Mitsumasa Nishi

How extensive should lymph node dissection be for cancer of the thoracic esophagus

From 1985 to 1992, 171 patients with cancer of the thoracic esophagus underwent esophagectomy with systematic dissection of regional lymph nodes including cervical nodes. The hospital mortality rate was 5.3%. The dissected nodes were classified into four groups: the deep cervical (C), upper mediastinal and cervical paratracheal (U), middle and lower mediastinal (L), and upper perigastric (G) groups. The U group mainly consisted of nodes beside the recurrent laryngeal nerves. The phase of cancer infiltration of lymph nodes was evaluated by the total number and the distribution of involved nodes. Of cases with nodal involvement, only 37% were in the late phase, in which more than seven nodes or in which the U, L, and G groups were all involved. Of cases in the earliest phase in which only one node was involved, 93% had either the U or G group involved. The C group of nodes was infrequently involved until the late phase. Cancer had metastasized to the U and G groups across a considerable anatomic distance even in earlier phases. Outcomes of the cases with nodal involvement not in the late phase were satisfactory; the cumulative survival was 60% at 3 years and 54% at 5 years. Systematic nodal dissection would benefit even cases with nodal involvement, unless the disease is in the late phase. Nodes beside the recurrent nerves and upper perigastric nodes should be dissected with higher priority, though they are located anatomically distant.

Combined intensive chemotherapy and radical surgery for incurable gastric cancer

AbstractBackground: To improve the poor prognosis of patients with advanced incurable gastric cancer, intensive chemotherapy combined with radical surgery was used. Patients and Methods: Thirty patients with incurable gastric cancer were treated with a combination of 5-fluorouracil (370 mg/m2) and leucovorin (30 mg/person), given intravenously for five consecutive days, followed by cisplatinum (70 mg/m2) and etoposide (70 mg/m2) on days 6 and 20, delivered through a catheter placed either in the aorta with its tip at the level of the ninth thoracic vertebra or in the celiac artery. This treatment (FLEP therapy) was repeated twice every 5 weeks. Radical or palliative surgery followed chemotherapy. Results: The overall response rate to the chemotherapy was 50.0% (15 of 30 patients, 95% confidence limit 0.305–0.671). Nineteen patients (15 with a partial response, three showing no change, and one with progressive disease) underwent surgery. Of these, nine underwent curative surgery and 10 palliative surgery. The median survival time was 6.5 months overall, 12.7 months for responders, and 4.7 months for nonresponders. Long-term survivors were exclusively found among patients with distant lymph node metastasis treated by curative surgery (55.6% at 5 years). Conclusions: Favorable results of this small phase II study justify a phase III trial.

Duct endoscopy and endoscopic biopsy in the evaluation of nipple discharge

SummaryMicrodochectomy is usually performed on patients with nipple discharge caused by intraductal proliferative lesions, such as intraductal papilloma and carcinoma. But this operation often sacrifices large amounts of normal mammary gland even when the lesion is a benign intraductal papilloma a few millimeters in diameter. We have developed duct endoscopy for the mammary duct system, and have reliably performed biopsies for intraductal proliferative lesions intraductally. From June 1989 to April 1990, we examined 22 cases by duct endoscopy, and performed endoscopic biopsy in 16 cases. The method of endoscopic biopsy is as follows. First, a bougie is inserted, without anesthesia other than Xylocaine jelly, into the orifice of the duct to enlarge it. Second, the outer cylinder and the inner needle are inserted; then the inner needle is removed, and the endoscope is inserted. After examination, the outer cylinder is moved up to the lesion to be biopsied and the endoscope is taken out. Then a sample is taken into the outer cylinder by aspiration. We diagnosed 10 cases of benign lesion and 5 cases of malignant lesion by cytological and/or histological examination. In conclusion, endoscopic biopsy, aided by duct endoscopy, is a useful and harmless diagnostic procedure in the evaluation of nipple discharge.

Chronological changes of characteristics of early gastric cancer and therapy: Experience in the Cancer Institute Hospital of Tokyo, 1950–1994

Gastric cancer, the leading cause of death from cancer in Japan, has long been studied. We received our first patient with early gastric cancer in 1950 and have since treated 2382 patients with this cancer up to 1990. The percentage of early gastric cancers diagnosed has been on the increase following the improvement in diagnostic skills and the establishment of mass screening. At present, more than half of the gastric cancers presenting are in the early stages. Chronological changes in diagnoses of early gastric cancer are characterized by the increased findings of (a) small tumors less than 4 cm in diameter (b) depressed-type carcinoma (c) lesions of the upper part of the stomach, and (d) undifferentiated-type adenocarcinoma. The standard method of treatment for early gastric cancer was standard radical operation in the 1970s. In the 1980s endoscopic mucosal resection and limited operation were adopted and their use has been increasing annually. The prognosis for early gastric cancer is quite favorable (the 5-year survival rate is more than 90%), and it is regarded as a disease with good prognosis. To obtain still better therapeutic results, it is essential to increase the proportion of early gastric cancers where endoscopic mucosal resection or limited operation is indicated, and improve the techniques of those procedures.

Cervicothoracic approach for total mesoesophageal dissection in cancer of the thoracic esophagus

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.

Surgical Treatment of Cancer of the Thoracic Esophagus in Association With a Major Pulmonary Operation

BACKGROUND Pulmonary complications have been a major cause of mortality after operations for cancer of the thoracic esophagus. Although the risk involved in esophagectomy associated with a major pulmonary operation is expected to be high, it has seldom been evaluated on the basis of clinical experience. STUDY DESIGN Of 408 patients who underwent esophagectomy, 8 had previously undergone major pulmonary operation (7 for tuberculosis and 1 for pulmonary cancer) and 10 underwent concurrent major pulmonary resection (7 for pulmonary invasion of esophageal cancer, 2 for synchronous pulmonary cancer, 1 for extensive bronchiectasia). All patients underwent systematic lymph node dissection for esophageal cancer, except one patient with mucosal cancer. To prevent postoperative complications, the operative approach and dissection procedures for esophageal cancer were modified according to the associated pulmonary operation and the extent of cancer invasion. All thoracotomies for esophagectomy were performed on the same side as the major pulmonary operation. Additional median sternotomy was performed when necessary. In the most recent 8 patients who underwent major pulmonary resection concurrent with esophagectomy, the bronchial stump was covered with a pedicle flap. RESULTS Of the 18 patients who underwent pulmonary operation, postoperative complications developed in 13 of the 18 object patients, but none was fatal. The 3-year survival rate was 45%. All deaths were caused by esophageal cancer or another cancer. CONCLUSIONS Aggressive esophagectomy associated with major pulmonary operation is not contraindicated in patients with fair risk conditions. The operative procedures for esophagectomy should be appropriately modified to minimize the effect of the associated pulmonary operation. Special care should be taken with respect to the approach for mediastinal dissection and closure of the bronchial stump.

An enzymatic differential assay for urinary diamines, spermidine, and spermine

SummarySubsequent to the hydrolysis of urinary conjugated amines by heating with hydrochloric acid, free amines were isolated by cation-exchange chromatography. SPD and SPM in an aliquot of amine extract were first oxidized by PAO from Penicillium chrysogenum, producing PUT and hydrogen peroxide. DIAs, which consist of the initially present DIAs plus PUT produced by PAO, were subsequently oxidized by PUO from Micrococcus rubens, producing hydrogen peroxide. In an another aliquot of the amine extract DIAs and SPD were oxidized by PUO, producing hydrogen peroxide. Quinone dye, derived from hydrogen peroxide generated in each end-point reaction, was measured spectrophotometrically at 555 nm, and the amounts of the respective amines in urine were calculated. Significantly elevated levels of DIA, SPD, SPM, and an elevated DIA to SPD ratio were found in urine from 46 cancer patients, as compared to 34 normal control subjects. An increase in DIA and the ratio of DIA to SPD was found at clinical tumor stage I of the alimentary tract. The levels of DIA remained fairly constant and the ratio of DIA to SPD was consistently decreased with advancing clinical tumor stages. In patients who had undergone curative resection, there were greater decreasing rates (80% of cases for DIA and 80% for SPD) than in patients who had undergone noncurative resection (45.5% for DIA and 36.4% for SPD).

Surgical treatment for carcinoma of the thoracic esophagus with major involvement in the neck or upper mediastinum

In carcinoma of the thoracic esophagus, most surgeons consider that esophagectomy is contraindicated in patients with clinical evidence of major extraesophageal involvement in the lower neck or peritracheal regions. However, metastases to these regions are commonly found even in early phases of carcinoma invasion. With recent progress in preoperative assessment, operative technique and adjuvant therapy, esophagectomy could possibly benefit appropriately selected patients.

Ultrastructure and immunohistochemical staining of a transplanted endodermal sinus tumor.

SummaryAn endodermal sinus (yolk sac) tumor was successfully transplanted into athymic nude mice. Histologic and ultrastructural investigations revealed that the transplanted tumor had a characteristic appearance with numerous Shiller-Duval bodies, endodermal sinus structures and ultrastructural profiles as previously described in human material. The endodermal sinus tumor and normal human yolk sac have been found to synthesize not only alpha-fetoprotein (AFP), but also other serum proteins, namely, albumin, prealbumin, alpha1-antitrypsin, and transferrin. Serological study by radioimmuno-assay demonstrated AFP, carcinoembryonic antigen (CEA) and human chorionic gonadotropin (HCG) in the sera of the tumor-bearing nude mice and in cyst fluid from the transplanted tumor. Immunohistochemical investigation using the unlabeled antibody peroxidase-antiperoxidase method showed that the tumor cells produced CEA, alpha1-antitrypsin, transferrin, HCG as well as AFP. These immunohistochemical staining properties were correlated with the findings on radioimmunoassay.

Neoadjuvant Chemotherapy with FLEP Regimen for Incurable Gastric Cancer

Although the results of treatment for gastric cancer in Japan have improved, the prognosis of advanced stage disease remains poor [1,2]. Neither chemotherapy nor surgery alone has produced long-term survivors among patients with advanced disease. Our database of gastric cancer cases (11489 cases treated in our hospital from 1946 to 1994) shows that median survival time was 6 months for patients with noncurative surgery and 4 months for nonsurgically treated cases [3]. Our conventional strategy for advanced gastric cancer (including extended radical surgery followed by postoperative chemotherapy) yielded a plateau in the survival benefit. However, recent chemotherapy regimens with high response rates [4, 5, 6, 7, 8, 9] seem to allow radical surgery for initially unresectable disease. Since 1989 at the Cancer Institute Hospital, Tokyo, we have attempted to treat advanced unresectable gastric cancer patients with a four-drug combination chemotherapy with systemic and regional delivery followed by radical gastrectomy. The treatment results have been reported elsewhere [10].