Ramucirumab Plus Paclitaxel as a Second-line Chemotherapy in Older Adults With Advanced Gastric Cancer (YCOG1601).

BACKGROUND/AIM: Ramucirumab plus paclitaxel has been widely used as a second-line chemotherapy for treating advanced gastric cancer. However, the real-world data of this regimen for older patients with gastric cancer (GC) remains unrevealed. The aim of this study was to clarify the feasibility and efficacy of this regimen for older patients with GC in a single-arm, phase II study. PATIENTS AND METHODS: Patients aged ≥70 years having unresectable or recurrent GC who met the eligible criteria were enrolled. Paclitaxel was administered at a dose of 80 mg/m2 on days 1, 8, and 15, and ramucirumab was administered at a dose of 8 mg/kg on day 1 and day 15 of a 4-week cycle. Primary endpoint was the incidence of adverse events and secondary endpoints were response rate, progression-free survival, and overall survival. A total of 25 patients were enrolled in the full-set analysis. RESULTS: Grade 3 or more adverse events were observed in 21 patients (84.0%). Neutropenia was most frequently observed (68.0%), followed by peripheral sensory neuropathy (12.0%), and febrile neutropenia (12.0%). Median progression-free survival and overall survival were 6.9 months and 13.4 months, respectively. Disease control rate was 88.0%, and response rate of patients with measurable lesions was 52.9%. Notably, no treatment-related deaths occurred. CONCLUSION: Ramucirumab plus paclitaxel as a second-line chemotherapy demonstrated acceptable oncological outcomes, despite the occurrence of frequent adverse events. It is necessary to carefully select patients and adjust treatment regimens in older patients with GC to safely administer chemotherapy and subsequently achieve satisfactory long-term outcomes.

Re-evaluation of the prognosis of alpha-fetoprotein-producing gastric cancer from a single center: a case series study.

BACKGROUND: Alpha-fetoprotein (AFP)-producing gastric cancer (AFPGC) is reported to have biologically aggressive features and poor prognosis. A relatively large number of patients with AFPGC have achieved a long-term prognosis after surgery in our institution. This study aimed to clarify the clinical features of and re-evaluate the long-term outcomes of AFPGC. METHODS: This analysis involved 465 patients who underwent surgery for gastric cancer (GC) at our institute between 1996 and 2020. The clinical features and long-term outcomes of the 24 patients with AFPGC were assessed. The differences in clinicopathological characteristics between AFPGC and non-AFPGC patients were statistically analyzed. RESULTS: In patients with AFPGC, the median preoperative serum AFP level was 232 ng/mL. Tumor invasion of AFPGC was classified and clinical characteristics of AFPGC patients were as follows: nodal metastasis, simultaneous liver metastasis, with malignant cells in ascites, lymphatic, and venous involvement. Postoperative surveillance revealed adjuvant therapy in fourteen, recurrence in eight, and four patients died of GC. The 3- and 5-year overall survival (OS) rates were 85.2% and 75.7% in AFPGC patients and 79.6% and 77.7% in non-AFPGC patients, respectively. The log-rank test identified no significant difference in OS between AFPGC and non-AFPGC patients. Tumor depth, nodal, and venous involvement showed significant differences between AFPGC and non-AFPGC patients. CONCLUSIONS: AFPGC has aggressive biological features, but long-term prognosis after surgery does not seem to be as poor as claimed in previous studies. Therefore, it may be important to detect and start treatment early when surgery is feasible.

Clinical significance of initial treatment for peritoneal lavage cytology-positive gastric cancer: outcomes according to treatment strategy.

BACKGROUND: Although patients with positive lavage cytology (CY1) are classified as having stage IV disease, long-term survival without other unresectable factors (P0CY1) has been reported. Conversion gastrectomy in patients with a change in cytology status after induction chemotherapy might improve survival, but appropriate treatment remains controversial. Here, we reviewed our experience in treating CY1 gastric cancer to evaluate the best treatment strategy. METHODS: Clinical and pathological findings of patients with a diagnosis of P0CY1 gastric cancer at Toranomon Hospital between February 2006 and April 2019 were retrospectively analyzed. Patients were classified into two groups according to initial treatment: a surgery-first group and a chemotherapy-first group. In addition, the patients were categorized into subgroups based on the subsequent treatment pattern. The surgery-first group was divided into two subgroups: adjuvant chemotherapy and palliative gastrectomy only. The chemotherapy-first group was divided into three subgroups with the subsequent treatment pattern depending on the response to chemotherapy: conversion gastrectomy, palliative gastrectomy after induction therapy, and palliative chemotherapy. RESULTS: In total, 38 patients were eligible for inclusion in this study. After initial assessment of cytology status, 21 patients underwent gastrectomy as initial treatment (surgery first) and 17 received induction chemotherapy (chemotherapy first). Ten patients underwent surgery first with adjuvant chemotherapy, 11 underwent palliative gastrectomy alone, 5 underwent conversion surgery, 5 with CY1 disease after induction chemotherapy underwent palliative gastrectomy, and 7 received palliative chemotherapy only. The 3-year survival rate was 23.4% (median survival, 17.7 months) in the surgery-first group and 27.3% (median survival, 19.7 months) in the chemotherapy-first group. The 3-year survival rate was 75% for conversion gastrectomy, 16.7% for palliative chemotherapy, and 0% for palliative gastrectomy after induction chemotherapy. CONCLUSIONS: There was no significant difference in outcome according to whether surgery or chemotherapy was performed first. The prognosis of conversion surgery with curative resection was better than that of the other types of treatment. However, the outlook after induction chemotherapy was poor. Patients with advanced gastric cancer should be treated cautiously until more effective treatment options become available.

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.

Importance of long-term surveillance after curative esophagectomy for esophageal squamous cell carcinoma.

BACKGROUND: The long-term outcomes after esophagectomy for esophageal cancer remain uncertain and the optimal surveillance strategy after curative surgery remains controversial. METHODS: In this study, the clinicopathological characteristics of patients who underwent curative thoracic esophagectomy between 1991 and 2015 at Toranomon Hospital were retrospectively analyzed and reviewed until December 2020. We evaluated the accumulated data regarding the pattern and rates of recurrence and second malignancy. RESULTS: A total of 1054 patients were eligible for inclusion in the study. Of these, 97% were followed up for 5 years, and the outcomes after 25 years could be determined in 65.5%. Recurrence was diagnosed in 318 patients (30.2%), and the most common pattern was lymph node metastasis (n = 168, 52.8%). Recurrence was diagnosed within 1 year in 174 patients (54.7%) and within 3 years in 289 (90.9%). Second malignancy possibly occurred through the entire study period after esophagectomy even in early-stage cancer, keeping 2%-5% of the incidental risk. There was no significant difference in the prognosis between 3-year survivors with and without a second malignancy. CONCLUSIONS: Most recurrences after resection of esophageal cancer occurred within 3 years regardless of disease stage. However, these patients have an ongoing risk of developing a second malignancy after esophagectomy. Further consideration is required regarding the efficacy of long-term surveillance.

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.

Nutritional Outcomes of Thoracic Duct Resection for Radical Esophagectomy by Assessing Body Composition Changes in One Year: A Single-Center Retrospective Study.

BACKGROUND: Thoracic duct (TD) resection is performed when the tumor or a metastatic lymph node directly invades the TD, and is sometimes indicated for radical lymphadenectomy during esophagectomy in esophageal cancer patients. However, the effect of TD resection on nutritional status has not been established. PATIENTS AND METHODS: In total, 174 consecutive patients from October 2015 to March 2019 who underwent radical esophagectomy for esophageal cancer in Toranomon Hospital were classified into thoracic duct preserved group (n = 51) and TD-resected (TD-R) group (n = 123). We compared laboratory data, body composition data from bioelectrical impedance analysis measured preoperatively and at 1 and 12 months after surgery, and postoperative complications between the two groups. RESULTS: Clinical stage was significantly more advanced in the TD-R group. Total body weight, body mass index, and fat mass continuously decreased in the two groups over 12 months after surgery, and the decreases were statistically greater in the TD-R group at 12 months after surgery. Skeletal muscle mass and fat-free mass decreased over 1 month after surgery and stayed in a reduced state until 12 months after surgery without statistically significant differences between the two groups. TD resection did not increase incidence of postoperative complications (Clavien-Dindo classification ≥ grade III), but TD resection increased incidence of chylothorax. CONCLUSIONS: Our results suggest that loss of body fat mass, which was a main contributor to body weight loss, was accelerated in the TD-R group, but TD resection does not deteriorate loss of muscle mass at 12 months after surgery.

Intestinal intussusception and progressive anemia due to pyogenic granuloma of the ileum: a case report.

BACKGROUND: Pyogenic granuloma is a benign vascular tumor, usually occurring on the skin or in the oral cavity. Small intestinal pyogenic granuloma is extremely rare, but intestinal intussusception due to the tumor is even rarer. Only 3 cases have been reported in the English literature at this writing. CASE PRESENTATION: An 86-year-old woman presented with abdominal pain and vomiting. Laboratory data discovered anemia. Contrast-enhanced computed tomography revealed small bowel obstruction due to intestinal intussusception. After decompression by long tube for 1 week, the obstruction did not improve and the anemia got worse. Therefore, laparoscopic assisted small bowel resection was performed as a diagnostic therapy. Pathology confirmed the diagnosis of pyogenic granuloma. The postoperative course was uneventful and the patient was discharged 10 days after surgery. CONCLUSIONS: We experienced a case of intestinal intussusception and progressive anemia due to pyogenic granuloma of the ileum. Although the condition is extremely rare, surgeons must take into consideration the tumor in similar cases, and complete surgical resection is required.

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.

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.

Comparative analysis of the prognostic utility of preoperative nutritional parameters in patients with resectable esophageal carcinoma.

OBJECTIVE: Although surgical resection is a mainstay in the management of esophageal carcinoma (EC), its postoperative outcomes remain unsatisfactory. To optimize surgical strategies for EC, a simple method of stratifying patients according to risk factors is desired. Controlling nutritional status (CONUT), the prognostic nutritional index (PNI), transthyretin and transferrin are nutritional parameters used to predict the long-term outcomes of EC patients. We aimed to comparatively evaluate the prognostic significance of these four markers, measured preoperatively, in patients with operable EC. METHODS: In total, 224 patients undergoing surgical resection for EC were retrospectively reviewed. Overall/cancer-specific survivals (OS/CSS) were estimated applying the Cox proportional hazard model to univariate and multivariate analyses. PNI, transthyretin and transferrin levels were treated as continuous variables in these analyses. RESULTS: Preoperative CONUT had significant associations with tumor location, depth and preoperative irradiation. The other three markers all showed significant relationships with age and tumor depth. On univariate Cox regression analysis, preoperative CONUT, PNI, transthyretin and transferrin all correlated significantly with OS and CSS. On multivariate Cox regression analysis, the preoperative transthyretin level was identified as an independent predictor of OS (HR 0.51 per 10 mg/dL increase, 95% CI 0.29-0.88, p = 0.017) and CSS (HR 0.50, 95% CI 0.27-0.91, p = 0.027) as well as tumor depth, nodal metastasis and preoperative irradiation, while the other three parameters were not. CONCLUSIONS: Preoperative transthyretin, as a continuous variable, independently predicted both OS and CSS in resectable EC patients, appearing to be the best prognosticator among conventional nutrition-related parameters.

Diaphragmatic herniation following total gastrectomy: review of the long-term experience of a tertiary institution.

PURPOSE: Diaphragmatic herniation (DH) is a rare but potentially fatal event after total gastrectomy (TG). Despite being life-threatening, risk factors for postoperative DH have yet to be elucidated. We conducted a retrospective analysis to identify clinical characteristics of patients developing DH after TG, along with a comprehensive review of the published literature. METHODS: Among 1361 consecutive patients undergoing TG for esophagogastric cancer between 1985 and 2013 in Toranomon Hospital, those requiring surgical intervention for postoperative DH were included. We also conducted a PubMed literature search on DH following TG. RESULTS: Five patients (four males, one female), with a median age of 68 at DH surgery, were identified. Intervals between TG and DH repair ranged from 2.9 to 189.0 (median, 78.1) months. Four patients had needed emergency surgery. Three patients had undergone open TG and two others laparoscopic TG, suggesting a significantly higher incidence of DH after laparoscopic TG (3/1302 vs. 2/59, p = 0.017). The diaphragmatic crus incision, creating the space for esophagojejunostomy, had been performed in all cases. The literature yielded seven relevant publications (16 patients). Intervals between TG and DH reduction ranged from 2 days to 36 months. All operations for DH had been carried out emergently. CONCLUSION: The risk of DH persisted after TG. DH is potentially a very late complication of TG, presenting as a surgical emergency. Laparoscopic TG was suggested to be a risk factor for postgastrectomy DH. Incising the crus might also be a predictor of DH. Measures to prevent DH, e.g., appropriate closure of the crus, would be recommended in minimally invasive TG.

Medullary carcinoma of the pancreas radiologically followed up as a cystic lesion for 9 years: a case report and review of the literature.

BACKGROUND: Medullary carcinoma of the pancreas (MCP) is a rare malignant pancreatic tumor. The World Health Organization classification defines the tumor as a subtype of pancreatic ductal carcinomas. MCP is histologically characterized as having highly pleomorphic cells with syncytial morphology, expansive tumor growth, and necrosis. The pathogenesis and clinical course of MCP are largely unknown. Herein, we report an unusual case of MCP that was radiologically followed up for 9 years prior to surgical intervention. CASE PRESENTATION: A 73-year-old Japanese woman with a nonspecific disease history was found to have an asymptomatic cyst in the pancreatic duct by abdominal ultrasonography. Thorough radiological investigation suggested it was not an aggressive neoplasm, and she received periodic check-ups under a clinical diagnosis of "a cystic pancreatic lesion of uncertain malignancy." Nine years after initial presentation, she experienced acute pancreatitis and underwent thorough re-evaluation. Dynamic computed tomography revealed no cyst; rather, a solid tumor was detected. Cytology of the pancreatic duct suggested adenocarcinoma. Pancreatoduodenectomy with D2 lymph node dissection was performed. The resected tumor was a non-mucinous, solid mass measuring 22 × 10 mm. Microscopically, the tumor had a well-demarcated pushing border. Lymphocytic infiltration was abundant, and stromal component was sparse. The tumor cells were composed of highly pleomorphic cells, proliferating in sheets without glandular formation. Neither lymphovascular invasion nor lymph node metastasis was detected. The histopathologic diagnosis was MCP, pT1aN0M0. The tumor carried a KRAS mutation, and MLH-1, MSH-2, MSH-6, and PMS-2 immunostaining results were normal, suggesting microsatellite stability. The patient has remained free of disease for 29 months following surgical intervention. CONCLUSION: A review of 20 previously reported cases plus the present case suggests that subsets of MCPs have genetic aberrations such as KRAS mutation and high microsatellite instability. MCP has been suggested to have a better prognosis than common ductal adenocarcinoma; however, 15 of 20 previously reported cases died from disease. Whether the asymptomatic cyst observed over 9 years contributed to the development of MCP in this patient is a subject for future study.