Response to chemotherapy could predict the prognosis of esophageal squamous cell carcinoma treated with neoadjuvant docetaxel, cisplatin, and fluorouracil (DCF) followed by surgery: long-term results in a single institute.

BACKGROUND: Preoperative chemotherapy with 5-fluorouracil and cisplatin (FP) followed by surgery has been considered a standard treatment for patients with stage II/III esophageal squamous cell carcinoma (ESCC) based on the results of a phase III trial (JCOG9907) in Japan. Subsequently, the phase III NExT trial (JCOG1109) revealed the survival benefit of the neoadjuvant DCF regimen, which adds docetaxel to FP, and it became a standard treatment. However, the long-term results and prognostic factors of neoadjuvant DCF therapy in the real world are unknown. METHODS: We retrospectively investigated 50 patients with ESCC treated with neoadjuvant DCF therapy from July 2012 to December 2017 at The University of Tokyo Hospital. RESULTS: Median overall survival (OS) and progression-free survival (PFS) were 32.3 [95% confidence interval (CI) 21.0-NA] and 10.0 months (95% CI 6.3-15.6), respectively. Median OS [not reached (95% CI 31.5-NA) vs. 21.4 months (95% CI 13.5-33.0); p = 0.028] and PFS [83.3 months (95% CI 6.4-NA) vs. 7.4 months (95% CI 6.0-12.8] were significantly longer in patients with an objective response than in non-responders. Of 44 surgical cases, median PFS tended to be longer in pathological lymph node metastasis-negative patients. Conversely, survival did not differ according to cStage (II/III vs. IV) or the average relative dose intensity (ARDI, ≥ 85% vs. < 85%). DISCUSSION: The response to neoadjuvant DCF therapy could predict patient prognosis. Additionally, pN+ tended to increase the recurrence risk, whereas cStage and ARDI did not influence survival.

Preoperative NUn score serves as a robust predictor of overall and disease-specific survivals following radical surgery for gastric cancer.

PURPOSE: Methods to preoperatively stratify oncological risks associated with gastric cancer (GC) are limited. Host inflammatory parameters, i.e., serum C-reactive protein (CRP) and albumin levels, are known to be associated with outcomes. We examined the relationships between disease-specific mortality and four CRP-albumin-based indices (CRP-albumin ratio [CAR], modified Glasgow prognostic score [mGPS], Osaka prognostic score [OPS], and NUn score) preoperatively measured in cases with resectable GC. METHODS: Survival outcomes of 1290 consecutive GC patients with oncological gastrectomy were reviewed. Predictive significances of preoperative CAR, mGPS, OPS, and NUn scores were assessed with time-dependent receiver operating characteristic curves and Cox regression analyses. RESULTS: Median follow-up was 107 months. Area under the curve for predicting overall and disease-specific survivals (OS/DSS) for the preoperative NUn score was clearly superior to those of the other parameters. On univariate Cox regression analysis, preoperative CAR, mGPS, OPS, and the NUn score all correlated significantly with OS/DSS. On multivariate Cox regression analysis, the preoperative NUn score, as a continuous variable, showed an independent relationship with OS (hazard ratio [HR] 1.32, 95% confidence interval [CI] 1.16-1.50, per 1-unit increase, P < 0.001) and even DSS (HR 1.23, 95% CI 1.02-1.49, P = 0.032). The other three markers failed to maintain independence for DSS. CONCLUSIONS: Preoperative NUn scores are stably associated with outcomes, including disease-specific mortality, possibly serving as a simple measure to define the likelihood of progression to systemic disease after meticulous surgery for GC, which may contribute to identifying patients who would benefit from additional modalities.

Laparoscopic and endoscopic cooperative surgery as palliative treatment for elderly patients with gastric cancer.

Oncological gastrectomy, despite remaining a mainstay of gastric cancer treatment, is reportedly associated with high morbidity and mortality in elderly patients. Less invasive modalities suitable for senior gastric cancer patients with insufficient surgical tolerance are thus needed. We adopted laparoscopic and endoscopic cooperative surgery as an alternative for elderly gastric cancer cases unsuitable for aggressive gastrectomy. To date, we have experienced three cases (80-86 years old) undergoing palliative laparoscopic and endoscopic cooperative surgery. Postoperative courses were uneventful in two cases, while sutural leakage occurred in the other, which was managed conservatively. Postoperative loss of body weight and skeletal muscle mass appeared to be minimal according to bioelectrical impedance analyses. No gastric cancer recurrence was detected in any of our three cases. As to the balance between radicality and safety, laparoscopic and endoscopic cooperative surgery is potentially a viable option for geriatric gastric cancer patients in whom conventional gastrectomy is contraindicated.

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.

Solitary Cardiac Metastasis from Esophageal Cancer.

A 72-year-old woman with past medical history of rectal cancer resection (adenocarcinoma, pT3N1aM0) presented with a 2-month history of dysphagia. Imaging studies found a thoracic esophageal cancer, for which subtotal esophagectomy with gastric conduit reconstruction via retrosternal route followed by chemoradiotherapy were performed (squamous cell carcinoma, pT4N1M0, RM1). Seven months after the esophagectomy, a contrast-enhanced computed tomography (CT) demonstrated a new asymptomatic mass inside the right atrium. A thrombus or a tumorous lesion was suspected. Positron emission tomography (PET)/CT showed abnormal uptake in the mass. After a thorough discussion by a multidisciplinary oncology group, we performed 1-week anticoagulant therapy first, resulting in mass enlargement. Then tumorectomy was carried out. The final pathological findings revealed that the mass was squamous cell carcinoma, yielding the diagnosis of cardiac metastasis from esophageal cancer. The patient's postoperative course was unremarkable. PET/CT may help to estimate malignancy and to omit invasive heart surgery.

Adenocarcinoma of the stomach and esophagogastric junction with low DNA methylation show poor prognoses.

BACKGROUND: Gastric cancer (GC) is characterized by unique DNA methylation epigenotypes (MEs). However, MEs including adenocarcinomas of the esophagogastric junction (AEG) and background non-neoplastic columnar mucosae (NM) remain to be clarified. METHODS: We analyzed the genome-wide DNA MEs of AEG, GC, and background NM using the Infinium 450 k beadarray, followed by quantitative pyrosequencing validation. Large-scale data from The Cancer Genome Atlas (TCGA) were also reviewed. RESULTS: Unsupervised two-way hierarchical clustering using Infinium data of 21 AEG, 30 GC, and 11 NM revealed four DNA MEs: extremely high-ME (E-HME), high-ME (HME), low-ME (LME), and extremely low-ME (E-LME). Promoter methylation levels were validated by pyrosequencing in 146 samples. Non-inflammatory normal mucosae were clustered into E-LME, whereas gastric or esophagogastric junction mucosae with chronic inflammatory changes caused by either Helicobacter pylori infection or reflux esophagitis were clustered together into LME, suggesting that inflammation status determined DNA MEs regardless of the cause. Three cases of Barrett's-related adenocarcinoma were clustered into HME. Among 94 patients whose tumors could be clustered into one of four MEs, 11 patients with E-LME cancers showed significantly shorter overall survival than that in the other MEs, even with the multivariate Cox regression estimate. TCGA data also showed enrichment of AEG in HME and a poorer prognosis in E-LME. CONCLUSIONS: E-LME cases, newly confirmed in this study, form a unique subtype with poor prognosis that is not associated with inflammation-associated elevation of DNA methylation levels. LME could be acquired via chronic inflammation, regardless of the cause, and AEG might preferentially show HME.

Combining nutritional status with TNM stage: a physiological update on gastric cancer staging for improving prognostic accuracy in elderly patients.

BACKGROUND: The tumor-node-metastasis (TNM) staging system does not take the patient's physiological status into consideration, reportedly making it insufficient for predicting survival outcomes in frail cancer patients. We assessed the prognostic values of several nutrition- and inflammation-based markers in combination with pTNM stage in gastric carcinoma (GC) patients. METHODS: In total, 1166 patients undergoing GC surgery were studied. The prognostic capabilities of 3 nutritional and 3 systemic inflammatory parameters were examined. We developed new staging systems by adding these markers, individually, to the pTNM stage. We then compared the prognostic capabilities of our new systems with that of pTNM stage alone. We also assessed the prognostic values of these systems by dividing our patient cohort into elderly (≥ 65 years) and non-elderly groups. RESULTS: Our novel staging systems had greater predictive capabilities for overall survival (OS) than pTNM alone. Most notably, survival discrimination was significantly increased for pTNM when it was combined with albumin-based nutritional indices (geriatric nutritional risk index (GNRI) and prognostic nutritional index (PNI)). Our new staging systems incorporating GNRI or PNI into pTNM had significantly better predictive capability for OS, especially non-GC mortality, than pTNM alone in elderly GC patients. In the non-elderly patients, the predictive capabilities of the new staging systems for OS differed minimally from that of pTNM. CONCLUSIONS: The predictive capability of pTNM stage was particularly enhanced when this parameter was combined with nutritional markers. Our new approach aids in predicting survival outcomes, especially non-GC-related death, in elderly GC patients.

Implications of Liver-Directed Therapy for Postoperative Hepatic Metastasis from Esophageal Cancer.

Background: Distant recurrence of esophageal cancer (EC), even after radical resection, is common, and the most frequent site of EC metastasis is the liver. However, a multidisciplinary treatment strategy for postoperative liver metastasis (LM) from EC has yet to be established; in particular, the role of liver-directed therapy (LDT) remains uncertain. We investigated the clinicopathological features and outcomes of patients undergoing post-esophagectomy LM with versus without LDT to explore its therapeutic implications. Methods: Among 624 consecutive patients undergoing R0/R1 esophagectomy for EC, 30 were identified in whom LM had developed as the initial recurrence. Their characteristics were retrospectively reviewed. Results: Six of the 30 subjects underwent LDT for metachronous LM. Five of those 6 also received systemic chemotherapy. A comparison between the 6 LDT and 24 non-LDT cases revealed no significant differences in major clinicopathological and operative factors, except for concurrent metastasis to extrahepatic organs (1/6 vs. 15/24, p=0.044). Twenty-nine of the 30 patients died during the study period, whereas 1 who had received multimodal treatment with LDT remained alive more than 200 months after multiple LM had been detected. Kaplan-Meier analysis for survival after LM demonstrated significantly prolonged survival in LDT cases compared to non-LDT cases treated with systemic chemotherapy alone (p=0.014). Even when the analysis was limited to patients without extrahepatic metastasis, this significant prognostic advantage of LDT was maintained (p=0.047). Conclusion: Multimodal treatment combined with LDT might be beneficial for patients with metachronous LM from EC and should therefore be considered a potential treatment option.

Idiopathic retroperitoneal fibrosis mimicking infiltrative malignancy: a case report.

The treatment strategy for an idiopathic retroperitoneal mass has not yet been established. Additionally, differentiating between benign and malignant is a challenge. Herein, we report a case in which we performed partial resection of a mass in a symptomatic patient with idiopathic retroperitoneal fibrosis that mimicked malignancy. A 44-year-old woman with an unremarkable medical history other than gallstones presented with a 1-month history of abdominal pain and repetitive vomiting. Imaging studies identified a large, retroperitoneal mass compressing the duodenum that had grown acutely over the preceding 2 weeks. The possibility that the mass was malignant could not be excluded. Considering the invasiveness and potential curability, we performed partial resection of the mass, which involved partial colonic resection with reconstruction, to allow for pathological diagnosis and intestinal obstruction treatment. The final pathological findings revealed that the mass consisted of hemorrhagic and fibrotic tissue without a tumorous component. The patient's postoperative course was unremarkable. She is alive 8 years postoperatively with no recurrence. In conclusion, a surgical approach, including biopsies, to idiopathic retroperitoneal fibrosis that mimics malignancy should be actively considered in symptomatic patients. Decisions regarding the required degree of surgical intervention call for sufficient, case-specific discussion.

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.

Identification of Preoperative Fat-Free Mass Index for the Prognosis of Curatively Resected Esophageal Cancer.

BACKGROUND: The progressive, systemic depletion of muscle mass is a poor prognostic factor for various types of cancers. However, the assessment of body composition for patients with esophagectomy remains unclear. Therefore, we evaluated the significance of the fat-free mass index (FFMI) and estimated the appropriate cutoff value. METHODS: We compiled clinicopathological characteristics of patients who underwent curative operation for esophageal cancer between October 2013 and March 2018 at Toranomon Hospital and reviewed them until December 2020. We analyzed the short- and long-term outcomes, compared to conventional nutritional factors, and calculated the area under the receiver operating characteristic (ROC) curve. RESULTS: A total of 200 patients were eligible for inclusion. FFMI was ineffective in predicting postoperative complications, with no correlation with other nutritional biomarkers. Preoperative low FFMI led to poor overall survival (OS), and the lower cutoff values based on the time-dependent ROC analysis were 14.4 and 16.8 kg/m2 in women and men, respectively. Multivariate analysis for OS revealed that low FFMI (p = 0.010, HR 2.437, 95% CI 1.234-4.815) and clinical stage (p = 0.010, HR 4.781, 95% CI 1.447-15.796) were independent prognostic factors. The 3-year survival rates were 68.9% in low FFMI and 88.6% in normal FFMI. CONCLUSIONS: The low FFMI was not predictive of postoperative complications but an independent prognostic factor in esophageal cancer with curative resection, having no correlation with other biomarkers. Our cutoff FFMI values could be useful in selecting the target for muscle improvement programs.

Esophageal Cancer Surgery in Dialyzed Patients: A Single Institution Case Series.

We sought to evaluate the feasibility of esophageal carcinoma (EC) surgery in cases requiring dialysis. Among 250 consecutive patients undergoing surgical resection for EC, three on maintenance dialysis were identified. We retrospectively analyzed their clinical characteristics. The three dialyzed patients were all males, 39-77 years old at EC surgery. The operations were thoracoscopic esophagectomy with nodal clearance (Case 1), cervical esophageal resection without thoracic procedures (Case 2), and thoracoscopic esophagectomy without reconstruction, emergently conducted for tumor bleeding (Case 3). Reoperation had been required for postoperative abdominal hematoma in Case 1. Postoperative tracheostomy had been performed due to severe pneumonia in Case 2. EC surgery for dialyzed patients, despite appearing to be feasible, might be associated with a high risk of life-threatening morbidities. To minimize surgical risk, therapeutic decision-making for such cases should be based on the balance between radicality and safety.

Successful laparoscopic resection of gastric lymphangioma under the intraoperative guidance of indocyanine green fluorescence imaging: A case report.

Gastric lymphangioma (GLA) is an extremely rare tumor without an established therapeutic strategy. Surgical resection is considered the mainstay of treatment, although there is a high risk of local recurrence if negative margins are not achieved. A 51-year-old man underwent routine abdominal ultrasonography, which incidentally detected a 20-mm tumor adjacent to the lesser curvature of the stomach. GLA was suspected based on its polycystic appearance. After a 16-month monitoring period, laparoscopic resection was performed because of tumor growth and involvement of the left gastric artery. Intraoperative indocyanine green (ICG) navigation system revealed lymphatic drainage from the tumor, which we used to help determine the optimal excision line and minimize the loss of gastric volume. Pathological examination confirmed complete resection with negative margins and supported a diagnosis of lymphangioma. We performed laparoscopic radical resection of GLA under guidance from intraoperative ICG fluorescence imaging, which allowed us to maximize residual gastric volume.

Factors Affecting Blood Loss During Thoracoscopic Esophagectomy for Esophageal Carcinoma.

BACKGROUND: Major intraoperative hemorrhage reportedly predicts unfavorable survival outcomes following surgical resection for esophageal carcinoma (EC). However, the factors predicting the amount of blood lost during thoracoscopic esophagectomy have yet to be sufficiently studied. We sought to identify risk factors for excessive blood loss during video-assisted thoracoscopic surgery (VATS) for EC. METHODS: Using simple and multiple linear regression models, we performed retrospective analyses of the associations between clinicopathological/surgical factors and estimated hemorrhagic volume in 168 consecutive patients who underwent VATS-type esophagectomy for EC. RESULTS: The median blood loss amount was 225 mL (interquartile range, 126-380 mL). Abdominal laparotomy (p<0.001), thoracic duct resection (p=0.014), and division of the azygos arch (p<0.001) were significantly related to high volumes of blood loss. Body mass index and operative duration, as continuous variables, were also correlated positively with blood loss volume in simple linear regression. The multiple linear regression analysis identified prolonged operative duration (p<0.001), open laparotomy approach (p=0.003), azygos arch division (p=0.005), and high body mass index (p=0.014) as independent predictors of higher hemorrhage amounts during VATS esophagectomy. CONCLUSION: As well as body mass index, operation-related factors such as operative duration, open laparotomy, and division of the azygos arch were independently predictive of estimated blood loss during VATS esophagectomy for EC. Laparoscopic abdominal procedures and azygos arch preservation might be minimally invasive options that would potentially reduce intraoperative hemorrhage, although oncological radicality remains an important consideration.

The different survival impacts of body mass index in elderly and non-elderly patients with gastric carcinoma.

BACKGROUND: The age-dependent survival impact of body mass index (BMI) remains to be fully addressed in patients with gastric carcinoma (GC). We investigated the prognostic impacts of BMI in elderly (≥70 years) and non-elderly patients undergoing surgery for GC. METHODS: In total, 1168 GC patients were retrospectively reviewed. Patients were stratified into 3 groups according to BMI; low (<20), medium (20-25) and high (>25). The effects of BMI on overall survival (OS) and cancer-specific survival (CSS) were assessed using univariate and multivariate Cox hazards models. RESULTS: There were 242 (20.7%), 685 (58.7%) and 241 (20.6%) patients in the low-, medium- and high-BMI groups, respectively. The number of patients with high BMI but decreased muscle mass was extremely small (n = 13, 1.1%). Patients in the low-BMI group exhibited significantly poorer OS than those in the high- and medium-BMI group (P < 0.001). Notably, BMI classification significantly demarcated OS and CSS curves (both P < 0.001) in non-elderly patients, while did not in elderly patients (OS; P = 0.07, CSS; P = 0.54). Furthermore, the survival discriminability by BMI was greater in pStage II/III disease (P = 0.006) than in pStage I disease (P = 0.047). Multivariable analysis focusing on patients with pStage II/III disease showed low BMI to be independently associated with poor OS and CSS only in the non-elderly population. CONCLUSIONS: BMI-based evaluation was useful for predicting survival and oncological outcomes in non-elderly but not in elderly GC patients, especially in those with advanced GC.

Adequate period of surveillance in each stage for curatively resected gastric cancer: analyzing the time and rates of recurrence.

BACKGROUND: Surveillance after curative surgery for gastric cancer is conventionally performed for 5 years. However, the appropriate follow-up period remains controversial. METHODS: This study retrospectively compiled a clinicopathological database of patients who underwent curative gastrectomy between 1975 and 2010 at Toranomon Hospital and were reviewed until March 2020. Analyzing the follow-up rate and recurrence rate for each stage in each postoperative year, we set each follow-up endpoint when the subsequent recurrence rate fell below 1%. RESULTS: A total of 5235 patients were eligible for inclusion in the study. The rate of patients followed up for 5 years was 90.3%. The rates of follow-up were 52.7% at 10 years, 38.3% at 15 years, and 10.3% at 20 years. Recurrence was confirmed in 850 patients in total (16.2%) and in 50 patients beyond 5 years. The adequate follow-up endpoints according to stage (with < 1% recurrence risk) were 2 years for stage IA, 4 years for IB, 6 years for IIA, 9 years for IIB, 7 years for IIIA, and 8 years for IV (curative). For stage IIIB and IIIC, the recurrence risk remained. CONCLUSIONS: The adequate surveillance duration of resected gastric cancer might be different in each stage. Although the follow-up duration for stage I disease could be reduced to less than 5 years, advanced gastric cancer such as stage III or IV disease has risk of recurrence beyond 5 years and therefore additional follow-up is required. These results could help decide the strategy for surveillance.

Management and outcomes of resectable gastric conduit cancer: a retrospective comparative study of 51 cases.

PURPOSE: Although gastric conduit cancer (GCC) arising after esophagectomy is increasingly being reported, therapeutic strategies for resectable GCC have yet to be optimized. We investigated clinicopathological features of patients undergoing endoscopic versus more invasive surgical treatments for GCC and compared their outcomes. METHODS: Fifty-one patients, who had a history of esophagectomy with gastric conduit reconstruction for esophageal cancer and underwent resection for metachronous GCC, were identified. Their characteristics and outcomes were retrospectively reviewed. RESULTS: There were 48 males and three females, ranging in age from 46-86 years. Twelve patients underwent surgery for GCC (group S) and 39 underwent only endoscopic resection (group E). The most common cause of death was pneumonia (10/51, 19.6%). Neither overall survival nor cumulative incidence of pneumonia-caused death differed significantly between the two groups (P = 0.60, 0.84, respectively). In group S, partial gastrectomy was performed in four cases and total gastrectomy in seven. Partial resections, including three antrectomy without sternotomy or intrathoracic procedures, were completed with significantly shorter operative durations than total resections (median 208 vs 513 min, P = 0.012). GCC recurrence was experienced in two cases: one undergoing open approach partial resection of the corpus and the other thoracoscopic total gastrectomy. CONCLUSION: Even compared with endoscopic treatment, outcomes following surgery for GCC appeared to be acceptable. Open approach total gastric gastrectomy could be the most radical modality, while other less invasive alternatives, e.g., antrectomy, are also an option. Clinicians may select a treatment strategy balancing radicality and patient status, reflecting tolerance to invasive procedures.