Review of US medical school finances, 1995-1996

We discussed the rational extent of the lymph node dissection for carcinoma of the lower third of the esophagus of T2 or T3 stage with abdominal lymph node metastasis. Lymph node metastasis developed in 89.5% of patients. Cervical lymph node metastasis was seen in 35.8%. In the cases with positive abdominal lymph node, 40.9% of the patients had cervical node metastasis. The most frequent site of the positive node in the neck is the area along the right recurrent laryngeal nerve. On the stand point of removal of metastatic lymph node, neck dissection should be required. Three-field dissection yielded better survival rate than two-field dissection but statistical significance was not obtained. When the patients have cervical lymph node metastasis, they have greater possibility of developing blood borne metastasis. However, this observation does not deny the validity of the three-field dissection. Because this dissection may help reducing nodal spread and nodal recurrence. We have to wait for accumulation of the patients to analyze the definite extent of node dissection for T2 or T3 stage of carcinoma of the lower third of the esophagus with positive abdominal lymph node.     

Autologous blood transfusion

BACKGROUND: The clinical significance of lymph node involvement along the recurrent laryngeal nerves in cancer of the thoracic esophagus is still controversial. Although these lymph nodes are anatomically located in a well-defined compartment (proximal mesoesophagus), appropriate procedures for dissecting them are not well established. STUDY DESIGN: We retrospectively investigated clinical results over the past 10 years in 276 patients who underwent systematic dissection of cervical, mediastinal, and upper abdominal lymph nodes. We routinely performed the cervical procedure before thoracotomy for total dissection of the proximal mesoesophagus and to minimize the operative risk. RESULTS: All macroscopically recognizable lesions were resected in 94% of the patients. The hospital mortality rate was 2.5%. Recurrent nerve palsy developed in 59 patients, but it was successfully managed without prolonged hoarseness in 50 of them. The recurrent nerve node group was most frequently involved (frequency of 25% in superficial cancer, 57% in non-superficial cancer). Supradiaphragmatic lymph node involvement was limited to the recurrent nerve nodes in 25% of the patients with positive supradiaphragmatic node. The 5-year survival rate in patients with positive recurrent nerve nodes was 34%. CONCLUSIONS: Dissection of the recurrent nerve lymph nodes is essential for curative esophagectomy even in the early phase of cancer invasion. Our cervicothoracic approach for total dissection of the proximal mesoesophagus yielded acceptable outcomes.     

Value of MRI, CT and findings in staging of gynecologic malignancies

PURPOSE: The present study was designed to compare the value of MRI, CT and clinical examination in local tumor staging of gynaecologic malignancies. PATIENTS AND METHODS: 99 patients with clinically suspected carcinoma of the cervix uteri, ovarian carcinoma or tumor recurrence after gynaecologic cancer underwent all three staging modalities. Furthermore CT and MRI were compared in detecting lymph node metastasis and peritoneal implants. RESULTS: MRI was superior to CT and clinical staging in local tumor staging with an accuracy of 77% for cervical carcinoma and of 88% for recurrent tumors, whereas CT achieved an accuracy of 65% and 55% and clinical staging 60% and 63% accuracy for carcinoma of the cervix and recurrent cancer. Especially for local staging of these two tumor entities MRI is very useful. MRI and CT reached comparable results in the detection of ovarian tumors with an accuracy of 73% for MRI and 69% for CI. Both imaging modalities also showed equal results in the detection of lymph node metastasis, so that primary the cost saving use of CT tumor staging for ovarian lesions and lymph node metastasis should be favoured.     

Localization of recurrent disease after extended lymph node dissection for carcinoma of the thoracic esophagus

BACKGROUND: The role of aggressive locoregional dissection in the treatment of carcinoma of the thoracic esophagus is controversial. The extent of disease spread for which resection can be performed is not yet fully established. STUDY DESIGN: Of 230 patients who underwent extended lymph node dissection, including the cervical nodes, the overall hospital mortality rate was 4.8 percent. Recurrent carcinoma was clinically confirmed by periodic follow-up examination with diagnostic imaging in 83 patients. We examined the exact anatomic sites of recurrent lesions and the clinical courses of patients. Recurrence patterns were classified into locoregional, distant, and mixed types. RESULTS: Recurrence of the carcinoma was locoregional in 35 patients, distant in 38 patients, and mixed in ten patients. The frequency of locoregional recurrence was significantly lower in patients with less than eight positive nodes and in patients without invasion of neighboring organs. Locoregional recurrence in the dissected area was mainly found in the region around the recurrent nerves and the main bronchi. Lymph nodes outside of the dissected area developed recurrence only in cases of markedly advanced disease apart from the abdominal para-aortic nodes. The group with locoregional recurrence and the group with distant recurrence had similar clinical courses over time. In patients in whom recurrent lesions could be treated with resection and adjuvant therapy, the one-year survival rate after recurrence was 83 percent. CONCLUSIONS: Unless the disease was markedly advanced, systematic lymph node dissection in our procedures yielded good locoregional control. The relatively low rate of distant recurrence with acceptable hospital mortality rates favors an extensive operation. When recurrent lesions were localized macroscopically, surgical removal of the recurrent lesions offered good palliation.     

Interindividual variability of histamine N-methyltransferase in the human liver and kidney

We report on a case of primary cutaneous adenoid cystic carcinoma with local recurrence and lymph node metastasis. The patient was a 52-year-old Japanese woman. The initial cutaneous lesion was a skin-colored, centrally elevated, thumb-sized nodule with hair loss on the scalp in the right side of the parietal region. Three and half years after the initial combined treatment consisting of surgery and irradiation, a recurrent nodule on the left side of the parietal region of the scalp and a lymph node metastasis with perinodal tissue involvement in the left retroauricular area were discovered. In the literature on primary cutaneous adenoid cystic carcinoma, the average age in the 37 cases reported, including the present case, is 58.1 years, and 23 of the patients are women. Thirty-two percent of the carcinomas (12 cases) occur on the scalp and 16% (6 cases) on the breast. The average size of the tumors in the 24 documented cases is 3.2 cm. The local recurrence rate is 51% (19 cases). Distant metastasis to the lungs and pleura are recorded in three cases. Lymph node metastasis is recorded only in two cases including the present case. Multiple modalities including surgery, irradiation, and chemotherapy should be used for this locally aggressive and potentially metastasizing carcinoma.     

Retrospective analysis of the treatment of patients with small cell lung cancer showing poor performance status

To assess the feasibility of treatments for patients with small cell lung cancer (SCLC) showing a poor performance status (PS, Eastern Cooperative Oncology Group; ECOG 3 or 4), we retrospectively reviewed the outcome for 13 SCLC patients showing poor PS treated at the National Cancer Center Hospital between January 1984 and May 1994. The main factors which contributed to poor prognosis were superior vena cava (SVC) syndrome, massive pleural effusion, tracheal stenosis due to lymph node swelling, pericardial effusion and pulmonary fibrosis (causing dyspnea in combination), brain metastasis resulting in neurological disturbance, cachexia, Eaton-Lambert syndrome causing muscle weakness, retroperitoneal lymph node metastasis causing abdominal pain, peritoneal effusion due to abdominal lymph node swelling, vertebral metastasis causing paraplegia, and dermatomyositis/polymyositis (DM/PM) causing muscle weakness. All of the patients received chemotherapy with or without radiotherapy. The PS of 8 patients improved with treatment, but no improvement was seen in 5. We analyzed these 13 patients and considered the treatments for those with poor PS. Chemo-radiotherapy was tolerable in SCLC patients showing PS 3, and improved their PS if severe conditions or combined disease did not arise concurrently. It was further suggested that PS 4 patients with severe conditions or combined disease should not be given the treatments.     

Administration of recombinant interleukin 12 prevents outgrowth of tumor cells metastasizing spontaneously to lung and lymph nodes

The present study investigates the ability of recombinant interleukin 12 (rIL-12) to modulate the growth of a primary tumor as well as the outgrowth of metastatic tumor cells in an ovarian carcinoma (OV-HM) model. This aggressive tumor displayed rapid growth of the primary tumor mass, high incidence of metastases to lung and lymph nodes, and invasion from the primary s.c. site to the peritoneal cavity. Starting 12 days after s.c. tumor cell implantation, several i.p. injections of rIL-12 at 2-3 day intervals resulted in regression of growing tumors. These treated mice did not show signs of metastases or tumor recurrence at the original site. One month after tumor implantation, untreated mice did not have visible lung metastasis, but some did have palpable lymph nodes. At this stage, the primary tumors of animals without palpable lymph nodes were surgically resected. When examined 2 months later, most animals had developed lymph node and lung metastases. In contrast, rIL-12 injections after tumor resection inhibited the development of metastases in both lung and lymph nodes. This contrasted with the failure of IL-2 to prevent metastases. Even for mice already showing signs of lymph node metastases or invasion of the abdominal wall, rIL-12 administration after tumor resection prevented further invasion to the peritoneal cavity and growth of metastatic tumor cells in lung. It was somewhat surprising that the IL-12 treatment of animals after 1 month of tumor growth without resection also resulted in complete tumor regression, as well as eradication of micrometastasis that would have occurred before the treatment. Moreover, they exhibited resistance to a rechallenge with the same tumor but not with a second tumor. Thus, this tumor system provides a relevant model to clinical situations in terms of treatment of advanced tumors and metastases. These results also indicate that IL-12 can induce a curative immune response, even in the face of an aggressive micrometastasizing tumor.     

Significance of full-thickness chest wall resection as a local treatment for sternum metastasis of breast cancer

Bone metastasis of breast cancer generally tends to be multiple. However, breast cancer frequently metastasizes to the sternum as solitary metastasis. Resection of the sternum was reported to be an effective surgical technique for sternum metastasis which could not be remarkably improved by chemo-endocrine therapy and locoregional recurrent breast cancer invading the skin. A first patient was diagnosed with sternum metastasis invading the skin 44 months after radical mastectomy for breast cancer of stage II. A second patient had breast cancer of stage IV simultaneously with metastases to the sternum and the lung. Only the lung metastasis was successfully controlled by chemo-endocrine therapy, but the sternum metastasis was progressive, following radical mastectomy. Both patients manifested solitary bone metastases and underwent full-thickness chest wall resection. The defect of the chest wall was reconstructed with the mucocutaneous flap using the dorsal latissimus muscle in case 1 and with the abdominal rectus muscle in case 2. Twenty months after the resection of the sternum, the first patient suffered from supraclavicular lymph node metastasis, and the multidisciplinary treatment including radiation therapy was indicated. This therapeutic procedure was effective, and the patient survived for 63 months after resection of the sternum. The second patient has made good progress for six months in maintaining complete remission with chemo-endocrine therapy. These findings suggested that surgical resection was a useful local treatment for solitary sternum metastasis.     

High-dose epirubicin in platinum-pretreated patients with ovarian carcinoma: the EORTC-GCCG experience

A follow up study of 20 cases of renal cell carcinoma with regional lymph node metastasis at the department of urology in Niigata Cancer Center Hospital from 1979 to 1993 is presented. During this period, we treated 249 patients with renal cell carcinoma with or without lymph node metastasis. Lymph node metastasis could be estimated in 188 out of 249 patients. Histologically, lymph node metastasis was classified as pN1 in 8 cases, pN2 in 7 cases, and pN3 in 5 cases. The 3- and 5-year survival rates of 20 patients with lymph node metastasis were 45.0% and 16.4%, respectively. Nine of the 20 cases had no distant metastasis and 11 cases had distant metastasis. Three of the 9 patients with distant metastasis had no recurrence. Two of these 3 patients are still alive after 10 years and 3 years and 1 patient died because of acute heart failure. These 3 patients had pN1 metastasis smaller than 1 cm lymph node. Four of the 11 patients with distant metastasis had more than a two-year survival. However, 3 patients died due to renal cell carcinoma although primary and metastatic regions were resected and IFN with chemotherapy were given. Only one patient is still alive without recurrence after 3 years. This case detected as right renal cell carcinoma with pN2 metastasis and bilateral pulmonary metastasis was treated with radical nephrectomy with regional lymph node dissection and administered Methotrexate, VP16 and CisPlatinum chemotherapy and IFN.(ABSTRACT TRUNCATED AT 250 WORDS)     

Surgical treatment of pulmonary metastasis of colorectal cancer. Prognostic survival factors

SURVIVAL RATES: Less than 5% of patients with pulmonary metastasis from colorectal carcinoma will survive at 5 years, but 30% will survive at 5 years after surgical treatment. MAIN PROGNOSTIC FACTORS: The number of nodules, presence of regional lymph node metastases, disease-free interval between treatment of the primary tumor and development of metastasis as well as serum CEA level are the main prognostic discriminants. INDICATIONS FOR SURGERY: An aggressive operative approach is indicated even when there are pulmonary and extra-pulmonary localizations. Repeat thoracotomy is warranted for recurrent disease.     

The postpubertal change in the playful defense of male rats depends upon neonatal exposure to gonadal hormones

Only 19 cases of metastases at the cannula insertion site after laparoscopy for gynecological malignancy have been reported in the literature. One case has been diagnosed with cervical squamous cell carcinoma, whereas the others have been diagnosed with ovarian cancer and borderline ovarian tumor. We present a novel case of laparoscopy-site abdominal wall metastasis from endometrial cancer after laparoscopic-assisted vaginal hysterectomy (LAVH). The 56-year-old female patient exhibited metastases of an abdominal wall trocar site and a perineal site after undergoing LAVH and laparoscopic-assisted (LA) bilateral pelvic lymph node sampling as well as LA para-aortic lymph node sampling for treating endometrial carcinoma, surgical staging IIIC, G3. The interval between the surgical extirpation of endometrial carcinoma and diagnosis of the tumor recurrence was 6 months, suggesting that overmanipulation of the diseased organ during laparoscopic surgery may have resulted in tumor spillage, intraperitoneal dissemination, and wound contamination. Although this procedure has been proven beneficial to patients with benign disease or early-stage gynecologic malignancies, laparoscopic-assisted vaginal hysterectomy may not be efficacious to eradicate advanced gynecological malignancy.     

In vitro diagnosis of axillary lymph node metastases in breast cancer by spectrum analysis of radio frequency echo signals

Axillary lymph node status is of particular importance for staging and managing breast cancer. Currently, axillary lymph node dissection is performed routinely in cases of invasive breast cancer because of the lack of accurate noninvasive methods for diagnosing lymph node metastasis. We investigated the diagnostic ability of ultrasonic tissue characterization based on spectrum analysis of backscattered echo signals to detect axillary lymph node metastasis in breast cancer in vitro compared with in vitro B-mode imaging. Immediately after surgery, individual lymph nodes were isolated from axillary tissue. Each lymph node was scanned in a water bath using a 10-MHz instrument, and radio frequency data and B-mode images were acquired. Spectral parameter values were calculated, and discriminant analysis was performed to classify metastatic and nonmetastatic lymph nodes. Forty histologically characterized axillary lymph nodes were enrolled in this study, including 25 nonmetastatic and 15 metastatic lymph nodes. A significant difference existed in the spectral parameter values (slope and intercept) for metastatic and nonmetastatic lymph nodes. Spectral parameter-based discriminant function classification of metastatic vs. nonmetastatic lymph nodes provided a sensitivity of 93.3%, specificity of 92.0%, and overall accuracy of 92.5%. In comparison, B-mode ultrasound images of in vitro lymph nodes provided a sensitivity of 73.3%, specificity of 84.0%, and overall accuracy of 80.0%. Receiver operating characteristic (ROC) analysis comparing the efficacy of both methods gave an ROC curve area of 0.9888 for spectral methods, which was greater than the area of 0.8980 for B-mode ultrasound. Hence, this in vitro study suggests that the diagnostic ability of spectrum analysis may prove to be markedly superior to that of B-mode ultrasound in detecting axillary lymph node metastasis in breast cancer. Because of these encouraging results, we intend to conduct an investigation of the ability of spectral methods to classify metastatic axillary lymph nodes in vivo.     

Distribution pattern and risk factors of pelvic and para-aortic lymph node metastasis in epithelial ovarian carcinoma

The distribution of lymph node metastasis and the clinicopathologic risk factors for nodal involvement in ovarian carcinoma need to be clarified based on systematic lymph node dissection. We studied 115 patients with ovarian carcinoma who underwent systematic pelvic and para-aortic lymph node dissection between 1987 and 1997. The incidence and distribution of lymph node metastasis are described and the clinico-pathologic risk factors for nodal involvement are investigated. Based on the occurrence of lymph node metastasis in the early stages, the incidence of solitary node involvement and the distribution of lymph node metastasis, we conclude that the primary site of nodal involvement in ovarian carcinoma is the para-aortic node (PAN), especially PAN superior to the inferior mesenteric artery (IMA). By univariate analysis, clinical stage, histologic type (mucinous vs. others), grade, multiple peritoneal metastases, peritoneal cytology, volume of ascites and serum CA125 level were correlated with overall incidence of lymph node metastasis. By performing a multivariate analysis with the clinical stage excluded, it was revealed that grade and peritoneal cytology were independent factors for PAN metastasis (p < 0.0025 and < 0.001, respectively) and that multiple peritoneal metastases and PAN metastasis were significant predictors of pelvic node metastasis (p < 0.01 and < 0.005, respectively). In conclusion, the PANs superior and inferior to IMA should be explored in staging of ovarian carcinoma that appears to be confined to the ovaries. To determine accurately the extent of disease, both the para-aortic and pelvic areas may need to be sampled or dissected in the case of ovarian carcinoma involving the peritoneal surfaces.     

Prognostic factors in oligodendrogliomas

Among 601 patients with early gastric cancer (EGC), the clinicopathological findings of 5 patients (invasion of the mucosal layer in 2 and of the submucosal layer in 3) with distant lymph node metastasis according to TNM classification (third- or fourth-tier lymph node metastasis according to the Japanese classification) were investigated. The proliferating-cell nuclear antigen (PCNA) expression of EGC was also examined immunohistologically. The sites of distant metastasis were the nodes at the root of the mesentery, in the hepatoduodenal ligament, and the paraaortic nodes. While the PCNA-positive rate of EGC with distant lymph node metastasis (35.4%) was significantly higher than that of EGC without lymph node metastasis (14.7% P = 0.01), it was similar to that of EGC with perigastric lymph node metastasis. The cumulative survival rate of the EGC patients with distant lymph node metastasis (5-year survival rate 20.0%) was significantly lower than that without lymph node metastasis (88.2%, P < 0.0001), first-tier lymph node metastasis (76.9%, P < 0.04), or second-tier lymph node metastasis (77.1%, P < 0.04). Thus, although the prognosis of EGC patients with distant lymph node metastasis was poor, a dissection of the distant lymph nodes should be performed when metastasis is suspected.     

Massive adrenal hemorrhage secondary to metastasis of lung cancer

Hemorrhagic adrenal metastasis from lung cancer is extremely rare, although adrenal involvement is common in widely disseminated cancer. We report a case of massive adrenal hemorrhage secondary to metastasis of lung cancer. A 47-year-old female was treated by left upper lobectomy and mediastinal lymph node resection for an adenocarcinoma with intrapulmonary metastasis in the left upper lobe. Eight months later, she presented with right flank and back pain, and abdominal ultrasonography and computed tomography showed a right solitary adrenal tumor with massive hemorrhage. The tumor was not resectable and partially responded to chemotherapy. A massive adrenal hemorrhage, secondary to metastasis of lung cancer, presents with nonspecific clinical signs and symptoms. In lung cancer patients with an acute flank or back pain, hemorrhagic adrenal metastasis should be considered in the differential diagnosis.     

Intra-arterial chemotherapy to improve quality of life in cases of unresectable advanced or recurrent breast cancer

We performed repetitive intra-arterial infusion chemotherapy (I.A.) with epirubicin in order to improve the quality of life (QOL) in 3 cases with locally advanced or recurrent breast cancer which were diagnosed as surgically unresectable and seemed uncontrollable by outpatient systemic chemotherapy. The patients were admitted to our hospital for chest wall invasion, lymph node metastasis, bleeding, pain, or edema in upper extremity. Therapeutic effects included 1 case of CR and 2 cases of PR in the primary site, and similar effects were obtained in metastasized lymph nodes. We could perform mastectomy in both of the 2 cases with locally advanced cancer after I.A., Although leukocytopenia, which was the dose limiting factor in this regimen, was observed in all 3 cases, it was Grade 2 or 3 and recovered by G-CSF. With regard to their QOL, symptoms which had driven them to inpatient treatment remarkably improved in all of the cases. Thus, after 2 series of I.A. they could receive maintenance systemic chemotherapy as outpatients. Our findings showed that the I.A. as a local control treatment in patients with unresectable advanced or recurrent breast cancer is useful for the improvement of their QOL.     

The structural organization of the neurocytes of the nodose ganglion of the vagus nerve that innervate different digestive tract organs in rats

Osteosarcoma lymph node metastasis are uncommon. This paper shows two patients having osteoblastic osteosarcoma with loco-regional lymph node involvement. In the first case two inguinal and pelvic adenomegalies were found to have tumor metastasis two years and a half after initial diagnosis in a control radiological study. Currently the patient is alive three months after the lymphadenectomy. In the second case, several inguinal high density tumoral nodules were identified during the workup of primary tumor.     

Visualising lymph nodes by aclarubicin bound to activated carbon particles in breast cancer surgery

A new dosage formulation (ACR-CH), composed of aclarubicin (ACR) bound to fine activated carbon particles, has been developed for the treatment of lymph node metastases in breast cancer. ACR-CH is designed to (a) adsorb a great amount of aclarubicin and desorb in a free state; (b) distribute a greater amount of ACR for a longer period of time selectively to the regional lymph nodes; (c) be decreased in the systemic toxicity; and (d) enhance its therapeutic effect on lymph node metastases. In this clinical trial in 20 patients with breast cancer, ACR-CH was injected intra- and peritumorally just before operation for breast cancer, and we examined the extent of blackened nodes produced by ACR-CH. ACR-CH blackened about 70% of the axillary lymph nodes with cancer metastasis as well as the nodes without metastasis. In conclusion, ACR-CH will be useful for dissection of lymph nodes by visualizing the nodes during operation for breast cancer.     

Surgical treatment for advanced carcinoma of the gastric remnant

BACKGROUND/AIMS: Carcinoma of the gastric remnant has increased in recent years, but a therapeutic strategy for this disease has not been established. This retrospective study was performed to determine the most appropriate surgical procedure for carcinoma of the gastric remnant. METHODOLOGY: A total of 25 patients who underwent operation for advanced carcinoma of the gastric remnant that had developed after distal gastrectomy (13 for benign gastric diseases, B group; 12 for gastric carcinoma, M group) were studied. Clinicopathological features, as well as the status of lymph node metastasis, were investigated in the B and M groups. RESULTS: There were more patients with carcinoma invading other organs, stage IV disease, and with N2 or more lymph node metastasis (especially, with a high metastatic rate to lymph nodes along the splenic artery) in the M group than in the B group. Forty percent of patients in the M group were treated by left upper abdominal evisceration (LUAE), but only 8% in the B group. The survival rate (5-year, 46.0%) of the B group was significantly higher than that (5-year, 11.9%) of the M group. When we compared the survival rate of carcinoma of the gastric remnant with that of primary carcinoma of the upper third of the stomach, there was no difference between the two groups in the curative resection cases. CONCLUSIONS: Almost the same surgical strategy can be adopted for the B group as for primary gastric carcinoma. On the other hand, for the M group, a radical surgical procedure, LUAE, should be recommended.     

The value of computed tomography in the diagnosis of the local and lymph node recurrences of head and neck tumors

544 CT studies of 231 patients were evaluated retrospectively to assess the role of CT in posttherapeutic monitoring of patients with head and neck tumours. CT (80%) was inferior to clinical evaluation (87%) in diagnosing recurrent malignancy due to a lack of specificity (76 vs. 92%). With CT small recurrencies were missed. Occasionally evaluation of the oral cavity was impaired by metal artifacts (dental fillings). However with larger recurrent tumours, CT offered important additional information regarding extent, infiltration of deeper compartments and bony destruction in 51% of the cases. CT (95%) was superior to clinical evaluation (80%) in diagnosing recurrent lymph node metastases. A baseline CT study at about 6-8 weeks after the end of therapy is of great importance for follow-up studies.