Safety and effectiveness of eribulin in Japanese patients with locally advanced or metastatic breast cancer: a post-marketing observational study.

Background This large-scale study was conducted to evaluate the safety and effectiveness of eribulin for the treatment of inoperable or recurrent breast cancer in real-world settings in Japan. Methods Between July and December 2011, eligible patients with inoperable or recurrent breast cancer receiving eribulin for the first time were centrally registered and observed for 1 year. Eribulin was administered intravenously (1.4 mg/m2) on days 1 and 8 of every 3-week cycle. The primary endpoint was the frequency and intensity of adverse drug reactions (ADRs). Secondary endpoints included overall response rate (ORR) and time to treatment failure (TTF). Results Of 968 patients registered at 325 institutions, 951 and 671 were included in the safety and effectiveness analyses, respectively. In the safety population, ADRs were observed in 841 patients (88.4%). The most common (≥15% incidence) were neutropenia (66.6%), leukopenia (62.4%), lymphopenia (18.4%), and peripheral neuropathy (16.8%). The most common grade ≥ 3 ADRs (>5% incidence) were neutropenia (59.8%), leukopenia (50.5%), lymphopenia (16.1%), and febrile neutropenia (7.7%). In the effectiveness population, ORR was 16.5% (95% confidence interval: 13.7, 19.4). The median TTF was 127 days (95% confidence interval: 120, 134). Conclusions The safety and effectiveness profile of eribulin was consistent with prior studies. Eribulin had a favorable risk-benefit balance when used in real-world clinical settings.

[Laparoscopic repair of incarcerated diaphragmatic hernia as a late complication of laparoscopic right hepatectomy: a case report].

Incarcerated diaphragmatic hernia after laparoscopic right hepatectomy is very rare. An 81-year-old man underwent laparoscopic right hepatectomy for giant hepatic hemangioma. Twenty months after the surgery, he began to complain of nausea and abdominal pain and was brought to our hospital. Chest X-ray showed an abdominal gas shadow above the right diaphragm and computed tomography showed herniation of the colon into the right thoracic cavity. We diagnosed ileus due to incarcerated diaphragmatic hernia and performed emergency operation under laparoscopic surgery. After successfully reducing the prolapsed colon back to the abdominal cavity, the diaphragmatic hernia orifice was repaired. Incarcerated diaphragmatic hernia sometimes causes the fatal state. Clinicians must therefore consider such findings a late complication of laparoscopic hepatectomy.

Totally laparoscopic colectomy with intracorporeal anastomosis achieved using a laparoscopic linear stapler: experience of a single institute.

PURPOSE: Laparoscopic colonic surgery is now widely accepted. We assessed the safety and effectiveness of using a total intracorporeal surgical strategy to perform intracorporeal functional end-to-end anastomosis with an endoscopic linear stapler to treat colon cancer. METHODS: Forty-three selected patients underwent elective laparoscopic colon resection for carcinoma. A total intracorporeal colon resection was performed in all patients, using a functional end-to-end anastomosis with an endoscopic linear stapler. RESULTS: Good results were achieved in all 43 patients, none of whom required conversion to open surgery with extracorporeal anastomosis. There have been no intraoperative complications related to this technique and no instances of postoperative anastomotic leakage, intra-abdominal abscess, or wound infection. CONCLUSION: Intracorporeal functional end-to-end anastomosis using a linear stapler can be performed safely and easily for the resection of any part of the colon. We consider it an effective modality for totally laparoscopic colon resection. Favorable results have been achieved by this method, particularly for small tumors, since natural-orifice transluminal endoscopic surgery remains a challenging method to perform.

Peroral placement of a self-expandable covered metallic stent using an overtube for malignant gastroduodenal obstructions.

PURPOSE: To evaluate the technical feasibility and safety of overtube-guided covered metallic stent placement as palliative treatment for patients with inoperable malignant gastric outlet obstructions. METHODS: To relieve the symptoms of severe nausea and recurrent vomiting in five patients with inoperable gastric cancer, we used an overtube (Long overtube; Sumitomo Bakelite, Tokyo, Japan) to place large-diameter, self-expandable, covered esophageal Ultraflex stents (inner diameter 22-28 mm, length 10 or 12 cm; Boston Scientific, Watertown, MA, USA). Success was defined both technically and clinically. RESULTS: The stent placement was technically successful in all patients and resulted in improvement of symptoms in all five patients, four of whom were thereafter able to ingest solid food. The remaining patient, a 94-year-old man, was unable to ingest food because of dysmasesis. During the mean follow-up of 17 weeks, there was no stent reocclusion and no life-threatening complications developed. CONCLUSIONS: The placement of a large diameter, self-expandable, covered esophageal stent using an overtube appears to be effective for the palliative treatment of malignant gastric outlet obstruction.

Intraoperative cholangiography using an endoscopic nasobiliary tube during a laparoscopic cholecystectomy.

PURPOSE: The goals of this report are to present the characteristics of biliary complications associated with laparoscopic cholecystectomies (LC) performed at a single center, and to evaluate the efficacy of intraoperative cholangiography (IOC) using an endoscopic nasobiliary tube (ENBT) during an LC in order to prevent biliary complications. METHODS: A retrospective audit was conducted on a total of 657 patients who underwent either LC or open cholecystectomies (OC). There were 19 patients who developed bile duct injury (BDI; n = 9) or bile leakage (BL; n = 10) during an LC and were actively treated. After May of 1999, the patients with a higher risk of developing biliary complications were selected for preoperative placement of an ENBT, and IOC was performed. RESULTS: Intraoperative cholangiography using ENBT was performed on 93 (27.1%) out of 343 patients who underwent either LC or OC after May of 1999. An LC was performed in 335 cases (97.7%), and a conversion from an LC to OC was necessary in only three cases. Even though BDI never occurred, BL from the cystic duct and gallbladder bed were recognized in five cases. CONCLUSIONS: The selective use of IOC using ENBT may help to prevent BDI during LC, thereby expanding the indications for LC, while also reducing the rate of conversion to open procedures.

Laparoscopic surgery for the diagnosis and treatment of a paracecal hernia repair: Report of a case.

Internal hernias are relatively rare viscous protrusions through a defect in the peritoneal cavity. Paracecal hernia is one of the least common types, and only a few cases have been reported to date. We herein present the case of a 43-year-old woman, who was preoperatively diagnosed to have a small bowel obstruction caused by a paracecal hernia resulting from intestinal protrusion and invagination into a paracecal pouch. Laparoscopic surgery was performed for definitive diagnosis and treatment. The surgery achieved a good outcome and the patient experienced an uneventful perioperative course.

Randomized trial of cyclophosphamide, epirubicin, and fluorouracil chemotherapy compared with cyclophosphamide, methotrexate, and fluorouracil with node-positive breast cancer in Japan.

BACKGROUND: To compare the cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy and the anthracycline-containing regimen cyclophosphamide, epirubicin, and fluorouracil (CEF) to evaluate the efficacy and safety of the latter. METHODS: A total of 294 patients with axillary node-positive primary breast cancer of STAGE I-IIIa were randomly assigned to either CEF [cyclophosphamide (CPA) 500 mg/m(2) i.v. days 1 and 8; epirubicin (EPI) 60 mg/m(2) i.v. day 1; and 5-fluorouracil (5-FU) 500 mg/m(2) i.v. days 1 and 8] or CMF [CPA 500 mg/m(2) i.v. days 1 and 8; methotrexate (MTX) 40 mg/m(2) i.v. days 1 and 8; and 5-FU 500 mg/m(2) i.v. days 1 and 8]. Both treatment regimens were comprised of six cycles at 4-week intervals. Tamoxifen (TAM) 20 mg/day was concomitantly given to estrogen receptor (ER)-positive patients and those with undetermined ER status for 2 years. RESULTS: The overall 5-year survival was 77.1% for CEF and 71.4% for CMF [p = 0.24; hazard ratio 0.79 (95% CI 0.50-1.24)], and the 5-year disease-free survival was 55.7% for CEF and 48.9% for CMF [p = 0.15; hazard ratio 0.80 (95% CI 0.57-1.12)]. Although the log-rank test did not show a significant difference, both overall and disease-free survivals were higher for CEF according to the point estimates. Adverse drug reactions (ADRs) occurred more frequently in CEF. CONCLUSION: Whereas CEF had a good trend compare with CMF, it could not be proven statistically significant. The principal cause of the failure seems to be insufficient power, that is, the dose intensity (EPI: 60 mg/m(2)) set 10 years ago, when the trial began, was low, and the number of trial subjects was small because of the background of the times, which made the accumulation of cases extremely difficult. However, the trial should be considered to be meaningful, as it was the first, formally conducted controlled trial on chemotherapy in Japan.

Surgical treatment of cecal cancer in a patient with Glanzmann's thrombasthenia: report of a case.

Glanzmann's thrombasthenia (GT) is a rare inherited platelet disorder with no specific treatment. Prophylactic and therapeutic platelet transfusions work only as supportive treatments. To date, there has been no report of surgical treatment for malignant disease in GT patients. We herein report the case of a 43-year-old woman presenting with cecal cancer with accompanying GT. The patient underwent a laparotomic procedure under general anesthesia for resection of the tumor. A good perioperative course was achieved by the transfusion of ABO-identical and antihistocompatibility locus antigen-matched platelets, without causing any accidental bleeding.

Clinicopathological characteristics of recurrence more than 10 years after surgery in patients with breast carcinoma.

BACKGROUND: As most recurrences in patients with breast cancer occur in the first 5 years after surgery, recurrences more than 10 years after surgery are not very frequent, and their recurrent pattern and prognosis have not been thoroughly analyzed in the literature. PATIENTS AND METHODS: A review of 1,114 patients with breast carcinoma surgically treated between January 1980 and December 1993 was carried out. There were 284 (25.5%) patients with recurrence. Out of these 284 patients, 12 (4.4%) whose recurrence occurred more than 10 years after surgery were entered in this study. RESULTS: No prognostic factors that specifically predicted recurrence more than 10 years after surgery were identified. From the time of recurrence, the 5-year survival rate was 78.9% and 27.0% in patients with breast carcinoma recurring more and less than 10 years after surgery, respectively (p<0.01). CONCLUSION: The response rate to therapy in patients with recurrence more than 10 years after surgery is high, and such patients have significantly better prognosis compared with other patients with recurrence, which means that aggressive therapy may be appropriate management for patients with very late recurrence.

Clinical significance of Smac/DIABLO expression in colorectal cancer.

Second mitochondria-derived activator of caspases/direct inhibitor of apoptosis-binding protein with low pI (Smac/DIABLO) is released by mitochondria in response to apoptotic stimuli and is thought to regulate apoptosis by antagonizing inhibitors of apoptosis proteins, which play an important role in sensitization of cancer cells to various therapeutic regimens. The expression of Smac/DIABLO has been demonstrated in various cancer cells, though little is known about its clinical significance with respect to colorectal cancer. The current study was designed to evaluate the relationship between prognosis and Smac/DIABLO expression by clinicopathological analysis of patients with colorectal cancer. Smac/DIABLO expression was evaluated using immunohistochemical staining in 121 consecutive patients with colorectal cancer and the relationship between Smac/DIABLO expression and clinicopathological factors was analyzed. Smac/DIABLO-positive expression was detected in 80 of the 121 patients (66%). The incidence of lymph node and distant metastasis in Smac/DIABLO-negative cancer was significantly higher than that in Smac/DIABLO-positive cancer (P=0.0004 and P=0.003, respectively). While univariate analysis showed that survival in patients with Smac/DIABLO-negative expression was significantly poorer than in Smac/DIABLO-positive cases (P<0.0001), Smac/DIABLO-negative expression was a prognostic indicator independent of Dukes' staging and lymph node metastasis by multivariate analysis. This study proposes that the decrease of Smac/DIABLO expression is an independent factor determining the poorer prognosis of patients with colorectal cancer.

Primary breast lymphoma in the right breast during treatment for left breast cancer.

BACKGROUND: Primary breast lymphoma is a rare condition, and distinguishing it from breast cancer is important because their treatments differ radically. Moreover, a recent report showed that mastectomy offered no benefit in the treatment of primary breast lymphoma. CASE PRESENTATION: A 59-year-old woman was treated with adjuvant chemotherapy and local radiation after surgery for left breast cancer. She presented with a rapidly growing mass in the right breast at 20 months after surgery. Mammography and computed tomography revealed a massive tumour. She was diagnosed with primary breast lymphoma by aspiration cytology, and surgery was performed. Histopathological and immunohistochemical findings confirmed a diffuse large B-cell type primary breast lymphoma. CONCLUSION: In this case, the lymphoma exhibited rapid growth despite chemotherapy for a malignancy in the contralateral breast. The patient had developed bronchiolitis obliterans organizing pneumonia due to radiation. Therefore, surgical treatment of the lymphoma was selected.

[The safety of docetaxel with cyclophosphamide (TC) therapy as adjuvant chemotherapy for Japanese women with operable breast cancer].

The safety of docetaxel (60 mg/m(2)) plus cyclophosphamide (600 mg/m(2)) every three weeks (TC) as adjuvant therapy for Japanese women with operable breast cancer was evaluated. Ehime TC Study Group initiated the randomized control study,which compared the effects of the TC course number (4 cycles versus 8 cycles) in the adjuvant setting on the treatment outcomes of breast cancer patients. Eight patients were investigated on the side effects of TC therapy, four of them were allocated to 4 cycles of TC, and four to eight cycles from May, 2004 to Feb. 2005. Leukocytopenia and neutropenia of grade 3 or 4 were seen in 50% and 63% of the cases, respectively. No febrile neutropenia was seen. Although the non-hematological side effects of grade 3 or 4 were not observed, alopecia, stomatitis, skin toxicities and edema of grade 2 were seen in 100%, 25%, 25%, 13% of cases, respectively. TC therapy was well tolerated. All anticancer drugs could be administered as scheduled. From these preliminary results, TC therapy seems to be able to be safely prescribed postoperatively for Japanese women operated for breast cancer.

[The efficacy and safety of docetaxel for elderly advanced breast cancer patients].

We studied the efficacy and safety of docetaxel (DOC) for elderly breast cancer patients. Between September 1997 and June 2003, five consecutive women with advanced breast cancers who were 75 years of age or older received DOC at a dose of 60 mg/m(2) every three weeks. No premedications to prevent hypersensitive reactions and fluid retention by DOC were given. The number of DOC dosages per case was 5-16 times (12 times the median) and the relative dose intensity (RDI) was 80-100% (95% of medians). Objective partial responses were observed in all patients. The median time to partial response was 21 days (range: 21-50 days). The median time to treatment failure was 12 months (range: 5-22 months). The grade and the frequency of major side effects were the following: leukocytopenia of grade 3 (80%), edema of grade 2-3 (40%), and alopecia of grade 2 (100%). It was concluded from these findings that DOC could be safely and effectively administered to elderly advanced breast cancer patients.

[Efficacy of tegafur/uracil plus oral leucovorin therapy for advanced or recurrent colorectal cancer].

The aim of this study was to evaluate the efficacy of tegafur/uracil (UFT) and oral Leucovorin(UZEL) in patients with advanced or recurrent colorectal cancer. Eight patients were treated with UFT/UZEL therapy as a first-line chemotherapy. UFT(300 mg/m(2)/day) and UZEL (75 mg/body/day) were administered orally for 28 consecutive days followed by a 7-day rest period, and this schedule was repeated every 5 weeks. The mean of treatment courses given to the patients was 7.6. Tumor response was evaluated in 7 patients who had assessable lesions, and the response rate was 86% (6 PR and 1 NC). Adverse reactions of grade 3 were observed in 2 patients (25%), but toxicity did not cause a discontinuance of treatment in any case. The UFT/UZEL therapy was considered to be a promising regimen for advanced or recurrent colorectal cancer from a standpoint of effect, safety and QOL of patients.

Long-term outcome of S-1 and cisplatin combination therapy in patients with advanced or recurrent gastric cancer.

BACKGROUND: Although combination therapy of S-1 and cisplatin (CDDP) has excellent efficacy against gastric cancer, the effect of the treatment on survival has been unclear. The aim of this study was to evaluate the long-term outcome of this combination therapy. METHODS: Sixty-three patients with advanced or recurrent gastric cancer were treated with S-1, with or without CDDP, as first-line chemotherapy, and the clinical results were compared retrospectively. S-1 was administered orally at a standard dose of 80 mg/m(2). In the treatment of the S-1 group, S-1 was given for 28 consecutive days, followed by a 14-day rest. In the treatment of the S-1/CDDP group, S-1 was given for 21 consecutive days, followed by a 14-day rest, and CDDP, at 60 mg/m(2), was infused on day 8. RESULTS: The incidence of adverse reactions of more than grade 3 was 22.5% in the S-1 group and 43.5% in the S-1/CDDP group, and the treatment compliance was better in the S-1 group. The overall response rate was 25.9% in the S-1 group, and 36.8% in the S-1/CDDP group. The combination of S-1 with CDDP had better effects on the primary lesion and on differentiated-type carcinoma than S-1 alone. However, there was no difference in survival between the two patient groups. The median survival time after the initiation of treatment in the S-1 group was 322 days, and that in the S-1/CDDP group was 319 days. CONCLUSIONS: Our results suggest that the combination of CDDP with S-1 does not improve the long-term outcome of S-1 therapy.

[A case of advanced esophageal cancer responding remarkably to chemotherapy of TS-1 and weekly CDDP combined with radiotherapy].

A 66-year-old patient, who had advanced esophageal cancer with lymph node metastasis, was treated by neoadjuvant chemo-radiotherapy, followed by curative surgery. Chemotherapy of TS-1 (80 mg/m2) was administered orally for 21 days, and weekly intravenous administration of CDDP (20 mg/m2) was done 3 times. Radiotherapy at 2 Gy/day was combined 15 times (total 30 Gy). The tumor responded well to the treatment, and the size was remarkably reduced. Chemoradiotherapy using TS-1 and weekly CDDP revealed their efficacy for esophageal cancer.