[A Case of Ipsilateral Breast Tumor Recurrence(IBTR)after Breast-Conserving Surgery Which Successfully Resected after Chemotherapy Using Carboplatin plus Gemcitabine].

A 39-year-old woman underwent partial mastectomy with sentinel lymph node biopsy for right triple negative breast cancer(T2N0M0, Stage ⅡA). Six months later, ipsilateral breast tumor recurrence(IBTR)was observed and paclitaxel plus bevacizumab therapy was started, but anaphylactoid symptoms appeared and the patient was discontinued. Subsequently, eribulin was started, but the IBTR was increased ineffectively. At that point, IBTR had progressed, apparently unresectable, with no distant metastases. We predicted from the patient's background that the patient may be associated with BRCA1 gene mutation and was sensitive to the platinum salts. Carboplatin plus gemcitabine was selected and 6 courses were performed. After the 6 courses, the IBTR were remarkably reduced and resectable, and mastectomy with axillary lymph node dissection were performed. One year after the operation, contralateral breast cancer develop and found to be hereditary breast and ovarian cancer syndrome (HBOC) by Genetic test. About 6 years have passed since local recurrence, but no distant metastases have been observed.

[Is the LHRH Agonist Recommended for Fertility Preservation ?].

The POEMS reportedan effect of goserelin for fertility preservation. The Clinical Practice Guideline for Breast Cancer by The Japanese Breast Cancer Society indicates that the use of the LHRH agonist (LHRHa) for preventing chemotherapy-induced early menopause is a grade C-1 recommendation, and its use for fertility preservation is a grade C-2 recommendation. Results from previous studies on the effects of LHRHa for fertility preservation have varied owing to differences in chemotherapy regimens, definitions of ovarian failure, and dosages of tamoxifen. In the POEMS, the primary endpoint of ovarian failure at 2 years was significantly lower, and the secondary endpoint of pregnancy outcomes was better in the combination group; however, precise interpretation is difficult because many cases were excluded. Currently, it is not necessary to revise The Clinical Practice Guideline; however, desirable results from future studies may allow the recommendation of a specific dosage of LHRHa for fertility preservation.

A sheet pocket to prevent cross-contamination of formalin-fixed paraffin-embedded block for application in next generation sequencing.

Formalin-fixed paraffin-embedded (FFPE) blocks are used as biomaterials for next-generation sequencing of cancer panels. Cross-contamination is detected in approximately 5% of the DNA extracted from FFPE samples, which reduces the detection rate of genetic abnormalities. There are no effective methods available for processing FFPE blocks that prevent cells from mixing with other specimens. The present study evaluated 897 sheets that could potentially prevent cell transmission but allow for the movement of various solvents used in FFPE blocks. According to the International Organization for Standardization and Japanese Industrial Standards, six requirements were established for the screening of packing sheets: 1) filter opening ≤5 µm, 2) thickness ≤100 µm, 3) chemical resistance, 4) permeability ≥1.0 × 10-3 cm/s, 5) water retention rate <200%, and 6) cell transit test (≤2 cells/10 high-power fields). Polyamide, polyethylene terephthalate, and polypropylene/polyethylene composite sheets met all criteria. A pocket, which was designed to wrap the tissue uniformly, was made of these sheets and was found to effectively block the entry of all cell types during FFPE block processing. Using a sheet pocket, no single cell from the cell pellet could pass through the outer layer. The presence or absence of the sheet pocket did not affect hematoxylin and eosin staining. When processing FFPE blocks as a biomaterial for next-generation sequencing, the sheet pocket was effective in preventing cross-contamination. This technology will in part support the precise translation of histopathological data into genome sequencing data in general pathology laboratories.

Small invasive colon cancer with systemic metastasis: a case report.

BACKGROUND: Recently, especially in Japan, several researchers have suggested that colorectal cancer can develop not only through an adenoma-carcinoma sequence but also from normal mucosa via a de novo pathway, and that these de novo cancers have more aggressive malignant potential. We report a case of aggressive colon cancer resulting in systemic metastasis despite small tumour size. CASE PRESENTATION: A 35-year-old woman presented at the referring hospital with swelling of the left cervical lymph node. Biopsy of the lymph node revealed metastatic adenocarcinoma; however, CT scan and mammography were unable to identify the site of the primary lesion. She was diagnosed with unknown primary cancer and referred to our hospital for further examination. Immunohistochemical reevaluation showed the cervical lymph node biopsy specimen to be positive for CDX2 and CK20 and negative for CK7 expression, leading us to suspect the presence of a primary colorectal cancer. We performed a total colonoscopy, and detected a small protruding lesion in the transverse colon. The tumour was only 12 mm in diameter, with a central depressed component and a severely thickened stalk, which suggested direct cancer invasion of the deep submucosa. We concluded that this lesion was the site of origin of the metastasis despite the small tumour size, and performed diagnostic endoscopic mucosal resection. The lesion was found to have an intramucosal cancer component, demonstrating that this lesion represented primary colon cancer. The patient was referred to the gastrointestinal oncology division for systemic chemotherapy. CONCLUSIONS: In this case, immunohistochemical findings strongly suggested the existence of a colorectal cancer. The non-polypoid gross appearance of the tumour suggested that it can originate de novo , thus providing a valuable case in support of the aggressive malignant potential of a de novo colorectal cancer pathway.

Cisplatin, Gemcitabine, and Paclitaxel as a Salvage Second-Line Therapy for Metastatic Germ-Cell Cancer.

BACKGROUND: Second-line salvage therapy for patients with metastatic germ-cell cancer (GCC) after the first-line combination of VIP (etoposide, ifosfamide, cisplatin) therapy has not been established. This study evaluated the efficacy and tolerability of the TGP (paclitaxel, gemcitabine, cisplatin) combination chemotherapy as a second-line salvage therapy. PATIENTS AND METHODS: The medical records of 16 consecutive patients with metastatic GCC who had been treated with first-line VIP therapy followed by second-line TGP therapy between 2005 and 2019 were reviewed and statistically analyzed. Ten patients, excluding the 6 patients treated with TGP without unequivocal progression, were included in the efficacy analysis. All 16 patients were included in the safety analysis. RESULTS: The median follow-up period from initial TGP administration was 78 months (interquartile range, 46-120 months). The estimated 5-year progression-free and overall survival rates for the 10 patients in the efficacy analysis were 70% and 100%, respectively. Grade 3/4 hematologic toxicity occurred in all 16 patients, but none developed uncontrollable infections or life-threatening bleeding. One patient died of treatment-related secondary leukemia, however. CONCLUSION: The present study is to our knowledge the first to examine the therapeutic outcomes and safety profile of second-line TGP chemotherapy. VIP followed by TGP might be an alternative first- and second-line conventional regimen for patients with metastatic GCC in this granulocyte colony-stimulating factor era, especially for patients at a high risk of bleomycin-induced pulmonary toxicity.

Influence of suboptimal treatment in patients with mediastinal primary nonseminomatous germ cell tumors.

OBJECTIVES: The aim of this study was to analyze the prognostic impact of suboptimal treatment in patients with mediastinal primary nonseminomatous germ cell tumor (MNSGCT). METHODS: We retrospectively reviewed the clinical data of 23 consecutive MNSGCT patients who were referred to the National Cancer Center Hospital between 1999 and 2007. Optimal treatment was defined as a primary chemotherapy regimen comprising a standard dosage of bleomycin + etoposide + cisplatin or etoposide + ifosfamide + cisplatin with sufficient dose intensity according to the guidelines of the European Germ Cell Cancer Consensus Group. RESULTS: Ten and 13 patients received optimal and suboptimal treatment, respectively. The progression-free survival was statistically different between the patients who received optimal and suboptimal treatment (p = 0.01), and the hazard ratio of the optimal treatment group relative to the suboptimal treatment group was 0.19 (95% CI, 0.04-0.89). Although the overall survival was not statistically different between the 2 patient groups (p = 0.12), the hazard ratio in this regard was 0.36 (95% CI, 0.10-1.38). CONCLUSIONS: Patients who receive suboptimal treatment have poor clinical outcomes. Providing treatment after considering evidence-based guidelines may be important for improving the clinical outcomes of MNSGCT patients.

Feasibility and usefulness of the 'Distress Screening Program in Ambulatory Care' in clinical oncology practice.

OBJECTIVE: Although the implementation of routine screening for distress is desirable, doing so is difficult in today's busy clinical oncology practice. We developed the 'Distress Screening Program in Ambulatory Care' (DISPAC program) as a practical means of screening for and facilitating the treatment of major depression and adjustment disorders in cancer patients. This study assessed the feasibility and usefulness of the DISPAC program in actual clinical situations. METHODS: As part of the DISPAC program, nurses administered a psychological screening measure, the Distress and Impact Thermometer (DIT), to consecutive cancer patients visiting an outpatient clinic in the waiting room. The attending physician then recommended psycho-oncology service referral to all positively screened patients. We compared the proportion of patients referred to a psycho-oncology service during the DISPAC period with the usual care period. RESULTS: Of the targeted 491 patients treated during the DISPAC period, 91.9% (451/491) completed the DIT; the results were positive in 37.0% (167/451), recommendations for referrals were given to 93.4% (156/167), and 25.0% (39/156) accepted the referral. Ultimately 5.3% (26/491) of the targeted patients were treated by psycho-oncology service as having major depression or adjustment disorders, a significantly higher proportion than during the usual care period (0.3%; p<0.001). The nurses required 132+/-58 s per person to administer the DIT. CONCLUSIONS: The DISPAC program is useful for facilitating the care of cancer patients with psychological distress. Nevertheless, the acceptance of referrals by patients and the reduction of the burden placed on nurses are areas requiring improvement.

Immunohistochemical expression of HER1, HER3, and HER4 in HER2-positive breast cancer patients treated with trastuzumab-containing neoadjuvant chemotherapy.

BACKGROUND AND OBJECTIVES: The aim of the present study was to examine the association between the expression of human epidermal receptor (HER) 1, HER3, and HER4 and pathologic complete response (pCR) in HER2-positive patients treated with trastuzumab-containing neo-adjuvant chemotherapy. METHODS: Immunohistochemical analyses of HER1, HER3, and HER4 were performed using tumor specimens obtained from patients treated with trastuzumab-containing neoadjuvant chemotherapy. The staining intensity of each biomarker was evaluated, and the correlations between the immunohistochemical profiles and pCR were examined. RESULTS: The present study included 44 patients with HER2-positive breast cancer treated with trastuzumab-containing neo-adjuvant chemotherapy. Seventeen patients achieved a pCR. The expressions of HER1, HER3, and HER4 were observed in 18.2%, 27.3%, and 18.2% of the specimens, respectively. A marginally significant negative correlation between the expression of HER1 and pCR was observed, irrespective of the expression of HER3 and HER4, whereas the expressions of HER3 and HER4 were not significantly correlated with pCR. CONCLUSION: The expression of HER1 might be an independently negative predictor of pCR in HER2-positive breast cancer patients treated with trastuzumab-containing neoadjuvant chemotherapy.

Factors that affect the duration of the interval between the completion of palliative chemotherapy and death.

BACKGROUND: The purpose of this study was to identify factors that affect the duration of the interval between the completion of palliative chemotherapy and death. METHODS: We retrospectively analyzed 255 cases in which patients had received palliative chemotherapy in the medical oncology division and died during the period 2002-2006. Univariate and multivariate analyses were performed to identify factors that affected the duration of the interval between the completion of chemotherapy and death. RESULTS: There were 133 cases of breast cancer, 77 cases of gynecological cancer, 24 cases of primary unknown cancer, and 21 cases of other cancers. The median interval between the completion of chemotherapy and death was 100 days (range, 5-1,206 days). Thirty-two patients (12.6%) died within 30 days, and 82 patients (32.3%) died within 60 days. Fifty-eight (22.7%) patients were symptomatic when chemotherapy was started, and 205 patients (80.4%) were provided information about palliative care units at the start of chemotherapy. The factors associated with a short interval between the completion of chemotherapy and death (< or = 90 days) according to the univariate analysis were male sex, young age (< or = 45 years), attending physician, poor Eastern Cooperative Oncology Group performance status score (3 or 4), obvious symptoms, and not having been given information about palliative care units. The results of the multivariate analysis indicated that young patients (< or = 45 years) who had not been referred to a palliative care unit and who had symptoms survived for a significantly shorter time interval. CONCLUSION: Young patients who were symptomatic tended to choose chemotherapy instead of entering a palliative care unit until the very near-the-end-of-life stage.

Relapse with malignant transformation after chemotherapy for primary mediastinal seminoma: case report.

This case report details a relapse with malignant transformation after the completion of bleomycin, etoposide and cisplatin chemotherapy for primary mediastinal seminoma, although the residual mass after chemotherapy was <3 cm in size and did not display an increased uptake of fluorodeoxyglucose when examined using positron emission tomography.

Immunohistochemical expression of PTEN and phosphorylated Akt are not correlated with clinical outcome in breast cancer patients treated with trastuzumab-containing neo-adjuvant chemotherapy.

The loss of PTEN and phosphorylated Akt (pAkt) expression is thought to be involved in the mechanism leading to trastuzumab resistance in patients with HER2-positive breast cancer. We retrospectively performed immunohistochemical analyses for estrogen receptor, progesterone receptor, HER2/neu, PTEN, pAkt, and p53 expression in tumor specimens obtained before and after trastuzumab-containing neo-adjuvant chemotherapy. The intensity of staining was evaluated for each biomarker, and the correlations between the immunohistochemical profiles and the clinical outcome were analyzed. The changes in the immunohistochemical profiles between specimens obtained before and after trastuzumab-containing neo-adjuvant chemotherapy were evaluated for patients with residual tumors. The present study included 44 patients with breast cancer who received trastuzumab-containing neo-adjuvant chemotherapy. Seventeen patients achieved a pathological complete response. The patients were positive for PTEN and pAkt (PTEN = 14%, N = 6/44; pAkt, 80%, N = 35/44). The expression of both PTEN and pAkt were not correlated with pathological complete response. Persistent HER2/neu over-expression after neo-adjuvant chemotherapy was significantly associated with recurrence. Among 27 patients with residual cancer, the percentages of patients with HER2/neu-positive or pAkt-positive tumors were low, but PTEN expression was elevated. The present study suggested that neither the immunohistochemical expression of PTEN nor the expression of pAkt was associated with the clinical outcome of trastuzumab-containing neo-adjuvant chemotherapy. Except among patients with pathological complete remission, the persistent over-expression of HER2/neu may be a poor prognostic factor.

Therapy-related acute promyelocytic leukemia caused by hormonal therapy and radiation in a patient with recurrent breast cancer.

We report a patient with therapy-related acute promyelocytic leukemia (APL) that may have been caused by regional radiation or hormonal therapy after surgery. A 36-year-old Japanese woman developed right breast cancer and underwent breast-conserving surgery and regional radiation to the right breast without adjuvant systemic therapy because she wished to preserve her fertility. Two years later, she developed multiple bone metastases of breast cancer and received hormonal therapy. During the second line hormonal therapy, she developed APL and received induction and consolidation chemotherapy with all-trans retinoic acid (ATRA) and a combination of anthracycline and cytarabine. After she achieved a complete remission (CR) of the APL, her bone metastases of breast cancer progressed. She received weekly paclitaxel treatments and her bone marrow function recovered. However, 9 months later, her APL relapsed; she achieved a second CR after undergoing ATRA therapy again. This patient is thought to be a rare case of secondary leukemia, since the leukemia might have been caused by hormonal therapy and regional radiation without chemotherapy.

Urachal Carcinoma with Peritoneal Dissemination Treated with Chemotherapy and Surgical Resection Leading to Prolonged Survival with No Recurrence.

A 56-year-old man was admitted to our hospital for urachal carcinoma with peritoneal dissemination. He received first-line chemotherapy with gemcitabine and cisplatin. After the fifth cycle, a computed tomography (CT) scan revealed abdominal fluid, and his serum tumor marker levels were increased. The patient was started on second-line therapy with FOLFIRI. After 11 cycles, his tumor decreased in size and no new metastatic lesions were detected. The patient underwent complete tumor resection with partial cystectomy and pelvic lymph node dissection. The tumor was removed, along with adhering surrounding organs, including the omentum, peritoneum, abdominal rectus muscle, and vermiform appendix. Although pathological examination confirmed peritoneal dissemination, his tumor markers normalized soon after surgery. The patient has survived 62 months after surgery without any adjuvant therapy and with no evidence of recurrence. To our knowledge, this is the longest duration of survival without recurrence of a patient with urachal carcinoma with peritoneal dissemination who received multimodal therapy.

A case of cisplatin-refractory advanced pure seminoma showing complete remission after treatment with high-dose carboplatin plus etoposide as fourth-line salvage chemotherapy.

We report the case of a patient who achieved complete remission (CR) of cisplatin-refractory metastatic pure seminoma after treatment with high-dose carboplatin and etoposide (CE) with peripheral blood stem cell transplantation as fourth-line chemotherapy. A 38-year-old man was diagnosed with advanced pure seminoma (pT3N3M1aS3). In the international germ cell consensus classification, his prognosis was classified as intermediate. He was treated with high-dose CE as fourth-line chemotherapy after treatment with BEP, VeIP, and TIN. After two cycles of high-dose CE, the concentrations of T-HCG and other tumor markers showed normal levels. A CT scan and PET-CT showed that the lymph node swelling had disappeared and there was no uptake. The CR has continued for 27 months after the treatment. High-dose CE might be less toxic and have a better prognostic outcome than other treatments as salvage chemotherapy for patients with cisplatin-refractory advanced testicular cancer.

Current trends and controversies over pre-operative chemotherapy for women with operable breast cancer.

The multi-disciplinary approach, including surgery, chemotherapy, endocrine therapy and radiation therapy, has become the standard treatment for primary breast cancer patients. The indication of pre-operative chemotherapy has been extended to women with potentially operable breast cancer based on the results of large randomized studies and has become an attractive option that extends the chance of breast conservation. The clinical and pathological responses to pre-operative chemotherapy correlates with long-term outcome. The anthracycline-containing regimen is now considered the standard. Sequential administration of non-cross-resistant drugs, namely taxanes, improves local tumor response but its long-term benefit has been controversial. Prediction of response to pre-operative chemotherapy still remains a challenge. Identification of useful predictive markers and development of molecular-targeted drugs is the key to individualized therapy in the future.

Tumor-marker analysis and verification of prognostic models in patients with cancer of unknown primary, receiving platinum-based combination chemotherapy.

OBJECTIVES: To evaluate the usefulness of tumor-marker measurements and to identify prognostic factors in patients with cancer of unknown primary (CUP), receiving platinum-based combination chemotherapy and to verify the adjustment of previously reported prognostic models in this population. METHODS: We conducted univariate and multivariate analyses in consecutive patients with CUP receiving platinum-based combination chemotherapy. Previously reported prognostic models were then validated in this population. RESULTS: A total of 93 patients were analyzed and the response rate to platinum-based chemotherapeutic regimens among the 93 patients was 39.8%. The median time to progression and overall survival period were 4.1 and 12.4 months, respectively. The ST-439 level was significantly higher in patients with histologically confirmed adenocarcinoma than in patients with poorly differentiated adenocarcinoma or poorly differentiated carcinoma. A multivariate analysis indicated that performance status, the number of involved organs, and the serum lactate dehydrogenase level were the prognostic factors of the outcome. Both the previously reported prognostic models for predicting the duration of survival in this population were shown to be valid. CONCLUSION: Tumor-marker measurements are not helpful in the management of patients with CUP. Previously reported prognostic models may be useful for selecting indication for chemotherapy or for stratifying the patients in clinical trial.

Correlation of p53 and MIB-1 expression with both the systemic recurrence and survival in cases of phyllodes tumors of the breast.

Phyllodes tumors are rare primary tumors of the breast. The study aimed at evaluating the immunohistochemical features of phyllodes tumors of the breast that may be useful for predicting the clinical outcome. We examined the immunohistochemical expression of the epidermal growth factor receptor (EGFR), HER2/neu, CD117/c-kit, p53, and MIB-1, and analyzed correlations between the immunohistochemical findings and the clinical outcome. The study included 41 patients with phyllodes tumor (20 benign, 5 borderline, and 16 malignant). Systemic recurrence occurred in 9 patients. The 2-year survival rate was 84%, and the 2-year recurrence-free survival rate was 77%. Six patients developed systemic recurrence within the first year after surgery. None of the phyllodes tumors was positive for HER2/neu or CD117/c-kit. Positive staining for p53 was seen in 10 phyllodes tumors (24%), and the median MIB-1 index was 10%. Both p53 expression and the MIB-1 index, but not the expression status of EGFR, were significantly correlated with the recurrence-free and overall survival. p53 expression status and MIB-1 index may be significant prognostic factors in patients with phyllodes tumors, and careful postoperative follow-up may be important in those cases showing positive expression of p53 and/or MIB-1 index.

[A feasibility study of doxorubicin/cisplatin (AP) for postoperative chemotherapy in patients with advanced endometrial cancer].

OBJECTIVE: We evaluated the feasibility of doxorubicin/cisplatin (AP) for postoperative chemotherapy in patients with advanced endometrial cancer. METHODS: Patients with newly diagnosed advanced endometrial cancer received AP (doxorubicin 60 mg/m(2), cisplatin 50 mg/m(2)) every 3 weeks. Treatment was continued until disease progression or completion of 6 courses. Toxicities were evaluated every cycle according to NCI-CTCAE Ver.3.0. RESULTS: Fifteen patients were enrolled from April 2004 through December 2005. All patients successfully completed therapy. There were two patients who needed dose reduction and nine patients with prolongation of treatment interval. Patients with over Grade 3/4 toxicity were observed to have leucopenia (47%), neutropenia (67%), anemia (26%), and vomiting (13%). No grade 3/4 cardiac and renal failure were observed. CONCLUSIONS: The doxorubicin/cisplatin (AP) regimen is tolerated and can be safely given without severe toxicity.

The incidence and management of metachronous testicular germ cell tumors in patients with extragonadal germ cell tumors.

OBJECTIVES: The optimal management of extragonadal germ cell tumor (EGGCT) and metachronous testicular germ cell tumor (MTGCT) has not been determined. PATIENTS AND METHODS: Fifty-one consecutive patients with EGGCT were identified. Testicular palpation or ultrasonography to rule out a primary testicular tumor was performed. Pretreatment testicular biopsies were not performed. The incidence and outcome of MTGCT, and the prognosis of EGGCT were evaluated. RESULTS: Twenty-five and 26 patients, respectively, had mediastinal and retroperitoneal EGGCT. Fourteen and 37 patients, respectively, had seminoma and nonseminoma. Five patients developed MTGCT in patients with retroperitoneal EGGCT. The median interval from the primary treatment for EGGCT to MTGCT diagnosis was 64 months (range 15-120). The cumulative risk of developing MTGCT was 8.3% at 6 y. Five patients underwent an orchiectomy and have survived in the 16-months median follow-up period (range 4-30). Among the patients with seminomatous and nonseminomatous EGGCT, the 5-year survival rate was 84.6% and 78.3%, respectively. Among the patients with retroperitoneal and mediastinal nonseminomatous EGGCT, the 5-year survival rate was 94.7% and 58.8%, respectively. CONCLUSIONS: The prognosis of EGGCT without testicular biopsies was sufficient. EGGCT patients, especially retroperitoneal EGGCT, need long-term follow-up for MTGCT.