Protocol of a phase II study investigating the efficacy and safety of trifluridine/tipiracil plus ramucirumab as a third-line or later treatment for advanced gastric cancer.

In Japan, systemic chemotherapy is the standard treatment for unresectable, advanced, or recurrent gastric cancer. However, numerous patients with gastric cancer do not receive late-line treatment because of the rapid progression of gastric cancer. Additionally, late-line treatments, such as nivolumab, trifluridine tipiracil (FTD/TPI), or irinotecan, have limited effects on improving clinical symptoms and delaying the onset of symptoms associated with cancer progression. Recently, a combination of FTD/TPI and ramucirumab was reported to have a high response rate in late-line treatment; however, owing to patient selection bias and a high rate of hematologic toxicity in that previous study, this regimen may not be feasible in real-world clinical applications. Our objective is to conduct a single-arm phase II study to assess the safety and efficacy of FTD/TPI plus ramucirumab combination therapy for gastric cancer after third-line treatment under real-world clinical conditions. This study will recruit 32 patients according to eligibility criteria and administer FTD/TPI (35 mg/m2) and intravenous ramucirumab (8 mg/kg). The primary endpoint will be the time to treatment failure. The secondary endpoints will include the overall survival time, progression-free survival time, overall response rate, disease control rate, relative dose intensity, and incidence of adverse events. The results will add new insights for improving the late-line treatment of advanced gastric cancer.

Testicular metastasis of colon cancer masquerading a hydrocele of testis.

A case of testicular metastasis of colon cancer, which clinically mimicked a hydrocele of the testis, is presented. Imaging study suggested a scrotal hydrocele, but slow yet gradual enlargement of the hydrocele and the past history of colon cancer prompted an orchiectomy for the pathologic diagnosis and treatment. The pathologic diagnosis was testicular metastasis of colon cancer. Testicular metastasis presenting as a hydrocele is unusual, and imaging and macroscopic findings useful for the differential diagnoses are discussed. A brief review of pertinent literature is also included.

[Evaluation of Intervention by an Antimicrobial Stewardship Team for Patients with Bacteremia].

In this study, antimicrobial stewardship team (AST) intervention was evaluated by comparing patient outcomes and consumption of broad-spectrum antibiotics [carbapenem antibiotics and tazobactam/piperacillin (TAZ/PIPC)] before and after the intervention. There was no fluctuation in the consumption rate of carbapenem, TAZ/PIPC and other antibiotics, but there was a decreased annual consumption of antibiotics after AST intervention compared to before intervention. For the carbapenems, antimicrobial use density (AUD) of meropenem (MEPM) was highest in both periods, at 20.1 and 20.4 before and after AST intervention, respectively, with no significant change after AST intervention. However, the days of therapy (DOT) for MEPM were 27.4 and 24.8 d, respectively, with a decreasing trend after AST intervention. AUD and DOT for TAZ/PIPC after AST intervention were 6.5 and 8.1 d, respectively, which were lower than the pre-intervention values. Rapid identification of the causative strain enables early de-escalation and may improve the economics of antibiotic use, but there was no difference from before to after AST intervention. Compared with before and after strain identification, the carbapenem administration rate after AST intervention was significantly lower than the pre-intervention rate (p<0.01). There was no difference in 28-day mortality and treatment period before and after AST intervention, and there were no differences in outcomes such as resolution of bacteremia, mortality, exacerbation and no change from before to after AST intervention. Based on these results, we suggest that AST intervention can reduce consumption of antibiotics without altering patient outcomes.

Investigation of the Efficacy of an Administration Plan for Tazobactam/Piperacillin (TAZ/PIPC) and the Incidence of Kidney and Hepatic Disorders.

Tazobactam/piperacillin (TAZ/PIPC) is widely used in the treatment of infectious disease. In this study, three hundred and sixty-three patients who were treated with the recommended dose of TAZ/PIPC were investigated for the proportion of time above the minimum inhibitory concentration (%TAM) and the frequency of renal and liver dysfunction. Of the whole patient population, 5.23%, exhibited increased creatinine levels, 9.37% and 8.82% exhibited increased aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, respectively. The patients who exhibited high serum creatinine (SCr) levels before administration, exhibited significant increases of AST (p=0.0121). The patients who exhibited low albumin levels before administration, exhibited significant decreases in renal function (p=0.0041). In the case of a breakpoint (BP) of 64 µg/mL, the arrival probabilities of %TAM of 30% and 50% were 99.4% and 76.9%, respectively. We suggested that the dose of TAZ/PIPC should be adjusted according to the interview form finding and a %TAM>50% (maximal bactericidal action).

[A case of advanced gastric cancer with tumor embolus in portal vein successfully treated by neoadjuvant chemotherapy, operation and chemoradiotherapy].

A 66-year-old man was admitted to our hospital with a diagnosis of advanced gastric cancer, with a tumor embolus in the portal vein and lymph node metastases. Since curative surgery was deemed impossible, we started neoadjuvant chemotherapy using S-1 plus CDDP. After 1 course of chemotherapy, the embolus in the portal vein disappeared. After additional chemotherapy, the primary tumor and lymph nodes were reduced in size, and a total gastrectomy with splenectomy and lymph node dissection was performed. Although he received S-1 medication as adjuvant chemotherapy, a tumor embolus in the portal vein appeared 8 months after the operation. Chemoradiotherapy(S-1+total of 50.4 Gy)was performed and the tumor embolus disappeared.

Treatment of intraabdominal desmoplastic small round cell tumor with ifosfamide-based chemotherapy.

Intraabdominal desmoplastic small round cell tumor (IDSRCT) is a rare tumor with poor prognosis that usually develops in the peritoneal cavity, often in childhood and adolescence. This tumor typically arises as single or multiple masses, and is characterized by diffuse peritoneal implants and the involvement of regional lymph nodes. Because most patients are unable to achieve a complete response with chemotherapy alone, extensive efforts have been made to develop more effective chemotherapy regimens. Here, we report on a case of IDSRCT in a 33-year-old man treated with ifosfamide (IFM)-based chemotherapy. Before treatment initiation, the patient had extensive ascites in the peritoneal cavity and was experiencing abdominal fullness and anorexia. Currently, 8 months after his initial presentation, he is still undergoing chemotherapy and is in good general condition.

[A case of superficial small cell carcinoma of the esophagus].

A 69-year-old man complaining of odynophagia visited a nearby hospital, and was referred to our hospital with endoscopic findings showing a flat-elevated lesion 35 cm from the incisors. Biopsy in our hospital revealed small cell carcinoma with a squamous cell carcinoma component. Thoracoabdominal enhanced CT detected neither lymph node metastases, nor distant organ metastases. We selected subtotal esophagectomy and retrosternal reconstruction of gastric tube. Since small cell carcinoma of the esophagus has a dismal prognosis, we conducted a minimally invasive operation with two-field lymph node dissection from the standpoint of local treatment, then shifted early to postoperative chemotherapy. The pathological diagnosis was an undifferentiated carcinoma, small cell type, inf beta, pT1b (pSM), ie (-), ly0, v1, pIM0, pN0. Postoperatively, he underwent chemotherapy with CDDP+CPT-11 following small cell carcinoma of the lung. Here mains alive without evidence of recurrence in the two years three months since the operation.

[A long survival case of unresectable pancreatic cancer by chemoradiotherapy with gemcitabine as key drug].

A 64-year-old man complaining of left hypochondriac pain visited our hospital. He was diagnosed as locally advanced unresectable cancer of the pancreatic body over 4 cm in size, because the pancreatic cancer involved the main artery and portal vein. Although chemotherapy of gemcitabine(GEM)(1.2 g/body/week)was started, he developed meningeal carcinomatosis after 2 courses of GEM. The size of the primary lesion decreased at this period, and total brain irradiation was selected to treat the meningeal carcinomatosis. He sequentially received GEM alone afterward until radiotherapy was performed for the progression of the primary lesion 24 months after the diagnosis. Although GEM alone was continued thereafter, vertebral metastases were detected 30 months following the diagnosis. He was treated with combined chemotherapy of GEM and S-1 that was effective. Finally, he died of peritoneal dissemination 42 months after diagnosis. The dose of GEM was reduced during the radiotherapy, and the total dose was 113.2 g.

Inflammatory myofibroblastic tumor (inflammatory fibrosarcoma) of the pancreas: a case report.

Inflammatory myofibroblastic tumors (inflammatory fibrosarcomas) of the pancreas are extremely rare. We report a 29-year-old woman who underwent pancreatoduodenectomy for a 6-cm tumor of the pancreas head causing obstructive jaundice. Tumor involvement was local, without apparent metastasis. The tumor was composed of proliferating fibroblastic/or myofibroblast-like spindle cells and aggregates of chronic inflammatory cells in a fibromyxoid matrix. Immunohistochemical examination demonstrated reactivity only to vimentin. This tumor has often been found in the peritoneal cavity, the retroperitoneum, or the pelvic cavity, but only very rarely in the pancreas.

Allelic imbalance at 1p36 in the pathogenesis of human hepatocellular carcinoma.

BACKGROUND/AIMS: It has been well accepted that there is an allelic imbalance at a subtelomeric region of chromosome 1p in various human malignancies including hepatocellular carcinoma. We conducted a detailed deletion mapping study at 1p36 loci in 65 hepatocellular carcinomas as an initial step towards positional cloning of the target gene. METHODOLOGY: We performed a fine-scale deletion mapping using 10 highly polymorphic microsatellite markers along the telomeric region of 1p (1p32-p36.3) and compared the clinicopathologic features with allelic imbalance of 1p36 loci. RESULTS: Allelic imbalance occurred in at least one locus on 1p in 32 (49.2%) of the 65 cases. Consequently, it was confirmed that a common region of overlaps was restricted to 1p36 and it was further clearly demonstrated that there were at least three independent regions in 1p36 (1p36.1, p36.2'36.3 and p36.3). An apparent trend towards significance has been demonstrated between allelic imbalance at 1p36 loci and tumors with classifcation T1-T2 (p<0.01). CONCLUSIONS: The present study demonstrated that the shortest region of overlap was confined within 1p36 chromosomal sub-band in human hepatocellular carcinoma, which might be involved in an early step of hepatocarcinogenesis, and it encourages future studies to identify the putative tumor suppressor gene(s) at 1p36.

Total pancreatectomy with segmental duodenectomy for benign or low-grade malignancy tumors of the whole pancreas.

Total pancreatectomy with segmental duodenectomy including major and minor papilla and preservation of the gastroduodenal artery is performed for low-grade malignancy tumor of the whole pancreas. Reconstruction of the alimentary tract was done by end-to-end duodenoduodenostomy and end-to-side choledochoduodenostomy. This is an easy, simple, safe and function-preserving operative procedure for benign or low-grade malignancy tumors of the whole pancreas.

Intraductal papillary mucinous tumor of the pancreas in a young man: report of a case.

We report the rare case of an intraductal papillary mucinous tumor (IPMT) in a man younger than 30 years of age. The patient was admitted with upper abdominal pain and an elevated amylase level of 662 IU/l. Ultrasonography showed a cystic mass in the pancreatic body and endoscopic retrograde cholangiopancreatography (ERCP) revealed a dilated pancreatic duct with a filling defect communicating with the tumor. He was successfully treated by segmental resection, which seems to be the best surgical option for pancreatic body tumors since it results in long-term survival and preserves as much pancreatic parenchyma as possible. Nevertheless, it can only be done in the absence of additional nodules along the pancreatic duct. A pathological diagnosis of intraductal papillary adenocarcinoma of the noninvasive type was confirmed, and both stumps were free of tumor.

Mitochondrial D-loop mutations as clonal markers in multicentric hepatocellular carcinoma and plasma.

PURPOSE: Hepatocellular carcinoma (HCC) is a highly malignant tumor prone to multicentric occurrence. Differentiation between a true relapse of HCC and a second primary tumor is of clinical importance. We sought to identify mitochondrial mutations in HCC and test their use as clonal markers in this disease. EXPERIMENTAL DESIGN: Primary HCC tissue samples were obtained from 19 patients and analyzed for mutations within the mitochondrial displacement loop (D-loop). The discovered mutations were used to determine tumor clonality and provided the basis for detection of tumor DNA in corresponding plasma samples. RESULTS: Thirteen of 19 HCC cases (68%) were identified as having D-loop mitochondrial DNA (mtDNA) mutations in at least one tumor. In 3 of these 13 cases, the same mutation was observed in multiple tumors, indicating monoclonal origin. Remarkably, in 8 of 13 mutated cases, we detected deletion/insertion mutations in the C-tract, a recently reported hotspot and potential replication start site of the closed, circular mitochondrial genome. In addition, we detected mutant mtDNA in 8 of 10 tested paired plasma DNA samples using a highly sensitivity molecular assay. CONCLUSIONS: mtDNA mutations within the D-loop control region are a frequent event in HCC, providing a molecular tool for the determination of clonality. In addition, detection of tumor-specific mtDNA mutations in plasma DNA needs to be explored further for monitoring patients with primary HCC.