The sterno-tracheal distance is an important factor of anastomotic leakage of retrosternal gastric tube reconstruction after esophagectomy.

BACKGROUND: Anastomotic leakage (AL) is a serious complication after esophagectomy. The retrosternal (RS) route has been selected majorly to reduce reflux and related pneumonia and considering mediastinal recurrences. AL has been developed more in RS than posterior mediastinal (PM) route reconstruction. Therefore, we suspected the sterno-tracheal distance (STD) might be related to AL and started the selection according to the STD from 2009. METHODS: A total of 221 patients who underwent a subtotal esophagectomy with gastric tube reconstruction during January 2004-April 2017 were investigated. The patients were classified into the 'after STD selection' (A; n = 144) group and the 'before STD selection' (B, n = 77) group. The incidences of and the risk factors for AL between the two groups were compared. RESULTS: The incidence of AL was high in the B group (18.2%), and 78.6% of the patients who developed AL were treated with RS route reconstruction. The median STDs of the patients with AL and no AL were 10.3 mm and 14.5 mm, respectively (p = 0.001). These results demonstrated that the STD was a risk factor for AL in the RS route. Based on these results, 13 mm was set as the cutoff value. After STD selection, the median STD increased from 14.0 to 17.3 mm (p = 0.001), and the incidence of AL decreased significantly from 26.2 to 11.1% in the RS route (p = 0.037). CONCLUSION: The STD was the independent risk factor for AL in the RS route. RS route reconstruction should be avoided for the patients with STD < 13 mm.

The effects of the herbal medicine Daikenchuto (TJ-100) after esophageal cancer resection, open-label, randomized controlled trial.

BACKGROUND: Daikenchuto (TJ-100), a traditional Japanese herbal medicine, is widely used in Japan. Its effects on gastrointestinal motility and microcirculation and its anti-inflammatory effect are known. The purpose of this prospective randomized controlled trial was to investigate the effect of TJ-100 after esophagectomy in esophageal cancer patients. METHODS: Forty patients for whom subtotal esophageal resection for esophageal cancer was planned at our institute from March 2011 to August 2013 were enrolled and divided into two groups at the point of determination of the operation schedule after informed consent was obtained: a TJ-100 (15 g/day)-treated group (n = 20) and a control group (n = 20). The primary efficacy end-points were maintenance of the nutrition condition and the recovery of gastrointestinal function. The secondary efficacy end-points were the serum C-reactive protein (CRP) level and adrenomedullin level during the postoperative course, the incidence of postoperative complications, and the length of hospital stay after surgery. RESULTS: We examined 39 patients because one patient in the TJ-100 group was judged as having unresectable cancer after surgery. The mean age of the TJ-100 group patients was significantly older than that of the control group patients.The rate of body weight decrease at postoperative day 21 was significantly suppressed in the TJ-100 group (3.6% vs. the control group: 7.0%, p = 0.014), but the serum albumin level was not significantly different between the groups. The recovery of gastrointestinal function regarding flatus, defecation, and oral intake showed no significant between-group differences, but postoperative bowel symptoms tended to be rare in the TJ-100 group. There was no significant between-group difference in the length of hospital stay after surgery. The serum CRP level at postoperative day 3 was 4.9 mg/dl in the TJ-100 group and 6.9 mg/dl in the control group, showing a tendency of a suppressed serum CRP level in the TJ-100 group (p = 0.126). The rate of increase in adrenomedullin tended to be high postoperatively, but there was no significant difference between the two groups. CONCLUSIONS: TJ-100 treatment after esophageal cancer resection has the effects of prompting the recovery of gastrointestinal motility and minimizing body weight loss, and it might suppress the excess inflammatory reaction related to surgery.

CXCR4 Expression is Associated with Poor Prognosis in Patients with Esophageal Squamous Cell Carcinoma.

BACKGROUND: Chemokines and their receptors are known to play important roles in the tumorigenesis of many malignancies. The chemokine CXCL12 and its receptors CXCR4 and CXCR7 were suggested to be involved in cancer invasion and metastasis. The aim of this retrospective study was to evaluate the prognostic impact of the expressions of CXCL12, CXCR4 and CXCR7 in patients with esophageal squamous cell carcinoma (ESCC). METHODS: We used immunohistochemistry (IHC) and reverse transcriptase-polymerase chain reaction (RT-PCR) to evaluate the expressions of CXCL12, CXCR4, and CXCR7 in ESCC patients' tumor biopsy specimens obtained during preoperative endoscopy or surgery. These results were compared with the patients' clinicopathological parameters and survival. RESULTS: IHC was conducted for 172 patients. High expression of CXCR4 in the cytoplasm and nuclei and that of CXCR7 were associated with poor cause-specific survival (CSS) (P= .002 and .010, respectively). The specimens from 52 of the 172 patients were examined by RT-PCR and quantitative real-time PCR. The expression levels of messenger RNA (mRNA) of CXCR4 and CXCR7 were significantly increased in the tumors compared with normal esophageal mucosae (P < .0001). The expression level of mRNA of CXCR4 was associated with poor recurrence-free survival and CSS (P = .012 and .038, respectively). CONCLUSIONS: CXCR4 expression is associated with poor prognosis in patients with ESCC.

Aldehyde dehydrogenase 1 expression is associated with poor prognosis in patients with esophageal squamous cell carcinoma.

BACKGROUND: Aldehyde dehydrogenase 1 (ALDH1) and CD44 act as important biomarkers in several solid tumors. However, few studies have examined the relationships between ALDH1 expression and the prognosis and clinical characteristics of esophageal squamous cell carcinoma (ESCC). METHODS: This study was a retrospective case-control study and included 152 patients with ESCC. A total of 56 patients underwent surgery (OP group), 40 patients received neoadjuvant chemotherapy involving weekly docetaxel plus 5-fluorouracil and low-dose cisplatin (DFP therapy) prior to undergoing surgery (NAC group), and 56 patients received initial systemic DFP therapy (CT group). The ALDH1 and CD44 immunohistochemical expression levels of each tumor were evaluated and compared with the prognosis and clinical characteristics of the ESCC patients. RESULTS: In the OP and NAC groups, multivariate analysis found that ALDH1 was independently associated with postoperative recurrence and prognosis (OP group, P=0.004 and 0.016, respectively; NAC group, P=0.026 and 0.014, respectively). In addition, CD44 was found to be associated with postoperative recurrence in the OP group and prognosis in the NAC group (P=0.024 and 0.047, respectively). Among the ALDH1-negative clinical stage II/III patients, the OP and NAC groups displayed better prognoses than the CT group (P<0.001). However, among the ALDH1-positive clinical stage II/III patients, the OP and NAC groups displayed poorer prognoses than the CT group (P=0.049). CONCLUSIONS: ALDH1 was found to be a predictor of postoperative recurrence and prognosis in ESCC, and CD44 might be a predictor of recurrence and prognosis. ALDH1 expression might affect the treatment strategy for ESCC.

[Pathological complete response in a case of advanced esophageal cancer invading aorta treated by preoperative chemotherapy with docetaxel and cisplatin plus 5-FU].

The patient was a 64-year-old man, diagnosed as cStage IVa esophageal cancer invading the aorta with lymph node metastasis. He received combination chemotherapy with docetaxel/cisplatin/5-FU(DFP therapy). After one course, CT and endoscopic examination showed remarkable reduction of the primary lesion and lymph node metastasis. We performed subtotal esophagectomy and gastric tube reconstruction by the retroposterior mediastinum route. The pathological specimen evidenced fibrosis and infiltration of inflammatory cells on almost all layers, but showed no viable malignant cells in the middle thoracic esophagus. Therefore, the pathological effect was judged as Grade 3(pCR). This case suggested that DFP combination chemotherapy may prove to be a useful treatment for advanced esophageal cancer with invasion to other organs.

Prognosis of esophageal squamous cell carcinoma in patients positive for human epidermal growth factor receptor family can be improved by initial chemotherapy with docetaxel, fluorouracil, and cisplatin.

BACKGROUND: The human epidermal growth factor receptor (HER) family, Ki-67 and p53 are important biomarkers for several malignancies. However, few studies have examined the role of these in prognosis and therapeutic sensitivity of esophageal squamous cell carcinoma (ESCC). The efficacy of triple-drug combination therapy with docetaxel, fluorouracil and cisplatin has recently been expected for ESCC. METHODS: Subjects comprised 142 patients with ESCC who underwent operation (OP group, n = 54), neoadjuvant chemotherapy with docetaxel, fluorouracil, and cisplatin (DFP therapy) followed by operation (NAC group, n = 37) or initial systemic DFP therapy (CT group, n = 51) between January 2004 and December 2010. Immunohistochemical expressions of epidermal growth factor receptor (EGFR), HER2, HER3, Ki-67, and p53 were evaluated and compared with prognosis and sensitivity to DFP therapy. RESULTS: Positive correlations existed between EGFR, HER2, and HER3 expressions. In the OP group, EGFR was independently associated with postoperative recurrence in multivariate analysis (P = .036). In the NAC group, EGFR correlated with pathological response to DFP therapy (P = .004). In the CT group, EGFR, HER2, and HER3 correlated with clinical response to DFP therapy and EGFR was independently associated with favorable prognosis in multivariate analysis (P = .022). CONCLUSION: EGFR represents a predictor of postoperative recurrence and sensitivity to triple-drug combination therapy including a taxane. EGFR-positive patients may show improved prognosis with taxane combination chemotherapy and molecular targeted therapy for HER family members.

Sentinel lymph node biopsy using intraoperative indocyanine green fluorescence imaging navigated with preoperative CT lymphography for superficial esophageal cancer.

BACKGROUND: The sentinel lymph node (SLN) concept has been gaining attention for gastrointestinal neoplasms but remains controversial for esophageal cancer. This study evaluated the feasibility of SLN identification using intraoperative indocyanine green (ICG) fluorescence imaging (IGFI) navigated by preoperative computed tomographic lymphography (CTLG) to treat superficial esophageal cancer. METHODS: Subjects comprised 20 patients clinically diagnosed with superficial esophageal cancer. Five minutes after endoscopic submucosal injection of iopamidol around the primary lesion using a four-quadrant injection pattern with a 23-gauge endoscopic injection sclerotherapy needle, three-dimensional multidetector computed tomography was performed to identify SLNs and lymphatic routes. ICG solution was injected intraoperatively around the tumor. Fluorescence imaging was obtained by infrared ray electronic endoscopy. Thoracoscope-assisted standard radical esophagectomy with lymphadenectomy was performed to confirm fluorescent lymph nodes detected by CTLG. RESULTS: Lymphatic vessels and SLNs were identified preoperatively using CTLG in all cases. Intraoperative detection rates were 100% using CTLG and 95% using IGFI. Lymph node metastases were found in four cases, including one false-negative case with SLNs occupied by bulky metastatic tumor that were not enhanced with both methods. The other 19 cases, including three cases of metastatic lymph nodes, were accurately identified by both procedures. CONCLUSIONS: Preoperative CTLG visualized the correct number and site of SLNs in surrounding anatomy during routine computed tomography to evaluate distant metastases. Referring to CTLG, SLNs were identified using IGFI, resulting in successful SLN navigation and saving time and cost. This method appears clinically applicable as a less-invasive method for treating superficial esophageal cancer.

[A case of a patient with stage IVa esophageal cancer surviving over 4 years by combination chemotherapy with docetaxel,5 -FU and cisplatin, without operation].

A male patient in his 50s was found to have lower thoracic advanced esophageal squamous cell carcinoma by upper gastrointestinal endoscopy with the chief complaint of dysphagia in July 2006. CT revealed supraclavicular lymph node metastasis, and he was diagnosed as clinical stage IVa. He underwent two courses of combination chemotherapy with docetaxel, 5-FU and cisplatin(DFP therapy: docetaxel at 25mg/m / / 2 on day 1, 5-FU at 370 mg/m2 on days 1-5, and cisplatin at 7 mg/m2 on days 1-5 were repeated weekly for 4 weeks). The primary tumor disappeared and the lymph node was reduced as observed by upper gastrointestinal endoscopy and CT. After 2 courses of DFP therapy, PET-CT revealed that the primary tumor and lymph node had no new accumulation. Because he refused both operation and chemoradiotherapy, the patient underwent oral chemotherapy. In January 2010, PET-CT and upper gastrointestinal endoscopy revealed that the primary tumor relapsed. DFP therapy was performed and was effective once again. He has survived for over 4 years and 4 months without operation.

Risk assessment of morbidities after right hemicolectomy based on the National Clinical Database in Japan.

OBJECTIVE: Nationwide databases are expected to provide critical data to improve medical practice. The present study used such data to develop risk models for clinically important outcomes after right hemicolectomy based on preoperative risk factors. METHODS: Japan's National Clinical Database (NCD) identified 38 030 cases of right hemicolectomy in the years 2011 and 2012. These were used to analyze correlations between mortality and eight selected clinical outcomes of interest by Pearson's correlation coefficient (r). To construct risk models for the eight selected clinical outcomes, 80% of all the examined cases were extracted randomly as a development cohort, and preoperative risk factors for each clinical outcome were identified using a forward stepwise selection method. Morbidities predicted from the risk models were used to find areas under the receiver operator curves among the remaining 20% of the testing cohort. RESULTS: The following clinical outcomes were identified as highly associated with operative mortality: systemic sepsis (r = .360), renal failure (r = .341), unplanned intubation (r = .316) and central nervous system (CNS) occurrences (r = .301). Risk models containing up to 21 preoperative variables were constructed for these eight postoperative clinical outcomes. Predictive values of the eight models were as follows: surgical site infections (0.634), anastomotic leakage (0.656), systemic sepsis (0.816), pneumonia (0.846), unplanned intubation (0.838), renal failure (0.883), CNS occurrences (0.833) and transfusion >5 units (0.846). CONCLUSIONS: This study indicated that the NCD-generated risk models for six of the eight selected critical postoperative outcomes had high discrimination among right hemicolectomy patients. These risk models can accurately identify high-risk patients prior to surgery.

Efficacy of percutaneous endoscopic gastrostomy on unplanned treatment interruption and nutritional status in patients undergoing chemoradiotherapy for advanced head and neck cancer.

OBJECTIVE: Efficacy of percutaneous endoscopic gastrostomy (PEG) on unplanned treatment interruption and nutritional status was examined in patients undergoing chemoradiotherapy (CRT) for advanced head and neck cancer. METHODS: We retrospectively reviewed hospital charts of 44 patients with advanced head and neck cancer who were treated with CRT. RESULTS: CRT-induced mucositis of grade 3 or worse and inadequate oral intake of less than one third of their usual intake developed in 33 patients who were recommended PEG placement, but not in 11 patients. Thirteen patients accepted PEG placement and then completed CRT (compliant group). However, among 20 patients who refused both PEG and nasogastoric tube (NGT) placements (non-compliant group), 10 required unplanned interruptions of CRT at a radiation dose around 30-40 Gy (UI-CRT group) while 10 others could complete CRT without interruption (C-CRT group) CRT. Total serum protein levels were significantly decreased after CRT in all patients. DISCUSSION: It is suggested that therapeutic PEG placement is useful for preventing unplanned interruption of CRT in patients with advanced head and neck cancer. After severe mucositis and inadequate oral intake have developed during CRT, PEG placement should be considered before the radiation therapy dose of 30 Gy.

Glutamine protects the small intestinal mucosa in anticancer drug-induced rat enteritis model.

Supportive therapy during chemotherapy has become essential, but effective preventive therapies to gastrointestinal mucosal injury are few. We investigated the efficacy of glutamine in rat anticancer drug-induced enteritis model. In this study, we used twenty male SD rats. They were divided into control, 5-fluorouracil (5-FU) (orally administered at 20 mg/kg day), 5-FU+glutamine (1000 mg/kg/day) and 5-FU+glutamine+fiber and oligosaccharide (GFO(®)) (1000 mg/kg/day) groups. All groups were sacrificed on day 6 and upper jejunums were excised. The jejunal villous height was measured in specimens. IgA level in jejunal washing solution, and serum diamine oxidase activity were also measured. The jejunal villous height was recognized as shorter in the specimen from 5-FU treated rats compared with 5-FU+glutamine treated rats (p<0.001). Serum diamine oxidase activity in 5-FU+glutamine group were significantly superior to that in 5-FU group (p=0.028). IgA level in jejunal washing solution tended to be higher in 5-FU+glutamine group than that in 5-FU group (p=0.076). On the other hand, serum diamine oxidase activity and IgA level in jejunal washing solution showed no significant difference between 5-FU+GFO and 5-FU treatment group. Our results suggest that glutamine showed protective effects on mucosal injury of small intestine in rat anticancer drug-induced enteritis model.

Alteration of the oral environment in patients undergoing esophagectomy during the perioperative period.

OBJECTIVE: During the perioperative period, oral ingestion is changed considerably in esophagectomy patients. The aim of this study was to investigate oral environment modifications in patients undergoing esophageal cancer treatments due to changes in dietary intake and swallowing functions. MATERIAL AND METHODS: Thirty patients who underwent operation for removal of esophageal cancer in Tokushima University Hospital were enrolled in this study. RESULTS: It was found that 1) the flow rate of resting saliva decreased significantly at postoperative period by deprived feeding for one week, although it did not recover several days after oral ingestion began, 2) the accumulation of dental plaque and the number of mutans streptococci in saliva decreased significantly after operation, while both increased relatively quick when oral ingestion began, and 3) the swallowing function decreased significantly in the postoperative period. CONCLUSIONS: These results suggest that dental professionals should emphasize the importance of oral health care and provide instructions on plaque control to patients during the perioperative period of esophageal cancer treatment.

The new era of staging as a key for an appropriate treatment for esophageal cancer.

Fluorodeoxyglucose-positron emission tomography (FDG-PET) and computed tomography (CT) have become the gold standard for staging of esophageal cancer by detecting distant metastases, but metastatic lymph nodes are often difficult to diagnose from the size and standardized uptake value (SUV). If we compare the diagnostic performance of endoscopic ultrasonography (EUS), CT, and FDG-PET in staging of esophageal cancer, EUS is the most sensitive method to identify the detection of regional lymph node metastases, whereas CT and FDG-PET are more specific tests. Combination study with CT, EUS and PETCT cannot make a precise diagnosis after neoadjuvant therapy (NAT). A precise staging might be determined by the fine needle aspiration biopsy (FNAB) under EUS and US screening in the neck and the abdomen even after NAT. Indication of endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) for superficial cancer is sensitive because of difficulty in T1b cancer diagnosis. Detailed examination about vessel invasion and the possibility of residual tumor with dissected specimen will offer an appropriate additional therapy. New strategy like sentinel lymph node (SLN) navigation could supply more information about lymphatic routes and metastatic nodes. SLN navigation with ESD might become a new less invasive strategy for superficial esophageal cancer.

Laparoscopic permanent sigmoid stoma creation through the extraperitoneal route.

About 50% of patients who have a permanent stoma experience some degree of parastomal hernia formation. To prevent this complication, the extraperitoneal route is considered to be more effective than the transperitoneal route in the case of open colorectal surgery. This technique also has superiority in avoiding postoperative intestinal obstruction. Although laparoscopic surgery for rectal cancer has not been proved to be as safe as open surgery by a randomized-controlled trial, some studies have shown the equality of long-term results with laparoscopic low anterior resection and laparoscopic abdominoperineal resection. It is anticipated that cases of laparoscopic abdominoperineal resection will increase in the near future. However, a laparoscopic technique for creation of a permanent stoma has hardly been discussed. Most operative procedures for laparoscopic stoma creation have been performed with transperitoneal route, which may cause parastomal hernia and/or intestinal obstruction. This report describes a laparoscopic technique for permanent sigmoid stoma creation through the extraperitoneal approach.

Resected xanthogranulomatous pancreatitis.

Xanthogranulomatous changes in the pancreas are extremely rare. A 66-year-old man presented with a 2-year history of epigastralgia. Computed tomography scan revealed a 4-cm low-density area around the body of the pancreas. Magnetic resonance imaging demonstrated that the mass appeared hyperintense on a T2-weighted image and isointense on a T1-weighted image. Based on a diagnosis of invasive ductal carcinoma of the pancreas, distal pancreatectomy and splenectomy were performed. Sections examined from the mass showed an aggregation of many foamy histiocytes, lymphocytes, and plasma cells. The surrounding pancreatic tissue showed fibrosis and chronic inflammation. These findings suggested a xanthogranulomatous inflammation, and resulted in a diagnosis of xanthogranulomatous pancreatitis.

New laparoscopic double-stapling technique.

BACKGROUND: Laparoscopic surgery for colon cancer has been shown by several randomized, controlled trials to be an acceptable alternative to open surgery; however, laparoscopic rectal surgery has not been evaluated in a randomized trial. One of the most serious problems associated with laparoscopic rectal surgery are bowel clamping, irrigation, and transection of the rectum, and laparoscopic rectal surgery has not been as reliable as open rectal surgery. MATERIALS AND METHODS: We present our new technique, the laparoscopic double-stapling technique, which eliminates these problems. This technique uses curved Doyen forceps introduced through the wound just above pubis symphysis for clamping the rectal wall at the anal side of the tumor. An endolinear stapler (length 60 mm) is inserted through the same wound, applied at the rectal wall parallel and caudal to the Doyen forceps, and transects the rectum under pneumoperitoneum. We used this technique for eight cases of rectal surgery. RESULTS AND DISCUSSION: The laparoscopic double-stapling technique provided secure bowel clamping and rectal irrigation. The number of cartridges used in laparoscopic double-stapling technique cases was not more than 2, with an average of 1.6 per patient. None of the laparoscopic double-stapling technique cases experienced major complications. CONCLUSION: We consider that many cases of rectal cancer that are suitable for laparoscopic low anterior resection can undergo laparoscopic surgery by using this technique, which will improve the quality of rectal surgery.