Serum NY-ESO-1 antibody as a predictive biomarker for postoperative recurrence of gastric cancer: a multicenter prospective observational study.

BACKGROUND: No reliable marker has been identified to predict postoperative recurrence of gastric cancer. We designed a clinical trial to investigate the utility of serum NY-ESO-1 antibody responses as a predictive marker for postoperative recurrence in gastric cancer. METHODS: A multicenter prospective study was conducted between 2012 and 2021. Patients with resectable cT3-4 gastric cancer were included. Postoperative NY-ESO-1 and p53 antibody responses were serially evaluated every 3 months for 1 year in patients with positive preoperative antibody responses. The recurrence rate was assessed by the positivity of antibody responses at 3 and 12 months postoperatively. RESULTS: Among 1001 patients, preoperative NY-ESO-1 and p53 antibody responses were positive in 12.6% and 18.1% of patients, respectively. NY-ESO-1 antibody responses became negative postoperatively in non-recurrent patients (negativity rates; 45% and 78% at 3 and 12 months, respectively), but remained positive in recurrent patients (negativity rates; 9% and 8%, respectively). p53 antibody responses remained positive in non-recurrent patients. In multivariate analysis, NY-ESO-1 antibody positivity at 3 months (P < 0.03) and 12 months (P < 0.001) were independent prognostic factors for a shorter recurrence-free interval. CONCLUSIONS: Serum NY-ESO-1 antibodies may be a useful predictive marker for postoperative recurrence in gastric cancer. CLINICAL TRIAL REGISTRATION: UMIN000007925.

[A Case of Concentrated Ascites Reinfusion Therapy(CART)for Abundant Refractory Ascites in Cecal Cancer with Peritoneal Dissemination Followed by the Readministration of Chemotherapy].

A 66-year-old man underwent laparoscopic ileocecal resection for cecal cancer with liver metastasis(cT3N1M1a, cStage Ⅳa). One month later, combination chemotherapy with capecitabine, oxaliplatin, and bevacizumab was administered for liver metastasis. However, during the treatment, peritoneal dissemination and abundant diuretic-resistant ascites was revealed, resulting in poor dietary intake. One year and 11 months after the surgery, the chemotherapy was interrupted and cell-free and concentrated ascites reinfusion therapy(CART)was undergone as palliative care. The initial volume of retrieved ascites was 6,500 mL, and the volume was increased gradually to a maximum of 14,020 mL without hemodynamic instability. Totally CART was administered 10 times during 7 months without any complications: mean volume of retrieved ascites; 9,780 mL/unit, the interval between therapies; 2-3 weeks. Serum albumin level did not decrease since CART administration. His oral intake and daily activities were improved by CART. These clinical outcomes contributed to the readministration of chemotherapy. We present a recent case of safe and periodical CART for abundant refractory ascites in cecal cancer with peritoneal dissemination, resulting in the improvement of QOL and the readministration of chemotherapy.

Significance of Comprehensive Analysis of Preoperative Sarcopenia Based on Muscle Mass, Muscle Strength, and Physical Function for the Prognosis of Patients with Esophageal Cancer.

BACKGROUND: The assessment of muscle mass loss, muscle strength, and physical function has been recommended in diagnosing sarcopenia. However, only muscle mass has been assessed in previous studies. Therefore, this study investigated the effect of comprehensively diagnosed preoperative sarcopenia on the prognosis of patients with esophageal cancer. METHODS: The study analyzed 115 patients with esophageal cancer (age ≥ 65 years) who underwent curative esophagectomy. Preoperative sarcopenia was analyzed using the skeletal mass index (SMI), handgrip strength, and gait speed based on the Asian Working Group for Sarcopenia 2019 criteria. Clinicopathologic factors, incidence of postoperative complications, and overall survival (OS) were compared between the sarcopenia and non-sarcopenia groups. The significance of the three individual parameters also was evaluated. RESULTS: The evaluation identified 47 (40.9%) patients with low SMI, 31 (27.0%) patients with low handgrip strength, and 6 (5.2%) patients with slow gait speed. Sarcopenia was diagnosed in 23 patients (20%) and associated with older age and advanced pT stage. The incidence of postoperative complications did not differ significantly between the two groups. Among the three parameters, only slow gait speed was associated with Clavien-Dindo grade 2 or greater complications. The sarcopenia group showed significantly worse OS than the non-sarcopenia group. Those with low handgrip strength tended to have worse OS, and those with slow gait speed had significantly worse OS than their counterparts. CONCLUSIONS: Preoperative sarcopenia diagnosed using skeletal muscle mass, muscle strength, and physical function may have an impact on the survival of patients with esophageal cancer.

Clinical Impact of Enhanced Recovery After Esophagectomy in Patients With Esophageal Cancer.

BACKGROUND/AIM: The enhanced recovery after surgery (ERAS) program is expected to improve perioperative outcomes in patients with esophageal cancer. However, how ERAS impacts the postoperative body composition and factors related to compliance rate of ERAS have not been fully investigated. PATIENTS AND METHODS: The study included 252 consecutive patients with thoracic esophageal cancer who underwent minimally invasive esophagectomy. We compared the postoperative outcomes including body composition between the old perioperative program and the new one that aimed to shorten postoperative length of stay (LOS). Compliance-related clinical factors were also examined. RESULTS: From 252 patients, 129 underwent the old program and 123 the new program. Postoperative LOS, postoperative complications, and hospital costs were reduced with the new program. Body weight loss was significantly improved with the new program at discharge and 3-months after esophagectomy (94.9% vs. 96.6%, p=0.013, 89.5% vs. 91.1%, p=0.028, respectively). Patients in the new program had better body composition at discharge than those in the old program [body fat mass (91.6% vs. 94.1%), lean body mass (95.2% vs. 97.2), and skeletal muscle mass (95.3% vs. 97.0%)]. Major reasons for incompliance were dysphagia, pneumonia, and anastomotic leakage. Multivariate analysis revealed that age ≥70 years at surgery and sex (male) were independent risk factors for incompliance with the postoperative program. CONCLUSION: The new ERAS program aimed to shorten postoperative LOS had clinical benefits in body composition early after esophagectomy. Personalized ERAS programs based on age might lead to better postoperative outcomes because of low compliance rates for older patients.

Iterative evaluation of novel access techniques for small bowel obstruction: combining image guided, percutaneous, and endoscopic methods.

Objective: To avoid the need for extensive adhesiolysis in patients with small bowel obstruction (SBO). We evaluated the feasibility of using advanced imaging, percutaneous access, and endoscopy as alternative therapies for SBO. Design: Retrospective case series (IDEAL [Idea, Development, Exploration, Assessment, and Long-term Study Collaborative] stages 1 and 2a). Setting: Single tertiary referral center. Participants: Twelve adults with chronic SBO resulting from inflammatory bowel disease, disseminated cancer, radiation, and/or adhesive disease. Participants were included if they underwent one of three novel access procedures. There were no exclusion criteria. The median age of participants was 67.5 years (range 42-81); two-thirds were women; and median American Society of Anesthesiology class was 3. Interventions: All participants underwent one of three novel access methods, followed by wire-guided balloon dilation of a narrowed area of small bowel. These methods combined endoscopic, fluoroscopic, and surgical techniques. The techniques were (1) a purely endoscopic approach aided by an over-the-scope double-balloon device, (2) a combined endoscopic and percutaneous approach, and (3) a cut-down approach. Main outcome measures: Procedural success (defined as successful access to the small bowel and successful balloon dilation of the stenotic area). Secondary outcomes included major complications, recurrence, length of stay, and procedure time. Results: Procedural success was achieved in 10 of 12 patients (83%). At the time of median follow-up of 10 months, recurrence of SBO was observed in two patients. In only one patient, the novel method did not change the treatment plan. No major complications occurred. Conventional operative intervention was avoided in all patients who achieved technical success with one of the novel approaches. The median postprocedure length of hospital stay was 4 days. Median procedure time was 135 min. Conclusions: Novel minimally invasive approaches to SBO represent feasible alternatives to surgical procedures in select patients. Further study should compare these approaches to standard ones as new methods are refined.

The potential clinical utility of cell-free DNA for gastric cancer patients treated with nivolumab monotherapy.

To assess the potential clinical utility of cell-free DNA (cfDNA)-based biomarkers for identifying gastric cancer (GC) patients who benefit from nivolumab. From 31 GC patients treated with nivolumab monotherapy (240 mg/body, Bi-weekly) in 3rd or later line setting, we prospectively collected blood samples at baseline and before the 3rd dose. We compared cfDNA-based molecular findings, including microsatellite instability (MSI) status, to tissue-based biomarkers. We assessed the clinical value of blood tumor mutation burden (bTMB) and copy number alterations (CNA) as well as the cfDNA dynamics. The concordance between deficient-MMR and cfDNA-based MSI-high was 100% (3/3). Patients with bTMB ≥ 6 mut/Mb had significantly better progression-free survival (PFS) and overall survival (OS); however, such significance disappeared when excluding MSI-High cases. The combination of bTMB and CNA positivity identified patients with survival benefit regardless of MSI status (both PFS and OS, P < 0.001), with the best survival in those with bTMB≥6mut/Mb and CNAnegative. Moreover, patients with decreased bTMB during treatment had a better disease control rate (P = 0.04) and longer PFS (P = 0.04). Our results suggest that a combination of bTMB and CNA may predict nivolumab efficacy for GC patients regardless of MSI status. bTMB dynamics have a potential utility as an on-treatment biomarker.

Preoperative diagnosis of tumor depth in gastric cancer using transabdominal ultrasonography compared to using endoscopy and computed tomography.

BACKGROUND: An accurate evaluation method for preoperative diagnosis has not yet been established in patients with gastric cancer (GC), though it is essential for optimal treatment. Current standard modalities are endoscopy and contrast computed tomography (CT). In this study, we investigated the efficacy and limitations of transabdominal ultrasonography (TUS) for the assessment of tumor invasion. METHODS: We enrolled 178 consecutive patients with GC evaluated by TUS, endoscopy, and contrast CT before gastrectomy. For the TUS examination, patients ingested water to fill their stomachs. The clinical staging determined using these modalities was compared to the pathological staging. RESULTS: The overall accuracy of clinical T staging using TUS was 47.8% (pT1a: 5.8% (2/35); pT1b: 58.8% (20/35); pT2: 69.6% (16/23); pT3: 66.7% (22/33); pT4a: 46% (23/50); pT4b: 100% (2/2)). Using endoscopy, contrast CT, and TUS, the overall accuracy was 60.7%. The accuracy of TUS was associated with the tumor region (U region: 50% (14/28); M: 31.8% (14/44); L: 53.7% (57/106); P = 0.048), but not with the cross-sectional parts (P = 0.49). Multivariate analysis identified inaccurate TUS as independently correlating with tumor region (M vs. U/L, odds ratio (OR) = 3.11, 95% confidence interval (CI) 1.41-6.87; P = 0.005) and pT (pT1 vs. pT2-4, OR = 3.00, 95%CI 1.31-6.87; P = 0.009). CONCLUSIONS: The present study demonstrated the importance of TUS in evaluating GC. Thus, TUS may be useful for clinical T staging in certain circumstances, leading to treatment optimization.

Use of a novel endoscopic overtube with bilateral tool channels for endoscopic resection of experimental lesions and repair of intestinal defects in the right colon: preclinical trial.

BACKGROUND: Endoscopic tumor resection and intestinal defect repair are technically challenging leading to invasive surgery and colectomy performed for resection of benign polyps. In this study, we evaluated the use of an endoscopic overtube with bilateral tool channels for these procedures. METHODS: Using a fresh porcine colorectum in a 3D ex vivo model, 3 cm lesions at the posterior wall of the transverse colon were removed by two different techniques: standard endoscopic submucosal dissection (ESD) technique (STD, n = 12) and ESD using the overtube with an endoscopic snare and grasper through the bilateral channels (OT, n = 12). Procedure times and the number of muscular injuries were evaluated. Using the same model, 5-10 mm full-thickness perforations within a 3 cm mucosal defect at the posterior wall of the transverse colon were closed by two different techniques: standard endoscopic closure technique (STD, n = 12) and endoscopic closure using the overtube with two graspers (OT, n = 12). The outcomes measured included bursting pressure and the number of endoscopic clips used for closure. RESULTS: Endoscopic resection of lesions was performed by the OT group in a significantly shorter total procedure time (STD vs. OT = median 38.9 min vs. 17.3, p < 0.001) and with fewer muscular injuries (median 0 vs. 2, p = 0.002), compared with the STD group. After repair of intestinal defects, the OT group showed higher median bursting pressures (STD vs. OT = 11.2 mmHg vs. 57.1, p = 0.008) despite using fewer clips (median 13 vs. 10, p < 0.001). CONCLUSION: This study demonstrates a novel traction technique with an endoscopic overtube using multiple instruments to remove lesions and repair intestinal defects in the colon more effectively. This endoscopic platform could provide a safe alternative to invasive surgical treatment.

[A Long-Term Survival Case of HER2-Positive Gastric Cancer with Distant Lymph Node Metastasis Receiving Multidisciplinary Therapy].

An 82-year-old man presented with right cervical swelling. Cervical ultrasonography revealed several swollen lymph nodes which were diagnosed with adenocarcinoma by fine needle aspiration cytology. Computed tomography showed right axillary lymph nodes were also swelling. Upper and lower gastrointestinal endoscopy found type 0-Ⅱa gastric cancer located at the posterior wall of the middle region. Pathology was HER2-positive moderately differentiated tubular adenocarcinoma. Doublet chemotherapy with S-1 and cisplatin was administered for unresectable gastric cancer(cT1bN0M1, cStage Ⅳb). One month later, doublet chemotherapy was changed to triplet chemotherapy with trastuzumab, capecitabine, and cisplatin. A month later, complete response(CR)was achieved. After 8 courses of triplet chemotherapy, we changed to doublet chemotherapy with trastuzumab and capecitabine due to impaired kidney function 8 months. Two months later from that, endoscopic mucosal dissection was performed for gastric cancer as local therapy(pathology: well differentiated tubular adenocarcinoma, pT1a, ly0, v0). Two years and 2 months after the beginning of chemotherapy, the right axillary lymph nodes were enlarged again and surgically resected(pathology: HER2-positive poorly differentiated adenocarcinoma). He had CR for 8 years and 2 months, and chemotherapy was canceled due to his decision. During 1 year and 7 months, disease progression was not observed. We present a long-term survival case of HER2-positive gastric cancer with distant lymph node metastasis receiving multidisciplinary therapy.

[A Case of Palliative Laparoscopic Surgery in an Older Woman with Advanced Gastric Cancer and a Large Hiatal Hernia].

A 94-year-old woman presented with anorexia, persisting for several months, and marked anemia. An upper gastrointestinal endoscopy revealed type 3 advanced gastric cancer in the antrum. CT imaging indicated a large esophageal hiatus hernia and the elevation of the gastric fornix to the level of the bronchus. Wall thickening in the antrum, surrounded by increased fat tissue density, and swollen lymph nodes along the common hepatic artery, were detected. She was diagnosed with advanced gastric cancer(cT3N1M0, cStage Ⅲ)and a large hiatal hernia. A laparoscopic hiatal hernia repair and distal gastrectomy were performed. The cancer was exposed outside the serosa in the antrum, yet there was no indication of ascites, liver metastasis or peritoneal dissemination. The esophageal hiatus was sutured, and a distal gastrectomy(Billroth-Ⅱ reconstruction)was conducted. To avert hernia recurrence, sutures were applied to the posterior wall of the abdominal esophagus and the crus of the diaphragm, as well as the fornix of the remnant stomach and the diaphragm. Her postoperative course was uneventful, and she was discharged on POD13. There were no instances of gastric cancer recurrence or hiatal hernia 7 months post-operation.

[A Case of Cardiodiaphragmatic Corner Lymph Node Recurrence after Surgery for Ascending Colon Cancer].

The case is a female, 50s. She presented to our hospital because of her intestinal obstruction. A CT scan at her visit showed wall thickening of her ascending colon. Colonoscopy revealed type 2 advanced cancer in the ascending colon. The pathological examination was a diagnosis of adenocarcinoma. Laparoscopic right hemicolectomy was performed for cT3N1M0, cStage Ⅲb ascending colon cancer. The pathological result was pT3N1M0, Stage Ⅲb. Contrast-enhanced CT was performed 10 months after the operation. As a result, she was found to have recurrent multiple liver metastases. A laparoscopic partial hepatectomy was performed at the site of recurrence. The pathological result was adenocarcinoma. It was a diagnosis of metastasis recurrence from colorectal cancer. A CT scan 16 months after primary surgery revealed enlarged cardiodiaphragmatic lymph nodes. A PET-CT scan revealed an accumulation of SUVmax 3.0 in the same area. She was diagnosed with lymph node recurrence of colorectal cancer and underwent resection. Histopathological result was adenocarcinoma. It was diagnosed as metastasis from ascending colon cancer.

Multicenter randomised trial of two versus three courses of preoperative cisplatin and fluorouracil plus docetaxel for locally advanced oesophageal squamous cell carcinoma.

BACKGROUND: The optimal number of neoadjuvant chemotherapy (NAC) cycles remains to be established for treating oesophageal squamous cell carcinoma (ESCC). We compared two versus three courses of NAC for treating locally advanced ESCC in a multi-institutional, randomised, Phase II trial. METHODS: We randomly assigned 180 patients with locally advanced ESCC at 6 institutions to either two (N = 91) or three (N = 89) courses of DCF (docetaxel 70 mg/m2, cisplatin 70 mg/m2 i.v. on day 1, fluorouracil 700 mg/m2 continuous infusion for 5 days) every 3 weeks, prior to surgery. The primary endpoint was 2-year progression-free survival (PFS) with an intention-to-treat analysis. RESULTS: Patient background parameters were well-balanced. The R0 resection rates were 98.9 and 96.5% in the two- and three-course groups, respectively (P = 0.830). In resected cases, the two- and three-course groups had comparable pN0 rates (P = 0.225) and histological responses (P = 0.898). The 2-year PFS rate was also comparable between the two groups (71.4 vs. 71.1%, P = 0.669). Among subgroups based on baseline characteristics, only patients aged under 65 years old showed a tendency for better survival with the three-course treatment (hazard ratio = 2.612, 95% confidence interval: 1.012-7.517). CONCLUSIONS: Two courses of a DCF regimen showed potential as an optional NAC treatment for locally advanced ESCC. CLINICAL TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry of Japan (identification number UMIN 000015788).

[A Case of Descending Colon Cancer with Long-Term Maintenance of QOL by Multidisciplinary Treatment Approach for Locally Recurrent Lesion with Hydronephrosis].

We report a case of recurrent descending colon cancer in which QOL was maintained for a long period by performing resection with intestinal reconstruction, chemotherapy, and radiotherapy for local recurrence with hydronephrosis. A man in his 60s with good ADL underwent laparoscopic left hemicolectomy for descending colon cancer. After 4.5 years postoperatively, computed tomography and positron emission tomography showed a local recurrence of 32 mm contacting with the left external iliac artery and sigmoid colon, and CAPOX plus BEV was started. When cholecystitis developed after 5 chemotherapy courses, the recurrent lesion was resected simultaneously. After 8 months, repeated recurrent lesion with a major axis of 13 mm with left hydronephrosis was observed at the same site. After 3 years of chemotherapy after placing the left ureteral stent, CEA level gradually increased, and tumor growth was observed. Because of the aggressive chemotherapy limitation due to high proteinuria, 66 Gy/22 Fr radiotherapy was performed. After 1 month of radiotherapy, the CEA level decreased and proteinuria improved in that period. Radiotherapy for local recurrence can be a useful interval for chemotherapy and effective local control.

[Postoperative Severe Dysphagia Due to Hypophosphatemia in a Patient with Peritoneal Dissemination of Gastric Cancer].

An 83-year-old man presented with melena and weight loss. Upper gastrointestinal endoscopy showed type 3 advanced gastric cancer with pyloric stenosis. Surgical findings revealed numerous peritoneal dissemination, then gastro-jejunum anastomosis was performed. The oral diet was resumed on POD4, however severe dysphagia occurred immediately on POD6. There were no specific findings on MRI/MRA and nasal endoscopy. Serum antibodies related to neuromuscular diseases and connective tissue diseases were also negative. Despite the rehabilitation, the dysphagia remained. Before total parenteral nutrition on POD16, hypophosphatemia was discovered(1.4 mg/dL). His dysphagia disappeared with the improvement in the serum phosphate level. Hypophosphatemia might be caused by an inadequate intake as urine phosphate, serum calcium and serum PTH levels were normal. We present a recent case of severe dysphagia due to hypophosphatemia in a patient with peritoneal dissemination of gastric cancer.

Use of an endoscopic flexible grasper as a traction tool for excision of polyps: preclinical trial.

Endoscopic submucosal dissection (ESD) is challenging in the right colon. Traction devices can make it technically easier. In this study, we evaluated a flexible grasper with articulating tip and elbow-like bending (IgE) through a double-balloon surgical platform (DESP), compared with an earlier generation grasper without elbow-like bending (Ig). The reach of Ig/IgE was investigated at eight locations using a synthetic colon within a 3D model. Using a fresh porcine colorectum, 4 cm pseudo-polyps were created at the posterior wall of the ascending colon. Fifty-four ESD procedures were performed using three techniques: standard ESD (STD), ESD using Ig (DESP + Ig), and ESD using IgE (DESP + IgE). IgE was able to reach the full circumference at all the locations, whereas the medial walls proximal to the descending colon were out of Ig's reach. Compared with the STD, both DESP + Ig and DESP + IgE showed significantly shorter procedure time (STD vs. DESP + Ig vs. DESP + IgE = median 48.9 min vs. 38.6 vs. 29.9) and fewer injuries (1.5 vs. 0 vs. 0). Moreover, the DESP + IgE had a shorter procedure time than the DESP + Ig (p = 0.0025). The IgE with DESP increased instrument reach compared to Ig, and likely represented a traction tool for excision of large pseudo-polyps in the right colon.

Intraluminal gas escape from biopsy valves and endoscopic devices during endoscopy: caution advised during the COVID-19 era.

Background and study aims The risk of aerosolization of body fluids during endoscopic procedures should be evaluated during the COVID-19 era, as this may contribute to serious disease transmission. Here, we aimed to investigate if use of endoscopic tools during flexible endoscopy may permit gas leakage from the scope or tools. Material and methods Using a fresh 35-cm porcine rectal segment, a colonoscope tip, and manometer were placed intraluminally at opposite ends of the segment. The colonoscope handle, including the biopsy valve, was submerged in a water bath. Sequentially, various endoscopic devices (forceps, clips, snares, endoscopic submucosal dissection (ESD) knives) were inserted into the biopsy valve, simultaneously submerging the device handle in a water bath. The bowel was slowly inflated up to 74.7 mmHg (40 inH 2 O) and presence of gas leakage, leak pressure, and gas leakage volume were measured. Results Gas leakage was observed from the biopsy valve upon insertion and removal of all endoscopic device tips with jaws, even at 0 mmHg (60/60 trials). The insertion angle of the tool affected extent of gas leakage. In addition, gas leakage was observed from the device handles (8 of 10 devices) with continuous gas leakage at low pressures, especially two snares at 0 mmHg, and an injectable ESD knife at 0.7 ±â€Š0.8 mmHg). Conclusions Gas leakage from the biopsy valve and device handles commonly occur during endoscopic procedures. We recommend protective measures be considered during use of any tools during endoscopy.

Lymph Node Response to Neoadjuvant Chemotherapy as an Independent Prognostic Factor in Metastatic Esophageal Cancer.

OBJECTIVE: The aim of this study was to evaluate primary tumor (PT) and lymph node (LN) responses to neoadjuvant chemotherapy (NACT) for predicting long-term survival in patients with metastatic esophageal cancer (EC). BACKGROUND: In evaluating NACT responses in patients with EC, imaging modalities typically target the PT in the esophagus, which is unmeasurable. Targeting measurable organs, like positive LNs, might provide more accurate assessments. METHODS: We enrolled 251 patients with EC and clinically positive LNs that underwent curative resections, after triplet NACT. The percent reduction of PT area was measured with bidimensional computed tomography. The LN response was defined as the percent reduction of the sum of the short diameters in all positive LNs. RESULTS: NACT reduced PTs and LNs by (median, range) 58.0% (38.1-94.9) and 34.5% (46.2-68.2), respectively. Based on the receiver-operating characteristic analyses for predicting a histological response and a 10% stepwise cutoff analyses of recurrence-free survival (RFS), responder/nonresponder cutoff values were ≥60% for PT area reductions and ≥30% for LN size reductions. 39.6% of patients showed discordant PT and LN responses. Compared with PT-responders, LN-responders had significantly less advanced pN (P < 0.0001) and pM (P = 0.015) in addition to less advanced pT (P < 0.0001) and better histological responses (P < 0.0001), and closer correlations to lymphatic, distant metastases and dissemination. A multivariate analysis of RFS identified 2 independent prognostic factors: the LN response [hazard ratio (HR) = 2.51, 95% confidence interval (CI) = 1.63-3.95, P < 0.0001] and the pN (HR = 2.72, 95% CI = 1.44-5.64, P = 0.0016), but not the PT response. CONCLUSIONS: The LN response to NACT predicted long-term survival more precisely than the PT response in patients with metastatic EC.