Biomedical subjects
Publications and source records attributed to S Ebihara.
An inferior rectus abdominis flap was transferred in an 83-year-old female patient with a cervical esophageal carcinoma. This flap can be a good option for pharyngoesophageal reconstruction when it is desirable to avoid laparotomy and to shorten the operating time in an elderly or high-risk patient.
We successfully fabricated a large maxillofacial prosthesis for replacement of a total mandibular defect resulting from surgical failure to reconstruct the mandible. Although a number of reports have described procedures for fabricating midfacial prostheses, there is little information on prostheses to compensate for total loss of the mandible. A 54-year-old woman was referred to the Dentistry and Oral Surgery Division of the National Cancer Center Hospital with total loss of the mandible and the surrounding facial soft tissue. The facial prosthesis we used to treat this patient is unique in that it is adequately retained without the use of extraoral implants and conventional adhesives. This prosthesis is retained by the bilateral auricles and the remaining upper front teeth. We present details of the design of this large silicone maxillofacial prosthesis, with which we successfully rehabilitated the patient.
Thirteen patients who had undergone ablative surgery for advanced squamous cell carcinoma in which more than half of the tongue had been resected underwent reconstruction in which the cutaneous nerve of a free flap was anastomosed to the stump of the transected lingual nerve. Eight of the patients underwent reconstruction with an innervated anterolateral thigh flap and five patients underwent reconstruction with an innervated rectus abdominis musculocutaneous flap. Sensory recovery of the flap at least 6 months postoperatively was compared in these 13 patients and in 16 additional patients who received noninnervated versions of the same flaps for the same defect. The degree of sensory recovery of innervated thigh flaps was significantly greater than that of noninnervated ones in all modalities and that of innervated rectus abdominis flaps was also greater than that of noninnervated flaps, except for hot and cold perception. These results indicate that sensory regrowth occurs in most areas through the surgically created pathways. However, results of Semmes-Weinstein testing showed that recovery did not reach the level of protective sensation in either type of innervated flap. Although these findings must be followed by additional objective and functional tests and the need for sensory reeducation should be considered, this simple operative procedure can improve postoperative intraoral function and should be attempted whenever possible after ablative surgery.
A late phase II clinical study of RP56976 (docetaxel), a new anticancer agent for advanced/recurrent head and neck cancer, was conducted in 29 institutions all over Japan as a multi-institutional cooperative study. Docetaxel was administered by 1 to 2-hour intravenous infusion at a dose of 60 mg/m2 every 3 to 4 weeks. Of 63 patients eligible in this study, 59 were judged as complete cases. Complete response (CR) was observed in 1 patient, partial response (PR) in 13, no change (NC) in 25, and progressive disease (PD) in 20, for an overall response rate of 22.2% (14/63, 95% CI: 12.7-34.5%) in eligible cases, and 23.7% (14/59, 95% CI: 13.6-36.6%) in complete cases. Previously treated patients showed a 17.9% (10/56) response rate, whereas treatment--naive patients showed a 57.1% (4/7) response rate. Among 46 patients who received prior chemotherapy, one CR and 7 PR were observed with a 17.4% response rate. Major hematological toxicities were leucopenia in 95.1% (> or = grade 3, 59.7%) and neutropenia in 90.3% (> or = grade 3, 79.0%). Other severe toxicities (> or = grade 3) included anorexia in 9.7% (6 cases), diarrhea in 3.2% (2 cases), dyspnea in 3.2% (2 cases), and fatigue in 3.2% (2 cases). One patient had a grade 3 interstitial pneumonia; however, symptoms were resolved by the administration of corticosteroids. During this study, one patient died due to multiple organ failure (MOF) caused by disseminated intravascular coagulation (DIC), and this case was reported as a therapy-related death. Based on these results, docetaxel is an active agent for treatment of head and neck cancer.
In order to study the mechanisms of ocular circadian rhythms in the pigeon, we measured melatonin and dopamine simultaneously from the eye using in vivo microdialysis. In experiment 1, the phase relationship between circadian rhythms of ocular melatonin and dopamine under light-dark cycles (LD) and continuous dim light (LLdim) was examined. Under LD, melatonin was high during the dark and low during the light. On the other hand dopamine was high during the light and low during the dark. These rhythms with the anti-phase relationship were maintained after the birds were transferred from LD to LLdim. In experiment 2, effects of a single light pulse on melatonin and dopamine rhythms were examined. A light pulse at CT18 rapidly suppressed melatonin release to the daytime level, whereas it rapidly increased dopamine release to the daytime level. The light pulse also affected the phases of melatonin and dopamine rhythms, inducing phase advances of both rhythm without changing the anti-phase relationship before the light pulse. In experiment 3, effects of an intraocular injection of dopamine or melatonin on their circadian rhythms were examined. A dopamine injection during the subjective night suppressed melatonin release and induced a light-pulse type phase shift in both melatonin and dopamine rhythms. On the other hand, a melatonin injection during the subjective day suppressed dopamine release and induced a dark-pulse type phase shift. These results are compatible with either one or two oscillator models, but the interaction between melatonin and dopamine is, in either case considered as an important mechanism regulating ocular circadian rhythms of the pigeon.
BACKGROUND: The incidence of cervical metastases after surgery for Stages I/II carcinoma of the tongue is 30-40%. Postoperative cervical metastases are an adverse prognostic factor for patients with this malignancy. The purpose of this study was to evaluate the clinicopathologic factors associated with late cervical metastases in patients with carcinoma of the tongue. METHODS: The clinicopathologic features of 44 patients with previously untreated Stage I/II carcinoma of the tongue were reviewed. All patients were treated with partial glossectomy only. RESULTS: Cervical metastases developed in 21 of 44 patients within 5 years. Factors significantly associated with the development of cervical metastases were invasive growth, differentiation, nuclear polymorphism in the deep portion, tumor border, nest formation, infiltrative growth ratio, depth, and thickness. No statistical correlations between cervical metastases and age, gender, tumor location, clinical stage, Brinkman index, alcohol index, mitosis, connective tissue, lymphocytic infiltration, or perineural invasion were found. Multivariate analysis demonstrated that only tumor thickness > 4 mm had a predictive value for cervical metastasis (risk ratio 9.4; 95% confidence interval, 1.5-57.7). CONCLUSIONS: The current study data indicate that patients with Stage I/II carcinoma of the tongue > 4 mm in thickness are at increased risk for subsequent cervical metastasis. Thus, conservative supraomohyoid neck dissection is indicated in patients with Stage I/II carcinoma of the tongue > 4 mm in thickness.
We detected rhodopsin gene expression in the pigeon lateral septum, a photosensitive deep brain region that is responsible for the photoperiodic gonadal response. The nucleotide sequence of the deep brain rhodopsin cDNA clone exactly matched that of the retinal one, indicating that a single rhodopsin gene is transcribed in the two tissues. Immunohistochemical analysis localized rhodopsin in the cerebrospinal fluid-contacting neurons, which have been assumed to be photoreceptive cells in the deep brain. Pigeon rhodopsin seems to play dual important roles in the visual and non-visual systems, the latter of which contributes to the photoperiodic response.
Although it is well known that visual image formation is mediated by rods and cones, photoreceptors implicated in entrainment of circadian rhythms remain unknown. In our previous study, 12-week-old CBA/J-rd/rd mice were found to show decreased sensitivity in circadian photoreception. Because rd gene induces different age-related degeneration of cones and rods, we have examined age-related changes in the sensitivity to a light pulse for phase-shifting the locomotor activity rhythms in CBA/J-rd/rd mice. Since mice have middlewave-sensitive cones (M-cone, 510 nm) and shortwave-sensitive cones (S-cone, 360 nm), a 15-min monochromatic light pulse (501.6 or 359 nm; 10 microW cm(-2) s(-1)) was given at circadian time (CT) 16, 2 weeks after being transferred to constant darkness (DD) and the magnitude of phase shift was determined. The amount of phase shift by a green light pulse (501.6 nm) gradually declined from 8 to 16 weeks after birth and the similar tendency was also observed on a UV pulse (359 nm). The similar pattern of age-related decline in the number of cones and circadian photosensitivity in CBA/J-rd/rd mice suggest that cones are involved in the circadian photoreception in mice.
OBJECTIVE: To report on a new concept and simple operative procedure to conform the diameter of the oral end of free jejunal grafts to that of pharyngeal defects for reconstruction of the lower pharyngeal space. DESIGN AND METHODS: A preliminary study showed that the jejunum is supplied by a highly vascular network and that longitudinal paramesenteric incisions can be made without disturbing the blood supply of the jejunum. We then developed the following operative procedure. The position of the highest point of the pharyngeal defect and the site of the recipient vessels are determined. The free jejunal graft is positioned with its mesentery in correspondence with the location of the recipient vessels. The position of a longitudinal incision 180 degrees to the highest point of the defect is then determined. After the oral border of the jejunum is opened with scissors, a pharyngojejunal end-to-end anastomosis is performed. PATIENTS: Eighteen patients with defects of the lower pharyngeal space after cancer treatment. RESULTS: We transferred jejunal grafts in 18 patients using this operative procedure. In 7 of these patients, paramesenteric incisions were made. The lengths of the incisions ranged from 2 to 8 cm. Transfer was successful in all 18 patients. Postoperative leakage occurred in 1 patient in whom an antimesenteric incision had been made; however, a fistula did not develop. CONCLUSIONS: Our method allows defects of the lower pharyngeal space to be reconstructed with end-to-end anastomosis of free jejunal grafts regardless of the location of the defect or of recipient vessels. This method is simple and appropriate for correcting large pharyngeal defects.
A patient with a locally advanced cervical esophageal carcinoma invading the trachea underwent total esophagopharyngolaryngectomy and resection of the posterior wall of the trachea. The esophagus was repaired with a gastric pull-up, and the posterior defect in the trachea was repaired with a free radial forearm flap, obtaining a satisfactory result.
We reviewed 109 consecutive patients with cancer of the hypopharynx or cervical oesophagus who underwent free flap transfer for immediate reconstruction after total pharyngolaryngo-oesophagectomy. The free flaps used were either free jejunal (n = 70) or radial forearm flaps (n = 39). Significantly more fistulas (3/70 compared with 15/39, p < 0.0001) and strictures (6/64 compared with 13/33, p = 0.0008) developed in the radial forearm than the jejunal flap group. However, functional donor site morbidity was minimal and there were no cases of total flap necrosis in the forearm flap group. We consider that the free jejunal flap should be the first choice for total reconstruction of pharyngo-oesophageal defects. However, the forearm flap is suitable for elderly, high risk patients, because it is less invasive and has minimal donor site morbidity, which facilitates early recovery.
Postoperative salivary fistulas still remain a serious and potentially lethal problem in head and neck reconstruction particularly if the fistula is large and involving one half or more of the circumference of the pharyngo-oesophagus. Pedicled flaps have traditionally been the flaps of choice for closure of these fistulas, but the results are often disappointing. During the period 1982 to 1995, we have used either a radial forearm free flap or a jejunal free flap to close large and complex pharyngo-oesophageal fistulas after resection for cancer in 15 patients. Although two patients developed major fistulas that required additional operations for closure, successful closure was achieved in all but one case: the success rate was therefore 14/15 (93%). We consider that jejunal flaps are suitable for circumferential pharyngo-oesophageal reconstruction and forearm flaps for non-circumferential defects.
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We performed six immediate free flap reconstructions after tumor ablation in 5 children under the age of 15 years presenting with head and neck malignancy. One patient underwent free flap transfer on two separate occasions because of tumor recurrence. There were no flap losses nor were there any complications related to microvascular surgery. Although a pediatric head and neck malignant tumor is rare, surgical resection is the primary therapeutic role for those that are amenable to complete excision. Pediatric microsurgery provides a safe and reliable procedure for reconstruction of head and neck defects after extirpation of the tumor.
A carcinoma originating from the posterior wall of the oropharynx is not common, and radiotherapy has been used for years in this event without acceptable success. A free flap patch was used in 4 patients to reconstruct the defect after resection of a T2 or T3 carcinoma on the posterior wall of the oropharynx without laryngectomy. The free flaps used were the radial forearm and the free jejunal patch in 2 patients each. There was no flap loss, and successful laryngeal preservation was obtained in 3 of 4 patients. Laryngeal preservation surgery using a free flap patch proved very useful in selected patients with carcinoma of the posterior wall of the oropharynx. Based on our clinical experience, the free jejunal patch seems superior to the free forearm flap with regard to postoperative functional results.
We have transferred 74 free or pedicled anterolateral thigh flaps, including those combined with other flaps, for reconstruction of various types of defects. We report several anatomic variations of the lateral circumflex arterial system and discuss some technical problems with this flap. Septocutaneous perforators were found in 28 of 74 cases (37.8 percent), and no perforators were found in 4 cases (5.4 percent). In the 70 cases with perforators, 171 tiny cutaneous perforators (an average of 2.31 per case) were found. Musculocutaneous perforators (81.9 percent) were much more common than septocutaneous perforators (18.1 percent). Perforators were concentrated near the midpoint of the lateral thigh, and the selection of perforators as nutrient vessels for the anterolateral thigh flap was related to the length of the pedicle and the thickness of the skin flap. Anatomic variations of the branching pattern of perforators were classified into eight types. Flaps with perforators that arise directly from the profunda femoris artery are difficult to combine with other free flaps. Because the perforators are extremely small and tend to thrombose soon after congestion develops, these flaps are difficult to salvage with recirculation surgery. Therefore, several perforators should be included with the flap, if possible. The descending artery of the lateral circumflex femoral artery was always accompanied by two veins with different back-flow strengths. Therefore, veins for microsurgical anastomosis must be chosen carefully. Because it is nourished by several perforators arising from the descending artery, the vastus lateralis muscle can be combined with the anterolateral thigh flap. However, splitting the muscle longitudinally without harvesting its blood supply is complicated because its fibers are oblique. The rectus femoris muscle can also be combined with the anterolateral thigh flap, but its pedicle is short and its origin is very near the site of anastomosis. When the anterolateral thigh flap is combined with the tensor fasciae latae musculocutaneous flap, the large skin area of the lateral part of thigh can be transferred to repair the massive defects. The anterolateral thigh flap has many advantages and can be used to reconstruct many types of defect. However, anatomic variations must be considered if the flap is to be used safely and reliably.
Endotoxemia is associated with impaired diaphragm contractility, and increased nitric oxide (NO) production has recently been implicated in this phenomenon. However, the precise nature of sepsis-related alterations in diaphragm myofiber function remains unclear. We tested the hypothesis that enhanced NO synthesis during sepsis produces diaphragm sarcolemmal injury with attendant abnormalities of myofiber membrane electrophysiology. Two different rat sepsis models were employed: acute (4 h) intraarterial endotoxin (LPS; 20 mg/kg) and subacute (24 h) peritonitis induced by cecal ligation and perforation (CLP). Diaphragm damage occurred after both LPS and CLP, as indicated by hyperpermeability of myofibers to a low molecular weight tracer dye, which is normally unable to penetrate the sarcolemma. Sarcolemmal injury was significantly correlated with reductions in the resting membrane potential (Em) of single diaphragm myofibers. Western analysis revealed increased diaphragmatic expression of the inducible isoform of NO synthase (iNOS) after LPS and CLP. An inhibitor of NOS activity, LNMMA, significantly decreased morphologic as well as electrophysiologic signs of myofiber membrane injury and dysfunction. Therefore, we conclude that both acute endotoxemia and subacute peritonitis models of sepsis lead to significant sarcolemmal damage and altered Em in diaphragm myofibers. These changes appear to be mediated, at least in part, through the pathway of increased nitric oxide production.
Thirty patients with tracheal invasion of differentiated thyroid cancer underwent partial resection of the tracheal wall between 1978 and 1996 at National Cancer Center Hospital. In most cases, the defect in the tracheal wall was reconstructed secondarily using a local flap. This method was easy in comparison with end-to-end anastomosis of the trachea following circumferential resection of the wall. Partial resection of the tracheal wall proved to be a effective treatment for thyroid cancer invasion of the tracheal, because of low incidence of local recurrence. When the defect of the tracheal wall was too large to be reconstructed using a local flap, hydroxylapatite was employed and good results were obtained.