Survival Outcomes of Patients with Esophageal Cancer and Post-chemoradiotherapy Surgical T4b Disease: Is Palliative Resection Justified?

BACKGROUND: In patients with locally advanced esophageal cancer who had undergone chemoradiotherapy (CRT), the limitations of radiological evaluation may necessitate surgical exploration to ascertain disease resectability. Upon intraoperative confirmation of T4b disease (sT4b), the optimal management strategy remains unclear. While some surgeons may opt against resection, others advocate for palliative esophagectomy (PE). Regrettably, the current literature does not provide a consensus on the most effective approach for managing these intricate cases. METHODS: The study cohort consisted of 68 patients with esophageal squamous cell carcinoma (ESCC) who presented with sT4b disease following CRT. The perioperative outcomes and overall survival (OS) were compared between patients who underwent PE (n = 56) and those who received an open-close (OC) procedure (n = 12). RESULTS: Patients who underwent an OC procedure experienced a shorter hospital stay (16.5 vs. 28.8 days; p = 0.052) and showed a non-significant reduction in the rate of major complications (33.9% vs. 25%; p = 0.549) and in-hospital mortality (0% vs. 5.4%; p = 0.412) than those who received PE; however, PE was associated with a superior 2-year OS rate than OC (9.6% vs. 0%; p = 0.009). In multivariable analysis, a pretreatment clinical stage of II/III (hazard ratio [HR] 0.51, 95% confidence interval [CI] 0.31-0.87; p = 0.013) and PE with retrosternal reconstruction (HR 0.38, 95% CI 0.15-0.49; p = 0.010) were independently associated with a more favorable OS. CONCLUSION: PE with retrosternal reconstruction may be a feasible approach for patients with ESCC exhibiting sT4b disease after CRT.

Temporal Trends in Survival Outcomes for Patients with Esophageal Cancer Following Neoadjuvant Chemoradiotherapy: A 14-Year Analysis.

BACKGROUND: The prognosis for patients with esophageal cancer who received neoadjuvant chemoradiotherapy (nCRT) followed by surgery has shown improvement in recent years. We sought to identify the critical factors contributing to enhanced survival outcomes. PATIENTS AND METHODS: We retrospectively examined 427 patients with esophageal cancer treated with nCRT and esophagectomy across two periods: P1 (from 1 January 2004 to 31 December 2011) and P2 (from 1 January 2012 to 31 December 2017). The introduction of the CROSS regimen and total meso-esophagectomy in P2 prompted an evaluation of their effects on perioperative outcomes and overall survival (OS). RESULTS: During P2, the occurrence of recurrent laryngeal nerve palsy increased significantly from 3.9 to 16.8% (p < 0.001), while pneumonia and in-hospital mortality rates remained unchanged. The median OS improved from 19.2 to 29.2 months (p < 0.001) between P1 and P2. Multivariable analysis identified higher nodal yields and the achievement of major response as favorable prognostic factors. Conversely, an involved circumferential resection margin (CRM), an advanced ypN stage, and pneumonia were independently associated with poor outcomes. Patients treated during P2 had a lower prevalence of involved CRM (10% vs. 25.1%, p < 0.001), a higher rate of major response (52.7% vs. 34.8%, p < 0.01), and a greater nodal yield (27.8 vs. 10.9, p < 0.001). CONCLUSIONS: The clinical outcomes following nCRT and surgery have improved significantly over time. This progress can be attributed to multiple factors, with the primary drivers being the refinement of nCRT protocols and the application of radical surgery.

Deep Learning-Based Nuclear Morphometry Reveals an Independent Prognostic Factor in Mantle Cell Lymphoma.

Blastoid/pleomorphic morphology is associated with short survival in mantle cell lymphoma (MCL), but its prognostic value is overridden by Ki-67 in multivariate analysis. Herein, a nuclear segmentation model was developed using deep learning, and nuclei of tumor cells in 103 MCL cases were automatically delineated. Eight nuclear morphometric attributes were extracted from each nucleus. The mean, variance, skewness, and kurtosis of each attribute were calculated for each case, resulting in 32 morphometric parameters. Compared with those in classic MCL, 17 morphometric parameters were significantly different in blastoid/pleomorphic MCL. Using univariate analysis, 16 morphometric parameters (including 14 significantly different between classic and blastoid/pleomorphic MCL) emerged as significant prognostic factors. Using multivariate analysis, Biologic MCL International Prognostic Index (bMIPI) risk group (P = 0.025), low skewness of nuclear irregularity (P = 0.020), and high mean of nuclear irregularity (P = 0.047) emerged as independent adverse prognostic factors. Additionally, a morphometric score calculated from the skewness and mean of nuclear irregularity (P = 0.0038) was an independent prognostic factor in addition to bMIPI risk group (P = 0.025), and a summed morphometric bMIPI score was useful for risk stratification of patients with MCL (P = 0.000001). These results demonstrate, for the first time, that a nuclear morphometric score is an independent prognostic factor in MCL. It is more robust than blastoid/pleomorphic morphology and can be objectively measured.

Identification of nodal micrometastasis in colorectal cancer using deep learning on annotation-free whole-slide images.

Detection of nodal micrometastasis (tumor size: 0.2-2.0 mm) is challenging for pathologists due to the small size of metastatic foci. Since lymph nodes with micrometastasis are counted as positive nodes, detecting micrometastasis is crucial for accurate pathologic staging of colorectal cancer. Previously, deep learning algorithms developed with manually annotated images performed well in identifying micrometastasis of breast cancer in sentinel lymph nodes. However, the process of manual annotation is labor intensive and time consuming. Multiple instance learning was later used to identify metastatic breast cancer without manual annotation, but its performance appears worse in detecting micrometastasis. Here, we developed a deep learning model using whole-slide images of regional lymph nodes of colorectal cancer with only a slide-level label (either a positive or negative slide). The training, validation, and testing sets included 1963, 219, and 1000 slides, respectively. A supercomputer TAIWANIA 2 was used to train a deep learning model to identify metastasis. At slide level, our algorithm performed well in identifying both macrometastasis (tumor size > 2.0 mm) and micrometastasis with an area under the receiver operating characteristics curve (AUC) of 0.9993 and 0.9956, respectively. Since most of our slides had more than one lymph node, we then tested the performance of our algorithm on 538 single-lymph node images randomly cropped from the testing set. At single-lymph node level, our algorithm maintained good performance in identifying macrometastasis and micrometastasis with an AUC of 0.9944 and 0.9476, respectively. Visualization using class activation mapping confirmed that our model identified nodal metastasis based on areas of tumor cells. Our results demonstrate for the first time that micrometastasis could be detected by deep learning on whole-slide images without manual annotation.

Diagnostic accuracy of 3.0T diffusion-weighted MRI for patients with uterine carcinosarcoma: Assessment of tumor extent and lymphatic metastasis.

BACKGROUND: Assessment of tumor extent and lymphatic metastasis of uterine carcinosarcomas is important for treatment planning. PURPOSE/HYPOTHESIS: To evaluate the diagnostic accuracy of 3.0T diffusion-weighted (DW) MRI for patients with uterine carcinosarcoma, in assessment of tumor extent and lymphatic metastasis. STUDY TYPE: Retrospective diagnostic accuracy study. POPULATION: A consecutive cohort of 68 patients with pathologically proved carcinosarcoma between January 2006 and July 2014. FIELD STRENGTH/SEQUENCE: 3T DW MRI. ASSESSMENT: Maximal tumor and uterus size, presence of deep myometrial invasion, cervical invasion, adnexal invasion, lymphadenopathy, and the apparent diffusion coefficient (ADC) values of each tumor were used. Histopathology was the gold standard. STATISTICAL TESTS: Diagnostic accuracy. Logistic regression. RESULTS: In all, 38 patients entered the final analysis, with median age of 58 years (range, 35-79 years). The sensitivity and specificity in detecting deep myometrial invasion, cervical stromal invasion, adnexal invasion, as well as pelvic and para-aortic lymph node metastases were 65% and 72%, 91% and 85%, 50% and 100%, 33% and 89%, and 33% and 100%, respectively. The largest tumor diameters predicted deep myometrium invasion (anteroposterior direction, P = 0.004) and cervical stroma invasion (craniocaudal direction, P = 0.008). Tumor ADCmin significantly predicted the lymphovascular permeation (P = 0.025; odds ratio = 0.96). DATA CONCLUSION: Preoperative DW MRI is useful to assess deep myometrial or cervical stromal invasion in uterine carcinosarcoma, yet the diagnostic performance for detecting adnexal invasion and lymphatic metastasis requires further improvement. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018.

Pleomorphic mantle cell lymphoma morphologically mimicking diffuse large B cell lymphoma: common cyclin D1 negativity and a simple immunohistochemical algorithm to avoid the diagnostic pitfall.

AIMS: To characterize the clinicopathological and genetic features of pleomorphic mantle cell lymphoma (PMCL), which morphologically mimics diffuse large B cell lymphoma (DLBCL). METHODS AND RESULTS: We screened systematically 500 B cell lymphomas morphologically compatible with DLBCL using an immunohistochemical algorithm of three markers (CD5, cyclin D1 and SOX11). Ten cases of PMCL were identified for further study and, surprisingly, four (40%) of them were cyclin D1-negative. These 10 patients were mainly elderly males with advanced disease, and their median survival was only 11 months. All cyclin D1-positive PMCLs tested showed an IGH-CCND1 translocation, whereas one of the four cyclin D1-negative PMCLs had a translocation involving CCND2 and a high CCND2 mRNA level (P < 0.000001). The genomewide copy number profiles of both cyclin D1-positive and cyclin D1-negative PMCLs were similar to those of classical mantle cell lymphoma (MCL) reported previously, confirming the diagnosis. Secondary genetic alterations involved in oncogenic pathways of MCL were observed more frequently in these PMCLs, possibly decreasing the dependence on the driving CCND1 translocation and accounting for the common cyclin D1 negativity. Copy number gains of PIK3CA and CCDC50 were detected in all cyclin D1-negative PMCLs but in only 40% of the cyclin D1-positive PMCLs. These additional oncogenic signals may compensate for the common absence of CCND2 translocation in cyclin D1-negative PMCL. CONCLUSION: We demonstrate for the first time that cyclin D1 negativity is surprisingly common in PMCL morphologically mimicking DLBCL, and the use of a simple immunohistochemical algorithm can prevent misclassification and inappropriate treatment.

Electrocautery device does not provide adequate pulmonary vessel sealing in transumbilical anatomic pulmonary lobectomy.

INTRODUCTION: Safe pulmonary vessel sealing device plays a crucial role in anatomic lung resection. In 2014, we reported high rates of massive bleeding complications during transumbilical lobectomy in a canine model due to difficulty in managing the pulmonary vessel with an endostapler. In this animal survival series, we aimed to evaluate the outcome of pulmonary vessel sealing with an electrocautery device to simplify the transumbilical thoracic surgery. METHODS: Under general anesthesia, a 3-cm longitudinal incision was made over the umbilicus. Under video guidance, a bronchoscope was inserted through the incision for exploration. The diaphragmatic wound was created with an electrocautery knife and used as the entrance into the thoracic cavity. Using the transumbilical technique, anatomic lobectomy was performed with electrosurgical devices and endoscopic vascular staplers in 15 canines. RESULTS: Transumbilical endoscopic anatomic lobectomy was successfully completed in 12 of the 15 animals. Intraoperative bleeding developed in three animals during pulmonary hilum dissection, where one animal was killed due to hemodynamic instability and the other two animals required thoracotomy to complete the operation. There were five delayed bleeding and surgical mortality cases caused by inadequate vessel sealing by electrosurgical devices. Postmortem examination confirmed correct transumbilical lobectomy in the twelve animals that survived the operations. CONCLUSION: Transumbilical anatomic lobectomy is technically feasible in a canine model; however, the electrosurgical devices were not effective in sealing the pulmonary vessel in the current canine model.

Feasibility of Subxiphoid Anatomic Pulmonary Lobectomy in a Canine Model.

Purpose Transthoracic thoracoscopic approach is the gold standard in surgical treatment for thoracic disease. However, it is associated with significant chronic postoperative wound discomfort. Currently, limited data are available regarding the subxiphoid approach to the thoracic cavity. The present study is aimed to evaluate the performance of a subxiphoid anatomic pulmonary lobectomy (SAPL) in a canine model. Methods The SAPL procedure was performed in 10 beagle dogs using a 3-cm incision over the xiphoid process. After thoracic exploration, SAPL was performed under flexible bronchoscopy guidance. The pulmonary vessel was divided with Ligasure and secured with a suture ligature. The bronchus was divided with endostapler. Surgical outcomes were evaluated by the success of SAPL and operative complications. Results SAPL was successfully completed in 9 animals. One animal required conventional thoracotomy to resuture the pulmonary artery stump. Another animal encountered small middle lobe laceration after SAPL and died at 8 days postoperation due to respiratory distress. Conclusion Subxiphoid anatomic pulmonary lobectomy is technically feasible. Refinement of endoscopic instruments combined with more research evidences may facilitate the development of subxiphoid platform in thoracic surgery.

A Pathological Study of Residual Cancer in the Esophageal Wall Following Neoadjuvant Chemoradiotherapy: Focus on Esophageal Squamous Cell Carcinoma Patients with False Negative Preoperative Endoscopic Biopsies.

BACKGROUND: Endoscopic biopsy examinations after neoadjuvant chemoradiotherapy (nCRT) are of limited value in patients with esophageal cancer due to the high rates of false negative (FN) findings. We sought to investigate the anatomical locations of residual tumors in esophageal squamous cell carcinoma (ESCC) patients with FN endoscopic biopsies with the ultimate goal of improving their clinical management. METHODS: ESCC patients with residual cancers after nCRT which were not identified by preoperative endoscopic biopsy were deemed eligible. All of the surgical specimens were re-reviewed with a special focus on (1) distribution of residual cancer in each esophageal layer; (2) tumor regression grade (TRG); and (3) shortest distance between the lumen and the residual tumor. RESULTS: Among the 49 ESCC patients with FN biopsy results, a strong 'layer-dependent' tumor regression was observed. There was a preferential clearing of esophageal cancer cells located in the adventitia, followed by muscle and the submucosal (SM) and mucosal (M) layers (p < 0.001). Residual malignancies located in the muscle layer or the adventitia without simultaneous involvement of the M/SM layers were rare (n = 3; 6.1 %). TRG following nCRT did not affect the rate of M/SM involvement (p = 0.55) but was inversely associated with the distance between the lumen and residual cancer (mean distance in patients with TRG of 2, 3, and 4 was 1.1, 0.82, and 0.37 mm, respectively; p = 0.041). CONCLUSION: Most ESCC patients who show FN endoscopic biopsies following nCRT still have detectable lesions in the M/SM layers. Aggressive biopsy protocols may potentially improve detection rates.

Prognostic significance of lymphovascular invasion in patients with esophageal squamous cell carcinoma treated with neoadjuvant chemoradiotherapy.

OBJECTIVE: To investigate the prognostic significance of lymphovascular invasion (LVI) in patients with esophageal squamous cell carcinoma (ESCC) treated with neoadjuvant chemoradiotherapy (nCRT). METHODS: We retrospectively reviewed the charts of 416 consecutive patients with ESCC who underwent surgical resection following nCRT at the Chang Gung Memorial Hospital between 1998 and 2008. After exclusion of patients with non-R0 resection or showing no residual tumor (ypT0Nx), the histological tumor sections of 231 patients were reviewed for LVI. Univariate and multivariate analyses were used to identify the independent predictors of overall survival (OS). RESULTS: LVI was observed in 85 patients (36.8 %). The presence of LVI was related to close circumferential resection margins (CRMs), a greater depth of invasion, poor tumor differentiation, and an increased occurrence of lymph node metastases (LNM). The 5 year OS was significantly lower (10 %) in patients with LVI than in those without (31 %; p < 0.001). By multivariate Cox regression analyses, LVI (hazard ratio [HR] 1.5; p = 0.002) and LNM (HR 1.6; p = 0.007) were identified as independent adverse prognostic factors for OS. The 5 year OS rates according to the number of risk factors present were 35, 21, 20, and 5 for LVI(-)LNM(-), LVI(+)LNM(-), LVI(-)LNM(+), and LVI(+)LNM(+) patients, respectively (p < 0.001). CONCLUSIONS: The presence of LVI is independently associated with shorter OS in ESCC patients receiving nCRT. Links between LVI and LNM may provide new clues for the prognostic stratification of esophageal cancer.

Transumbilical Thoracoscopy Versus Conventional Thoracoscopy for Lung Wedge Resection: Safety and Efficacy in a Live Canine Model.

PURPOSE: Transumbilical single-port surgery has been associated with less postoperative pain and offers better cosmetic outcomes than conventional 3-port laparoscopic surgery. This study compares the safety and efficacy of transumbilical thoracoscopy and conventional thoracoscopy for lung wedge resection. METHODS: The animals (n = 16) were randomly assigned to the transumbilical thoracoscopic approach group (n = 8) or conventional thoracoscopic approach group (n = 8). Transumbilical lung resection was performed via an umbilical incision and a diaphragmatic incision. In the conventional thoracoscopic group, lung resection was completed through a thoracic incision. For both procedures, we compared the surgical outcomes, for example, operating time and operative complications; physiologic parameters, for example, respiratory rate and body temperature; inflammatory parameters, for example, white blood cell count; and pulmonary parameters, for example, arterial blood gas levels. The animals were euthanized 2 weeks after the surgery for gross and histologic evaluations. RESULTS: The lung wedge resection was successfully performed in all animals. There was no significant difference in the mean operating times or complications between the transumbilical and the conventional thoracoscopic approach groups. With regard to the physiologic impact of the surgeries, the transumbilical approach was associated with significant elevations in body temperature on postoperative day 1, when compared with the standard thoracoscopic approach. CONCLUSIONS: This study suggests that both approaches for performing lung wedge resection were comparable in efficacy and postoperative complications.

Feasibility of transumbilical anatomic pulmonary lobectomy in a canine model.

PURPOSE: Transthoracic thoracoscopic lobectomy is the preferred method of surgical treatment for early lung cancer. Current methods require a transthoracic approach and are associated with chronic postoperative pain in up to 25% of patients. Single-port transumbilical uniport surgery may offer advantages over multiport surgery with less postoperative pain and better cosmetic results. The aim of this study was to evaluate the feasibility of a transumbilical anatomic lobectomy of the lung (TUAL) in a canine model. METHODS: TUAL was performed in 12 beagle dogs using a 3-cm umbilical incision combined with a 2.5-cm diaphragmatic incision. Variables evaluated for surgical outcomes were operating time, operative complications, body rectal temperature, respiratory rate, white blood cell count, and arterial blood gases. RESULTS: TUAL was successfully completed in ten animals. There were six bleeding complications related to surgery. In four animals, an avulsion of pulmonary vessel causes intraoperative bleeding, requiring simultaneous pulmonary artery and bronchus resections. In one animal, slipping of endoclip after vessel clipping caused perioperative bleeding. The other animal encountered bleeding complication during dissection of inferior pulmonary vein. Both animals required conventional thoracotomy to complete the surgery. CONCLUSIONS: TUAL in the canine model is feasible but associated with significant morbidity. With further development and refinement of instruments, comparative studies between the novel transumbilical lobectomy and the current video-assisted transthoracic lobectomy will clarify the role of transumbilical lobectomy in thoracic surgery.

Feasibility of transumbilical surgical lung biopsy and pericardial window creation.

BACKGROUND: To date there are no practical platforms for performing natural orifice transluminal endoscopic surgery in the thoracic cavity. This study evaluates the feasibility of transumbilical thoracosopy for lung biopsy and pericardial window creation. METHODS: Eleven dogs (6 in the nonsurvival group and 5 in the survival group) were used for this study. A homemade metallic tube was advanced into the abdominal cavity via a 12-mm umbilical incision. The metallic tube was advanced into the thoracic cavity through a subxyphoid diaphragmatic incision under video guidance. Access to the thoracic cavity was achieved by a flexible bronchoscope via the metallic tube. Surgical lung biopsy and pericardial window creation were performed using an electrocautery loop and needle knife. The animals were euthanized 20 minutes after the surgery was complete (nonsurvival group) or 14 days postsurgery (survival group) for necropsy evaluation. RESULTS: Eight pericardial window creations and 21 of 22 preplanned lung biopsies were completed in a median time of 72.18 minutes (range 50-105 minutes). One dog in the nonsurvival group died after tension pneumothorax due to postprocedure massive air leaks. In the survival group, the postoperative period was uneventful in all 5 dogs. Autopsies revealed no signs of vital organ injury and complete healing of the diaphragmatic incision occurred in all animals. CONCLUSIONS: The study demonstrated that transumbilical thoracoscopic surgical lung biopsy and pericardial window creation is feasible. The safety and efficacy of the transumbilical approach need to be verified by a more detailed survival study.

Identification of CD5/SOX11 double-negative pleomorphic mantle cell lymphoma.

Cyclin D1 protein-positive diffuse large B cell lymphoma (DLBCL) has an immunophenotype of CD5(-) cyclin D1(+) SOX11(-), and most cases lack a CCND1 rearrangement and have a gene expression profile of DLBCL. Rarely, cyclin D1 protein-positive DLBCL harbors a CCND1 rearrangement, and some genetic copy number features typical of mantle cell lymphoma (MCL) have been detected. Since gene expression studies have not been performed, whether such CCND1-rearranged cases represent cyclin D1 protein-positive DLBCL or CD5/SOX11 double-negative pleomorphic MCL remains unclear. To date, no cases of CD5/SOX11 double-negative MCL have been reported. In this study, we collected eight cases initially diagnosed as cyclin D1 protein-positive DLBCL, including four with a CCND1 rearrangement and four without. Immunohistochemically, all four CCND1-rearranged cases had >50% of tumor cells positive for cyclin D1 protein, whereas only one (25%) non-rearranged case had >50% positive tumor cells. Analysis of genome-wide copy number, mutational, and gene expression profiles revealed that CCND1-rearranged cases were similar to MCL, whereas CCND1-non-rearranged cases resembled DLBCL. Despite the SOX11 negativity by immunohistochemistry, CCND1-rearranged cases had a notable trend (P = 0.064) of higher SOX11 mRNA levels compared to non-rearranged cases. Here, we show for the first time that CCND1 rearrangement could be useful for identifying CD5/SOX11 double-negative pleomorphic MCL in cases diagnosed as cyclin D1 protein-positive DLBCL. Cases with >50% cyclin D1 protein-positive tumor cells immunohistochemically and higher SOX11 mRNA levels are more likely to have a CCND1 rearrangement, and fluorescence in situ hybridization can be used to detect the rearrangement.

Feasibility and safety of endoscopic transumbilical thoracic surgical lung biopsy: a survival study in a canine model.

BACKGROUND: Transumbilical laparoscopy allows the patient to undergo various surgical procedures associated with abdominal disease. The aim of this study was to evaluate the feasibility and safety of transumbilical thoracic exploration and surgical lung biopsy in a canine survival model. METHODS: We performed the procedure in 12 dogs weighting 7.1-9.1 kg. The thoracic cavity was accessed using a metal tube inserted via umbilical and diaphragmatic incisions. After transumbilical thoracoscopy, we resected the predetermined lung lobe with an electrocautery loop. We carried out daily clinical examinations, including determination of respiratory rate and rectal temperature. Laboratory parameters (white blood cell count) and inflammatory parameters, including serum interleukin-6 and C-reactive protein, were measured before surgery and at postoperative days 1, 3, 7, and 14. We performed necropsies 2 wk after surgery. RESULTS: We successfully performed corrected surgical lung biopsies for the predetermined lung lobe in all animals, with a median time of 43.5 min (range, 32-65 min). We observed two perioperative complications: One dog had minor postoperative air leakage and one had hemodynamic collapse because of inadequate ventilation. These animals recovered well without signs of perioperative infection. Necropsies at 2 wk after surgery showed no evidence of mediastinitis or peritonitis. CONCLUSIONS: Exposure of the thoracic cavity and surgical lung biopsy via a transumbilical incision is feasible in this canine model of survival. This procedure may have potential advantages over currently used transthoracic thoracoscopy techniques.

Clinicopathologic parameters and immunohistochemical study of endometrial stromal sarcomas.

We aimed to investigate the clinicopathologic features, immunohistochemical studies, and prognosis in patients with endometrial stromal sarcoma (ESS). Clinical information was reviewed retrospectively for cases of ESS (1985-2009). A histologic review and immunohistochemical staining for the estrogen receptor, progesterone receptor, c-Kit, CD-10, Ki-67, and m-TOR were performed. Sixty-one patients (median age, 44 y; range, 22-71) were eligible for analysis (1988 International Federation of Gynecology and Obstetrics Stage I, 43; Stage II, 2; Stage III, 11; Sage IV, 4; unstaged, 1). The median follow-up period for survivors was 73 mo. Of those, the patients who underwent an adnexectomy and a pelvic lymphadenectomy, 15% and 13%, respectively, revealed metastasis. There were 20 relapses/persistence, including 13 (65%) in the pelvis and abdomen and 7 (35%) in distant sites. Eight patients died from ESS at a median duration of 14.5 mo (range, 2-50 mo) after relapse. Five- and 10-yr cancer-specific survival (CSS) rates were 88% and 85%, respectively; and 5- and 10-yr progression-free survival rates were 69% and 57%, respectively. Stage, residual disease, and high proliferative index of Ki-67 were significant prognostic factors for both progression-free survival and CSS in a univariate analysis, in addition to mitotic index for CSS. Multivariate analysis selected only residual disease as an independent variable for progression-free survival and stage and residual disease for CSS. Our results support using clinical Stage I, no residual disease, low proliferative index of Ki-67, and estrogen receptor/progesterone receptor overexpression as potential biomarkers to select patients with ESS for fertility-preservation surgery (5 such patients were alive and free).

Endoscopic Resection of Residual or Recurrent Lesions after Circumferential Radiofrequency Ablation for Flat Superficial Esophageal Squamous Cell Neoplasias.

The optimal treatment of residual/recurrent superficial esophageal squamous cell neoplasias (SESCNs) after circumferential radiofrequency (RFA) remains unclear. We aimed to report the efficacy and safety of endoscopic resection (ER) of residual/recurrent SESCNs after RFA. Patients who underwent circumferential RFA with residual/recurrent SESCNs and were treated with ER were retrospectively collected. SESCN patients treated with primary endoscopic submucosal dissection (ESD) served as the control group. Eleven patients who underwent RFA had a total of 17 residual (n = 8) or recurrent (n = 9) SESCNs and were treated for ER. EMR failed to remove one residual SESCN. Of the 16 resected specimens, 10 were high-grade intraepithelial neoplasia (HGIN) and six were cancer. Eight cases had neoplasia extending to esophageal ducts/submucosal glands (SMGs). The pathological results may imply three possible routes in which residual/recurrent SESCNs occurred: HGIN without ductal/SMG involvement (37.5%), HGIN with ductal/SMG involvement (25.0%), and SCC with muscularis mucosae or deeper involvement (37.5%). Compared with the control group, the study group had similar procedural speed, en bloc resection rate, R0 resection rate, and complication rate. In conclusion, the safety and efficacy of post-RFA ESD were similar to those of primary ESD. ESD should be the treatment of choice for residual/recurrent SESCNs after initial RFA.

Synchronous Head and Neck Cancer and Superficial Esophageal Squamous Cell Neoplasm: Endoscopic Treatment or No Treatment for the Superficial Esophageal Neoplasm.

There are no studies on treating synchronous head and neck cancer (HNC) and superficial esophageal squamous cell neoplasm (SESCN). We aimed to report the outcomes of endoscopic resection (ER) and no treatment (NT) of SESCN in patients with synchronous HNC and SESCN (SHNSESCN). This retrospective study included 47 patients with SHNSESCN. Treatment for SESCN was ER (n = 30) or NT (n = 17). The ER group had significantly lower Charlson comorbidity index scores and a higher proportion of Eastern Cooperative Oncology Group performance status (ECOG PS) scores ≤1. The location and stage of the two tumors did not differ significantly between the groups. The 1-year, 3-year, and 5-year OS rates of the ER group were significantly better than those in the NT group. Treatment-related morbidity and mortality were not significantly different between the two groups. In the subgroup analysis of synchronous advanced HNC and SESCN, ER for SESCN also had a higher OS rate. Multivariate analysis showed that ECOG PS score and HNC disease progression were the two independent indicators of OS. In conclusion, treatment of SESCN with ER is the recommended approach for patients with SHNSESCN, but further randomized controlled trials are needed to confirm this.