The Association of Thymidine Phosphorylase with Gastric Cancer Prognosis.

BACKGROUND: Thymidine phosphorylase(TP)plays an important role in angiogenesis and solid tumor invasion. This study aimed to investigate TP expression in gastric cancer(GC), its correlation with clinicopathological features, and its prognostic significance. METHODS: Clinical data and tumor specimens were retrospectively collected from patients with GC in Ikeda Municipal Hospital between January 2005 and December 2006. Tumor specimens were immunohistochemically analyzed for TP expression graded as 0, 1+, 2+, or 3+ and divided into low(0/1+)and high(2+/3+)TP expression groups. To determine its potential prognostic value, any correlation between TP expression and the clinicopathological features of the patients was statistically assessed. RESULTS: Among 111 patients with GC, 33 had high TP expression(29.7%)and 78 had low TP expression(70.3%). There were significant differences in tumor size, tumor depth, venous invasion, lymphatic invasion, and clinical stage between the two groups. Analysis of the Kaplan-Meier survival curves revealed that the high TP group had significantly shorter overall survival(OS; p<0.01)and progression-free survival(PFS; p<0.01)than the low TP group. Moreover, the high TP group had significantly shorter OS(p=0.040)and a trend toward a shorter PFS(p=0.064) than the low TP group in patients with stage Ⅱ, Ⅲ, and Ⅳ cancer. Multivariate analysis revealed that high TP expression was significantly associated with tumor size, tumor type, and lymphatic invasion in patients with GC. CONCLUSIONS: Our results suggest that high TP expression might predict poor prognosis in GC.

[A Case of Pancreaticoduodenectomy for Vater Papillary Cancer with Celiac Axis Stricture].

During the follow‒up of Vater papillary adenoma, a 74‒year‒old man was admitted to our hospital with a chief complaint of upper abdominal pain and diagnosed as cholangitis with obstructive jaundice. Cholestasis had been considered to be caused by papillary adenoma, however, EUS exam showed continuous bile duct wall irregularity from papilla of Vater. So we diagnosed as papillary carcinoma with extension to the distal bile duct. Preoperative CT showed the stenosis at the root of celiac artery, and hepatic blood flow was considered to be supplied via the pancreatic head arcade from superior mesenteric artery, so an anastomosis of gastroduodenal artery and inferior pancreaticoduodenal artery was performed during pancreaticoduodenectomy( PD). Like this case, when performing PD with celiac artery stricture, it is important to evaluate hepatic blood flow before and during surgery and prepare for the arterial reconstruction.

[Analysis of 16 Cases of Primary Duodenal Carcinoma in Our Hospital].

Primary duodenal carcinoma is a rare disease among gastrointestinal malignancies and has little evidence. We evaluated retrospectively the treatment status of 16 cases of primary duodenal carcinoma in our hospital between 2010 and 2019. The median age was 72(58-88)years and 63% of patients were male, and Each stage were Stage 0 in 4 cases, Stage Ⅰ in 1 case, Stage ⅢA in 2 cases, Stage ⅢB in 3 cases, and Stage Ⅳ in 6 cases(UICC 8th edition). Initial treatment was endoscopic therapy in 3 cases, surgery in 10 cases, chemotherapy in 1 case, and best supportive care in 2 case. The 2-year survival rate was 51.3% and the MST was 25.4 months in all cases. The Stage 0, Stage Ⅰ cases had all recurrence-free survival, while the Stage ⅢA or higher cases, 2-year survival rate was 33.8% and the MST was 20.0 months. Also, XELOX was often selected as the first-line treatment for chemotherapy regimens including recurrence treatment.

[A Case of Long-Term Progress Control of Unresectable Progressive Gastric Cancer with Nivolumab Introduced during Effective Duration of Secondary Treatment].

A 65-year-old man with 1 month of general malaise was admitted to our hospital. Thoracoabdominal CT showed that the supra-clavicular, sub-carina, and para-aortic lymph nodes were swelling. Upper gastrointestinal endoscopy revealed 2 type 1 tumors at the esophagogastric junction, and the biopsy showed Group 5, well to moderately differentiated adenocarcinoma. The clinical diagnosis was cardiac gastric cancer and cStage Ⅳ(cT3N3M1[LYM]). We started capecitabine plus oxaliplatin as the first-line chemotherapy, and weekly paclitaxel plus ramucirumab was administered as the second-line treatment. The second-line treatment was successful, and the effect of PR was obtained. However, considering the period of TTF, while the therapeutic effect continued, we switched to third-line treatment with nivolumab after 7 courses of the second treatment. With the third-line treatment, PR was maintained for 1 year and 3 months, and good quality of life and performance status were obtained for a long period without irAE. However, after 32 courses, because the tumor marker was elevated and lymph nodes were enlarged, we judged PD and switched to the fourth-line treatment with nab-paclitaxel plus ramucirumab. The tumor marker levels decreased, the lymph nodes shrank, and PR was achieved again with the fourth-line treatment. The treatment is still ongoing 2 year and 8 months after the diagnosis.

[A Case of Hepatocellular Carcinoma with Extrahepatic Growth-A Difficult Preoperative Diagnosis].

A 75-year-old man was admitted to our hospital for breathing difficulty. CT showed a 20 cm mass with clear boundaries and internal non-uniformity, which we suspected to be a gastrointestinal stromal tumor(GIST). Surgical resection was been considered to be risky because the mass was close to surrounding organs, such as the stomach, liver and diaphragm. Thus, we chose imatinib therapy. After 2 months, he was admitted to our hospital for anemia. CT showed the size of mass to be smaller, but the area of low density with internal non-uniformity had increased. We diagnosed intratumoral bleeding, and chose surgical resection. The mass was under the omentum, and had infiltrated the extrahepatic area and lesser curvature of the stomach. We diagnosed the mass derived from the stomach, and performed partial gastrectomy with partial liver resection. Pathological diagnosis was extrahepatically growing hepatocellular carcinoma(HCC, pT3N0M0, pStage Ⅲ).

[Two Cases of Resectable Gastric Cancer with Extensive Nodal Metastasis That Received Preoperative DOS Therapy].

Case 1: A 67-year-old male had a type 1 tumor in the stomach with a lymph node metastasis 50 mm in size. He was diagnosed with cT4aN(+)M0, cStage Ⅲ and received preoperative docetaxel plus oxaliplatin plus S-1(DOS)therapy. After 3 courses of the regimen, the patient underwent laparoscopic total gastrectomy. The final stage was ypT3N1(1/38) M0, ypStage ⅡB, R0, and the pathological response was Grade 2b. Case 2: A 64-year-old male had a type 3 tumor in the abdominal esophagus and a lymph node metastasis 15 mm in size. He was diagnosed with cT3N(+)M0, cStage Ⅲ and received preoperative DOS therapy. After 3 courses, he underwent laparoscopic esophagectomy. The final stage was ypT0N0M0, ypStage 0, R0, and the pathological response was Grade 3. DOS therapy may be effective as a neoadjuvant chemotherapy.

[Two Cases of Large Gastrointestinal Stromal Tumors Safely and Completely Resected by Laparoscopic Surgery Followed by Neoadjuvant Imatinib Therapy].

Case 1, the patient was a 51-year-old man. Upper gastrointestinal endoscopy revealed a submucosal tumor with delle at the posterior wall of the gastric body, and the biopsy demonstrated a diagnosis of GIST. Abdominal CT scan showed a tumor at the size of 130×110×90 mm. Six months after administration of 400 mg/day of imatinib, the maximum diameter was reduced to 55 mm, then partial gastrectomy was performed by laparoscopic surgery. He continued to take imatinib after the surgery for 3 years, and he is alive without recurrence 4 years postoperatively. Case 2, the patient was a 68-year-old man. An abdominal CT scan showed a tumor at the size of 160×120×85 mm on the posterior outside of the stomach, but no submucosal tumor could be identified by upper gastrointestinal endoscopy. Gastric GIST was suspected and he started taking imatinib 400 mg/day. Because the Grade 3 generalized eruption was appeared, imatinib was discontinued, and then the dose was reduced. Nine months after the initiation of the treatment, the maximum diameter was reduced to 90 mm, and laparoscopic partial gastrectomy was performed. The patient is followed up without administration of imatinib after the surgery, and is alive without recurrence for 1 year and 6 months postoperatively. We report 2 cases that the large gastric GIST was able to be resected safely and completely due to tumor shrinkage by neoadjuvant imatinib therapy.

[A Case of Pancreatic Pseudocyst Recurrence after Surgery for Remnant Pancreatic Cancer].

The patient was a 72-year-old man with a history of pancreatic cancer and IPMA treated with distal pancreatectomy. He had recurrence-free period after adjuvant chemotherapy with S-1. But 6 years after the surgery, a diameter of 1 cm mass was noted in the remnant pancreas on MRI examination after hepatocellular carcinoma treatment. The mass was diagnosed as remnant pancreatic cancer, and he had undergone partial pancreatectomy of remnant pancreas. The pathological diagnosis was pancreatic ductal carcinoma with negative margin. However, 6 months after the reoperation, epigastric pain appeared, and CT scan showed a pseudocyst of 10 cm in size. The diagnosis was local recurrence with positive cytology, and then puncture drainage was performed. After repeated drainages, adhesion of the cystic lesion, and chemotherapy, the cytology became negative and the cystic lesion disappeared, but peritoneal dissemination metastasis also appeared. The patient died of the primary disease 7 years and 8 months after the first surgery and 1 year and 11 months after the second surgery. There has been no report of local recurrence in the form of pancreatic pseudocyst after pancreatic cancer surgery, and we report this case with literature discussion.

Primary adenosquamous carcinoma of the liver detected during cancer surveillance in a patient with primary sclerosing cholangitis.

Primary sclerosing cholangitis (PSC) is associated with significant risk for hepatobiliary cancers. Primary hepatic adenosquamous carcinoma (ASC), a rare subtype of cholangiocarcinoma, is composed of both adenocarcinoma and squamous cell carcinoma components. We herein report the case of a patient with PSC who was diagnosed with ASC of the liver during cancer surveillance. A 74-year-old male patient was diagnosed with PSC based on blood chemistry and magnetic resonance cholangiopancreatography findings, and regular surveillance for hepatobiliary cancers was initiated. Four years later, the level of carbohydrate antigen 19-9 rapidly increased, and abdominal imaging studies revealed a cystic mass, 40 mm in diameter, containing a solid component in the right liver lobe. Right lobectomy was performed with a pre-operative diagnosis of cholangiocarcinoma; however, the definitive diagnosis was ASC based on the presence of adenocarcinoma and squamous cell carcinoma components in the resected tumor. The patient did not receive post-operative chemotherapy, but was alive for more than 4 years without recurrence at last follow-up. The present case illustrates that regular surveillance and curative resection might achieve long-term survival in hepatic ASC, which has a poor prognosis.

[Case of Gastric Cancer with Para-Aortic Lymph Node Metastases Successfully Treated with S-1/Docetaxel Chemotherapy].

A 78-year-old man diagnosed with advanced gastric cancer and para-aortic lymph node metastases at clinical stage cT3 (SS)N1M1(LYN), Stage Ⅳwas treated with S-1/docetaxel(S-1/DTX)therapy. Eight months later, lymph node metastases resolved on abdominal CT, and the primary lesion appeared scarred when viewed by upper gastrointestinal endoscopy; this was considered to be a complete response(CR). S-1/DTX therapy was administered for a total of 16 courses, followed by 13 courses ofS -1 therapy. During the treatment, CR was maintained. Though chemotherapy was completed 2 years and 2 months after its initiation, the patient's serum CEA level was found to be elevated. As the serum CEA level gradually increased, S-1/DTX therapy was resumed. Three months after chemotherapy was restarted, PET-CT revealed multiple bone metastases. The chemotherapy protocol was changed to paclitaxel/ramucirumab therapy followed by nivolumab therapy. Disease control was difficult, and the patient died 9 months after reinstituting chemotherapy(3 years and 8 months after the first chemo- therapy). This case report summarizes our treatment ofa patient with advanced gastric cancer using S-1/DTX therapy for an extended period of time.

[A Long-Survived Case of Gastric Cancer with Multiple Liver Metastases Who Underwent Gastrectomy and Received Chemotherapy].

A 70-year-old man visited our hospital because of a body weight loss. Upper gastrointestinal fiberscope revealed a type 3 tumor and an enhanced MRI showed 30 or more liver metastases. He received docetaxel plus cisplatin plus S-1(DCS)therapy. Although main tumor had shrinked only partially, multiple liver metastases could not be detected. Thus, he was performed distal gastrectomy. After gastrectomy, he received S-1 plus oxaliplatin(SOX)therapy followed by S-1 therapy. Two years and 2 months after surgery, chemotherapy was finished because of no signs of tumor progression. He is alive without recurrence for 2 years and 11 months after gastrectomy.

[A Case Report of Hepatocellular Carcinoma with Complete Spontaneous Regression].

This is the case of a 77-year-old man with hepatitis C. AFP was increased by 95.9 ng/mL, and abdominal computed tomography(CT)revealed a 20 mm mass in the S6 segment of the liver. Therefore, the patient was referred to our hospital for further examination. Abdominal echo at our hospital showed a 10 mm, low echoic lesion in S6, which tended to shrink. Similarly, CT showed a low-concentration nodule of 10 mm in S6, but the contrast effect in the arterial phase was not clear. EOB-MRI showed a 10 mm nodule of DWI hyperintensity and hepatocyte phase hypointensity in S6. Based on these, a diagnosis of hepatocellular carcinoma(T1N0M0, StageⅠ)was made, and we decided to perform surgery. Intraoperative findings showed no tumor on the liver surface, and echo did not reveal a reproducible nodule. The tumor site was estimated using a 3-dimensional image analysis system created preoperatively. Laparoscopic partial resection of the liver S6 segment was performed at a position distant from the estimated tumor site. Rapid pathological examination showed no malignant findings, but no significant lesion was found in the residual liver, and the surgery was completed. The postoperative pathological diagnosis revealed no clear tumor. EOB-MRI was performed again postoperatively, but no tumor was found in the residual liver. The tumor site that had been indicated preoperatively was resected, and we hypothesized that the hepatocellular carcinoma had spontaneously regressed. Although several mechanisms have been reported for the spontaneous regression of hepatocellular carcinoma, few cases of spontaneous regression during surgery have been reported. We do not have a definite opinion on the treatment protocol for hepatocellular carcinoma that regresses spontaneously; therefore, we will report on past cases.

[Adjuvant Chemotherapy and the Prognosis of ypStageâ Gastric Cancer].

The efficacy of postoperative chemotherapy for patients with ypStageⅠgastric cancer has not been evaluated. We investigated the characteristics and prognosis of7 patients with ypStage Ⅰgastric cancer. cStages were ⅡA, ⅡB, ⅢB, and Ⅳin 1, 1, 1, and 4 patients, respectively. S-1 plus cisplatin and docetaxel plus cisplatin plus S-1 were administered in 5 and 2 patients, respectively, for 2-8 courses before gastrectomy. Microscopic curative resection was performed for all patients. ypStage was 0, ⅠA, and ⅠB in 1, 2, and 4 patients. All patients received postoperative chemotherapy with S-1 or docetaxel plus S-1(DS). The 5-year recurrence-free survival was 71% and the 5-year overall survival was 68%. Two patients developed recurrence. One patient developed recurrence 1 year and 1 month after gastrectomy in spite of S-1 treatment for 4 months. Another patient developed recurrence 11 months after gastrectomy after DS treatment for 4 months followed by S-1. The other 5 patients received S-1 for 1-5 years and have survived without recurrence. Although the prognosis ofypStage Ⅰgastric cancer was comparatively good, the regimen and courses ofpostoperative chemotherapy should be evaluated in a prospective study.

[Two Cases of Liver Metastasis from Gastric Cancer Achieving Long-Term Survival Successfully Treated with Stereotactic Body Radiotherapy(SBRT)].

We report 2 cases with long-term survival following stereotactic body radiotherapy(SBRT)for liver metastasis from gastric cancer. Case 1 was a 65-year-old man. We performed distal gastrectomy for gastric cancer with liver metastasis prior to chemotherapy due to pyloric stenosis. Postoperative S-1 chemotherapy was administered. Two liver metastases observed before the operation were temporarily reduced in size but subsequently enlarged; therefore, SBRT was performed 13 months postoperatively. The liver metastases showed a complete response(CR)and the patient is alive 4 years and 11 months after SBRT(6 years postoperatively). Case 2 was a 71-year-old woman. After performing distal gastrectomy, liver metastasis emerged during postoperative S-1 adjuvant chemotherapy; therefore, SBRT was performed 11 months postoperatively. She was then administered weekly paclitaxel. However, she underwent a right hepatic lobectomy 13 months after SBRT for suspected remnant or marginal recurrence by abdominal enhanced CT. Histopathological examination showed that the tumors contained fibrotic connective tissue with no viable cancer cell remnants; therefore, the therapeutic effect was determined to be of Grade 3. The patient is alive without recurrence in the remnant liver 4 years and 7 months after SBRT(5 years and 6 months after the operation of gastric cancer). Thus, SBRT for liver metastasis from gastric cancer may be considered an effective local treatment.

[A Case Report of Long Survival in Pancreatic Cancer with Superior Mesenteric Arterial Invasion Following Multimodal Therapy].

The prognosis of pancreatic cancer with superior mesenteric arterial invasion is very poor and judgment of surgical indication is very difficult. We report a case that received multimodal therapy for pancreatic cancer with superior mesenteric arterial invasion. A 43-year-old woman consulted a local doctor because of upper abdominal pain. Ultrasonography revealed a nodule in the pancreatic body and elevated CA19-9 values. She was referred to our hospital for evaluation and therapy. Computed tomography showed a low-density area in the pancreatic body and around the superior mesenteric artery. The clinical diagnosis was pancreatic cancer with superior mesenteric arterial invasion. She received chemoradiation therapy(RT, 50.4 Gy, gemcitabine[GEM]plus TS-1)followed by distal pancreatectomy. She received adjuvant chemotherapy(TS-1)for 6 months. However, follow-up CTperformed 10 months after surgery revealed local recurrence. The patient received chemotherapy( GEM)for 8 months and GEM plus nab-PTX for 22 months. She died from the cancer 50 months after the primary operation.

[A Case Report of Advanced Gastric Cancer with Synchronous Liver Metastasis Treated with Conversion Surgery after S-1 plus Oxaliplatin Chemotherapy].

Gastroscopy ofa 79-year-old man complaining ofanemia showed a type 3 tumor at the lesser curvature ofthe gastric body. A biopsy revealed poorly differentiated HER2-negative adenocarcinoma. Abdominal CT showed the tumor at the lesser curvature ofthe gastric body, multiple lymph nodes with a maximum diameter of 25mm at the lesser curvature, and a mass measuring 50mm with ring enhancement on S6 ofthe liver. The clinical diagnosis was cT4aN2M1(Hep), cStage Ⅳ. He was treated with chemotherapy comprising 4 courses ofS -1 plus oxaliplatin. Although the tumor had shrunk remarkably, chemotherapy was discontinued because of anorexia. Therefore, we performed total gastrectomy and hepatic partial resection(S6). The final staging was ypT3N0M0, ypStage ⅡA. We achieved R0 resection, and he has shown no recurrence without adjuvant chemotherapy for 3 years.

[A Case of Chemotherapy with Abscess Drainage for Pancreatic Cancer Detected Due to Peritonitis].

A 69-year-old woman was admitted to our hospital because of abdominal pain. Abdominal CT revealed free air, so we performed an emergency operation. Although the perforation site could not be confirmed, pancreatic cancer invading the stomach, spleen, and transverse colon was found. As a splenic abscess and peritoneal dissemination were also found, we created a colostomy and placed drains. Although the postoperative course was good, the splenic abscess continuous with the tumor remained. We thought that early removal of the drain would be difficult, so chemotherapy was introduced while continuing drainage. Fortunately, the pancreatic cancer was controlled, and the abscess tended to shrink, so we removed the tube 137 days after the surgery. After that, we continued chemotherapy, but in the second year after the surgery, the liver metastasis acutely exacerbated and DIC also developed, resulting in cancer death. If surgical intervention is difficult, as in this case, chemotherapy may be considered as an option, keeping in mind the possibility of exacerbation of infection.

[A Case of Gastric Cancer with Ramucirumab-Related Colon Perforation after a Subtotal Colectomy].

A 61-year-old man with advanced gastric cancer underwent distal gastrectomy after chemotherapy. Fifteen months later, peritoneal metastasis and colon stenosis were detected. Therefore, subtotal colectomy and ileosigmoidostomy were performed. Three weeks later, paclitaxel(PTX)treatment was initiated, followed by nab-PTX with ramucirumab(Ram)treatment at 7 weeks postoperatively. The patient experienced sudden abdominal pain diagnosed as gastrointestinal perforation 13 weeks postoperatively. Operative findings showed that the anastomosis of the ileosigmoidostomy was perforated, and this was treated using sutures. Angiogenesis inhibitors should be carefully administered even 4 weeks or more after surgery.

[A Case of Esophagogastric Junction Adenocarcinoma with Multiple Esophageal Intramural Metastases].

We experienced a case of multiple esophageal intramural metastasis from adenocarcinoma of the esophagogastric junction. A 58-year-old man was admitted complaining of dysphagia. Upper gastrointestinal endoscopy revealed a type 3 tumor at the esophagogastric junction. Biopsy showed Group 5, poorly differentiated adenocarcinoma. Abdominal CT indicated regional and para-aortic lymph node metastasis. Then the clinical diagnosis was established as Siewert type Ⅲ adenocarcinoma and cT4aN2M1(LYM), cStage Ⅳ. After conducting 4 courses of SP(S-1/cisplatin)therapy, endoscopy showed partial response of the primary tumor and the submucosal nodules in the lower esophagus. We performed lower esophagectomy and total gastrectomy by left thoracotomy and laparotomy. Six esophageal nodules were identified in the lower esophagus, and pathological examination proved the poorly differentiated adenocarcinoma. The esophageal tumors were diagnosed as intramural metastases. The patient showed hepatic and lymphatic recurrence 9 months after surgery, and died 15 months after surgery. Esophageal intramural metastasis from esophagogastric junction adenocarcinoma is relatively rare. We discuss this case along with a review of the literature.

[A Case of Peritoneal Dissemination of Hepatocellular Carcinoma after Laparoscopic Hepatectomy].

A 69-year-old man was found to have a hepatocellular carcinoma of 2.3 cm in diameter, with extrahepatic growth in liver S4 during follow-up for chronic hepatitis C and liver cirrhosis. We performed a laparoscopic partial liver resection, but the tumor capsule was injured by the retractor used to keep the working space at the bleeding site. The pathological diagnosis was moderately differentiated hepatocellular carcinoma(pT2N0M0, pStage Ⅱ). 7 months after the surgery, intrahepatic reoccurrence appeared. Thus, transcatheter arterial chemoembolization(TACE)and radiofrequency ablation were performed. However, a single recurrence ofperitoneal dissemination appeared 8 months after the reoperation. We selected laparoscopic operation this time. Intraperitoneally, we found 4 peritoneal disseminated lesions and resected all the lesions macroscopically. However, even after the resection, peritoneal dissemination recurred and increased. Therefore, we continued treatment with sorafenib and S-1 as systemic therapy, TACE and transcatheter arterial infusion(TAI)for the multiple recurrences in the liver, and radiotherapy for the peritoneal dissemination focuses. However, his general condition worsened, and liver failure occurred. Thus, he was shifted to complete palliative treatment and died 2 years 6 months after the initial operation. The recurrent form ofhepatocellular carcinoma is mainly an intrahepatic recurrence, and recurrence ofperitoneal dissemination is rare. In this case, the intraoperative operation was considered to be the possible cause ofthe recurrence.