Combined thoracoscopic and axillary subcutaneous endoscopic thyroidectomy: a novel approach for cervicomediastinal goiters.

PURPOSE: After our group described the first remote-access thyroidectomy series in 2000, the procedure has been further developed. Although a thoracoscopic approach with a conventional open cervical incision for thyroid goiters with mediastinal extension has been performed at many institutions, remote-access thyroidectomy for cervicomediastinal goiters has not been established. We have performed combined thoracoscopic and axillary subcutaneous endoscopic thyroidectomies (axillo-thoracic endoscopic thyroidectomies). Here, we describe a novel technique for performing a remote-access thyroidectomy for a cervicomediastinal goiter (CMG). PATIENTS AND METHODS: The patients with CMGs who agreed to an axillo-thoracic endoscopic thyroidectomy at one of two hospitals in Japan underwent a remote-access thyroidectomy. RESULTS: We performed the axillo-thoracic endoscopic right or left hemithyroidectomy successfully, but most of the patients did not require the thoracoscopic procedure. None of the patients had complications, and none was converted to an open thyroidectomy. CONCLUSIONS: Most thyroid goiters with substernal extension can be removed by the axillary approach, but some cases require a thoracoscopic approach. The novel approach described herein (axillo-thoracic endoscopic thyroidectomy) enables the safe excision of a CMG with high patient satisfaction for selected patients.

Influence of preoperative chemotherapy-induced leukopenia on survival in patients with esophageal squamous cell carcinoma: exploratory analysis of JCOG9907.

BACKGROUND: The relationship between chemotherapy-induced leukopenia (CIL) and survival has not been investigated in patients undergoing preoperative chemotherapy for esophageal squamous cell carcinoma (ESCC). We analyzed the association of CIL with survival outcomes using data from JCOG9907 on the efficacy of preoperative chemotherapy for stage II/III ESCC. METHODS: Preoperative chemotherapy consisted of two courses of 5-FU (800 mg/m2 days 1-5) and cisplatin (80 mg/m2 day 1) repeated every 3 weeks. Patients in the preoperative chemotherapy arm receiving at least one course of chemotherapy and undergoing subsequent surgery in JCOG9907 were divided into two subgroups: CIL ( +), those with grade 2-4 leukopenia at least once during preoperative chemotherapy; and CIL (-), those with grades 0-1. The association of CIL with overall survival (OS) and progression-free survival (PFS) was analyzed. RESULTS: Among 164 patients enrolled in JCOG9907, 152 patients were included in this analysis, 52 in CIL ( +) and 100 patients in CIL (-) subgroups. The 3-year OS for CIL ( +) was inferior to that for CIL (-) (48.1% vs. 73.9%); hazard ratio (HR) = 1.94 (95% CI 1.18-3.16, P < .01). For 3-year PFS, a similar tendency was observed (44.2% vs. 55.8%; HR = 1.38 (95% CI 0.88-2.17, P = .16). Multivariable analysis revealed that CIL was not an independent factor for OS (HR = 1.14, 95% CI 0.63-2.07, P = .67). CONCLUSION: We showed that CIL during preoperative chemotherapy might not be a prognostic factor in patients with ESCC.

Prognostic Impact of Postoperative Morbidity After Esophagectomy for Esophageal Cancer: Exploratory Analysis of JCOG9907.

OBJECTIVE: To investigate the influence of infectious complications on the outcome of current standard preoperative chemotherapy followed by surgery for clinical stage II/III esophageal cancer. BACKGROUND: The impact of postoperative infectious complications on survival after transthoracic esophagectomy remains controversial. METHODS: Data from a randomized controlled trial (JCOG9907) were used. Infectious complications were classified into three groups: pneumonia, anastomotic leakage, and others. Univariate and multivariate analyses using the Cox proportional hazard model were performed. RESULTS: Among the 152 analyzed patients, the incidence of pneumonia, leakage, and overall infectious complication were 22 (14%), 21 (14%), and 54 (36%). Overall survival (OS) of patients with any infectious complication was shorter than that of patients without infectious complication [hazard ratio, HR 1.66, 95% confidence interval, CI, (1.02-2.71)] and progression-free survival (PFS) also tended to be shorter in patients with any infectious complication [HR 1.44, (0.92-2.24)]. The OS of patients with pneumonia was shorter than that of patients without pneumonia [HR 1.82, (1.01-3.29)], and PFS also tended to be shorter in patients with pneumonia [HR 1.50, (0.85-2.62)]. The OS of patients with anastomotic leakage (n = 21) was nearly identical to that for patients without leakage [HR 1.06, (0.52-2.13)] and PFS showed the same tendency [HR 1.28, (0.71-2.32)]. Multivariate analysis revealed that pneumonia tended to compromise OS and PFS [HR 1.66, (0.87-3.17) and HR 1.37, (0.75-2.51)]. CONCLUSIONS: These results indicate that postoperative infectious complications may worsen patient prognosis after esophagectomy. Performing esophagectomy without postoperative complications, especially pneumonia, may be beneficial for improving survival outcomes.

Results of a nation-wide retrospective study of lymphadenectomy for esophagogastric junction carcinoma.

BACKGROUND: Esophagogastric junction (EGJ) carcinoma has attracted considerable attention because of the marked increase in its incidence globally. However, the optimal extent of esophagogastric resection for this tumor entity remains highly controversial. METHODS: This was a questionnaire-based national retrospective study undertaken in an attempt to define the optimal extent of lymph node dissection for EGJ cancer. Data from patients with EGJ carcinoma, less than 40 mm in diameter, who underwent R0 resection between January 2001 and December 2010 were reviewed. RESULTS: Clinical records of 2807 patients without preoperative therapy were included in the analysis. There are distinct disparities in terms of the nodal dissection rate according to histology and the predominant tumor location. Nodal metastases frequently involved the abdominal nodes, especially those at the right and left cardia, lesser curvature and along the left gastric artery. Nodes along the distal portion of the stomach were much less often metastatic, and their dissection seemed unlikely to be beneficial. Lower mediastinal node dissection might contribute to improving survival for patients with esophagus-predominant EGJ cancer. However, due to low dissection rates for nodes of the middle and upper mediastinum, no conclusive result was obtained regarding the optimal extent of nodal dissection in this region. CONCLUSIONS: Complete nodal clearance along the distal portion of the stomach offers marginal survival benefits for patients with EGJ cancers less than 4 cm in diameter. The optimal extent of esophageal resection and the benefits of mediastinal node dissection remain issues to be addressed in managing patients with esophagus-predominant EGJ cancers.

Comparison between neoadjuvant chemotherapy followed by surgery and definitive chemoradiotherapy for overall survival in patients with clinical Stage II/III esophageal squamous cell carcinoma (JCOG1406-A).

BACKGROUND: Neoadjuvant chemotherapy followed by surgery (NAC-S) represents the standard treatment for patients with Stage II/III esophageal squamous cell carcinoma (ESCC) in Japan. Chemoradiotherapy (CRT) is performed in patients who refuse or have contraindications to surgery. However, randomized clinical trials that compare NAC-S with CRT have not been conducted. The aim of this study was to explore subgroups of patients undergoing CRT to identify those with survival outcomes potentially equivalent to NAC-S. METHODS: Pooled data from two clinical trials in patients with Stage II/III ESCC, the JCOG9907 trial and the JCOG9906 trial were used. JCOG9907 demonstrated that NAC-S resulted in superior overall survival (OS) compared with surgery followed by adjuvant chemotherapy. JCOG9906 was a single-arm trial that explored the efficacy and safety of CRT. The eligibility criteria in the two trials were almost identical. Subgroup analyses of clinical data (serum albumin, cT, cN, cstage and tumor location) were conducted with Cox proportional hazards regression models for patients assigned to receive NAC-S in JCOG9907 and patients in JCOG9906. RESULTS: The analysis comprised 163 patients from JCOG9907 in NAC-S arm (NAC-S group) and 73 patients from JCOG9906 who received CRT (CRT group). Baseline characteristics were similar between the two groups. OS was better in the NAC-S group than the CRT group (adjusted hazard ratio 1.72; 95% confidence interval 1.19-2.50). All subgroups in the NAC-S group had longer OS compared with those in the CRT group. CONCLUSIONS: OS was superior after NAC-S rather than CRT. None of the CRT subgroups had similar OS to the NAC-S groups.

Esophageal stenosis and the Glasgow Prognostic Score as independent factors of poor prognosis for patients with locally advanced unresectable esophageal cancer treated with chemoradiotherapy (exploratory analysis of JCOG0303).

BACKGROUND: The aim of this study was to investigate the possible prognostic factors and predictive accuracy of the Glasgow Prognostic Score (GPS) for patients with unresectable locally advanced esophageal squamous cell carcinoma (LAESCC) treated with chemoradiotherapy. METHODS: One hundred forty-two patients were enrolled in JCOG0303 and assigned to the standard cisplatin and 5-fluorouracil (PF)-radiotherapy (RT) group or the low-dose PF-RT group. One hundred thirty-one patients with sufficient data were included in this analysis. A Cox regression model was used to analyze the prognostic factors of patients with unresectable LAESCC treated with PF-RT. The GPS was classified based on the baseline C-reactive protein (CRP) and serum albumin levels. Patients with CRP ≤1.0 mg/dL and albumin ≥3.5 g/dL were classified as GPS0. If only CRP was increased or only albumin was decreased, the patients were classified as GPS1, and the patients with CRP >1.0 mg/dL and albumin <3.5 g/dL were classified as GPS2. RESULTS: The patients' backgrounds were as follows: median age (range), 62 (37-75); male/female, 119/12; ECOG PS 0/1/2, 64/65/2; and clinical stage (UICC 5th) IIB/III/IVA/IVB, 3/75/22/31. Multivariable analyses indicated only esophageal stenosis as a common factor for poor prognosis. In addition, overall survival tended to decrease according to the GPS subgroups (median survival time (months): GPS0/GPS1/GPS2 16.1/14.9/8.7). CONCLUSIONS: Esophageal stenosis was identified as a candidate stratification factor for randomized trials of unresectable LAESCC patients. Furthermore, GPS represents a prognostic factor for LAESCC patients treated with chemoradiotherapy. CLINICAL TRIAL INFORMATION: UMIN000000861.

Inter-institutional survival heterogeneity in chemoradiation therapy for esophageal cancer: exploratory analysis of the JCOG0303 study.

It is important to examine variation in the treatment effects of patients with esophageal cancer in order to generalize treatment outcomes. We aimed to investigate the range of prognostic differences among hospitals in the treatment of locally advanced esophageal cancer. The JCOG0303 study compared the efficacy of radiotherapy plus low-dose cisplatin and 5-fluorouracil with that of high-dose cisplatin and 5-fluorouracil for unresectable esophageal cancer. Of 32 institutions participating in the JCOG0303 study, the 18 institutions that enrolled three or more patients were included in this study. We predicted the 1-year survival in each institution by using a mixed-effect model. We found that the predicted 1-year survival in the 18 institutions with three or more patients was a median of 60.9%, with a range of 60.9-60.9%. This study is the first to investigated heterogeneity of survival in patients who received definitive chemoradiotherapy for locally advanced esophageal squamous cell carcinoma.

Randomized study of low-dose versus standard-dose chemoradiotherapy for unresectable esophageal squamous cell carcinoma (JCOG0303).

Low-dose cisplatin and 5-fluorouracil (LDPF) chemotherapy with daily radiotherapy (RT) is used as an alternative chemoradiotherapy regimen for locally advanced esophageal carcinoma. We evaluated whether RT plus LDPF chemotherapy had an advantage in terms of survival and/or toxicity over RT plus standard-dose cisplatin and 5-fluorouracil (SDPF) chemotherapy in this study. This multicenter trial included esophageal cancer patients with clinical T4 disease and/or unresectable regional lymph node metastasis. Patients were randomly assigned to receive RT (2 Gy/fraction, total dose of 60 Gy) with SDPF (arm A) or LDPF (arm B) chemotherapy. The primary endpoint was overall survival (OS). A total of 142 patients (arm A/B, 71/71) from 41 institutions were enrolled between April 2004 and September 2009. The OS hazard ratio in arm B versus arm A was 1.05 (80% confidence interval, 0.78-1.41). There were no differences in toxicities in either arm. Arm B was judged as not promising for further evaluation in the phase III setting. Thus, the Data and Safety Monitoring Committee recommended that the study be terminated. In the updated analyses, median OS and 3-year OS were 13.1 months and 25.9%, respectively, for arm A and 14.4 months and 25.7%, respectively, for arm B. Daily RT plus LDPF chemotherapy did not qualify for further evaluation as a new treatment option for patients with locally advanced unresectable esophageal cancer. This study was registered at the UMIN Clinical Trials Registry as UMIN000000861.

Prognostic Factors in Patients Receiving Neoadjuvant 5-Fluorouracil plus Cisplatin for Advanced Esophageal Cancer (JCOG9907).

OBJECTIVE: Neoadjuvant chemotherapy with 5-fluorouracil plus cisplatin and subsequent esophagectomy with two- to three-field lymphadenectomy is a standard treatment for patients with clinical stage II/III squamous cell carcinoma (SCC) of the esophagus. This study investigates the prognostic factors for patients who received neoadjuvant chemotherapy. METHODS: Of 164 patients assigned to receive neoadjuvant chemotherapy in the JCOG9907 trial, multivariate analyses were performed for 159 and 149 patients to evaluate the preoperative and the combined preoperative and postoperative prognostic factors, respectively. RESULTS: The multivariate analyses using preoperative factors showed that clinical stage T3 [vs. cT1-2; hazard ratio (HR) 3.60, p = 0.0007] and serum albumin (Alb) <4.0 g/dl (vs. ≥ 4.0 g/dl; HR 2.29, p = 0.0005) were associated with a poor prognosis. Four independent prognostic factors were identified by multivariate analysis of both preoperative and postoperative factors: pathological curability B (pB; R0 with stage IV or pD < pN) or pC [microscopic or macroscopic residual tumor (R1/R2)] [vs. pA (R0); HR 1.93, p = 0.015], pathological stage N1 (vs. pN0; HR 3.86, p = 0.0012), cT3 (vs. cT1-2; HR 2.80, p = 0.0073), and serum Alb <4.0 g/dl (vs. ≥ 4.0 g/dl; HR 2.03, p = 0.0069). CONCLUSIONS: Preoperative cT stage, Alb, and postoperative pathological findings are independent prognostic factors for patients undergoing neoadjuvant chemotherapy for advanced thoracic esophageal SCC. This analysis may aid in stratification according to individual patient risk.

Which is the optimal response criteria for evaluating preoperative treatment in esophageal cancer: RECIST or histology?

BACKGROUND: Preoperative treatment is a promising strategy for improving long-term outcomes in advanced esophageal cancer. Two tumor response evaluation criteria for preoperative treatment are available: response evaluation criteria in solid tumors (RECIST) and histological criteria. This prospective study aimed to identify which was a better surrogate end point for survival in the preoperative setting. METHODS: We analyzed all eligible patients (n=164) from the preoperative treatment group in a phase III trial comparing preoperative versus postoperative 5-fluorouracil plus cisplatin for clinical stage II or III esophageal cancer. Intercriteria reliability was evaluated with the proportion of agreement and the kappa coefficient. For validity analyses, hazard ratios (HR) of response to nonresponse and differences in response rates between short- and long-term survivors were evaluated. RESULTS: The clinical and histological response rates were 37.8% (62 of 164) and 20.1% (33 of 164), respectively. The proportion of agreement for response to nonresponse between the 2 criteria was 70.3%, and the kappa coefficient was 0.34. The HR for death in patients with histological response (0.22, 95% confidence interval 0.09-0.55, P<0.001) was lower than for those with RECIST response (0.55, 95% confidence interval 0.33-0.91, P=0.018). The difference in response rates between short- and long-term survivors according to histological criteria (27 vs. 7%, P<0.001) was larger than with RECIST (42 vs. 30%, P=0.13). CONCLUSIONS: Intercriteria agreement was relatively low, and histological criteria yielded more valid assessments of response than RECIST. Histological response rate seemed to be the better surrogate end point of survival in the preoperative setting.

Three-arm phase III trial comparing cisplatin plus 5-FU (CF) versus docetaxel, cisplatin plus 5-FU (DCF) versus radiotherapy with CF (CF-RT) as preoperative therapy for locally advanced esophageal cancer (JCOG1109, NExT study).

A three-arm Phase III trial was started in November 2012. Preoperative chemotherapy with cisplatin plus 5-fluorouracil is the current standard treatment for locally advanced esophageal cancer in Japan, while preoperative chemoradiotherapy with cisplatin plus 5-fluorouracil is the standard in Western countries. Preoperative chemotherapy with docetaxel, cisplatin plus 5-fluorouracil is another promising regimen. The purpose of this study is to confirm the superiority of docetaxel, cisplatin plus 5-fluorouracil over cisplatin plus 5-fluorouracil and the superiority of cisplatin plus 5-fluorouracil with chemoradiotherapy over cisplatin plus 5-fluorouracil as preoperative therapy for squamous cell carcinoma of esophagus. A total of 501 patients will be accrued from 41 Japanese institutions within 6.25 years. The primary endpoint is overall survival and the secondary endpoints include progression-free survival, %R0 resection, response rate, pathologic complete response rate and adverse events.

Induction chemotherapy and hepatic artery embolization followed by extended resection for locally advanced gallbladder cancer: a case report.

BACKGROUND: Surgical resection plays a critical role in the curative therapy of patients with gallbladder cancer. However, extended resection for locally advanced gallbladder cancer is a controversial procedure because of the high operative morbidity, mortality, and poor prognosis after surgery, without consensus of its suitability. Several reports have described preoperative treatment modalities to reduce the risk of mortality and morbidity and improve the curability of surgery for locally advanced GBCA. However, only a few well-designed studies have verified the benefits of these preoperative strategies. CASE PRESENTATION: A 62-year-old male patient presented to our department with a gallbladder tumor detected on abdominal ultrasound during an annual medical checkup. Multi-phase enhanced CT revealed a gallbladder tumor with a maximum diameter of 34 mm, invading the right hepatic artery, pancreatic head, hepatic flexure of the colon, and first portion of the duodenum. We diagnosed gallbladder carcinoma as cT4 cN0 cM0 cStage IVA in the Union for International Cancer Control (UICC) classification 8th edition. After administration of 12 cycles of gemcitabine and cisplatin plus S-1 regimen, tumor shrinkage was observed on computed tomography, and elevated serum CA19-9 levels were reduced to normal limits. After preoperative hepatic artery embolization, we performed gallbladder bed resection with pancreaticoduodenectomy (minor hepatopancreatoduodenectomy) and combined resection of the right hepatic artery and hepatic flexure of the colon. Histological examination revealed no evidence of lymph node metastasis (ypT4 ypN0 ycM0 yp Stage IVA in the 8th edition of the UICC). The proximal bile duct and dissected margins were negative. CONCLUSIONS: The combination of induction chemotherapy and preoperative hepatic artery embolization, followed by minor hepatopancreatoduodenectomy and combined resection of the involved arteries and partial colon, could be a feasible treatment strategy for patients with locally advanced gallbladder cancer invading neighboring organs.

Incidence and risk factors of postoperative delirium in patients with esophageal cancer.

BACKGROUND: Postoperative delirium is a common complication after major surgery and is characterized by acute confusion with fluctuating consciousness. The aim of this study was to investigate the incidence and risk factors of postoperative delirium in patients with esophageal cancer. METHODS: We conducted a retrospective cohort analysis of 306 consecutive patients who had undergone an esophagectomy at Keio University Hospital from January 1998 to December 2009. All data were assessed by psychiatrists, and delirium was diagnosed according to criteria of the Diagnostic and Statistical Manual Disorder, fourth edition. Univariate and multivariate analyses were performed. RESULTS: Postoperative delirium developed in 153 (50.0 %) of 306 patients. One hundred fourteen (37.3 %) of the 306 patients required psychoactive medication for symptoms associated with delirium. Univariate analyses showed that older age, male gender, additional flunitrazepam for sedation in intensive care unit (ICU) after surgery, longer periods of time under mechanical ventilation after surgery, longer ICU stays, occurrence of postoperative complications, and longer hospital stays were significantly associated with postoperative delirium. Multivariate analysis revealed that development of delirium was linked to older age, additional flunitrazepam in ICU, and occurrence of postoperative complication. CONCLUSIONS: The development of postoperative delirium in patients with esophageal cancer is a problem that cannot be ignored. Our results suggest that the risk of developing delirium is associated with older age, use of flunitrazepam in ICU, and postoperative complications.

A randomized trial comparing postoperative adjuvant chemotherapy with cisplatin and 5-fluorouracil versus preoperative chemotherapy for localized advanced squamous cell carcinoma of the thoracic esophagus (JCOG9907).

BACKGROUND: Patients with esophageal carcinoma receiving postoperative chemotherapy showed superior disease-free survival than those receiving surgery alone in a Japan Clinical Oncology Group trial (JCOG9204). The purpose of this study was to evaluate optimal perioperative timing-that is, before or after surgery-for providing chemotherapy in patients with locally advanced esophageal squamous cell carcinoma. METHODS: Eligible patients with clinical stage II or III, excluding T4, squamous cell carcinoma were randomized to undergo surgery followed (group 1) or preceded (group 2) by chemotherapy consisting of two courses of cisplatin plus 5-fluorouracil. The primary end point was progression-free survival. RESULTS: We randomized 330 patients, with 166 assigned to group 1 and 164 to group 2, between May 2000 and May 2006. The planned interim analysis was conducted after completion of patient accrual. Progression-free survival did not reach the stopping boundary, but overall survival in group 2 was superior to that of group 1 (P = 0.01). Therefore, the Data and Safety Monitoring Committee recommended early publication. Updated analyses showed the 5-year overall survival to be 43% in group 1 and 55% in group 2 (hazard ratio 0.73, 95% confidence interval 0.54-0.99, P = 0.04), where the median follow-up of censored patients was 61.6 months. Concerning operative morbidity, renal dysfunction after surgery in group 2 was slightly higher than in group 1. CONCLUSIONS: Preoperative chemotherapy with cisplatin plus 5-fluorouracil can be regarded as standard treatment for patients with stage II/III squamous cell carcinoma.

Estrogen deficiency attenuates neovascularization in a murine model of hindlimb ischemia.

BACKGROUND: The possible relation between menopause and the development of peripheral arterial disease, especially lower extremity disease, has not been fully studied. To explore this issue, we investigated whether estrogen deficiency affected neovascularization in a murine model of hindlimb ischemia. METHODS: Ischemia was surgically induced in one hindlimb of oophorectomized and control female BALB/c mice. Neovascularization in the ischemic hindlimbs was evaluated using laser Doppler blood flow analysis and capillary density analysis of the adductor muscle. The expression of endothelial nitric oxide synthase protein in the adductor muscle of the ischemic hindlimbs was assessed. RESULTS: The plasma 17-ß estradiol levels were significantly lower in the oophorectomized mice than in the control mice. The oophorectomized mice also had a significantly reduced blood perfusion index and capillary density on day 21 after the induction of hindlimb ischemia and significant suppression of endothelial nitric oxide synthase protein expression on day 3 after ischemia induction. CONCLUSIONS: Estrogen deficiency attenuated neovascularization in a murine model of hindlimb ischemia. Impaired neovascularization in oophorectomized mice might correlate with a reduction in endothelial nitric oxide synthase expression caused by estrogen deficiency.

Radiotherapy quality assurance review for a multi-center randomized trial of locally advanced esophageal cancer: the Japan Clinical Oncology Group (JCOG) trial 0303.

BACKGROUND AND PURPOSE: The purpose of this study was to evaluate the radiotherapy (RT) quality assurance (QA) for JCOG 0303. METHODS AND MATERIALS: JCOG 0303 was a multi-center phase II/III trial that compared two types of chemotherapy administered concomitantly with RT for locally advanced esophageal cancer. RT requirements included a total dose of 60 Gy in 30 fractions and CTV with a 2-cm margin cranio-caudally to the primary tumor. The QA assessment was given as per protocol (PP), deviation acceptable (DA), violation unacceptable (VU), and incomplete/not evaluable following predefined criteria for quality parameters. RESULTS: A total of 142 cases were accrued. After excluding 36 incomplete/not evaluable, 106 (75%) were fully evaluable for RT quality review. Of these 106, there were 4 VU (4%) and overall RT compliance (PP + DA) was 96%. Comparing the incidence of VU based on the numbers enrolled by institution, the highest quarter of enrollment (≥7 cases) had no VU, while all VU (4; 11%) were from institutions enrolling <7 patients. CONCLUSIONS: The results of the RTQA assessment for JCOG 0303 were sufficient to provide reliable results. Additional improvements will be needed for institutions with low accrual rates.

[A case of bone marrow carcinomatosis from breast cancer treated with weekly Paclitaxel].

We report a case of bone marrow carcinomatosis originating from breast cancer that was treated with weekly paclitaxel (PTX). A 42-year-old female patient underwent mastectomy with axillary lymph node dissection for breast cancer in 2001. Multiple bone metastases were diagnosed in 2008, but she remained stable with chemotherapy and hormonal therapy for about two years. In 2010, thrombocytopenia occurred, and she was diagnosed with bone marrow carcinomatosis after bone marrow biopsy. She was treated with weekly PTX(80 mg/m2), and recovered successfully after treatment. About one year has elapsed since initiation of therapy, and there has been no recurrence. Bone marrow carcinomatosis originating from breast cancer is very rare, and is regarded as a disease with a poor prognosis. However, weekly PTX could be a valid treatment for prolonging survival of bone marrow carcinomatosis originating from breast cancer.

Upper gastrointestinal tract cancers as double-cancers in elderly patients with oral squamous cell carcinoma.

Against a background of a rapidly aging society, the number of patients with oral cancers in Japan is increasing yearly. The number of double-cancers with oral cancer as the first malignancy is also reportedly on the rise. Esophageal and gastric cancers are the most common second malignancies. At our institution, our policy is to proactively perform upper gastrointestinal (GI) fiberscopy (GIF) in patients with oral cancer. In anticipation of a probable further increase in the number of patients with double-cancers consisting of oral and GI tract malignancies, we retrospectively analyzed the occurrence of upper GI tract cancers in patients with oral squamous cell carcinoma (OSCC). The cohort consisted of 171 patients in whom OSCC had been diagnosed and who had undergone upper GIF between March 1996 and August 2008. Multivariate analysis was performed. Upper GIF identified 8 patients (7 men, 1 woman, totaling 4.7% of 171 patients) with double-cancer in the upper GI tract. One patient had a triple malignancy consisting of oral, esophageal and gastric cancers. Seven patients had esophageal cancer, while two had gastric cancer. An age of over 65 years was significantly higher in patients with double-cancers including esophageal cancer than in patients without esophageal cancer (OR=10.454, 95% CI=1.143-95.621). None of the other analyzed patient factors (sex, smoking habit, drinking habit, site of OSCC, TNM classification, staging results) showed a significant difference. These results indicate that, when treating elderly patients with oral cancers, physicians need to devise suitable treatment plans which take into account the possibility of upper GI tract cancer, particularly esophageal cancer, as a double-cancer.

Remote-access hemithyroidectomy in a patient with papillary thyroid cancer after ipsilateral irradiation: a case report.

Remote-access thyroidectomy (RAT) is becoming a more frequently used approach that can avoid scars in the neck and provide better cosmetic results than open surgery. However, there has been no surgical indication for RAT in patients who have a history of cervical treatment (surgery or irradiation), and the use of RAT has been avoided in such patients. Here, we report a case in which a remote-access endoscopic hemithyroidectomy and central lymph node dissection by the anterior chest approach was successfully performed in a patient with papillary thyroid carcinoma (a 77-year-old Japanese male) after he had undergone ipsilateral cervical radiation therapy to parotid gland cancer (mucoepidermoid carcinoma) thirteen years earlier. Regarding trocar insertion, a 30-mm skin incision was made in the left anterior chest approx. 5 cm below the clavicle. Two 5-mm trocars were inserted through the 30-mm incision. We then insufflated with carbon dioxide to 6 mmHg. One additional 5-mm trocar was placed cephalad to the 30-mm incision. When we performed this RAT, we detected no effect of the prior irradiation. To the best of our knowledge, this is the first report of RAT after irradiation. The cosmetic outcome of RAT is clearly superior, and the present case demonstrates that a RAT can be safely performed in carefully selected patients even after irradiation.

[Neoadjuvant chemotherapy followed by surgery as standard treatment for stage II + III thoracic esophageal squamous cell carcinoma in Japan].

In Japan, the overall 5-year survival rates after surgery alone for thoracic esophageal squamous cell carcinoma are 88% in patients with stage I and 52% in patients with stage II + III disease. Because of the poor outcome of stage II + III patients, multimodality approaches based on chemotherapy or chemoradiotherapy have been evaluated as adjuvant therapy. Neoadjuvant chemoradiotherapy has mainly been evaluated in the USA, while adjuvant chemotherapy for systemic effects has mainly been evaluated in Japan. In 2003, the results of a randomized study (Japan Clinical Oncology Group [JCOG] 9204) comparing surgery alone with postoperative chemotherapy with cisplatin and fluorouracil were reported, confirming that adjuvant chemotherapy prevents relapse in patients with esophageal cancer after surgery. In 2008, another study (JCOG 9907) comparing postoperative and preoperative chemotherapy was reported, and those results showed that preoperative chemotherapy induced downstaging and R0 reduction and improved overall survival without additional serious adverse events. Preoperative chemotherapy with cisplatin and fluorouracil followed by surgery can be regarded as the standard treatment for stage II + III thoracic esophageal squamous cell carcinoma in Japan.