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Background With the improved survival rate of patients with esophageal cancer, secondary cancers, including pharyngolaryngeal cancer, have become a problem. Phanryngolaryngeal cancer surgery often requires esophagogastric anastomosis resection in patients with a previous history of subtotal esophagectomy. Owing to adhesions, especially surrounding the esophagogastric anastomosis, caused by the initial surgery, the second surgery might cause postoperative complications. Case presentation A 65-year-old man was diagnosed with early stage esophageal squamous cell carcinoma and underwent endoscopic mucosal dissection. However, the histopathological depth of the tumor was pT1b, and additional treatment was required. After administration of the neoadjuvant chemotherapy, he underwent thoracoscopic esophagectomy and retrosternum reconstruction via a gastric tube (pT1N3M0 stage III). Eight months after the first surgery, tumor recurrences were observed at the anastomosis and left cervical lymph node. Definitive chemoradiotherapy was performed for the recurrences, and complete response was achieved. Seven months after chemoradiotherapy, he was diagnosed with hypopharyngeal squamous cell carcinoma in the right piriform fossa (cT2N2bM0 stage IVA), and salvage surgery was chosen as treatment. The surgical findings revealed strong adhesion around the remnant esophagus, which was difficult to dissect from surrounding tissue and was associated with a risk of breaking of the anastomosis. However, indocyanine green fluorescence imaging findings indicated sufficient blood flow to preserve the remnant esophagus, including the anastomosis, even after the interruption of blood flow from the proximal side of the esophagus by total pharyngolaryngectomy. Finally, approximately 4 cm of the remnant esophagus was preserved, and the free jejunum reconstruction with cervical vascular anastomosis was performed. Moreover, the patient was discharged without complications on postoperative day 38. After 10 months of the second surgery, a metastatic lymph node was observed in the right neck. Immune checkpoint inhibitors and chemotherapy were administered, and the patient is alive and under treatment 1.5 years after the second surgery. Conclusions Blood supply to the remnant cervical esophagus was thought to be from the gastric conduit over the anastomosis and surrounding capillaries. Thus, the preservation of the remnant esophagus can be considered in total pharyngolaryngectomy even after

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.

Background Killian–Jamieson diverticulum, which is a relatively rare pharyngoesophageal diverticulum, is difficult to distinguish from Zenker’s diverticulum. Because major points of the relevant surgical procedures for these two entities differ, it is important to make an accurate diagnosis. We herein report a case of Killian–Jamieson diverticulum initially diagnosed as Zenker’s diverticulum. Case presentation A 56-year-old man complaining of discomfort during swallowing was diagnosed with pharyngoesophageal diverticulum. He was initially diagnosed with Zenker’s diverticulum before surgery, but the diverticulum actually arose from the left side of the esophageal wall, at the level of the cricoid cartilage and below the cricopharyngeal muscle. We therefore ultimately diagnosed this case as Killian–Jamieson diverticulum during surgery, and were able to preserve the muscle above the diverticulum, which would normally have to be cut when treating a case of Zenker’s diverticulum. Conclusion To make an accurate diagnosis, clinical and surgical findings are important to consider, including the location of the diverticulum and the relationship between the diverticula and cricopharyngeal muscles or between the diverticula, thyroid cartilage and cricoid cartilage.

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. 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. 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. 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.

The immune microenvironment plays a pivotal role in cancer development and progression. Therefore, we studied the status of immune cells in esophageal adenocarcinoma (EAC) and adjacent Barrett's esophagus (BE) and their association with the clinical course of patients. We included 87 patients with EAC who underwent surgical resection or endoscopic submucosal dissection. CD3, CD8, Foxp3, p53, and Ki-67 were immunolocalized in EAC and adjacent BE (N = 87) and BE without EAC (N = 13). BE adjacent to EAC exhibited higher CD3+ lamina propria lymphocyte (LPL) numbers than BE without EAC. Abundant Foxp3+ LPLs in BE were associated with dysplasia and increased Ki-67 labeling index (LI) in BE glandular cells and tended to link to aberrant p53 expression. Abundant CD8+ LPLs in adjacent BE were associated with worse prognosis of EAC patients (P = 0.019). Results of our present study firstly revealed the potential influence of the tissue immune microenvironment of BE adjacent to EAC on cancer development and eventual clinical outcome of EAC patients. T cell infiltration could play pivotal roles in facilitating the dysplasia-adenocarcinoma sequence in BE. The number of Foxp3+ T cells is increased at the early stage of carcinogenesis and could help identify patients harboring dysplastic and highly proliferating cells. CD8+ T cells could reflect unfavorable inflammatory response in adjacent tissue microenvironment and help predict worse prognosis of EAC patients.

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. 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. 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

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. 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. 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. 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.

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. 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. 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. 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.

p16 is generally considered to be a surrogate maker of human papillomavirus (HPV) infection and also a predictive marker of favorable clinical outcome of patients with squamous cell carcinoma of the oropharynx. p16 overexpression is also known to be induced by deregulation of RB1 in neuroendocrine carcinomas. In highly malignant esophageal neoplasms, however, the status of p16 has remained largely unknown. We immunolocalized p16 and Rb1 in 82 surgically resected esophageal high-grade squamous cell carcinomas (46 poorly differentiated and 36 basaloid squamous cell carcinomas) and 15 esophageal small-cell carcinomas in order to clarify the clinical and biological significance of p16. p16 immunoreactivity was detected in 7/82 (9%) high-grade squamous cell carcinomas and 15 (100%) small-cell carcinomas. p16 immunoreactivity was significantly associated with Rb1 protein loss in both groups (P

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.

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. 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. 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. 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.

An aberrant right subclavian artery (ARSA) is an anatomical abnormality that occurs at a frequency of 0.4–2 %. It is important to be aware of this abnormality when performing radical esophagectomy for esophageal cancer because many patients with an ARSA have a right nonrecurrent inferior laryngeal nerve (NRILN) and right thoracic duct. We report three cases of esophageal cancer with ARSA treated by thoracoscopic esophagectomy. Case 1 was a 59-year-old woman with a relapse of a thoracic esophageal cancer after definitive chemoradiotherapy (CRT). Case 2 was a 76-year-old man with upper thoracic esophageal cancer who had received no treatment before the surgery. Case 3 was a 69-year-old man with upper thoracic esophageal cancer pretreated with neoadjuvant CRT. It was possible to predict an ARSA by computed tomography and the right thoracic ducts by magnetic resonance imaging before surgery in all three cases. Thoracoscopic esophagectomy with two-field lymph node dissection was performed, and the NRILN and the right thoracic duct were detected and preserved in all three cases. Because of ARSA, the operative field is limited around the left recurrent nerve, so a careful procedure is needed to avoid nerve palsy.

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/m2; cisplatin, 70 mg/m2; 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.

Verrucous carcinoma of the esophagus (VCE) is a rare, slow-growing, well-differentiated squamous cell carcinoma. Histologically, superficial layers of this cancer tend to have less atypical epithelium with non-specific inflammatory change, which therefore makes diagnosis of malignancy extremely difficult unless a surgical specimen is obtained. We recently encountered a case in which a malignant tumor was suspected on initial endoscopic evaluation, but two biopsies revealed no carcinoma cells. Analysis of a third biopsy finally suggested the possibility of squamous cell carcinoma. A subsequent surgical specimen revealed the tumor as VCE. In addition, immunohistochemical examination revealed that Ki67 immunopositive cells were distributed along the basal layer of the VCE, regarded as a pattern unique to this type of cancer. It is important to know of the existence of VCE. In cases in which this tumor is endoscopically suspected, repeated deep biopsy is strongly recommended and the only curative treatment for this type of cancer is resection.

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