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.

S-1 and Oxaliplatin Versus Tegafur-uracil and Leucovorin as Postoperative Adjuvant Chemotherapy in Patients With High-risk Stage III Colon Cancer (ACTS-CC 02): A Randomized, Open-label, Multicenter, Phase III Superiority Trial.

BACKGROUND: The efficacy of S-1 plus oxaliplatin (SOX) as postoperative adjuvant chemotherapy for colon cancer has not been established. This randomized phase III study was designed to verify the superiority of SOX over tegafur-uracil and leucovorin (UFT/LV) in patients with high-risk stage III colon cancer (any T, N2, or positive nodes around the origin of the feeding arteries). PATIENTS AND METHODS: Patients who underwent curative resection for pathologically confirmed high-risk stage III colon cancer were randomly assigned to receive either UFT/LV (300 mg/m2 of UFT and 75 mg/day of LV on days 1-28, every 35 days, 5 cycles) or SOX (100 mg/m2 of oxaliplatin on day 1 and 80 mg/m2 of S-1 on days 1-14, every 21 days, 8 cycles). The primary endpoint was disease-free survival (DFS). RESULTS: A total of 478 patients in the UFT/LV group and 477 patients in the SOX group were included in the primary analysis. The 3-year DFS was 60.6% (95% confidence interval [CI], 56.0%-64.9%) in the UFT/LV group and 62.7% (95% CI, 58.1%-66.9%) in the SOX group. The stratified hazard ratio for DFS was 0.90 (95% CI, 0.74-1.09; stratified log-rank test, P = .2780). In the N2b subgroup, the 3-year DFS was 46.0% (95% CI, 37.5%-54.0%) in the UFT/LV group and 54.7% (95% CI, 45.7%-62.7%) in the SOX group (hazard ratio, 0.76; 95% CI, 0.55-1.05). CONCLUSION: As postoperative adjuvant chemotherapy, SOX was not superior to UFT/LV in terms of DFS in patients with high-risk stage III colon cancer.

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.

Treatment of spontaneous esophageal rupture (Boerhaave syndrome) using thoracoscopic surgery and sivelestat sodium hydrate.

BACKGROUND: The mortality rate of spontaneous esophageal rupture remains 20% to 40% due to severe respiratory failure. We have performed thoracoscopic surgery for esophageal disease at our department since 1994. Sivelestat sodium hydrate reportedly improves the pulmonary outcome in the patients with acute lung injury (ALI). METHODS: We retrospectively evaluated the usefulness of thoracoscopic surgery and perioperative administration of sivelestat sodium hydrate for spontaneous esophageal rupture in 12 patients who underwent thoracoscopy at our department between 2002 and 2014. RESULTS: The patient cohort included 11 males and one female (median age, 61 years). The lower left esophageal wall was perforated in all patients. Surgical procedures consisted of thoracoscopic suture and thoracic drainage in six patients, transhiatal suture and thoracoscopic thoracic drainage in five, and thoracoscopic esophagectomy and thoracic drainage in one. The median time from onset to surgery was 8 hours with a surgical duration of 210 minutes, blood loss 260 mL, postoperative ventilator management 1 day, intensive care unit (ICU) stay 5 days, and interval to restoration of oral ingestion 13 days. Postoperative complications included respiratory failure in four patients, pyothorax in three, and leakage in one. There was no instance of perioperative mortality. Regarding perioperative administration of sivelestat sodium hydrate, the postoperative arterial oxygen partial pressure-to-fractional inspired oxygen ratio (P/F) and C-reactive protein (CRP) levels in the administration group were significantly better than those in the non-administration group on postoperative days 4 (P=0.035) and 5 (P=0.037), respectively. In contrast, there was no significant difference between the groups in median time of ventilator management, ICU stay, oral ingestion following surgery, or hospital stay. CONCLUSIONS: Thoracoscopic surgery obtained acceptable results in all patients, including two with a significant time elapse from onset to treatment. Furthermore, sivelestat sodium hydrate was suggested to help improve postoperative respiration and inflammatory response.

A case of gastrointestinal bleeding due to right hepatic artery pseudoaneurysm following total remnant pancreatectomy: A case report.

INTRODUCTION: Pseudoaneurysm is a serious complication after pancreatic surgery, which mainly depends on the presence of a preceding pancreatic fistula. Postpancreatectomy hemorrhage following total pancreatectomy is a rare complication due to the absence of a pancreatic fistula. Here we report an unusual case of massive gastrointestinal bleeding due to right hepatic artery (RHA) pseudoaneurysm following total remnant pancreatectomy. PRESENTATION OF CASE: A 75-year-old man was diagnosed with intraductal papillary mucinous carcinoma recurrence following distal pancreatectomy and underwent total remnant pancreatectomy. After discharge, he was readmitted to our hospital with melena because of the diagnosis of gastrointestinal bleeding. Gastrointestinal endoscopy was performed to detect the origin of bleeding, but an obvious bleeding point could not be detected. Abdominal computed tomography demonstrated an expansive growth, which indicated RHA pseudoaneurysm. Emergency angiography revealed gastrointestinal bleeding into the jejunum from the ruptured RHA pseudoaneurysm. Transcatheter arterial embolization was performed; subsequently, bleeding was successfully stopped for a short duration. Because of improvements in his general condition, the patient was discharged. DISCUSSION: To date, very few cases have described postpancreatectomy hemorrhage following total remnant pancreatectomy. We suspect that the aneurysm ruptured into the jejunum, possibly because of the scarring and inflammation associated with his two complex surgeries. CONCLUSION: Pseudoaneurysm should be considered when the fragility of blood vessels is suspected, despite no history of anastomotic leak and intra-abdominal abscess. Our case also highlighted that detecting gastrointestinal bleeding is necessary to recognize sentinel bleeding if the origin of bleeding is undetectable.

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.

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.

Outcomes of a staged surgical treatment strategy for aortoesophageal fistula.

BACKGROUND: Evolution of thoracic endovascular aortic repair (TEVAR) appears to have influenced the pathogenesis and treatment strategy for aortoesophageal fistula (AEF). The purposes of this study are to evaluate our current surgical strategy for AEF and to provide insight to further improve the prognosis of such a devastating condition. METHODS AND RESULTS: Between 2005 and 2013, we retrospectively reviewed the clinical charts of 10 patients requiring surgical treatment for AEF in Tohoku University Hospital. Four cases were primary and 6 were secondary. Initially, bridging TEVAR to control bleeding with concomitant subtotal esophagectomy and complete debridement of infected mediastinal tissue was performed. After a short interval, the patients underwent in situ aortic replacement with cryopreserved homografts or rifampicin-bonded Dacron grafts with omentopexy. Esophageal reconstruction was planned following general physical status improvement after 3-6 months. In-hospital mortality in the acute phase was 30%. Although the completion of the staged strategy achieving successful esophageal reconstruction was possible in 5 patients, no local relapses of infection were observed in these patients. Overall survival at 1 and 5 year were 68.6 and 42.9%, respectively. CONCLUSIONS: The staged surgical treatment strategy for AEF consisted of prompt TEVAR to control bleeding with concomitant subtotal esophagectomy and subsequent in situ reconstruction of the aorta with an aortic homograft. This procedure enabled us to control local mediastinal infection with acceptable mortality. Avoiding delay in the diagnosis and initial treatment and resolving complications at each treatment step should further improve AEF treatment.

Comparison of short-term outcomes between prone and lateral decubitus positions for thoracoscopic esophagectomy.

BACKGROUND: Prone thoracoscopic esophagectomy was introduced at our institution from 2012. This study describes our experiences of the main differences between thoracoscopic esophagectomy in the prone and traditional left lateral decubitus positions together with an analysis of the short-term surgical outcomes. METHOD: In total, 87 patients undergoing thoracoscopic esophagectomy between January 2012 and October 2013 at Tohoku University Hospital were enrolled; of these, 54 and 33 patients were operated in the prone (Group P) and lateral decubitus (Group L) positions, respectively. RESULTS: The background of the patients was similar, and there was no in-hospital mortality. There were no significant differences between the groups in terms of whole surgical duration, thoracic duration, and number of dissected lymph nodes. Total blood loss and thoracic estimated blood loss were significantly lower in Group P than Group L. Furthermore, postoperative pulmonary complications, intensive care unit stay, and hospital stay were significantly lower in Group P. CONCLUSION: Thoracoscopic esophagectomy in the prone position is feasible and safe. The prone position technique may be superior to conventional lateral decubitus position esophagectomy.

Complications following recurrent laryngeal nerve lymph node dissection in oesophageal cancer surgery.

OBJECTIVES: The recurrent laryngeal nerve lymph node is one of the most common metastatic sites in oesophageal cancer, and dissection of this lymph node is considered beneficial. Although the risk of complications from this procedure, such as recurrent laryngeal nerve palsy, is well known, few reports have detailed those risks in a large number of cases. Our study examined the risks of recurrent laryngeal nerve lymph node dissection, with a special focus on recurrent laryngeal nerve palsy. METHODS: Retrospectively collected data from 661 patients, who underwent transthoracic oesophagectomy for oesophageal cancer, were analysed. RESULTS: Recurrent laryngeal nerve palsy occurred in 36% of the patients. Among these patients, except those in whom recurrent laryngeal nerve was intentionally excised due to metastatic lymph node, permanent palsy was detected in 12%. Bilateral recurrent laryngeal nerve lymph node dissection, cervical anastomosis and upper oesophageal cancer were independent risk factors for recurrent laryngeal nerve palsy. Although recurrent laryngeal nerve palsy was a risk factor for aspiration, tracheostomy and postoperative pneumonia, it did not directly correlate with death caused by pneumonia. Among postoperative complications, only recurrent laryngeal nerve palsy correlated with bilateral recurrent laryngeal nerve lymph node dissection. CONCLUSIONS: Recurrent laryngeal nerve palsy is a complication that should be avoided but does not seem to be severe enough to affect patient survival after surgery. Although bilateral recurrent laryngeal nerve lymph node dissection can induce recurrent laryngeal nerve palsy in patients who undergo transthoracic oesophagectomy, this procedure did not correlate with aspiration and pneumonia.

A human thyroid cancer cell line, DH-14-3, newly established from poorly differentiated thyroid carcinoma.

Poorly differentiated thyroid carcinoma (PDTC) is a newly recognized histological type of malignant thyroid tumor, accounting for about 2 - 13% of all thyroid carcinomas. PDTC is considered as a morphologically and biologically intermediate stage between well-differentiated thyroid carcinoma and anaplastic thyroid carcinoma. PDTC preferentially manifests bone metastases. We here established a cell line from a resected tumor specimen from a 70-year-old male patient with PDTC who presented with multiple bone metastases. This new thyroid tumor cell line was designated as DH-14-3 and was subsequently grown in culture for several years. DH-14-3 cells express thyroglobulin in the cytoplasm and thyroid transcription factor-1 in the nuclei, both proteins of which are specific markers for the thyroid gland. Importantly, triiodothyronine (T3) was detected in the cultured medium of DH-14-3 cells, in which, however, thyroxine (T4) was undetectable. Moreover, DH-14-3 cells secreted interleukin-8, transforming growth factor-ß1, vascular endothelial growth factor, matrix metalloproteinase-1 and parathyroid hormone-related protein, all of which may be responsible for the aggressiveness or bone metastasis of PDTC. Thus, the production of these proteins may reflect the metastatic potential of this cell line. DH-14-3 cells also express CXC chemokine receptor-4 and epidermal growth factor receptor, and carry a missense mutation in the p53 tumor suppressor gene. In fact, transplantation of DH-14-3 cells into the back of nude mice resulted in the formation of tumors, thereby confirming the capability of tumorigenesis. DH-14-3 cells may be useful for investigating the biological features of PDTC and will contribute to the therapeutic study of thyroid cancer.

A strategy for supraclavicular lymph node dissection using recurrent laryngeal nerve lymph node status in thoracic esophageal squamous cell carcinoma.

BACKGROUND: The desirability of supraclavicular lymph node (LN) dissection, which is the cervical part of three-field LN dissection, has been discussed for a long time. In this study, we examine the pattern of supraclavicular LN metastasis in esophageal cancer, with a particular focus on the correlation between recurrent laryngeal nerve (RLN) LN and supraclavicular LN metastasis. METHODS: In all, 220 cases of R0 resected T1 to T3 squamous cell carcinomas were retrospectively examined. All of these patients underwent bilateral RLN LNs dissection; none received cancer treatment before surgery. RESULTS: Of 21 upper esophageal cancer cases, 33.3% of the patients had metastasis in the supraclavicular LN. Every patient in whom supraclavicular LN metastasis developed had metastasis in the RLN LN. Of 141 cases of middle esophageal cancer, 19.1% had metastasis in the supraclavicular LN. Among the patients whose RLN LN metastasized, 38.3% had metastasis in the supraclavicular LN. A similar correlation between RLN LN and supraclavicular LN metastasis was observed in lower esophageal cancer cases, especially in T3 cases. When considering cancers of the esophagus and patients who had metastasis in the supraclavicular LN, our data demonstrated that RLN LN metastasis did not always lead to metastasis on the same side of the supraclavicular LN. CONCLUSIONS: The status of the RLN LN can be an indicator of supraclavicular LN dissection in upper esophageal cancer patients and advanced cases of middle and lower esophageal cancer patients. Bilateral supraclavicular LN dissection should be recommended even when only unilateral RLN LN metastasis occurs.

Murine double minute 2 and its association with chemoradioresistance of esophageal squamous cell carcinoma.

BACKGROUND: Definitive chemoradiotherapy (dCRT) has been established as the standard treatment for esophageal squamous cell carcinoma (ESCC). However, many patients develop persistent or recurrent disease following dCRT. We investigated factors related to chemoradioresistance and treatment outcomes in patients with ESCC who underwent salvage esophagectomy after dCRT. PATIENTS AND METHODS: We selected 38 patients with persistent disease and 24 with recurrent disease who underwent salvage esophagectomy after dCRT, immunolocalized p53, p16, p27, murine double minute 2 (MDM2), cyclin D1, Ki-67, and epidermal growth factor receptor, and correlated the findings with clinicopathological features. RESULTS: MDM2 positivity was significantly higher among patients with persistent disease than among those with recurrent disease (p<0.0001). In addition, negative p16 expression was a predictor of poor prognosis among patients with persistent disease. CONCLUSION: MDM2 overexpression plays an important role in chemoradioresistance of ESCC; furthermore, negative p16 expression can predict poor prognosis of patients with persistent disease.

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.