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Background: Weight loss (WL) after gastrectomy for gastric cancer is associated with both decreased compliance with adjuvant chemotherapy and impaired survival. This study examined the effects of administering oral nutritional supplements (ONS) for 3 months after gastrectomy in terms of compliance with adjuvant chemotherapy and survival outcomes., Methods: This large-scale, multicenter, open-label, randomized controlled trial enrolled 1,003 gastric cancer patients undergoing curative gastrectomy. Patients were assigned to the control group (n = 503) or ONS group (n = 500). In the ONS group, 400 kcal/day of ONS was recommended in addition to a regular diet for 3 months after gastrectomy. Compliance with adjuvant chemotherapy and survival outcomes were compared between the two groups., Results: Compared with the control group, the ONS group showed significantly decreased WL at 3 months after gastrectomy (8.6 ± 6.1 vs. 7.2 ± 5.7%, respectively, P = 0.0004). The control and ONS groups did not differ regarding the induction rate of adjuvant chemotherapy (84.9 vs. 82.8%, respectively, P = 0.614) or the continuation rate at 3 months postoperatively (75.3 vs. 76.6%, respectively, P = 0.809). Oral nutritional supplements for 3 months showed no survival benefit; the 3- and 5-year overall survival (OS) rates were 91.3% and 87.6% in the control group and 89.6% and 86.4% in the ONS group, respectively, indicating no significant difference (P = 0.548). Subgroup analysis could not detect a population in which ONS administration increased OS., Conclusions: Administration of ONS for 3 months after gastrectomy was not associated with increased compliance with adjuvant chemotherapy or with improved prognosis., (© 2024. Society of Surgical Oncology.)

Purpose: The aim of this study was to clarify whether ghrelin infusion is useful for suppressing inflammatory responses after esophagectomy., Methods: A phase I study of ghrelin administration after esophagectomy was performed in 20 patients with esophageal cancer. The anti-inflammatory effect of ghrelin was compared with 20 consecutive patients who did not receive ghrelin infusion. Additionally, 10 patients with intermittent infusion for 10 days were compared with 10 patients with continuous infusion for 5 days. The primary endpoint was the duration of systemic inflammatory response syndrome (SIRS). Secondary endpoints included postoperative complications, serum C-reactive protein (CRP), interleukin-6 (IL-6), and growth hormone (GH) levels., Results: No adverse events of ghrelin administration occurred. Patients with ghrelin infusion had higher plasma ghrelin levels on postoperative day (POD) 3 (p = 0.003) and shorter SIRS duration (p = 0.007) than patients without ghrelin infusion. Although SIRS duration was similar (p = 0.19), patients with continuous ghrelin infusion had significantly higher plasma ghrelin (p < 0.001) and GH levels (p = 0.002) on POD 3 than patients with intermittent ghrelin infusion. Serum CRP and IL-6 levels on POD 3 tended to be lower in the continuous infusion versus intermittent infusion group., Conclusions: Ghrelin was safely administered after esophagectomy and may reduce excess postoperative inflammatory responses. Continuous infusion is better for this purpose than intermittent infusion.

Background: With the improvement of sensor technology, the trend of Internet of Things (IoT) is affecting the medical devices. The aim of this study is to verify whether it is possible to "visualize instrument usage in specific procedures" by automatically accumulating the digital data related to the behavior of surgical instruments/forceps in laparoscopic surgery., Methods: Five board-certified surgeons (PGY 9-24 years) performed laparoscopic cholecystectomy on 35-kg porcine (n = 5). Radio frequency identifier (RFID) was attached to each forceps with RFID readers installed on the left/right of the operating table. We automatically recorded the behavior by tracking the operator's right/left hands' forceps with RFID. The output sensor was installed in the electrocautery circuit for automatic recordings of the ON/OFF times and the activation time. All data were collected in dedicated software and used for analysis., Results: In all cases, the behaviors of forceps and electrocautery were successfully recorded. The median operation time was 1828 s (range 1159-2962 s), of which the electrocautery probe was the longest held on the right hand (1179 s, 75%), followed by Maryland dissectors (149 s, 10%), then clip appliers (91 s, 2%). In contrast, grasping forceps were mainly used in the left hand (1780 s, 93%). The activation time of electrocautery was only 8% of the total use and the remaining was mainly used for dissection. These situations were seen in common by all operators, but as a mentor surgeon, there was a tendency to change the right hand's instruments more frequently. The median activation time of electrocautery was 0.41 s, and these were confirmed to be 0.14-0.57 s among the operators., Conclusion: By utilization of IoT for surgery, surgical procedure could be "visualized." This will improve the safety on surgery such as optimal usage of surgical devices, proper use of electrocautery, and standardization of the surgical procedures.

Background: Surgery often introduce inflammatory response, which may promote tumor growth and metastasis of residual cancer cells. We investigated the impacts of methylprednisolone on the tumor growth and peritoneal seedings in mice treated with lipopolysaccharide (LPS), which mimics systemic inflammation induced by surgical stress and postoperative complications., Methods: The serum interleukin-6 (IL-6) levels, tumor volume, tumor weight, and the number of peritoneal nodules were investigated in tumor growth model and peritoneal seeding model using BALB/c mice and murine CT26 cancer cell lines in vivo. We conducted functional analyses of IL-6 in Western blotting and proliferation assays in vitro. We also investigated whether preoperative administration of methylprednisolone decreased postoperative serum IL-6 levels in cancer patients in a randomized clinical study., Results: In the in vivo study, methylprednisolone inhibited the LPS-induced increase of serum IL-6 levels (mean, 33,756 pg/ml vs. 5917 pg/ml; P < 0.001), tumor volume (mean, 397 mm 3 vs. 274 mm 3 ; P = 0.019), tumor weight (mean, 0.38 g vs. 0.15 g; P = 0.020), and the number of peritoneal nodules (mean, 112 vs. 47; P = 0.002). In the in vitro study, IL-6 enhanced JAK/STAT signaling and increased the cell proliferation, and IL-6R-neutralizing antibody attenuated these effects. In the clinical study, serum IL-6 levels were significantly decreased by methylprednisolone (median, 97.5 pg/ml vs. 18.0 pg/ml; P = 0.030)., Conclusions: Surgical stress and postoperative complications may enhance tumor growth due to the increase of IL-6. However, methylprednisolone can decrease serum IL-6 levels, thus inhibiting tumor growth and peritoneal seeding.

Background: The fourth edition of New Japanese classification system for esophageal achalasia was revised after a long interval of 30 years in 2012. In this new system, achalasia is morphologically classified into 3 types, based on its X-ray findings. However, the system has been limitedly used in Japan and has not been fully validated in terms of its predictive capability of postoperative outcomes. The purpose of this study was to clarify the validity of new Japanese classification system for esophageal achalasia, as an index of patient characteristics and as a predictor of operative and mid/long-term postoperative outcomes., Patients and Methods: Fifty-nine cases of achalasia underwent laparoscopic Heller-Dor surgery between 2005 and 2018. We evaluated retrospectively patient characteristics, intraoperative findings, esophageal manometry, 24-h pH monitoring and postoperative course., Results: There were 34 St and 25 Sg/aSg cases. Age of St group was lower than Sg group. Preoperative duration of disease of St group was shorter than Sg. There were no differences in the results of surgical outcomes and prognoses., Conclusion: The new Japanese classification system may give additional insight and information in understanding epidemiology of esophageal achalasia; however, our study failed to demonstrate "inter-disease type" differences in surgical outcomes and prognoses.

Background: c-Met relies on CD44v6 for its activation and signaling in several cancer cell lines. However, the correlation of c-Met and CD44v6 expression and its biological significance in esophageal squamous cell carcinoma (ESCC) remains unknown., Methods: Expression of c-Met and CD44v6 was examined by immunohistochemistry (IHC) in 147 ESCC specimens. We analyzed the impact of c-Met and CD44v6 expression on clinicopathological parameters, including chemoresistance or prognosis in ESCC., Results: High expression of c-Met and CD44v6 in cancerous lesions was identified in 49.7% and 50.3% of all patients, respectively. The c-Met-high group comprised more advanced pT and pM stages than the c-Met-low group. In addition, more patients in the c-Met-high group received neoadjuvant chemotherapy (NACT) than the c-Met-low group (64.4% vs. 43.2%, P = 0.010). On the other hand, the CD44v6-high group was associated with more advanced pT/pN stages and a poorer clinical response to NACT (response rate 53.5% vs. 77.8%, P = 0.025) than the CD44v6-low group. Double-positive immunostaining of c-Met and CD44v6 was identified in 28.6% of all cases, and multivariate analysis of overall survival (OS) identified them (hazard ratio 1.79, 95% confidence interval 1.03-3.04, P = 0.038) as independent prognostic factors in addition to pN and pM stage., Conclusions: c-Met/CD44v6 were associated with tumor progression or chemoresistance. Double-positive expression of c-Met and CD44v6 negatively impacted patient prognosis in ESCC, implying that c-Met and CD44v6 are candidates for targeted therapy in ESCC.

Background: Although tumor regression and nodal status are reported to be useful prognostic factors for patients with oesophageal cancer who are treated with neoadjuvant chemoradiotherapy, the clinical effects of those factors remain to be explained fully in neoadjuvant chemotherapy. Additionally, factor predictive of systemic disease after neoadjuvant therapy remain unexplored., Methods: The impact of pathological tumor regression and the number of involved lymph nodes on survival and the occurrence of systemic disease were examined in 405 patients with esophageal squamous cell carcinoma who received neoadjuvant chemotherapy, RESULTS: Among the 405 patients studied, 96 (23.7%) achieved good response, whereas 309 (76.3%) were classified as poor response to neoadjuvant chemotherapy. Systemic disease occurred in 136 patients (34.6%) of 393 patients who underwent curative esophagectomy. The number of involved lymph nodes and pathological tumor regression were associated with survival and the occurrence of systemic disease. Multivariate analysis showed that the number of involved lymph nodes was identified as an independent factor associated with both survival and the occurrence of systemic disease, together with the latest AJCC ypstage. However, tumor regression was not found to be an independent factor associated with survival and systemic disease in multivariate analysis., Conclusions: Posttreatment nodal status rather than pathological tumor regression seems to be useful for predicting prognosis and the occurrence of systemic disease in patients with esophageal squamous cell carcinoma who underwent neoadjuvant chemotherapy. Additional systemic therapy may be needed in patients with several involved lymph nodes remaining after neoadjuvant therapy.

Introduction: We aimed to analyze the clinical and histological effects of chemotherapy in superficial esophageal squamous cell carcinoma (SESCC)., Methods: We analyzed tumor samples from five patients with cT1bN1M0 who underwent subtotal esophagectomy following two courses of a new triplet chemotherapy regimen including docetaxel, cisplatin, and 5-fluorouracil (DCF). To assess the histological effects of chemotherapy, resected specimens were analyzed by macroscopic examination, hematoxylin & eosin (HE) staining, immunohistochemical (IHC) staining (p53, Ki-67 and cytokeratin) and periodic acid-Schiff (PAS) staining., Results: All five patients had a pathological T stage of T0/1a-LPM/1a-MM/1b (1/2/1/1) and histological grade of grade1a/1b/2/3 (1/1/2/1). Endoscopic examination revealed substantial shrinkage of lugol-voiding lesions (LVLs) in all cases. One case showed complete LVL disappearance, and resected specimen examination confirmed pathological complete response (pCR). IHC and PAS staining revealed that most initial LVLs were PAS-negative. Obvious viable cells were confirmed in two cases. The other three cases exhibited nuclear atypia and strong expression of p53 and Ki-67 in the basal layer of mucosa or lamina propria mucosae, even though the superficial layer of mucosa showed no obvious LVLs with PAS-positive. p53-positive lesions were also observed in Ki-67-positive. This indicated discordance between the endoscopic findings and histopathological evaluation., Conclusion: DCF chemotherapy alone had a substantial therapeutic effect on SESCC in all cases. However, despite the normal appearance of the mucosal surface, viable cancer cells remained below the basal layer of mucosa. Careful attention should be paid when diagnosing clinical CR, or securing a resection margin of SESCC after DCF chemotherapy.

Background: Intestinal ischemia can lead to fatal complications if left unrecognized during surgery. The current techniques of intraoperative microvascular assessment remain subjective. Probe-based confocal laser endomicroscopy (pCLE) has the potential to objectively evaluate microvascular blood flow in real-time setting. The present study evaluated the technical feasibility of real-time intestinal bloodstream evaluation using pCLE in a porcine intestinal ischemia model., Methods: Seven pigs were used. The intestinal ischemia model was prepared by sequentially dividing the mesenteric blood vessels. The intestinal bloodstream was evaluated on its serosal surface using pCLE (Cellvizio 488 probe, Ultra Mini O) at every 1-cm segment from a vessel-preservation border (i.e., the cut end of the vessel). Images of the blood vessels and flow of red blood cells (RBCs) in each visualized vessel were semi-qualitatively assessed using a 3-scale scoring system. In addition, 25 surgeons blindly assessed the 10 movies recorded at 0, 1, 2, 3, and 5 cm from a vessel-preservation border using a 4-scale scoring system to confirm the consistency of the evaluation of the pCLE system., Results: Images of the blood vessels were successfully obtained from the cut end of the vessel to the segment 4 cm away. Good unidirectional flow of RBCs was observed from the cut end to the 2-cm segment, whereas the flow became bidirectional between 2 and 3 cm segments. Beyond 4 cm, no flow images were obtained. The specimen obtained from the segment beyond 4 cm showed remarkable mucosal color change, which was confirmed as a necrotic change histologically. The evaluations from the cut end of the vessel to the segment 1 cm away by surgeons were excellent or good and it was almost consistent., Conclusions: Real-time bloodstream evaluation using pCLE is feasible and potentially effective for predicting intestinal ischemia during surgery.

Background: Autophagy plays a major role in cellular homeostasis and is implicated in cancer progression. Damaged mitochondria are scavenged and eliminated by mitochondrial autophagy, referred to as mitophagy, which can promote cancer cell survival. This study investigated the expression and effects of the autophagy-related protein LC3 and the mitophagy-related protein Pink1 in human esophageal squamous cell carcinoma (ESCC)., Methods: Both LC3 and Pink1 were analyzed by immunohistochemistry in tissues from 217 ESCC patients, including 159 patients undergoing neoadjuvant chemotherapy. The relationships between LC3 and Pink1 expression and various clinicopathologic factors were determined. In vitro assays were performed to assess the role of LC3 and Pink1 in ESCC chemoresistance., Results: High LC3 expression was observed in 47.9% and high Pink1 expression in 48.4% of the ESCC patients. Pink1 expression was significantly higher in patients who underwent chemotherapy than in patients who did not (p = 0.032). High LC3 and Pink1 expression was significantly correlated with poor response to chemotherapy (p = 0.004 and p < 0.001, respectively), and high expression of Pink1, but not LC3, was significantly correlated with a poor prognosis for patients treated with preoperative chemotherapy (p = 0.007). Multivariate analysis identified Pink1 expression as an independent prognostic factor (p = 0.042). In vitro assays demonstrated that LC3-II and Pink1 expression increased after chemotherapeutic treatment in the ESCC cell line, and inhibition of autophagy and mitophagy using chloroquine and siPink1, respectively, restored chemosensitivity., Conclusions: High expression of Pink1 is associated with chemoresistance and a poor prognosis for ESCC patients undergoing neoadjuvant chemotherapy.

Background: Controversy remains whether preoperative pneumatic balloon dilation (PBD) influences the surgical outcome of laparoscopic esophagocardiomyotomy in patients with esophageal achalasia. The aim of this study was to evaluate whether preoperative PBD represents a risk factor for surgical complications and affects the symptomatic and/or functional outcomes of laparoscopic Heller myotomy with Dor fundoplication (LHD)., Methods: A retrospective chart review was conducted on a prospectively compiled surgical database of 103 consecutive patients with esophageal achalasia who underwent LHD from November 1994 to September 2014. The following data were compared between the patients with preoperative PBD (PBD group; n = 26) and without PBD (non-PBD group; n = 77): (1) patients' demographics: age, gender, body mass index, duration of symptoms, maximum transverse diameter of esophagus; (2) operative findings: operating time, blood loss, intraoperative complications; (3) postoperative course: complications, clinical symptoms, postoperative treatment; and (4) esophageal functional tests: preoperative and postoperative manometric data and postoperative profile of 24-h esophageal pH monitoring., Results: (1) No significant differences were observed in the patients' demographics. (2) Operative findings were similar between the two groups; however, the incidence of mucosal perforation was significantly higher in the PBD group (n = 8; 30.7 %) compared to the non-PBD group (n = 6; 7.7 %) (p = 0.005). (3) Postoperative complications were not encountered in either group. The differences were not significant for postoperative clinical symptoms, the incidence of gastroesophageal reflux disease, or necessity of postoperative treatments. (4) Lower esophageal sphincter pressure was effectively reduced in both groups, and no differences were observed in manometric data or 24-h pH monitoring profiles between the two groups. Multivariate logistic regression analysis showed that preoperative PBD and the maximum transverse diameter of esophagus were significantly associated with intraoperative mucosal perforation., Conclusions: Although postoperative outcomes were not affected, additional caution is recommended in identifying intraoperative mucosal perforation in patients with preoperative PBD when performing LHD.

Background: Surgical interventions for cervical esophageal cancer (CEC), particularly larynx-preserving procedures, have not yet been standardized in terms of short- and long-term outcome., Methods: We retrospectively analyzed 100 consecutive surgeries for CEC in our department. We compared clinicopathological parameters and long-term outcomes between larynx-preserving esophagectomies (LP group) and nonpreserving procedures (NP group). We also evaluated preoperative predictive parameters for larynx-preservation., Results: Compared with the NP group, the LP group had significantly lower cT (P < 0.001) and cStage (P = 0.001) and shorter tumor length (P = 0.0108). Multivariate logistic regression analysis identified early cT stage, early cStage, and response to preoperative treatment as significant predictive parameters of larynx preservation. Larynx-preserving procedures could be performed for 90.5 % of T1-2 tumors regardless of preoperative treatment response. In contrast in T3-4 tumors, most nonresponders (92.3 %) were ineligible for larynx-preservation (P = 0.0012), whereas 54.3 % of responders could achieve larynx preservation. The average shortening of upward extension in T3-4 tumors after preoperative treatment was 20.0 mm in the LP group vs. 10.2 mm in the NP group (P = 0.051). The two groups were similar in terms of overall morbidity (including pneumonia), mortality, and postoperative hospital days. Importantly, larynx preservation for CEC neither worsened patient prognosis nor increased locoregional recurrence compared to the NP group., Conclusions: Larynx-preserving esophagectomy for CEC is feasible and oncologically acceptable. The cT, cStage, and clinical response to preoperative treatment are important preoperative predictors of a patient's suitability for larynx-preservation.

Background: In digestive cancers, it is mandatory to diagnose peritoneal metastasis prior to selecting therapy. Therefore, exploratory laparoscopy has gained wider clinical acceptance. In laparoscopy, the peritoneal metastasis is pathologically confirmed by excisional biopsy; however, there remain technical difficulties in performing precise diagnosis and adequate biopsy on small peritoneal lesions without damaging organs. We have focused on "optical biopsy" using probe-based confocal laser endomicroscopy (pCLE). The aims of this study were (1) to optimize current CLE system for real-time observation of peritoneal metastases and (2) to assess its potential usefulness as diagnostic modality in preclinical settings., Methods: To optimize condition and evaluate feasibility, we prepared peritoneal metastasis mice model with gastric cancer cell line (MKN-45). On Day 10 after seeding, the mice were laparotomized and performed pCLE observations with CellvizioLAB (LSU-F 400/488 nm, Mauna Kea Technologies, Paris, France). We evaluated two different CLE probes, three different dyes, and optimal interval time. The detected sites were excised and pathologically evaluated on its morphology. Next, the feasibility and safety were validated in porcine model for clinical usage. After injection of fluorescein, pCLE was applied for the observation of intra-abdominal organs., Result: A miniature probe-type pCLE system with 60 μm focal depth (UltraMini O) and 1 % fluorescein dye was chosen for good visualization in mice model. The irregular microarchitecture images suspected to malignancy were obtained from the metastases. In the porcine model, observation of abdominal organs was feasible without any organ injury in the laparoscopic procedures. The dosage of 1 % fluorescein (3 ml/body) was appropriate in observing intra-abdominal organs, and each intra-abdominal organ was clearly observed with the same imaging quality we obtained in mice model., Conclusion: The pCLE was feasible and safe and potentially useful for the diagnosis of the peritoneal metastasis in in vivo animal models.

Background: For some types of cancer, postoperative complications can negatively influence survival, but the association between these complications and oncological outcomes is unclear for patients with esophageal cancer who receive preoperative treatments., Methods: Data were retrospectively analyzed for patients who underwent curative resection following preoperative chemotherapy for esophageal squamous cell carcinoma from 2001 to 2011. Clinicopathological parameters and cancer-specific survival (CSS) were compared between patients with and without severe postoperative complications, grade III or higher, using the Clavien-Dindo classification., Results: Of 255 patients identified, 104 (40.8 %) postoperatively developed severe complications. The most common complication was atelectasis in 61 (23.9 %), followed by pulmonary infection in 22 (8.6 %). Three-field lymphadenectomy, longer operation time, and more blood loss were significantly associated with a higher incidence of severe complications. Multivariate analysis of CSS revealed severe complications [hazard ratio (HR) = 1.642, 95 % confidence interval (95 % CI) 1.095-2.460, p = 0.016] as a significant prognostic factor along with pT stage [HR = 2.081, 95 % CI 1.351-3.266, p < 0.001] and pN stage [HR = 3.724, 95 % CI 2.111-7.126, p < 0.001], whereas postoperative serum C-reactive protein value was not statistically significant. Among all complications, severe pulmonary infection was the only independent prognostic factor [HR = 2.504, 95 % CI 1.308-4.427, p = 0.007]., Conclusions: The incidence of postoperative infectious complications, in particular pulmonary infection, is associated with unfavorable prognosis in patients with esophageal cancer undergoing preoperative chemotherapy.

Background: Pyruvate kinase M2 (PKM2) is a key glycolytic enzyme that regulates the Warburg effect and is necessary for tumor growth. However, its role in chemoresistance has not been fully elucidated., Methods: PKM2 expression was examined by immunohistochemistry in 205 tissue samples from thoracic esophageal squamous cell carcinoma patients who had undergone curative surgery (100 patients with surgery alone and 105 patients with preoperative chemotherapy). The relationship between PKM2 expression and clinicopathological factors, including chemotherapy response was examined. In vitro assays were performed to determine the mechanism of PKM2-related chemoresistance, using esophageal squamous cell carcinoma cell lines., Results: PKM2 expression significantly correlated with tumor cell differentiation, tumor depth, and tumor stage. Strong PKM2 expression significantly correlated with decreased survival rates and poor response to chemotherapy. In vitro assays showed that PKM2 inhibition significantly decreased cisplatin resistance and increased apoptosis. In siPKM2-transfected cells, pyruvate kinase activity paradoxically increased, followed by increased intracellular reactive oxygen species levels. The ratio of NADPH/NADP, which is an indicator of glucose influx into pentose phosphate pathway (PPP), significantly decreased in siPKM2-transfected cells upon cisplatin treatment compared with control cells., Conclusions: PKM2 expression is associated with esophageal squamous cell carcinoma chemoresistance. PKM2 inhibition can restore cisplatin sensitivity by inactivating PPP.

Background: Esophageal cancer occurs predominantly in elderly people. To date, there is no standardized treatment protocol for elderly patients with esophageal cancer. The aim of the present study was to assess the effect of old age (≥ 80 years) on treatment and outcome of esophageal cancer., Methods: We divided 722 patients who underwent esophagectomy between January 2000 and December 2012 into 4 age groups (<70, ≥ 70 to <75, ≥ 75 to <80, and ≥ 80 years) and analyzed the differences among the groups in treatment strategy (preoperative treatment and surgery) and short- and long-term outcome after esophagectomy., Results: Preoperative chemotherapy was significantly less frequently used for the octogenarians than the other groups. Three-field lymphadenectomy was less frequently used with increasing age. Advanced age tended to be associated with higher frequency of postoperative pulmonary and cardiovascular complications, but not with change in mortality rate, compared with younger patients. The overall survival rate was significantly lower in patients of the group ≥ 75 to <80 and group ≥ 80, compared with group<70 (p = 0.011, p = 0.002). Advanced age, low body mass index, postoperative complications, and pathological stage were independent and significant prognostic factors in elderly patients who underwent esophagectomy., Conclusions: Elderly patients aged 75 years and more, especially octogenarians, showed relatively poor prognosis compared with younger patients partly because they less often received neoadjuvant therapy. Aggressive treatment may be recommended for elderly patients after taking into careful consideration the overall physical condition.

Background: There is no consensus about the extent of lymphadenectomy for patients with esophageal squamous cell carcinoma at the cervicothoracic junction (CT-ESCC). The purpose of this study was to examine the pattern of lymph node spread in patients with CT-ESCC and the extent of lymphadenectomy that is necessary., Methods: We included 64 consecutive patients with CT-ESCC who underwent surgery. All patients were divided into two groups based on the location of the epicenter or anal edge of the primary tumor. Using the height of the epicenter, 27 and 37 patients were classified as having cervical-centered and thoracic-centered tumors, respectively; while, using the height of the anal edge, 38 and 26 patients had tumors that were cervical-localized and thoracic-invading, respectively., Results: In the patients with cervical-centered tumors, the incidences of metastasis and/or recurrences in the cervical paraesophageal, supraclavicular, and upper mediastinal nodes were 21.4-28.5 %. No patient had metastasis or recurrence in the middle and lower mediastinal and perigastric nodes. In patients with thoracic-centered tumors, the lymph node metastasis and/or recurrence spread to the cervical paraesophageal (41.7 %), supraclavicular (25 %), and upper mediastinal (55.6 %) nodes, as well as the middle (22.2 %) and lower mediastinal (8.3 %) and perigastric (19.4 %) nodes. There was no difference in the distribution and incidence of lymphatic spread between patients with the cervical-localized and thoracic-invading classifications., Conclusions: Our results indicate a cervical and upper mediastinal lymphadenectomy is better indicated for patients with cervical-centered CT-ESCC, whereas patients with thoracic-centered CT-ESCC should be treated with a three-field lymphadenectomy.

Background: The 7th edition of the Union for International Cancer Control-TNM (UICC-TNM) classification for esophageal carcinoma made considerable modifications to the definition of N-staging by the number of involved lymph nodes and the regional node boundary. There were few validations of the regional boundary. We evaluated the nodal status of this classification for esophageal squamous cell carcinoma (ESCC)., Methods: There were 665 patients reviewed who had ESCC and underwent esophagectomy between 1997 and 2012. We evaluated the impact of the location of lymph node metastasis on overall survival., Results: There were 414 patients (61.7 %) who had lymph node metastases. The overall 5-year survival rate was 54.7 %. There were no significant differences in survival among N2, N3, and M1 patients. Cox regression analysis revealed that common hepatic or splenic node involvements (P = 0.001), pT stage (P = 0.0002), and pN stage (P < 0.0001) were independent predictors of survival, but supraclavicular node involvement (P = 0.29) was not. We propose a modified nodal status that designates supraclavicular node as regional: m-N0 (5-year survival = 79 %; n = 251); m-N1 (5-year = 56 %; n = 212); m-N2 (5-year = 30 %; n = 114); m-N3 (5-year = 18 %; n = 52); m-M1 (5-year = 6.2 %; n = 36). This modified nodal staging predicts survival better than the current staging system., Conclusions: The modification of supraclavicular lymph node from nonregional to regional in the 7th UICC classification of ESCC may allow for better stratification of overall survival.