT therapy, characterized by high epithelial mesenchymal transition signatures. Serial circulating tumor DNA (ctDNA) sequencing could predict PFS outcomes to combination therapy. CONCLUSIONS: GAT therapy exhibits a promising antitumor activity and manageable toxicities in patients with RM-NPC. Patients with repeated radiotherapy and an interval of less than 12 months from the last radiotherapy should be carefully selected for antiangiogenic therapies. MRGPRF expression and serial ctDNA monitoring could identify patients that derive benefits from the combination therapy. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04073784. FUNDING: This research was funded by the National Natural Science Foundation of China (nos. 81772895 and 82002857), the Key-Area Research and Development of Guangdong Province (2020B1111190001), the Special Support Program for High-level Talents in Sun Yat-sen University Cancer Center, the Guangzhou Science and Technology Plan Project (202103010001), and the National "Ten Thousand Talents Program" Science and Technology Innovation Leading Talents (84000-41180005).

Efficacy of local therapy to metastatic foci in nasopharyngeal carcinoma: large-cohort strictly-matched retrospective study.

Background: Studies of local therapy (LT) to metastatic foci from nasopharyngeal carcinoma (NPC) are inconsistent and controversial. Here, we aimed to explore the survival benefit of LT directed at metastatic foci from NPC. Methods: A retrospective analysis was conducted in NPC patients with liver, lung, and/or bone metastases. The postmetastatic overall survival (OS) rate was analyzed using the Kaplan-Meier method and compared by the log-rank test. Multivariate analysis was performed using the Cox hazard model. Subgroup analyses evaluating the effect of LT were performed for prespecified covariates. Propensity score matching was applied to homogenize the compared arms. Results: Overall, 2041 of 2962 patients were eligible for analysis. At a median follow-up of 43.4 months, the 5-year OS improved by an absolute difference of 14.6%, from 46.2% in the LT group versus 31.6% in the non-LT group, which led to a hazard ratio of 0.634 for death (p < 0.001). Matched-pair analyses confirmed that LT was associated with improved OS (p = 0.003), and the survival benefits of LT remained consistent in the subcohorts of liver and lung metastasis (p = 0.009 and p = 0.007, respectively) but not of bone metastasis (BoM; p = 0.614). Radiotherapy was predominantly used for BoM and biological effective dose (BED) >60 Gy was found to yield more survival benefit than that of BED ⩽ 60 Gy. Conclusions: The addition of LT directed at metastasis has demonstrated an improvement to OS compared with non-LT group in the present matched-pair study, especially for patients with liver and/or lung metastases.

Corrigendum: LCN2 Is a Potential Biomarker for Radioresistance and Recurrence in Nasopharyngeal Carcinoma.

[This corrects the article DOI: 10.3389/fonc.2020.605777.].

Modifications of the Langendorff Method for Simultaneous Isolation of Atrial and Ventricular Myocytes from Adult Mice.

A single cardiomyocyte is a vital tool in the cellular and subcellular level studies of cardiac biology and diseases as a fundamental unit of contraction and electrical activity. Hence, isolating viable, high-quality cardiomyocytes from the heart is the initial and most crucial experimental step. Comparing the various protocols for isolating the cardiomyocytes of adult mice, the Langendorff retrograde perfusion is the most successful and reproducible method reported in the literature, especially for isolating ventricular myocytes. However, isolating quality atrial myocytes from the perfused heart remains challenging, and few successful isolation reports are available. Solving this complicated problem is extremely important because apart from ventricular disease, atrial disease accounts for a large part of heart diseases. Therefore, further investigations on the cellular level to reveal the mechanisms are warranted. In this paper, a protocol based on the Langendorff retrograde perfusion method is introduced and some modifications in the depth of aorta cannulation and the steps that may affect the digestion process to isolate atrial and ventricular myocytes were simultaneously made. Moreover, the isolated cardiomyocytes are confirmed to be amenable to patch clamp investigation.

Erratum: Oncogenic roles of carbonic anhydrase IX in human nasopharyngeal carcinoma.

[This corrects the article on p. 2942 in vol. 7, PMID: 25031713.].

The impact of induction chemotherapy on long-term quality of life in patients with locoregionally advanced nasopharyngeal carcinoma: Outcomes from a randomised phase 3 trial.

BACKGROUND: Our previous trial confirmed that induction chemotherapy (IC) improved long-term survival outcomes in patients with locoregionally advanced nasopharyngeal carcinoma (NPC). In this study, we investigated the impact of IC on long-term quality of life (QoL) in this cohort. METHODS: Our trial was a randomised, open-label phase 3 trial comparing IC followed by concurrent chemoradiotherapy (CCRT) versus CCRT alone in patients with stage III-IVB (except T3N0-1) NPC. All participants completed two self-administered questionnaires, the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30) and the EORTC QLQ Head and Neck Cancer-Specific Module (H&N35). As per protocol, the questionnaires had to be completed before knowledge of treatment allocation by the patient (baseline). Patients were then approached to enroll at the time of the present study period. RESULTS: Ultimately, QoL data from 228 patients were included in the analysis. Most scales were both statistically and clinically decreased in both groups between baseline and the latest follow-up. The IC followed by CCRT group had significantly better outcome in role functioning, cognitive functioning, social functioning, fatigue, pain, and constipation in QLQ-C30 scales at the last follow-up. Similarly, in H&N35 scales, a significantly better result was observed in pain, sexuality, sticky saliva, pain killers use, nutritional supplements, and weight loss, but a poorer result in senses problems, for those treated by IC followed by CCRT. CONCLUSION: IC followed by CCRT seemed to have better long-term QoL outcomes compared with CCRT alone in patients with locoregionally advanced NPC.

Transcervical endoscopic retropharyngeal lymph node (RPLN) dissection in nasopharyngeal carcinoma with RPLN recurrence.

BACKGROUND: Surgical access for retropharyngeal lymph node (RPLN) dissection is difficult. We aimed to examine the efficacy of transcervical endoscopic RPLN dissection (TSE-RPLND) for recurrent RPLN in nasopharyngeal carcinoma (NPC). METHODS: From April 2013 to February 2019, a total of 31 patients with NPC diagnosed with RPLN recurrence underwent TSE-RPLND. The clinical characteristics, complications, and survival outcomes were retrospectively analyzed. RESULTS: The mean duration of surgery, quantity of bleeding and postoperative hospitalization stay were 347.9 minutes, 107.7 mL, and 8.7 days, respectively. After a median follow-up of 31.0 months, the 2-year locoregional relapse-free survival, distant metastasis-free survival, progression-free survival, and overall survival rates were 63.9%, 95.2%, 59.9%, and 83.3%, respectively. The long-term incidences of swallowing problems, permanent nutrient tube, tongue atrophy, and shoulder problems were 6 (19.4%), 3 (9.7%), 3 (9.7%), and 3 (9.7%), respectively. CONCLUSIONS: TSE-RPLND is an effective method to treat RPLN recurrence in NPC, but nerve injury-related complications should not be ignored.

Transoral Robotic Retropharyngeal Lymph Node Dissection in Nasopharyngeal Carcinoma With Retropharyngeal Lymph Node Recurrence.

OBJECTIVES: Nasopharyngeal carcinoma (NPC) patients with retropharyngeal lymph node (RPLN) recurrence typically undergo reirradiation and experience severe radiotoxicity. Salvage open surgery is challenging because gaining access to the retropharyngeal space is complex and risky. Thus, only several centers can perform this procedure, and complications are common. We applied transoral robotic surgery RPLN dissection (TORS-RPLND) to NPC patients with RPLN recurrence to address the problem with open surgery. MATERIALS AND METHODS: From March 2017 to October 2020, 10 NPC patients with RPLN recurrence underwent TORS-RPLND using the da Vinci Si/Xi Surgical System. We applied the balloon occlusion test to protect the internal carotid artery, induction chemotherapy to shrink large tumors preoperatively, and ultrasound positioning to effectively locate unrecognizable RPLNs during surgery. Clinical characteristics, complications, and survival outcome data were retrospectively collected. RESULTS: Of 10 patients, 8 underwent en bloc resection via TORS-RPLND, and the remaining 2 patients were converted to open surgery because we failed to identify the RPLN during TORS. After introducing intraoperative ultrasound positioning, no such failure occurred. The mean operative time and intraoperative blood loss were 297 ± 120 min and 40 ± 43 ml, respectively. All surgical margins were negative. TORS-related complications were mild, and the most severe one was grade 3 dysphagia in one patient who underwent conversion to open surgery (10%). With a median follow-up of 19 months, only 1 (10%) patient developed cervical recurrence. CONCLUSIONS: TORS-RPLND is feasible, safe, and effective in the treatment of NPC patients with RPLN recurrence, especially with the help of intraoperative ultrasound positioning. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E1895-E1902, 2021.