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Background: Although chemoradiotherapy (CRT) is one of the curative treatments for thoracic esophageal squamous cell carcinoma (ESCC) with submucosal invasion, the risk of local recurrence after CRT remains a clinical problem. This retrospective study aimed to analyze the predictive factors for local recurrence after CRT., Methods: Ninety-one patients with clinical or pathological (c/p) T1bN0M0 thoracic ESCC who underwent CRT from 2004 to 2017 in our institution were analyzed retrospectively. Sixty-three patients were diagnosed with pathological T1b after undergoing initial endoscopic resection (ER) and treated with additional CRT; meanwhile, 28 patients were clinically diagnosed with T1b and underwent definitive CRT. We investigated the predictors of disease-specific survival (DSS) and local recurrence-free survival (LRFS) by performing univariate and multivariate analyses., Results: The median observation period was 59.8 months. The 5-year DSS and LRFS rates were 84.3% (95% confidence interval [CI]: 76.1-92.5) and 87.1% (95% CI: 79.1-95.1), respectively. The multivariate analysis revealed no significant predictors associated with DSS. On the contrary, ER (hazard ratio [HR]: 0.11, 95% CI: 0.02-0.48, p = 0.003) and tumor length (HR: 6.78, 95% CI: 1.28-36.05, p = 0.025) were recognized as independent predictive factors for LRFS. During follow-up, recurrence was observed in 18 patients (19.8%). With regard to the patterns of relapse, local recurrence was the most common in 11 patients, and salvage ER was performed in 9 of 11 patients., Conclusions: ER and tumor length were independent predictive factors for LRFS. Our study suggested that performance of ER prior to CRT improved the local control in patients with c/p T1bN0M0 ESCC. In addition, most of the patients who experienced local recurrence were treated with salvage ER, which contributed to preserving the organs., (© 2022. The Author(s).)

We hypothesize that there is a risk of ipsilateral breast tumor recurrence (IBTR) in surgical margin-free invasive ductal carcinoma (IDC) in the presence of ductal carcinoma in situ (DCIS) component affecting surgical margins in early stage. From 1990 to 2014, 343 patients with IDC in which the DCIS component constitute have received radiotherapy (RT) following breast-conserving surgery (BCS). All patients received whole breast irradiation with a prescribed dose of 50 Gy in 20 fractions (four times a week). This one-arm cohort with boost RT (253 patients) was compared for IBTR with a non-cohort group receiving no boost RT because of freedom from positive margins (90 patients). Median observation months were 98 (boost group) vs 119 (no boost group), respectively. The 15-year local recurrence-free survival (LRFS) rates were 98.5% and 85.6% in the boost and no boost groups, respectively (Cox proportional hazards model univariate analysis; p = 0.013, HR 0.13). Similarly, for other background factors, there was a significant difference in the LRFS between age groups. The 15-year LRFS rate was 91.8% in patients aged 45 years or younger and 94.6% in patients older than 46 years (p = 0.031, HR 0.21), respectively. Only these two factors were independently significant in Cox proportional hazards model multivariate analysis. IBTR risk in margin-free IDC with DCIS component was independently decreased by boost RT in the cohort setting. Tumor size, extensive intraductal component (EIC), boost dose, the presence of lymph node (LN) metastasis and hormonal therapy were not IBTR risk factors in this study., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Objectives: The prognosis for highly advanced esophageal squamous cell carcinoma (ESCC) remains poor, and there is currently no standard treatment. The purpose of this study was to examine the benefits of trimodality therapy [chemoradiation plus surgery, (CRT + S)] by evaluating the surgical outcomes of patients with ESCC in Keiyukai Sapporo Hospital, Japan. We assessed the preoperative and postoperative adverse events, treatment effects of preoperative CRT, metastatic diagnosis of the dissected lymph nodes, and survival., Patients and Methods: Between 2012 and 2018, 148 patients with highly advanced ESCC who underwent preoperative CRT + S were analyzed for diagnosis and staging, preoperative complications, clinical and histopathological effects of CRT in the resected specimens, survival rates, and recurrences., Results: The grade 3 and higher complications of preoperative CRT were neutropenia in 3 cases and thrombocytopenia in 1 case. Among the postoperative complications, there were 2 cases (1.4%) of direct surgical death, only tracheobronchial bleeding and liver failure. Using the 11 th edition of the classification of esophageal cancer by the Japanese Esophageal Society, 60 patients (40.5%) were classified as grade 3 (negative for cancer cells, pathological complete response). However, 20 of them (33.3%) had metastatic tumor cells in the lymph nodes. The overall 5-year survival rate was 58.5%. Including references to the pathological findings and recurrence patterns, there is no effective diagnostic method for selecting the subsequent approach based on the effectiveness of CRT., Conclusion: Planned surgery following CRT was the only solution for achieving better treatment results. CRT + S is a promising treatment with low direct surgical mortality.

Background: Metastatic breast cancer (MBC) is generally considered to be incurable. Although many options are available for treating MBC, physicians often encounter difficulties in choosing the most appropriate treatment because the MBCs of individual patients respond differently even to the same treatments. Thus, predictive markers for therapeutic efficacy are urgently needed. Neutrophil- and platelet-to-lymphocyte ratios (NLR and PLR, respectively), have been studied and established as prognostic markers for breast cancer patients but whether either or both of these markers are predictive of treatment responses is still unclear. Herein, we investigated predictive markers for eribulin-based treatment responsiveness in patients with MBC, by examining clinicopathological features, including several markers of immunocompetent cells in peripheral blood., Methods: Clinicopathological features of the 104 patients with metastatic/Stage IV breast cancer given eribulin-based regimens were investigated in relation to clinical responses to eribulin-based treatments and progression-free-survival (PFS)., Results: Special histological types and high NLR at baseline were independently related to poor clinical responses to the treatments (p = 0.023 and 0.039, respectively). The Cox hazard model revealed that patients with oestrogen receptor (ER)-negative tumours and high NLR, monocyte-to-lymphocyte ratio (MLR) and PLR showed significantly shorter PFS (p = 0.021, 0.005, 0.008 and 0.030, respectively). On multivariate analysis, only ER status and NLR remained independent factors related to PFS (p = 0.011 and 0.003, respectively)., Conclusions: Our data revealed that special histological types and high NLR might be factors related to low responsiveness to eribulin-based regimens in patients with MBC.

Purpose: The main purpose was to investigate the differences of the esophageal motion (EM) and the internal target volume (ITV) margins for the esophagus between clinical T1-T3 (cT1-T3) and cT4 cases, using 4-dimensional computed tomography. A secondary purpose was to assess the metastatic lymph nodal motion (NM) and the ITV margins for lymph nodes (LNs) using the datasets of patients with nodal involvement pathologically defined., Methods and Materials: We analyzed patients with thoracic esophageal cancer consecutively treated with definitive chemoradiation, measuring the EM and the ITV margins in the left-right, anteroposterior, and superoinferior directions. All esophageal contours were divided at the carina. The EM and NM were measured from the displacement of the centroid point between 0% images (at the end of inhalation) and 50% images (at the end of exhalation). The ITV margins were defined as the maximum distance in each direction from the clinical target volume at the 4-dimensional computed tomography average images to the intersection of the clinical target volume at the 0% and 50% images of complete coverage in each patient., Results: The EM below the carina in cT4 was significantly smaller than that in cT1-T2 in all directions ( P < .01) and than that in cT3 in all directions (left-right: P = .03, anteroposterior and superoinferior: P < .01). The EM in the case of a cT4 tumor located below the carina was smaller than that in the case of cT4 tumor located above the carina. The NM of abdominal-LNs was much larger than that of cervicothoracic-LNs and the EM below the carina. These tendencies were similar in the ITV measurements., Conclusions: The EM and the ITV margins in cT4 were significantly smaller than those in cT1-T3. The NM and the ITV margins of abdominal LNs were much larger than those of cervicothoracic LNs and the esophagus. In clinical radiation therapy planning for esophageal cancer, we should take cT stage into consideration.

Background: Multimodality treatment is widely performed for clinical T1N0M0 (UICC-TNM classification, 7th edition) thoracic esophageal squamous cell carcinoma (ESCC), but available articles regarding treatment results are limited. This study assessed the outcomes of clinical T1N0M0 thoracic ESCC invading the muscularis mucosa (MM) or submucosa (SM) treated with radiotherapy (RT) or chemoradiotherapy (CRT)., Methods: We retrospectively reviewed the medical charts of 90 patients with clinical T1N0M0 thoracic ESCC treated with RT or CRT in our hospital in 2004-2011. Of these 90 patients, we analyzed the cases of 71 patients who met our inclusion criteria. All 71 patients had MM or SM cancer. In the 47 patients treated with CRT, the chemotherapy regimen of 5-fluorouracil (5-FU) plus cisplatin (CDDP) was used for 46 patients and 5-FU and nedaplatin was used for one patient. Forty-five patients underwent endoscopic resection (ER) followed by RT or CRT as an additional treatment. Elective nodal irradiation (ENI) was used in 39 patients. For all analyses, statistical significance was defined as 0.05, and the Bonferroni correction was used for the multivariate analysis., Results: The median age was 70 years (range 47-84). With a median follow-up of 43.6 months (range 1.5-124.2), the 5-year overall survival (OS), disease-specific survival (DSS) and disease-free survival (DFS) rates were 64.0, 72.8 and 50.0 %, respectively. The multivariate analysis showed that performance status (PS) was an independent prognostic factors for DSS and DFS (DSS, p < 0.001; DFS, p < 0.001). Chemotherapy in addition to RT showed a trend for better DSS (p = 0.032) but was not significant following Bonferroni correction. ER and ENI were not significant predictive factors for DSS and DFS., Conclusions: PS was an independent prognostic factor for DSS and DFS. ER and ENI had no significant relationship with DSS or DFS. The present results may be helpful in treatment decisions for clinical T1N0M0 thoracic ESCC.

Purpose: We evaluated the relationship between dosimetric parameters (DPs) and the incidence of radiation pneumonitis (RP) and investigated the feasibility of a proposed treatment planning technique with the potential of reducing RP in esophageal cancer patients treated with definitive chemoradiotherapy using extended fields., Patients and Methods: A total of 149 patients with locally advanced esophageal cancer were prospectively enrolled for extended-field radiotherapy (EFRT) to three-field regional lymphatics between September 2004 and June 2009. We retrospectively reviewed 86 consecutive patients who were treated with a total dose of 50.4 Gy (plus an optional 9 Gy boost) and were available for dose-volume analysis. Lung DPs of patients in the Grade 0-1 RP (RPG≤1) group and the Grade 2-5 RP (RPG≥2) group were compared. We compared the proposed plan with the conventional plan to 50.4 Gy on DPs for each case., Results: Of these 86 patients, 10 (12%) developed RPG≥2 (Grade 2, n = 2 patients; Grade 3, n = 3; Grade 4, n = 3; Grade 5, n = 2). The patients in the RPG≤1 group showed significantly lower (P < 0.05) V5 and V10 values for the whole lung compared with those in the RPG≥2 group. There were two advantages gained from the proposed plan for V5 (<55%) and V10 (< 37%) values and the conformity of the PTV., Conclusion: The increase in the volume of the lung exposed to low doses of EFRT was found to be associated with the incidence of RP. Our proposed plan is likely to reduce the incidence of RP.

Patients with myxoma normally present with cardiovascular symptoms due to mitral valve obstruction caused by the tumor. However, some cases are difficult to diagnose because the findings of auscultation are normal and there are no cardiovascular symptoms. A 62-year-old man presented at a nearby clinic with a fever. No cardiac murmurs were heard on a physical examination. Abdominal ultrasonography was conducted to evaluate the origin of the fever, and a giant left atrial myxoma was discovered incidentally. Although many myxoma cases are found on transthoracic echocardiography, we herein describe a case of a giant left atrial myxoma incidentally discovered on abdominal ultrasonography.

Acarbose was administered at 300 mg/day to patients with type 2 diabetes mellitus (T2DM) who had been taking 25 mg/day of alogliptin, and levels of blood glucose were analyzed by continuous glucose monitoring (CGM) for 3 days. The mean blood glucose level with acarbose (136.4 ± 30.7 mg/dL) did not differ significantly from that without acarbose (141.7 ± 28.3 mg/dL). However, in the condition of the combination therapy, there were significant decreases in the standard deviation of the mean blood glucose levels for the 24-hour period (27.6 ± 9.1 vs. 16.2 ± 6.9 mg/dL, p<0.001) and mean amplitude of glycemic excursions (MAGE) (65.8 ± 26.1 vs. 38.8 ± 19.2 mg/dL, p=0.010). In addition, a meal tolerance test was conducted to monitor changes in insulin secretion and active GLP-1 and total GIP values. Ten subjects (5 males, 5 females) of 54.9 ± 6.9 years with BMI 25.9 ± 5.2 kg/m² and HbAlc 9.2 ± 1.2% were enrolled. In the meal tolerance test, active GLP-1 values before and after acarbose administration were 17.0 ± 5.8 and 24.1 ± 9.3 pmol·hr/mL (p=0.054), respectively, showing an increasing tendency, and total GIP(AUC0-180) values were 685.9 ± 209.7 and 404.4 ± 173.7 pmol·hr/mL, respectively, showing a significant decrease (p=0.010). The results indicate that the combined administration of both inhibitors is effective not only in decreasing blood glucose fluctuations and preventing postprandial insulin secretion. The beneficial effects may also protect the endocrine pancreas and inhibit body weight gain.

Aim: To analyze retrospectively the results of postoperative external beam radiotherapy (EBRT) for resected pancreatic adenocarcinoma., Patients and Methods: The records of 47 patients treated with gross complete resection (R0: 24 patients, R1: 23 patients) and post-operative EBRT were reviewed. The median dose of EBRT was 50 Gy (range, 12-60 Gy), and chemotherapy was used in 37 patients (78.7%). The median follow-up period for all 47 patients was 14.4 months (range, 0.9-67.9 months)., Results: At the time of this analysis, 24 patients (51.1%) had disease recurrence. Local failure was observed in 10 patients (21.3%), and the 2-year local control (LC) rate in all patients was 68.7%. Patients treated with EBRT and chemotherapy had a significantly more favorable LC (2-year LC rate: 76.0%) than those treated with EBRT alone (2-year LC rate: 40%, p=0.0472). The median survival time and the 2-year actuarial overall survival (OS) in all 47 patients were 30.0 months and 54.5%, respectively. Patients treated with EBRT and chemotherapy had a significantly more favorable OS (2-year OS rate: 61.6%) than those treated with EBRT alone (2-year OS: 25.0%, p=0.0454). On univariate analysis, chemotherapy use alone had a significant impact on OS, and on multivariate analysis, chemotherapy use also was a significant prognostic factor. There were no late morbidities of NCI-CTC Grade 3 or greater., Conclusion: Post-operative EBRT with chemotherapy yields a favorable LC rate for resected pancreatic adenocarcionoma, and EBRT combined with chemotherapy confers a survival benefit compared to EBRT alone.

The hydrogen-bonding property of water--ethanol in Japanese sake, a kind of brewage, was examined on the basis of both (1)H NMR chemical shifts of the OH of water--ethanol and the Raman OH stretching spectra. In 20% (v/v) EtOH-H(2)O solution, amino acids as well as organic acids caused low-field chemical shifts, i.e., the development of a hydrogen-bonding structure. Additional functional groups, apart from the essential amino- and carboxyl groups, in amino acids caused differences in their effects. The low-field chemical shifts caused by solutes were demonstrated under constant pH conditions maintained by sodium hydrogen citrate. Using both the measurement of (1)H NMR chemical shifts and Raman OH stretching spectra, the strength of the hydrogen bond of water--ethanol in Japanese sake products was found to be correlated with the total concentration of organic acids and amino acids. Glucose or saccharides should not have a strengthening effect on the hydrogen bond of water--ethanol. The effects of the main inorganic ions and amines were also discussed. It was concluded that chemical components originating from the starting material, rice, or products produced by microorganisms during the ethanol fermentation affect the hydrogen-bonding structure in Japanese sake.

Background: Previous randomized trials have shown a survival advantage of concurrent platinum-based chemoradiotherapy with or without adjuvant chemotherapy for advanced nasopharyngeal cancer. Applicability of these data to a Japanese population is an important issue which remains to be solved., Methods: A retrospective survey of treatment of patients with nasopharyngeal cancer in 17 institutions in Japan was done with special reference to the relationship between the type of chemotherapy and survival outcome. Chemotherapy used was classified according to: (i) whether > or =2 courses of platinum plus 5-fluorouracil (FP) was given; or (ii) whether platinum was administered concurrently with radiotherapy (RT). This resulted in three groups being produced consisting of (i)/(ii) = YES/YES, other miscellaneous (MISC) and RT alone., Results: Of 333 evaluable replies, 67 patients (20%) corresponded to the YES/YES, 192 (58%) to the MISC and 74 (22%) to the RT alone group. The YES/YES group achieved a better overall survival than RT alone for patients with intermediate stage (T3N0 or T1-3N1, 81.9 versus 60.7% at 5 years, P = 0.042) and advanced stage (T4 or N2/3, 56.6 versus 31.5%, P = 0.017) disease. The MISC group achieved an almost identical survival rate to that in the YES/YES group for patients with intermediate stage disease (81.9% at 5 years, P = 0.968), whereas it was not significantly different from that of the RT alone group for patients with advanced stage disease (44.0%, P = 0.261)., Conclusion: The results of this survey mirrored the data from previous randomized trials for patients with intermediate and advanced stage nasopharyngeal cancer in Japan. However, confirmatory prospective trials are required to test the efficacy of less toxic approaches for patients with intermediate stage disease.

The vertebrate neural tube consists of a series of neuromeres along its anteroposterior axis. Between amphioxus that possesses no neuromeres and gnathostomes, the lamprey occupies a critical position in the phylogeny for the origin of the segmented brain. To clarify the rhombomeric configuration of the Japanese lamprey, Lampetra japonica, we injected rhodamine- and fluorescein-labeled dextrans into the larval spinal cord, and retrogradely labeled the reticulospinal neurons. We also isolated prosomere marker genes from the embryonic cDNA library of L. japonica, and performed in situ hybridization on the embryonic brain. Of the genes examined, LjOtxA, LjPax6, LjPax2/5/8, LjDlx1/6, and LjTTF-1 were expressed in clearly demarcated polygonal domains. In the telencephalon, LjDlx1/6, LjPax6, and a putative paralogue of LjEmx were expressed in different domains; the LjEmx paralogue was expressed in the dorsal region, and LjDlx1/6 and LjPax6 in a complimentary fashion of the middle part. These expression patterns implied existence of a tripartite configuration of the lamprey telencephalon similar to that in gnathostomes. All these evidences strongly suggest that the segmental and compartmental architecture of the vertebrate brain was already established before the divergence of agnathans and gnathostomes.

Agnathan cognates of vertebrate homeobox genes, Emx and Dlx, were isolated from embryonic cDNA of a Japanese marine lamprey, Lampetra japonica. Analyses of amino acid sequences indicated that the Dlx cognate was closely related to the common ancestor of gnathostome Dlx1 and Dlx6 groups and termed LjDlx1/6. Southern blot analyses could not rule out the possibility that L. japonica possesses more than one paralog for both LjDlx1/6 and LjEmx, the lamprey cognate of Emx. Expression of LjDlx1/6 was regulated spatially as well as developmentally, and its transcripts were mainly found in the craniofacial and pharyngeal mesenchyme and in the forebrain. The expression pattern of LjEmx changed dramatically during embryogenesis; expression was seen initially in the entire neural tube and mesoderm, which were secondarily downregulated, and secondarily in cranial nerve ganglia and in the craniofacial mesenchyme. No specific expression of LjEmx was seen in the telencephalon. Comparisons of Dlx and Otx gene expression patterns suggested a shared neuromeric pattern of the vertebrate brain. Absence of Emx expression implied that the patterning of the lamprey telencephalon is not based on the tripartite plan that has been presumed in gnathostomes. Expression domains of LjDlx1/6 in the upper lip and of LjEmx in the craniofacial mesenchyme were peculiar features that have not been known in gnathostomes. Such differences in expression pattern may underlie distinct morphogenetic pathway of the mandibular arch between the agnathans and gnathostomes.

Purpose: With the conventional approach of surgery and postoperative radiotherapy for patients with Masaoka Stage III thymoma, progress has been slow for an improvement in the long-term survival rate over the past 20 years. The objective of this study was to evaluate the pattern of failure and survival after surgery and postoperative radiotherapy in Stage III thymoma and search for a new direction for better therapy outcome., Methods and Materials: Between 1975 and 1993, 111 patients with thymoma were treated at Massachusetts General Hospital. Of these, 32 patients were determined to have Masaoka Stage III thymoma. The initial treatment included surgery for clinically resectable disease in 25 patients and preoperative therapy for unresectable disease in 7 patients. Surgical procedure consisted of thymectomy plus resection of involved tissues. For postoperative radiotherapy (n = 23), radiation dose consisted of 45-50 Gy for close resection margins, 54 Gy for microscopically positive resection margins, and 60 Gy for grossly positive margins administered in 1.8 to 2.0 Gy of daily dose fractions, 5 fractions a week, over a period of 5 to 6.6 weeks. In preoperative radiotherapy, a dose of 40 Gy was administered in 2.0 Gy of daily dose fractions, 5 days a week. For patients with large tumor requiring more than 30% of total lung volume included in the target volume (n = 3), a preoperative radiation dose of 30 Gy was administered and an additional dose of 24-30 Gy was given to the tumor bed region after surgery for positive resection margins., Results: Patients with Stage III thymoma accounted for 29% (32/111 patients) of all patients. The median age was 57 years with a range from 27 to 81 years; gender ratio was 10:22 for male to female. The median follow-up time was 6 years. Histologic subtypes included well-differentiated thymic carcinoma in 19 (59%), high-grade carcinoma in 6 (19%), organoid thymoma in 4 (13%), and cortical thymoma in 3 (9%) according to the Marino and Müller-Hermelink classification. The overall survival rates were 71% and 54% at 5 and 10 years, respectively. Ten of the 25 patients who were subjected to surgery as initial treatment were found to have incomplete resection by histopathologic evaluation. The 5- and 10-year survival rates were 86% and 69% for patients (n = 15) with clear resection margins as compared with 28% and 14% for those (n = 10) with incomplete resection margins even after postoperative therapy, p = 0.002. Survival rates at 5 and 10 years were 100% and 67% for those with unresectable disease treated with preoperative radiation (n = 6) and subsequent surgery (n = 3). Recurrence was noted in 12 of 32 patients and 11 of these died of recurrent thymoma. Recurrences at pleura and tumor bed accounted for 77% of all relapses, and all pleural recurrences were observed among the patients who were treated with surgery initially., Conclusion: Incomplete resection leads to poor results even with postoperative radiotherapy or chemoradiotherapy in Stage III thymoma. Pleural recurrence is also observed more often among patients treated with surgery first. These findings suggest that preoperative radiotherapy or chemoradiotherapy may result in an increase in survival by improving the rate of complete resection and reducing local and pleural recurrences.

The records of 102 patients with squamous cell carcinoma of the oropharynx treated at National Sapporo Hospital with external and/or interstitial radiotherapy between 1978 and 1996 were reviewed to evaluate the treatment results, focusing on primary control and functional preservation. Ninety-five patients had been primarily treated with curative intent initially. Of these 95 patients, 4% were in stage I, 19% in stage II, 42% in stage III and 34% in stage IV. Twenty-one patients (22%) had been treated with multidisciplinary chemotherapy, and 19 patients (20%) had been boosted with brachytherapy mainly using Au-198 grains. The cause-specific survival rates at 5 and 10 years were 63% and 52%, respectively. The local control rates at 5 and 10 years were 70% and 51%, respectively. The most important factors affecting local control were the subsite of the primary tumor and N stage. Based on these findings, it is considered that radiotherapy combined with/without chemotherapy except for N3 and the posterior wall type is an effective method of achieving tumor control and preserving organ function, compared with other methods including surgical procedures.

Neural crest cells contribute extensively to vertebrate head morphogenesis and their origin is an important question to address in understanding the evolution of the craniate head. The distribution pattern of cephalic crest cells was examined in embryos of one of the living agnathan vertebrates, Lampetra japonica. The initial appearance of putative crest cells was observed on the dorsal aspect of the neural rod at stage 20.5 and ventral expansion of these cells was first seen at the level of rostral somites. As in gnathostomes, cephalic crest cells migrate beneath the surface ectoderm and form three major cell populations, each being separated at the levels of rhombomeres (r) 3 and r5. The neural crest seems initially to be produced at all neuraxial levels except for the rostral-most area, and cephalic crest cells are secondarily excluded from levels r3 and r5. Such a pattern of crest cell distribution prefigures the morphology of the cranial nerve anlage. The second or middle crest cell population passes medial to the otocyst, implying that the otocyst does not serve as a barrier to separate the crest cell populations. The three cephalic crest cell populations fill the pharyngeal arch ventrally, covering the pharyngeal mesoderm laterally with the rostral-most population covering the premandibular region and mandibular arch. The third cell population is equivalent to the circumpharyngeal crest cells in the chick, and its influx into the pharyngeal region precedes the formation of postotic pharyngeal arches. Focal injection of DiI revealed the existence of an anteroposterior organization in the neural crest at the neurular stage, destined for each pharyngeal region. The crest cells derived from the posterior midbrain that express the LjOtxA gene, the Otx2 cognate, were shown to migrate into the mandibular arch, a pattern which is identical to gnathostome embryos. It was concluded that the head region of the lamprey embryo shares a common set of morphological characters with gnathostome embryos and that the morphological deviation of the mandibular arch between the gnathostomes and the lamprey is not based on the early embryonic patterning., (Copyright 1999 Academic Press.)

From 1986 through 1992, 144 patients with metastatic brain tumors of lung cancer were treated with X-ray irradiation to whole brain or a comparatively wide field of the brain. To identify the subset of patients indicated for boost therapy like a stereotactic radiotherapy, we have analyzed the treatment results concerning both survival and performance status (PS). Median survival time of the patients in good PS (0-2) was 6.7 months, which was significantly better than 2.3 months in poor PS (3-4). Complete tumor-resectability, age, steroid therapy and condition within two months after the beginning of brain irradiation, seemed to be important prognostic indicators correlated with PS by both univariate and multivariates analyses.

We defined one group of patients who underwent radiotherapy within 75 days from the beginning of treatment as the early RT group, whereas another group of patients who underwent radiotherapy at least 75 days after the beginning of treatment was defined as the late RT group. The response rate (CR + PR) of the early RT group was 92.1% while that of the late RT group was 72.3%. The response rate for radiation therapy thus was significantly better in the early RT group. The 2 and 5-year actuarial survival rates of the early RT group were 22.1% and 9.2%, while those of the late RT group were 19.1% and 8.5%. Then respective median survival times (MST) were 14 months and 13 months. There was no significant difference in survival rates between the two groups. As much as the quality of life is concerned, early RT group would show here better results.

Results were reviewed in 46 patients who had stage I and II head and neck non-Hodgkin's lymphoma, and received five to six cycles of CVP chemotherapy after regional irradiation. Disease-free survival, pattern of relapse, and time of relapse were compared with those of 64 patients, who received regional irradiation alone. Adjuvant, post irradiation CVP significantly improved five-year survival in stage I (and IE) disease, 49.6% to 81.9% (p less than 0.05), but was less successful in patients with heavier tumor burden, such as stage II disease or advanced loco regional disease in Waldeyer's ring (48.3% to 63.7%; p greater than 0.10 in stage II patients). In addition, in those who relapsed, the time and pattern of relapse were not altered by adjuvant CVP chemotherapy. This easily tolerated, mild adjuvant chemotherapy, we conclude, failed to prove significant in preventing relapse, especially in patients with heavier tumor burden.

A review has been made of 36 patients who, after initial treatment for early non-Hodgkin's lymphoma originating in the head or neck, incurred a relapse, and factors relating to their chances of long-term survival, i.e., greater than three years, have been sought. Informatively, the overall 1-year and 5-year survival after such a relapse has been 18% and 15% respectively. The factor most significantly related to long-term survival was the site of the lymphoma and the extent of the initial relapse. For those affected in the neck region alone, four out of five survived for more than 48 months after the relapse (p less than 0.0001). The pathological subtype of the initial lymphoma was the second most significant factor (p less than 0.02). Another factor drawing our attention was the history of the prophylactic adjuvant therapy. No patient survived for more than a year after relapse if they had a history of prophylactic adjuvant therapy (0/10), whereas five long-term survivors were patients with no history of such therapy (0.1 less than p less than 0.2).