The first case of primary malignant melanoma of the esophagus to achieve pathologic complete response after preoperative ipilimumab + nivolumab followed by resection.

Primary malignant melanoma of the esophagus is a rare disease with a poor prognosis. Surgical resection is common, but there is no consensus on perioperative treatment. Studies have reported the efficacy of programmed cell death-1 inhibitors (e.g., nivolumab, pembrolizumab) and anti-cytotoxic T-lymphocyte-associated antigen 4 agents (e.g., ipilimumab) in treating malignant melanoma. Here, we present the first case of primary malignant melanoma of the esophagus with lymph node metastases treated with nivolumab and ipilimumab followed by resection, achieving a pathologic complete response. A 75-year-old man presented with dysphagia. Esophagogastroduodenoscopy revealed a black, elevated lesion in the mid-thoracic esophagus. Biopsy confirmed primary malignant melanoma of the esophagus, showing tumor cells with melanin deposition, positive for HBM45 and S-100 staining. Computed tomography showed enlarged lymph nodes in the subclavian and mediastinum regions, suggesting metastases. After two courses of preoperative chemotherapy with ipilimumab and nivolumab, which significantly shrank the tumor, the patient underwent robot-assisted subtotal esophagectomy and 3-field lymph node dissection. Histopathological examination revealed no tumors or lymph node metastases, confirming a pathologic complete response. Given the rarity and poor prognosis of primary malignant melanoma of the esophagus, this case provides valuable insights for treatment strategies.

Efficacy of chemotherapy for patients with gastric cancer with early recurrence during or after adjuvant chemotherapy with S-1 alone: a multicenter retrospective study.

This study aimed to survey the efficacy of chemotherapy regimens in the real world setting and explore the most promising regimen for patients experiencing early recurrence for gastric cancer. We retrospectively reviewed the clinical course of 207 patients with gastric cancer, who developed early recurrence during or within 6 months after completing S-1 adjuvant therapy at 19 Japanese institutions between 2012 and 2016. The treatment regimens after recurrence were fluoropyrimidines plus platinum-based regimens (FP) in 91 (44%) patients, paclitaxel-based regimens (PTX) in 102 (49%), and irinotecan-based regimens (IRI) in 14 (7%). The overall response and disease control rates were 28.7% and 54.1%. Median progression-free survival (PFS) and overall survival (OS) were 5.1 and 12.9 months, respectively. In the FP, PTX, and IRI regimens, the median PFS and OS were 5.9, 4.1, 4.1 months and 12.8, 12.9, and 11.8 months, respectively. The combination of PTX and ramucirumab showed survival comparable to capecitabine plus platinum. Multivariate analyses for OS showed that recurrence during adjuvant chemotherapy and undifferentiated histological type were independent poor prognostic factors. Although the prognosis of patients with early recurrence even with adjuvant S-1 was poor, PTX plus ramucirumab therapy could be a potential treatment option.

Laparoscopic Radical Total Gastrectomy and Pancreatosplenectomy for Synchronous Cancer of the Stomach and Pancreas.

The safety of laparoscopic surgery for advanced gastric and pancreatic cancers has been established individually, but there is little evidence for synchronous cancers. In this case, a 59-year-old man with a history of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) treatment for diffuse large B-cell lymphoma underwent laparoscopic surgery for a suspected pancreatic invasion of advanced gastric cancer. Pathology revealed double cancer of the stomach and pancreas. Laparoscopic total gastrectomy and distal pancreatectomy were successfully performed. The patient had a pancreatic leak on postoperative day seven but was discharged from the hospital on postoperative day 21. This case suggests the possibility of expanding the indications for laparoscopic surgery for similar cancers in the future. Additionally, the anatomical reticulum can be resected as a single mass using laparoscopy alone.

Successful Robot-Assisted Surgery for Advanced Metachronous Cancer in a Gastric Conduit after Esophagectomy: A Case Report.

The incidence of gastric tube cancers has increased due to improved survival rates in patients after esophagectomy. However, the optimal surgical approach for gastric tube cancer remains controversial. Here, we report the case of a 70-year-old man with advanced gastric cancer arising from a retrosternally placed gastric conduit, 12 years after thoracic esophagectomy for esophageal cancer. Total resection of the gastric conduit was performed with robotic assistance. Although the working space was limited, secure resection was possible. Continuous en bloc mobilization was achieved with neck dissection, and reconstruction was performed via the same retrosternal route using the ileocolon. The patient was discharged on the 14th postoperative day without any adverse events. Robot-assisted surgery can overcome the technical limitations of laparoscopic mediastinal surgery and has advantages such as improved ergonomics, comfort, and elimination of hand tremors, and therefore may be an option for future minimally invasive surgeries.

Risk factors for early recurrence after radical gastrectomy followed by adjuvant chemotherapy for stage II or III gastric cancer: a multicenter, retrospective study.

BACKGROUND: Radical gastrectomy followed by adjuvant chemotherapy is the standard treatment for stage II or III gastric cancer in Asian countries. Early recurrence during or after adjuvant chemotherapy is associated with poor prognosis; however, risk factors for early recurrence remain unclear. METHODS: In this multicenter, retrospective cohort study including six institutions, we evaluated the clinicopathological factors of 553 patients with gastric cancer undergoing gastrectomy followed by adjuvant chemotherapy between 2012 and 2016. Patients were divided into the following groups: early recurrence (recurrence during adjuvant chemotherapy or within 6 months after adjuvant chemotherapy completion) and non-early recurrence, which was further divided into late recurrence and no recurrence. Early-recurrence risk factors were investigated using multivariate Cox proportional hazard model. The chronological changes in the recurrence hazard were also examined for each factor. RESULTS: Early recurrence and late recurrence occurred in 83 (15.0%) and 73 (13.2%) patients, respectively. Based on the Cox proportional hazards model, a postoperative serum carcinoembryonic antigen level of ≥5 ng/mL (hazard ratio: 2.220, 95% confidence interval: 1.089-4.526) and a neutrophil-to-lymphocyte ratio of >1.8 (hazard ratio: 2.408, 95% confidence interval: 1.479-3.92) were identified as independent risk factors of early recurrence, but not late recurrence. The recurrence hazard ratios for neutrophil-to-lymphocyte ratio significantly decreased over time (P < 0.001) and carcinoembryonic antigen also had the same tendency (P = 0.08). CONCLUSIONS: A carcinoembryonic antigen level of ≥5 ng/mL and a neutrophil-to-lymphocyte ratio of >1.8 are predictors of early recurrence after radical gastrectomy and adjuvant chemotherapy for stage II or III gastric cancer.

Clinical Outcomes of Preserving Bronchial Arteries During Radical Esophagectomy: A Propensity-Score Matched Analysis.

BACKGROUND: Postoperative pneumonia is a common and major cause of mortality after radical esophagectomy. Intraoperative preservation of the bronchial arteries is often aimed at avoiding tracheobronchial ischemia; however, it is unknown whether this contributes to a reduction in postoperative pneumonia. PATIENTS AND METHODS: We enrolled 348 consecutive patients who underwent radical esophagectomy for esophageal cancer at Toranomon Hospital from January 2011 to July 2018. We classified patients into a bronchial artery-resected (BA-R) group (n = 93) and a bronchial artery-preserved (BA-P) group (n = 255) and compared the incidence of postoperative pneumonia between the two groups. A propensity score-matching analysis for bronchial artery preservation versus resection was performed. RESULTS: Overall, 182 patients were matched. Univariate analysis of the propensity score-matched groups showed that Brinkman index ≥ 400, vital capacity (%VC) < 80%, and bronchial artery resection were associated with the development of postoperative pneumonia. Multivariate analysis revealed three significant factors associated with postoperative pneumonia: Brinkman index ≥ 400 [p = 0.006, odds ratio (HR) 3.302, 95% confidence interval (95% CI) 1.399-7.790], %VC < 80% (p = 0.034, HR 6.365, 95% CI 1.151-35.205), and bronchial artery resection (p = 0.034, HR 2.131, 95% CI 1.060-4.282). The incidence of postoperative complications (CD grade III) was higher in the BA-R group (BA-R 42.8% versus BA-P 27.5%, p = 0.030). There was no significant difference in overall survival between the two groups at 5 years (BA-R 63.1% versus BA-P 72.1%, p = 0.130). CONCLUSION: Preserving the bronchial artery is associated with a decreased incidence of postoperative pneumonia.

Total pancreatectomy with remnant stomach preservation in a patient with a history of proximal gastrectomy and interposed jejunal reconstruction with right gastroepiploic conduit preservation: a case report.

BACKGROUND: Pancreatic head resection following proximal gastrectomy jeopardizes the blood flow of the remnant stomach owing to right gastroepiploic conduit sacrifice, thereby necessitating total gastrectomy. However, owing to its high invasiveness, concomitant remnant total gastrectomy with pancreatectomy should be avoided as much as possible. Herein, we describe our experience of total pancreatectomy with right gastroepiploic conduit preservation in a patient with a history of proximal gastrectomy and reconstruction by jejunum interposition. CASE PRESENTATION: A 78-year-old woman with a history of gastric cancer was followed up at our institute for multiple intraductal papillary mucinous neoplasm, and main pancreatic duct stricture in the pancreatic head was newly detected. The cystic lesion was extended to the pancreatic body. Proximal gastrectomy and reconstruction by jejunal interposition were previously performed, and the mesenteric stalk of the interposed jejunum was approached through the retrocolic route. We planned total pancreatectomy with right gastroepiploic conduit preservation. Following adhesiolysis, the interposed jejunum and its mesentery lying in front of the pancreas were isolated. The arterial arcade from the common hepatic artery to the right gastroepiploic artery was detached from the pancreas. Furthermore, the right gastroepiploic vein was isolated from the pancreas. The pancreatic body and tail were pulled up in front of the remnant stomach, and the splenic artery and vein were resected. The pancreatic body and tail were pulled out to the right side, and the pancreatic head was divided from the pancreatic nerve plexus to the portal vein. The jejunal limb for entero-biliary anastomosis was passed through the hole behind the superior mesenteric artery and vein, and gastrointestinal anastomosis using the antecolic route and Braun anastomosis were performed. CONCLUSIONS: To avoid remnant total gastrectomy, right gastroepiploic conduit preservation is an optional procedure for pancreatic head resection in patients who have undergone proximal gastrectomy with reconstruction by jejunal interposition.

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.

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.

A rare case of Helicobacter pylori-uninfected foveolar-type gastric cancer with submucosal invasion and lymph node metastasis.

Gastric cancer without Helicobacter pylori infection accounts for less than 1% of all gastric cancers, and is generally considered to be less invasive. This report describes a rare case of H. pylori-uninfected gastric cancer with deep submucosal invasion and lymph node metastasis. Endoscopic submucosal dissection was performed, and pathological examination revealed tubular adenocarcinoma with deep submucosal invasion. We diagnosed foveolar-type gastric adenocarcinoma. While many cases of foveolar-type gastric adenocarcinoma, especially of the white elevated type, are reported as early stage gastric cancer, this case is very rare because it showed submucosal invasion and lymph node metastasis.

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.

Indocyanine green fluorescence angiography-guided simultaneous laparoscopic distal gastrectomy and spleen-preserving distal pancreatectomy for conserving the gastrosplenic ligament: A case report.

INTRODUCTION AND IMPORTANCE: Indocyanine green (ICG) fluorescence angiography is being increasingly performed intraoperatively to detect restricted blood flow intraoperatively for the prevention of postoperative organ ischemia and anastomotic leakage. This is the first case report of simultaneous laparoscopic distal gastrectomy (LDG) and spleen-preserving distal pancreatectomy (LSPDP) involving ICG angiography use to avoid the remnant stomach ischemia. CASE PRESENTATION: A 55-year-old man was diagnosed with early cancer of the stomach body and intraductal papillary mucinous neoplasms of the pancreatic tail. We performed simultaneous LDG with D2 dissection and LSPDP to conserve the gastrosplenic ligament and preserve blood supply to the remnant stomach. Intraoperatively, blood flow to the remnant stomach was visualized using ICG fluorescence angiography, after which Roux-en-Y reconstruction was performed. There was no perioperative remnant stomach ischemia. CLINICAL DISCUSSION: Despite the preserved splenic artery and vein, complete splenic infarction occurs after LSPDP possibly due to thrombus formation during surgical procedures. In this patient, we conserved the gastrosplenic ligament for the short gastric artery, which supplied blood to the remnant stomach; however, remnant stomach ischemia may occur. Therefore, we performed ICG fluorescence angiography during this operation to ensure that sufficient blood supply to the remnant stomach was maintained. CONCLUSION: Our experience demonstrates that ICG angiography may be useful for the prevention of remnant stomach ischemia.

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.

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.

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.

Reducing the risk of postoperative pancreatic fistula in radical gastrectomy: pre-assessment with computed tomography for the diagnosis of pancreatic steatosis.

PURPOSE: To determine whether pancreatic steatosis (PS) is associated with the risk of postoperative pancreatic fistula (POPF) after radical gastrectomy, and if so, to investigate whether pre-assessment by diagnostic imaging can mitigate the risk. METHODS: The clinical records of 276 patients with cStage I gastric cancer who underwent laparoscopic gastrectomy with D1 + lymphadenectomy between 2012 and 2015 were reviewed. In the first phase up to July 2013 (n = 138), PS was classified from computed tomography (CT) findings into type S (superficial fat deposition) or type D (diffuse fatty replacement) and examined for association with POPF. In the second phase (n = 138), the preoperative CT assessment of PS was routinized. Separate samples from pancreatoduodenectomy consistent with each type were histologically examined. RESULTS: In the first phase, the incidence of POPF was significantly higher in group S, but not in group D, compared with normal pancreas (16.3% and 9.1% vs. 3.6%, respectively; P = 0.03). The drain amylase level was lowest in group D, reflecting exocrine insufficiency. Histologically, the loose connective-tissue space between the fat infiltrating the pancreas and the peripancreatic fat containing the lymph nodes was unclear in type D but conserved in type S. In the second phase, surgery was performed with more intention on accurately tracing the dissection plane and significantly lowered incidence of POPF in Group S (16.3% to 2.1%; P = 0.047). CONCLUSION: Peripancreatic lymphadenectomy is more challenging and likely to cause POPF in patients with PS. However, the risk may be reduced using appropriate dissection techniques based on the CT pre-assessment findings.

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.