X-ray irradiation negatively affects immune responses in the lymphatic network.

Immune checkpoint inhibitor therapy has been attracting attention as a new cancer treatment and is likely to be widely used in combination with radiotherapy. Therefore, examination of the effects of X-ray irradiation on sentinel lymph nodes and lymphatic vessels, which are involved in antigen presentation, is important for therapy. The hindlimbs of mice were irradiated with X-rays (total radiation doses: 2, 10, and 30 Gy), and X-ray computed tomography (CT) imaging was performed using 15-nm or 2-nm gold nanoparticles (AuNPs) as contrast agents on days 7, 14, and 28 after irradiation to evaluate the diameter of the collecting lymph vessels and lymph flow within the irradiated area. X-ray CT imaging data using 15-nm AuNPs on day 28 after irradiation showed that the diameter of the collecting lymph vessels was significantly larger in all irradiated groups compared to the control group (p ≤ 0.01). CT imaging with 2-nm AuNPs showed that lymphatic drainage was significantly reduced in the lymph nodes irradiated with 10 Gy and 30 Gy compared to the lymph nodes irradiated with 2 Gy (p ≤ 0.05). Additionally, immunohistochemical analyses were conducted to evaluate the area density and morphology of high endothelial venules (HEVs) in the lymph nodes, which are important vessels for naive T cells to enter the lymph nodes. The expression level of MECA-79, which specifically localized to HEVs, was significantly decreased in the 10 Gy and 30 Gy irradiation groups compared to the control group (p ≤ 0.05). There was a significant decrease in normal HEV morphology (p ≤ 0.05) and a significant increase in abnormal HEV morphology (p ≤ 0.05) in all irradiated groups. These results also showed that X-ray irradiation induced a time- and radiation dose-dependent increase in the diameter of the collecting lymph vessels, stagnation of intralymphatic lymph flow, and a reduction in the area density of HEVs and their abnormal morphology, demonstrating that X-ray irradiation affected the immune responses. Therefore, these findings suggest that X-ray irradiation to lymph nodes may impair the opportunity for antigen presentation in the lymph nodes, which is the key to cancer immunity, and that for this reason, it is important to carefully plan irradiation of sentinel lymph nodes and develop treatment strategies according to future treatment options.

Prognostic impact of carcinoembryonic antigen in 1822 surgically treated esophageal squamous cell carcinoma: multi-institutional study of the Japan Esophageal Society.

BACKGROUND: Previous studies have evaluated the clinicopathological significance of carcinoembryonic antigen (CEA) of esophageal cancer in relatively small numbers of patients. Therefore, this study aimed to clarify the prognostic significance of CEA in 1822 patients with esophageal squamous cell carcinoma (SCC). METHODS: Based on the Japanese Esophageal Society nationwide multi-institutional retrospective study, a total of 1,748 surgically treated ESCC from 15 hospitals were enrolled to evaluate prognostic impact of preoperative CEA values. Among them, 605 patients were categorized to up-front surgery group, and 1,217 patients were categorized to neoadjuvant therapy group. The CEA threshold for positivity was 3.7 ng/ml. The clinicopathological and prognostic impact of CEA was evaluated by univariate and multivariate analysis in each treatment modality groups. RESULTS: In total, the CEA positive rate was 25.8% (470/1822). CEA-positive status was significantly associated with distant metastasis (P = 0.004) but not associated with other factors. CEA-positive status was associated with poor overall survival (P < 0.001) in univariate analysis as well as multivariate analysis (P = 0.003). CONCLUSIONS: CEA was an independent prognostic determinant of overall survival in esophageal SCC. Based on the subgroup analysis, regardless of the treatment modality, patients with high pretreatment CEA showed poor overall survival.

Maximum standardized uptake value change rate before and after neoadjuvant chemotherapy can predict early recurrence in patients with locally advanced esophageal cancer: a multi-institutional cohort study of 220 patients in Japan.

BACKGROUND: Neoadjuvant chemotherapy (NAC) followed by esophagectomy can improve the prognosis of locally advanced esophageal cancer (LAEC). However, LAEC reportedly recurred in 17-21% of patients within 6 months post surgery. Thus, current treatment strategies may be inadequate for LAECs with poor prognosis. Preoperative identification of patients with poor prognosis might aid in modification of treatment strategies. This study aimed to evaluate the usefulness of the maximum standardized uptake value change rate (ΔSUVmax) in predicting treatment effects on the primary lesion, prognosis, and LAEC recurrence. METHODS: This study involved 220 esophageal cancer patients who underwent esophagectomy after NAC at three facilities in Japan. The optimal cut-off point for ΔSUVmax in predicting tumor regression grade (TRG) was calculated and used to assess the correlation between ΔSUVmax and postoperative survival. RESULTS: The optimal cut-off point for ΔSUVmax was 0.5. The 5-year overall survival rate in patients with ΔSUVmax ≥ 0.5 was significantly higher than that in patients with ΔSUVmax < 0.5 (71.5% vs. 50.5%, P = 0.001). Multivariate analysis identified ΔSUVmax (hazards ratio, 0.496; P = 0.004) as an independent prognostic factor. Among 199 patients evaluated for recurrence, 24 (12.1%) showed recurrence within 6 months post surgery. Univariate analysis revealed ΔSUVmax as the only predictor for early recurrence (odds ratio, 0.222; P = 0.004). CONCLUSION: ΔSUVmax before and after NAC is clinically useful as it could help predict TRG, survival outcome, and early recurrence within 6 months post esophagectomy and is easily obtainable in general clinical practice. We believe that it may also help determine suitable treatment strategies for LAEC.

Correlation between TXNRD1/HO-1 expression and response to neoadjuvant chemoradiation therapy in patients with esophageal squamous cell carcinoma.

BACKGROUND: Thioredoxin reductase 1 (TXNRD1) and heme oxygenase-1 (HO-1) are both involved in the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway and play key roles in antioxidant responses. In patients with esophageal squamous cell carcinoma (ESCC), the correlation between the expression of these two proteins and the therapeutic response to neoadjuvant chemoradiation therapy (NACRT), as well as the difference in their expression after chemoradiotherapy, remains unknown. METHODS: Proteins involved in the Nrf2 pathway were immunolocalized in carcinoma cells in ESCC patients on NACRT with 5-fluorouracil and cisplatin, followed by esophagectomy. The 8-hydroxydeoxyguanosine (8-OHdG) levels were used to quantify reactive oxygen species. The changes in immunoreactivity before and after NACRT (Δ) were assessed. RESULTS: Tumor reduction following NACRT was significantly attenuated in pre-therapeutic biopsy specimens associated with high HO-1 status. TXNRD1Δ, HO-1Δ, and 8-OHdGΔ were significantly different in the ineffective and effective groups. The overall survival was significantly lower in high Nrf2 and TXNRD1 groups. In addition, high TXNRD1 expression was an independent prognostic factor in the multivariate analysis of overall survival. CONCLUSIONS: The study findings indicate that HO-1 status in pre-therapeutic biopsy specimens could predict response to NACRT, and TXNRD1 status could predict overall survival of ESCC patients.

Novel Criterion Using Esophageal Major and Minor Axes is Useful to Evaluate the Therapeutic Effect and Prognosis After Neoadjuvant Chemotherapy Followed by Surgery in Locally Advanced Esophageal Cancer.

BACKGROUND: An appropriate strategy is needed to determine the therapeutic effect of chemotherapy on primary lesions in esophageal cancer. This multicenter cohort study aimed to examine the usefulness of a novel criterion obtained by multiplying the lengths of the major and minor esophageal axes from helical computed tomography as a tool to evaluate the therapeutic effect of neoadjuvant chemotherapy and to predict prognosis after surgery in locally advanced esophageal cancer. MATERIALS AND METHODS: A first investigation evaluated the reproducibility of the new criterion between two independent examiners. In a second investigation, we examined the association of the novel criterion with pathological tumor regression grade and long-term outcomes. Pretreatment primary lesions less than 20 mm on computed tomography were excluded. RESULTS: In an initial cohort of 81 patients, the intraclass correlation coefficient for the novel criterion was higher than that for the tumor major axis both before and after neoadjuvant chemotherapy. In the second cohort of 255 patients, the novel criterion significantly correlated with tumor regression grade (p = 0.0003), overall survival (p < 0.0001), and disease-free survival (p < 0.0001). It was also an independent predictor for overall survival (p = 0.0023), along with age, tumor regression grade, and pathological stage. CONCLUSIONS: The measurement derived by multiplying the esophageal major and minor axes on computed tomography is easy to obtain and has better objectivity and reproducibility for tumors of any shape. This novel criterion may be clinically useful because it can estimate therapeutic effect, tumor regression grade, and prognosis after neoadjuvant chemotherapy followed by surgery for esophageal cancer.

Evaluating the effect of Neoadjuvant chemotherapy for esophageal Cancer using the RECIST system with shorter-axis measurements: a retrospective multicenter study.

BACKGROUND: Evaluating the effect on primary lesions is important in determining treatment strategies for esophageal cancer. The Response Evaluation Criteria in Solid Tumors system, which employs the longest diameter for measuring tumors, is commonly used for evaluating treatment effects. However, the usefulness of these criteria in assessing primary esophageal tumors remains controversial. Thus, we evaluated this issue by measuring not only the longest diameter but also the shorter axis of the tumor. METHODS: We retrospectively reviewed data from 313 patients with esophageal cancer treated with neoadjuvant chemotherapy followed by esophagectomy at three major high-volume centers in Japan. All patients underwent contrast-enhanced computed tomography before and after chemotherapy. The longest and shortest tumor diameters were measured in each case. Treatment effects were adapted to the Response Evaluation Criteria in Solid Tumors system. Correlations between pathological and survival data were also analyzed. RESULTS: Inter-observer discrepancies were examined for changes in the longest diameter and shorter axis of the tumor (the intraclass correlation coefficients were 0.550 and 0.624, respectively). The shorter axis was correlated with the pathological response in the multivariate analysis (p < 0.001). The shorter axis was significantly associated with overall survival and disease-free survival (both p < 0.001), whereas this association was not observed for the longest tumor diameter. CONCLUSIONS: This multicenter study demonstrated that the Response Evaluation Criteria in Solid Tumors system is useful for predicting pathological response and survival by incorporating the shorter axis of the primary esophageal tumor.

Per-oral endoscopic myotomy (POEM) for a sigmoid type of achalasia: short-term outcomes and changes in the esophageal angle.

BACKGROUND: Per-oral endoscopic myotomy (POEM) is an endoscopic procedure whereby the esophageal muscle is incised in order to lower the lower esophageal sphincter (LES) pressure. Since the time it was first performed in 2008 and subsequently reported on in 2010 by Inoue et al., POEM has been shown to be safe and effective for straight type of achalasia. On the other hand, the efficacy of POEM had been controversial for patients with achalasia of the sigmoid type, in which a high LES pressure is accompanied by morphological changes, including dilation, acute angulation, and rotation. The aim of this study is to evaluate the safety and efficacy of POEM in patients with sigmoid type of achalasia. METHODS: Between May 2015 and December 2017, 16 patients with a sigmoid type of achalasia underwent POEM in our institute. The POEM procedure was the same as that for the straight type of achalasia. The double-scope technique was used to check the distal end of the submucosal tunnel from the gastric side. The primary endpoint was improvement of Eckardt score at 2 months after POEM. The secondary endpoints comprised operating time, change in the esophageal angulation, and adverse events. RESULTS: All patients underwent POEM without severe adverse events. The respective parameters before and after POEM significantly differed in terms of mean (SD) Eckardt score [4.9 (2.0) vs. 0.4 (0.6), p < 0.01], LES pressure [19.4 (10.2) vs. 9.2 (6.4), p < 0.01], and integrated relaxation pressure [17.6 (9.2) vs. 7.9 (5.5), p < 0.01]. The average operation time was 94.7 ± 31.4 min. The average esophageal angulation was 88.4° ± 23.1° before POEM and 109.5° ± 16.7° after POEM (p < 0.01). Four patients had postoperative complications that were treated conservatively. CONCLUSIONS: POEM can improve both LES pressure and esophageal angulation in patients with sigmoid achalasia.

Glucocorticoid receptor and serum- and glucocorticoid-induced kinase-1 in esophageal adenocarcinoma and adjacent Barrett's esophagus.

Barrett's esophagus (BE) is a consequence of gastroesophageal reflux disease and is predisposed to esophageal adenocarcinoma (EAC). EAC is an exemplar model of inflammation-associated cancer. Glucocorticoids suppress inflammation through glucocorticoid receptor (GR) and serum- and glucocorticoid-induced kinase-1 (Sgk1) expressions. Therefore, we immunolocalized GR and Sgk1 in EAC and the adjacent BE tissues and studied their association with clinical disease course in 87 patients with EAC who underwent surgical resection (N = 58) or endoscopic submucosal dissection (N = 29). Low GR and Sgk1 expressions in adjacent BE tissues were associated with adverse clinical outcomes (P = 0.0008 and 0.034, respectively). Patients with low Sgk1 expression in EAC cells exhibited worse overall survival (P = 0.0018). In multivariate Cox regression analysis, low GR expression in the adjacent nonmalignant BE tissues was significantly associated with worse overall survival (P = 0.023). The present study indicated that evaluation of GR and Sgk1 expressions in both the EAC cells and adjacent nonmalignant BE tissues could help to predict clinical outcomes following endoscopic and surgical treatments. In particular, the GR status in BE tissues adjacent to EAC was an independent prognostic factor.

[Per-oral endoscopic myotomy for esophageal achalasia following distal gastrectomy].

The patient was a male in his 70s with a history of distal gastrectomy and Billroth-I reconstruction. He was suspected of having esophageal achalasia and was started on calcium blockers in X-2 year. The symptoms worsened, and he presented to our hospital in X year. We diagnosed esophageal achalasia (Chicago classification ver. 3.0;type I), and conducted per-oral endoscopic myotomy (POEM). His postoperative course was uneventful with no postoperative symptoms. In cases of esophageal achalasia following distal gastrectomy, it is important to consider adhesions, mobility of the remaining stomach, and preservation of the short gastric artery and vein. Since the Heller-Dor operation can be difficult, POEM may be a reasonable alternative in these cases.

The Influence of the Perioperative Nutritional Status on the Survival Outcomes for Esophageal Cancer Patients with Neoadjuvant Chemotherapy.

BACKGROUND: Studies have shown a variety of nutritional indices to be prognostic predictors for esophageal cancer patients. However, which nutritional index should be used and when it should be measured during the perioperative period remain unclear. This study attempted to clarify the details surrounding predictive nutritional evaluation by assessing the longitudinal data of serologic indices in perioperative esophageal cancer patients. METHODS: The study included 141 esophageal cancer patients who underwent neoadjuvant chemotherapy after radical esophagectomy at Tohoku University Hospital from April 2008 to December 2017. The nutritional status was retrospectively assessed during the perioperative period, and the prognostic factors related to survival were analyzed. RESULTS: Use of the controlling nutritional status (CONUT) score showed that malnutrition occurred only from 14 days after surgery in most cases. Use of the prognostic nutritional index (PNI) showed that the ratio of malnutrition increased gradually from presurgery to 14 days after surgery. The timing of malnutrition that affected survival was 14 days after surgery with the CONUT score and presurgery and 4 months after surgery with the PNI. A multivariable analysis of independent prognostic factors predicting survival identified malnutrition 14 days after surgery with the CONUT score and a low PNI before surgery, invasion depth of the primary lesion, and node metastasis. CONCLUSIONS: Malnutrition occurring during the perioperative state of esophageal cancer was shown to be a survival prognostic factor. Development of an optimal nutritional intervention is recommended for esophageal cancer patients to prevent malnutrition both before and after surgery.

Esophageal Carcinosarcoma with Basaloid Squamous Cell Carcinoma: A Case Report and Review of the Literature.

Esophageal carcinosarcoma is a rare tumor composed of neoplastic squamous epithelium and sarcomatous spindle cells. The origin of spindle cells remains unknown; however, the majority of sarcomatous components are currently considered to be derived from existing carcinomatous cells via epithelial-mesenchymal transition (EMT). We report a case of esophageal carcinosarcoma harboring basaloid squamous cell carcinoma successfully treated with preoperative chemotherapy. A 78-year-old man complaining dysphagia was diagnosed as esophageal carcinosarcoma. After two courses of preoperative chemotherapy with cisplatin and 5-fluorouracil, curative esophagectomy with lymph node dissection was performed thoracoscopically. Histopathological findings of the resected specimen revealed the mixture of basaloid squamous cell carcinoma and sarcomatous spindle cells. A transitional zone between both components was also detected. As fibrosis was identified around both two components, the findings indicated that both carcinomatous and sarcomatous neoplasms disappeared by preoperative chemotherapy. Final pathological diagnosis was esophageal carcinosarcoma with basaloid squamous cell carcinoma. No recurrent lesions have been detected for 25 months after the surgery. Sarcomatous spindle cells could be derived from the components of basaloid squamous cell carcinoma in our present case due to the presence of histological transition between two components. In addition, the marked immunoreactivity of vimentin (an EMT marker) detected in the tumor cells of basaloid squamous cell carcinoma could be consistent with the concept of monoclonal origin via EMT. The regimen targeting squamous cell carcinoma could also be effective in the treatment of sarcomatous components. Preoperative therapy might achieve the improvement of clinical outcome of patients with esophageal carcinosarcoma.

Reconstructed gastric conduit obstruction caused by a bezoar after esophagectomy: a case report.

BACKGROUND: Bezoars are rare but may cause gastrointestinal obstruction and ulcers. To the best of our knowledge, only two cases of bezoars in the reconstructed gastric conduit have been reported, but there has been no report on reconstructed gastric conduit obstruction due to bezoars. CASE PRESENTATION: A 60-year-old man presented to our clinic with abdominal pain and vomiting that occurred suddenly after dinner. Three years before presentation, he had undergone radical thoracoscopic esophagectomy followed by reconstruction of the gastric conduit through the posterior sternum, for esophageal cancer. Enhanced computed tomography scans showed distension of only the gastric conduit without ischemia and distension of the small intestine. According to our findings, we initially diagnosed the patient with postoperative intestinal obstruction caused by adhesions. After conservative treatment failed, the patient underwent an endoscopic study that showed a bezoar at the pylorus ring. We initially failed to remove the bezoar endoscopically because of its large size; hence, we attempted enzymatic dissolution. Three days after the first endoscopic study, the bezoar was disintegrated using a snare and extracted during a second endoscopy. The patient recovered uneventfully and presented with no complications during the 1-year follow-up interval. CONCLUSION: In cases wherein the discharge of materials in the reconstructed gastric conduit is delayed, bezoars should be considered in the differential diagnosis, and an endoscopic study should be performed to verify the cause of obstruction.

[Thoracoscopic Esophagectomy with Mediastinal Lymphadenectomy in Prone Position].

Recently, thoracoscopic esophagectomy has been widely accepted as a minimally invasive surgery and a possible standard procedure for esophageal cancer patients. Furthermore, it has an advantage for meticulous lymph node dissection by providing a magnification view and less blood loss. Mediastinal lymphadenectomy, especially upper mediastinal lymph node dissection, is a key point for esophageal cancer surgery because of its high frequency of metastasis and dissection efficacy. To avoid complications such as recurrent laryngeal nerve palsy, pneumoniae, chylothorax and unexpected injury in mediastinal lymph node dissection, detailed anatomical knowledge and careful procedures are required for surgeon. An appropriate operative procedure or technique will lead to good short- and long-term outcomes for the patients with esophageal cancer.

Evaluation of the impact of psoas muscle index, a parameter of sarcopenia, in patients with esophageal squamous cell carcinoma receiving neoadjuvant therapy.

BACKGROUND: The impact of sarcopenia on digestive cancer is widely known. Muscle mass, defined as the psoas muscle index (PMI), is an important parameter of sarcopenia. However, the relationship between esophageal cancer and PMI has not been fully investigated, especially in patients receiving neoadjuvant therapy. METHODS: To elucidate the influence of the PMI on patients with esophageal squamous cell carcinoma receiving neoadjuvant therapy, the progression of sarcopenia defined by the PMI, the relationship between pretherapeutic/preoperative sarcopenia and patient characteristics, and patient survival were retrospectively investigated in 82 patients with esophageal squamous cell carcinoma who underwent neoadjuvant therapy. RESULTS: The PMI decreased by more than 20 mm2/m2 between the pretherapeutic and preoperative periods in 75.6% of the patients. Pretherapeutic sarcopenia (low PMI) correlated with the pathological therapeutic response, postoperative recurrence, and pretherapeutic body mass index. Neoadjuvant chemoradiotherapy was associated with the progression of sarcopenia. The pretherapeutic sarcopenia group (low PMI) had worse disease-free survival (DFS) than the non-sarcopenia group. Furthermore, pretherapeutic sarcopenia (low PMI) was an independent prognostic risk factor of DFS according to univariate and multivariate analyses. CONCLUSIONS: The PMI may decrease during neoadjuvant therapy, especially during neoadjuvant chemoradiotherapy. Pretherapeutic sarcopenic (low PMI) patients should be followed-up more carefully postoperatively because higher risks of recurrence and poorer rates of disease-free survival are associated with these patients.

Esophageal cancer with severe funnel chest treated by simultaneous funnel chest surgery and thoracoscopic esophagectomy: a case report.

BACKGROUND: Funnel chest is the most common chest deformity, occurring in 0.06-0.3% of the general population. When it occurs concomitantly with esophageal cancer, it hinders intrathoracic surgery that is necessary for treatment. Although there are a few reports of esophagectomy performed in patients with funnel chest, simultaneous treatment of esophageal cancer and funnel chest with funnel chest surgery (Nuss method) and esophagectomy has not been reported. We report the first case of advanced esophageal cancer complicated by severe funnel chest that was treated using the Nuss method and radical thoracoscopic esophagectomy. CASE PRESENTATION: A 59-year-old man was diagnosed with advanced thoracic esophageal cancer and severe funnel chest. Because his sternum was almost attached to the vertebral bone, thereby creating a narrow space in the mediastinum, esophageal surgery was expected to be complicated. After the patient underwent neoadjuvant chemotherapy, we used the Nuss method to reconstruct the chest and widen the mediastinum. Subsequently, radical thoracoscopic esophagectomy was performed with the patient in the left decubitus position without any difficulty, and the postoperative course was uneventful. CONCLUSION: Simultaneous funnel chest surgery (Nuss method) and thoracoscopic esophagectomy with the patient in the left decubitus position are recommended for esophageal cancer patients with severe funnel chest.

Definitive chemoradiotherapy with docetaxel, cisplatin, and 5-fluorouracil (DCF-R) for advanced cervical esophageal cancer.

BACKGROUND: Recently, definitive chemoradiotherapy (dCRT) has become one of the essential treatment strategies for esophageal squamous cell carcinoma (ESCC) and has been especially gaining prevalence for cervical ESCC to preserve the larynx. Our department recently introduced dCRT concomitant with docetaxel, cisplatin, and 5-fluorouracil (DCF-R) for treating advanced cervical ESCC. This study aims to assess the safety and outcomes of DCF-R in patients with advanced cervical ESCC. METHODS: We retrospectively assessed 11 patients with advanced cervical ESCC (clinical stage: II-IV, including T4b and/or M1 lymph node) who received DCF-R as the first-line treatment between December 2010 and February 2015. RESULTS: Our patient cohort comprised 8 males and 3 females (median age 68 years; range 54-76 years). The pretreatment clinical stage included stage II (1), stage III (7), and stage IV (3) cases [including 3 patients with T4b (2 trachea and 1 thyroid) and 3 patients with M1 lymph node]. We attained complete response (CR) in 10 patients and stable disease in 1 patient. Of 10 patients with CR, 5 experienced recurrence and 5 continued exhibiting CR. Furthermore, grade 3 or more adverse events included leucopenia (91%), neutropenia (91%), febrile neutropenia (45%), and pharyngeal pain (55%). While the 2-year overall survival rate was 72%, the 2-year recurrent-free survival rate was 64%, respectively. CONCLUSIONS: DCF-R treatment for advanced cervical esophageal cancer could be completed by the careful administration; although a strong blood toxicity might occur, this treatment may provide the chance to obtain favorable prognosis with larynx preservation.

Impact of routine recurrent laryngeal nerve monitoring in prone esophagectomy with mediastinal lymph node dissection.

BACKGROUND: The problem of recurrent laryngeal nerve (RLN) paralysis (RLNP) after radical esophagectomy remains unresolved. Several studies have confirmed that intraoperative nerve monitoring (IONM) of the RLN during thyroid surgery substantially decreases the incidence of RLN damage. This study tried to determine the feasibility and effectiveness of IONM of the RLN during thoracoscopic esophagectomy in the prone position for esophageal cancer. METHODS: All 108 patients who underwent prone esophagectomy at Tohoku University Hospital between July 2012 and March 2015 were included in this study. We divided patients into two groups: a control group (No-Monitoring group, surgery without IONM; n = 54) and a study group (Monitoring group, surgery with IONM; n = 54). In Monitoring group, neural stimulation was performed for both RLNs before and after dissection in the thoracic procedure, then for RLNs and vagus nerves (VNs) in the cervical procedure. The feasibility of IONM in Monitoring group and early surgical outcomes were retrospectively compared with those in No-Monitoring group. RESULTS: IONM could be performed for 47 cases (87.0%) in Monitoring group. Reasons for discontinuation were use of muscle relaxants (3 patients), change in thoracotomy procedure (2 patients), past rib bone fracture (1 patient), and allergic shock by transfusion (1 patient). Right RLNPs were identified postoperatively in 4 patients, and left RLNPs in 23 patients. IONM sensitivities were 92.7 and 88.0% for the right and left VNs, respectively. Incidences of postoperative RLNP, aspiration, and primary pneumonia did not differ significantly between groups. CONCLUSIONS: This study confirmed the feasibility and safety of IONM of the RLN for thoracoscopic esophagectomy in the prone position. No significant differences in postoperative outcomes were seen between esophagectomy with and without IONM.

Herpes simplex virus-1 encephalitis induced by chemoradiotherapy and steroids in an esophageal cancer patient: a case report.

BACKGROUND: Systemic chemotherapy combined with steroids used as prophylactic antiemetics have been reported to induce immunosuppression. Further, herpes simplex virus-1 (HSV-1) infection has been reported to occur in patients with small cell carcinomas after chemoradiotherapy that includes brain irradiation. Here, we report a case of HSV-1 encephalitis that occurred in a patient undergoing chemoradiotherapy for advanced esophageal cancer. CASE PRESENTATION: A 77-year-old woman received chemoradiotherapy (5-fluorouracil, 700 mg/m(2); cisplatin, 70 mg/m(2); and radiotherapy, 60 Gy in total) for stage III esophageal cancer. The total radiation dose was administered concurrently with the first two courses of chemotherapy, together with dexamethasone as a prophylactic antiemetic. Two days before completion of the fourth course of chemotherapy, the patient developed acute neurological symptoms of disorientation, clouding of consciousness, and fever. T2-weighted magnetic resonance imaging showed a high intensity area in the bilateral temporal lobes and insular cortex. Furthermore, DNA PCR testing of cerebrospinal fluid showed clear positivity for HSV-1 DNA, and the patient was diagnosed with herpetic encephalitis. Intravenous administration of acyclovir for 3 weeks led to gradual improvement of consciousness, and the patient was able to respond to verbal cues. CONCLUSION: In advanced esophageal cancer patients, standard treatment involves chemoradiotherapy and surgery. However, primary infection with or reactivation of endogenous latent HSV-1 in the brain cortex during chemoradiotherapy combined with administration of a steroid may compromise the benefits of treatment.

Characteristics of Postoperative Recurrence in Lymph Node-Negative Superficial Esophageal Carcinoma.

BACKGROUND: This study aimed to evaluate the recurrence rates, timings, locations, and risk factors, and survival in patients with lymph node-negative superficial esophageal squamous cell carcinomas (ESCCs). METHODS: We investigated 167 patients with pathological T1 thoracic ESCC who underwent curative esophagectomy with lymphadenectomy between 1986 and 2013. They were classified into lymph node-negative and lymph node-positive groups, each of which included 15 relapsed patients. The recurrence rates, timings, locations, and risk factors, and survival were examined retrospectively. RESULTS: Significantly better recurrence (12.4 %) and the 5-year overall survival (85.7 %) rates were seen in patients with node-negative superficial ESCC compared with those with node-positive superficial ESCC. Relapsed patients with node-negative superficial ESCC showed a 5-month delay in the time to recurrence compared with relapsed patients with node-positive superficial ESCC, but the recurrence locations were similar. Upper thoracic tumors and the presence of lymph node metastases were independent risk factors for recurrence in superficial ESCC patients, but we did not determine any risk factors in patients who were node negative only. The 5-year overall survival rates did not differ between relapsed node-negative and node-positive patients. Furthermore, the mean times to death and the survival rates from recurrence to death were similar in the node-negative (20.3 months and 9.3 %, respectively) and in the node-positive patients (19.1 months and 13.6 %, respectively) who had relapsed. CONCLUSIONS: Node-negative and node-positive superficial ESCC patients should be followed up similarly, because when recurrences occur, the prognoses and the times to death are similar in node-negative and node-positive superficial ESCC patients.

Murine double minute 2 predicts response of advanced esophageal squamous cell carcinoma to definitive chemoradiotherapy.

BACKGROUND: Definitive chemoradiotherapy (dCRT) has recently become one of the most effective therapies for the treatment of esophageal squamous cell carcinoma (ESCC). However, it is also true this treatment has not been effective in all patients. Therefore, it is very important to evaluate the surrogate marker of dCRT in order to improve clinical outcomes of patients with ESCC. On the other hand, our previous study had suggested that murine double minute 2 (MDM2) and p16 were associated with chemoradioresistance in ESCC. METHODS: We selected pretreatment biopsy specimens of ESCC patients from our prospective clinical study on dCRT. Seventy-nine cases histologically diagnosed as ESCC were used. We immunohistochemically investigated these specimens using antibodies against MDM2, p53, p16, and Ki-67. RESULTS: The patients included 68 males and 11 females with a mean age of 63.3 years. The number of patients in each clinical stage was as follows: 22 in c-Stage I; 17 in c-Stage II; and 40 in c-Stage III. cT, cN, and cStage were significantly more advanced in the Failure group (including patients with persistent and recurrent disease after dCRT) than in the complete response (CR) group (patients with persistent CR after dCRT). The clinical stage inversely correlated with the CR rate and the rescue rate after failure. The overall survival rate was significantly worse in the patients with advanced cT, cN, and cStage levels, and in the Failure group. MDM2 positivity was significantly higher in the Failure group than in the CR group in cStageIII (P = 0.014). The number of patients with an absence of p16 immunoreactivity was significantly higher in the Failure group than in the CR group in cStageIII (P = 0.010) but not in cStageI or cStageII. Moreover, the overall survival with a Ki-67 ≥ 33.7% was significantly better than that with <33.7% for patients in cStageIII (P = 0.024). CONCLUSIONS: The results of this study suggested that MDM2 and p16 are predictive markers for chemoradioresistance in cStageIII ESCC and Ki-67 is a prognostic marker following dCRT in cStageIII ESCC. These issues could contribute to the formulation of treatment strategy for patients with advanced ESCC.