Colorectal adenocarcinoma, the most common tumor that metastasizes to the ovary, is often difficult to distinguish from primary ovarian mucinous adenocarcinoma (POMA). Obtaining the correct diagnosis is difficult but crucial to treatment and prognosis.

We evaluated the immunohistochemical (IHC) expression of cytokeratin 7 (CK7), cytokeratin 20 (CK20), CDX2, CEA, MUC2, MUC5AC and -methylacyl-CoA racemase (AMACR) in 22 POMAs and 41 metastatic colorectal adenocarcinomas (MCAOs) involving ovaries.

MCAOs, in contrast with POMAs, were almost always negative for MUC5 (97.6%), often negative for CK7 (82.9%), focal or diffuse positive for CDX2 (73.2%), diffuse positive for CK20 (65.9%), focal or diffuse positive for MUC2 (51.2%), diffuse positive for CEA (41.5%) and negative for AMACR (41.5%). We therefore considered CK7 (–), CK20 (diffuse +), CDX2 (+) and MUC2 (+) to be colonic markers and regarded cases with expression of more than two colonic markers as MCAO, those with no expression of colonic markers as POMA and those with expression of one colonic marker as indeterminate. Using CK7/CK20/CDX2/MUC2, 82.5% of the cases were correctly classified, 6.3% were misclassified and 6.3% were indeterminate.

CK7, CK20, CDX2 and MUC2 IHC staining is a useful adjunctive diagnostic tool to differentiate MCAOs from POMAs, in addition to clinical history and gross and microscopic findings.

We retrospectively evaluated long-term oncological outcomes in patients with germ cell tumors (GCTs) primarily treated at our institution and assessed late recurrence and second primary malignancies.

This study included a total of 139 males with newly diagnosed GCTs of the testis or extragonadal origin who received treatment, including surgery, chemotherapy and radiation therapy, at our hospital between 1980 and 2005. We reviewed late recurrence that occurred at least 2 years after the initial disease-free status and secondary malignancies as well as oncological outcomes.

In patients with seminoma, 5-year progression-free survival and cause-specific survival rates were 87.2% and 100% for Stage I, 88.9% and 100% for Stage II, and 50.0% and 50.0% for Stage III, respectively, whereas in those with non-seminomatous GCTs, they were 79.1% and 96.3% for Stage I, 89.5% and 89.4% for Stage II, and 85.7% and 78.4% for Stage III, respectively. Late recurrence was found in five (3.6%) patients and all of them responded to salvage treatment and achieved disease-free status. Second primary hematological neoplasms occurred in three (2.2%), although they had a long-term free of the primary disease. All died of the second primary disease.

Late recurrence was successfully managed with appropriate treatments, although its incidence was not negligible. Periodic follow-up may be necessary for >5 years in patients with GCTs for early detection of late recurrence. In addition, care should be taken to watch for the development of life-threatening second primary malignant disease during long-term follow-up.

This study aims to assess the efficacy and safety of sunitinib in Japanese patients with metastatic renal cell carcinoma (RCC).

Fifty-one Japanese patients with prior nephrectomy, 25 treatment-naive patients (first-line group) and 26 cytokine-refractory patients (pretreated group) were enrolled in this phase II trial. Patients received sunitinib 50 mg orally, once daily, in repeated 6-week cycles (4 weeks on treatment, 2 weeks off). The primary endpoint was RECIST-defined objective response rate (ORR) with tumour assessments every 6 weeks via computed tomography or magnetic resonance imaging. Toxicity was assessed regularly. In the primary efficacy analysis of the intent-to-treat (ITT) population, ORR and 95% confidence interval were calculated based on independent review. Secondary time-to-event endpoints, such as progression-free survival (PFS), were estimated using the Kaplan–Meier method.

In the ITT population, ORR was 48.0% in the first-line group (after a median 4 cycles), 46.2% in the pretreated group (5 cycles) and 47.1% overall, with median times to tumour response of 7.1, 10.7 and 10.0 weeks, respectively. Median PFS was 46.0, 33.6 and 46.0 weeks, respectively. The most common treatment-related grade 3/4 adverse events and laboratory abnormalities were fatigue (20%), hand-foot syndrome (14%) and hypertension (12%), decreased platelet count (55%), decreased neutrophil count (51%), increased lipase (39%) and decreased lymphocyte count (33%).

In Japanese patients with RCC, sunitinib is consistently effective and tolerable with similar risk/benefit as that in Western patients, though there was a trend toward greater antitumour efficacy and higher incidence of haematological adverse events in Japanese patients.

Although the surgical–pathological classification can be considered the ‘gold standard' of T-N staging, it could not provide satisfactory and accurate estimation of survival rates in early-stage non-small cell lung cancer (NSCLC).

In our study, the expression of carcinoembryonic antigen (CEA), p53 and intracytoplasmic keratin (AE1/AE3) using haematoxylin–eosin (HE) staining negative lymph nodes (LNs) in 28 patients with early-stage NSCLC were analysed using fluorescent quantitation reverse transcription–polymerase chain reaction (FQ–PCR) and immunohistochemistry (IHC).

One hundred and ninety-three LNs were analysed. Two patients staged as I up-staged to II, and six patients staged as II up-staged to III. About 32, 19 and 36 LNs were positive, respectively, for CEA mRNA (32/193, 16.6%), p53 (19/193, 9.84%) and AE1/AE3 (36/193, 18.65%) compared with control LNs. Only FQ–PCR test for CEA mRNA could detect micrometastases in stage I NSCLC patients with N0 LNs (2/13, 15.4%). Disease-free time in patients with CEA mRNA (P = 0.000), p53 protein (P = 0.013) and AE1/AE3 (P = 0.003) positive were significantly inferior to those with micrometastases negative. Moreover, the results demonstrated that the positive LNs for CEA mRNA (P = 0.028), p53 protein (P = 0.048) and AE1/AE3 (P = 0.007) were associated with the relapse time, respectively. However, Cox proportional hazards test showed that only clinical stage was the independent risk factor of relapse, and denied the correlation between micrometastases in LNs and recurrence.

Detection of CEA mRNA, p53, AE1/AE3 in HE-negative LNs may improve veracity of N staging and predict its prognosis in patients with early-stage NSCLC. Furthermore, micrometastases in stage I may be performed by FQ–PCR more sensitive than IHC.

We aimed to understand the biology of osteosarcoma of the flat bone, which is a rare tumor entity.

Cases with osteosarcoma of the flat bone were compared with those of the extremity in order to evaluate their clinicopathologic characteristics. And the influences of heterogeneous treatment modalities on outcome were analyzed.

Tumors of the flat bone comprised 91 (11.3%) of 806 osteosarcoma cases. Eight cases were secondary osteosarcoma associated with previous radiotherapy. Patients with a flat bone tumor were significantly older and more likely to present with metastases at diagnosis than extremity tumor. The proportions of female sex and chondroblastic subtype were higher among flat bone tumors than among extremity tumors. The 5-year overall survival and event-free survival rates were 35.2 ± 5.4% and 24.7 ± 5.5%, respectively. Although age and histologic response to pre-operative chemotherapy were not related to outcome of flat bone tumors, treatment modality influenced the survival. Patients treated surgically had better outcomes than those treated by another means. Radiation therapy did not appear to be an effective local control measure as surgery.

Treatment outcome of the tumor of the flat bone was worse than extremity tumors. Further studies are needed to identify effective local control measures that can substitute for surgery and to determine the biologic characteristics of osteosarcoma of the flat bone.

The role of pelvic lymphadenectomy in patients with lymph node-negative bladder cancer at radical cystectomy (RC) has not yet been examined in detail. We retrospectively reviewed patients who underwent RC with pelvic lymphadenectomy for bladder cancer from January 1987 to March 2008.

We identified consecutive data on 169 patients who underwent RC for bladder cancer. The mean follow-up was 64 months (range: 1–253 months). Node-positive status (pN(+)) was seen in 16 patients and 91 were diagnosed as node-negative (pN(–)). The lymph node status of the remaining 62 patients was unclear (pN(x)). We analysed the association between lymph node status and cancer-specific survival (CSS), and examined the role of the number of retrieved lymph nodes, particularly in pN(–).

The median number of retrieved nodes was 12.9 and 10.2 for stage pN(+) and stage pN(–), respectively. In 91 patients with pN(–), multivariate analysis revealed that pathological T3-4 (P = 0.0276) and less than nine retrieved lymph nodes (P = 0.0108) were independent risk factors for CSS. In a subgroup of 83 patients with pT3-4, Kaplan–Meier curves showed that the 5-year CSS rate in pN(–) patients with less than nine retrieved lymph nodes was 38.8%, which was extremely similar to the 40.8% in pN(+) and 45.1% in pN(x).

Our results demonstrate that at least nine lymph nodes should be removed to improve the survival of pN(–) patients at RC and lymphadenectomy, and would provide information not only on prognosis but also on the therapeutic impact on pT3-4 invasive bladder cancer.

Capecitabine is effective and well tolerated in patients with anthracycline- and/or taxane-pre-treated metastatic breast cancer. We compared the efficacy and safety of capecitabine monotherapy between 1st, 2nd, 3rd and ≥4th line settings for advanced and metastatic breast cancer pre-treated with/without anthracycline and taxanes.

Subjects comprised 84 patients with histologically confirmed advanced or metastatic breast cancer and at least one measurable metastatic lesion. We evaluated time to disease progression (TTP), response rate (RR) and clinical benefit rate (CBR) for 1st (n = 17), 2nd (n = 28), 3rd (n = 23) and ≥4th (n = 16) line setting treatments of capecitabine monotherapy.

Median number of cycles of capecitabine monotherapy was 12 cycles in 1st line, 11 cycles in 2nd line, 9 cycles in 3rd line and 11 cycles in ≥4th line. RR and CBR were 23.5% and 58.8% in 1st line, 21.4% and 53.6% in 2nd line, 21.7% and 52.2% in 3rd line, and 18.8% and 50.0% in ≥4th line, respectively. No significant differences in TTP were seen between each line setting (P = 0.843).

Capecitabine monotherapy is effective and well tolerated in all line settings of chemotherapy in patients with metastatic or advanced breast cancer, and is suitable for outpatient therapy.

Metaplastic breast carcinomas (MBC) are a rare type of breast cancer and are generally characterized by hormone receptor and human epidermal growth factor receptor 2 (HER2) negativity. There is a paucity of information on prognosis according to hormone receptor and HER2 expression for these rare tumors. The aim of this study was to compare the clinical features and prognosis between triple-negative metaplastic carcinoma (TNMC) and non-triple-negative metaplastic carcinoma (NTNMC).

We retrospectively analyzed MBC patients treated at Seoul National University Hospital between 1996 and 2006. The medical records were reviewed.

Fifty-one patients were identified. At a median follow-up of 40.8 months, the 3-year disease-free survival (DFS) and overall survival (OS) rates were 75.5% and 86.3%, respectively. Non-triple negativity (P = 0.012) correlated significantly with OS in multivariate analysis. Of the 51 patients, 41 (80.4%) had TNMC and 10 (19.6%) had NTNMC. The two groups did not differ significantly by age, tumor size or nodal status. In patients with NTNMC, the positivity rates for estrogen receptor, progesterone receptor and HER2 were 20.0%, 30.0% and 80.0% in NTNMC. The 3-year OS rates in patients with TNMC and NTNMC were 93.4% and 58.2%, respectively (P = 0.007). With respect to DFS, there was no statistically significant difference between patients with TNMC and those with NTNMC (P = 0.149).

In MBC, the non-triple-negative group had a poor prognosis compared with the triple-negative group, which is contrary to what has been reported in patients with invasive ductal carcinoma of breast. Further research exploring the mechanism underlying this result is needed.

In this study, we compared the pharmacokinetic profiles of 5-fluorouracil (5-FU), tegafur, 5-chloro-2,4-dihydroxypyridine (CDHP) and potassium oxonate (Oxo) after administration of S-1 at 35 or 40 mg/m² bid for 28 consecutive days, in Cycles 1 and 3, in patients with advanced gastric cancer.

Three patients were enrolled for each dosage. S-1 dosage was assigned based on body surface area (BSA), which is different from the Japanese dosing system. The median daily dose per BSA was 76 mg/m², ranging from 70 to 88 mg/m².

Plasma levels of 5-FU, tegafur, CDHP and Oxo at 4 h post-dose reached steady-state on day 8. The estimated steady-state level was dependent on S-1 dosage. There were no intercyclic differences of pre-dose and 4 h post-dose levels between Cycles 1 and 3, implying no cumulative effect of S-1 was shown probably due to 2-week drug-resting period. Pharmacokinetic profiles on day 28 were similar to previous Japanese report. C_max and AUC_{0–48 h} values of each S-1 component increased depending on S-1 dosage. Pharmacokinetic parameters were not correlated with tumor response or toxicity.

We suggest that these pharmacokinetic profiles of Asian population could provide a basis for schedule optimization and for additional studies on interaction with other antitumor drugs.

To evaluate the effectiveness of vaginal misoprostol in overcoming an unsatisfactory colposcopy in the patients who had abnormal cervical cytology and to evaluate side effects of vaginal misoprostol.

Sixty patients with an unsatisfactory colposcopy during the period of September 2007–November 2008 were recruited and randomly allocated to receive either two tablets of 200 µg misoprostol (400 µg) or two tablets of similar-looking placebo vaginally. Colposcopic re-examination was performed ~6 h later. The results and side effects before and 2 weeks after the colposcopic re-examination were recorded.

Six out of 30 patients in the misoprostol group (20.0%) had a satisfactory colposcopic re-examination compared with 2 out of 27 patients (7.4%) in the placebo group without statistically significant difference (P = 0.172). Three patients in the placebo group dropped out due to not present at the appointment time. Six out of 30 patients (20.0%) and 1 out of 30 patients (3.3%) in the misoprostol group had side effects before and 2 weeks after the colposcopic re-examination orderly. Twenty-seven patients in the placebo group did not have any side effects before and 2 weeks after the colposcopic re-examination. All side effects occurred were minimal and well tolerated.

Four hundred micrograms of vaginal misoprostol were not proved to be effective in converting an unsatisfactory to a satisfactory colposcopy.

The objective of this study was to evaluate the efficacy and toxicity of docetaxel in combination with prednisolone in Japanese patients with hormone refractory prostate cancer.

Twenty patients with hormone refractory prostate cancer (HRPC) were administered a treatment regimen consisting of docetaxel 75 mg/m² once every 3 or 4 weeks and prednisolone 5 mg twice daily at our institution between 2006 and 2008.

The patients received a median of 5.5 cycles of treatment (range, 2–11 cycles). Nine of the 20 patients (45%) had a ≥50% decrease in serum prostate-specific antigen (PSA). The median duration of response was 4 months (range, 1–12 months). The number of cycles performed, the presence of bone metastasis and the extent of disease had statistically significant associations with the response. Three patients had a transient PSA rise among the patients who ultimately had a response. Grade 3/4 leukopenia and neutropenia occurred in 80.0% and 85.0% of the patients, respectively. Interstitial pneumonia occurred in only one patient; however, the patient recovered. Finally, no treatment-related deaths were seen during the observation period.

The combination of docetaxel 75 mg/m² every 3 weeks and prednisolone 10 mg daily was effective and well tolerated in Japanese patients with HRPC. The results of this study suggest that a decision concerning discontinuation of this treatment should be carefully considered because a transient PSA rise was observed. Although interstitial pneumonia was rare, the potential risk of its development should be taken into consideration.

The aim of this study was to analyze the clinical results of our adaptive radiation therapy scheme of a two-step intensity-modulated radiotherapy (IMRT) method for nasopharyngeal cancer (NPC) at Kinki University Hospital.

Between 2000 and 2007, 35 patients with Stage I–IVB NPC treated by IMRT were included. For all patients, treatment-planning computed tomography was done twice before and during IMRT to a total dose of 60–70 Gy/28–35 fractions (median 68 Gy). Chemotherapy (cisplatin 80 mg/m²/3 weeks x 1–3 courses) was given concurrently with IMRT for 31 patients.

The 3- and 5-year overall survival rates for the 31 patients treated with concurrent chemotherapy were 88% and 83%, respectively. The 3- and 5-year loco-regional control rates for the 31 patients were 93% and 87%, respectively. Planning target volume delineation for the primary site or involved nodes was insufficient for three early cases, resulting in marginal recurrence in the three patients (9%). Except for one patient with early death, xerostomia scores at 1–2 years were: Grade 0, 11; Grade 1, 17; Grade 2, 5; Grade 3, 1.

Excellent overall survival and loco-regional control rates were obtained by a two-step IMRT method with concurrent chemotherapy for NPC, although marginal recurrence was noted in some early cases.

Patients with T1G3 bladder cancer are at high risk of progression to muscle-invasive cancer, and early cystectomy is considered as a treatment option in this particular situation. On the other hand, understaging of T1G3 bladder cancer has been gradually proven as second or repeat transurethral resection (TUR) has been widely applied. To evaluate the real rate of progression, we investigated the prognosis of T1G3 bladder cancer in which a muscle layer was histologically confirmed in the TUR specimens.

We retrospectively reviewed 48 patients with primary T1G3 bladder cancer in which a muscle layer in the TUR specimens was confirmed between 1990 and 2006 in our institute. We investigated recurrence and progression in 45 patients, excluding 3 who were immediately treated with radical cystectomy. Fifteen and 12 patients received intravesical treatment with bacillus Calmette–Guérin (BCG) and anticancer agents just after TUR, respectively. The remaining 18 did not have any such treatment.

Recurrence and progression were observed in 21 (47%) and 3 patients (6.7%), respectively, during a median follow-up period of 42.1 months. The 3-year recurrence-free and progression-free survival rates were 54% and 91%, respectively. No significant differences were observed in the rates between the patients with and without BCG treatment in the study.

There is a possibility that the progression rate in patients with T1G3 bladder cancer is not as high as previously reported when only patients whose muscle layer was histologically confirmed were analyzed. An adequate technique for TUR that unmistakably collects the muscle layer may be important to predict the outcome accurately.

The optimal management of elderly patients with limited-disease small cell lung cancer (LD-SCLC) has not been established.

The records of elderly (≥70 years of age) patients with LD-SCLC who had been treated with etoposide and cisplatin chemotherapy with early concurrent twice-daily thoracic radiotherapy (TRT) were reviewed retrospectively.

Of the 25 elderly patients with LD-SCLC identified, 12 (48%) individuals received etoposide–cisplatin chemotherapy with early concurrent twice-daily TRT. The main toxicities of this treatment regimen were hematologic, with neutropenia of Grade 4 being observed in all patients and febrile neutropenia of Grade 3 in eight patients during the first cycle of chemoradiotherapy. The toxicity of TRT was acceptable, with all patients completing the planned radiotherapy within a median of 29 days (range, 19–33). No treatment-related deaths were observed. The median progression-free survival and overall survival times were 14.2 months (95% confidence interval, 4.3–18.2) and 24.1 months (95% confidence interval, 11.3–27.2), respectively.

Etoposide–cisplatin chemotherapy with early concurrent twice-daily TRT was highly myelotoxic in elderly patients with LD-SCLC, although no treatment-related deaths were observed in our cohort. Prospective studies are required to establish the optimal schedule and dose of chemotherapy and TRT in such patients.

Autofluorescence imaging (AFI) videobronchoscopy is a new endoscopic tool that improves visualization of neoplastic changes in the bronchial mucosa. The major aim of our study was to determine sensitivity and specificity of the technique in the assessment of tumor extent (margins). The secondary objective was to evaluate the possible effect of AFI on the change in therapeutic decisions of lung cancer treatment.

In this prospective trial, we enrolled 104 patients in whom we performed 624 targeted biopsies, 3 from the pathologically altered mucosa (red-brownish or magenta colored) and 3 from randomly picked normal areas. We were using the Olympus BF-F260 videobronchoscope and EVIS LUCERA system. White light videobronchoscopy (WLB) preceded AFI examination and biopsy collection. All biopsy specimens were examined by a pathologist blinded to bronchoscopy findings, and where applicable surgically resected specimens were examined.

In 14.4% of the patients, AFI revealed a greater extent of the tumor than WLB, and in 11.5% that finding led to change in therapeutic decision (lesser or greater resection or avoidance of surgery). We found a significant correlation between tumor extent determined by AFI and changes in therapeutic decisions (P < 0.01). Sensitivity, specificity, positive predictive value and negative predictive value for AFI in the assessment of tumor extension were 93%, 92%, 92% and 93%, respectively. Corresponding results for WLB were 84%, 79%, 77% and 85%, respectively. Relative sensitivity of AFI is 1.11.

Our results confirm that AFI videobronchoscopy significantly improves the assessment of central lung cancer extension and influences the therapeutic strategy. This technique has greater sensitivity and specificity, in assessment of tumor margins, than WLB alone.