[Significance of Endocrine Therapy for Unresected Primary Breast Cancer].

At present, surgery is still the recommended principal treatment for breast cancer. However, there are conditions in which surgery is not suitable, for example in elderly or high-risk patients and those who do not wish to undergo the procedure. This study presents a case series of 8 patients with unresected breast cancer who were administered hormonal therapy as an optional treatment. Patients included in the study were diagnosed with Stage I-III breast cancer from 2012 to 2015 at our institution. The patients were administered hormonal therapy for an average duration of 20.1 months. Complete responses were seen in 4 patients, while 1 and 3 patients were noted to have a partial response and stable disease, respectively. No disease progression was seen in any patients during the study period. Endocrine therapy may be an effective and safe option for patients with unresected breast cancer.

Renal Failure Without Hemodialysis Is a Risk Factor for Postoperative Complications in Colorectal Cancer Surgery.

Background/Aim: Surgical outcomes of colorectal cancer (CRC) in patients with renal failure (RF) remain to be clarified. The objective of this research was to investigate how RF impacts the surgical outcomes in patients with CRC. Patients and Methods: A retrospective analysis was performed on clinical data from 633 patients who underwent colorectal resection for CRC between January 2017 and December 2021. Outcomes of the patients with and without RF were compared. RF was defined as estimated Glomerular Filtration Rate less than 30. Results: Forty-five (7%) patients with RF were identified. RF was a significant risk factor for postoperative complications after colorectal cancer surgery (odds ratio=2.19, 95% confidence interval=1.08-4.42, p=0.0284). The patients with RF had significantly more comorbidity (p=0.016), and higher American Society of Anesthesiologists physical status (p<0.01). Hemoglobin level (p<0.01) and PNI (p<0.01) were significantly lower in those with RF. Postoperative complications were significantly higher (p=0.016), and the postoperative hospital stay was significantly longer (p<0.01) among patients with RF compared to those without RF. Patients with RF, excluding those undergoing hemodialysis, had significantly more complications compared to those without RF (p=0.004). Conclusion: Careful attention should be paid to perioperative management in RF colorectal cancer patients.

[A multicenter study of epirubicin-docetaxel(ET)as primary chemotherapy for patients with inflammatory breast cancer(IBC)].

We evaluated the efficacy and safety of the epirubicin plus docetaxel(ET)regimen, which is a combination of active agents given to patients with inflammatory breast cancer(IBC)as a primary therapy. Nineteen patients received ET(60, 60mg/m2) every 3 weeks for 4 courses, and appropriate surgery was offered unless disease progression occurred. Seventeen patients completed the ET regimen and 1 patient was excluded because of no diffuse erythema, leaving 18 patients evaluable for the response and safety profile of this regimen. Grade 3/4 hematological toxicities were neutropenia in 15 patients(79%), febrile neutropenia in 8 patients(42%)and anemia in 3 patients(16%). Six patients(63%)received granulocyte colony-stimulating factor for febrile neutropenia. Febrile neutropenia was observed only for 1 course in all 6 patients and progression to apparent infection was not observed. Grade 3/4 non-hematological toxicities were constipation in 3, nausea in 2, anorexia in 2, fatigue in 1, vomiting in 1, diarrhea in 1, and stomatitis in 1 patient. The ET regimen was given to 16 patients(89%)as planned. The median number of courses was 4(range: 2-4). The clinical response rate was 44%. The median time to progression was 9 months, and median overall survival was 26 months. It is concluded that the ET regimen was well tolerated and effective as a primary chemotherapy for IBC.

Objective response with lapatinib in patients with meningitis carcinomatosa derived from HER2/HER1-negative breast cancer.

A 45-year-old woman with HER2(-)/HER1(-) breast cancer underwent radical mastectomy, followed by radiation and chemotherapy. However, her symptoms progressed rapidly owing to meningitis carcinomatosa and she was fitted with a urethral catheter. She also had difficulty in walking. However, immediately after treatment with lapatinib, her symptoms almost completely disappeared. The catheter was removed and she no longer needed a wheelchair. Unfortunately, after treatment was stopped, the bilateral upper limb skin metastases reappeared, the brain metastases relapsed, and she again experienced symptoms of meningitis carcinomatosa. Lapatinib was restarted, resulting in an immediate improvement in the symptoms and a reduction in the skin and brain metastases. Immunohistochemical staining of the lapatinib-sensitive metastatic skin tumor showed it to be HER2(2+), FISH(-)/HER1(-). This result suggested that the lapatinib-sensitive lesions in the brain and meninges were also HER2-positive. Carcinomatosa meningitis has a very poor prognosis and no effective treatment has yet been developed. Here, we report the first case in which lapatinib has been used to effectively treat meningitis carcinomatosa in HER2(-)/HER1(-) relapsed breast cancer.

Clinical significance of CEA and CA19-9 in postoperative follow-up of colorectal cancer.

BACKGROUND: We evaluated the efficiency of CEA and CA19-9 as tools for diagnosing recurrence in the postoperative surveillance of colorectal cancer. MATERIALS AND METHODS: A total of 227 patients who underwent curative resection for colorectal cancer between 1999 and 2003 at our hospital received complete follow-up according to the schedule determined prospectively. Using receiver operating characteristic (ROC) analysis, performance of postoperative values of CEA or CA19-9 for detecting recurrence was assessed. RESULTS: The sensitivity (1.000) and specificity (0.978) of the postoperative values of CEA in the high preoperative CEA group were very high. Even in the normal preoperative CEA group, the area under the curve (AUC) of the ROC curve of CEA (0.740, 95% confidence interval [95% CI], 0.628-0.852) was significantly larger than 0.5 (P < 0.001). The postoperative values of CA19-9 showed high sensitivity (0.833) and specificity (0.900) in the high preoperative CA19-9 group, while the AUC of the ROC curve of the normal preoperative group was as small as 0.510 (95% CI, 0.376-0.644). In the high preoperative CA19-9 group, however, there was no significant difference between the AUC of CA19-9 (0.904, 95% CI, 0.786-1.000) and that of CEA (0.869, 95% CI, 0.744-0.994) (P = 0.334). CONCLUSIONS: The measurement of CEA is an efficient way to detect recurrence. The efficiency of measuring CA19-9 for the purpose of detecting recurrence is low, especially in patients with a normal level of preoperative CA19-9. Even in patients with a high preoperative level of CA19-9, CEA might be able to fill the role of CA19-9.

Infectious complications after gastric cancer surgery accelerate a rapid hepatic recurrence.

BACKGROUND/AIMS: Rapid hepatic recurrence is sometimes experienced after gastric or pancreatobiliary cancer surgery. The aim of this study was to investigate the risk factors for the timing of hepatic recurrence. METHODOLOGY: The medical records of 20 patients who had hepatic recurrence after either a gastrectomy for gastric cancer (11 patients) or a pancreatoduodenectomy for pancreatobiliary cancer (9 patients) between 2002 and 2007 were retrospectively reviewed. The cumulative recurrence rate of liver metastasis was calculated using the Kaplan-Meier method, and 14 possible factors affecting the rapid hepatic recurrence were analyzed by univariate and multivariate analyses. RESULTS: The median time for the hepatic recurrence after the operation was 4.9 months (range 1 to 20.4 months). Among 14 factors, only postoperative infectious complications significantly accelerated the hepatic recurrence based on a univariate analysis (p = 0.049). Two more factors, gastric cancer and preoperative tumor marker elevation, had a tendency to affect the rapid recurrence, but did not show statistical significance (both p = 0.06). A multivariate analysis revealed that postoperative infectious complications (p = 0.005) and gastric cancer (p = 0.04) were significant and independent factors. Five of 11 patients with gastric cancer suffered from postoperative infectious complications, 4 of which were associated with pancreatic leakage after a pancreatosplenectomy, and all 5 patients had hepatic recurrence within 3 months after the operation. CONCLUSIONS: Postoperative infectious complications are thus considered to accelerate a rapid hepatic recurrence after a gastrectomy for gastric cancer.

[Complete response obtained with first-line therapy as S-1, followed by second-line 5'-DFUR plus paclitaxel therapy in a patient with multiple liver and lymph node metastases from gastric cancer].

A 82-year-old man with advanced gastric cancer underwent distal gastrectomy in January 2006. The histological diagnosis was poorly-differentiated adenocarcinoma, T2(MP), pN2, sH0, sP0, CY0; fStage III A. Three months after the operation, two metastatic nodules were noticed on the liver. The patient was treated with S-1 in April 2006. After the 8 courses of S-1 treatment, a complete response was achieved. However, a lymph node metastasis was newly found adjacent to the remnant stomach 2 months after the complete response to S-1. 5'-DFUR+paclitaxel combination therapy was then performed. After the 2 courses, the metastatic lymph node completely disappeared. We continued a total of 18 courses of the 5'-DFUR+paclitaxel therapy approximately for 1 year without critical drug toxicity. The patient has been alive without any recurrent site. Thus 5'-DFUR+paclitaxel as a second-line therapy following S-1 should be recommended for a gastric cancer patient with a recurrent tumor.

Expression of the hMLH1 gene is a possible predictor for the clinical response to 5-fluorouracil after a surgical resection in colorectal cancer.

The loss of a DNA mismatch repair occurs in approximately 15% of sporadic colorectal cancer (CRC) and is usually caused by the lack of expression of the hMLH1 gene due to promoter methylation. Despite undergoing adjuvant 5-fluorouracil (5-FU) therapy after a curative surgical resection, some patients with advanced-stage CRC develop recurrence. In the present study, we investigated whether the hMLH1 mRNA expression or promoter methylation is a prognostic factor in CRC patients treated with adjuvant 5-FU. The hMLH1 mRNA expression levels were measured by quantitative reverse transcription PCR in cancer and normal epithelial cells that were obtained from 94 CRC patients using a laser capture microdissection. Then, the methylation status of the hMLH1 promoter in the CRC tissues was examined by methylation-specific PCR. The hMLH1 mRNA expression levels were significantly lower in the cancer cells than in the normal mucosa (p<0.01) and the hMLH1 mRNA expression levels in the cancer cells were significantly lower in the CRC tissues with methylated versus unmethylated hMLH1 (p<0.01) in the 94 patients. Among the 35 patients receiving adjuvant 5-FU, the disease-free survival rate was significantly better in the patients demonstrating a low hMLH1 mRNA expression in the cancer cells in comparison to that of the patients with a high hMLH1 mRNA expression (p<0.01). Moreover, a multivariate analysis revealed that hMLH1 mRNA expression was a significant independent prognostic factor for tumor recurrence in CRC patients treated with adjuvant 5-FU. However, hMLH1 methylation was not correlated with the survival in these 35 patients. These data suggest that the hMLH1 mRNA quantitation in colorectal cancer cells may be helpful for evaluating the prognosis of CRC patients receiving 5-FU-based adjuvant chemotherapy after a surgical resection.

Helicobacter pylori infection is an independent risk factor for Runx3 methylation in gastric cancer.

Runx3, a member of the human runt-related transcription factor family, is known as a possible tumor suppressor gene for gastric cancer. Runx 3 expression is frequently suppressed by the promoter hypermethylation in gastric cancer cell lines and tissues. However, the precise mechanism of the induction of Runx3 methylation, which is considered to be a critical step in gastric carcinogenesis, remains to be elucidated. In the present study, we evaluated runx3 gene methylation in 57 resected early gastric cancer specimens. Then, we correlated Runx3 methylation in the cancer tissue specimens with clinicopathological factors as well as the mucosal backgrounds, such as intestinal metaplasia surrounding the cancer cells and Helicobacter pylori (H. pylori) infection. Runx3 methylation was observed in 30 of the 57 (52.6%) cancer specimens, whereas methylation was detected in 10 of the 57 (17.5%) corresponding non-cancerous mucosae. In comparison to the clinicopathological factors, Runx3 methylation was significantly correlated with both age and tumor location. A multivariate analysis demonstrated that age and tumor location as well as H. pylori infection were independent risk factors for Runx3 methylation. We demonstrated for the first time that H. pylori infection contributes to Runx3 methylation in gastric cancer tissues. When a persistent infection by H. pylori continues in the middle/lower stomach for a long period, Runx3 methylation may be induced and the subsequent loss of Runx3 expression may therefore affect gastric carcinogenesis.

Comparison of the efficacy of granulocyte and monocyte/macrophage adsorptive apheresis and leukocytapheresis in active ulcerative colitis patients: a prospective randomized study.

BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory bowel disease associated with recurring inflammation of the colorectal mucosa. Recently, cytapheresis has emerged as a new treatment for patients with UC. Removal methods are mainly performed with beads [granulocyte and monocyte/macrophage adsorptive apheresis (GMCAP)] or filters [leukocytapheresis (LCAP)]. Both treatments have been reported to be effective for active UC. There have been few trials, however, comparing the efficacy of GMCAP and LCAP. In this study, we prospectively evaluated the efficacy of LCAP and GMCAP for the treatment of active UC. METHODS: Thirty-nine patients [18 male, 21 female; mean age 38.7 years; duration of disease 6 years; clinical activity index (CAI) >6 points] with moderate-to-severe active UC were randomly assigned to the LCAP (n=21) or GMCAP group (n=17). Adacolumn (cellulose acetate beads; Japan Immunoresearch Laboratories, Takasaki, Japan) for GMCAP and Cellsorba EX (polyethylene phthalate fibers; Asahi Medical Co. Ltd, Tokyo, Japan) for LCAP were used for leukocyte removal. Patients received two sessions of cytapheresis in the first week, followed by four weekly administrations. Steroid doses were tapered if patients achieved clinical improvement. When the CAI score had decreased by 5 points or more, the patient was considered to have improved. RESULTS: Thirteen patients in the GMCAP group and 14 in the LCAP group achieved clinical improvement. No significant difference was found in clinical response and clinical course between LCAP and GMCAP. Hemoglobin levels were significantly decreased immediately after one session of cytapheresis in the LCAP group. No severe adverse effects were observed in any of the patients. No significant differences were observed in any clinical parameters predictive of a response to either LCAP or GMCAP. But in all patients receiving cytapheresis, a high CAI score was a significant risk factor for treatment failure. All of the cytapheresis nonresponders had CAI scores >or=16. CONCLUSION: Both GMCAP and LCAP were effective treatments for active UC. Patients with severe UC and a high CAI score were, however, refractory to treatment.

Quantitative double-fluorescence immunohistochemistry (qDFIHC), a novel technology to assess protein expression: a pilot study analyzing 5-FU sensitive markers thymidylate synthase, dihydropyrimidine dehydrogenase and orotate phosphoribosyl transferases in gastric cancer tissue specimens.

To evaluate the protein expression level in formalin-fixed cancer tissue specimens, the authors devised quantitative double-fluorescence immunohistochemistry (qDFIHC). Using this method, the 17 gastric cancer biopsy specimens, before undergoing S-1 based neoadjuvant chemotherapy, were assessed in order to determine the expression levels of the thymidylate synthase (TS), orotate phosphoribosyltransferase (OPRT) and dihydropyrimidine dehydrogenase (DPD) which determines S-1 efficacy. The ratios of OPRT/TS, OPRT/DPD and OPRT/(DPD+TS) which have been proposed to show a good correlation with S-1 efficacy, were calculated and compared with the clinical response. A significant difference was thus observed in OPRT/TS (P=0.0049), OPRT/DPD (P=0.0067) and OPRT/(DPD+TS) (P=0.0013) between the responder and the non-responder groups. Therefore, the ratios assessed by qDFIHC may be a potentially effective predictor of the S-1 efficacy. Furthermore, qDFIHC may also be a useful method for assessing various protein levels in cancer tissues.

Successful wound management for infected perineum in recurrent rectal cancer by a two-step operation using muscle flaps: a case report.

Perineal wound failure associated with infection is one of the intractable complications after abdominoperineal resection including pelvic exenteration. It is supposed that there is a strong possibility of this complication occurring in patients with infected perineal lesions after radiation therapy. We describe herein a case of a 56-year-old female who received pelvic exenteration for recurrent rectal cancer, the perineal wound of whom was successfully managed by a two-step operation using muscle flaps. The patient had a recurrent tumor in her pelvis after abdominoperineal resection for locally advanced rectal cancer. She had been treated with chemoradiotherapy for the recurrent tumor. The tumor was exposed to the perineum and was associated with bacterial infection. The tumor was curatively resected by total pelvic exenteration. The perineal wound infection was controlled by a lay-open method after reconstruction of the pelvic floor using a rectus abdominis muscle. The perineal wound was secondarily closed using gracilis mycocutaneous flaps 14 days after pelvic exenteration. She was discharged uneventfully 14 days after perineal closure. The strategy in the present report may be a useful option for perineal wound management in patients with a high risk of perineal wound failure due to infection after abdominoperineal resection.

Comparison of the postoperative outcome after a pancreatoduodenectomy using the Billroth I and II type of reconstruction.

BACKGROUND/AIMS: Several types of gastrointestinal reconstruction have been employed after a pancreatoduodenectomy (PD), however, it remains controversial as to which type is the most beneficial. The aim of this study was to investigate the effects of a gastrointestinal reconstruction on the postoperative outcome after PD. METHODOLOGY: The medical records of 68 patients who underwent a PD between 1994 and 2004 were retrospectively reviewed. A total of 28 patients underwent a Billroth I reconstruction while 40 had the Billroth II reconstruction. Both the occurrence of postoperative complications and the nutritional status were compared between the two groups. RESULTS: The patient age, gender, preoperative symptoms, and operation profiles were the same between the two groups. The morbidity and mortality did not differ between the two groups; however, the prevalence of leakage after a hepaticojejunostomy was higher in the Billroth II group than that in the Billroth I group (23% vs. 0%, P = 0.007). All cases of bile leakage were successfully treated by conservative therapy. The day that oral intake was resumed and the length of the hospital stay also did not differ between the two groups. Both groups showed a similar postoperative nutritional status after a PD, as assessed by body weight, the serum albumin and cholesterol concentrations, and the number of lymphocytes. CONCLUSIONS: Bile leakage tends to occur after a PD using a Billroth II reconstruction, however, this can be easily managed by conservative therapy, and it does not influence morbidity, the resumption of oral intake, or the length of hospital stay. Therefore, we could not clearly identify any advantages of one group or another in terms of postoperative complications and the nutrition status after PD. Further investigations from other points of view are therefore necessary to clarify the effect of a gastrointestinal reconstruction after PD.

Significance of pancreatic exocrine function in the perioperative management of pancreatoduodenectomy.

BACKGROUND/AIMS: The significance of pancreatic exocrine function in the perioperative management of pancreatoduodenectomy (PD) has not been well understood. The aim of this study was to clarify this issue. METHODOLOGY: Clinical records of 60 Japanese patients who underwent PD were reviewed retrospectively. Patients were divided into two groups, normal (n=33) and low (n=27) pancreatic exocrine function, according to the preoperative value of N-benzoyl-L-tyrosyl-p-aminobenzoic acid excretion test (normal value >70%). We compared the perioperative events and nutritional status between the two groups. RESULTS: The preoperative and operative characteristics between the two groups were not significantly different. Postoperative pancreatic juice output from the remnant pancreas during the initial 7 days after PD was greater (1145 +/- 618 vs. 741 +/-612mL, P=0.02), and the prevalence of pancreatic anastomotic leakage was higher (10/23, 30% vs. 1/27, 4%, P=0.008) in the group with normal pancreatic exocrine function than that in the insufficient group. Perioperative body mass index and serum albumin concentration, which reflect the nutritional status of patients, were significantly lower in the group with low pancreatic exocrine function (P=0.007 and 0.04, respectively). CONCLUSIONS: Surgeons should pay more attention to pancreatic anastomotic leakage in patients with normal pancreatic exocrine function after PD. On the other hand, in patients with insufficient exocrine function, perioperative nutritional support should be considered.

Asymptomatic adenocarcinoma arising from a gastric duplication cyst: A case report.

INTRODUCTION: Duplication of the alimentary tract is a relatively uncommon congenital anomaly and most cases occur in childhood. Malignancy arising from a gastric duplication cyst is extremely rare. We herein report a very rare case of malignant transformation of a gastric duplication cyst. PRESENTATION OF CASE: A 47-year-old asymptomatic Japanese woman was referred to our hospital with a large abdominal mass adhered to the stomach. Since there was a possibility of malignant transformation, complete resection of the cyst and segmental gastrectomy without regional lymphadenectomy were performed. DISCUSSION: To our knowledge, this is the 2nd report of asymptomatic adenocarcinoma arising from a gastric duplication cyst in the English-language literature. Unfortunately, the patient developed peritoneal metastasis and ascites seven months after the surgery and died. CONCLUSION: From our long-term follow-up experience of this gastric duplication cyst, we recommend making accurate diagnosis as soon as possible with biopsy using endoscopic ultrasonography. When the disease is diagnosed as malignant, we recommend gastrectomy with lymphadenectomy. Even if the disease is diagnosed as benign, we recommend close observation with imaging modalities.

Differential expression of Janus kinase 3 (JAK3), matrix metalloproteinase 13 (MMP13), heat shock protein 60 (HSP60), and mouse double minute 2 (MDM2) in human colorectal cancer progression using human cancer cDNA microarrays.

In this study, we applied commercially available cDNA microarray systems (1068 genes) to investigate the genetic changes in six colorectal cancers (CRC). Thirty-two genes fell into the group of commonly upregulated genes. In addition, we immunohistochemically investigated the expression of the four top ranked upregulated genes, Janus kinase 3 (JAK3), matrix metalloproteinase 13 (MMP13), heat shock protein 60 (HSP60), and mouse double minute 2 (MDM2), in 44 CRC. JAK3 staining was located in the cancer cells. A comparison of JAK3 immunostaining and clinicopathological parameters showed a significant association of tumor differentiation, pT, and TMN stage. Staining of MMP13 and HSP60 was noted mainly in the cytoplasm of cancer cells. A significant association of these expressions was observed with tumor differentiation and pT. MDM2 staining was noted in the nucleus of cancer and non-cancer cells. No significant association of clinicopathological parameters with MDM2 expression was observed. In multivariate analysis, JAK3 immunoreactivity showed independent prognostically unfavorable predictors. These data suggest that JAK3, in particular, is a highly significant, prognostic immunohistochemical marker in CRC. This study proves that cDNA microarrays, plotted by a small number of genes from a few samples, are both practical and useful.

Modification of lymph node dissection for colon cancer by clinical diagnosis.

BACKGROUND/AIMS: Less invasive procedures for colon cancer that are available now increase the needs of modified lymph node dissection. The aim of the present study is to establish oncologically safe criteria for modifying lymph node dissection for colon cancer by clinical diagnosis. METHODOLOGY: We evaluated the central extent of lymph node metastasis in 276 patients who underwent curative surgery for colon cancer according to clinicopathologic factors and analyzed the accuracy of clinical assessment of the factors. RESULTS: Only the degree in depth of invasion determined the maximum extent of lymph node metastasis. None of pTis-pT2 tumors showed metastasis to nodes along the main vessels including apical nodes, demonstrating that patients with pTis-pT2, but not pT3-pT4, tumors could be candidates for modified lymph node dissection. While the accuracy in clinical assessment of depth for pTis, pT1, and pT2 tumors was only 59.1%, 73.7%, and 53.6%, respectively, none of the clinically assessed as Tis or T1 tumors was finally diagnosed as a pT3-pT4 tumor. On the other hand, 30.8% of T2 tumors were revealed to be pT3 tumors. CONCLUSIONS: Modification of lymph node dissection by clinical diagnosis should be performed for Tis-T1 but not for T2-T4 tumors when bowel resection is performed.

CpG island methylation of BNIP3 predicts resistance against S-1/CPT-11 combined therapy in colorectal cancer patients.

Aberrant gene methylation is frequently observed in various cancers and plays an important role in carcinogenesis, cancer progression and drug responsiveness. The aim of this study is to identify colorectal cancer specific gene methylation determining chemosensitivity to S-1/CPT-11 therapy. The gene methylation of CHFR, p16, RUNX3, E-cadherin, MGMT, hMLH1, ABCG2, UGT1A1 and BNIP3 genes were analyzed in 27 colorectal cancer tissues by quantitative methylation-specific PCR (q-MSP). All 27 patients were postoperatively treated by S-1/CPT-11 therapy targeting the metastatic lesion and the recurrent tumor. Thereafter, the patients were divided into a responder group (RG) or a non-responder group (NRG) according to the effect of the chemotherapy. There were 13 cases of RG (48.1%) and 14 cases of NRG (51.9%). The methylation level in CHFR, RUNX3 and BNIP3 was significantly higher in cancer lesions in comparison to the non-cancerous lesion. Only methylation of the BNIP3 gene was significantly higher in primary cancer tissue of the NRG than the RG. The correlation between the BNIP3 methylation status and time to progression (TTP) suggested that the low methylation group (n=16) resulted in a significantly longer TTP, in comparison to the high methylation group (n=11; P=0.004). The methylation level of BNIP3 showed a significant inverse correlation with the mRNA expression suggesting the DNA methylation suppressed BNIP3 expression (r=-0.466, P=0.021). In conclusion, BNIP3 gene methylation is a possible marker predicting a poor response to the S-1/CPT-11 combined therapy in colorectal cancer.

A long-time survivor of alpha-fetoprotein-producing gastric cancer successfully treated by fluoropyrimidine-based chemotherapy: a case study.

A 67-year-old male with advanced gastric cancer and lymph node metastasis as well as a tumor embolus in the portal vein was treated by S-1/cisplatin therapy. The serum alpha-fetoprotein levels were elevated to 836 ng/ml at the first visit. After one course of chemotherapy, the patient showed stable disease; the serum level of alpha-fetoprotein also decreased to 626 ng/ml after a transient increase, and therefore reduction surgery was performed. A total gastrectomy with a distal pancreatectomy, splenectomy, and regional lymph node dissection was performed. The resected specimen was diagnosed to be alpha-fetoprotein-producing gastric cancer. There were no metastatic foci in the resected lymph nodes, presumably due to the preoperative chemotherapy. S-1/cisplatin therapy was continued after the operation to treat the remaining tumor embolus in the portal vein. After one course of this therapy, the tumor embolus disappeared. However, a lymph node measuring 1.5 cm in diameter appeared in the hepatoduodenal ligament. Therefore, the chemotherapy was changed to paclitaxel monotherapy. After 2 courses of paclitaxel monotherapy, the lymph node swelled, and thus 5'-deoxy-5-fluorouridine was added to the paclitaxel regimen. After 5 courses of this regimen, the lymph node swelling disappeared without any other new lesions and a total of 21 courses were performed. The patient remained stable for over 8 years without recurrence. The expression of chemoresistance-related proteins was retrospectively analyzed by immunohistochemistry to evaluate the chemoresistance. The ortate phosphoribosyltransferase expression was strongly positive, and the good outcome in this case may have been associated with this result.