A case of anaplastic ductal carcinoma of the pancreas with production of granulocyte-colony stimulating factor

We report a case of anaplastic ductal carcinoma of the pancreas with production of granulocytecolony stimulating factor in a 46-year-old man. He underwent distal pancreatectomy, total gastrectomy with Roux-en-Y reconstruction and splenectomy. He recovered uneventfully postoperatively and was discharged from hospital on the 22nd postoperative day. Histological examination showed anaplastic ductal carcinoma (giant cell type) of the pancreas. However, three months after the operation, multiple liver metastases were demonstrated by CT scan and the peripheral leukocyte count rose to 81,800/microL. Serum granulocyte-colony stimulating factor concentration was 155pg/mL (normal 5.78-27.5 pg/mL). Therefore, we diagnosed granulocyte-colony stimulating factor-producing pancreatic cancer. Anaplastic ductal carcinoma of the pancreas with production of granulocyte-colony stimulating factor is very rare. Tumors with production of granulocyte-colony stimulating factor are highly malignant, and this patient died of hepatic failure four months after the operation.     

Safety and efficacy profile of G-CSF therapy in patients with acute on chronic liver failure

BACKGROUND/AIM: We aimed to evaluate safety and efficacy of granulocyte-colony stimulating factor treatment in patients with acute on chronic liver failure and the effect of granulocyte-colony stimulating factor on the expression level of CXCR4, vascular endothelial growth factor receptor and very late activation antigen 4. METHODS: Twenty-four patients with acute on chronic liver failure were randomised to receive standard therapy, standard therapy+granulocyte-colony stimulating factor (5 microg/kg/day for 6 days) and standard therapy+granulocyte-colony stimulating factor (15 microg/kg/day s.c. for 6 days). Data on CD34+cell mobilisation were compared to age-matched peripheral blood haematopoietic stem cell donors treated with granulocyte-colony stimulating factor. On day third of treatment, the expression level of CXCR4, vascular endothelial growth factor receptor and very late activation antigen 4 was analysed in mobilised CD34+ cells. RESULTS: CD34 cell count increased after the second day of granulocyte-colony stimulating factor injection in both treatment groups compared to the linear increase observed in control. After the fifth day the increase was significantly higher in healthy donors versus patients with acute on chronic liver failure. A decrease in the expression of CXCR4, very late activation antigen 4 and vascular endothelial growth factor receptor compared to premobilisation values was observed. No major side effects were observed. CONCLUSIONS: Granulocyte-colony stimulating factor treatment is able to induce CD34 mobilisation in patients with acute on chronic liver failure. The expression pattern of CXCR4, very late activation antigen 4 and vascular endothelial growth factor receptor suggests that these molecules are involved in the granulocyte-colony stimulating factor-induced stem cell mobilisation.     

Meningitis carcinomatosa originating from an alpha fetoprotein-producing gastric cancer

Alpha fetoprotein (AFP)-producing gastric cancer is relatively rare and meningitis carcinomatosa is similarly a rare manifestation among the neoplastic diseases. There have been no previous reports of meningitis carcinomatosa originating from AFP-producing gastric cancer. A 68-year-old man with AFP-producing gastric cancer was treated with cisplatin and doxifluridine because of multiple liver metastases. Although the liver lesion was reduced to 30% of pretreatment size after 6 courses of chemotherapy, meningitis carcinomatosa subsequently occurred. Immunostaining of AFP and magnetic resonance imaging (MRI) were useful in the diagnosis of meningitis caused by AFP producing cancer cells.     

Leiomyosarcoma of the sigmoid colon with multiple liver metastases and gastric cancer: a case report

ABSTRACT: BACKGROUND: Leiomyosarcoma (LMS) of the gastrointestinal tract is an extremely rare high-grade neoplasm with poor prognosis. For advanced LMS with distant metastasis, the decision as to the choice of the most appropriate therapeutic strategy, including chemotherapy and surgery, is difficult. Here, we present an unusual case of LMS of the sigmoid colon with liver metastases and gastric cancer. The survival of this patient was prolonged by a combined modality therapy involving chemotherapy and surgery. CASE PRESENTATION: A 66-year-old woman who had been diagnosed with advanced gastric cancer and multiple liver metastases was referred to our hospital. The initial treatment with docetaxel and S-1 considerably reduced both the gastric cancer and liver tumors; consequently we performed surgical resection. Pathological examination revealed that no viable tumor cells remained in the stomach and chemotherapy resulted in complete remission of the gastric cancer. The liver tumors were immunohistochemically diagnosed as LMS. A tumor of the sigmoid colon was subsequently discovered and the liver tumors were found to have recurred. The surgically resected sigmoid colon and liver tumors were all immunohistochemically diagnosed as LMS. These findings indicated that the multiple liver metastases arose from the LMS in the sigmoid colon, and that they were accompanied by advanced gastric cancer. We performed another surgical resection and administered chemotherapy to treat the recurring liver metastases. The patient survived for 4 years and 10 months after initial presentation at our hospital. CONCLUSION: Colonic LMS is rare and its joint occurrence with gastric cancer is extremely unusual. Although LMS is a high-grade neoplasm, a multimodal therapeutic approach can increase patient survival time even when multiple liver metastases are present.     

Pathological complete response of synchronous multiple liver metastases associated with advanced gastric cancer to gastrectomy and prompt S-1 treatment in combination with fractional cisplatin: report of a case

Systemic chemotherapy is the treatment recommended for prolonged survival in cases of metastatic gastric cancer. There have been a number of clinical reports of surgical resection of liver metastasis in selected patients with gastric cancer. Here, we report on a case of treatment of far advanced gastric cancer with synchronous multiple liver metastases with prompt S-1 in combination with fractional cisplatin sandwiched between twostage surgery. Metastases including peritoneal dissemination and extensive lymph node involvement were absent so it was feasible to completely remove all of the macroscopic liver metastases. Each step of the chemotherapy progressed satisfactorily and histological examination after the hepatectomy yielded a pathologically complete response of liver metastases from the gastric cancer. This strategy provides a promising treatment for far advanced gastric cancer with a limited number of synchronous liver metastases. The referral to surgical oncology is a crucial step for the documentation of pathological complete response.     

Surgical management for metastatic liver tumors

BACKGROUND/AIMS: This study investigated the results of hepatectomy for multiple liver metastases and repeated hepatectomy for recurrent hepatic metastases. A proposed treatment strategy for liver metastases is discussed. METHODOLOGY: Fifty-seven consecutive cases of liver metastases were studied. The metastases originated from colon cancer (24 cases), rectal cancer (11 cases), gastric cancer (14 cases), or gastrointestinal stromal tumors (two cases). The other cases included one each of gastric carcinoid, carcinoma of the papilla of Vater, cystic duct cancer, esophageal cancer, choriocarcinoma and breast cancer. RESULTS: The overall 5-year survival rate for the 57 cases was 45.4%; there was no significant difference between patients with colon cancer (56.3%), rectal cancer (45.5%), or gastric cancer (41.6%). The cumulative 5-year survival rates for synchronous and metachronous metastases were 38.3% and 50.8%, respectively (difference not statistically significant; NS). The survival rates for single and multiple metastases were 56.0% and 31.3% (NS), and those for monolobar and bilobar metastases were 48.5% and 40.9% (NS), respectively. Concerning the operative procedure, the survival rates for partial resection and hemi-hepatectomy were 49.5% and 26.9%, respectively (NS). The survival rates for surgical margins <4mm and >5mm were 45.9% and 45.4%, respectively (NS), and those for single and repeat hepatectomy were 40.5% and 58.2% (NS). Preoperative portal embolization was performed in seven cases because of multiple metastases or a tumor located in a deeper site in the liver. There was no hospital death among the 57 cases. CONCLUSIONS: These results show that hepatectomy may offer longer survival, even in patients with multiple or bilobar metastases. Neither the operative procedure nor the size of the surgical margin had any influence on survival after hepatectomy. The prognosis was improved not only for metastases from colorectal cancer, but also for gastric cancer. An increased survival benefit was obtained by repeat hepatectomy for recurrent hepatic metastases. Preoperative portal embolization extended the indication for hepatectomy and provided postoperative safety.     

Outcome and management of pregnancies in severe chronic neutropenia patients by the European Branch of the Severe Chronic Neutropenia International Registry

Long-term granulocyte-colony stimulating factor treatment has been shown to be safe and effective in severe chronic neutropenia patients. However, data on its use during pregnancy are limited. To address this issue, we analyzed all pregnancies reported to the European branch of the Severe Chronic Neutropenia International Registry since 1994. A total of 38 pregnancies in 21 women with chronic neutropenia (16 pregnancies in 10 women with congenital, 10 in 6 women with cyclic, 12 in 5 women with idiopathic neutropenia) were reported. Granulocyte-colony stimulating factor was administered throughout pregnancy in 16 women and for at least one trimester in a further 5 women. No major differences were seen between treated and untreated women with respect to pregnancy outcome, newborn complications and infections. In addition, we evaluated the genetic transmission of known or suspected genetic defects in 16 mothers having 22 newborns as well as in 8 men fathering 15 children. As a proof of inheritance, neutropenia was passed on to the newborn in 58% from female and in 62% from male patients with ELANE mutations, but also to some newborns from parents with unknown gene mutation. Based on our results, granulocyte-colony stimulating factor therapy has been shown to be safe for mothers throughout pregnancies and for newborns without any signs of teratogenicity. With an increasing number of adult patients, genetic counseling prior to conception and supportive care of mothers during pregnancy are crucial. The acceptance of having affected children may reflect the high quality of life obtained due to this treatment.     

A case of alpha-fetoprotein-producing gastric cancer with hepatic metastasis successfully treated with combination chemotherapy

The patient was a 79-year-old woman. We became introduction consultation than a nearby doctor in alpha-fetoprotein(AFP)high level. Abdominal ultrasonography showed 30mm great tumor in liver lateral segment area and gastric fiber showed type2 tumor which is AFP producing gastric cancer. On admission AFP level is high(403ng/ml). Multiple liver metastases were noted it by abdominal angiography. We started FLAP(5-fluorouracil, leucovorin, etoposide, cisplatin)combination chemotherapy by a diagnosis of AFP producing gastric cancer StageIV. It is reduction of a liver tumor after one course, and the stomach lesion almost disappeared after three courses end points.     

Alpha-fetoprotein- and des-gamma-carboxy prothrombin-producing advanced gastric cancer

A case of alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) producing gastric cancer with multiple liver metastasis is reported. The simultaneous presence of Borrmann I gastric cancer and IIa aggregating type gastric cancer was noted. Borrmann I gastric cancer was a poorly differentiated adenocarcinoma, while IIa aggregating type gastric cancer was a moderately differentiated adenocarcinoma. Plasma levels of AFP and DCP were 247,000 ng/ml and 320,000 mAU/ml, respectively. Immunohistochemical staining confirmed the production of these two proteins in Borrmann I gastric cancer.     

Prognostic studies on gastric cancer with concomitant liver metastases.

BACKGROUND/AIMS: The aim of this study was to clarify prognostic factors after surgical treatments in gastric cancer patients having synchronous liver metastases. METHODOLOGY: Clinicopathological features and prognosis were retrospectively reviewed in 43 surgical patients with gastric cancer with concomitant liver metastases from 1984 to 1998. RESULTS: More than half of the patients (51.2%) had numerous liver metastases (H3). Rates of peritoneal metastases (P1, P2, P3: 34.9%), tumor serosal invasion (T3 or T4: 73.8%) and widespread lymph node metastases (N3, N4: 69.8%) were also high. Although the gastric resection was performed in 29 patients (67.5%), concomitant hepatectomy resection was performed in only 3 patients (7.0%). Univariate analysis revealed that the grade of liver metastases (H1, H2, H3) was only a statistically significant prognostic factor (P = 0.008). Concerning surgical treatments, the resection group had tendency to better survival than the nonresection group (P = 0.074). Eight cases survived more than 1 year. Seven of the 8 cases (87.5%) were patients with gastrectomy. All of the 5 two-year survivors were patients with gastrectomy. CONCLUSIONS: In patients with gastric cancer with concomitant liver metastases, the grade of liver metastases indicate prognosis. In addition, there is possibility of palliative gastrectomy increasing the survival rare to more than one year.     

Severe hypoglycemia associated with insulin-like growth factor II-producing liver metastasis from gastric carcinoma treated with overnight total parenteral nutrition via a central vein catheter reserve port

Hypoglycemia caused by insulin-like growth factor II is difficult to control. A 77-year-old woman was diagnosed with gastric cancer and multiple liver metastases in September 2006 and underwent chemotherapy; however, at that time there were no symptoms of hypoglycemia. From January 2007 onwards, hypoglycemic comas and symptoms of hypoglycemia began to appear frequently. Her serum level of insulin was normal; thus, we suspected the presence of big insulin-like growth factor II was causing the hypoglycemia. This was proven by Western immunoblotting and we diagnosed non-islet cell tumor hypoglycemia associated with gastric cancer. Overnight nutrition provided via a central venous catheter port to prevent hypoglycemia allowed the patient to become ambulant and to remain free of hypoglycemic coma at follow-up until her death 7 months later.     

Severe hypoglycemia and hypokalemia in association with liver metastases of gastric cancer

We report an 80-year-old man who presented with non-islet cell tumor hypoglycemia (NICTH) in association with hepatic recurrence of gastric cancer. His serum potassium was reduced from 3.9 to 3.1 mmol/l 5 weeks after gastrectomy, and he subsequently developed hypoglycemic coma. He was diagnosed as having NICTH because of the presence of serum big IGF-II and positive staining for IGF-II in gastric cancer cells obtained at surgery. A computed tomography showed multiple liver metastases. His hypoglycemia was refractory to steroid therapy. This case suggested that NICTH could develop in association with hepatic metastases of gastric cancer. Unexpected hypokalemia may be a manifestation of occult NICTH.     

Conversion surgery after S-1 plus oxaliplatin combination chemotherapy for advanced gastric cancer with multiple liver metastases

Conversion therapy for gastric cancer is a new therapeutic concept. We report a case of a patient with advanced gastric cancer who underwent conversion surgery due to a remarkable regression of multiple liver metastases following chemotherapy. A 71-year-old man was referred to our hospital with gastric cancer. Esophagogastroduodenoscopy (EGD) revealed an irregular, nodular, ulcerated lesion in the lower third of the stomach. Analysis of biopsy specimens revealed a poorly differentiated adenocarcinoma. Abdominal contrast-enhanced computed tomography (CT) showed multiple liver mass lesions. The patient was clinically diagnosed with advanced gastric cancer with liver metastases and received S-1 plus oxaliplatin chemotherapy. After 6 cycles of chemotherapy, CT and magnetic resonance imaging showed complete resolution of the liver metastases, and EGD detected mucosal irregularities only. Since there was no evidence of further metastatic lesions in other organs, the patient underwent distal gastrectomy with D2 lymphadenectomy. The gross appearance of the surgically resected specimen showed a slightly elevated tumor measuring 4.5?×?3.5 cm. Pathological examination confirmed the diagnosis of a moderately differentiated gastric adenocarcinoma invading the muscularis propria with no lymph node metastases. The postoperative course was uneventful. The patient has continued to receive S-1 and oxaliplatin chemotherapy, and there has been no evidence of recurrence for 3 months following the operation. We propose that conversion therapy might be an effective treatment for patients with advanced gastric cancer; however, further studies and assessments are needed to confirm and establish this treatment strategy.     

Combination chemotherapy using TS-1, Paclitaxel and cisplatin for multiple lung metastases from AFP-producing gastric cancer: a case report

A 61-year-old male had undergone distal gastrectomy followed by right hepatectomy for alpha-fetoprotein-producing gastric cancer and liver metastasis. Subsequently, multiple lung metastases were detected by follow-up chest examinations. Despite treatment with TS-1/Irinotecan (CPT-11)/Cisplatin (CDDP) combination therapy, the metastases increased gradually in size and number. Combination therapy with TS-1/Paclitaxel (TXL)/CDDP was effective, as confirmed by marked reduction in tumor size on chest computed tomography. TS-1/TXL/CDDP chemotherapy was administered repeatedly for relapse of lung metastases. The relapse was controlled twice with this chemotherapy regimen, and the patient remains alive at 52 months after gastrectomy without pulmonary symptoms such as hemosputum. Although patients with postoperative lung metastases from AFP-producing gastric cancer have a dismal prognosis, our clinical experience suggests that TS-1/TXL/CDDP combination therapy may be a useful regimen for such conditions.     

Intrahepatic micrometastases around liver metastases from gastric cancer

Background/Purpose

We aimed to clarify the association between the presence of micrometastases around liver metastases from gastric cancer and the results of hepatic resection. In addition, we investigated the influence of E-cadherin and matrix metalloproteinase (MMP)-7 expression on the development of micrometastases.

Methods

Micrometastases around liver metastases were examined microscopically in 31 metastatic liver tumor specimens resected from 17 patients who had undergone hepatic resection for liver metastases from gastric cancer. E-cadherin and MMP-7 expression in the primary gastric tumor, the liver metastases, and the micrometastases were examined immunohistochemically.

Results

Hepatic micrometastases were present in around 48% of the liver metastases, accounting for 59% of the patients. The tumor recurrence rate in the remnant liver after hepatic resection was significantly higher, and survival significantly poorer, in patients with such micrometastases than in those without. Micrometastases tended to appear around the liver metastases that had reduced E-cadherin expression. Most of the micrometastases in the lymph ducts and sinusoids showed reduced E-cadherin expression. MMP-7 expression was not correlated with the presence of micrometastases.

Conclusions

About half of the hepatic metastases from gastric cancer had seeded off micrometastases, and the presence of these micrometastases was associated with a poorer result of hepatic resection. Reduced E-cadherin expression in metastatic liver tumors may be associated with the development of micrometastases.     

Secondary acute promyelocytic leukemia following chemotherapy for gastric cancer: A case report

Therapy-related acute myeloid leukemia(t-AML) refers to a heterogeneous group of myeloid neoplasms that develop in patients following extensive exposure to either cytotoxic agents or radiation. The development of t-AML has been reported following treatment of cancers ranging from hematological malignancies to solid tumors; however, to our knowledge, t-AML has never been reported following treatment of gastric cancer. In this study, we report the development of t-acute promyelocytic leukemia in a cT 4N1M0 gastric cancer patient after an approximate 44 mo latency period following treatment with 4 cycles of oxaliplatin(OXP)(85 mg/m2 on day 1) plus capecitabine(1250 mg/m2 orally twice daily on days 1-14) in combination with recombinant human granulocyte-colony stimulating factor treatment. Karyotype analysis of the patient revealed 46,XY,t(15;17)(q22;q21)[15]/46,idem,-9,+add(9)(p22)[2]/46,XY[3], which, according to previous studies, includes some “favorable” genetic abnormalities. The patient was then treated with all-trans retinoic acid(ATRA, 25 mg/m2/d) plus arsenic trioxide(ATO, 10 mg/d) and attained complete remission. Our case illuminated the role of certain cytotoxic agents in the induction of t-AML following gastric cancer treatment. We recommend instituting a mandatory additional evaluation for patients undergoing these therapies in the future.     

Surgery for Liver Metastases From Gastric Cancer: A Meta-Analysis of Observational Studies

The role of surgical therapy in patients with liver metastases from gastric cancer is still controversial. In this study, we investigated the results obtained with local treatment of hepatic metastases in patients with gastric cancer, by performing a systematic literature review and meta-analysis.We performed a systematic review and meta-analysis of observational studies published between 1990 and 2014. These works included multiple studies that evaluated the different survival rate among patients who underwent local treatment, such as hepatectomy or radiofrequency ablation, for hepatic metastases derived from primary gastric cancer. The collected studies were evaluated for heterogeneity, publication bias, and quality, and a pooled hazard ratio (HR) was calculated with a confidence interval estimated at 95% (95% CI).After conducting a thorough research among all published works, 2337 studies were found and after the review process 11 observational studies were included in the analysis. The total amount of patients considered in the survival analysis was 1010. An accurate analysis of all included studies reported a significantly higher survival rate in the group of patients who underwent the most aggressive local treatment for hepatic metastases (HR 0.54, 95% CI 0.46–0.95) as opposed to patients who underwent only palliation or systemic treatment. Furthermore, palliative local treatment of hepatic metastases had a higher survival rate if compared to surgical (without liver surgery) and systemic palliation (HR 0.50, 95% CI 0.26–0.96). Considering the only 3 studies where data from multivariate analyses was available, we found a higher survival rate in the local treatment groups, but the difference was not significant (HR 0.50, 95% CI 0.22–1.15).Curative and also palliative surgery of liver metastases from gastric cancer may improve patients’ survival. However, further trials are needed in order to better understand the role of surgery in this group of patients.     

A case of granulocyte-colony stimulating factor producing ductal adenocarcinoma of the pancreas]

We report a case of pancreatic ductal adenocarcinoma producing granulocyte-colony stimulating factor (G-CSF). A 56-year-old Japanese man was admitted to our hospital with back pain and high fever. An abdominal CT scan revealed masses in the pancreatic body to the tail, and both lobes of the liver. A biopsy specimen of the hepatic tumor demonstrated metastatic poorly differentiated adenocarcinoma. We administered oral S-1 in combination with gemcitabine. However, his general condition gradually worsened, and a high serum level of G-CSF persisted. He died 135 days after admission. The diagnosis of autopsy was pancreatic ductal adenocarcinoma. Immunohistochemical staining showed the presence of G-CSF in tumor cells. The final diagnosis was G-CSF-producing pancreatic carcinoma.     

Treatment with Ramucirumab-paclitaxel in a metastatic gastric cancer patient undergoing hemodialysis: A case report

Rationale:Ramucirumab, a human Ig 1 monoclonal antibody against vascular endothelial growth factor receptor-2, in combination with paclitaxel is a second-line chemotherapy for patients with metastatic gastric cancer. Several reports have suggested that dose adjustments of cetuximab, an anti- epidermal growth factor receptor antibody, are not required in patients with renal impairment. However, the combination chemotherapy of ramucirumab and cytotoxic drug for hemodialysis (HD) patients has not been reported.Patient concerns:A 65-year-old man on HD was diagnosed with gastric cancer and underwent a subtotal gastrectomy with D2 lymphadenectomy. Abdominal computed tomography (CT) was examined after completion of 8 cycles of adjuvant chemotherapy with capecitabine combination oxaliplatin.Diagnosis:The patient was diagnosed with advanced gastric cancer at stage IIIb (pT3N2M0) 11 months ago. Unfortunately, 9 months after the start of adjuvant chemotherapy, multiple liver metastases from gastric cancer were found by abdominal CT.Interventions:He began receiving weekly paclitaxel(80 mg/m²) and every 15-day ramucirumab (8 mg/kg). HD was performed next day after administration of chemotherapy and repeated 3 times a week.Outcomes:He was treated with ramucirumab without dose adjustment. The metastatic liver mass had a partial response, after 2 and 4 cycles of chemotherapy and had a stable disease up to 12 cycles of chemotherapy. No obvious adverse effect was observed during treatment. However, after 14 cycles chemotherapy, follow-up abdominal CT revealed progression disease of multiple liver metastasis and lymph nodes invasion.Lessons:The paclitaxel chemotherapy with ramucirumab is effective and safe in HD patients with metastatic gastric cancer. As seen in patients with normal kidney function, ramucirumab can be safely administered without a dose reduction.