Prognosis after curative resection for stage IA gastric cancer in elderly patients: endoscopic submucosal dissection versus surgery.

PURPOSE: To establish whether gastrectomy for early gastric cancer (EGC) in elderly patients is related to poor survival. METHODS: The subjects of this retrospective study were patients aged ≥ 75 years with primary stage IA EGC, who underwent curative resection with endoscopic submucosal dissection (ESD) or surgery. RESULTS: We analyzed data on 365 patients who underwent ESD and 170 patients who underwent surgery. Overall survival (OS) was not significantly different for the ESD group vs. the surgery group (5-year cumulative rates, 81.5% vs. 79.7%; log-rank test, P = 0.506). Multivariate analysis revealed that treatments; namely, ESD or surgery, were not associated with OS (hazard ratio 1.09, 95% confidence interval 0.77-1.51). Similar results were observed even in the subgroups with worse conditions, such as age > 80 years, Eastern Cooperative Oncology Group performance status 2-3, Charlson comorbidity index ≥ 2, and prognostic nutritional index ≤ 46.7. Using propensity score matching, we selected 88 pairs of patients who underwent ESD or surgery with baseline characteristics matched and found that OS was not different between the two groups (log-rank test, P = 0.829). CONCLUSION: OS was comparable for elderly patients who underwent ESD and those who underwent surgery for EGC. Surgical invasiveness did not worsen the prognosis, even for elderly patients.

[Traumatic Neuroma Mimicking Lymph Node Metastasis of Pancreatic Neuroendocrine Neoplasms Developed after Pancreatoduodenectomy-A Case Report].

A traumatic neuroma is a benign tumor consisting of a non-neoplastic growth of injured nerves as a result of trauma or surgery. It is rarely found in an abdominal cavity, but some reports showed that it occurred around the bile duct. We report a case of a 72-year-old man who underwent subtotal stomach-preserving pancreatoduodenectomy for pancreatic neuroendocrine neoplasms 4 years ago. An abdominal contrast-enhanced CT follow-up examination revealed a growing nodule on the dorsal surface of the portal vein. The lesion showed a mild increase in fluorodeoxyglucose uptake in FDG-PET⊘CT. A lymph node metastasis of pancreatic neuroendocrine neoplasms was suspected. Nodule resection was performed for purpose of diagnosis and treatment. The final pathological diagnosis was traumatic neuroma with no evidence of recurrence. Traumatic neuromas developed after pancreatoduodenectomy have not been reported. Postoperative masses around the bile ducts should also be considered traumatic neuromas.

Cutaneous metastasis of cecum cancer with MSI-high and BRAFV600E mutation: a case report.

BACKGROUND: Cutaneous metastases of colorectal cancer (CRC) are rare, occurring in 0.7% to 5% of cancer patients. Furthermore, the molecular subtypes of cutaneous metastasis of CRC are unclear. Here, we present a rare case of cutaneous metastasis of high-frequency microsatellite instability (MSI-high)/BRAFV600E-mutant cecum cancer. CASE PRESENTATION: A 77-year-old woman presented at the outpatient clinic with a subcutaneous mass on her left back. An excisional biopsy was performed and metastatic cutaneous adenocarcinoma was diagnosed. A computed tomography scan of the thorax and abdomen showed thickening of the cecum wall, the presence of pericolic lymph nodes, multiple masses in the liver, and a single nodule in the right lung. Right colectomy with D2 lymphadenectomy and functional end-to-end anastomosis was performed because of the almost-complete intestinal obstruction. The expression of KRAS wild type, BRAFV600E mutation, and MSI-high was detected in the cecum cancer using molecular pathological examination. She received chemotherapy with XELOX + BEV regimen (capecitabine + oxaliplatin + bevacizumab). After four administrations, a computed tomography scan showed reduction of distant metastases, which suggested partial response. CONCLUSIONS: We encountered a rare case of cutaneous metastasis of MSI-high and BRAFV600E-mutant cecum cancer. In the future, it will be necessary to accumulate more cases to identify clinical features and more effective treatments for CRCs with cutaneous metastasis.

Simultaneous laparoscopic hiatal hernia repair and pyloroplasty for a type 3 hiatal hernia with post-ESD pyloric stenosis for early gastric cancer.

We present a case of early gastric cancer in the pylorus with a type 3 hiatal hernia, which was treated by endoscopic submucosal dissection (ESD). A 70-year-old man was referred to our hospital with a hiatal hernia. Endoscopy revealed early gastric cancer, and we performed an ESD adaptation at the pylorus. The ESD was successful, but post-ESD pyloric stenosis occurred. Symptoms of hiatal hernia worsened because of the pyloric stenosis. Laparoscopic hiatal hernia repair with Toupet fundoplication and Heineke-Mikulicz pyloroplasty was simultaneously performed. The postoperative course was good, and follow-up after discharge was uneventful. To our knowledge, there have been no reports in which laparoscopic hiatal hernia repair, fundoplication, and pyloroplasty were simultaneously performed for a substantial hiatal hernia with post-ESD pyloric stenosis.

Acute cholecystitis caused by gallbladder metastasis from non-small cell lung cancer: a case report.

Although non-small cell lung cancer can metastasize to any part of the body, metastasis to the gallbladder is extremely rare. We present a case of acute cholecystitis caused by gallbladder metastasis from non-small cell lung cancer. A 66-year-old man diagnosed with primary stage IV T4N3M1b non-small cell lung cancer was admitted to our hospital to receive chemotherapy, during which he presented with right upper abdominal pain. Abdominal contrast-enhanced computed tomography showed an enhanced mass at the neck of the gallbladder and gallbladder distension with obvious wall thickening. Acute cholecystitis caused by obstruction of the gallbladder neck by malignancy was suspected. Open cholecystectomy, extrahepatic bile duct resection, and Roux-en-Y choledochojejunostomy were performed. Pathological and immunohistochemical examinations revealed gallbladder metastasis originating from non-small cell lung cancer. In conclusion, when a patient with lung cancer presents with acute cholecystitis, the rare possibility of gallbladder metastasis should be considered.

[Two Cases of Stevens-Johnson Syndrome after Nivolumab Therapy for Gastric Cancer].

Case 1: A 51-year-old man with advanced gastric cancer and peritoneal metastasis was referred to our hospital. He received fourth-line chemotherapy with nivolumab, but it became PD. Next, he received S-1 plus docetaxel therapy as fifth- line therapy. After 2 courses of S-1 plus docetaxel, erythema and blisters appeared on his limbs, with erosions of the oral mucosa and penis. We diagnosed Stevens-Johnson syndrome(SJS)based on the clinical and pathological findings. He received steroid treatment, but the cutaneous symptoms persisted; therefore, it was impossible to continue the chemotherapy because of the SJS. Case 2: A 75-year-old woman with recurrence of peritoneally disseminated gastric cancer received third-line chemotherapy with nivolumab. After 1 course of nivolumab, erythema appeared on her body and limbs, with erosion of the lips and oral mucosa. We diagnosed SJS based on the clinical findings. She received steroid treatment, but the cutaneous symptoms persisted; therefore, it was impossible to continue chemotherapy because of the SJS. It should be noted that the onset of serious irAEs, such as SJS, might make continuous chemotherapy difficult.

Association Between Immune-Related Adverse Events and the Prognosis of Patients with Advanced Gastric Cancer Treated with Nivolumab.

BACKGROUND: Little is known about the association between immune-related adverse events (irAEs) and the efficacy and survival outcomes of nivolumab in patients with advanced gastric cancer (AGC). OBJECTIVE: The present study examined the association between irAEs and the prognosis of patients with AGC treated with nivolumab. PATIENTS AND METHODS: From July 2017 to November 2020, patients who had been diagnosed with advanced unresected gastric cancer and treated with nivolumab at our institution were included in this analysis. We compared the clinical and survival outcomes between the irAE and non-irAE groups. We also evaluated the factors associated with better survival in patients treated with nivolumab. RESULTS: A total of 52 patients were included in the present study, and irAEs were observed in 13 (25%). Among the patients with measurable lesions (n = 29), the disease control rates were significantly higher in the irAE group than in the non-irAE group (88 vs. 24%; P = 0.0033). At the 8- and 12-week landmark analyses, the median overall survival (OS) in the irAE group was significantly longer than that in the non-irAE group, whereas the median progression-free survival was comparable between the groups. A multivariate analysis by Cox proportional hazard regression at the 8-week landmark revealed that the development of irAEs (hazard ratio 0.18; 95% confidence interval 0.0099-0.86) alone was positively associated with a longer OS. CONCLUSIONS: The development of irAEs might be associated with survival outcomes with nivolumab treatment in patients with AGC.

Indocyanine green fluorescence imaging for subtotal esophagectomy due to esophageal stenosis after acute esophageal necrosis: a report of two cases.

Although esophageal stricture after acute esophageal necrosis (AEN) is often refractory to dilation therapy, there have been few reports of surgical intervention. We report two rare cases of successful subtotal esophagectomy and esophagogastrostomy for esophageal strictures after AEN using indocyanine green (ICG) fluorescence imaging. In case 1, emergent esophagogastroduodenoscopy (EGD) in a 56-year-old man with coffee-ground emesis revealed black esophageal mucosa in the middle to lower esophagus, indicating AEN. Despite conservative therapy, an esophageal stricture developed after 2 weeks. Repeated endoscopic balloon dilation (EBD) did not resolve the stenosis; esophagectomy was thus performed approximately 6 months after AEN onset. We evaluated the blood flow to the esophagus using ICG fluorescence imaging to determine the proximal surgical resection line. The postoperative course was uneventful. In case 2, an 81-year-old woman with upper gastrointestinal bleeding with hematemesis and chest pain was diagnosed with AEN by EGD and was treated with conservative therapy. An esophageal stricture developed after 3 weeks, and repeated EBD was ineffective. Approximately 2 months after AEN onset, she underwent esophagectomy using ICG fluorescence imaging. The postoperative course was uneventful. Considering that AEN is a blood flow disorder, ICG fluorescence imaging is a useful technology to prevent surgical morbidity.

[Laparoscopic Left Hemicolectomy-It Is Confirmed That the Accessory Middle Colonic Artery Branched from the Splenic Artery Showed by Preoperative 3D-CT].

There is a wide variety of vessel types in the transverse colon region. Among them, it is very rare that the accessory middle colonic artery(A-MCA)is branched from the splenic artery. We found a transverse colon cancer. The dominant vessel of the cancer was the A-MCA branched from the splenic artery. This vessel type was confirmed by preoperative 3D-CT. We performed a laparoscopic left hemicolectomy for the cancer. In this study, we report a case of safe laparoscopic surgery in which we separate the A-MCA branched from the splenic artery using the preoperative 3D-CT image.

A rare maternal gastrointestinal stromal tumor found in the second trimester of pregnancy: A case report.

Gastrointestinal stromal tumors are rare, and in pregnancy they are extremely rare. We present a case of a maternal gastrointestinal stromal tumor found in the second trimester of pregnancy. A 29-year-old woman, gravida 1 para 0, complained of bloody vomiting at 14 weeks of gestation. She had no significant medical history. We performed plain computed tomography and upper gastrointestinal endoscopy. Precise examination revealed a large mass in the stomach and an exposed blood vessel on the surface. An exposed blood vessel can be harmful for mother and fetus as it might rupture during the pregnancy. We performed a distal gastrectomy at 16 weeks of gestation. Histology confirmed a localized gastrointestinal stromal tumor with a high risk of recurrence, and adjuvant imatinib was recommended. The patient elected to delay adjuvant imatinib until after delivery. The postoperative and antenatal course was favorable, and the patient was followed up by ultrasound every 2 months after the operation. After she gave birth at 40 weeks of gestation, she started adjuvant imatinib 400 mg/day. There was no evidence of recurrence 1 year after surgery. There are no guidelines for the management of gastrointestinal stromal tumors in pregnancy. Given the treatment challenges, we believe that pregnant patients should be managed by a multidisciplinary team with expertise in gastrointestinal tumors and fetal-maternal medicine.

A rare case of enlarged gastric heterotopic pancreas with retention cysts: A case report and literature review.

INTRODUCTION: Gastric heterotopic pancreas (HP) is usually asymptomatic and benign; however, it may become evident when it is complicated by pathological changes such as inflammation, bleeding, and malignant transformation. PRESENTATION OF CASE: A 43-year old man was diagnosed with gastric HP 18 years prior suffered a haemorrhage from the enlarged gastric HP with multiple cystic lesions. Although endoscopic ultrasonography-guided fine needle aspiration showed no malignancy, he underwent a partial gastrectomy for diagnosis and treatment. Postoperative histological findings revealed ectopic pancreatic tissue with retained cysts that consisted of dilated pancreatic ducts without malignancy. DISCUSSION: This is a first report of enlarged gastric HP due to the expansion of retained cysts. Gastric HP is rarely enlarged by pathological changes including inflammation, retention cysts, or malignant neoplasms. CONCLUSION: Symptomatic enlarged gastric HP should be respected and further examined histologically to ensure diagnostic accuracy.

Successful Use of Negative Pressure Wound Therapy for Abdominal Wall Necrosis Caused by a Perforated Ascending Colon Using the ABThera System.

BACKGROUND: The practice of leaving the abdomen open after an emergency laparotomy has gained increasing popularity recently. Negative pressure wound therapy (NPWT) is known as an effective technique in the management of an open abdomen (OA). A new device, the ABThera™ Open Abdomen Negative Pressure Therapy System (KCI USA, San Antonio, TX, USA), was specifically designed to achieve a temporary abdominal closure (TAC) in the management of an OA. This study was aimed at presenting a successful experience of treating a case of abdominal wall necrosis caused by a perforated ascending colon using the ABThera System. Case Presentation. A 66-year-old man was admitted to our hospital with complaints of severe pain in the abdomen. On admission, abdominal contrast-enhanced computed tomography (CT) showed fluid collection, an air pocket in the subcutaneous fat layer of the abdominal wall, and edematous changes in the adipose tissue in the peritoneum and abdominal wall. Based on a diagnosis of peritonitis resulting from a perforated ascending colon, emergency surgery was performed. A right hemicolectomy, ileostomy construction, and debridement of the necrotic tissues were performed. However, necrotizing fasciitis rapidly spread; therefore, more necrotic tissue was debrided in a second operation. The abdominal wall defect was left open, and the ABThera System was used in the management of the OA; this device promoted wound healing. A reduction was observed in the size of the open wound with visible granulation tissue. The defect was finally covered with a mesh split-thickness skin graft and anterolateral thigh flap. CONCLUSIONS: In the management of a case of a massive wound with infection, it can be of great benefit to treat the wound with NPWT initially to decrease its size. The ABThera System could facilitate early and safe management of an OA by surgeons.

[Simultaneous Distal Gastrectomy, Distal Pancreatectomy, and Splenectomy Based on Remnant Gastric Blood-Flow Evaluation with Intraoperative ICG Fluorescence].

The splenic artery and vein are important to the remnant stomach after distal gastrectomy(DG). Hence, total gastrectomy is recommended when performing gastrectomy and distal pancreatectomy(DP)with splenectomy(S). In the present case, a man in his 70s was diagnosed with early gastric cancer. Abdominal CT detected a dilated main pancreatic duct. Chronic pancreatitis was suspected, but malignancy could not be completely ruled out. Thus, DG with Roux-en-Y reconstruction and DP with S were performed simultaneously. The remnant gastric blood flow was evaluated with intraoperative indocyanine green(ICG)fluorography and the blood flow was confirmed. Finally, the remnant stomach was preserved. The postoperative course was uneventful, except for the occurrence of anastomosis edema. This result suggests that ICG fluorescence is useful to evaluate remnant gastric blood flow and that it may be possible to perform DG and DP with S simultaneously depending on the case.

Immune Modulation by Telomerase-Specific Oncolytic Adenovirus Synergistically Enhances Antitumor Efficacy with Anti-PD1 Antibody.

The clinical benefit of monotherapy involving immune checkpoint inhibitors (ICIs) such as anti-programmed death-1 antibody (PD-1 Ab) is limited to small populations. We previously developed a telomerase-specific oncolytic adenovirus, Telomelysin (OBP-301), the safety of which was confirmed in a phase I clinical study. Here, we examined the potential of OBP-502, an OBP-301 variant, as an agent for inducing immunogenic cell death (ICD) and synergistically enhancing the efficacy of OBP-502 with PD-1 Ab using CT26 murine colon cancer and PAN02 murine pancreatic cancer cell lines. OBP-502 induced the release of ICD molecules such as adenosine triphosphate (ATP) and high-mobility group box protein 1 (HMGB1) from CT26 and PAN02 cells, leading to recruitment of CD8-positive lymphocytes and inhibition of Foxp3-positive lymphocyte infiltration into tumors. Combination therapy involving OBP-502 intratumoral administration and PD-1 Ab systemic administration significantly suppressed the growth of not only OBP-502-treated tumors but also tumors not treated with OBP-502 (so-called abscopal effect) in CT26 and PAN02 bilateral subcutaneous tumor models, in which active recruitment of CD8-positve lymphocytes was observed even in tumors not treated with OBP-502. This combined efficacy was similar to that observed in a CT26 rectal orthotopic tumor model involving liver metastases. In conclusion, telomerase-specific oncolytic adenoviruses are promising candidates for combined therapies with ICIs.

[Effect on Prognosis of Immune-Related Adverse Events after Nivolumab Treatment in Gastric Cancer].

BACKGROUND: The clinical efficacy of nivolumab has been shown as a third-line treatment for advanced gastric cancer; however, nivolumab sometimes causes immune-related adverse events(irAEs). We retrospectively examined the clinical features and influence on treatment in cases of irAEs after nivolumab treatment. METHOD: We retrospectively examined 43 patients who received nivolumab treatment at our institution between October 2017 and December 2019. RESULT: The incidence of irAEs was 23.2%(10/43), and Grade 3 or higher irAEs included interstitial pneumonia, hypoadrenalism, Stevens- Johnson syndrome(SJS), and type 1 diabetes. Three patients showed long-term disease control after irAE onset. Meanwhile, SJS prevented patients from continuing treatment for gastric cancer. DISCUSSION: Nivolumab is effective in some patients with gastric cancer, while irAEs made subsequent treatment difficult. Trifluridine/tipiracil or irinotecan are also known to be effective as therapeutic drugs after third-line treatment for gastric cancer in addition to nivolumab; therefore, the choice of the third-line drug and management of irAEs owing to individual cases are considered desirable. CONCLUSION: Long-term efficacy is expected with nivolumab, but it may be necessary to recognize that the onset of serious irAEs might make subsequent treatment difficult.

[Total Pelvic Exenteration and Perineal Reconstruction with a Gracilis Myocutaneous Flap for Local Recurrence of Rectal Cancer].

The case involved a female in her 70s. Six years prior, she had undergone an abdominoperineal rectal resection for rectal cancer. Local recurrence was observed during follow-up so preoperative chemoradiotherapy was performed to shrink the tumor, followed by a total pelvic exenteration, bilateral ureterocutaneous fistula, and perineal reconstruction with a gracilis myocutaneous flap. She was discharged from hospital 39 days following surgery with no major complications. We herein report on a case of a good postoperative course due to surgery including a total pelvic exenteration and perineal reconstruction with a gracilis myocutaneous flap for postoperative local recurrence.

Polyarteritis Nodosa with Marked Eosinophilia, Associated with Severe Gastrointestinal Tract Involvement and Recurrent Venous Thrombosis.

A 45-year-old man was admitted with acute abdominal pain and eosinophilia. Abdominal computed tomography revealed thickness of the ascending and transverse colon with decreased contrast enhancement and a small amount of ascites. In an emergency operation, the necrotic colon was resected. Histopathology showed subserous medium-sized arteritis with abundant eosinophil infiltrates and thrombosis in the portal vein branches. He was diagnosed with polyarteritis nodosa (PAN), and immunosuppressive therapy improved his condition. Two years later, the disease recurred with ischemic cutaneous lesions and marked eosinophilia. Our experience suggests that marked eosinophilia in PAN may imply severe organ involvement, including gastrointestinal necrosis, as well as the association of venous thrombosis.

PD-L1 expression combined with microsatellite instability/CD8+ tumor infiltrating lymphocytes as a useful prognostic biomarker in gastric cancer.

While the importance of programmed death-ligand 1 (PD-L1), mutation burden caused by microsatellite instability (MSI), and CD8+ tumor infiltrating lymphocytes (TILs) has become evident, the significance of PD-L1 expression on prognosis still remains controversial. We evaluated the usefulness of combined markers of PD-L1 and MSI or CD8+ TILs as a prognostic biomarker in gastric cancer. A total of 283 patients with gastric cancer were reviewed retrospectively. PD-L1 expression on >5% tumor cells was defined as PD-L1-positive. PD-L1-positive rate was 15.5% (44/283). PD-L1 positivity was significantly correlated with invasive and advanced cancer and also significantly correlated with MSI, whereas no significance was observed with CD8+ TILs. Kaplan-Meier analysis showed that PD-L1 positivity significantly correlated with a poor prognosis (p = 0.0025). Multivariate analysis revealed that PD-L1 positivity was an independent poor prognostic factor (hazard ratio [HR]: 1.97, p = 0.0106) along with diffuse histological type and lymph node metastases. Combinations of PD-L1 and MSI (HR: 2.18) or CD8+ TILs (HR: 2.57) were stronger predictive factors for prognosis than PD-L1 alone. In conclusion, combined markers of PD-L1 and MSI or CD8+ TILs may be more useful prognostic biomarkers in gastric cancer, and better clarify the immune status of gastric cancer patients.

Advanced gastric cancer with features of a submucosal tumor diagnosed by endoscopic ultrasound-guided fine needle aspiration and boring biopsy preoperatively: A case report and literature review.

INTRODUCTION: Gastric cancer with features of a submucosal tumor (GCSMT) is rare, and the preoperative diagnosis is very difficult. We present a case of GCSMT diagnosed by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) and boring biopsy (deeper biopsy), successfully treated with distal gastrectomy and lymph node dissection. PRESENTATION OF CASE: An 81-year-old man with a history of myocardial infarction and type 2 diabetes mellitus was admitted to our hospital for further examination of a gastric submucosal tumor. Endoscopic examination of the gastrointestinal tract showed a 30-mm submucosal tumor at the lower gastric body. Enhanced computed tomography revealed a tumor located at the lower body of the stomach and pyloric lymph node swelling. EUS-FNA and boring biopsy from the tumor revealed adenocarcinoma. Accordingly, distal gastrectomy with lymph node dissection was performed. Histopathological examination showed a poorly differentiated adenocarcinoma. Postoperative diagnosis was GCSMT with lymph node metastasis (T2, N1, M0, stage IIA). CONCLUSION: We report a rare case of GCSMT with lymph node metastasis. Preoperative diagnosis of GCSMT is necessary to guide surgical management. EUS-FNA and boring biopsy could aid in obtaining adequate quantities of the specimens for histopathological and immunohistochemical diagnosis.

Endoscopic Ultrasound-Guided Transgastric Drainage of an IntraAbdominal Abscess following Gastrectomy.

Endoscopic ultrasound (EUS)-guided transgastric drainage has been performed as a less invasive procedure for pancreatic fistulas and intra-abdominal abscesses occurring after surgery in recent years. However, there are no reports of EUS-guided transgastric drainage of intra-abdominal abscesses following gastrectomy. This case report describes 2 patients who developed an intra-abdominal abscess following gastrectomy and underwent EUS-guided transgastric drainage. Both patients underwent laparoscopy-assisted distal gastrectomy with Billroth-I reconstruction for gastric cancer. The intra-abdominal abscesses were caused by postoperative pancreatic fistula that developed following gastrectomy. One patient underwent naso-cystic drainage and the other underwent only a needle puncture of the abscess cavity. EUS-guided drainage was performed safely and effectively, although 1 patient developed gastroduodenal anastomotic leakage related to this procedure. In summary, EUS-guided transgastric drainage is safe and technically feasible even in post-gastrectomy patients. However, it is necessary to be careful if this procedure is performed in the early period following gastrectomy.