Efficacy and Safety of the Combination of Nano-Liposomal Irinotecan and 5-Fluorouracil/L-Leucovorin in Unresectable Advanced Pancreatic Cancer: A Real-World Study.

INTRODUCTION: This retrospective study investigated the efficacy and safety of nano-liposomal irinotecan (nal-IRI) plus 5-fluorouracil/L-leucovorin (5-FU/l-LV) treatment in the second-line or later setting for advanced pancreatic cancer under real-world conditions. METHODS: Between June 2020 and September 2021, a total of 44 patients with unresectable advanced pancreatic cancer treated with nal-IRI + 5-FU/l-LV in our affiliated hospitals were included. The prognosis, predictive factors (including systemic inflammation-based prognostic indicators), and adverse events were investigated. RESULTS: The median age was 68 (interquartile range 62-73) years old, and 22 patients (50.0%) were male. Concerning tumor factors, 9 patients (20.5%) had local advanced disease and 35 patients (79.5%) had metastases. Twenty-five of the 44 patients were receiving second-line treatment, and 19 were receiving third-line or later treatment. The median overall survival (OS) and progression-free survival were 9.0 (range, 0.7-15.4) months and 4.4 (range, 0.6-15.4) months, respectively. The overall response rate was 5.3%. The disease control rate was 44.7%. Patients with a neutrophil-to-lymphocyte ratio of ≥2.7 had a significant risk of a poor OS (HR = 0.275, p = 0.017). Adverse events were manageable, although gastrointestinal symptoms and neutropenia were observed. The most common grade ≥3 adverse event was neutropenia, which was reported in 20% of patients. CONCLUSIONS: Nal-IRI + 5-FU/l-LV therapy was considered to be a useful regimen as second-line or later treatment for unresectable advanced pancreatic cancer, even in clinical practice.

[A Case of Hepatocellular Carcinoma Complicated by Liver Metastasis of Colon Cancer during the Course of Treatment].

A 72‒year‒old man with hepatocellular carcinoma(HCC)was treated with transarterial chemoembolization(TACE)and radiofrequency ablation(RFA). Six months after RFA, gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid(Gd‒ EOB‒DTPA)‒enhanced magnetic resonance imaging(MRI)revealed multiple metastatic recurrences in the liver. TACE was performed for the recurrent HCC. However, the treatment response on the Gd‒EOB‒DTPA‒enhanced MRI showed that the lesions had advanced and that the liver metastatic nodules had ring‒shaped contrast effects. We suspected metastatic liver cancer based on the MRI findings and performed colonoscopy. Finally, we diagnosed the patient with multiple hepatic metastases of sigmoid colon cancer based on the results of the endoscopic colon biopsy and percutaneous liver tumor biopsy. In conclusion, we had a teachable case of the treatment of HCC.

A prospective randomized controlled study of endoscopic sphincterotomy with the Endocut mode or conventional blended cut mode.

BACKGROUND: Although the potential advantages of the Endocut mode (E-mode) of endoscopic sphincterotomy (EST) over the conventional blended cut mode (C-mode) have been reported, the problems, including the small sample size and retrospective analysis, that occurred in previous studies make it difficult to conclude the advantage of the E-mode regarding the safety and efficacy. We performed a prospective randomized controlled study to compare these modes. METHODS: A total of 360 patients with choledocholithiasis or stenosis of the bile duct were randomly assigned to one of the modes. To avoid the technical bias due to multiple operators or institutions, the main operator and the institution were restricted to only one experienced doctor and 3 institutions at his place of employment, respectively. We defined pancreatitis, bleeding, and perforation as complications of EST. Besides, bleeding includes endoscopically evident bleeding that was defined as visible during the procedure of sphincterotomy and temporary slight oozing. RESULTS: The complications occurred in 20 (11.2%) patients from the E-mode group: pancreatitis in 6 (3.4%) and endoscopically evident bleeding in 14 (7.8%). In contrast, the complications occurred in 25 (13.8%) patients from the C-mode group: pancreatitis in 7 (3.9%) and endoscopically evident bleeding in 18 (9.9%), although these findings were not statistically significant. Overall, there were no severe complications. There were no significant differences in completion ratio of EST and the time taken for the sphincterotomy between both groups. CONCLUSIONS: The E-mode could not surpass the C-mode in safety and efficacy under the operation by a single endoscopist.

[A case of gastric mucosal laceration due to seat belt injury].

A 69-year-old man was involved in a road traffic accident wherein his car hit a telegraph pole and turned over. He reported wearing a seatbelt and denied any injuries or pain at that time. Six hours after the accident, however, he developed melena and hematemesis. Computed tomography performed on admission to our hospital revealed no evidence of traumatic pneumothorax, intra-abdominal bleeding, or pneumoperitoneum. However, there was evidence of contrast medium leakage from the stomach. Emergency endoscopy revealed a mucosal laceration on the lesser curvature in the cardiac region, with evidence of arterial hemorrhage from visible vessels. Hemostasis was achieved endoscopically by injection of hypertonic saline-epinephrine and clipping. Endoscopic treatment of gastric injury following blunt abdominal trauma is rare. Here we report a case and present a review of the relevant literature.

An autopsy case of alpha-fetoprotein-producing large duodenal adenocarcinoma.

We report an autopsy case of a large duodenal adenocarcinoma that produced alpha-fetoprotein (AFP). The patient was a man in his 70s with diabetes mellitus. He presented with epigastralgia and was referred to our hospital. Upper gastrointestinal endoscopy and abdominal computed tomography revealed a large tumor of 11 cm in diameter in the descending limb of the duodenum. A tumor biopsy showed poorly differentiated adenocarcinoma. Although his carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels were within the normal range, his AFP levels were significantly elevated (42,078.4 ng/mL). Due to vascular invasion, curative resection was not feasible, and chemotherapy was chosen as the treatment option. After gastrojejunostomy was performed to enable oral intake, one cycle of modified leucovorin/5-fluorouracil/oxaliplatin (mFOLFOX6) therapy was administered. However, it proved ineffective, and the patient's anorexia gradually worsened. Ultimately, he succumbed to the progression of cancer cachexia. Autopsy findings revealed a 14-cm-long duodenal carcinoma primarily located in the duodenal bulb, with direct invasion into the stomach, pancreas, and liver. A pathological examination confirmed a diagnosis of poorly differentiated adenocarcinoma with AFP production. Duodenal cancer is rare, and AFP-producing duodenal cancer is even rarer, with only 21 reported cases, including our own. We present this autopsy case of AFP-producing duodenal adenocarcinoma and review the cases reported in the relevant literature.

Successful Treatment of Metastatic Gallbladder Carcinoma with a High Tumor Mutational Burden Using Pembrolizumab.

A woman in her 70s presented with gallbladder carcinoma with liver metastases and peritoneal dissemination. After standard chemotherapy failed, a liver biopsy was performed. A FoundationOne CDx analysis showed that the tumor mutational burden (TMB) was high (34 mutations/megabase). Treatment with pembrolizumab, which is an immune checkpoint inhibitor (ICI), resulted in a partial response, and there were no significant immune-related adverse events. According to recently published reports, the frequency of TMB-high biliary tract cancer (BTC) is 3.4-4%, which makes it extremely rare. In conclusion, ICIs may be effective in patients with TMB-high BTC.

[Recurrent gastric volvulus resolved surgically after therapeutic percutaneous endoscopic gastrostomy in Duchenne muscular dystrophy].

A 20-year-old man with Duchenne muscular dystrophy (DMD) with recurrent gastric volvulus underwent percutaneous endoscopic gastrostomy (PEG). Four months later, he developed vomiting and consciousness disturbance. CT revealed gastric volvulus recurrence along the gastrostomy axis. Endoscopic repositioning failed and fistula perforation necessitated emergency surgery. The upper position of the stomach was twisted counter-clockwise and revolved on the gastrostomy axis sliding between the lower stomach and abdominal wall. The fistula showed necrotic perforation and was thus resected. The anterior stomach wall was fixed to the abdominal wall at 3 triangular points. Thereafter, gastric volvulus did not recur. PEG is reportedly effective for preventing gastric volvulus, but there are rare cases of postgastrostomy recurrence. This successfully managed case provides valuable clinical insights.

Two cases of rapid progression of esophageal varices after atezolizumab-bevacizumab treatment for hepatocellular carcinoma.

We report two cases of rapid progression of esophageal varices after atezolizumab-bevacizumab treatment for hepatocellular carcinoma (HCC). Case 1: a man in his 60s with hepatitis C-related liver cirrhosis after viral eradication by direct acting antiviral. He was diagnosed with HCC 8 years previously. He had undergone surgical resection 4 times, radio-frequency ablation (RFA) several times, and transcatheter arterial chemoembolization (TACE). However, HCC progressed and could not be controlled by locoregional treatment. Systemic chemotherapy was, therefore, selected. Atezolizumab-bevacizumab was administered after lenvatinib and sorafenib failure. Before starting treatment, his liver function was preserved (Child-Pugh score 5 and class A). His alpha fetoprotein and des-gamma-carboxyprothrombin levels were 3.6 ng/mL and 443 mAU/mL, respectively. Esophagogastroduodenoscopy showed no remarkable esophageal varices before atezolizumab-bevacizumab treatment. Nine months after the initiation of atezolizumab-bevacizumab, the patient was admitted for hematemesis from esophageal varices. The disease control of HCC was classified as stable disease (SD) for the liver and lung metastases, and partial response for the lymph node metastases. Neither AST nor ALT was markedly elevated in the clinical course. Endoscopic variceal ligation (EVL) for the spurting point of large esophageal varices with red wale signs was able to successfully achieve hemostasis. Atezolizumab-bevacizumab was stopped and additional EVL eradicated the esophageal varices. However, the post-banding ulcer was prolonged in comparison to usual cases. Case 2: a man in his 60s with hepatitis C-related liver cirrhosis after viral eradication by direct acting antiviral therapy. He was diagnosed with HCC 6 years previously. He had received RFA 2 times and TACE 7 times. Atezolizumab-bevacizumab was administered after lenvatinib failure. The disease control of HCC was classified as SD; however, the esophageal varices ruptured after 15 courses of atezolizumab-bevacizumab. Neither AST nor ALT were markedly elevated in the clinical course. The esophageal varices of these patients did not require treatment before atezolizumab-bevacizumab; however, they rapidly worsened and ruptured during atezolizumab-bevacizumab treatment. Although rare, similar cases with rapid progression of portal hypertension after atezolizumab-bevacizumab have been reported. We should pay attention to the worsening of esophageal varices during atezolizumab-bevacizumab treatment and poor wound healing after EVL.

A case of conversion hepatectomy for huge ruptured hepatocellular carcinoma after transarterial embolization and lenvatinib therapy.

We herein report a successfully treated case of huge ruptured hepatocellular carcinoma (HCC) by conversion hepatectomy after transarterial embolization (TAE) and lenvatinib therapy. A 33-year-old male patient with right hypochondralgia and liver tumor was referred to our hospital. He had a history of surgery for heart malformation. The tumor at the right lobe was 15 cm in diameter with bloody ascites. Right atrial thrombus 4.5 cm in diameter and marked cardiac dilatation were observed. TAE with ethanol suspended in lipiodol and gelatin sponge achieved hemostasis of the ruptured HCC. Although viable HCC remained after TAE, surgical treatment was abandoned because of abdominal wall invasion and his heart function. Lenvatinib and rivaroxaban were then initiated for HCC and atrial thrombus, respectively. Lenvatinib treatment resulted in a reduction in tumor marker levels and the tumor size. First, we planned conversion hepatectomy after 5 months of lenvatinib. However, recurrence of atrial thrombus prompted us to put off the surgery, and lenvatinib was re-administered. After improvement of atrial thrombus, we finally performed conversion hepatectomy 10 months after starting lenvatinib administration. The tumor was completely removed by combined resection of the diaphragm, and the patient has been doing well without any signs of recurrence.

Imatinib and nutritional support can make successful treatment for a case of huge liver metastasis of duodenal gastrointestinal stromal tumor that initially showed jaundice and cachexia.

It is very difficult to treat patients with liver metastasis presenting with jaundice or cachexia. We herein report a successfully treated case of huge liver metastasis of gastrointestinal stromal tumor (GIST) that initially showed jaundice and cachexia. The patient was a woman in her early 40 s. She had a history of duodenal GIST 4 years before this admission. She was admitted to our hospital for abdominal fullness and anorexia. Abdominal computed tomography revealed huge liver metastasis of GIST. She showed jaundice and cancer cachexia with a modified Glasgow Prognostic Score of 2. After applying nutritional support, 400 mg of imatinib was administered. Although leg edema transiently worsened, the withdrawal of imatinib and administration of diuretics improved it. Imatinib was re-administered, and nutritional support was continued. The total bilirubin level decreased, and the serum albumin level increased. The tumor gradually decreased in size. Finally, she received surgical resection after 16 months of treatment with imatinib. Although adjuvant imatinib administration was continued after surgery, and no recurrence was observed as of 18 months after surgery.

Microsatellite Instability-high Intrahepatic Cholangiocarcinoma with Portal Vein Tumor Thrombosis Successfully Treated with Pembrolizumab.

A 60-year-old man presented with postoperative recurrence of intrahepatic cholangiocarcinoma with right portal vein tumor thrombosis (PVTT). After failure of standard chemotherapy, a liver biopsy showed that his microsatellite instability (MSI) status was high. Treatment with the immune checkpoint inhibitor (ICI) pembrolizumab was commenced, which resulted in a partial response and resolution of the PVTT. There were no significant immune-related adverse events. According to recently published reports, the frequency of MSI-high biliary tract cancer (BTC) is about 0-2.1%, which is extremely rare. However, ICIs may be effective in patients with MSI-high BTC, such as the present patient.

Adrenal Ewing's Sarcoma in an Elderly Man.

Ewing's sarcoma usually arises in the bones of children and adolescents. We herein report a 74-year-old man with Ewing's sarcoma in the adrenal gland. The diagnosis was confirmed by a genetic test, pathological studies, and several imaging studies. He already had multiple liver metastases when he was transferred to our hospital and died on the 37th day. The diagnosis was further confirmed by autopsy studies. Adrenal Ewing's sarcoma is very rare, and our patient was older than other reported cases. Ewing's sarcoma should be considered even in elderly patients with adrenal tumors.

New endoscopic classification of cascade stomach, a risk factor for reflux esophagitis.

BACKGROUND: We recently demonstrated that cascade stomach detected by barium studies was correlated with upper gastrointestinal symptoms. We developed a new endoscopic classification of cascade stomach and examined its relationship with reflux esophagitis. METHODS: Study 1: the classification (grades 0-3) was based on detecting a ridge that runs from the cardia toward the anterior wall crossing the greater curvature. Inter-observer variation was evaluated by kappa statistics when ten experienced endoscopists used this classification three times each. Study 2: in 710 consecutive subjects (500 men and 210 women) undergoing endoscopic screening, the grade of cascade stomach and incidence of reflux esophagitis were compared. RESULTS: In study 1, the kappa values at the third assessment were 0.85, 0.58, 0.50, and 0.78 for each grade, respectively, while overall agreement was 0.68. In study 2, the incidence of reflux esophagitis in men was 20 % in grade 0, 17 % in grade 1, 25 % in grade 2, and 30 % in grade 3, showing significant differences. Among women, the incidence of reflux esophagitis in each grade was 9, 3, 6, and 35 %, respectively, also showing significant differences. Multivariate analysis showed that independent risk factors for reflux esophagitis were cascade stomach (odds ratio = 2.20), body mass index, and hiatus hernia in men, as well as cascade stomach (odds ratio = 9.01) and smoking tobacco in women. CONCLUSIONS: This endoscopic classification of cascade stomach showed acceptable inter-observer variation. Cascade stomach is a risk factor for reflux esophagitis.

A prospective randomized controlled trial of AJG522 versus standard PEG+E as bowel preparation for colonoscopy.

Polyethylene glycol- (PEG-) based bowel preparations for colonoscopies are often poorly tolerated due to the large volumes of fluid intake required. We compared low-volume "modified" PEG + ascorbic acid (AJG522) with standard PEG with electrolytes (PEG+E) in addition to a stimulant laxative and an agent to improve bowel function for the bowel cleansing before colonoscopy to evaluate its efficacy, safety, and acceptability. Outpatients scheduled to undergo colonoscopy were randomized to receive either AJG522 or PEG+E. Bowel cleansing conditions were assessed via macroscopic fecal findings by blinded and independent investigators. A survey of the patients' feedback regarding the preparation was conducted by questionnaire. Successful cleansing was achieved in all cases, except for 4 cases in the PEG+E group, at 3 hours after taking the preparation. The fecal properties were significantly clearer in the AJG522 group than in the PEG+E group at 2 hours after taking each preparation (P=0.013). Although the total liquid volume of the bowel preparation was not reduced, the AJG522 preparation could significantly reduce the required volume of the preparation (P<0.0001). Moreover, the patients in the AJG522 group had better acceptability (P=0.010). There were no significant differences in the safety profiles between groups (UMIN000013892).

More severe upper gastrointestinal symptoms associated with non-erosive reflux disease than with erosive gastroesophageal reflux disease during maintenance proton pump inhibitor therapy.

BACKGROUND: During maintenance proton pump inhibitor (PPI) therapy, patients with gastroesophageal reflux disease (GERD) sometimes complain of upper gastrointestinal symptoms. AIM: To evaluate upper gastrointestinal symptoms in patients on maintenance PPI therapy for erosive GERD or non-erosive reflux disease (NERD) without endoscopic mucosal breaks by using a new questionnaire. METHODS: At Gunma University Hospital over a 12-month period during 2011-2012, we enrolled 30 consecutive patients with erosive GERD and 46 patients with NERD. All patients had been on maintenance PPI therapy for more than 1 year. We used the modified frequency scale for the symptoms of GERD (mFSSG) questionnaire to assess upper gastrointestinal symptoms. We also asked patients about their satisfaction with maintenance therapy and whether they wished to change their current PPI. RESULTS: The NERD patients had significantly higher symptom scores than the erosive GERD patients. There was no difference in the treatment satisfaction rate between patients with erosive GERD and NERD, but more patients with NERD wanted to change their PPI therapy. There was no difference in the mFSSG score between NERD patients who wished to change their current PPI therapy and those who were satisfied with it. CONCLUSIONS: During maintenance PPI therapy, upper gastrointestinal symptoms were more severe in NERD patients than in patients with erosive GERD. NERD patients often wished to change their PPI therapy, but this was not dependent on the severity of their upper GI symptoms.

Enteropathy-type T-cell lymphoma that was pathologically diagnosed as celiac disease.

A 63-year-old woman was referred and admitted to our department for further examination of protein-losing enteropathy (PLE), which was diagnosed by alpha-anti trypsin test. Her symptoms were frequent vomiting, watery diarrhea and hypoproteinemia. Although intensive examination for PLE was performed in her previous hospital, the origin of the disease was not detected. Abdominal computed tomography revealed diffuse enlargement and swelling of the intestine wall and a 5-cm diameter mass with unclear margin, which involved the mesenteric arteries and veins. Total colonoscopy showed a diffuse edematous lesion with hemorrhage at the terminal ileum. Enteropathy-type T-cell lymphoma (ETL) was diagnosed based on a biopsy of the lesion and CD45 gating analysis. Immediate start of chemotherapy (CHOP) led to a transient regression of the tumor even though her symptoms were not improved. During the second cycle of CHOP, the patient died of massive hemorrhage throughout the intestine. The pathological study revealed that intraepithelial CD3-positive clonal T-cells were present in the lesion, indicating that this case could be associated with celiac disease. In light of the histological findings, we concluded that this was a case of ETL associated with celiac disease, which is extremely rare in Japan.