Maximum phonation time: an independent predictor of late-onset pneumonia after esophageal cancer surgery.

Dysphagia after esophagectomy is a major risk factor for aspiration pneumonia, thus preoperative assessment of swallowing function is important. The maximum phonation time (MPT) is a simple indicator of phonatory function and also correlates with muscle strength associated with swallowing. This study aimed to determine whether preoperative MPT can predict postoperative aspiration pneumonia. The study included 409 consecutive patients who underwent esophagectomy for esophageal cancer between 2017 and 2021. Pneumonia detected by routine computed tomography on postoperative days 5-6 was defined as early-onset pneumonia, and pneumonia that developed later (most often aspiration pneumonia) was defined as late-onset pneumonia. The correlation between late-onset pneumonia and preoperative MPT was investigated. Patients were classified into short MPT (<15 seconds for males and <10 seconds for females, n = 156) and normal MPT groups (≥15 seconds for males and ≥10 seconds for females, n = 253). The short MPT group was significantly older, had a lower serum albumin level and vital capacity, and had a significantly higher incidence of late-onset pneumonia (18.6 vs. 6.7%, P < 0.001). Multivariate analysis showed that short MPT was an independent risk factor for late-onset pneumonia (odds ratio: 2.26, P = 0.026). The incidence of late-onset pneumonia was significantly higher in the short MPT group (15.6 vs. 4.7%, P = 0.004), even after propensity score matching adjusted for clinical characteristics. MPT is a useful predictor for late-onset pneumonia after esophagectomy.

Circular Stapled Technique Versus Modified Collard Technique for Cervical Esophagogastric Anastomosis After Esophagectomy: A Randomized Controlled Trial.

OBJECTIVE: This study was performed to investigate the efficacy of the modified Collard (MC) technique for reducing anastomotic stricture after esophagectomy compared with the circular stapled (CS) technique. SUMMARY BACKGROUND DATA: The currently available techniques of anastomosis after esophagectomy are associated with a significant risk of anasto-motic complications. However, the optimal anastomotic technique after esophagectomy has not yet been established. METHODS: We randomly allocated patients to either the CS group or the MC group. The primary endpoint was the incidence of anastomotic stricture. The secondary endpoints included the incidence of postoperative complications (including anastomotic leakage) and quality of life (QoL). All anastomoses were performed after indocyanine green evaluation for objective homogeni-zation of blood flow to the gastric conduit between the 2 techniques. RESULTS: Among 100 randomized patients (CS group, n = 50; MC group, n = 50), anastomotic strictures were observed in 18 (42%) patients in the CS group and in no patients in the MC group. There were no significant between-group differences in anastomotic leakage (CS group, 7% vs MC group, 8%; P = 0.94). Quality of life domains of dysphagia and choking when swallowing at 3 months after surgery were significantly better in the MC group than in the CS group. CONCLUSIONS: The MC technique reduces the incidence of anastomotic stricture and improves postoperative quality of life. Furthermore, the incidence of anastomotic leakage is comparable between the 2 techniques based on accurate comparison under objective homogenization of the gastric conduit condition.

Significance of Antimicrobial Prophylaxis for the Prevention of Early-Onset Pneumonia After Radical Esophageal Cancer Resection: A Retrospective Analysis of 356 Patients Undergoing Thoracoscopic Esophagectomy.

BACKGROUND: Postoperative pneumonia is a common complication after esophagectomy and is associated with a high mortality rate. Although many randomized, controlled trials have been conducted on the prevention of postoperative pneumonia, little attention has been paid to the efficacy of antimicrobial prophylaxis. The purpose of this study was to investigate the impact of antimicrobial prophylaxis on the prevention of postoperative pneumonia. METHODS: Data of patients with esophageal cancer who underwent thoracoscopic esophagectomy between 2016 and 2020 were collected. Early-period patients received cefazolin (CEZ) per protocol as antimicrobial prophylaxis (n = 250), and later-period patients received ampicillin/sulbactam (ABPC/SBT) (n = 106) because of the unavailability of CEZ in Japan. The incidence of pneumonia was compared between treatments in this quasi-experimental setting. Pneumonia detected by routine computed tomography (CT) on postoperative Days 5-6 was defined as early-onset pneumonia, and pneumonia that developed later was defined as late-onset pneumonia. RESULTS: The incidence of early-onset pneumonia was significantly lower (3.8% vs. 13.6%, P = 0.006), and the median length of postoperative hospital stay was significantly shorter (17 vs. 20 days, P < 0.001) in the ABPC/SBT group than in the CEZ group. The incidence of late-onset pneumonia was similar between groups (9.4% vs. 10.0%, P = 0.870). The incidence of Clostridioides difficile infections and the incidence of multidrug-resistant organisms were similar between groups. Multivariate analyses consistently showed the superiority of ABPC/SBT to CEZ in preventing early-onset pneumonia (odds ratio: 0.20, P = 0.006). CONCLUSIONS: ABPC/SBT after esophagectomy was better at preventing early-onset pneumonia compared with CEZ and was feasible regarding the development of antimicrobial resistance.

Should the Supraclavicular Lymph Nodes be Considered Regional Lymph Nodes in Cervical Esophageal Cancer?

BACKGROUND: The importance of supraclavicular lymph node (SCLN) metastases in esophageal cancer (EC) remains unknown. Few studies have reported on the prognostic impact of SCLN metastases on patients with cervical EC (CEC). This study aimed to investigate whether SCLNs should be considered regional lymph nodes and be dissected in patients with CEC. METHODS: This retrospective study enrolled 835 consecutive patients who underwent radical esophagectomy. Of these patients, 67 underwent radical surgery for CEC. These 67 patients were divided into three groups based on the presence of lymph node metastases with or without metastatic SCLNs or the absence of lymph node metastases. RESULTS: Of the 67 patients, 23 (34.3%) did not have metastatic lymph nodes (pN-negative group), 27 (40.3%) had metastatic lymph nodes except for metastatic SCLNs (pN-positive group without metastatic SCLN), and 17 (25.4%) had metastatic lymph nodes including metastatic SCLNs (pN-positive group with metastatic SCLNs). The 5-year overall survival rate was 58.4% for the pN-negative group, 46.2% for the pN-positive group without metastatic SCLNs, and 7.8% for the pN-positive group with metastatic SCLNs. The pN-positive group with metastatic SCLNs tended to show residual tumor cells and complications after surgery. The presence of metastatic SCLNs was a significantly poor prognostic factor (p = 0.004). The efficacy index was lowest for the lymph nodes in the supraclavicular region. CONCLUSIONS: The prognosis of the CEC patients with metastatic SCLNs was dismal. Although the cervical esophagus is located adjacent to the SCLNs, the SCLNs may be considered extra-regional lymph nodes in patients with CEC.

Long-Term Outcome of Patients with Locally Advanced Clinically Unresectable Esophageal Cancer Undergoing Conversion Surgery after Induction Chemotherapy with Docetaxel Plus Cisplatin and 5-Fluorouracil.

BACKGROUND: Although definitive chemoradiotherapy (CRT) is recommended for patients with locally advanced unresectable esophageal cancer, the outcome is unsatisfactory. We previously demonstrated the safety and efficacy of induction chemotherapy with docetaxel plus cisplatin and 5-fluorouracil (DCF) and subsequent conversion surgery (CS) for patients with locally advanced unresectable esophageal cancer. However, whether or not induction DCF chemotherapy and subsequent CS improve the long-term outcomes of patients with locally advanced unresectable esophageal cancer is unclear. METHODS: A total of 177 consecutive patients with locally advanced unresectable esophageal cancer without distant metastasis were included in this study. Of these, 55 patients received DCF induction chemotherapy, of whom 36 underwent CS. We divided these 36 patients into two groups according to clinical response, which was analyzed retrospectively. RESULTS: The toxicities related to DCF chemotherapy were manageable. The response rate to induction DCF chemotherapy was 67%. R0 resection was achieved in 81% of the 36 patients who underwent subsequent CS. No serious postoperative complications were observed. Histopathological CR was achieved in 17% of the 36 patients, and the 3- and 5-year survival rates after CS were 61% and 54%, respectively. The outcomes of the patients who obtained good clinical response was better than the outcomes of patients who did not. CONCLUSIONS: Induction DCF chemotherapy and subsequent CS show acceptable toxicity and offer the chance of long-term survival in patients with locally advanced clinically unresectable esophageal cancer.

Aggressive and frequent resection of recurrences in retroperitoneal sarcoma contributes to long-term survival.

PURPOSE: Retroperitoneal sarcoma (RPS) is a rare tumor with a poor prognosis and is often undetected until it is significantly enlarged. While surgical resection remains the primary treatment, there is little research on its benefits, especially that concerning the reoperation of recurrent disease. This study investigated the impact of surgical procedures, especially reoperation of recurrent RPS, on prognosis. METHODS: This retrospective study included 51 patients who underwent radical resection surgery (R0 status) for primary or recurrent RPS without distant metastasis. Patient outcomes and prognosis were defined in terms of the clinicopathologic factors and surgical techniques performed. RESULTS: In all cases, the 5-year disease-free survival (DFS) rate was 28.2%, 5-year overall survival rate was 89.9%, and 5-year no residual liposarcoma rate was 54.3% after operation and re-reoperation. There was a statistically significant difference between the 5-year DFS rate and 5-year no residual liposarcoma rate due to frequent re-reoperation (p = 0.011). On univariate analysis of primary and recurrent lesions, the histological type and the number of organs involved were identified as statistically significant prognostic factors. Patients with well-differentiated liposarcomas had a statistically better prognosis than those with other cancer types (primary RPS, p = 0.028; recurrence, p = 0.024). CONCLUSIONS: Aggressive and frequent resection of recurrent RPS with combined resection of adjacent organs contributes to long-term survival. The establishment of a surgical strategy for RPS will require a prospective study.

[Secondary Dementia Due to Leptomeningeal Metastasis of Breast Cancer Improved by Whole Brain Radiation].

A 62-year-old woman received chemotherapy for breast cancer with bone metastasis and malignant pleural and pericardial effusion. She was examined by imaging for progressive cognitive impairment and headache. Enhanced MRI findings showed multiple solid tumors on brain surface, and brain perfusion scintigraphy showed blood flow decrease in both parietal lobes. She was diagnosed with secondary dementia due to leptomeningeal metastases of breast cancer, and whole brain external irradiation was performed(30 Gy/15 Fr). After treatment, multiple tumors were decreased in size and her cognitive impair- ment was improved.

Clinical validation of the suppressive impact of letrozole on liver fibrosis in patients with breast cancer undergoing continuous letrozole administration: A retrospective study.

Treatment strategies for preventing liver fibrosis have not yet been established. Letrozole, widely used for breast cancer, has recently been reported to suppress liver fibrosis in murine models. Therefore, we aimed to validate the suppressive effects of letrozole on liver fibrosis in the clinical setting. From 2006 to 2020, 23 consecutive patients who received continuous letrozole treatment for 24 months or more and had a liver fibrosis marker FIB-4 index of ≥ 2.30, were included. Forty-three patients who underwent anastrozole treatment for 24 months or more and had a liver fibrosis marker FIB-4 index of ≥ 2.30, were also included as controls. The Fisher exact, chi-square, unpaired Student t, and paired Student t test were used to analyze the data. The patient characteristics were similar between the letrozole- and anastrozole-treated patient groups. Among the letrozole-treated patients, the mean FIB-4 index tended to decline during letrozole treatment; a significant decrease was observed at 18 and 24 months compared with the baseline values (p = 0.044 and p = 0.013). In addition, the mean aspartate aminotransferase-to-platelet ratio index (APRI) decreased during letrozole treatment; the values at 18 and 24 months were significantly lower than those at baseline (p = 0.024 and p = 0.026). In contrast, among anastrozole-treated patients, the mean FIB-4 index and APRI did not change during anastrozole treatment. When changes in the FIB-4 index were further examined in a limited number of patients with a FIB-4 index ≥ 2.67, a significant reduction in the FIB-4 index at 24 months compared with baseline was also observed in letrozole-treated patients (p = 0.023), but not in anastrozole-treated patients. In conclusion, our findings support a possible suppressive effect of letrozole on liver fibrosis in the clinical setting. Further studies are required to better understand the pharmacological effects of letrozole.

Robot-assisted enucleation of a giant submucosal tumor in the upper esophagus.

Few reports have demonstrated robotic surgery for large tumors in the upper esophagus. We report a case of a 52-year-old woman with a giant submucosal tumor in the upper esophagus successfully enucleated using robotic surgery. She presented with odynophagia and dysphagia, with subsequent evaluation revealing a submucosal mass measuring approximately 10 cm in diameter in the upper esophagus. The mass was compressing the trachea and enlarged over 3 years. Endoscopic ultrasound fine needle aspiration of the tumor was non-diagnostic. Robot-assisted esophageal submucosal tumor enucleation was performed for diagnosis and treatment. Flexible forceps control allowed for a multi-directional approach to dissect the tumor and stable forceps handling was critical in this delicate procedure. Subsequent pathological review revealed a well-differentiated esophageal liposarcoma. While surgical margins were not entirely negative, the local recurrence rate of the tumor is low. At the patient's request, we decided to observe the patient without additional resection.

Effect of Body Composition Change during Neoadjuvant Chemotherapy for Esophageal Squamous Cell Carcinoma.

Effects of changes in body composition during neoadjuvant chemotherapy (NAC) on perioperative complications and prognosis are unknown in patients with esophageal squamous cell carcinoma (ESCC). A total of 175 patients who underwent surgery for ESCC in our hospital between 2016 and 2019 were examined. The psoas muscle index (PMI) was calculated from the total psoas muscle area, and the visceral fat mass (VFM) at the umbilical level was measured. We defined body composition change (BCC) group as those with increased VFM of ≥ 3% and decreased PMI of ≥ 3% during NAC. Sarcopenia (S) was defined as PMI < 5.89 (male) and <4.06 (female). Nutritional assessment using the Subjective Global Assessment tool was performed upon admission. The percentages of BCC group, pre-NAC S, and post-NAC S was 32.5%, 79.4%, and 80.0%, respectively. BCC group had significantly more postoperative complications (p < 0.01) and longer hospital stays (p = 0.03) than groups pre-NAC S and post-NAC S. Overall survival (OS) analysis using the Cox hazard model showed that stage III (p < 0.01) and post-NAC S (p = 0.03) were poor prognostic factors. Changes in body composition during NAC affected perioperative complications and prognosis of patients with ESCC.

Synchronous Resection of Parotid Metastasis With Esophagectomy: A Case Report.

BACKGROUND: Preoperative diagnosis of parotid tumor is mainly performed via imaging and cytology to avoid both facial nerve injury and tumor seeding. Synchronous resection of solitary parotid metastasis with esophagectomy for esophageal squamous cell carcinoma is rarely performed. CASE REPORT: This is a case report of a 58-year-old male patient with a left preauricular tumor, which was cytologically diagnosed as squamous cell carcinoma. Esophageal squamous cell carcinoma was pathologically diagnosed following 18F-fluorodeoxyglucose positron emission tomography with computed tomography. His diagnosis was cT2N0M0 esophageal squamous cell carcinoma with cT3N0M0 parotid carcinoma. Esophagectomy for esophageal cancer, as well as parotidectomy were performed. Pathological diagnosis of pT1bN1M1 (parotid) esophageal squamous cell carcinoma was based on exclusion diagnosis of no primary tumor from several specialists and pathological findings including immunohistochemical staining. CONCLUSION: Reporting of more cases of rare synchronous metastasectomy and esophagectomy is needed to clarify treatment strategies.

Bronchial fistula and esophageal stricture following endoscopic trans-gastric drainage for a mediastinal pancreatic pseudocyst.

A 43-year-old man with alcoholic cirrhosis and chronic alcoholic pancreatitis was referred for evaluation of chest pain and an enlarging pleural effusion. Computed tomography revealed a bilateral pleural effusion and longitudinal multilocular pancreatic pseudocysts extending to the posterior mediastinum along the esophagus. He was diagnosed with a mediastinal pancreatic pseudocyst rupturing into the pleural cavity and was initially treated with endoscopic ultrasound-guided trans-gastric drainage. After 4 months of stable disease, dysphagia and a severe cough developed due to an esophageal stricture and main bronchial fistula. Considering the inadequate drainage, the trans-gastric drainage stent was surgically exchanged for a percutaneous external drain and the bronchial fistula was repaired using an intercostal muscle flap. After improvement of the mediastinal abscess and the symptoms, he was discharged on post-operative day 72. Two years post-operatively, he is in good health with no recurrence. We herein report a rare case of a bronchial fistula and esophageal stricture after endoscopic trans-gastric drainage of a mediastinal pancreatic pseudocyst. Endoscopic trans-gastric drainage is an effective treatment for mediastinal pancreatic pseudocysts, but it is important to provide appropriate alternative treatment depending on the course of treatment.

Repair of antegrade anastomosis between ileal segment and amputated ureter for recurrent rectal cancer.

We describe a case of repair of the antegrade anastomosis between the "ileal segment" and amputated ureter for recurrent rectal cancer, in which some postoperative complications occurred but eventually resolved. If the length of the ureter is inadequate for end-to-end anastomosis, an ileal segment can be used as a conduit. This surgical technique is not difficult because an ileal conduit is typically created during total pelvic exenteration of rectal cancers. Therefore, anastomosing the ureter to an "ileal segment" is easy and feasible. Hence, we consider that knowledge of this technique would be beneficial for surgical oncologists who perform colorectal surgeries.

Gastric lymphangioma coexisting with mucosal gastric cancer: a rare case report.

We describe a case of gastric lymphangioma coexisting with mucosal gastric cancer. A 76-year-old man was diagnosed with an advanced gastric cancer (cT2N0M0, Stage I) presenting a nodular protruded lesion with irregular central depression. The surgically resected specimen showed a 4 × 3 cm sessile protruded lesion in the anterior wall of the lower stomach. Histopathological examination revealed a mucosal adenocarcinoma was located immediately above the lymphangioma and was elevated by the cystic component of lymphangioma without admixture, which suggested that the two components arose separately. The mucosal adenocarcinoma was masquerading as an advanced gastric cancer due to the protrusion by the lymphangioma.

Surgical Strategy for Rectovaginal Fistula After Colorectal Anastomosis at a High-volume Cancer Center According to Image Type and Colonoscopy Findings.

BACKGROUND/AIM: The reported incidence of rectovaginal fistula is very low. Although some case reports have described surgical procedures, no systematic approach to the treatment of rectovaginal fistula according to diagnostic image and colonoscopy findings has been proposed. We present a comprehensive surgical strategy for rectovaginal fistula after colorectal anastomosis according to diagnostic image and colonoscopy findings. PATIENTS AND METHODS: This retrospective study included 11 patients who developed rectovaginal fistula after colorectal anastomosis. Rectovaginal fistula was classified into 4 types according to contrast enema images and colonoscopy findings, i.e., "Alone type", "Dead space type", "Anastomotic stricture type", and "Dead space and Anastomotic stricture type". The surgical strategies were "Diversion (Stoma)", "Percutaneous drainage", "Anastomotic stricture type", "Endoscopic balloon dilation", "Curettage of foreign bodies", "Simple full-thickness closure", "Split-thickness closure", "Pedicled flaps packing", and "Reanastomosis". The surgical strategy appropriate for each rectovaginal fistula type was investigated. RESULTS: Among "Alone type" cases, 5 (71.4%) healed with "only Diversion (Stoma)". "Alone type" cases (n=11) and all other cases (n=4) healed with "only Diversion (Stoma)" (n=5) or any other method (n=6) (p=0.022). CONCLUSION: For treatment of rectovaginal fistula after colorectal anastomosis, less invasive treatment approaches should be attempted first.

Evaluation of human hepatocytes cultured by three-dimensional spheroid systems for drug metabolism.

We investigated the utility of three-dimensional (3D) spheroid cultures of human hepatocytes in discovering drug metabolites. Metabolites of acetaminophen, diclofenac, lamotrigine, midazolam, propranolol and salbutamol were analyzed by liquid chromatography-tandem mass spectrometry (LC/MS/MS) to measure enzyme activities in this system cultured for 2 and 7 days. Sequential metabolic reactions by Phase I and then Phase II enzymes were found in diclofenac [CYP2C9 and UDP-glucuronyltransferases (UGTs)], midazolam (CYP3A4 and UGTs) and propranolol (CYP1A2/2D6 and UGTs). Moreover, lamotrigine and salbutamol were metabolized to lamotrigine-N-glucuronide and salbutamol 4-O-sulfate, respectively. These metabolites, which are human specific, could be observed in clinical studies, but not in conventional hepatic culture systems as in previous reports. Acetaminophen was metabolized to glucuronide and sulfate conjugates, and N-acetyl-p-benzo-quinoneimine (NAPQI) and its metabolites were not observed. In addition, mRNA of drug-metabolism enzymes [CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4, UGT1A1, UGT2B7, sulfotransferase 1A1 (SULT1A1) and glutathione S-transferase pi 1 (GSTP1)], which were measured by qRT-PCR, were expressed in the human hepatocyte spheroids. In conclusion, these results suggest that human hepatocyte spheroids are useful in discovering drug metabolites.

Development of a novel ampholyte buffer for isoelectric focusing: electric charge-separation of protein samples for X-ray crystallography using free-flow isoelectric focusing.

The purification of biological macromolecules has remained a severe bottleneck in three-dimensional structure determination in the field of protein crystallography. By the use of the Free Flow Electrophoresis (ProTeam FFE; TECAN Group Ltd) apparatus, target protein samples can be purified in a high yield, while a preparative separation is performed in solution without using solid matrices such as polyacrylamide gel. A novel ampholyte buffer suitable for crystallization in the use of the ProTeam FFE apparatus has been developed. This buffer is able to generate pH gradients owing to the use of low-molecular-weight electrolytes. The effect of the flow rate on the pH gradient using the novel ampholyte buffer has been elucidated. When the flow rate was lowered to 78 ml h(-1), the pH gradient in the electrophoretic chambers was generated in an almost linear fashion.