Successful subtotal gastrectomy and hepatectomy for HER2-positive gastric cancer with liver metastasis after trastuzumab-based chemotherapy: a case report.

BACKGROUND: Conversion surgery (CS) after chemotherapy is weakly recommended as a promising tool for improving prognoses in patients with unresectable gastric cancer. Moreover, several investigators have demonstrated the clinical efficacy of subtotal gastrectomy (sTG) with a small remnant stomach for the nutritional status and surgical outcome compared with total gastrectomy. Here, we report a patient with liver metastasis from human epidermal growth factor receptor 2 (HER2)-positive gastric cancer who underwent sTG and hepatectomy after trastuzumab-based chemotherapy. CASE PRESENTATION: An 84-year-old male patient was diagnosed with HER2-positive gastric cancer with a single liver metastasis. He was treated with eight courses of trastuzumab in combination with S-1 and oxaliplatin as first-line chemotherapy. The primary tumor and liver metastasis shrank significantly. The metastatic liver lesion's reduction rate was 65%. According to the Response Evaluation Criteria in Solid Tumors, the patient had a partial response. Therefore, he underwent an sTG with D2 lymphadenectomy and partial hepatectomy of segment 2. Histopathological examination revealed a grade 3 histological response without lymph node metastases from the primary tumor. No viable cancer cells were observed in the resected liver specimens. The patient received adjuvant chemotherapy with S-1. The postoperative quality of life (QOL) evaluated using the Postgastrectomy Syndrome Assessment Scale-45 was maintained, and the patient was still alive 8 months after the CS without recurrence. CONCLUSIONS: An sTG with a small remnant stomach might be clinically useful for preventing a decline in QOL and improving prognoses in patients with stage IV gastric cancer after chemotherapy.

Significance of M2-polarized tumor-associated macrophage in pancreatic cancer.

BACKGROUND: The roles of infiltrating macrophages within the tumor microenvironment are complex because of their functional variety. The aim of this study is to examine the role and prognostic significance of tumor-associated macrophages (TAMs) that have an M2 polarized function in pancreatic cancer. MATERIALS AND METHODS: Formalin-fixed, paraffin-embedded blocks were obtained from 76 patients with pancreatic head cancer. All patients underwent macroscopic curative resection. We assessed the number of infiltrating macrophages within the tumor invasive front by not only CD68 but also by CD163 and CD204, which are specific receptors on M2-polarized macrophages. Furthermore, to evaluate lymphangiogenesis, we measured the density of lymphatic vessels in the tumor invasive front by using D2-40. RESULTS: High incidence of lymph node metastasis was shown in cases with a high number of CD163- or CD204-positive macrophages. Significantly increased lymphatic vessel density (LVD) was shown in cases with lymph node metastasis compared with cases without lymph node metastasis (P=0.0094). Significantly increased LVD (P=0.0175) and a poor prognosis (P=0.0171) were shown in cases with a high number of macrophages that express CD163 or CD204, however, there was no significant difference according to the number of CD68-positive macrophages. CONCLUSIONS: M2-polarized TAMs in the invasive front of pancreatic cancer are associated with a poor prognosis due to accelerated lymphatic metastasis, and inhibition of the functional interaction between M2-polarized TAMs and tumor cells may improve the prognosis.

[Clinical usefulness of FDG-PET for pancreatic cancer].

PURPOSE: The purpose of this study was to estimate the usefulness of positron emission tomography (PET) in dividing the uptake with and without the main tumor for the treatment of patients with pancreatic cancer. METHODS: Ninety-eight patients with primary pancreatic cancer were evaluated with 18F-FDG-PET. For the main tumor, the maximum standardized uptake values(SUVmax)were compared with clinicopathological factors and analyzed. We examined the site of accumulation and the rate of malignancy without the main tumor. RESULTS: For the accumulation of FDG in the main tumor, the high SUVmax level was significantly correlated with T-category in TNM classification (p=0. 003), tumor invasive size (>3 cm) (p <0. 001), CA19-9 levels>100 U/mL) (p=0. 002). The overall survival of the group in which SUVmax was less than 7. 5 was better than that of the group in which it was more than 7. 5 (p=0. 03). Meanwhile, 58 patients (59%) showed the accumulation of FDG except for the main tumor. Lymph node uptake was shown in 44% of them. As for visceral accumulation, the liver was 11, lung 10, pancreas except main tumor 9, thyroid 7, peritoneal wall 3, colon 2, gall bladder 2, and bone 1. As for the rate of malignancy among them, the liver was 100%, lung 50%, pancreas except main tumor 0%, thyroid 29%, peritoneal wall 67%, colon 50%, gall bladder 50%, and bone 0%. CONCLUSIONS: We conclude that FDG-PET is a useful tool for predicting the prognosis in pancreatic cancer, and for detection of distant metastases and hidden malignant disease. FDG-PET has an important clinical impact on the selection of proper treatment.

[Chemoradiotherapy for locally recurrence after primary resection of biliary-pancreatic cancer].

Chemoradiotherapy for the unresectable pancreatic cancer and biliary cancer has been used for improving survival. In this study, we examined its safety and efficacy in cases with the local recurrence of pancreatic or biliary cancer after primary resection. Seven consecutive patients with recurrence of carcinoma of pancreas (n=3) and biliary system (n =4) were treated chemoradiotherapy. Local recurrence occurred around the portal vein in 6 patients and remnant pancreas in one patient respectively. Disease free survival after primary surgery was 22 months (range: 5-84). All patients received 50 Gy of conformal three-dimensional radiotherapy with concurrent 5-FU, Gemcitabine or S-1. Grade 3 of anorexia and elevation of transaminase level occurred in one patient respectively. Local tumor response was observed in two patients of pancreatic and biliary cancer respectively. Median survival calculated from the start of the chemoradiotherapy was 14.5 months (range: 6.4-23.9) in pancreatic cancer and 13.5 months (range: 10.8-19.8)in biliary cancer. Our data suggest that chemoradiotherapy is feasible and effective treatment option in patients who present local recurrence after primary surgery in pancreatic or biliary cancer.

Comparison of hyper-fractionated accelerated and standard fractionated radiotherapy with concomitant low-dose gemcitabine for unresectable pancreatic cancer.

BACKGROUND: Concurrent chemoradiotherapy with gemcitabine improves median survival for patients with unresectable pancreatic cancer. Recently, hyperfractionated accelerated radiotherapy (HART) has been used to treat these patients; however, the safety and efficacy are not well defined. PATIENTS AND METHODS: The standard-fractionated radiotherapy (SFRT) group (n=17) received 50.4 Gy in 28 fractions of 1.8 Gy/day. The HART group (n=18) received 50 Gy in 40 fractions of 1.25 Gy twice/day. Concurrent gemcitabine was administered to both groups. RESULTS: Median survival times were 11.3 months (SFRT) and 12.9 months (HART). One- and two-year survival rates were 37.5% and 18.8% (SFRT) and 47.1% and 17.6% (HART), respectively. The response rates did not differ significantly. The HART regimen required significantly fewer treatment days (35.5) than did the SFRT regimen (41.3). The toxicity profiles were similar. CONCLUSION: The HART/gemcitabine regimen has equivalent efficacy and a shorter treatment time as compared with the SFRT/gemcitabine regimen for patients with unresectable pancreatic cancer.

[A case of effective treatment with chemosensitivity test-guided chemotherapy for advanced pancreatic and gastric cancer with peritoneal metastasis].

A 63-year-old man with abdominal pain was diagnosed as locally advanced pancreatic tail cancer and gastric cancer with peritoneal metastasis based on computed tomography (CT) and gastrointestinal series. Preoperative serum CA19- 9 was 1,357 U/mL. During laparotomy, peritoneal dissemination was observed and confirmed pathologically. An ileoileostomy was performed and peritoneal tissue was submitted to a chemosensitivity test. Based on the chemosensitivity test, CPT-11 (50 mg/body), 5-FU (750 mg/body), and Leucovorin (375 mg/body) were administered intravenously once a week for 3 weeks with a 1-week rest as 1 course. The patient received 9 courses of chemotherapy until progressive disease. Stable disease in tumor size was observed and serum CA19-9 level dropped to 81 U/mL. He remained well without any symptoms and pursued normal activity for 15 months. He died of peritoneal dissemination 26 months after diagnosis. Chemosensitivity test-guided chemotherapy seems to be an effective regimen as individualized chemotherapy for advanced pancreatic and gastric cancer.

[A resected case of effective treatment with gemcitabine for advanced pancreatic cancer with peritoneal metastasis].

We report a resected case of advanced pancreatic cancer after successful chemotherapy. A 69-year-old man with abdominal pain was diagnosed as locally advanced pancreatic tail cancer with peritoneal metastasis based on computed tomography (CT). Preoperative serum CA 19-9 was 5,046 U/mL. In the outpatient setting, gemcitabine (GEM) at a dose of 1,000 mg/m(2)was administered once a week for 3 weeks with a 1-week rest as 1 cycle. Abdominal CT scan after 5 cycles of chemotherapy revealed that ascites disappeared and the tumor dramatically shrank. Serum CA 19-9 also dropped to 12 U/mL. Thus, we considered the patient had a partial response, and performed distal pancreatectomy and splenectomy with D 3 lymph node dissection. Peritoneal seeding was not found and peritoneal washing cytology was negative. Histological examination of the primary lesion revealed a small amount of residual cancer cells. However, he died of peritoneal metastasis only 3 months after the operation. Surgical resection following chemotherapy should be performed carefully after close evaluation of the antitumor efficacy including residual isolated tumor cell for patients with previously distant metastases.

Pancreatic mucinous cyst adenocarcinoma producing CA 19-9. A case report.

CONTEXT: We herein present a rare case of a mucinous cystic neoplasm of the pancreas producing CA 19-9 and the clinical implications are discussed. CASE REPORT: A 35-year-old woman with no history of abdominal surgery presented at Saisei Kai Sendai Hospital with an upper abdominal distention. Abdominal CT showed a large lobulated cystic tumor at the pancreatic tail. No distant metastases were identified. The preoperative serum CA 19-9 level was 6,200 U/mL (reference range: 0-37 U/mL). A mucinous cystic neoplasm of the pancreas was diagnosed and elective surgery was performed. On laparotomy, a round tumor 15 cm in diameter was encountered in the upper left abdomen. No invasion of neighboring organs or the portal vein was apparent. The entire tumor was curatively resected with a distal pancreatectomy. The final histopathological analysis revealed mucinous cystadenocarcinoma with no invasive component. Immunohistochemical staining disclosed CA 19-9 expression within the tumor cells. The CA 19-9 level normalized rapidly postoperatively and, although a minor pancreatic fistula occurred, this was resolved conservatively. She was discharged on the 45th postoperative day with no sign of tumor relapse; her CA 19-9 level was within the normal range 20 months postoperatively. CONCLUSION: We present this rare case of a mucinous cystic neoplasm producing CA 19-9 and discuss the relevant literature. The CA 19-9 production in this tumor does not appear to be directly correlated to aggressive clinical behavior.

[A case of gemcitabine-based chemo-radiation therapy for locally advanced unresectable pancreatic cancer].

A 49-year-old man was admitted to our hospital with vomiting. Abdominal CT revealed an avascular tumor at the uncinate process of the pancreas measuring 36x30 mm. Preoperative serum CA 19-9 was 361 U/ml. During laparotomy,the tumor was deemed unresectable (T4NXM0, Stage IVa),and duodenojejunostomy was performed. External-beam radiotherapy (EBRT) (50.4 Gy/28Fr) with concurrent twice-weekly gemcitabine (GEM) (40 mg/m(2)/day) was delivered. In the outpatient setting, and 1,000 mg/m(2) of GEM was administered intravenously on days 1, 8, and 15. Cycles were repeated every 28 days. The patient received 13 cycles of GEM chemotherapy until the appearance of a grade 2 facial rash. A decrease in tumor size was observed, and the serum CA 19-9 level dropped to 16 U/ml. He remained well without any symptoms and pursued normal activity for 33 months. He died of peritoneal dissemination 43 months after diagnosis. Gemcitabine-based chemo-radiation seems to be a safe and effective regimen for unresectable pancreatic cancer.

Role of positron emission tomography in decisions on treatment strategies for pancreatic cancer.

BACKGROUND/PURPOSE: The purpose of this study was to estimate the usefulness of positron emission tomography (PET) in deciding on strategies for the treatment of pancreatic cancer. The following two parameters were evaluated: the ability of PET to provide an estimation of the progression of pancreatic cancer, and the ability of PET to predict survival and the effect of chemoradiotherapy. METHODS: Forty-two patients underwent PET as part of the procedure for making a diagnosis of pancreatic tumors. The maximum standardized uptake value (SUVmax) levels were compared with clinicopathological factors and analyzed. RESULTS: PET provided a sensitivity of 87%, a specificity of 67%, and an overall accuracy of 85% for the diagnosis of pancreatic malignancy. Tumors with distant metastases showed significantly higher SUV levels than tumors without metastasis. In the patients who received chemoradiotherapy, the overall survival of the group in which SUVmax was less than 7.0 was better than that of the group in which SUVmax was more than 7.0. CONCLUSIONS: We conclude that PET is a useful tool for determining pathological status and distant metastasis in pancreatic cancer, and for predicting the prognosis of patients receiving chemoradiotherapy.

[A case of malignant peritoneal mesothelioma successfully treated with carboplatin and paclitaxel].

A 71-year-old woman was seen at our hospital because of abdominal fullness and dyspnea. Examinations revealed a tumor in the pelvis with fluid collection and dissemination was seen in the abdomen and chest. Moreover, hyaluronate in ascites rose to 20,000 mg/dl. Finally, by cytology of ascites using immunohistochemistry, the patient was diagnosed as malignant peritoneal mesothelioma with disseminations in the abdomen and chest. After intraperitoneal administration of 25 mg of cisplatin (CDDP), we started carboplatin (CBDCA) plus paclitaxel (PTX) combination chemotherapy (each treatment course consisted of 100 mg of PTX and 400 mg of CBDCA on day 1 and PTX 100 mg on day 8 and day 15 by intravenous administration followed by 2 drug-free weeks). After the sixth course, a complete remission was observed. Malignant mesothelioma is known to have a poor prognosis. However, we successfully treated malignant peritoneal mesothelioma with CBDCA and PTX combined chemotherapy. Our case suggests that we could improve the prognosis of malignant mesothelioma by aggressive chemotherapy.

Value of magnetic resonance cholangiopancreatography with secretin stimulation in the evaluation of pancreatic exocrine function after pancreaticogastrostomy.

BACKGROUND/PURPOSE: The aim of this study was to assess the value of magnetic resonance cholangiopancreatography with secretin stimulation (secretin-MRCP) in evaluating the remnant pancreatic exocrine reserve after pancreaticogastrostomy with pancreaticoduodenectomy. METHODS: Forty-three patients who had undergone pancreaticoduodenectomies and who were given pancreaticogastrostomies for reconstruction were studied. Dynamic MRCPs, using a half-Fourier acquisition single-shot turbo spin-echo (HASTE) sequence were obtained before and up to 10 min after secretin administration. The morphologic features and diameter of the main pancreatic duct were monitored and graded before and after secretin stimulation. The results were compared with those of endoscopic findings, secretin stimulation testing with a collection of pancreatic fluid, N-benzoyl- L-tyrosyl-p-aminobenzoic acid (BT-PABA) excretion testing, and fecal chymotrypsin concentration. RESULTS: The results of secretin-MRCP were classified into three distinct groups: a good-secretion group (group 1; n=22; 51%), a moderate-secretion group (group 2; n=10; 23%), and a poor-secretion group (group 3; n=11; 26%). This MRCP classification correlated significantly with the concentrations of the pancreatic enzymes p-type amylase, lipase, and trypsin in the gastric juice. The BT-PABA test value was 59.8% in group 1, 46.1% in group 2, and 46.5% in group 3, and was significantly higher in group 1 than in groups 2 or 3. The fecal chymotrypsin concentration was 20.5 U/g in group 1, 14.5 U/g in group 2, and 0.7 U/g in group 3, and there was a significant correlation between the MRCP classification and fecal chymotrypsin concentration. CONCLUSIONS: MRCP with secretin stimulation favorably reflected the presence of remnant pancreatic exocrine function. Therefore, secretin-MRCP is a feasible and effective follow-up examination method to evaluate remnant pancreatic exocrine function after pancreaticogastrostomy.

Thymidine phosphorylase suppresses Fas-induced apoptotic signal transduction independent of its enzymatic activity.

Thymidine phosphorylase (TP) has chemotactic and angiogenic activities resulting from its enzymatic activity in vitro, and it also promotes tumor growth and inhibits apoptosis in vivo. Recently, we have reported that TP plays an important role in Fas-induced apoptosis. Caspase-8 cleavage, subsequent cytochrome c release, and caspase-3 cleavage were prevented in KB cells transfected with a TP cDNA (KB/TP cells). In this study, treatment with thymidine phosphorylase inhibitor (TPI) or thymidine did not affect cell survival of KB/TP cells during Fas-induced apoptosis. Moreover, treatment with thymine or 2-deoxy-D-ribose (degradation products of thymidine generated by TP) also did not affect cell survival of control transfectant (KB/CV) cells during Fas-induced apoptosis. These findings indicate that TP suppresses Fas-induced apoptotic signal transduction independent of its enzymatic activity.

Length and quality of survival after external-beam radiotherapy with concurrent continuous 5-fluorouracil infusion for locally unresectable pancreatic cancer.

PURPOSE: The purpose of this study was to evaluate whether external-beam radiotherapy (EBRT) with concurrent continuous 5-fluorouracil (5-FU) infusion affects the length and quality of survival in patients with locally unresectable pancreatic cancer. METHODS: Thirty-one patients with histologically proven locally advanced and unresectable pancreatic cancer without distant metastases were evaluated in this prospective randomized trial. Sixteen patients received EBRT (50.4 Gy/28 fractions) with concurrent continuous infusion of 5-FU (200 mg/m(2)/day), whereas 15 patients received no chemoradiation. The length and quality of survival was analyzed and compared for the two groups. RESULTS: The median survival of 13.2 months and the 1-year survival rate of 53.3% in the chemoradiation group were significantly better than the respective 6.4 months and 0% in the group without chemoradiotherapy (p = 0.0009). The average monthly Karnofsky score, a quality of life indicator, was 77.1 in the chemoradiation group, which was significantly higher than the 65.5 in the group without chemoradiotherapy (p < 0.0001). The number of hospital days per month of survival was significantly less in the chemoradiation than in the no-therapy group (12.3 vs. 19.0 days, p < 0.05). In the chemoradiation group, 5 patients (31%) had a partial response, and 9 (56%) had radiologically stable disease at a median duration of 6.1 months. The patients who had chemoradiation had a lower rate of liver and peritoneal metastases than patients without chemoradiotherapy (31% vs. 64%). Of 10 patients who experienced pain before chemoradiation, 8 (80%) received pain relief that lasted a median of 5.2 months. CONCLUSIONS: EBRT with concurrent continuous 5-FU infusion increased the length and quality of survival as compared to no chemoradiotherapy and provided a definite palliative benefit for patients with unresectable pancreatic cancer.