Effects of the preoperative use and dosage of steroids on postoperative complications of gastric cancer surgery.

PURPOSE: To investigate the effects of preoperative steroid administration, including dosage, on complications after gastrectomy for gastric cancer. METHODS: We reviewed patients who underwent gastrectomy for gastric and esophagogastric junctional adenocarcinoma between 2013 and 2019 at the Department of Gastrointestinal Surgery, The University of Tokyo. RESULTS: Among the total 764 patients eligible for inclusion in the study, 17 were on steroid medication preoperatively (SD group) and 747 were not (ND group). The hemoglobin, serum albumin levels, and respiratory functions were significantly lower in the SD group than in the ND group. The incidence of postoperative complications classified as Clavien-Dindo (C-D) ≥ 2 was significantly greater in the SD group than in the ND group (64.7% vs. 25.6%, p < 0.001). Intra-abdominal infection (35.2% vs. 9.6%, p < 0.001) and anastomotic leakage (11.8% vs. 2.1%, p < 0.001) occurred more frequently in the SD group than in the ND group. On multiple logistic regression analysis for C-D ≥ 3 postoperative complications, the odds ratio for oral steroid use ≥ 5 mg per day as prednisolone had the highest value, of 13.0 (95% confidence interval 2.46-76.2, p < 0.01). CONCLUSION: Preoperative oral steroid use was identified as an independent risk factor for postoperative complications after gastrectomy for gastric cancer. Furthermore, the complication rate appears to increase as the oral steroid dosage is increased.

Optimal criteria for predicting lymph node metastasis in esophageal squamous cell carcinoma by anatomical location using preoperative computed tomography: a retrospective cohort study.

PURPOSE: Predicting lymph node metastasis (LNM) in esophageal squamous cell carcinoma (ESCC) is critical for selecting appropriate treatments despite the low accuracy of computed tomography (CT) for detecting LNM. Variation in potential nodal sizes among locations or patients' clinicopathological background factors may impact the diagnostic quality. This study explored the optimal criteria and diagnostic ability of CT by location. METHODS: We retrospectively reviewed preoperative CT scans of 229 patients undergoing curative esophagectomy. We classified nodal stations into six groups: Cervical (C), Right-upper mediastinal (UR), Left-upper mediastinal (UL), Middle mediastinal (M), Lower mediastinal (L), and Abdominal (A). We then measured the short-axial diameter (SAD) of the largest lymph node in each area. We used receiver operating characteristics analyses to evaluate the CT diagnostic ability and determined the cut-off values for the SAD in all groups. RESULTS: Optimal cut-offs were 6.5 mm (M), 6 mm (C, L, and A), and 5 mm (UR and UL). Diagnostic abilities differed among locations, and UR had the highest sensitivity. A multivariate analysis showed poor differentiation to be an independent risk factor for a false-negative diagnosis (p = 0.044). CONCLUSIONS: Optimal criteria and diagnostic abilities for predicting LNM in ESCC varied among locations, and poor differentiation might contribute to failure to detect LNM.

A design of forceps-type coincidence radiation detector for intraoperative LN diagnosis: clinical impact estimated from LNs data of 20 esophageal cancer patients.

PURPOSE: To reduce postoperative complications, intraoperative lymph node (LN) diagnosis with 18F-fluoro-2-deoxy-D-glucose (FDG) is expected to optimize the extent of LN dissection, leading to less invasive surgery. However, such a diagnostic device has not yet been realized. We proposed the concept of coincidence detection wherein a pair of scintillation crystals formed the head of the forceps. To estimate the clinical impact of this detector, we determined the cut-off value using FDG as a marker for intraoperative LN diagnosis in patients with esophageal cancer, the specifications needed for the detector, and its feasibility using numerical simulation. METHODS: We investigated the dataset including pathological diagnosis and radioactivity of 1073 LNs resected from 20 patients who underwent FDG-positron emission tomography followed by surgery for esophageal cancer on the same day. The specifications for the detector were determined assuming that it should measure 100 counts (less than 10% statistical error) or more within the intraoperative measurement time of 30 s. The detector sensitivity was estimated using GEANT4 simulation and the expected diagnostic ability was calculated. RESULTS: The cut-off value was 620 Bq for intraoperative LN diagnosis. The simulation study showed that the detector had a radiation detection sensitivity of 0.96%, which was better than the estimated specification needed for the detector. Among the 1035 non-metastatic LNs, 815 were below the cut-off value. CONCLUSION: The forceps-type coincidence detector can provide sufficient sensitivity for intraoperative LN diagnosis. Approximately 80% of the prophylactic LN dissections in esophageal cancer can be avoided using this detector.

Comparison of short-term outcomes between transthoracic and robot-assisted transmediastinal radical surgery for esophageal cancer: a prospective study.

BACKGROUND: The present study aimed to assess the lower invasiveness of robot-assisted transmediastinal radical esophagectomy by prospectively comparing this procedure with transthoracic esophagectomy in terms of perioperative outcomes, serum cytokine levels, and respiratory function after surgery for esophageal cancer. METHODS: Patients who underwent a robot-assisted transmediastinal esophagectomy or transthoracic esophagectomy between April 2015 and March 2017 were included. The perioperative outcomes, preoperative and postoperative serum IL-6, IL-8, and IL-10 levels, and respiratory function measured preoperatively and at 6 months postoperatively were compared in patients with a robot-assisted transmediastinal esophagectomy and those with a transthoracic esophagectomy. RESULTS: Sixty patients with esophageal cancer were enrolled. The transmediastinal esophagectomy group had a significantly lower incidence of postoperative pneumonia (p = 0.002) and a significantly shorter postoperative hospital stay (p < 0.0002). The serum IL-6 levels on postoperative days 1, 3, 5, and 7 were significantly lower in the transmediastinal esophagectomy group (p = 0.005, 0.0007, 0.022, 0.020, respectively). In the latter group, the serum IL-8 level was significantly lower immediately after surgery and on postoperative day 1 (p = 0.003, 0.001, respectively) while the serum IL-10 level was significantly lower immediately after surgery (p = 0.041). The reduction in vital capacity, percent vital capacity, forced vital capacity, and forced expiratory volume at 1.0 s 6 months after surgery was significantly greater in the transthoracic esophagectomy group (p < 0.0001 for all four measurements). CONCLUSIONS: Although further, large-scale studies are needed to confirm our findings, robot-assisted transmediastinal esophagectomy may confer short-term benefits in radical surgery for esophageal cancer. TRIAL REGISTRATION: This trial was registered in the UMIN Clinical Trial Registry ( UMIN000017565 14/05/2015).

One-by-One Comparison of Lymph Nodes Between 18F-FDG Uptake and Pathological Diagnosis in Esophageal Cancer.

PURPOSE: Esophagectomy with extended lymph node (LN) dissection is a standard treatment for resectable esophageal cancer to prevent recurrence, but severe, potentially life-threatening postoperative complications are still important issues. Accurate diagnosis of LN metastases would enable the decision to dissect or leave the LNs in regions with high risk of complications. Advancements in intraoperative gamma probe and radioactivity detectors have made intraoperative navigation surgery possible using a radiotracer as a marker. F-FDG is one such candidate markers, and the diagnostic power of FDG through counting the radioactivity close to each LN should be elucidated. MATERIALS AND METHODS: In 20 patients, 1073 LNs including 38 metastatic LNs were prospectively investigated. Preoperative FDG PET was performed on the same day before esophagectomy and visually surveyed in each LN station to identify abnormal uptake. The FDG radioactivity of each individual dissected LN was measured by a well-type counter, and the pathological diagnosis was compared with LN radioactivity on a one-by-one basis and with the preoperative FDG PET findings for each LN station. RESULTS: Lymph node station-based analysis showed a sensitivity and specificity of 28.6% and 96.7%, respectively. One-by-one LN-based analysis using a cutoff value obtained from the receiver operating characteristic curve showed a sensitivity and specificity of 94.7% and 78.7%, respectively, demonstrating higher accuracy compared with the use of LN weight or the shortest diameter. CONCLUSIONS: The FDG uptake by each LN is a potentially useful marker for navigation surgery in esophageal cancer and has higher accuracy than LN weight or diameter.

Intratumoral pseudoaneurysm within a liver metastasis of gastric cancer: a case report.

BACKGROUND: Intrahepatic artery pseudoaneurysms are mostly iatrogenic and result from hepatobiliary interventions. The incidence of intrahepatic artery pseudoaneurysms within liver tumors without prior intervention is extremely rare. We presented herein the first report of a case of an intratumoral pseudoaneurysm within a liver metastasis of gastric cancer without any prior intervention during chemotherapy. CASE PRESENTATION: A 59-year-old male patient underwent a distal gastrectomy and D2 lymph node dissection for gastric cancer. He was treated in the emergency room for right abdominal pain following the 4th cycle of nivolumab administration as second-line chemotherapy after adjuvant chemotherapy with S-1 and first-line chemotherapy for a liver metastasis of gastric cancer with ramucirumab plus paclitaxel. CT showed a 72-mm metastatic liver tumor containing a 9-mm pseudoaneurysm and fluid collection around the hepatic edge. Intrahepatic artery pseudoaneurysm within the metastatic liver tumor was diagnosed, with the surrounding fluid indicating potential, active bleeding. An emergency angiography confirmed the presence of a pseudoaneurysm in the intrahepatic artery, which was embolized using microcoils. The contributory causes of the intratumoral pseudoaneurysm were assumed to be the following: (1) tumor necrosis leading to encasement, erosion of the vessel wall, and subsequent arterial wall weakening; and (2) inhibition of vascular endothelial growth by ramucirumab resulting in a vessel wall breach and pseudoaneurysm formation. CONCLUSION: It is necessary to recognize that pseudoaneurysms can arise within a metastatic liver tumor during chemotherapy.

Long-term health-related quality of life following robot-assisted radical transmediastinal esophagectomy.

BACKGROUND: The good short-term and oncological outcomes of robot-assisted radical esophagectomy have been demonstrated, although its impact on long-term health-related quality of life (HRQoL) remains to be investigated. This study aimed to assess long-term HRQoL in patients after robot-assisted radical transmediastinal esophagectomy (TME), which is characterized as non-transthoracic esophagectomy comprising a robotic transhiatal approach and a video-assisted cervical approach, and transthoracic esophagectomy (TTE). METHODS: The European Organization for Research and Treatment of Cancer generic and disease-specific modules (QLQ-C30 and QLQ-OES18), nutritional status and body composition data were prospectively collected in patients undergoing TME or TTE before and at 3, 6, 12, 18, and 24 months after surgery. The results of long-term (≥ 2 years) survivors without recurrence were compared between the two groups. RESULTS: A total of 37 patients (TME; n = 18, TTE; n = 19) were included for analysis. Longitudinal survey of function scales revealed scores of physical, role, social, and emotional function to be significantly better in the TME group than in the TTE group at many points postoperatively. Markedly, the symptoms of general pain, esophageal pain, and dry mouth greatly worsened after surgery in the TTE group, but did not deteriorate in the TME group. In contrast, symptoms relating to eating difficulties, body composition data, and nutritional status did not differ between the groups over time. At 24 months after surgery, TME provided significantly higher scores of global QOL (P = 0.01) and emotional function (P = 0.01) and also resulted in significantly fewer problems of fatigue (P = 0.04), general pain (P = 0.04), insomnia (P = 0.02), and dry mouth (P = 0.03), as compared to TTE. CONCLUSION: This study indicates that TME can provide better long-term HRQoL outcomes than TTE.

Relationships among body composition, muscle strength, and sarcopenia in esophageal squamous cell carcinoma patients.

PURPOSE: Relationships among body composition indices assessed by various modalities remain to be addressed in patients with esophageal squamous cell carcinoma (ESCC), in whom being underweight is more strikingly prevalent than in those with other malignancies. We investigated the relationships of body composition parameters with the sarcopenia prevalence of ESCC patients. METHODS: In this prospective study, we analyzed preoperative data obtained from 75 ESCC patients undergoing esophagectomy. Body composition data included body mass index (BMI), skeletal muscle index (SMI) assessed by computed tomography, and parameters calculated by bioelectrical impedance analysis (skeletal muscle mass (SMM), body fat mass). Muscle strength was evaluated by handgrip strength (HGS). Sarcopenia was defined as having both low SMI and low HGS. RESULTS: The median BMI value was 22.5 (range 15.2-28.7) in our ESCC cohort. BMI correlated significantly with fat mass (r = 0.84, P < 0.001), SMM (r = 0.57, P < 0.001) and SMI (r = 0.49, P < 0.001). Similarly, SMI showed a significant correlation with SMM (r = 0.45, P < 0.001). Meanwhile, HGS was highly correlated with SMM (r = 0.67, P < 0.001), while showing significant but weak associations with both BMI and SMI (r = 0.33, 0.34, respectively, P < 0.001). Notably, sarcopenia prevalence differed markedly according to BMI category; 28.6%, 12.2%, and 0% in the low (< 20), medium (20-25), and high (> 25) BMI groups, respectively. CONCLUSIONS: BMI reflects comprehensive information on body composition in ESCC patients, although its correlation with muscle mass and muscle strength was moderate. Decreased BMI might serve as an indicator for sarcopenia in this population, in which the presence of sarcopenic obesity is rare.

Right inferior phrenic artery pseudoaneurysm after a laparoscopic gastrectomy: a case report.

BACKGROUND: Ruptured pseudoaneurysms are a rare complication of gastrectomy, but when they do develop, they are often fatal. We presented herein the first report of a case of pseudoaneurysm arising from the right inferior phrenic artery (RIPA) after a laparoscopic gastrectomy. CASE PRESENTATION: A 61-year-old male patient underwent a laparoscopic distal gastrectomy and D1+ lymph node dissection with Roux-en-Y reconstruction for early gastric cancer. He was discharged on postoperative day (POD) 9 without any complications, such as anastomotic or pancreatic leakage. On POD 19, he was referred to the emergency room for upper abdominal pain. Enhanced abdominal computed tomography revealed a 60 × 70 mm hematoma, indicating intra-abdominal bleeding and a 10-mm pseudoaneurysm in the RIPA. Selective digital subtraction angiography confirmed the presence of a pseudoaneurysm in the RIPA, which was embolized using multiple microcoils. Thereafter, no clinical signs were observed, and the patient was discharged from the hospital 15 days after angiography without any recurrence of bleeding. We hypothesized that the cause of the pseudoaneurysm was mechanical vascular injury due to the thermal spread of the ultrasonically activated devices (USADs) during lymphatic node dissection. CONCLUSION: Given the thermal spread of USADs, safe and appropriate lymph node dissection based on precise anatomical knowledge is crucial to preventing postoperative pseudoaneurysms.

Mediastinoscopic view of the bronchial arteries in a series of surgical cases evaluated with three-dimensional computed tomography.

BACKGROUND: We have routinely performed three-dimensional computed tomography (3-D CT) prior to video-assisted transmediastinal esophagectomy to evaluate the small arteries in the mediastinal operative field. This evaluation would be helpful in performing mediastinoscopic esophagectomy. METHODS: Thirty-one patients who underwent transmediastinal esophagectomy with preoperative evaluations by 3-D CT were the study subject. The bronchial arteries depicted by the 3-D CT were classified by their origin and laterality. In 18 of the 31 cases, the surgical video was available and the identification rate in the video was reviewed for each of the categorized bronchial arteries. RESULTS: The detection rates of each classified artery were as follows (abbreviations, detection rate); the intercostal-bronchial trunk (IBT, 22/31), the direct left bronchial artery (LBA, 17/31), the common trunk of bronchial arteries (CTB, 7/31), the direct right bronchial artery (RBA, 2/31), and the ectopic arteries (16/31). The ectopic arteries arose from the aortic arch (11 cases), the right subclavian artery (6 cases) or the left subclavian artery (1 case). The identification rates of IBT, LBA, CTB, RBA and any of the ectopic arteries in the video review were 12/13, 4/8, 3/4, 1/1 and 2/10, respectively. CONCLUSIONS: Preoperative 3-D CT was a highly sensitive evaluation for the bronchial arteries encountered during transmediastinal esophagectomy. Orthotopic arteries except for LBA were frequently identified at the predicted sites. Although RBA and CTB were present infrequently, they often flowed into regional nodes at the bilateral bronchi or the tracheal bifurcation and, therefore, should be preoperatively evaluated.

Quality of life after robot-assisted transmediastinal radical surgery for esophageal cancer.

BACKGROUND: The aim of this retrospective study was to assess postoperative quality of life (QOL) after robot-assisted radical transmediastinal esophagectomy, defined as a nontransthoracic esophagectomy with radical mediastinal lymphadenectomy combining a robotic transhiatal approach and a video-assisted cervical approach. The results were compared to those of transthoracic esophagectomy. METHODS: In this study, all consecutive patients who underwent robot-assisted radical transmediastinal esophagectomy or transthoracic esophagectomy for esophageal cancer at University of Tokyo between January 2010 and December 2014 were included. The European Organization for Research and Treatment of Cancer (EORTC)'s quality of life questionnaires QLQ-C30 and QLQ-OES18 were sent to all patients that were still living, had no recurrence or other malignancy, and had not undergone a reoperation because of complications after esophagectomy. RESULTS: We were able to survey 63 (98.4%) of 64 eligible patients. We assessed and compared the QOL scores of both groups of patients. Compared to transthoracic esophagectomy, transmediastinal esophagectomy was associated with better QOL. Global health status and the physical, role, and cognitive function scale scores were significantly superior in the transmediastinal esophagectomy group (P = 0.004, < 0.0001, 0.007, 0.002, respectively). Fatigue, nausea and vomiting, pain, appetite loss, reflux, and taste scores were significant lower (superior) in the transmediastinal esophagectomy group (P = 0.003, 0.032, 0.025, 0.018, 0.001, 0.041, respectively). CONCLUSIONS: This study indicates that robot-assisted radical transmediastinal esophagectomy is associated with better postoperative QOL compared to transthoracic esophagectomy. A larger study and prospective analyses are needed to confirm the current results.

A surgical case of radiotherapy induced esophageal perforation accompanying pyogenic spondylodiscitis: a case report.

BACKGROUND: Stereotactic body radiotherapy has been a treatment choice for lung cancer, especially in medically inoperable patients. However, the acute and late toxicity to adjacent organs have been reported as an uncommon but severe adverse effect. CASE PRESENTATION: A 65-year-old male was presented with his back pain and pyrexia. He had been followed up for non-small-cell lung cancer, which was treated by the stereotactic body radiotherapy 4 years prior to the current visit. The endoscopy revealed an esophageal perforation on its left side in the upper thoracic locus. Because of his poor lung function, he was managed by the conservative treatment. After 3 months, his back pain recurred with developing paraplegia in the lower extremities. The MRI revealed an abscess formation at the posterior side of the upper thoracic esophagus which destroyed the vertebral body and compressed the spinal cord. Laminectomy and two-stage operation-the first stage, nontransthoracic esophagectomy, cervical and transhiatal approach using mediastinoscope and laparoscope, and the second stage, esophageal reconstruction-were performed. CONCLUSION: This complex disease status was successfully managed by the orthopedic surgery followed by a two-stage esophagectomy without transthoracic approach.

Preclinical study of transcervical upper mediastinal dissection for esophageal malignancy by robot-assisted surgery.

BACKGROUND: Robotic surgical systems are potentially applicable to transcervical mediastinal lymph dissection for esophageal malignancy. METHODS: Robot-assisted surgery was performed on a male fresh-frozen human cadaver. Devices for single-port laparoscopic surgery were deployed via one small incision in the left clavicular area. The task for the robot-assisted surgery was the upper mediastinal dissection to the level of the left main bronchus and en bloc harvest of the lymph nodes adherent to the left recurrent laryngeal nerve. RESULTS: An up-angled 30° scope in the 6 o'clock port and two robotic arms from the 3 and 9 o'clock ports worked effectively together. No collisions of the devices inside the cadaveric body or unexpected traumatic events occurred. CONCLUSION: The robotic surgical system can be used safely for the upper mediastinal dissection. Copyright © 2016 John Wiley & Sons, Ltd.

The secretogranin II gene is a signal integrator of glutamate and dopamine inputs.

Cooperative gene regulation by different neurotransmitters likely underlies the long-term forms of associative learning and memory, but this mechanism largely remains to be elucidated. Following cDNA microarray analysis for genes regulated by Ca(2+) or cAMP, we found that the secretogranin II gene (Scg2) was cooperatively activated by glutamate and dopamine in primary cultured mouse hippocampal neurons. The Ca(2+) chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester (BAPTA-AM) and the mitogen-activated protein kinase (MAPK) kinase (MEK) inhibitor PD98059 prevented Scg2 activation by glutamate or dopamine; thus, the Ca(2+) /MEK pathway is predicted to include a convergence point(s) of glutamatergic and dopaminergic signaling. Unexpectedly, the protein kinase A inhibitor KT5720 enhanced Scg2 activation by dopamine. The protein-synthesis inhibitor cycloheximide also enhanced Scg2 activation, and the proteasome inhibitor ZLLLH diminished the KT5720-mediated augmentation of Scg2 activation. These results are concordant with the notion that dopaminergic input leads to accumulation of a KT5720-sensitive transcriptional repressor, which is short-lived because of rapid degradation by proteasomes. This repression pathway may effectively limit the time window permissive to Scg2 activation by in-phase glutamate and dopamine inputs via the Ca(2+) /MEK pathway. We propose that the regulatory system of Scg2 expression is equipped with machinery that is refined for the signal integration of in-phase synaptic inputs. We proposed hypothetical mechanism for the regulation of the secretogranin II gene as a signal integrator of glutamate and dopamine inputs. Glutamate or dopamine activates the Ca(2+) /MEK/ERK pathway, which thus contributes to the signal integration. Concurrently, activation of the PKA inhibitor KT5720-sensitive pathway by dopamine leads to accumulation of the repressor protein X that is otherwise susceptible to proteasome degradation. This repression system may determine the time window permissive to the cooperative activation by in-phase glutamate and dopamine inputs.