Identification of biomarkers for personalized peptide vaccination in 2,588 cancer patients.

Peptide­based cancer vaccines have failed to provide sufficient clinical benefits in order to be approved in clinical trials since the 1990s. To understand the mechanisms underlying this failure, the present study investigated biomarkers associated with the lower overall survival (OS) among 2,588 patients receiving personalized peptide vaccination (PPV). Survival data were obtained from a database of 2,588 cancer patients including 399 patients with lung, 354 with prostate and 344 with colon cancer. They entered into phase II clinical trials of PPV in which 2 to 4 of 31 warehouse peptides were selected for vaccination on an individual patient basis based on human leukocyte antigen (HLA) class IA­types and pre­existing peptide­specific IgG levels. Higher pre­vaccination neutrophil, monocyte and platelet counts, and lower pre­vaccination lymphocyte and red blood cell counts were inversely associated with OS, with higher sensitivities in the proportions of neutrophils and lymphocytes, respectively. The most potent unfavorable and favorable factors for OS were the median percentage of neutrophils (≥64.8%) or percentage of lymphocytes (≥25.1%) with correlation coefficients (R2) of 0.98 and 0.92, respectively. Higher pre­vaccination levels of c­reactive protein and other inflammatory soluble factors were inversely associated with OS. Pre­vaccination peptide­specific immunity levels had no effect on OS, although lower immune boosting levels were inversely associated with OS. None of the 31 peptides was inversely associated with OS, although a few peptides were positively associated with it. On the whole, the findings of the present study suggested that pre­vaccination inflammatory signatures, but not those of post­vaccination immune induction, were associated with lower clinical benefits of PPV.

Polypoid gallbladder neuroendocrine tumor diagnosed as benign polyp before surgery: A case report.

Gallbladder neuroendocrine tumors (GB-NETs) comprise only 0.5% of all NET cases, and their biology has been incompletely characterized. In the present study we report the case of a 50-year-old male patient with GB-NET who was admitted to Naito Hospital with diarrhea as the main complaint. At initial diagnosis, serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels were within the normal range. Abdominal ultrasonography and contrast-enhanced computed tomography (CT) revealed gallbladder adenomyomatosis and cholecystitis, and an 8-mm pedunculated polypoid lesion was found in the neck of the gallbladder using drip infusion cholecystocholangiography-CT. As it was considered a benign polyp, laparoscopic cholecystectomy was performed. Pathological examination revealed a polypoid lesion that comprised NET cells with a cord-like or ribbon-like arrangement, and the cells exhibited positive immunostaining for chromogranin A and synaptophysin. In addition, immunohistochemical staining showed a Ki-67 index (i.e., proliferation index) of <1%, and no necrosis or mitotic figures were observed in the background. Based on these observations, we diagnosed the following: GB-NET, G1, 10x12 mm in size and located in the gallbladder neck. According to the World Health Organization 2010 classification, NET G1 is a well-differentiated tumor, with the tumor cells having a low proliferative potential [Ki-67 index ≤2%; mitotic figure number <2 (/10 HPF)]. It is regarded as a low- to mild-grade malignancy. Low-grade GB-NET occurs relatively rarely, and no clear guidelines have been formulated regarding its surgical treatment, such as minimal surgical excision margins or lymph node dissection. Detailed treatment recommendations should be developed after systematic studies of additional cases of GB-NET.

Identification of heterozygous p.Y150C and p.V274M mutations in the HJV gene in a Japanese patient with a mild phenotype of juvenile hemochromatosis: A case report.

Juvenile hemochromatosis (JH) is known as a progressive iron-storage disease, and causes severe organ impairments, including cardiomyopathy and liver cirrhosis. However, JH is a rare genetic disorder, and information for genetic mutations and phenotypes is limited. Here, we report a case of JH with heterozygous p.Y150C and p.V274M mutations in the HJV gene. A 39-year-old Japanese man was referred to Kurume University Hospital, Kurume, Japan, for fatigue and liver injury, which first appeared at the age of 25 years. There was no history of alcohol abuse and medication, and viral hepatitis, autoimmune liver diseases, and Wilson's disease were absent. However, transferrin saturation, serum ferritin, and fasting serum hepcidin levels were 98.4%, 6421 ng/mL, and 7.4 ng/mL, respectively. Furthermore, a marked reduction in signal intensity of the liver in T1/T2-weighted magnetic resonance images was seen and the R2* maps showed hepatic iron overload. Family history of hemochromatosis and severe organ impairment, such as cardiac dysfunction and diabetes mellitus, were negative. In addition, the HFE and HAMP genes did not show any mutation. However, we identified novel heterozygous p.Y150C and p.V274M mutations in the HJV gene in the patient. The p.Y150C and p.V274M mutations were seen in his mother and father, respectively. After phlebotomy, fatigue disappeared and serum transaminase levels were normalized. Furthermore, R2* maps showed a reduction of hepatic iron concentration. We first demonstrated heterozygous p.Y150C and p.V274M mutations in the HJV gene of patients with a mild JH phenotype. Thus, genetic testing should be considered even in patients with a mild phenotype of hemochromatosis.

Clinical Study on the Medical Value of Combination Therapy Involving Adoptive Immunotherapy and Chemotherapy for Stage IV Colorectal Cancer (COMVI Study).

BACKGROUND: Adoptive immunotherapy for cancer has evolved through development of novel technologies for generating a large number of activated killer cells, such as αß T-cells, γδ T-cells, and natural killer cells. There has been no prospective trial of combination therapy involving adoptive immunotherapy and first-line chemotherapy for stage IV colorectal cancer. The present pilot study aimed to evaluate the safety and feasibility of combination therapy involving adoptive immunotherapy and chemotherapy for stage IV colorectal cancer (COMVI study). PATIENTS AND METHODS: The COMVI study was a prospective, single-arm pilot trial. Therapy in each 21-day treatment cycle involved XELOX (130 mg/m2 of oxaliplatin on day 1 plus 1,000 mg/m2 of capecitabine twice daily on days 1-14), bevacizumab (7.5 mg/kg on day 1), and αß T-lymphocytes (over 5×109 on day 18) cultured ex vivo with an immobilized antibody to CD3 and interleukin-2. RESULTS: The study included six patients (two men and four women) between June 2013 and September 2014. The median patient age was 68 years (range=55-75 years). The overall response rate was 83.3% [complete response in two (33.3%); partial response in three (50.0%); stable disease in one (16.7%); no cases of progressive disease]. The tumor volume reduction rate was 53% (range=38.0-100%). The median progression-free and overall survival durations were 567 and 966 days, respectively. Most adverse events were mild-to-moderate in intensity, and no grade 4 adverse events occurred in the six patients. Only one patient experienced grade 3 hypertension and ileus. Immunotherapy-associated toxicity was minimal in this study. CONCLUSION: Combination therapy involving adoptive immunotherapy and chemotherapy for stage IV colorectal cancer is feasible and safe. Phase II prospective studies are needed to confirm the safety and efficacy of such chemoimmunotherapy.

A randomized phase II trial of personalized peptide vaccine with low dose cyclophosphamide in biliary tract cancer.

Since the prognosis of advanced biliary tract cancer (aBTC) still remains very poor, new therapeutic approaches, including immunotherapies, need to be developed. In the current study, we conducted an open-label randomized phase II study to test whether low dose cyclophosphamide (CPA) could improve antigen-specific immune responses and clinical efficacy of personalized peptide vaccination (PPV) in 49 previously treated aBTC patients. Patients with aBTC refractory to at least one regimen of chemotherapies were randomly assigned to receive PPV with low dose CPA (100 mg/day for 7 days before vaccination) (PPV/CPA, n = 24) or PPV alone (n = 25). A maximum of four HLA-matched peptides were selected based on the pre-existing peptide-specific IgG responses, followed by subcutaneous administration. T cell responses to the vaccinated peptides in the PPV/CPA arm tended to be greater than those in the PPV alone arm. The PPV/CPA arm showed significantly better progression-free survival (median time: 6.1 vs 2.9 months; hazard ratio (HR): 0.427; P = 0.008) and overall survival (median time: 12.1 vs 5.9 months; HR: 0.376; P = 0.004), compared to the PPV alone arm. The PPV alone arm, but not the PPV/CPA arm, showed significant increase in plasma IL-6 after vaccinations, which might be associated with inhibition of antigen-specific T cell responses. These results suggested that combined treatment with low dose CPA could provide clinical benefits in aBTC patients under PPV, possibly through prevention of IL-6-mediated immune suppression. Further clinical studies would be recommended to clarify the clinical efficacy of PPV/CPA in aBTC patients.

Personalized Kampo Medicine Facilitated Both Cytotoxic T Lymphocyte Response and Clinical Benefits Induced by Personalized Peptide Vaccination for Advanced Esophageal Cancer.

We retrospectively evaluated if personalized Kampo medicine (PKM) could facilitate CTL responses and clinical benefits induced by personalized peptide vaccination (PPV), in which HLA-matched vaccines were selected and administered based on the preexisting host immunity, for advanced esophageal cancer (aEC) patients. Among 34 aEC patients entered in the clinical study, 23 patients received PKM and PPV without (n = 12) or with chemotherapy (n = 11), while the remaining 11 patients did not receive PKM but received PPV without (n = 6) or with chemotherapy (n = 5), respectively. Incidence of adverse events was significantly lower or higher in PKM and PPV arm (n = 23) or PPV and chemotherapy arm (n = 16) as compared to that of the counter arm (n = 11 or 18), respectively. Postvaccination PBMCs from the patients undergoing PKM and PPV showed significantly higher CTL responses as compared to the counter arm. The median progression-free survival (PFS) or median survival time (MST) of 34 patients was 2.9 or 7.6 months, respectively. The combination therapy in PPV and PKM arm, but not that in PPV and chemotherapy arm, significantly (P = 0.02) prolonged MST. These results could warrant a next step of prospective clinical study of PKM and PPV for aEC patients.

Adoptive Chemoimmunotherapy Using Activated αß T Cells for Stage IV Colorectal Cancer.

BACKGROUND/AIM: Adoptive immunotherapy of cancer is evolving with the development of novel technologies that generate proliferation of large numbers of αß and γδ T cells. We evaluated the safety and efficacy of the combination of adoptive immunotherapy using αß T cells with chemotherapy for stage IV colorectal cancer (CRC). PATIENTS AND METHODS: Fifteen patients with advanced or recurrent CRC received XELOX + bevacizumab + ex vivo expanded αß T lymphocytes as a first-line chemoimmunotherapy. RESULTS: Median age of the 15 patients (4 men, 11 women) was 65 years (range=49-80). Median progression-free survival was 21.3 months. Response rate was 80% (complete response (CR)=26.7%, partial response (PR)=53.3%, stable disease (SD)=20% and progressive disease (PD)=0%). Most adverse events were mild to moderate regarding their intensity and immunotherapy-associated toxicity was minimal. CONCLUSION: Combination of adoptive αß T cell immunotherapy with chemotherapy for stage IV CRC is feasible and safe.

CD4+ T-lymphocytes are activated by surgical stress following colorectal resection in cancer patients.

The aim of the present study was to measure adenosine triphosphate (ATP) levels in CD4+ T cells as a marker of T-cell activity following surgery for colorectal cancer using the ImmuKnow assay kit. A total of 16 consecutive patients who underwent surgical resection for colorectal cancer between August and December, 2012 were enrolled in this study, of whom 7 underwent laparoscopic resection and 9 underwent open abdominal surgery. The intracellular ATP levels in CD4+ T-lymphocytes were measured using the ImmuKnow assay kit preoperatively and on the 1st, 4th and 8th postoperative days, as were the white blood cell (WBC) count, lymphocyte count and C-reactive protein (CRP) levels. The ATP level of the CD4+ T-cells was significantly elevated on the 1st day following surgery compared to the preoperative level (P<0.01) and gradually returned to preoperative levels; the lymphocyte count was significantly decreased on the 1st postoperative day (P<0.001). In addition, the ImmuKnow assay demonstrated that only the ATP level, but not the WBC count, lymphocyte count or CRP level, exhibited a significant difference on the 1st (P=0.080) and 8th (P=0.042) postoperative days between the laparoscopic and open abdominal surgery groups. In conclusion, the ATP level of CD4+ T-lymphocytes was increased in response to surgical stress, in tandem with a decrease in the lymphocyte count. Therefore, the ImmuKnow assay kit may be clinically applicable for monitoring the immune response following surgery, as it exhibits a higher sensitivity compared to other assays.

Administration of chemotherapy via the median cubital vein without implantable central venous access ports: port-free chemotherapy for metastatic colorectal cancer patients.

BACKGROUND: Repeated venous punctures are usually required during chemotherapy administration for cancer patients. Central venous catheters and implantable port systems have substantially facilitated vascular access, and safe, easy-to-handle port systems have become an integral part of daily clinical routines in oncology. However, several serious complications are associated with central venous ports (CV-ports), and recent developments of combined oral capecitabine and oxaliplatin (XELOX) therapies allow CV-port-free administration. In this study, the safety and efficacy of CV-port-free chemotherapy administration via the median cubital vein was assessed in metastatic colorectal cancer patients. METHODS: This study included 144 patients who received XELOX + bevacizumab (BV) or XELOX therapy for metastatic colorectal cancer without CV-port implantation. RESULTS: Eighty-five patients experienced transient vascular pain. The drip infusion route was switched to the opposite side following vascular pain in only 1 patient. No patients required CV-port implantation or delayed treatment due to adverse events associated with drug administration via the peripheral vein. Grade 3 or higher hemotoxicity and grade 3 or higher non-hematological toxicity was noted in 12.5 and 17.4 % of patients, respectively. CONCLUSIONS: Port-free-chemotherapy administration via the median cubital vein is appropriate for patients with colorectal cancer, thereby avoiding complications associated with CV-ports.

A Report of Disseminated Carcinomatosis of the Bone Marrow Originating from Transverse Colon Cancer Successfully Treated with Chemotherapy Using XELOX plus Bevacizumab.

A 61-year-old male, who had been admitted to another hospital due to disseminated intravascular coagulation (DIC), was referred to our hospital. Total colonoscopy, abdominal dynamic CT and positron-emission tomography revealed bone metastasis and multiple lymphocytic metastases from transverse colon cancer in addition to disseminated carcinomatosis of the bone marrow (DCBM). We immediately performed chemotherapy with XELOX + bevacizumab and denosumab against DCBM from transverse colon cancer in order to avoid radical surgery. In addition, we initiated the administration of recombinant human soluble thrombomodulin for 1 week to treat DIC. The patient was able to tolerate and receive 4 cycles of chemotherapy without any severe side effects. After receiving the 4 cycles of treatment, he recovered from DIC, and the bone and multiple lymphocytic metastases disappeared.

Efficacy of XELOX plus Bevacizumab in Brain Metastasis from Rectal Cancer.

Brain metastasis (BM) is rare in colorectal cancer (CRC) patients. Although BM from CRC is a late-stage phenomenon with an extremely poor prognosis, some subsets of patients would benefit from a multidisciplinary management strategy. The prognosis of patients with BM from CRC was associated with the curability of the therapy for BM and the number of metastatic organs. Metastatic brain tumors are generally treated with radiotherapy because many anticancer drugs cannot cross the blood-brain barrier. Here, we present a case treated with XELOX (capecitabine and oxaliplatin) plus bevacizumab for BM from rectal cancer. To our knowledge, this is the first report of a patient who was successfully treated for BM from CRC without radiotherapy. The findings could lead to a paradigm shift in the use of chemotherapy for BM from CRC.

[A case of unresected gastric cancer that maintained long tumor dormancy by use of paclitaxel+S-1 combination therapy].

Here we report a case of unresected gastric cancer that maintained long tumor dormancy by use of paclitaxel+S-1 combination therapy. A 58-year-old woman was admitted to the hospital for peritoneal dissemination of unresectable gastric cancer. The patient further showed ileus with peritoneal dissemination in computed tomography(CT), and we performed resection of the intestine to release the stenosis. In addition, combination chemotherapy using paclitaxel(60mg/m2, weekly) and S-1(80mg/m2, every 2 weeks)was started after the operation. The patient was discharged from the hospital 7 3 days after the operation, and we continued combination chemotherapy as an outpatient over the following 3 years without serious side effects. Furthermore, tumor makers for gastric cancer were stable, although we could not examine tumor size since the patient rejected examinations such as CT. After 3 years, the patient was admitted to the hospital with cholecystitis, and we were able to evaluate the benefit of the chemotherapy against gastric cancer. The tumor size clearly remained unchanged compared to previous measurements, suggesting that the tumor maintained dormancy in this case.

[A case of unresectable gastric cancer with poor ingestion].

We encountered cases of unresectable gastric cancer in which patients had difficulty with ingestion because of pyloric stenosis and diffuse invasion. We examined the improvement in the quality of life(QOL)of patients and the effect and usefulness of S-1 treatment in such cases. The median survival time(MST; 310 days)of patients who received S-1 as primary treatment was significantly longer than that(105 days)of patients who did not receive S-1 treatment(p=0.0001). Of the 25 patients who underwent gastrojejunostomy, S-1 was administered to 10 patients(MST: 384 days). The MST of patients who received drugs other than S-1 was 121 days. Thus, the MST of patients who did receive S-1 was significantly longer than that of patients who did not receive S-1. In univariate analysis, oral ingestion, performance status(PS), best supportive care(BSC), and S-1 administration were prognostic factors. Of these factors, oral ingestion(p=0.0278, hazard ratio[HR]: 2.992)and S- 1 administration(p=0.0002, HR: 14.956)were prognostic factors in multivariate analysis. Gastrojejunostomy is desirable for the treatment of cases of unresectable gastric cancer with poor ingestion. In addition, the use of postoperative chemotherapy with S-1 alone or with S-1 as combination therapy may help improve prognosis.

Autologous CLL cell vaccination early after transplant induces leukemia-specific T cells.

BACKGROUND: Patients with advanced hematologic malignancies remain at risk for relapse following reduced-intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (allo-HSCT). We conducted a prospective clinical trial to test whether vaccination with whole leukemia cells early after transplantation facilitates the expansion of leukemia-reactive T cells and thereby enhances antitumor immunity. METHODS: We enrolled 22 patients with advanced chronic lymphocytic leukemia (CLL), 18 of whom received up to 6 vaccines initiated between days 30 and 45 after transplantation. Each vaccine consisted of irradiated autologous tumor cells admixed with GM-CSF-secreting bystander cells. Serial patient PBMC samples following transplantation were collected, and the impact of vaccination on T cell activity was evaluated. RESULTS: At a median follow-up of 2.9 (range, 1-4) years, the estimated 2-year progression-free and overall survival rates of vaccinated subjects were 82% (95% CI, 54%-94%) and 88% (95% CI, 59%-97%), respectively. Although vaccination only had a modest impact on recovering T cell numbers, CD8+ T cells from vaccinated patients consistently reacted against autologous tumor, but not alloantigen-bearing recipient cells with increased secretion of the effector cytokine IFN-γ, unlike T cells from nonvaccinated CLL patients undergoing allo-HSCT. Further analysis confirmed that 17% (range, 13%-33%) of CD8+ T cell clones isolated from 4 vaccinated patients by limiting dilution of bulk tumor-reactive T cells solely reacted against CLL-associated antigens. CONCLUSION: Our studies suggest that autologous tumor cell vaccination is an effective strategy to advance long-term leukemia control following allo-HSCT. TRIAL REGISTRATION: Clinicaltrials.gov NCT00442130. FUNDING: NCI (5R21CA115043-2), NHLBI (5R01HL103532-03), and Leukemia and Lymphoma Society Translational Research Program.

Pilot study of the early start of chemotherapy after resection of primary colorectal cancer with distant metastases (Pearl Star 01).

BACKGROUND: The start of chemotherapy usually requires a delay of about 4 weeks after surgical resection of colorectal cancer. However, there is no evidence for the required length of this delay interval. In addition, there is a chance that a patient may die because postoperative chemotherapy was not started soon enough and a metastatic tumor was able to develop rapidly. We therefore conducted a pilot study to determine the safety and feasibility of an early start of chemotherapy after the resection of colorectal cancer with distant metastases. METHODS: Five patients were enrolled. They received XELOX therapy (130 mg/m2 of oxaliplatin on day 1 plus 1,000 mg/m2 of capecitabine twice daily on days 1 to 14) on the 7th postoperative day and XELOX + bevacizumab (7.5 mg/kg of bevacizumab on day 1) after the 2nd cycle of chemotherapy. RESULTS: Five patients underwent open surgery. The procedures included right hemicolectomy in 1 patient, sigmoidectomy in 2 patients, high anterior resection in 1 patient, and Hartmann procedure in 1 patient. All patients started chemotherapy on postoperative day 7. The median number of cycles of chemotherapy was 11 (8 to 22). No postoperative complications were observed. The tumor reduction rate was 44.3% (32.0 to 66.6%). Progression-free survival was 10.3 months. CONCLUSIONS: An early start of chemotherapy after surgery is feasible and safe. These findings suggest possible changes in the start time of chemotherapy after surgery in the future. We have already started a new phase II trial to confirm the effects of the early start of chemotherapy after surgery. TRIAL REGISTRATION: UMIN000004361.

CD40L-Tri, a novel formulation of recombinant human CD40L that effectively activates B cells.

CD40L has a well-established role in enhancing the immunostimulatory capacity of normal and malignant B cells, but a formulation suitable for clinical use has not been widely available. Like other TNF family members, in vivo and in vitro activity of CD40L requires a homotrimeric configuration, and growing evidence suggests that bioactivity depends on higher-order clustering of CD40. We generated a novel formulation of human recombinant CD40L (CD40L-Tri) in which the CD40L extracellular domain and a trimerization motif are connected by a long flexible peptide linker. We demonstrate that CD40L-Tri significantly expands normal CD19+ B cells by over 20- to 30-fold over 14 days and induces B cells to become highly immunostimulatory antigen-presenting cells (APCs). Consistent with these results, CD40L-Tri-activated B cells could effectively stimulate antigen-specific T responses (against the influenza M1 peptide) from normal volunteers. In addition, CD40L-Tri could induce malignant B cells to become effective APCs, such that tumor-directed immune responses could be probed. Together, our studies demonstrate the potent immune-stimulatory effects of CD40L-Tri on B cells that enable their expansion of antigen-specific human T cells. The potent bioactivity of CD40L-Tri is related to its ability to self-multimerize, which may be facilitated by its long peptide linker.

[Evaluation of bevacizumab for advanced colorectal cancer].

BACKGROUND: Recently, Bevacizumab became one of the major therapeutics in the care of advanced and recurrent colorectal cancer patients in Japan. The present study evaluated the efficacy and the adverse events in 23 patients who were treated with Bevacizumab. METHODS: From April, 2007 to February, 2009, 23 colorectal cancer patients were treated with Bevacizumab. We evaluated the adverse events and the time to progression (TTP). RESULTS: The median age of the patients was 60 years old. Advanced cases were 14 and recurrence cases were 9. The basic combination chemotherapy with Bevacizumab included FOLFOX (14 patients), FOLFIRI (8 patients), and IFL (1 patient). Although grade 3 of melena was recognized in one patient, the other mild adverse events were treated without accident. The median TTP was 108 days, and was not significantly different between combination with mFOLFOX6 or FOLFIRI. In combination therapy of Bevacizumab and mFOLFOX6, the TTP of Bevacizumab first-line treatment was significantly longer than that of second-line treatment (p<0. 05). In contrast, the TTP was no different in FOLFIRI therapy with or without Bevacizumab. CONCLUSION: Although one grade 3 side effect was observed, most patients were treated safely with Bevacizumab. mFOLFOX6 with Bevacizumab was recommended for first-line therapy of advanced or metastatic colorectal cancer.

Prospective randomized trial of a closed-suction drain versus a Penrose drain after a colectomy.

BACKGROUND/AIMS: Prospective studies in the gastroenterological surgery literature have shown fewer wound related complications with a closed-suction drainage than with an open passive drainage. This study compared the SSI and cost of closed-suction drainage and open passive drainage in a randomized trial. METHODOLOGY: This study involved 112 patients undergoing colectomy from December, 2003 through April, 2007. A closed-suction or an open (Penrose) drainage was used based on the surgeon's preference. The cost and the incidence of complications including SSI was compared in the two drain types. RESULTS: The SSI rate was 13/112 cases 11.6%, but there was no significant difference between the drain groups. In addition, 18 laparoscopic surgery cases did not show any wound infection or drain infections. The closed-suction drain was not expensive regarding personnel expenses and the cost of changing the dressings. CONCLUSIONS: No statistically significant postoperative differences were observed between a closed-suction drain or an open drain after a colectomy. However, a closed-suction drain management is useful for the reduction of a cost, labor saving, and the decrease of medical waste.

[A case of gastric cancer with posterior mediastinal lymph node metastasis responding to combination therapy of Paclitaxel and S-1].

The patient was a 73-year-old man who was hospitalized with advanced gastric cancer. Computer tomography showed multiple liver and mediastinum lymph node metastases. Therefore, he was diagnosed as unresectable gastric cancer(Stage IV). We attempted low-dose combination therapy of CDDP and S-1, but it was ineffective against advance gastric cancer. We decided to change the chemotherapy, using combination therapy of paclitaxel and S-1. In the regimen, paclitaxel (60 mg/m/2) was administered on day 1, day 8, and day 15. S-1 (80 mg/m2) was administered 4 weeks with a 2-week rest. After the 2 courses, computer tomography showed reduction of the liver metastasis and disappeared of the lymph node metastases. Therefore, he could undergo total gastrectomy and radiofrequency ablation of liver metastases. He continued this combination therapy one year after the operation. The cancer has not recurred thus far. When combination chemotherapy of paclitaxel and S-1 was effective against Stage IV gastric cancer, we suggested that radical surgery is possible for those cases.

Multi-centric pancreatic cancer without PanIN lesion.

The patient was a 67-year-old man under follow-up after gastric cancer surgery. An abdominal CT scan performed 1 year earlier had shown an approximately 14-mm hypovascular mass in the pancreatic body; however, he did not consent to treatment and was followed up for 1 year. A blood workup showed that the fasting blood glucose level, which had been within normal limits, was elevated to 174 mg/dl (normal, 70-109 mg/dl), and the HbA1c level was 12.0% (normal, 4.3-5.8%). Abdominal CT revealed an approximately 20-mm mass in the pancreatic body and an approximately 12-mm mass in the pancreatic tail, and magnetic resonance imaging cholangiopancreatography (MRCP) showed discontinuity of the main pancreatic duct (MPD). Since these findings led to the suspicion of invasive ductal carcinoma (IDC) of the pancreas developing in the pancreatic body and tail, we performed distal pancreatectomy with splenectomy. Histologically, IDCs were observed in the pancreatic body and tail. However, PanIN was not observed in the MPD between the two carcinomas. They were diagnosed as independent invasive ductal carcinomas of the pancreas.