Temporary loop ileostomy versus transverse colostomy for laparoscopic colorectal surgery: a retrospective study.

PURPOSE: To compare the surgical outcomes of ileostomy vs. transverse colostomy and investigate which is more suitable for a diverting stoma. METHODS: We assessed stoma-related complications and surgical outcomes, retrospectively, for 146 patients who underwent laparoscopic colorectal surgery with a temporary loop ileostomy or transverse colostomy. Complications after secondary stoma closure surgery were also analyzed. RESULTS: After the primary surgery, the incidence of prolapse was significantly higher in the transverse colostomy group, whereas high-output stoma and skin irritation were seen more frequently in the ileostomy group. The median interval to stoma closure was shorter in the ileostomy group than in the transverse colostomy group (144 vs. 196 days). After secondary closure surgery, the incidence of wound infection was significantly higher in the transverse colostomy group than in the ileostomy group. None of the patients in the ileostomy group had severe complications. The median postoperative hospital stay was significantly shorter in the ileostomy group than in the transverse colostomy group (10 vs. 13 days). CONCLUSIONS: The findings of this study suggest that ileostomy should be the procedure of choice for short-term temporary diverting stoma, but that transverse colostomy is more appropriate for patients who require a long-term or permanent stoma.

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.

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.

SOX2 and Rb1 in esophageal small-cell carcinoma: their possible involvement in pathogenesis.

Clinicopathological features and pathogenesis of esophageal small-cell carcinoma remain unclear. We hypothesized common cellular origin and pathogenesis in small-cell carcinoma of esophagus and lung associated with SOX2 overexpression and loss of Rb1. Expression of squamous-basal markers (CK5/6 and p40), glandular markers (CK18 and CEA), SOX2, and Rb1 were evaluated in 15 esophageal small-cell carcinomas, 46 poorly differentiated squamous cell carcinomas, and 88 small-cell lung carcinoma, as well as 16 embryonic esophagus. Esophageal small-cell carcinoma expressed higher levels of glandular markers and lower levels of squamous-basal markers than poorly differentiated squamous cell carcinoma. No significant differences were observed in immunohistochemistry profiles between small-cell carcinoma of the esophagus and the lung. SOX2 expression was high in esophageal small-cell carcinoma (70%±33% of nuclei), small-cell lung carcinoma (70%±26%), and the embryonic esophagus (75%±4%), and it was significantly lower in poorly differentiated squamous cell carcinoma (29%±28%). Rb1 expression was significantly lower in esophageal small-cell carcinoma (0.3%±1%), small-cell lung carcinoma (2%±6%), and the embryonic esophagus (7%±5%), and it was significantly higher in poorly differentiated squamous cell carcinoma (51%±24%). The immunohistochemistry profiles of small-cell carcinoma of the esophagus and the lung are highly similar. The loss of Rb1 function is a key contributor to the pathogenesis of both neoplasms. In addition, SOX2 overexpression observed in esophageal and lung small-cell carcinoma as well as in the embryonic esophagus indicated that esophageal small-cell carcinoma may arise from embryonic-like stem cells in the esophageal epithelium. The two distinct differentiation patterns (neuroendocrine and glandular) of esophageal small-cell carcinoma further support the fact that SOX2 has a pivotal role in the differentiation of pluripotent stem cells into esophageal small-cell carcinoma cells.

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.

c-Met in esophageal squamous cell carcinoma: an independent prognostic factor and potential therapeutic target.

BACKGROUND: c-Met is widely known as a poor prognostic factor in various human malignancies. Previous studies have suggested the involvement of c-Met and/or its ligand, hepatocyte growth factor (HGF), in esophageal squamous cell carcinoma (ESCC), but the correlation between c-Met status and clinical outcome remains unclear. Furthermore, the identification of a novel molecular therapeutic target might potentially help improve the clinical outcome of ESCC patients. METHODS: The expression of c-Met and HGF was immunohistochemically assessed in 104 surgically obtained tissue specimens. The correlation between c-Met/HGF expression and patients' clinicopathological features, including survival, was evaluated. We also investigated changes in cell functions and protein expression of c-Met and its downstream signaling pathway components under treatments with HGF and/or c-Met inhibitor in ESCC cell lines. RESULTS: Elevated expression of c-Met was significantly correlated with tumor depth and pathological stage. Patients with high c-Met expression had significantly worse survival. In addition, multivariate analysis identified the high expression of c-Met as an independent prognostic factor. Treatment with c-Met inhibitor under HGF stimulation significantly inhibited the invasive capacity of an ESCC cell line with elevated c-Met mRNA expression. Moreover, c-Met and its downstream signaling inactivation was also detected after treatment with c-Met inhibitor. CONCLUSIONS: The results of our study identified c-Met expression as an independent prognostic factor in ESCC patients and demonstrated that c-Met could be a potential molecular therapeutic target for the treatment of ESCC with elevated c-Met expression.

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.

Decreased expression of ARID1A contributes to infiltrative growth of esophageal squamous cell carcinoma.

The clinical outcome for esophageal squamous cell carcinoma (ESCC) patients is often poor because of the invasive nature of this tumor type. AT-rich interactive domain 1A (ARID1A) functions as a tumor suppressor, and its gene mutation has been reported in various human malignancies. ARID1A is a non-catalytic subunit of the SWItch/Sucrose Non Fermentable (SWI/SNF) chromatin-remodeling complex that regulates gene transcription. Decreased expression of ARID1A protein has been reported to decrease the expression of E-cadherin, an adhesion protein. However, the correlation between ARID1A and E-cadherin expression status in ESCC remains largely unknown. To address this issue, we examined the expression of ARID1A and E-cadherin in tumor specimens excised from 83 ESCC patients using immunohistochemical analysis. The intensity of the ARID1A immunoreactivity was significantly lower in tumors with a growth pattern characterized by ill-defined borders than that in tumors with an expansive growth pattern having a well-demarcated border or tumors with an intermediate growth pattern. Thus, decreased ARID1A immunoreactivity correlated with infiltrative growth of ESCC. In contrast, E-cadherin status did not correlate with the infiltrative growth pattern of ESCC. Moreover, ARID1A expression status did not significantly correlate with any of other clinicopathological factors, E-cadherin expression levels, or the clinical outcome of the patients. On the other hand, the patients with tumors expressing low levels of E-cadherin exhibited significantly lower survival rates than those with high expression. In conclusion, reduced ARID1A expression in tumor tissues contributes to infiltrative growth of ESCC, irrespective of E-cadherin expression levels.

Activating transcription factor 3 (ATF3) in the human adrenal cortex: its possible involvement in aldosterone biosynthesis.

The activating transcription factor 3 (ATF3) is a member of the cAMP-responsive element-binding (CREB) protein family of transcription factors. ATF3 is expressed in H295R human adrenocortical carcinoma cells and considered a rapid-responder gene to angiotensin-II stimulation. However, the functions of ATF3 in human adrenocortical tissues have remained unknown. In this study, we analyzed the localization and possible regulatory mechanisms of ATF3 in human adrenocortical cells and tissues. The expression levels of ATF3 mRNA were analyzed in 66 aldosterone-producing adenomas (APA) and 14 cortisol-producing adenomas (CPA) using real-time RT-PCR. To localize the ATF3 protein, we performed immunohistochemical analysis in 20 non-pathological adrenal glands, 9 adrenal glands with idiopathic hyperaldosteronism (IHA), 20 APA, and 5 CPA using a mouse monoclonal antibody against human ATF3. We showed that ATF3 mRNA levels were higher in APA compared to CPA (P = 0.0053). ATF3 was immunolocalized to the zona glomerulosa of non-pathological adrenal glands and adrenal glands with IHA, and diffusely detected in the tumor cells of APA and CPA. Subsequently, H295R cells were treated for 6 h with each inhibitor of Src kinase (SRC), PKC, JAK2, and calcium-dependent calmodulin kinase-II (CaMKII) in the presence or absence of angiotensin-II. The expression levels of ATF3 mRNA were increased by angiotensin-II (about 3.5-fold induction), but the magnitude of the induction was significantly decreased in the presence of an inhibitor for SRC (PP2) or CaMKII (KN93). These results suggest that ATF3 is a downstream target of SRC and CaMKII signaling, and may be involved in adrenocortical aldosterone synthesis.

Blood flow ratio in the gastric conduit measured by laser Doppler flowmetry: A predictor of anastomotic leakage after esophagectomy.

Background: Anastomotic leakage after esophagectomy is a common complication. Laser Doppler flowmetry (LDF) can quantitatively evaluate the blood flow in the gastric conduit. Methods: A total of 326 patients who underwent thoracoscopic/robot-assisted esophagectomy followed by gastric conduit reconstruction and end-to-side anastomosis were enrolled. We divided the gastric conduit into zones I (dominated by the right gastroepiploic vessels), II (dominated by the left gastroepiploic vessels), and III (perfused with short gastric vessels). Before pulling up the gastric conduit to the neck, LDF values were measured at the pylorus, the border between zones I and II (zone I/II), the border between zones II and III (zone II/III), and the gastric conduit tip (tip). The blood flow ratio was calculated as the LDF value divided by the LDF value at the pylorus. Results: Anastomotic leakage developed in 32 of 326 patients. Leakage was significantly associated with the blood flow ratio at the tip (p < 0.001), but not at zone I/II, zone II/III, and the anastomotic site. The receiver-operating characteristic curve analysis identified an anastomotic leakage cutoff ratio of 0.41 (at the tip). A multivariate Cox analysis showed that a blood flow ratio <0.41 at the tip was an independent risk factor for anastomotic leakage (p < 0.001). Conclusion: Anastomotic leakage after esophagectomy was significantly associated with the blood flow ratio at the tip of the gastric conduit. Preservation of the blood supply to the tip via the gastric wall might contribute to a decreased incidence of anastomotic leakage.

Significance of CD133 expression in esophageal squamous cell carcinoma.

BACKGROUND: CD133 was recently reported to be a cancer stem cell marker and a prognostic marker for several tumors. However, few studies have investigated CD133 expression in esophageal squamous cell carcinoma (ESCC). Therefore, we examined whether CD133 could serve as a prognostic marker of ESCC and investigated the correlation between CD133 expression and the clinicopathological findings of ESCC patients and several markers. METHODS: We studied 86 ESCC patients who underwent curative surgery without neoadjuvant treatment at Tohoku University Hospital (Sendai, Japan) between January 2000 and December 2005. We analyzed tissue specimens by immunohistochemical staining for CD133, p53, p16, p27, murine double minute 2 (MDM2), Ki-67, and epidermal growth factor receptor (EGFR). RESULTS: Pathological tumor depth and tumor stage were significantly more advanced among CD133-negative patients than among CD133-positive patients. A log-rank test showed that CD133 immunoreactivity was significantly correlated with the overall survival of the patients (P = 0.049). However, multivariate analysis showed that it was not significantly correlated (P = 0.078). Moreover, CD133 was significantly positively correlated with p27 immunoreactivity (P = 0.0013) and tended to be positively correlated with p16 immunoreactivity (P = 0.057). In addition, p16 immunoreactivity was correlated with smoking history (P = 0.018), pathological lymph node status (P = 0.033), and lymphatic invasion (P = 0.018). CONCLUSIONS: This study indicated that CD133 immunoreactivity is a good predictor of prognosis in ESCC patients. In addition, CD133 may play a role in the regulation of tumor cell cycle through p27 and p16 in ESCC. At present, it thus remains controversial whether CD133 expression is a valid prognostic marker for ESCC. To elucidate this relationship, further investigations are required.

Distinguishing Killian-Jamieson diverticulum from Zenker's diverticulum.

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.

Esophageal Intramural Pseudodiverticulosis Diagnosed by Combining Esophagogastroduodenoscopy, Esophagography, and High-resolution Manometry.

Esophageal intramural pseudodiverticulosis (EIPD) is a rare disease. A 78-year-old man with dysphagia presented to our hospital. The presence of diffuse esophageal spasm was suspected by his primary-care doctor. High-resolution manometry (HRM) showed no abnormal findings. The patient was diagnosed with EIPD and Candida esophagitis, by esophagogastroduodenoscopy (EGD) and esophagography. His symptoms improved after symptomatic treatment for Candida esophagitis with oral administration of an antifungal drug. EIPD should be considered in patients with dysphagia; EGD and esophagography should be performed when diagnosing EIPD.

MMR markers correlate with clinical outcome in patients with esophageal squamous cell carcinoma.

BACKGROUND: The DNA mismatch repair system is one of the defense mechanisms in the body, and the inactivation of mismatch repair plays a pivotal role in secondary carcinogenesis and progression. However, the significance of mismatch repair in esophageal squamous cell carcinoma (ESCC) has not been established. In this study, we explored the diagnostic and prognostic significance of mismatch repair markers, mutL homologue 1 (MLH1), post-meiotic segregation increased 2 (PMS2), mutS homologue 2 (MSH2), and mutS homologue 6 (MSH6), in patients with ESCC. METHODS: We used a notation based on the proportion of immunoreactivity/expression for immunohistochemistry (PRIME notation), which allows the comparison of mismatch repair expression by assigning a score to PRIME notation. MLH1, PMS2, MSH2, and MSH6 were examined immunohistochemically in 189 surgically resected ESCC specimens. RESULTS: A total of 100/189 patients with ESCC (53%) received preoperative chemotherapy. The rates of ESCC cases with decreased mismatch repair status were 13.2%, 15.3%, 24.8%, and 12.6% for MLH1, PMS2, MSH2, and MSH6, respectively. The decreased status of individual mismatch repair markers was significantly correlated with worse prognosis in patients with ESCC. Additionally, MSH2, MSH6, and PMS2 were significantly associated with response to preoperative chemotherapy. Multivariate analysis revealed that MLH1, PMS2, and MSH2 are independent prognostic factors. CONCLUSION: Our results suggest that mismatch repair is a prognostic biomarker for ESCC and could contribute to the selection of appropriate adjuvant therapy for patients with ESCC.

Benign multicystic peritoneal mesothelioma occurring in bilateral inguinal canals metachronously: a case report.

BACKGROUND: Benign multicystic peritoneal mesothelioma (BMPM) is a benign tumor that usually occurs in middle-aged females. Although several published studies have reported the occurrence of this tumor in the abdominal cavity, few have documented its development in the inguinal region. CASE PRESENTATION: We present a case of a 48-year-old female presenting with a bulge in her left inguinal region. Physical examination revealed a golf ball-sized nodule in the left inguinal region that could not be pushed back into the abdominal cavity. Contrast-enhanced computed tomography showed a multicystic tumor; therefore, the patient was diagnosed with inguinal hernia or hydrocele of the Nuck's canal. We performed surgical resection and hernia repair using the mesh plug method. The resected specimen was 80 mm in length and contained a multicystic tumor. Pathological examination showed that the cyst wall was lined by a single layer of cuboidal to single layer squamous epithelium. Immunohistochemistry revealed positivity for calretinin in the epithelial cells, for which a diagnosis of BMPM was established. The patient returned to our hospital after 5 years with symptoms similar to the previous episode, but this time in the right inguinal region. Imaging studies showed a tumor in the right inguinal region with the same characteristics as the previous one. The patient underwent tumor resection and hernia repair using the same technique. The resected tumor was 45 mm in length and had characteristics similar to the previously resected tumor. The presence of calretinin and D2-40 on immunohistochemistry led to the diagnosis of BMPM. There was no recurrence of BMPM for 33 months after the secondary surgery. CONCLUSIONS: Here we present the first report of metachronous BMPM occurring in bilateral inguinal canals. Although the pathogenesis of BMPM remains unclear, reactive changes have been suggested to cause tumors originating from the groin. The treatment of choice for BMPM is surgical resection. For diagnosis, pathological examination with immunostaining can be useful. The most appropriate postoperative follow-up for inguinal BMPM is controversial, and the accumulation of more inguinal BMPM cases is needed.

Murine Double Minute 2 Antagonist Nutlin-3 Enhanced Chemosensitivity in Esophageal Squamous Cell Carcinoma.

BACKGROUND/AIM: Murine double minute 2 (MDM2) is well known to inhibit p53 function and its over-expression is associated with poor prognosis in several human malignancies. Nutlin-3, a small-molecule inhibitor of MDM2, exerts antitumor effects on various solid tumors harboring wild-type p53. We aimed to clarify its effects on esophageal cancer. MATERIALS AND METHODS: We first examined the potential antitumor effects of nutlin-3 according to MDM2 status using esophageal carcinoma cell lines (KYSE 170/180). We then immunolocalized MDM2 immunoreactivity in 62 surgical cases of esophageal squamous cell carcinoma undergoing neoadjuvant chemotherapy followed by esophagectomy and correlated the findings with clinicopathological variables. RESULTS: MDM2 mRNA expression in KYSE 170 was significantly higher than that in KYSE 180 cells. No significant changes were detected in both cell lines when nutlin-3 was added. However, cell proliferation was significantly decreased in KYSE 170 cells treated with nutlin-3 and cisplatin compared to cisplatin alone but not in KYSE 180. MDM2 immunoreactivity was also significantly associated with poor sensitivity to neoadjuvant chemotherapy in the cases examined. CONCLUSION: The combination of nutlin-3 with chemotherapeutic agents may become a novel therapeutic strategy in esophageal cancer over-expressing MDM2.

Determination of the best surgical strategy for thoracic esophageal resection concurrent with double aortic arch using a three-dimensional model: a case report.

Background: A double aortic arch (DAA) is a relatively rare vascular malformation, which rarely causes problems once the patients reach adulthood. However, a DAA makes an esophageal cancer surgery difficult to perform, especially during upper mediastinal dissection. Herein, we report a strategy for surgery in esophageal cancer patients concurrent with DAA. Case Description: A 73-year-old man was diagnosed with middle thoracic esophageal cancer of cT3N4M0 stage III (UICC-TNM 7th) concurrent with DAA. After two courses of neoadjuvant chemotherapy, surgical intervention was planned. To develop a surgical strategy for an esophagectomy with this complicated malformation, we created a three-dimensional printer model for this case. According to this simulation, the bilateral thoracoscopic approach with prone position seemed to be an ideal method for upper mediastinal dissection. As we expected, the dissection of upper mediastinum was difficult only with the right-side approach; especially, the oral side of esophagus posterior to the right aortic arch (RAA) was impossible to dissect from the right side. By switching the approach from left side, oral esophagus was easily dissected by retracting the oral esophagus from the cranial side of the left aortic arch (LAA). Surgery was successfully performed, and the patient was discharged 26 days after surgery without major complications. Conclusions: To the best of our knowledge, this is the first surgical report using a three-dimensional printer for esophageal cancer. The bilateral approach is appropriate for esophageal cancer surgery concurrent with a DAA. A three-dimensional printer is useful for simulating esophageal surgery with major vascular malformations.

Perioperative Administration of Cystine and Theanine Suppresses Inflammation and Facilitates Early Rehabilitation and Recovery after Esophagectomy: A Randomized, Double-Blind, Controlled Clinical Trial.

Oral administration of cystine and theanine (CT) increases glutathione levels to modulate the inflammatory response, which has yet to be sufficiently explored for patients' recovery and early rehabilitation. We planned a randomized, double-blind, placebo-controlled trial to determine whether perioperative oral administration of CT promotes recovery after esophagectomy. Patients were randomized into either CT or placebo groups, who received preoperative and postoperative treatments for 4 and 13 days, respectively. The main outcome measures were triaxial accelerometer readings, inflammation indicators, a 6 min walk test (6MWT), and a quality of life questionnaire (QoR-40). The study involved 32 patients. Although the CT group (n = 16) showed better patient activity across the investigated period, there was no significant difference between the two groups. However, white blood cell count on postoperative days (POD) 2 and 10, neutrophil count (POD 2, 7, and 10), and C-reactive protein level (POD 13) in the CT group were significantly lower than in the placebo group. Furthermore, 6MWT on POD 7 and QoR-40 on POD 13 were significantly higher in the CT group than those in the placebo group. This study suggests that perioperative administration of CT may contribute to early recovery and rehabilitation after esophagectomy via suppression of inflammatory response.

A potential preventive method for scar stenosis after esophageal endoscopic mucosal resection using human amniotic epithelial cells in a porcine model.

Objectives: The current methods employed for esophageal endoscopic mucosal resection (EMR) involve the risk of adverse postprocedural complications. Therefore, this study aimed to develop a new method to prevent stenosis following a resection procedure using human amniotic epithelial cells in a porcine model. Methods: With the consent of a woman who underwent a cesarean section, amniotic epithelial cells were isolated from the amniotic membrane of the delivered placenta. Six swine were used for this study. Under general anesthesia, four EMRs using cap-fitted microscope ulcers were performed on each porcine esophagus. Of the four ulcers, the two on the oral side were treated by injecting human amniotic epithelial (AE group) cells, and the remaining two on the anal side were left untreated (control group). One week after the procedure, the swine were sacrificed, and the ulcers were evaluated. The epithelialization rate was calculated by dividing the length of the epithelialized portion of each section by the length of the ulcer, which was determined using an optical microscope. Moreover, the mucosal thickening in each section was measured in terms of diameter. Results: The epithelialization rate was significantly higher in the AE group than in the control group. Mucosal thickening was not significantly different between the groups. Conclusions: Transplanting amniotic epithelial cells into the ulcer promoted ulcer epithelialization. Amniotic epithelial cell transplantation is a potential method for the management of ulcer scar stenosis following esophageal endoscopic submucosal dissection.

Definitive Chemoradiotherapy with Docetaxel, Cisplatin, and 5-Fluorouracil for Advanced Cervical Esophageal Cancer: A Medium-Term Outcome.

BACKGROUND: Definitive chemoradiotherapy (dCRT) is widely considered as a treatment option for cervical esophageal squamous cell carcinoma (ESCC) toward preserving the larynx. We have reported favorable outcomes, including the treatment response rate and short-term survival of dCRT concomitant with docetaxel, cisplatin, and 5-fluorouracil (DCF-RT) for advanced cervical ESCC. The aim of this paper was to report the subsequent progress of the study. METHODS: We assessed 18 patients with advanced (clinical stage II-IV, including T4b and/or M1 lymph node) cervical ESCC at our department who received DCF-RT as the first-line treatment between December 2010 and June 2020. RESULTS: A total of 14 men and 4 women underwent the study regimen. The pretreatment clinical stage included stage II, stage III, stage IVA, and stage IVB cases (including 9 patients with T4b) [8 trachea and 2 thyroids] and 7 patients with the M1 lymph node. The complete response (CR) was achieved in 15 patients, stable disease in 2, and progressive disease in 1. Of 15 patients with CR, 7 experienced recurrence, and 8 had continued CR. Frequent cases of grade ≥3 adverse effects included leucopenia, neutropenia, febrile neutropenia, and pharyngeal pain. The 3-year overall survival rate, disease-free survival rate, and disease-specific survival rate were 44.2%, 47.7%, and 48.6%, respectively. CONCLUSION: DCF-RT for advanced cervical esophageal cancer could achieve a favorable prognosis with larynx preservation. Further observations are warranted to establish the long-term prognosis, late complications of radiotherapy, and the significance of salvage surgery.