Quality of life following esophagectomy with three-field lymphadenectomy for carcinoma, focusing on its relationship to vocal cord palsy.

To clarify the quality of life of patients who underwent esophagectomy for carcinoma by right thoracotomy, laparotomy and cervical anastomosis, 116 patients who were cancer free at the time of mailing a questionnaire were analyzed. A significant decrease in vital capacity for 3 years postoperatively, as well as in the percentage of ideal body weight, between 3 and 5 years were observed in 57 patients with three-field lymphadenectomy. Patients' quality of life undergoing three-field dissection was worse than those with less radical lymphadenectomy (59 cases) in terms of the performance status and difficulty in talking at 60 months or more postoperatively. Around 20% of all patients reported severe hoarseness due to permanent recurrent nerve paralysis, resulting in poor quantity of food intake at 24 months or less postoperatively and restricted daily activity and difficulty in talking at 60 months or more after the operation. When a patient suffers from vocal cord insufficiency caused by permanent paralysis of the recurrent nerve, early treatment before discharge from the hospital should be performed to improve the quality of life of such a patient.

Human papillomavirus detected in female breast carcinomas in Japan.

To investigate the aetiological role of human papillomavirus (HPV) in breast cancer, we examined the presence, genotype, viral load, and physical status of HPV in 124 Japanese female patients with breast carcinoma. Human papillomavirus presence was examined by PCR using SPF10 primers, and primer sets targeting the E6 region of HPV-16, -18, and -33. The INNO-LiPA HPV genotyping kit was used to determine genotype. Human papillomavirus DNA was detected in 26 (21%) breast carcinomas. The most frequently detected HPV genotype was HPV-16 (92%), followed by HPV-6 (46%), HPV-18 (12%), and HPV-33 (4%). In 11 normal epithelium specimens adjacent to 11 HPV-16-positive carcinomas, 7 were HPV-16-positive. However, none of the normal breast tissue specimens adjacent to HPV-negative breast carcinomas were HPV-positive. The real-time PCR analysis suggested the presence of integrated form of viral DNA in all HPV-16-positive samples, and estimated viral load was low with a geometric mean of 5.4 copies per 10(4) cells. In conclusion, although HPV DNA was detected in 26 (21%) breast carcinomas and, in all HPV-16-positive cases, the HPV genome was considered integrated into the host genome, their low viral loads suggest it is unlikely that integrated HPV is aetiologically involved in the development of Japanese breast carcinomas that we examined.

Endoscopic quadrantectomy for breast cancer with sentinel lymph node navigation via a small axillary incision.

A great deal of clinical experience has firmly established the concept of the sentinel lymph node (SN) in breast cancer. SN biopsy allows treatment without axillary lymphadenectomy and has made it possible to perform a surgical intervention via just a small skin incision. In partial resection of the breast (quadrantectomy), we use a double retractor to form a workspace under the skin via a small axillary incision. Resection does not require a large incision even in cases in which the cancer lesion is located in the upper inner or lower inner quadrant of the breast, as the endoscope allows the surgeon to see the workspace formed by the double retractors.

Expression of desmoglein-I cell-adhesion molecule in primary tumors and metastatic lymph-nodes of esophageal cancer.

The expression of desmoglein I (DGI) in both primary turners and metastatic lymph node of esophageal carcinoma was studied immunohistochemically in 102 patients using an anti-DGI monoclonal antibody. Normal squamous epithelial cells strongly expressed DGI at their cell-cell boundaries. DGI expression in the tumors was divided into DGI (++), DGI (+), DGI (-) according to the staining intensity. DGI (+) or DG (-) tumors had lymph node metastases more frequently than DGI (++) tumors (p<0.01). DGI expression was the same or of less intensity, than in the primary tumor in 128 (85%) out of 151 metastatic lymph nodes. These results indicate that reduction or loss of DGI expression may promote lymph node metastases.

Difference in incidence and transmission mode of methicillin-resistant Staphylococcus aureus among surgery, orthopedics, and pediatrics wards: a prospective study at a university hospital.

The incidence and circumstances of colonization by methicillin-resistant Staphylococcus aureus were prospectively investigated. Among 404 patients, 15 (3.7%) were carriers on admission, and 43 (10.6%) became colonized, mainly after surgical operation. A different mode of transmission was suggested in each ward.

Enhanced efficacy of bleomycin adsorbed on silica particles against lymph node metastasis in patients with esophageal cancer: a pilot study.

BACKGROUND: Lymph node metastases occur very frequently and extensively in patients with esophageal cancer. The aim of this pilot study was to try the targeting chemotherapy for lymph node metastases by use of bleomycin adsorbed on silica particles (BLM-SI). METHODS: BLM-SI or bleomycin solution (BLM-SOL) was injected into the submucosa of the esophageal wall by means of endoscopy 3 days before operation in 16 patients with middle thoracic esophageal cancer. The distribution of bleomycin in the regional lymph nodes and surrounding connective tissues was studied. RESULTS: When BLM-SI was administered, bleomycin activity was found in both the regional lymph nodes and connective tissues, not only in the mediastinal region but also in the cervical and abdominal region. Bleomycin activity was significantly higher in all regions after BLM-SI administration than after BLM-SOL administration. Degenerative or necrotic changes were microscopically observed in 11 of 36 lymph nodes with metastatic foci. Bleomycin activity in the blood was significantly lower after BLM-SI was administered than after BLM-SOL. Serious systemic side effects except for fever were not observed in any patients. CONCLUSIONS: These results indicate that BLM-SI could be a useful treatment modality for targeting lymph node metastasis of esophageal cancer without serious side effects.

Urea polyacrylamide gel electrophoresis of PCMB precipitate as a sensitive test for the detection of the unstable hemoglobin subunit.

A sensitive test for the detection of the abnormal subunit of unstable hemoglobins is described. The unstable hemoglobin subunit was selectively precipitated by paramercuribenzoic acid treatment of the carboxy hemolysate, and the precipitate was studied by urea polyacrylamide gel electrophoresis for globin composition. The test enabled the detection of an electrophoretically silent, alpha-chain unstable variant comprising only 1% of total hemoglobin. Other applications included the demonstration of Hb Köln in a cord blood, and the detection and purification of very slightly unstable hemoglobin variants.

Positive impact on surgical treatment for asymptomatic patients with esophageal carcinoma.

BACKGROUND/AIMS: The prognosis of patients with esophageal carcinoma remains unsatisfactory. The purpose of this study was to clarify the clinicopathologic characteristics of asymptomatic patients. METHODOLOGY: We retrospectively compared 78 cases of asymptomatic esophageal carcinoma (AEC) with 341 cases of symptomatic esophageal carcinoma (SEC). RESULTS: In 47 of 78 patients with AEC, the tumors were discovered by mass screening and in 31 patents by follow-up examination for other disease. Nearly 70% of the patients with AEC had a carcinoma in situ (Tis) or T1 tumor, whereas nearly 70% of the patients with SEC had T3 or T4 tumors. The incidences of lymph node metastasis, lymphatic invasion and vascular invasion were significantly lower in patients with AEC than in those with SEC. The 5-year survival rate in AEC and SEC were 59.3% and 22.9%, respectively. With regard to the cause of death, 26.8% (11/41) of patients with AEC and 59.9% (166/277) of patients with SEC died of esophageal carcinoma. CONCLUSIONS: In order to improve the prognosis of esophageal carcinoma, an effort should be made to detect early esophageal carcinoma among patients at risk for tumors when they are still asymptomatic.

Analysis of macroscopic appearance and p53 expression in superficial esophageal carcinoma.

BACKGROUND/AIMS: The purpose of the present study was to investigate the relationship between macroscopic appearance of superficial esophageal carcinoma, with particular attention to the horizontal and vertical extent of tumor growth, clinicopathologic findings and p53 expression. METHODOLOGY: Eighty-seven patients with superficial esophageal carcinoma were divided into three groups: 1) group A, patients with protruding or distinct depressed lesions (n = 28); 2) group B, patients with superficial and flat lesions > or = 5 cm in length (n = 45); and, group C, patients with superficial and flat lesions (5 cm in length (n = 14). Tumors were examined immunohistochemically for p53 expression. RESULTS: The incidence of submucosal invasion, lymph node metastasis and lymphatic invasion was significantly higher in group A than in groups B and C. The rate of p53 expression was significantly lower in group B than in the other two groups. The prognosis in groups B and C was better than that in group A. CONCLUSIONS: Vertical extent was more strongly associated with tumor depth, lymph node metastasis and prognosis than was horizontal extent, although p53 overexpression was related to both the vertical and horizontal extent of tumors. Analysis of the macroscopic appearance of superficial esophageal carcinoma is useful in choosing treatment strategies.

[Diurnal sleep apnea in myotonic dystrophy].

We investigated diurnal sleep apnea in myotonic dystrophy with respiratory inductive plethysmography. Five of eight patients met criteria for sleep apnea syndrome and had central apnea mainly. In a case showing periodic breathing with apnea like Cheyne-Stokes type breathing, the duration of apnea and breath was even and the tidal volume went waxing and waning regularly. In the other four cases, central apneas were observed in sequence, but the duration of apnea and the tidal volume changed variously. Large breaths between apneas elevated arterial oxygen saturation rather than stable breaths without apnea. We suspected that hypoxemia, which exacerbated by involvement of respiratory muscles, supine position and sleep, initiated the hyperventilation between apneas. And then the saturation of oxygen raised by hyperventilation would cause central sleep apnea.

[Aggravation of hypoxemia in supine position in myotonic dystrophy].

Myotonic dystrophy (MyD) involves a variety of systems. Respiratory disorders are common, namely elevation of diaphragm, alveolar hypoventilation, aspiration pneumonia and sleep apnea. We evaluated respiratory involvement. The subjects were 11 patients with MyD. Also 6 patients with limb girdle muscular dystrophy (LG) were examined to be compared with MyD. Both groups had the similar activities of daily living. All of them never complained of dyspnea. Arterial blood gas studies were performed in supine position and standing position. A new evidence was found that hypoxemia was aggravated and alveolar-arterial oxygen pressure difference was increased in supine position in MyD. Next, pulmonary function tests were done in supine position and sitting position. Functional residual capacity (FRC) were more reduced in supine position in MyD compared with LG. The value to subtract closing capacity from FRC was negative in supine position in MyD, showing closing phenomenon. We propose the mechanism of the aggravation of hypoxemia may be the following. The reduction of FRC caused by respiratory muscle involvement brings out the closing phenomenon. Abnormal uneven distribution of ventilation-perfusion ratio happens and then hypoxemia is worsened in supine position in MyD.

[Enzyme saturation of sevoflurane in piglets at clinically-used concentrations].

To investigate if sevoflurane saturates the metabolic capacity of the enzymes responsible for sevoflurane at clinically-used concentration ranges, we compared plasma fluoride levels and urinary excretion of inorganic fluoride in piglets after (1) low concentration sevoflurane anesthesia versus (2) high concentration sevoflurane anesthesia. Eleven male piglets, weighing 18-23.5 kg, were randomly divided into two groups: 1) L group: five animals were anesthetized for two hours with sevoflurane at 0.8% end-tidal concentration (0.4 MAC); 2) H group: six animals were anesthetized for two hours with sevoflurane at 3.0% end-tidal concentration (1.4 MAC). Plasma inorganic fluoride levels, blood sevoflurane concentration, urinary inorganic fluoride concentration and urine volume were measured. The blood sevoflurance concentration in both groups reached their plateau levels 30 min after the start of anesthesia. The plateau levels in the H and L groups were 275-306 microM and 105-115 microM, respectively. The plasma fluoride concentrations reached plateau levels 60 min after the start of anesthesia in both groups. The H group showed significantly higher plasma fluoride levels than the L group during sevoflurane anesthesia. The H group also showed significantly higher urinary excretion of inorganic fluoride than the L group. Therefore, metabolite production levels in the H group were significantly higher than the L group. These results suggest that low concentration sevoflurane anesthesia did not saturate the metabolic capacity of the enzymes responsible for defluorination of sevoflurane in piglets.

[Comparative study on the macroscopic and histopathological diagnosis of lymph node metastases in cancer patients].

Macroscopic diagnosis for lymph node metastases was compared with histopathological diagnosis in 444 patients with carcinoma of the esophagus, stomach, colon, thyroid and breast. The former indicated lymph node metastases in 181 patients. In all of them, none or less than five node metastases were proven by routine histopathological diagnosis. Detailed histological study revealed lymph node metastases in 25 out of 263 patients with macroscopically negative nodes, the rate of false negative being 9.5 per cent. The study also demonstrated no lymph node metastases in 51 of 181 patients with macroscopically positive nodes. Three additional specimens were obtained from originally examined 693 lymph nodes and reexamined microscopically in these 51 patients. Involvement by cancer cells was detected in 9 nodes (1.3 per cent) in 8 patients. Metastases were found from additional specimens in 7 of 9 nodes, indicating that metastatic carcinoma had been overlooked in the remaining two nodes. Additional specimens or embedding-techniques were recommended in such cases as macroscopic metastases were strongly suspected or lymph vessel invasions were remarkable. In 24 patients with esophageal cancer, one to one correspondence was available in the analysis of macroscopic diagnosis. Seventy-eight out of 108 involved nodes were macroscopically judged as involved (sensitivity; 72.2 per cent), and 1166 out of 1260 nodes without macroscopical metastases were judged as cancer-free (specificity; 92.5 per cent). Overestimation of macroscopic diagnosis was due to thickened capsule, fibrosis, inflammation and enlargement in size more than 10 mm in diameter of the nodes. Underestimation was observed in case of nodes with metastatic area less than one-third and with smaller size less than 5mm in diameter.

[Quality of life of patients after esophagectomy for esophageal cancer].

Quality of life of 79 patients who underwent esophagectomy for esophageal cancer and survived more than one year was evaluated by a questionnaire method. About 90% of patients had a good appetite, taking ordinary solid foods, and 69% were satisfied with the daily amount of foods. About 40% of patients complained of passage disturbance on swallowing, abdominal pain or diarrhea after meal. Fifty seven per cent of patients had frequent episodes of cough and sputum, and 20% were not able to go up the stairs to the third floor because of short breath. Thirty two per cent of patients with recurrent nerve paresis and even 5% without paresis had a trouble in daily conversation. These physical distresses were thought to be useful indicators for the doctor to evaluate the quality of life of patients. Additionally, about 30% of patients had a tendency of mental depression postoperatively. Fifty six per cent of patients who had worked before operation returned to work or were doing a lighter work than before. The psychological factor and social rehabilitation were suggested to be very important, when evaluated from the patient's side. Especially in case of aggressive surgery for esophageal cancer, postoperative quality of life of patients should be carefully considered from the viewpoints of both the patient and doctor.

[Clinicopathological studies of the recurrence of esophageal squamous cell cancer--with special reference to the mode of recurrence and operative procedure].

In 93 out of 201 patients (46%) with squamous cell carcinoma of the esophagus who underwent radical resection (excluding death within 30 days after operation), the site of recurrence could be identified by means of X-ray, CT, ultrasonography, and biopsy. Recurrence was found in 55% of 93 cases within 12 months after surgery and in 86% of 93 cases within 24 months. Of 93 patients with recurrences, lymph node recurrences were present in 44 cases, visceral recurrences in 32 cases, both lymph node and visceral recurrences in 11 cases and others in 6 cases. Neck and/or upper mediastinal lymph node recurrences were found in 10 out of 15 patients who had recurrences within 3 months after surgery. Careful examination should be made in the left recurrent nerve chain and extended lymph node resection of upper mediastinal region should be performed under the adequate indication. Esophageal squamous cell cancer has a tendency to recur in the lymph nodes initially, and visceral metastases may occur thereafter. The incidence of visceral recurrence increased remarkably, when neck and/or upper mediastinal lymph nodes were involved at the time of operation. Accordingly, both irradiation and chemotherapy should also be applied for improving the prognosis of esophageal carcinoma.

[Lymph node metastases in the thoraco-cervical transitional region in thoracic esophageal cancer--with ultrasonic detection and a comment on the guide lines].

Lymph node metastases in the thoraco-cervical transitional region (TCTR) and its ultrasonic detection were evaluated in 64 patients with thoracic esophageal cancer, who received radical esophagectomy with modified neck dissection. Lymph node metastases in TCTR were found in 19 of 64 cases (29.7%). Nodal metastases in the supraclavicular region were found in similar incidence of 23.4% (15 of 64 cases). Lymph nodes in both regions were infiltrated in 8 cases. Direct metastases to supraclavicular region and metastases in single region of TCTR were indicated in 4 cases equally. The degree of lymph node metastases of 11 patients suffered from middle intra-thoracic esophageal (Im) cancer with nodal involvement in TCTR were divided into three groups, two cases of n2, one of n3 and eight of n4, according to the Guide Lines. Convex type probe excelled in description of TCTR. Swollen lymph nodes were detected in 12 out of 19 cases with metastases by preoperative ultrasound using this probe (sensitivity of 63.2%). Forty-four of 45 cases without metastases were diagnosed as such (specificity of 97.8%). The partition of TCTR in the Guide Lines should be reconsidered for better evaluation of the results on lymph node metastases in this region.

[Pre-operative staging in advanced gastric cancer by ultrasound; with special reference to para-aortic lymph node metastases].

Extraluminal cancer spreadings such as peritoneal dissemination, liver metastases, lymph node metastases and infiltration to surrounding organs were examined in 236 patients with gastric cancer by ultrasound (US). Peritoneal dissemination was found in 36 of 236 cases. Ascites, nodules in the cul-de-sac and thickened wall of the transverse colon could be detected by US in 24 of 36 cases (sensitivity of 67%). Liver metastases were detected in 18 out of 23 cases (78%). Infiltration to the surrounding organs, mainly to the pancreas, was impossible to demonstrate by US. Sensitivity was 44% (17/39). Lymph node metastases in the region around the celiac axis were indicated in 30 of 40 cases (75%) by US. Para-aortic nodal metastases were also detected in 27 of 34 cases (79%). Ultrasonic images of para-aortic lymph node metastases were classified into four figures: plate type, sandwich type, unilateral multiple type, unilateral solitary type. These types were not necessarily the same in indication of laparotomy, selection of combined or adjuvant therapy, significance of nodal dissection and also prognosis. Solitary involved para-aortic node near the left renal vein should be removed in a case free from peritoneal dissemination or liver metastases. Ultrasound could be very useful in screening patients with gastric cancer for peritoneal dissemination, liver metastases and lymph node metastases.

[Thyroid nodules; evaluation of malignancy by ultrasonography].

Preoperative ultrasonic examination was correlated to final pathological diagnosis in 102 cases which underwent thyroidectomy in our clinic from 1979 to May 1985. Preoperative ultrasonic diagnosis was as follows: Sensitivity was 78% (45/58 cases), and specificity was 86% (38/44 cases). Four factors in ultrasonic image were considered: Shape, boundary, internal echo and margin were featured, and correlated to malignancy in 75 cases with mainly solid nodules. Among 34 nodules with irregular shape, 33 (97%) were pathologically malignant and 40 of 42 (95%) with rugged boundary were also malignant. Whether internal echo was even or not could not be used as a diagnostic criteria. Similarly, whether a nodule had well defined margin or not was found not to be a significant criteria in order to differentiate malignant from benign lesions. In 15 of 34 cases with lymph node metastases, metastatic lymph nodes were detected by ultrasonography. Lymph node metastases must be also evaluated by ultrasonography preoperatively in thyroid diseases. Each of these factors must be considered individually in the diagnosis of thyroid nodules. By evaluation of the ultrasonography findings the pathological characteristics may be inferred, and consequently being possible to reach a correct diagnosis.

[Clinical evaluation of the esophageal lymph flow system based on RI uptake of dissected regional lymph nodes following lymphoscintigraphy].

For surgical treatment of esophageal cancer, the importance of evaluating lymph node metastasis and the lymph flow of the esophagus can not be overemphasized. In oder to investigate the lymph flow of the esophagus, we preoperatively performed lymphoscintigraphy by endoscopic local injection of 99mTc Rhenium Colloid into the esophageal wall in 42 esophageal cancer cases and 4 gastric cancer cases. Postoperatively, the RI uptake of each dissected regional lymph nodes was examined by a Scintillation Counter. The findings were as follows. From the upper third of the thoracic esophagus, the main lymph flow was ascending to the neck and upper mediastinum. From the middle third, the lymph flow was ascending to the neck and upper mediastinum and descending into the abdomen. From the lower third, the main lymph flow was descending to the abdomen. In some cases, the lymph flow to the tracheal bifurcation nodes or to the lymph nodes around the left renal vein was observed. In 61% of the esophageal cancer cases with a partial bilateral neck dissection, the lymph flow to the bilateral supraclavicular lymph nodes was predominant compared to the upper mediastinum nodes.

[Histopathological features of the lymph node metastases in patients with thoracic esophageal cancer].

Histopathological features of the lymph node involvement were studied in 104 patients with thoracic esophageal cancer who underwent subtotal esophagectomy combined with extended radical lymph adenectomy in cervicothoracoabdominal region. Metastatic involvement was found in a total number of 503 lymph nodes from 73 patients by histologic examination. The mean of long and short diameter was found to be less than 5mm in 125 (24.9%) of these 503 nodes. The involved area on the section was less than one third in 149 nodes (29.6%), and was significantly smaller in mediastinal lymph nodes than those in cervical or abdominal ones. Sixty-seven (13.3%) of 503 nodes were partially invaded by micrometastasis of 1mm or less in diameter. Micrometastasis also more frequently occurred in mediastinal nodes with a statistically significant difference. Extranodal proliferation (ENP) of cancer cells was found in 106 nodes (21.1%), and extranodal lymphatic and/or blood vessel invasion (ENly, v) was also recognized in 60 nodes (11.9%). Micrometastasis and ENP with or without ENly, v were found in 24 (32.9%) and 29 (39.7%) of 73 patients with positive lymph node metastasis, respectively. Postoperative survival rate in patients with micrometastasis and/or ENP with or without ENly, v was inferior to that in patients with neither of them.