Comparison of hand-sewn and circular stapled esophagogastric anastomoses in the neck after esophagectomy for thoracic esophageal cancer: a propensity score-matched analysis.

Esophagectomy is a highly invasive surgical procedure; however, anastomotic leakage is one of the major surgical complications that should be prevented. Institutions have their own inherited or specialized anastomosis methods. The superior anastomosis procedure remains unknown despite the many studies to determine the optimal method. The present study enrolled 341 patients who underwent esophagectomy at Keio University Hospital, Tokyo, Japan, between January 2009 and January 2019. The anastomosis method was changed from circular stapled anastomosis to hand-sewn anastomosis in February 2014 to reduce the risk of anastomotic leakage. We retrospectively compared short-term results (anastomotic leakage and stricture) between hand-sewn and circular stapled anastomoses. Analysis of heterogeneity after propensity score matching between the 107 patients in the hand-sewn anastomosis group and 107 patients in the circular stapled anastomosis group revealed almost equal distributions. The incidence rate of anastomotic leakage was significantly lower in the hand-sewn anastomosis group than in the circular stapled anastomosis group (9 vs. 20%, hazard ratio: 2.521; 95% confidence interval: 1.112-5.716; P = 0.027). No significant difference was found in the incidence of anastomotic stricture (16 vs. 18%, P = 0.844). Furthermore, no significant difference was found in the incidence of anastomotic leakage in any of the tumor locations between the two anastomosis procedures. For esophagogastric anastomosis in the neck after esophagectomy, hand-sewn anastomosis is superior to circular stapled anastomosis with regard to reducing the risk of anastomotic leakage.

Exploratory prospective study of the influence of radical esophagectomy on perioperative physical activity in patients with thoracic esophageal cancer.

Sarcopenia, which involves two important aspects, namely skeletal muscle loss and decreased physical function, was suggested as a poor prognostic factor in esophageal cancer surgery. The purpose of this study was to clarify the perioperative change in daily physical activity and propose effective preventive strategies. We prospectively enrolled patients with esophageal cancer who were scheduled to undergo radical esophagectomy. Their daily physical activities were recorded using an accelerometer before surgery, immediately after discharge, and 6 months after surgery. The relationships of physical activity level and the perioperative factors, especially skeletal muscle change, with the risk factors of low daily activity level were investigated. The data of 20/28 enrolled patients were analyzed. The mean activity level of the 20 patients decreased after discharge and subsequently recovered on postoperative month 6. The percentage of activity levels >1.5 metabolic equivalents/day after discharge significantly correlated to the change rate in total muscle cross-sectional area from baseline to POM 6 (r = 0.452, P = 0.045). In a stepwise multiple regression analysis, age, neoadjuvant chemotherapy, and anastomotic leakage were identified as negative associated factors of activity time at >1.5 metabolic equivalents at postoperative month 6. Activity level immediately after discharge was significantly associated with skeletal muscle loss at postoperative month 6 in patients with esophageal cancer who underwent esophagectomy. Elderly patients and patients who received neoadjuvant chemotherapy and had an anastomotic leakage might require intensive prevention. Prospective interventions aimed at increasing daily activity can prevent sarcopenia.

Preoperative maximum phonation time as a predictor of pneumonia in patients undergoing esophagectomy.

PURPOSE: Esophagectomy is a highly invasive procedure, associated with several postoperative complications including pneumonia, anastomotic leakage, and sepsis, which may result in multiorgan failure. Pneumonia is considered a major predictor of poor long-term prognosis, so its prevention is important for patients undergoing surgery for esophageal cancer. METHODS: The subjects of this study were 137 patients who underwent esophagectomy at Keio University Hospital, Tokyo, Japan, between January, 2012 and December, 2016. Patients who underwent R0 or R1 resection or esophagectomy with organ excision were included. Patients who underwent salvage surgery or resection of recurrent laryngeal nerve, and those with preoperative recurrent laryngeal nerve palsy, were excluded. We investigated the effect of the maximum phonation time on the development of postoperative pneumonia. RESULTS: Pneumonia developed more frequently in patients with a long operative time, clinically left recurrent nerve lymph node metastasis, and a short preoperative maximum phonation time (p = 0.074, 0.046, and 0.080, respectively). Pneumonia was also more common in men with an abnormal maximum phonation time (p = 0.010). CONCLUSIONS: The maximum phonation time is a significant predictor of postoperative pneumonia after esophagectomy in men.

Relationship Between Early Postoperative Change in Total Psoas Muscle Area and Long-term Prognosis in Esophagectomy for Patients with Esophageal Cancer.

PURPOSE: Postoperative sarcopenia following esophagectomy for esophageal cancer has become a severe problem due to the increasing number of elderly patients undergoing surgery. This study aimed to clarify the relationship between early postoperative skeletal muscle change and cancer prognosis, and propose effective interventions to prevent sarcopenia. METHODS: This study retrospectively analyzed 152 patients who underwent esophagectomy for esophageal cancer. Total psoas muscle area (TPA) was measured before surgery as baseline and on postoperative day 7 (± 2). The effect of early postoperative skeletal muscle loss on 5-year survival was investigated. Moreover, 5-year survival in patients with postoperative complications and a high inflammatory status, which were previously reported as poor prognostic factors of esophageal cancer, was also investigated. RESULTS: Among the 152 patients, 52 (34.2%) showed a decrease in TPA, while 100 (65.8%) maintained their TPA. The TPA decreasing group exhibited poor 5-year overall survival (OS) (p = 0.003) and 5-year recurrence-free survival (RFS) (p < 0.001). The TPA decreasing group also showed a poor 5-year OS in patients who developed severe postoperative complications (p = 0.015). Multivariate analyses showed that decreased TPA was found to be independently associated with OS (p = 0.017) as well as RFS (p = 0.002). CONCLUSIONS: Our findings suggested a relationship between decreased TPA within 1 week after esophagectomy and long-term prognosis among patients with esophageal cancer. If TPA can be maintained, the prognosis was better even in cases with serious complications.

Usefulness of Neutrophil to Lymphocyte Ratio at Recurrence for Predicting Long-Term Outcomes in Patients with Recurrent Esophageal Squamous Cell Carcinoma.

BACKGROUND: Although radical esophagectomy with multifield lymph node dissection is a promising treatment to achieve long-term survival for resectable esophageal cancer, survival after postoperative recurrence remains poor. To select the optimal treatment for patients with recurrent esophageal cancer, simple, objective indicators for predicting of long-term outcomes are needed. PATIENTS AND METHODS: We conducted a single-institution, retrospective cohort study between 2004 and 2019, wherein 586 patients underwent transthoracic esophagectomy for primary esophageal squamous cell carcinoma. Of these, 133 patients with postoperative recurrence were included in this analysis. Several predictors of survival after recurrence were investigated. RESULTS: Among all patients, the 1- and 3-year survival rates after recurrence were 48.0% and 23.1%, respectively. On multivariate analysis, the neutrophil to lymphocyte ratio (NLR) at recurrence was identified as a significant predictor of death after recurrence (hazard ratio 1.061; 95% confidence interval 1.002-1.125; p = 0.043). Time-dependent receiver operating characteristics curves showed that the area under the curve value of the NLR at recurrence was superior to the modified Glasgow Prognostic Score at recurrence in all terms. To simulate the clinical decision process, we set the cut-off NLR at recurrence for survival using survival classification and regression tree (CART) and defined the optimal cut-off value as 3.374. CONCLUSIONS: NLR at recurrence was a significant indicator of survival after recurrence in patients with recurrent esophageal cancer. CART analysis was used to determine the optimal cut-off value for the prediction of survival, allowing the NLR to be used clinically to facilitate decision making.

Prognostic Significance of the Number and Extent of Metastatic Lymph Nodes in Patients with Esophageal Cancer: Comparison of the Union for International Cancer Control 8th Edition and Japan Esophageal Society Japanese Classification of Esophageal Cancer 11th Edition Classifications for Esophageal Cancer.

BACKGROUND: The tumor, node, metastasis staging system of the Union for International Cancer Control (UICC) has been used worldwide for esophageal cancer, and, in Japan, the Japan Esophageal Society Japanese Classification of Esophageal Cancer (JES) has also been used; however, there is a big difference between the two classifications with regard to node staging. We hypothesized that these two node staging systems may lead to different outcome predictions in terms of tumor location. METHODS: This study enrolled 409 patients who underwent esophagectomy at Keio University Hospital, Tokyo, Japan, between January 2005 and December 2017. We included those who underwent R0 or R1 resection or esophagectomy with additional organ excision, and excluded those who underwent salvage surgery. Thereafter, we investigated how the number or spread of metastatic lymph nodes affected the prognosis. RESULTS: For all 409 patients, the 5-year overall survival rate was 64.1% and the 5-year recurrence-free survival rate was 58.4%. The concordance indices were 0.756 for UICC 8th edition pathological node staging and 0.732 for JES 11th edition pathological node staging (p = 0.06). Based on tumor location, the difference in the concordance indices between these two classifications was greatest for lower thoracic esophageal tumors (p = 0.02). CONCLUSIONS: For all patients, the UICC 8th edition node staging system tended to reflect survival more precisely than that of the JES 11th edition. For lower thoracic esophageal tumors in particular, the former node staging system could be more useful.

Validation Study of Fibrinogen and Albumin Score in Esophageal Cancer Patients Who Underwent Esophagectomy: Multicenter Prospective Cohort Study.

PURPOSE: To arrange multidisciplinary treatment for esophageal cancer, a simple and accurate predictive marker for prognosis is required. The current multicenter prospective study aims to validate the prognostic significance of fibrinogen and albumin score (FA score) for esophageal cancer patients. PATIENTS AND METHODS: Patients who were planned to undergo surgical resection for esophageal cancer at four participating institutions were enrolled in this study. Patient background, clinicopathological factors, and blood concentration of plasma fibrinogen and albumin were collected. Patients with elevated fibrinogen and decreased albumin levels were allocated a score of 2; those with only one of these abnormalities were allocated a score of 1; and those with neither of these abnormalities were allocated a score of 0. Recurrence-free survival (RFS) and overall survival (OS) were evaluated as a primary endpoint. RESULTS: From four participating institutions, 133 patients were registered for the current analysis. The distribution of FA score of 0/1/2 was 84 (63%)/34 (26%)/15 (11%), respectively. In the analysis of primary endpoint, the preoperative FA score significantly classified RFS (FA score 1/2: HR 2.546, p = 0.013/6.989, p < 0.001) and OS (FA score 1/2: HR 2.756, p = 0.010/6.970, p < 0.001). We further evaluated the prognostic significance of FA score under stratification by pStage. As a result, with increasing FA score, RFS and OS were significantly worse in both pStage 0-I and II-IV groups. CONCLUSIONS: The prognostic impact of preoperative FA score was confirmed for esophageal cancer patients in the current multicenter prospective trial. FA score can be considered to predict postoperative survival and rearrange the treatment strategy before esophagectomy.

Lymphocyte-to-C-Reactive Protein Ratio as a Novel Marker for Predicting Oncological Outcomes in Patients with Esophageal Cancer.

BACKGROUND: Esophageal cancer has a poor prognosis because of its rapid progression and early and extensive lymph node metastasis. Simple, objective indicators for predicting long-term outcomes are needed to select optimal perioperative treatment and appropriate follow-up for patients with esophageal cancer. The aim of this study is to investigate the relationship between the lymphocyte-to-C-reactive protein ratio (LCR) and the survival of patients with esophageal cancer, by performing time-dependent receiver operating characteristic (ROC) curve analysis. The results were compared to those of traditional inflammation-based markers. METHODS: This study enrolled 495 patients who underwent thoracic esophagectomy for esophageal cancer as the primary treatment between 2000 and 2019 in our department. We investigated the predictability of the LCR for oncological outcomes compared to that of other traditional inflammatory markers. RESULTS: The 3-year overall survival (OS) and recurrence-free survival (RFS) were 72.6% and 57.5%, respectively. Low LCR was significantly associated with higher cancer stage, included depth of invasion (p < 0.001), lymph node metastasis (p < 0.001) and cStage (p < 0.001). The LCR had the highest AUC value (0.675) for predicting OS compared to the other examined inflammatory markers. In multivariate analysis, the LCR (optimal cutoff threshold = 19,000) was identified as a significant predictor of death (hazard ratio, 2.24; 95% confidence interval [CI], 1.61-3.12; p < 0.001) and recurrence (hazard ratio, 1.97; 95%CI, 1.48-2.63; p < 0.001). CONCLUSION: The LCR is novel indicator for oncological outcomes for patients with esophageal cancer and may assist to facilitate personalized multidisciplinary treatments.

The Results of Sentinel Node Mapping for Patients with Clinically Early Staged Gastric Cancer Diagnosed with pT2/deeper Tumors.

BACKGROUND: Sentinel node (SN) mapping based on the SN concept has been applied to early gastric cancer. However, it is still controversial whether or not the oncological safety is ensured in case pathological stage was advanced in these patients. The aim of this study was to investigate the validity of SN mapping in patients with clinically early staged gastric cancer diagnosed with pT2/deeper tumors. METHODS: We retrospectively analyzed 40 patients with a diagnosis of cT1N0 or cT2N0 single-lesion gastric cancer who were shown to have pT2 or deeper tumors after gastrectomy with SN mapping. We adopted a dual-tracer method using a radioactive colloid and blue dye to detect SNs. The diagnostic accuracy and distribution of SNs at each tumor site were analyzed. RESULTS: Of the 40 patients, 24 (60%) were postoperatively diagnosed as pT2, and 16 (40%) as pT3 or T4. SNs were detected in all patients. The false negative rate was 9% (1/11), and in that patient, the non-SN metastasis was observed within the SN basin. Diagnostic accuracy was 98% (39/40). Overall distribution of SNs was similar to that for patients with early gastric cancer. No significant differences in overall and recurrence-free survival were observed between the patients who underwent standard gastrectomy and those who underwent function-preserving gastrectomy, based on the results of SN mapping. CONCLUSIONS: Our results confirmed validity of SN mapping for patients with clinically early staged gastric cancer diagnosed with pT2/deeper tumors after gastrectomy. Closed surveillance without additional surgical treatment is an option for these patients.

Association of preoperative sarcopenia with postoperative dysphagia in patients with thoracic esophageal cancer.

BACKGROUND: The purpose of the current study was to clarify the relationship between clinical features of dysphagia after esophagectomy and preoperative sarcopenia. METHODS: A total of 187 cases were included in the current study. The psoas cross-sectional area on pre-treatment computed tomography was measured in thoracic esophageal cancer patients who underwent curative resection. The psoas muscle index (PMI) cut-off levels for sarcopenia were 6.36 cm2/m2 for men and 3.92 cm2/m2 for women. Swallowing function was evaluated using videofluoroscopic swallowing study (VFSS) and fiberoptic endoscopic evaluation of swallowing (FEES) at postoperative days 7-15, and classified according to the food intake level scale (FILS). Perioperative swallowing rehabilitation was performed in all cases. RESULTS: In the 187 included patients, the median PMI was 5.42 cm2/m2 for men and 3.43 cm2/m2 for women, and 133 cases (71%) met the sarcopenia criteria. The FILS <4 (no oral intake) was 15% in the non-sarcopenia group, and 38% in the sarcopenia group (P = 0.003). There was no significant difference in the incidence of postoperative complications, including pneumonia and re-admission due to pneumonia, between the two groups. Preoperative sarcopenia and recurrent laryngeal nerve palsy were be independent risk factors for postoperative dysphagia. CONCLUSIONS: Sarcopenic patients with esophageal cancer develop postoperative dysphagia more often than non-sarcopenic patients. Prehabilitation and nutritional support for patients with preoperative sarcopenia could play an important role to mitigate postoperative dysphagia.

Clinical usefulness of sputum culture on the first postoperative day to predict early postoperative pneumonia after esophagectomy for esophageal cancer.

BACKGROUND: Postoperative pneumonia is a serious prognostic problem that can appear after esophagectomy in patients with esophageal cancer. The past reports have considered the usefulness of perioperative culture examinations for predicting postoperative pneumonia; however, the direct relationship between these examinations and postoperative complications remains unclear. METHODS: This study retrospectively analyzed esophageal cancer patients who underwent esophagectomy followed by sputum culture on the first postoperative day. The bacterial species that frequently cause hospital-acquired pneumonia were chosen as the target species in this study. The relationship between culture examination and postoperative pneumonia within one week (7 days) after esophagectomy was investigated. RESULTS: Sputum cultures on the first postoperative day were investigated in 238 patients who underwent esophagectomy for esophageal cancer. Forty-one patients developed pneumonia within one week after surgery. The target bacterial species were detected in 26 of 238 sputum cultures (10.9%). In the univariate analysis, a Brinkman index, detection of target bacterial species, detection of Gram-positive cocci, and Gram-negative rods were significantly associated with postoperative pneumonia. In the three independent multivariate analyses, the target bacterial species, Gram-positive cocci, and Gram-negative rods (p = 0.001, 0.042, and < 0.001) were individually identified as independent risk factors of postoperative pneumonia in addition to a Brinkman index. CONCLUSIONS: Detection of target bacterial species by sputum culture on the first postoperative day after esophagectomy was an independent risk factor of postoperative pneumonia within 7 days after surgery. Prospective studies for the prevention of early postoperative pneumonia using sputum culture on the first postoperative day can be considered.

Clinical outcomes of laparoscopic and endoscopic cooperative surgery for submucosal tumors on the esophagogastric junction: a retrospective single-center analysis.

BACKGROUND: Laparoscopic and endoscopic cooperative surgery (LECS) technique for gastric submucosal tumor (SMT) has developed, but treatment of SMT on the esophagogastric junction (EGJ) remains technically difficult because excessive resection may result in postoperative transformation of the EGJ and cause stenosis, and intervention to lower esophageal sphincter may result in gastroesophageal reflux. The study aim was to evaluate the feasibility and safety of LECS for SMT on the EGJ. METHODS: Between September 2012 and December 2018, LECS was performed for 21 patients with SMTs on the EGJ. Fundoplication was performed after LECS according to the intraoperative findings for each case. The patients' backgrounds, operative outcomes, and follow-up data, including endoscopic findings of gastroesophageal reflux disease (GERD) and proton pomp inhibitor (PPI) use, were reviewed. RESULTS: In all 21 cases, LECS was completed with a mean operation time of 225 min, and a mean blood loss of 8.8 mL. All patients were alive without recurrence within the mean follow-up period of 30.5 months. Both GERD and PPI use tended to be less frequent when fundoplication was performed, although these differences were not statistically significant. (7.7% vs. 37.5%; P = 0.091, 23.1% vs. 50.0%; P = 0.204, respectively). CONCLUSIONS: We demonstrated the feasibility and safety of LECS for SMTs even on the EGJ. Fundoplication after LECS may be an approach for the prevention of postoperative reflux esophagitis. Future research is warranted to validate the efficacy of the addition of fundoplication.

Clinical outcomes of non-exposed endoscopic wall-inversion surgery for gastric submucosal tumors: long-term follow-up and functional results.

BACKGROUND AND AIMS: To avoid the risk of iatrogenic dissemination during procedures, we have developed a combined laparoscopic and endoscopic surgery with a nonexposure technique for resection of gastric tumors. The study aim was to evaluate the feasibility and safety of non-exposed endoscopic wall-inversion surgery (NEWS) for gastric submucosal tumors (SMTs). METHODS: Between August 2013 and February 2018, NEWS was performed for 42 patients with gastric SMTs ≤ 3 cm in diameter at our institution. We retrospectively investigated the patients' backgrounds, operative and perioperative outcomes, tumor pathological characteristics, and follow-up data. RESULTS: All tumors were resected with negative margins by NEWS. The median operation time was 198 min, and the median estimated blood loss was 5.0 mL. Adverse events occurred in one patient with pneumonia. All patients were alive without recurrence within the median follow-up period of 29.2 months. The average body weight loss rate was 0.3 ± 4.0%. No food residue was observed at endoscopic follow-up. CONCLUSIONS: On the basis of slight body weight loss and the absence of food residue observed in the postoperative endoscopy, NEWS appeared to be safe and feasible for gastric SMTs and to preserve function of the remnant stomach.

Utility of the one-step nucleic acid amplification assay in sentinel node mapping for early gastric cancer patients.

BACKGROUND: To safely perform minimized gastrectomy based on sentinel node (SN) concept for early gastric cancer patients, intraoperative diagnostic accuracy is indispensable. This study aimed to evaluate the clinical utility of the one-step nucleic acid amplification (OSNA) assay in the intraoperative diagnosis of SN metastasis in early gastric cancer patients compared with that of histopathological examination. METHODS: We conducted a prospective study using the OSNA assay for 43 patients with cT1N0M0 gastric cancer undergoing gastrectomy with SN mapping. All the SNs and selected non-SNs were examined by routine histopathological diagnosis, and the OSNA assay. RESULTS: We performed permanent histopathology (PH) in 1732 lymph nodes (LNs) (286 SNs and 1446 non-SNs) obtained from 43 patients. We also evaluated 439 LNs (286 SNs and 153 non-SNs) with the OSNA assay in addition to PH. Intraoperative histopathology (IH) was performed in 214 LNs (213 SNs and 1 non-SN). PH revealed LN metastasis in 6 patients (14%), all of whom showed positive SNs by PH. The diagnostic accuracy to predict the LN status based on the SN concept by histological examination was 100%. The concordance rate between the OSNA assay and the PH and IH were 0.970 and 0.981 respectively. Discordant results between PH and OSNA assay were observed in 13 LNs. The sensitivity and specificity of the OSNA assay compared with those of PH were 0.636, and 0.988, and compared with those of IH were 0.800, and 0.995. CONCLUSION: Our results suggest that the OSNA assay is a useful and convenient tool for the intraoperative detection of SN metastasis in early gastric cancer patients.

Assessment of lymphatic flow based on the sentinel node concept in early gastric adenocarcinoma that satisfies expanded endoscopic resection criteria.

BACKGROUND: Even though indications for endoscopic resection (ER) in early gastric cancer are determined based on the potential risk of lymph node metastasis, the criteria for ER remain controversial. Sentinel node (SN) mapping for early gastric cancer can help determine regional lymphatic flow patterns. The aim of this study was to assess lymphatic flow according to the SN concept in patients with early gastric cancer, especially those who satisfy the expanded criteria for ER. METHODS: We retrospectively enrolled 301 patients diagnosed with pT1 adenocarcinoma who had undergone gastrectomy with SN mapping and had no lymphovascular invasion. Patients were categorized into six groups based on oncological assessment. We analyzed lymphatic flow, including the number of identified SN and SN basin, and the rate of SN metastasis in each group. RESULTS: Of the 301 patients, 128 (42.5%) met the criteria for ER, with 18 in the absolute group and 110 in the expanded group; 173 (57.5%) were assigned to the surgical group. SN metastasis rate tended to be higher in surgical group patients than in ER criteria patients. In the expanded criteria group, the sub-group of patients with intramucosal, undifferentiated adenocarcinoma measuring 20 mm or less had a significantly greater number of identified SNs (p = 0.013) and SN basins (p = 0.032). Furthermore, SN metastasis was observed only in this group. CONCLUSIONS: Patients with intramucosal, nonulcerated, undifferentiated adenocarcinoma measuring 20 mm or less could develop a lymphatic network. For these patients, careful follow-up is required after ER.

Effectiveness of active nasal surveillance culture for Methicillin-resistant Staphylococcus aureus in patients undergoing colorectal surgery.

OBJECTIVE: The aim of this study was to clarify the role of Methicillin-resistant Staphylococcus aureus (MRSA) carriers in the development of surgical site infection (SSI) after colorectal surgery. SUMMARY BACKGROUND DATA: MRSA is commonly implicated in hospital-acquired infections. Active surveillance culture (ASC) using the nasal swab test is useful to detect MRSA in surgical patients. We hypothesized that MRSA carriers would be more susceptible to SSI after colorectal surgery METHODS: Patients who underwent ASC between 2010 and 2013 were included in this study. The incidence of SSI was compared between MRSA carriers and non-carriers using the chi-square test. The odds ratio for SSI was computed using logistic regression analyses. RESULTS: Among 355 patients, 12 (3.4%) were identified as MRSA carriers and 343 as non-carriers. Of all the patients, 65 patients (18.3%) developed an SSI. Of these, 6 cases were in MRSA carriers and 59 cases were in non-carriers (p < 0.01). This meant that half of the 12 MRSA carriers developed an SSI, compared with only 17.2% of non-carriers (59 cases out of 343 patients). Therefore, MRSA carriers had a significantly higher risk of SSI (adjusted odds ratio = 4.77 [1.37 to 16.6], p = 0.01). CONCLUSIONS: Detection of MRSA via ASC is significantly associated with the development of SSI after colorectal surgery. These findings indicate that ASC for MRSA is useful to predict an SSI.

Determination of the optimal surgical procedure by identifying risk factors for pneumonia after transthoracic esophagectomy.

BACKGROUND: Esophagectomy is associated with a high risk of postoperative complications, and the respiratory complications are the most common. Therefore, stratification of patients based on preoperative risk factors is essential. This study aimed to identify the risk of postoperative pneumonia (POP) based on the preoperative factors and determine the optimal perioperative surgical management strategy. METHODS: This retrospective study involved 207 patients who underwent esophagectomy. The patients were divided into two groups, namely, with POP and without POP. To identify the risk factors for POP, the pre- and perioperative characteristics were analyzed. A receiver operating characteristics curve was used to determine a cutoff value of 2.40 L for the forced expiratory volume in 1 s (FEV1.0) and the cohort was divided into a high- and low-FEV1.0 group. A second analysis was then performed to determine the optimal surgical management for patients at a high risk for POP. RESULTS: POP occurred in 45 (21.7%) patients. A multiple logistic regression analysis showed that FEV1.0 was significantly lower in the POP (+) group (P = 0.020); thus, a low FEV1.0 was found to be a risk factor for POP. Multiple logistic regression analysis showed that open thoracotomy was a significant risk factor for POP in low FEV1.0 patients (P = 0.013). CONCLUSIONS: A low FEV1.0 and an open thoracotomy are risk factors for POP. Therefore, patients with low FEV1.0 should be managed carefully and video-assisted thoracic surgery should be considered.

The perioperative presepsin as an accurate diagnostic marker of postoperative infectious complications after esophagectomy: a prospective cohort study.

BACKGROUND: Presepsin is suggested to be an accurate sepsis diagnostic biomarker, playing an important role in distinguishing infection from no-infection status. However, to date, there is no study determining presepsin's role in diagnosing post-esophagectomy infectious complications. METHODS: Thirty patients who underwent esophagectomy for esophageal carcinoma were included in this prospective observational study. We investigated preoperative presepsin levels' changes and evaluated the relationship between infectious complications and presepsin levels. Moreover, we analyzed the classification and regression tree (CART) to determine presepsin's optimal cutoff values for discriminating infectious complications. RESULTS: For 10 patients with infectious complications, median presepsin levels were 168, 337, 303, 271, 314, 978, and 752 pg/ml, pre- and immediately post-surgery, and 1, 2, 3, 5, 7 days post-surgery, respectively. Presepsin levels were significantly higher in the infectious complication group exclusively from preoperation to POD 7 (p = 0.048). Furthermore, area under the curve's value of presepsin on POD 5 and 7 was higher than the other three biomarkers included for discriminating infectious complications (i.e., procalcitonin, leukocyte, and C-reacted protein). We set an optimal cutoff value for presepsin calculated by CART. Specifically, on POD 5, the cutoff was 888 pg/ml with a sensitivity of 60% and a specificity of 90%, and on POD 7, the cutoff was 668 pg/ml with a sensitivity of 60% and a specificity of 85%. CONCLUSIONS: Presepsin levels on POD 5 and 7 after esophagectomy are a valuable indicator of infectious complication's detection vs. leukocyte, C-reacted protein, and procalcitonin.

Clinical significance of preoperative serum concentrations of interleukin-6 as a prognostic marker in patients with esophageal cancer.

BACKGROUND: Although the clinical outcome of esophageal cancer has recently improved, the relapse rate remains high for all disease stages. At present, there is no diagnostic method to predict the long-term outcome for esophageal cancer. In this study, we evaluated serum preoperative proinflammatory cytokine levels and investigated the correlation between preoperative interleukin-6 (IL-6) and IL-8 levels and survival of patients with esophageal cancer. METHODS: Between 2008 and 2015, we evaluated preoperative serum cytokine levels in 122 patients who underwent esophagectomy for esophageal cancer. Serum IL-6 and IL-8 levels were measured by enzyme-linked immunosorbent assays. We investigated the relationship between serum cytokine levels and the response to chemotherapy and survival. RESULTS: The preoperative IL-6 levels were significantly associated with shorter recurrence-free survival (RFS, p = 0.001) and overall survival (OS, p = 0.001) after esophagectomy. Higher IL-8 levels were significantly associated with RFS (p = 0.018). In the multivariate analysis, age, preoperative chemotherapy, lymph node metastasis, serum C-reactive protein (CRP) levels and serum IL-6 levels (hazard ratio (HR), 2.888; p = 0.049) were significantly independent prognostic factors of RFS. Additionally, age, pathological stage, and serum IL-6 levels (HR, 3.247; p = 0.027) were shown to be significantly independent prognostic factors of OS. Serum IL-6 levels were significantly higher in the non-responder group (pathological response pGrade0 and pGrade1) after neoadjuvant therapy. CONCLUSIONS: High preoperative serum IL-6 levels are associated with a poor response to chemotherapy or chemoradiotherapy and poor prognosis after esophagectomy. Preoperative serum IL-6 levels may be a useful independent prognostic marker for esophageal cancer patients.

THUMP domain containing 2 protein possibly induces resistance to cisplatin and 5-fluorouracil in in vitro human esophageal squamous cell carcinoma cells as revealed by transposon activation mutagenesis.

BACKGROUND: Although chemotherapy is a core treatment for esophageal cancer, some patients develop drug resistance. Gene screening with transposons (i.e. mobile genetic elements) is a novel procedure for identifying chemotherapy-resistant genes. Transposon insertion can randomly affect nearby gene expression. By identifying the affected genes, candidate genes can be found. The present study aimed to identify cisplatin (CDDP)/5-fluorouracil (5-FU)-resistant genes in in vitro human esophageal squamous cell carcinoma with transposons. METHODS: After establishing transposon-tagged cells, we obtained CDDP/5-FU-resistant colonies. A polymerase chain reaction and sequencing were used to identify the transposon inserted site and candidate CDDP/5-FU resistant genes. Focusing on one candidate gene, we confirmed CDDP/5-FU resistance by comparing the IC50 between drug-resistant and wild-type cells. Furthermore, we investigated gene expression by a real-time polymerase chain reaction. Finally, we mediated the candidate gene level with small interfering RNA to confirm the resistance. RESULTS: Thirty-nine candidate genes for CDDP/5-FU resistance were identified. Nineteen were for CDDP resistance and 27 were for 5-FU resistance. Seven genes, THUMP domain-containing protein 2 (THUMPD2), nuclear factor interleukin-3-regulated protein (NFIL3), tyrosine-protein kinase transmembrane receptor 2 (ROR2), C-X-C chemokine receptor type 4 (CXCR4), thrombospondin type-1 domain-containing protein 2 (THSD7B) alpha-parvin (PARVA) and TEA domain transcription factor 1 (TEAD1), were detected as candidate genes in both colonies. Regarding THUMPD2, its expression was downregulated and knocking down THUMPD2 suggested drug resistance in both drugs. CONCLUSIONS: Thirty-nine candidate genes were identified with transposons. The downregulation of THUMPD2 was suggested to play a role in multidrug resistance in in vitro esophageal squamous cell carcinoma.