[Five Cases of Breast Cancer Developed after Silicone Breast Implant].

We report 5 cases of breast cancer that developed after cosmetic augmentation using silicone breast implants. The chief complaints were breast tumor in 3 cases, skin change in 1 case, and nipple bleeding in 1 case. Intervals between silicone breast implants and breast cancer surgeries ranged from 10 to 31 years. The pTNM stages included were Stage 0, Ⅰ, ⅡA, ⅢB, and Ⅳ, respectively, and the subtypes included were 3 Luminal types and 2 Luminal-HER2 types. Silicone bag rupture was noted in 1 case, and all bags were removed during surgery. The breast cancer surgeries performed were four breast- conserving surgeries and one mastectomy. The follow-up period ranged between 1.8 and 14 years(mean 5.1 years). All cases survived, but 2 cases had recurrences; the Stage ⅢB case experienced lung metastasis 2 years postoperatively and Stage Ⅳ case had induced pCR by chemotherapy postoperatively, but therapeutic self-interruption led to recurrences at the contralateral axillary nodes and contralateral breast and lung metastases 3 years postoperatively. Judging from limited reports of breast cancer after silicone breast implant in Japan, their incidence seems to be extremely low, and the incidence in our clinic during these 15 years(5 out of 1,851 primary breast cancers)is 0.27%.

[Nine Cases of Pregnancy and Delivery after Breast Cancer].

The present study reviewed 9 cases of pregnancy and delivery after breast cancer in our clinic, between 2007 and 2019, to evaluate treatment options for their safe and successful management. The mean age at primary surgery was 31.7 years(27- 37); the study included 1, 5, 2, and 1 cases of pTNM Stage 0, Ⅰ, ⅡA, and ⅡB, respectively. The pregnancies were allowed after at least 1 year since completion of treatment to wash out chemotherapy or endocrine therapy agents. There were a total of 17 natural pregnancies, including 15 natural deliveries and 2 spontaneous abortions. Four patients achieved 1 birth, 4 achieved 2 births, and 1 achieved 3 births. The mean age at the first delivery after surgery was 36 years(30-40), and the highest age at the last delivery was 45 years. The molecular subtypes of breast cancer involved included 5 Luminal types, 1 Luminal-HER2 type, 1 HER2-enrich type, and 2 triple-negative types. The mean interval between the primary surgery and the first delivery was 4.3 years(3-6). Six patients were disease-free, and 3 patients experienced recurrences. Among the 3 patients with recurrence, 1 patient suffered from a local recurrence 43 months after the surgery; it was successfully resected, and she delivered 2 children after the second surgery and is now disease-free. One patient delivered 2 children after surgery; 12 years after surgery, she suffered from bone metastasis, but fortunately, endocrine therapy plus zoledronic acid treatment induced complete remission. One patient achieved pregnancy 4 years after the surgery and routine examination demonstrated the liver and bone metastases. The patient safely delivered at 9th-month pregnancy; the metastases and recurrences were treated chemo-endocrine therapy, and the patient is currently doing well. In conclusion, although the present study includes only 9 patients with 15 births, it suggests that a safe and successful pregnancy and delivery can be achieved through a variety of patient-orientated post-surgical treatment options that consider fertility preservation.

[Clinical Impact of First Metastasis Sites and Subtypes in the Outcome of Brain Metastases of Breast Cancer].

Brain metastasis(BM)is the final stage of metastatic breast cancer(MBC), but its course and outcomes after the first metastasis(FM)to various sites are not fully clarified. Furthermore, the survival of patients with BM appears to be improving with the recent development in MBC control according to the subtype analysis. The present study included 35 patients with BM between 2008 and 2018, and was designed to clarify the effects of the FM sites and subtypes on the outcome of these patients. Subtypes included 8 Luminal(L), 8 L-HER2+(LH), 8 HER2(H), and 11 triple-negative(TN)types, and FM sites included 14 lungs or pleurae, 4 livers, 4 brains, 4 bones, and 9 local or lymph node(LN)metastases. The median interval between FM and BM(IFB)was 33 months(M)for overall patients; 50M for LH, 37M for L, 22M for H, and 19M for TN (p=0.0463); and 24M for the high risk(HR)FM(lung, pleura, liver)and 47M for the low risk(LR)FM group(bone, local, LN)(p=0.0385). The median overall survival(OS)after BM diagnosis was 13M for overall patients; 27M for LH, 13M for H, 10M for L, and 5M for TN(p=0.0112). There were no significant differences in the OS after BM diagnosis between HR FM and LR FM patients. Multivariate analyses for OS after BM revealed that patients with HER2(+)and estrogen receptor(+) tumors had a significantly better survival(risk ratio[RR]=0.644, p=0.0413; RR=0.290, p=0.0251, respectively). Three patients are surviving longer than 10 years after BM, including 2 with L-type and 1 with LH-type tumors, and their FM sites were 1 local, 1 brain, and 1 liver. The present study indicated that subtypes and FM site(HR or LR)had significant impact on the clinical course and prognosis of patients with BM. Focusing on the subtypes and FM site can improve the early detection and treatment results of BM.

[Radiation-Associated Angiosarcoma That Developed in the Irradiated Residual Breast after Breast-Conserving Surgery for Breast Cancer-A Case Report and Review of the Literature].

We report a radiation-associated angiosarcoma(RAAS)of the breast, which is a rare but important complication after breast-conserving surgery(BCS)and radiotherapy(RT)for breast cancer. A7 2-year-old woman had undergone BCS for invasive ductal carcinoma of the right breast(pT2pN1M0, StageⅡB), followed by RT of 50 Gy; she was treated with doxifluridine and anastrozole for 5 year. She noticed a bloody cutaneous bulla in the right breast 64 months later, and the skin lesions gradually expanded. She was brought to our clinic for the treatment of massive bleeding from the skin lesions. Ulcer biopsy revealed cutaneous AS(cells were CD31[+], CD34[+], VEGF[-], and VEGF-R[+]). She underwent mastectomy and latissimus dorsal flap surgery. She died of local recurrence and liver metastasis 13 months later. RAAS is rare, but it should be considered in patients with skin lesions, such as erosion and bloody bulla, after BCS and RT for breast cancer. To our knowledge, only 12 cases of RAAS, including the present case, have been reported in Japan, and we reviewed the Japanese RAAS cases in comparison with those reported in the Western literature.

[A Retrospective Analysis on Comparative Treatment Results for Breast Cancer between Elderly Women Aged 70 and More Than 80 Years].

This study compared the treatment results of over 80-year-old(O-80) 54 and 157 septuagenarian(70s)women with breast cancer(BC)from 1996 to 2015, to clarify the best treatment option for O-80BC patients. No differences were observed in the stages and subtypes. More than 70% of women in both groups underwent breast-conserving surgery(BCS), and 48.1% and 12.1% of O-80BC and 70sBC patients did not undergo axillary dissection, respectively. About 3.2% and 18.5% of 70sBC and O-80BC patients did not receive adjuvant therapies, respectively. Most ER-positive patients in both groups received endocrine therapy. Most patients in both groups received no intravenous chemotherapy; however, oral chemotherapy was administered in 80.3% of 70sBC and 64.8% of O-80BC patients. Approximately 75.2% of 70sBC and 11.1% of O-80BC patients received post-surgical radiotherapy(RT). No differences in both relapse-free survival and overall survival (OS)rates were observed between the 2 groups. Breast cancer-related death(57.1%)and natural death from old age (57.1%)were the most commonly observed cause of death in the 70sBC and O-80BC groups, respectively. Multivariate analyses on OS demonstrated that BCS and intravenous chemotherapy were significantly associated with poor prognosis and RT was significantly associated with better prognosis in 70sBC group, whereas BCS was significantly associated with better prognosis in O-80BC group. In conclusion, surgery, especially BCS, plays an important role in the primary treatment of O- 80BC patients; however, axillary dissection, RT, endocrine therapy, and chemotherapy cannot be performed.

[Third- and Fourth-Line Chemotherapies including Paclitaxel and Bevacizumab for Metastatic Breast Cancer].

The present study was designed to estimate the clinical efficacy of bevacizumab(BV)combined with paclitaxel(PTX)(BVPTX) as third- and fourth-line therapies in 31 patients with metastatic breast cancer(MBC). Most patients were previously treated with docetaxel and/or epirubicin. Patients were intravenously treated with BV at 5-10mg/kg and PTX at 3-5mg/kg at 2-3week intervals, and when the effect of BV-PTX was low, other chemotherapeutic agents(CTAs)and/or trastuzumab (Tr)were additionally administered. Twelve MBC patients were treated with BV-PTX alone and 19 MBC patients were treat- ed with other CTAs and/or Tr in addition to BV-PTX. No serious adverse events were observed in any regimen. Three complete responses(9.7%), 4 partial responses(12.9%), 8 stable diseases(25.8%), and 16 progressive diseases(51.6%)were observed; the response rate was 22.6%, and the clinical benefit rate was 48.4%. The median progression-free survival(PFS) and median overall survival(OS)after the initiation of BV-PTX were 7.0 and 16.0 months, respectively. All 13 HER2-positive MBC patients were treated with Tr in addition to BV-PTX, and the OS and PFS were significantly higher in the BV-PTX+Tr+ CTAs group than in the BV-PTX+Tr group. In 18 HER2-negative MBC patients, PFS and OS were better in the BV-PTX+CTAs group than in the BV-PTX alone group, though this difference was not significant. Multivariate analyses demonstrated that an additional CTAs was a variable for significantly better PFS, and additional CTAs, Tr, and endocrine therapy were significant variables for better OS. These results indicated that additional CTAs and Tr should be combined with BV-PTX for third- and fourth-line chemotherapies.

[A Multivariate Analysis of the Efficacy of Adjuvant Chemotherapy in Triple-Negative Breast Cancer].

Triple-negative breast cancers(TNBCs)are associated with early recurrence after surgery and unfavorable prognoses. To date, no effective therapies for TNBCs have been established. The present study was designed to evaluate the efficacy of adjuvant chemotherapy(ACT)for 111 TNBCs using a retrospective multivariate analysis(MVA). The intravenous(iv)ACTs included docetaxel, epirubicin, gemcitabine, and vinorelbine. The oral ACTs included UFT, doxifluridine, and cyclophosphamide. The 10-year disease-free survival(DFS)and overall survival(OS)rates were 77.5% and 86.0%, respectively. Recurrences were observed in 17 patients, and the first recurrence was most frequently located in the lung. MVA revealed that pT was a significant independent variable for poor DFS and OS. UFT was the only significant independent variable for improved DFS. The survival analysis also demonstrated that UFT alone may be an effective option for Stage I TNBCs. Furthermore, it suggested that the addition of further iv ACTs to UFT could improve the outcome in patients with Stage II-III TNBCs.

A rare case of non-invasive ductal carcinoma of the breast coexisting with follicular lymphoma: A case report with a review of the literature.

The double presentation of breast cancer and follicular lymphoma is extremely rare, and only six cases have previously been reported in the literature. In the present study, a case of synchronous ductal carcinoma in situ (DCIS) of the breast and follicular lymphoma is reported. During an annual breast screening procedure, a 49-year-old female presented with a hard induration under the nipple of the right breast and swelling of a soft lymph node (LN) in the right axilla. Mammography and ultrasonography revealed two lesions in the right breast: One was a tumor with microcalcification, 1.0 cm in diameter, and the other was a large, crude calcification, 2.5 cm in diameter. In addition, computed tomography and positron emission tomography revealed swellings of the bilateral axillary (Ax) LN and intra-abdominal para-aortic LN. The patient underwent excisions of the large calcified mass, a micro-calcified tumor and the right AxLN. The pathological and immunohistochemical studies revealed fat necrosis and DCIS of the breast, which was positive for the estrogen receptor and the progesterone receptor, while human epidermal growth factor receptor II protein expression was evaluated as 2+ and stage was classified as pTis pN0 M0, stage 0. Furthermore, the Ax node was diagnosed as follicular lymphoma, which was positive for cluster of differentiation (CD)20, CD79a, CD10 and B-cell lymphoma (Bcl)-2 protein, but negative for Bcl-6 protein. The clinical stage was classified as stage III. The patient was administered chemotherapy followed by radiotherapy to the conserved breast. Two years have passed since the surgery, and the patient is disease-free.

Lymphoepithelioma-like carcinoma of the breast: a case report with a special analysis of an association with human papilloma virus.

UNLABELLED: Lymphoepithelioma-like carcinoma (LELC) of the breast is a very rare tumor, and fewer than 20 cases have been reported. A recent report suggested the implication of human papilloma virus (HPV) in the pathogenesis of breast LELC. We report a case of LELC of the breast with a review of its relevance to an association with HPV. A 45-year-old female patient presented with a solid mass in the outer-upper part of her left breast, which was diagnosed as malignant (ductal carcinoma) by fine-needle aspiration cytology. The patient underwent a quadrantectomy of the breast and axillary sentinel node biopsy. Pathological examination revealed cohesive sheets or nests of malignant epithelial cells, with unclear circumscription in a background of diffuse lymphoid infiltration; the postsurgical clinical stage was pT1pN0M0, stage 1. Immunohistochemistry demonstrated that the tumor was triple negative and basal-like breast cancer. In the present case in situ hybridization demonstrated positive HPV signals in a few tumor cells; however, polymerase chain reaction study failed to detect HPV in tumor cells. CONCLUSION: To the best of our knowledge, this is the second report on HPV infection associated with breast LELC.

Ductal carcinoma in situ arising within a benign phyllodes tumor: A case report with a review of the literature.

Phyllodes tumor (PT) is a rare type of breast tumor that rarely occurs with breast carcinoma. This study evaluated a 53-year-old female patient with a benign PT with ductal carcinoma in situ (DCIS) within the tumor. A firm, painless, well-demarcated tumor measuring 4-5 cm was noted in the left breast. Over the course of the previous 14 years, the patient underwent excision of a breast tumor four times at the same site in the left breast. The pathological diagnosis of the first tumor was a fibroadenoma (FA), and those of the following three were benign PTs. The tumor was the 5th one noted over the course of the previous 14 years, following the previously recorded surgeries. A firm tumor with a diameter of 3.5 cm was located beneath the scar from the previous surgery, just above the nipple of the left breast. Mammography revealed a high-density irregularly shaped mass with a clear margin. An ultrasound showed low but heterogeneous echogenicity. A computed tomography scan revealed a well-defined enhanced tumor. These image examinations were compatible with recurrent PT. Fine-needle aspiration cytology revealed that the tumor was likely a benign FA. The patient underwent a partial mastectomy with a 1.0 cm margin from the tumor edge, and the firm, attached scar tissue was also resected. Macroscopic examination showed a hard elastic mass, which was encapsulated by thin fibrous tissue and which adhered firmly to the adjacent scar tissue. Microscopic examination showed a 5 mm in diameter DCIS of the cribiform type in a section of the PT epithelial component with an apparently benign stroma. The DCIS cells were strongly positive for estrogen and progesterone receptors, but HER2 expression was negative (score 0). The patient received local irradiation following surgery and no evidence of recurrence or metastasis was detected in the 2 years following surgery. This was a noteworthy case of a DCIS arising in benign PT. To the best of our knowledge, a total of 28 breast carcinomas were previously reported to arise in PT. In this case report, a female patient who presented with a PT was evaluated. A review of the literature is also discussed.

Placement of an expandable metallic stent improves the efficacy of chemoradiotherapy for pancreatic cancer with malignant portal vein stenosis or obstruction.

BACKGROUND: Advanced or recurrent pancreatic cancer can sometimes cause obstruction or stenosis of the portal vein (PV), resulting in various symptoms of portal hypertension (PH), such as ascites, pancytopenia, hemorrhagic tendencies and liver dysfunction. We placed an expandable metallic stent into the PV to improve PH-associated complications and liver function. The placement of the PV stent was beneficial for administering chemotherapeutic agents and radiotherapy (RT) safely, and resulted in an improved response rate (RR) and survival. PATIENTS AND METHODS: In the present study, 14 patients with malignant portal obstruction due to advanced or recurrent pancreatic cancer received PV stent placement to manage their PH-associated symptoms. After a mini-laparotomy at the ileocecal region, the ileocecal vein was cut and an expandable metallic stent (6-8 mm in diameter and 6-8 cm in length) was inserted into the PV under image roentgenography. After placement of the PV stent, the patients received anti-coagulation treatment with heparin and biaspirin for 1-3 months. All patients received chemotherapy with UFT, cyclophosphamide (CPA) and gemcitabine (GEM), and 11 patients also received RT. RESULTS: The RR was 43% (3 complete (CR), 3 partial (PR), 3 stable disease (SD), and 5 progressive disease (PD)), and the mean survival times (MST) after the initiation of therapy or placement of the PV-stent were 12.6 and 9.5 months, respectively, while the 1-year survival rates were 54.5% and 35.1%, respectively. In the 3 CR patients, 2 died of carcinomatous ascites 13 and 21 months later, and 1 is still disease free. In the PR and SD patients, pain and PH-associated symptoms such as ascites and hyperglycemia were also improved. CONCLUSION: The placement of a PV stent is beneficial for improving PH-associated symptoms as well as facilitating chemo-RT and the efficacy of therapy.

High incidence of synchronous or metachronous breast cancer in patients with malignant and benign thyroid tumor or tumor-like disorders.

BACKGROUND: Although many reports indicated an association between thyroid diseases and breast cancer, such an association still remains controversial. The present study was aimed to clarify the association of thyroid diseases with the breast cancer incidence. In the patients with benign and malignant thyroid tumor or tumor-like disorders, the incidence of other malignancies was surveyed, and the frequency of thyroid cancer in patients with breast cancer was also surveyed. PATIENTS AND METHODS: Between 1982 and 2005, a total of 201 female patients received surgery for tumor or tumor-like disorders, including 65 carcinoma, 68 adenoma, 61 adenomatous goiter and 7 chronic thyroiditis cases. Their outcomes were surveyed in December 2006. Furthermore, during the same periods, 340 female patients underwent breast cancer surgery and their outcomes were also surveyed in December 2006. RESULTS: The overall incidence rate of breast cancer was 16.4% (33/201) in the patients, who received thyroid surgeries and was much higher than other malignancies: 2.0% gastric cancer, 1.0% uterine and colorectal cancer. The incidence rate of breast cancer in each disease was 13.8% for thyroid cancer, 16.2% for adenoma and 21.3% for adenomatous goiter, but no incidence for chronic thyroiditis. On the other hand, in the patients with breast cancer during the same period in our department, the frequency of thyroid cancer was only 2.1% (7/340). CONCLUSION: It appears that thyroid cancer, adenoma and adenomatous goiter were associated with the risk of breast cancer, but chronic thyroiditis was not related.

GEP100 links epidermal growth factor receptor signalling to Arf6 activation to induce breast cancer invasion.

Epidermal growth factor (EGF) receptor (EGFR) signalling is implicated in tumour invasion and metastasis. However, whether there are EGFR signalling pathways specifically used for tumour invasion still remains elusive. Overexpression of Arf6 and its effector, AMAP1, correlates with and is crucial for the invasive phenotypes of different breast cancer cells. Here we identify the mechanism by which Arf6 is activated to induce tumour invasion. We found that GEP100/BRAG2, a guanine nucleotide exchanging factor (GEF) for Arf6, is responsible for the invasive activity of MDA-MB-231 breast cancer cells, whereas the other ArfGEFs are not. GEP100, through its pleckstrin homology domain, bound directly to Tyr1068/1086-phosphorylated EGFR to activate Arf6. Overexpression of GEP100, together with Arf6, caused non-invasive MCF7 cells to become invasive, which was dependent on EGF stimulation. Moreover, GEP100 knockdown blocked tumour metastasis. GEP100 was expressed in 70% of primary breast ductal carcinomas, and was preferentially co-expressed with EGFR in the malignant cases. Our results indicate that GEP100 links EGFR signalling to Arf6 activation to induce invasive activities of some breast cancer cells, and hence may contribute to their metastasis and malignancy.

[Evaluation of therapeutic regimens for taxane-resistant recurrent/metastatic breast cancer].

Taxanes (TX) were administered to 246 of 292 patients with recurrent/metastatic breast cancer (MBC) who were treated in Hiei Hospital between January 2001 and May 2006. Recently, TX has been increasingly prescribed for preoperative treatment and postoperative adjuvant therapy. To improve the prognosis of MBC, regimens effective for TX-resistant cancer patients should be developed. In this study, with respect to hormone receptor (HR) and Her 2/neu (HER 2), we retrospectively investigated whether our series responded to the regimens used after TX resistance was acquired. As post TX-resistance therapy (trastuzumab was combined in HER2-positive patients), 387 treatment regimens were administered to 166 patients. The following regimens achieved a response rate (patients achieving PR or CR/patients who could be evaluated) of 10% or more: combination therapy with TX and capecitabine (11/61, 18%), CPT-11 (10/57, 17.5%), vinorelbine (5/46, 10.9%), MFL-P (continuous treatment with MTX, 5-FU, LV, and CDDP) (12/47, 25.5%), and DMpC (5'-DFUR, MPA, CPA p.o.) (5/16, 31.2%). The latter 2 regimens achieved a high response rate,and some HR (-) and HER 2 (-) patients also responded to these regimens. In HR (+) or HER 2 (+) patients who responded to TX, survival was longer than that of non-responders. However, there was no difference in the treatment responsiveness of post-TX regimens between TX-responders and non-responders, suggesting the survival-prolonging effect of TX.

Expression of orotate phosphoribosyl transferase in human pancreatic cancer: implication for the efficacy of uracil and tegafur-based adjuvant chemotherapy.

The enzyme orotate phosphoribosyl transferase (OPRT) is involved in the metabolism of the anticancer drug 5-fluorouracil (5-FU), and is a key enzyme for conversion of 5-FU to its active form in tumor tissue. Little is known regarding the significance of OPRT in human pancreatic cancer. The present study was designed to assess the association between the activity of OPRT in the tumor, and the clinicopathological status and prognosis of human resectable pancreatic cancer, especially regarding its relevance to the efficacy of adjuvant chemotherapy with uracil and tegafur (UFT), cyclophosphamide (CPA) and/or gemcitabine (GEM). The present study included 99 resectable pancreatic cancers, which were all invasive ductal tubular carcinomas. OPRT was immunostained with a rabbit anti-human OPRT polyclonal antibody. OPRT was positively stained in 54 (54.5%) of 99 pancreatic cancers. The post-surgical survival rate of the OPRT (+) pancreatic cancers was significantly higher than that of the OPRT (-) ones. In the OPRT (+) group, the survival rate of the patients, who received adjuvant chemotherapy (ACT) with UFT, CPA or GEM, was significantly higher than that of the patients without ACT; however, in the OPRT (-) group, there was no difference in the survival between the ACT (+) and (-) groups. Multivariate analyses demonstrated that for all patients, primary tumor, status of nodal involvement (pN), residual tumor, level of dissection and CPA were significant variables for the prognosis: in OPRT (+) groups, primary tumor, nodal involvement, GEM and CPA were significant variables. In contrast, in the OPRT (-) group, pN was the only significant variable. The present study is the first report on the significance of OPRT in human pancreatic cancer, and the results indicate that the expression of OPRT may be useful to predict the response to adjuvant chemotherapy in human pancreatic cancer.

Cyclophosphamide augments the anti-tumor efficacy of uracil and tegafur by inhibiting dihydropyrimidine dehydrogenase.

The present study assesses the effects of neo-adjuvant chemotherapy (NAC) with uracil and tegafur (UFT) alone vs UFT plus cyclophosphamide (CPA), on the activity of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) in breast cancer tissues. Breast cancer patients were randomly assigned to 3 groups; the control (no-treatment) group (n=13), the UFT (5-8 mg/kg/day) alone group (n=10) and the UFT plus CPA (1 mg/kg/one day interval) (UC) group (n=9), and they received NAC for 2-4 weeks. A total of 32 invasive ductal breast carcinomas were used to assay for TS and DPD activity. There were no statistically significant differences in tumor size or stage classification between the 3 groups. The DPD activity was inversely and significantly correlated with the tumor size and pT, but the TS activity was not correlated with these clinicopathological factors. The TS activity was decreased by NAC with UFT, and the addition of CPA resulted in an increased inhibition of TS activity. In contrast, DPD activity was increased by NAC with UFT administration, but its increased activity was significantly inhibited by the addition of CPA. Multiple regression analyses demonstrated that the total dose of UFT was a significant variable for inhibiting TS activity, and that CPA was a significant variable for inhibiting DPD activity. The DPD activity increased by UFT can be inhibited by CPA, and this may represent one of the possible mechanisms responsible for the anti-tumor activity of 5-FU or its derivatives as enhanced by CPA.

Immunohistochemical expression of HER-1 and HER-2 in extrahepatic biliary carcinoma.

The clinicopathological significance of HER-1- and HER-2-overexpressions (OE) (HercepTest score 2+ or 3+) in biliary cancer and their relationship to the efficacy of adjuvant chemotherapy (ACT) were assessed. In 72 biliary cancer (28 gallbladder and 44 bile duct cancer), HER-1 and HER-2 were stained immunohistochemically in formalin-fixed, paraffin-embedded specimens. The ACT included uracil and tegafur (UFT)-based chemotherapies. Out of the 72 cancer, OE was observed in 31 specimens (43%) for HER-1 and 47 (65%) for HER-2. However, their OEs were not correlated with each other. HER-2-OE was inversely correlated with the clinical stage (p=0.0482). HER-1-OE was correlated with distant metastasis (p=0.0263), but not with the clinical stage. Neither the OE of HER-1 or HER-2, nor their co-expression, showed any significant effect in term of patient survival. In the HER-1-OE (-) patients, the survival rate of the ACT group was significantly higher than that of the surgery-alone (SA) group (p=0.0423), but in the HER-1-OE (+) patients, there was no statistical difference in survival rate between the ACT and the SA group. In contrast, HER-2-OE had no significant effect on the efficacy of ACT. Multivariate analysis also demonstrated that the histological grade and ACT were significant variables, but T, N, M and HER-1 and HER-2 were not significant variables. In conclusion, neither HER-1-OE or HER-2-OE were prognostic factors of the biliary cancer. However, HER-1-OE may be a useful marker for the indication of ACT.

[Pancreatic acinar cell carcinoma successfully treated with combination of oral TS-1 and intra-arterial cisplatin].

Pancreatic acinar cell carcinomas are rare, and little is reported on their chemotherapy. We report a 49-year old male patient with pancreatic acinar cell carcinoma and multiple liver metastases, which responded to oral TS-1 and hepatic arterial infusion of cisplatin. The patient underwent a partial hepatectomy, MCT abrasions and excision of the pancreatic tumor. Postoperative pathological studies revealed metastases of acinar cell carcinoma to the liver and lymph nodes; the primary lesion was undetermined. After surgery, the patient was treated with hepatic arterial infusion of cisplatin and oral TS-1. Metastatic tumors completely disappeared, and serum lipase decreased to normal levels. Abdominal CT one year after surgery revealed a pancreatic body tumor, which was surgically removed. Pathological studies showed primary pancreatic acinar cell carcinoma, while previous metastases remained under control. To summarize, TS-1 and cisplatin can be effective treatments for pancreatic acinar cell carcinomas.

[Comparison of pBcl-2 and pBax expression in primary invasive ductal pancreatic cancer between Chinese and Japanese patients].

OBJECTIVE: To clarify the clinicopathologic significance of the expression of the Bcl-2 protein (pBcl-2) and the Bax protein (pBax), and their clinical implications in Chinese and Japanese patients with human invasive ductal carcinomas (IDCs) of the pancreas. METHODS: The study included 59 Chinese and 65 Japanese patients with IDCs of the pancreas. pBcl-2 and pBax expression were immuno-stained with streptavidin-biotin (SAB) method. RESULTS: pBcl-2 (+) was seen in 35.6% of Chinese and in 23.1% of Japanese patients. pBax (+) was seen in 49.2% of Chinese and 64.7% of Japanese patients. A comparison between them showed that there were significant differences in the male patients, in the patients with the moderately differentiated cancer, and in the elderly patients (chi squared = 4.447, P = 0.035; chi squared = 4.114, P = 0.043; chi squared = 6.657, P = 0.010 respective). In both Chinese and Japanese patients, those with pBcl-2 positive expression had a significantly higher survival rate than those with negative one (chi squared = 9.99, P = 0.0016; chi squared = 7.63, P = 0.0058). The group with pBax positive expression had a significantly higher survival rate in Japanese patients (chi squared = 9.37, P = 0.0022). Japanese patients whose tumors exhibited pBcl-2 and pBax positive immunostaining survived significantly longer than Chinese patients did (chi squared = 4.48, P = 0.0342; chi squared = 5.23, P = 0.023). CONCLUSIONS: The expressions of both pBcl-2 and pBax are high found in Chinese and Japanese patients. The pBcl-2 positive expression implies a better prognosis in both Chinese and Japanese patients with IDCs of the pancreas. The effect of pBax expression on prognosis is different between Chinese and Japanese patients.

Immunohistochemical expression of receptor-tyrosine kinase c-kit protein and TGF-beta1 in invasive ductal carcinoma of the pancreas.

BACKGROUND: The receptor tyrosine kinase c-kit is known to play an important role in the progression of gastrointestinal stromal tumors, but its biological significance in other solid malignancies is unclear. Recent publications have suggested a regulatory role for TGF-beta1 in c-kit-mediated cell growth. The present study assessed the clinicopathological significance of c-kit protein (KIT) and TGF-beta1 expression in resectable invasive ductal carcinomas (IDCs) of the pancreas. PATIENTS AND METHODS: This study included 91 pancreatic IDC patients who received a pancreatectomy between 1982 and 2003. The expression of KIT and TGF-beta1 was analyzed by immunohistochemistry. RESULTS: KIT and TGF-beta1 were expressed in 77% (70/91) and 59% (54/91) of the IDC, respectively. The expression of KIT was not correlated with that of TGF-beta1. TGF-beta1 expression correlated inversely with nodal involvement, but KIT expression did not correlate with any clinicopathological factors. KIT expression had no significant influence on the survival of the patients, whereas the survival rate of TGF-beta1 (+) IDC patients was significantly higher than that of TGF-beta1 (-) IDC patients. Co-expression analysis of KIT and TGF-beta1 indicated that, in patients with KIT (+) IDC, the TGF-beta1 (+) group showed a significantly better survival rate than the TGF-beta1 (-) group. Neither KIT expression nor TGF-beta1 expression had a significant effect on the efficacy of adjuvant chemotherapy (ACT). In multivariate analysis, TGF-beta1 expression was one of the significant variables for survival in IDC patients overall, but KIT expression was not. CONCLUSION: TGF-beta1 expression is suggested to have a significant influence on c-kit-mediated cell proliferation in human pancreatic IDCs.