Evaluation of Intraoperative Neural Monitoring During Thoracoscopic Surgery for Esophageal Cancer.

BACKGROUND/AIM: Recurrent laryngeal nerve paralysis (RLNP) induces aspiration pneumonia and reduces the patient's quality of life. To decrease the incidence of RLNP, we performed intraoperative neural monitoring (IONM) during thoracoscopic surgery for esophageal cancer and evaluated its usefulness. PATIENTS AND METHODS: A total of 737 consecutive patients who underwent thoracoscopic surgery for esophageal cancer were enrolled in this study. Between May 1995 and March 2016, thoracoscopic esophagectomies were performed using video-assisted thoracoscopic surgery (VATS) with a small incision, whereas from April to June 2023, we used positive pressure pneumothorax with port placement only [minimum invasive esophagectomy (MIE)]. A total of 110 consecutive patients who underwent thoracoscopic surgery with IONM (IONM group) were retrospectively compared with those who underwent VATS or MIE without IONM (No-IONM group). RESULTS: The incidence of RLNP [Clavien-Dindo (CD) classification of ≥1] on postoperative day (POD) 5 was 13.9% in the IONM group, which was significantly lower than that of the no-IONM group (31.2%, p<0.001). Even when comparing only patients who underwent MIE, the incidence of RLNP on POD5 was 13.9% in the IONM group, which was significantly lower than that in the no-IONM group (26.2%, p=0.035). The incidence of postoperative pneumonia (CD ≥2) was 10.9% in the IONM group, which was significantly lower than that in the no-IONM group (26.1%, p=0.005). Bilateral RLNP did not occur in any of the IONM groups. CONCLUSION: IONM is a useful tool for reducing RLNP incidence and postoperative pneumonia after thoracoscopic surgery for esophageal cancer.

[A Case of Perforation at the Stump of Descending Colon after Hartmann's Operation Performed after Transverse Colostomy].

A 77-year-old man with complaining of anemia and abdominal pain was admitted to our hospital. An abdominal computed tomography showed the sigmoid colon tumor with bowel obstruction. Laparoscopic transverse colostomy was performed to release intestinal obstruction. After first operation, he was diagnosed the sigmoid colon cancer: cT4b(bladder), cN0, cM0, and cStage Ⅱc. Radical laparoscopic operation(Hartmann's operation)was performed. On the 4th postoperative day, fecal juice was discharged from the abdominal drain placed in the Douglas fossa, so emergency laparotomy was performed. The intraoperative findings showed perforation in the blind end of the descending colon. The descending colon was resected from a site approximately 5 cm anal side of the transverse colostomy to the blind end. It was thought that perforation occurred due to an increase in internal pressure in the residual intestinal tract after Hartmann's surgery without blood flow disorder. We believe that further attention is required to the management of residual intestinal tract at the blind end for the obstructive colorectal cancer.

[Association between the Preoperative Nutritional Index and Postoperative Complications/Prognosis in Older Adults with Gastric Cancer Who Have Undergone a Gastrectomy].

We analyzed the relationship between preoperative nutritional indices and postoperative complications/prognoses in patients with pStage Ⅰ and Ⅱ gastric cancer aged ≥75 years who had undergone gastrectomy in our hospital. Between January 2012 and March 2021, a total of 79 cases of pStage Ⅰ and Ⅱ gastric cancer were examined in individuals aged ≥75 years who had undergone gastrectomy. We investigated the correlation between short- and long-term outcomes and the nutritional index. CONUT, GPS, and GNRI were employed as indicators of nutritional status. CONUT and GPS showed associations with postoperative complications and an extended postoperative hospital stay, whereas GNRI did not exhibit such associations. Among the patients, 7 deaths were attributed to primary diseases, whereas 16 deaths were attributed to other diseases. No correlation was found between survival rate and preoperative nutritional status. Conclusions: There were minimal cancer recurrences among older adults with gastric cancer who had undergone gastrectomy. Although preoperative nutritional status was associated with postoperative complications, it did not show an association with prognosis.

The safe removal of a superior mediastinal foreign body by mediastinoscopy: a case report.

BACKGROUND: Mediastinal foreign bodies might cause mediastinal organ injury or mediastinal abscess. The prompt removal surgery of mediastinal foreign bodies is needed to prevent those complications. We report a case in which a mediastinal foreign body was removed by video-mediastinoscopy. CASE PRESENTATION: The patient, a 74-year-old man with a chief complaint of hoarseness, was referred to our department for surgical management of a wooden foreign body that had traumatically migrated into the superior mediastinum. During the surgery, the video-mediastinoscopy was introduced under the pneumomediastinal pressure. We could dissect the scar tissue and remove the azalea tree branch safely and carefully, without damaging the other mediastinal organs. He was discharged on postoperative day 5, with no complications. CONCLUSIONS: Video-mediastinoscopic approach under pneumomediastinal pressure is minimally invasive and could provide wide surgical view. Therefore, we consider it useful and effective for removal of foreign bodies in the mediastinum.

High-Dose Chemotherapy With Autologous Stem Cell Transplantation in a Case of Refractory Peripheral T Cell Lymphoma With Tracheoesophageal Fistula: A Case Report.

A 46-year-old woman with a sore throat was diagnosed with anaplastic lymphoma kinase-negative anaplastic large cell lymphoma that had spread from the piriform fossa to the cervical esophagus. Tracheoesophageal fistula developed after induction chemotherapy. Because conservative repair was not applicable, intensified chemotherapy, including autologous stem cell transplantation was performed with the fistula remaining open. Laryngopharyngectomy and cervical esophagectomy were performed 6 months after transplantation. The optimal strategy for refractory lymphoma with active tracheoesophageal fistula remains undetermined. To the best of our knowledge, this is the first report describing the successful treatment of a patient with tracheoesophageal fistula who received high-dose chemotherapy supported by autologous stem cell transplantation.

[Small Bowel Obstruction Due to Internal Hernia Caused by the Vermiform Appendix, Mesentery of the Small Intestines, and Greater Omentum in a Patient with No History of Abdominal Surgery].

Our patient was a 69-year-old man being treated for hyperlipidemia. He was admitted to our hospital with the chief complaint of vomiting and abdominal pain. Abdominal computed tomography(CT)showed dilation of the distal small intestines, a small amount of ascites in the small intestines near the right pelvis, and a closed loop of the small intestine. Enhanced abdominal CT was performed to evaluate intestinal ischemia. Given the adequate blood flow to the wall, the small intestines forming the closed loop, and no increase in ascites, the patient was treated conservatively. Diagnostic laparoscopy was performed because of the narrowed lumen and incomplete obstruction observed on the abdominal CT and contrast- enhanced imaging of the ileal tube. The tip of the appendix adherent to the mesentery of the small intestines, approximately 80 cm from the ileum, and the omentum adherent to the bottom of the right pelvis caused the obstruction. A cord dissection and appendectomy were performed. Making the diagnosis was difficult because there was no history of appendicitis and the small intestinal obstruction was caused by adhesions in 2 places with no history of laparotomy.

[A Case Report of an Appendiceal Goblet Cell Carcinoid].

A 56-year-old woman complaining of right lower abdominal pain was admitted to our hospital. An abdominal computed tomography showed the enlarged appendix tip and a high density area around the appendix to retroperitoneum. The patient was diagnosis with acute appendicitis and underwent emergency laparoscopic appendectomy. Histopathological findings of the resected specimens revealed a component with signet ring cell carcinoma morphology that was positive for neuroendocrine markers by immunohistochemical staining, which led to the diagnosis of goblet cell carcinoid(GCC)of appendix. GCC cells were found to infiltrate the surrounding serosa and Ly positive. An additional laparoscopic ileocecal resection with D3 dissection was performed. In the appendix GCC, additional resection is considered because the lymph node metastasis rate increases(SS/13%)as the depth of wall progresses. Appendiceal tumors including GCC may develop acute appendicitis and may be followed by additional resection. Therefore, it is important to consider how to deal with the first surgery.

[A Case of Multiple Small Bowel GIST Complicated with von Recklinghausen's Disease].

The case was a 55-year-old woman. She have been pointed out von Recklinghausen's disease for several years. She was referred to our hospital due to multiple abdominal tumor and severe anemia. Enhanced CT examination revealed multiple intraabdominal tumors with central necrosis. The tumors diagnosed mesenchymal tumors associated with von Recklinghausen's disease, and tumor resection was indicated under laparotomy. Tumors were resected together with small and large bowel. The tumor in the pelvic space was resected together with the uterus and right ureter. She was discharged without any postoperative complications at 15 days after the operation. Because immunostaining was positive for CD34, c-kit and DOG1 and Ki-67-positive cells were 18%, the tumors were diagnosed with high-risk GIST for small bowel.

[Outcomes of Salvage Thoracoscopic Esophagectomy after Definitive Radiochemotherapy for Clinical Stage â £a Esophageal Cancer].

We investigated the clinical outcomes of salvage thoracoscopic esophagectomy for residual or recurrent cases after radical radiochemotherapy for cStage Ⅳa esophageal cancer. Thoracic procedure was started thoracoscopically in all cases, but converted to thoracotomy in 2 cases. The operation time was 315 minutes and the blood loss was 300 mL. Lymph node metastasis was diagnosed in 5 cases, and 2 cases were finished in R1or 2. Nine cases died of recurrence and 1 case died of pneumonia. The 2-year and 5-year survival rates(OS)of all cases were 46.1% and 28.3%, respectively. R1,2 cases and pN+ cases had significantly poor prognosis. Surgical treatment after radical radiochemotherapy for cStage Ⅳa esophageal cancer can be safely performed thoracoscopically. If R0 is not obtained, the long-term prognosis cannot be expected, and selection of R0 resectable cases is important.

[Clinical Outcomes of Recurrent Diseases after Esophagectomy According to Time of Recurrence].

We analyzed retrospectively the difference in treatment selection and prognosis according to timing of recurrence after radical resection of esophageal cancer. Of 190 patients who underwent radical esophagectomy for esophageal cancer from April 2010 to December 2017, 56 patients(29.5%)had recurrent diseases during the postoperative periods. These cases were divided into 27 cases with recurrence diagnosed less than 180 days after initial surgery(Group A)and 29 cases with recurrence diagnosed more than 180 days(Group B). Although there was no difference in the pathological staging, preoperative treatment, and type of recurrence between the 2 groups, there were significantly more cases with symptomatic recurrence in Group A. Surgical intervention was possible in 1 case in Group A and 10 cases in Group B, respectively. There was significantly more in Group B. Second-line treatment was possible in only 5 cases in Group B. Survival after recurrence was tend to have better in Group B. There are few cases who indicated surgical intervention and second-line treatment in early recurrence cases after radical esophagectomy for esophageal cancer, and the prognosis is poor in such cases.

Predictive factors of difficulty of thoracoscopic esophagectomy in the left decubitus position.

BACKGROUND: We have sometimes experienced technical difficulty performing thoracoscopic esophagectomy because of the position of the descending aorta or width of the mediastinal space. In this study, we retrospectively investigated predictive preoperative factors that influence the procedure of thoracoscopic esophagectomy with a focus on the position of the descending aorta and width of the mediastinal space. METHODS: Ninety-five patients who underwent thoracoscopic esophagectomy for esophageal cancer by two specialists were included in this study. Thirty patients in whom both the operation time and blood loss in the thoracic region exceeded the median were categorized to the difficult group. The remaining 65 patients were categorized into the common group. During the evaluation of the position of the descending aorta, we measured the aorta-vertebra angle at the level of the left inferior pulmonary vein. During the evaluation of the width of the mediastinal space, we measured the sternum-vertebra distance at the level of the tracheal bifurcation. RESULTS: A forward stepwise logistic regression analysis revealed the following independent predictive factors of the technical difficulty of thoracoscopic esophagectomy: aorta-vertebra angle (≥ 30°), sternum-vertebra distance (< 100 mm), and clinical T stage (T3). CONCLUSIONS: The position of the descending aorta, width of the mediastinal space, and clinical T stage are predictive factors of the technical difficulty of thoracoscopic esophagectomy. These factors might become supporting indices for the indication for thoracoscopic esophagectomy among trainees or the surgeons who introduce this procedure.

Influence of incomplete neoadjuvant chemotherapy on esophageal carcinoma.

BACKGROUND: Neoadjuvant chemotherapy (NAC) involving two cycles of cisplatin plus fluorouracil is recommended in Japan as a standard treatment for resectable, locally advanced esophageal squamous cell carcinoma (ESCC). We have encountered patients who were administered incomplete chemotherapy because of adverse events or the patient's refusal of treatment. Here, we retrospectively investigated the influence on perioperative outcomes and long-term prognosis of patients with ESCC who underwent complete (two cycles) or incomplete (one cycle) NAC. METHODS: We retrospectively investigated 133 patients with locally advanced ESCC of the thoracic esophagus who underwent NAC. We compared the perioperative results and prognoses of patients who underwent complete or incomplete NAC because of adverse events or the patient's refusal of treatment. RESULTS: Of 133 patients, 37 patients did not receive the second cycle of NAC; the remaining 96 patients received the second cycle of NAC as scheduled. There were no significant differences in the clinical backgrounds, surgical results, or operative morbidity rates between the groups. Patients in both groups were similarly administered postoperative chemotherapy regimens. There was no significant difference in disease-free survival or overall survival. CONCLUSIONS: We suggest that perioperative outcomes and long-term prognosis of patients with locally advanced ESCC were not significantly influenced, even if the patients did not receive a complete cycle of NAC. When certain adverse events occur after the first cycle of NAC, we believe that it is nevertheless possible to discontinue chemotherapy.

Safety and feasibility of thoracoscopic esophagectomy after neoadjuvant chemotherapy for esophageal cancer.

PURPOSE: Neoadjuvant chemotherapy (NAC) with cisplatin and fluorouracil is the recommended standard treatment for resectable locally advanced esophageal cancer (EC) in Japan. We investigated the effects of NAC on the safety and feasibility of thoracoscopic esophagectomy with total mediastinal lymphadenectomy for EC. METHODS: This retrospective study analyzed data from 225 consecutive patients who underwent thoracoscopic esophagectomy with lymph node dissection between April 2007 and December 2015. Patients with clinical stage IB, IIA, IIB, IIIA, or IIIB EC, and no active concomitant malignancy were included. We compared intraoperative outcomes, and postoperative morbidity and mortality between patients who received NAC (n = 139; NAC group) and patients who did not (n = 86; non-NAC group). RESULTS: Preoperative laboratory data revealed that anemia, thrombopenia, and renal dysfunction were more common in the NAC group than in the non-NAC group. There were no differences between the groups in operating times, blood loss, number of dissected lymph nodes, overall complication rates, or length of postoperative hospital stay. CONCLUSION: Based on our findings, thoracoscopic esophagectomy is safe and effective for locally advanced EC, even after NAC.

[Pneumocystis Pneumonia during Adjuvant Chemotherapy for Advanced Colon Cancer - A Case Report].

We report a case of pneumocystis pneumonia (PCP) during adjuvant chemotherapy for advanced sigmoid colon cancer. A 70-year-old Japanese man was referred to our hospital after complaining of bloody stools. He was diagnosed with advanced sigmoid colon cancer, T2N2aM1b, Stage IV B. After 3 cycles of mFOLFOX6 plus panitumumab as first-line chemotherapy, he received FOLFIRI plus bevacizumab as second-line chemotherapy because of progressive disease. Aprepitant and steroids were administered as antiemetic agents for a short period during each chemotherapy session. During the 2 cycle of FOLFIRI plus bevacizumab, he developed a high fever without respiratory symptoms. Chest CT revealed ground-glass opacities in both the lungs. We first treated him with antibiotics (PIPC/TAZ plus GRNX), suspecting bacterial pneumonia. However, based on the elevation of serum b -D-glucan (148 pg/mL), we diagnosed PCP and initiated SMX/TMP in addition to PIPC/TAZ. The inflammation promptly decreased, and follow-up chest CT revealed the disappearance of the ground-glass opacities. If a patient develops a fever or respiratory symptoms during a course of chemotherapy, we should consider the possibility of PCP and perform careful examinations.

C-reactive Protein is a Useful Marker for Early Prediction of Anastomotic Leakage after Esophageal Reconstruction.

BACKGROUND: Esophageal anastomotic leakage is one of the most fatal complications after esophagectomy and increases the hospitalization length. We aimed to identify a convenient clinical marker of anastomotic leakage in the early postoperative period. METHODS: In total, 108 patients who underwent esophagectomy were retrospectively screened, and 96 were used to validate the overall results. All 108 patients underwent physical examinations and determination of their white blood cell count, C-reactive protein level, platelet count, fibrinogen level, fibrin degradation product level, and antithrombin III level until postoperative day 6. RESULTS: Anastomotic leakage occurred in 21 of the 108 patients (median detection, 8 days). The C-reactive protein level on postoperative day 3 and fibrinogen level on postoperative day 4 in the leakage group were significantly higher than those in the nonleakage group. Receiver operating characteristic curves for detection of anastomotic leakage were constructed; the cutoff value of C-reactive protein on postoperative day 3 was 8.62 mg/dL, and that of fibrinogen on postoperative day 4 was 712 mg/dL. Anastomotic leakage occurred in 23 of the 96 patients in the validation group. There was a significant difference between the leakage and nonleakage groups when the C-reactive protein threshold on postoperative day 3 was set at 8.62 mg/dL. However, there was no difference between the groups when the fibrinogen threshold on postoperative day 4 was set at 712 mg/dL. CONCLUSIONS: The C-reactive protein level on postoperative day 3 is a valuable predictor of anastomotic leakage after esophagectomy and might allow for earlier management of this complication.

Hypomethylation of Alu repetitive elements in esophageal mucosa, and its potential contribution to the epigenetic field for cancerization.

BACKGROUND: Aberrant hypermethylation of specific genes is present in esophageal squamous cell carcinomas (ESCCs). Such hypermethylation is also present in normal-appearing esophageal mucosae of ESCC patients and is considered to contribute to the formation of a field for cancerization. On the other hand, the presence of global hypomethylation in ESCCs or in their background esophageal mucosae is unknown. METHOD: We collected 184 samples of esophageal mucosae (95 normal mucosae from healthy subjects, and 89 non-cancerous background mucosae from ESCC patients) and 93 samples of ESCCs. Methylation levels of repetitive elements (Alu, LINE1) and cancer/testis antigen genes (NY-ESO-1, MAGE-C1) were measured by bisulfite pyrosequencing and quantitative methylation-specific PCR, respectively. RESULTS: Methylation levels of Alu, LINE1, NY-ESO-1, and MAGE-C1 were significantly lower in ESCCs than in their background and normal mucosae. Also, in the background mucosae, a significant decrease of the Alu methylation level compared with the normal mucosae was present. In ESCCs, methylation levels of the two repetitive elements and the two cancer/testis antigen genes were correlated with each other. CONCLUSION: This is the first study to show the presence of global hypomethylation in ESCCs, and even in their non-cancerous background mucosae. Alu hypomethylation might reflect the severity of an epigenetic field for cancerization.

[Thoracoscopic radical esophagectomy for cancer treatment].

More than 15 years have passed since thoracoscopic surgery was first employed in Japan as a treatment for esophageal cancer with curative intent. Because of the proliferation of techniques that can be used to obtain an adequate operative field, such as hand assist, placing the patient in the prone position, etc., the number of approaches to thoracoscopic surgery has been increasing, contrary to expectations of standardization. The technique of mediastinal dissection has been refined with increasing knowledge of microanatomy, which can be clarified under the magnified view provided in thoracoscopic surgery. Comparable pulmonary function and survival are achieved after both thoracoscopic surgery and open-chest surgery. The accreditation board of the Japan Society for Endoscopic Surgery is now standardizing the thoracoscopic technique. To avoid surgical mistakes, thorough knowledge and adherence to the proper indications are essential.

Identification and validation of DNA methylation markers to predict lymph node metastasis of esophageal squamous cell carcinomas.

BACKGROUND: The presence of lymph node metastasis in esophageal squamous cell carcinoma (ESCC) patients is a critical factor for decision of treatment strategy. However, there have been no molecular markers to assess lymph node metastasis. In this study, we aimed to identify CpG islands (CGIs) whose DNA methylation statuses are associated with the presence of lymph node metastasis. MATERIALS AND METHODS: A total of 96 ESCCs were divided into a screening set (n = 48) and a validation set (n = 48). Genome-wide methylation analysis was performed by methylated DNA immunoprecipitation-CGI microarray analysis. Methylation levels were analyzed by quantitative methylation-specific PCR (qMSP). RESULTS: Genome-wide methylation analysis identified 25 CGIs differentially methylated between 8 ESCCs with lymph node metastasis and 4 without. In the screening set, 7 CGIs had significantly different methylation levels (P < 0.05) between the ESCCs with and without lymph node metastasis, and cut-off methylation levels for these CGIs were determined. The validation set was analyzed with the prefixed cut-offs, and methylation statuses of 2 CGIs in the vicinities of PAX6 and ENST00000363328 were validated to be associated with the presence of lymph node metastasis. Using these 2 markers, the presence was predicted with a sensitivity of 93% and specificity of 57%. In addition, the methylation statuses of the 2 CGIs were significantly associated with disease-free survival (P = 0.006). CONCLUSIONS: Methylation statuses of these 2 CGIs were significantly associated with the presence of lymph node metastasis of ESCCs. These CGIs are promising markers to predict the presence of lymph node metastases.

[A case of SIADH developed during neoadjuvant chemotherapy using nedaplatin and 5-fluorouracil in a patient with esophageal cancer].

A 77-year-old male with thoracic esophageal cancer (cT3N3M0, Stage III) received nedaplatin at 80mg/m2 for 1 day and 5-fluorouracil at 800mg/m2 for 5 days as neoadjuvant treatment. On the fifth day of treatment, he lapsed into a coma (Japan Coma Scale 30), and his serum sodium concentration was found to be decreased to 116mEq/L. We concluded hyponatremia due to SIADH (syndrome of inappropriate secretion of antidiuretic hormone) induced by chemotherapy based on the fact that the patient had no finding of dehydration, particular history of related disorders, serum hypoosmolality accompanied by urine hyperosmolality and persistent urinary sodium excretion. We treated him with fluid restriction, sodium supplement and administration of loop diuretic. Then he regained consciousness and appropriate serum sodium level. Thereafter, hyponatremia was corrected without recurrence, and the patient underwent radical esophagectomy safely. He has been in good condition without recurrence of esophageal cancer after surgery.

Development of a novel output value for quantitative assessment in methylated DNA immunoprecipitation-CpG island microarray analysis.

In DNA methylation microarray analysis, quantitative assessment of intermediate methylation levels in samples with various global methylation levels is still difficult. Here, specifically for methylated DNA immunoprecipitation-CpG island (CGI) microarray analysis, we developed a new output value. The signal log ratio reflected the global methylation levels, but had only moderate linear correlation (r = 0.72) with the fraction of DNA molecules immunoprecipitated. By multiplying the signal log ratio using a coefficient obtained from the probability value that took account of signals in neighbouring probes, its linearity was markedly improved (r = 0.94). The new output value, Me value, reflected the global methylation level, had a strong correlation also with the fraction of methylated CpG sites obtained by bisulphite sequencing (r = 0.88), and had an accuracy of 71.8 and 83.8% in detecting completely methylated and unmethylated CGIs. Analysis of gastric cancer cell lines using the Me value showed that methylation of CGIs in promoters and gene bodies was associated with low and high, respectively, gene expression. The degree of demethylation of promoter CGIs after 5-aza-2'-deoxycytidine treatment had no association with that of induction of gene expression. The Me value was considered to be useful for analysis of intermediate methylation levels of CGIs.