Results of surgical treatments of primary hepatocellular carcinoma: Some aspects to improve long-term survival

From 1973 through 1982 we have treated 226 patients with primary hepatocellular carcinoma, including 103 by hepatectomy and 93 by hepatic artery ligation. Most were associated with cirrhosis or related liver diseases and one-third with esophageal varices. As in other Japanese and Asian series, our long-term overall results for the 90 patients who survived hepatectomy were poor in comparison with Western series dealing with non-cirrhotic patients. However, the actuarial survival rate at 3 years was 90% in patients with carcinomas smaller than 3 cm in diameter (n = 18). The 5-year survival rate was 70.8% in the 25 patients whose carcinoma had a curative resection, and 100% at 3 years in the 16 patients in whom a tumor smaller than 5 cm had been resected. Eighty-four patients survived hepatic artery ligation; in 50 of them the area of ischemia was thought to include all the neoplastic lesions within the liver. The survival rate of these 50 patients was superior to that of the patients who had undergone noncurative hepatic resection. We conclude that early detection and curative resection is the best way to improve the long-term results in cirrhotic patients with hepatocellular carcinoma and that hepatic artery ligation is better than incomplete (noncurative) resection.

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Resumen Hemos tratado 226 pacientes con carcinoma hepatocelular primario entre 1973 y 1982, incluyendo 103 con hepatectomía y 93 con ligadura de la arteria hepática. La mayoría apareció asociada con cirrosis o enfermedades hepáticas relacionadas y un tercio con varices esofágicas. Al igual que en otras series japonesas y asiáticas, nuestros resultados globales a largo término para los 90 pacientes que sobrevivieron la hepatectomía fueron pobres en comparación con las series occidentales que incluyen pacientes no cirróticos. Sin embargo, la tasa de supervivencia actuarial a 3 años fue del 90% en pacientes con carcinomas menores de 3 cm de diámetro (n= 18). La tasa de supervivencia en 5 años fue de 70,8% en los 25 pacientes cuyos carcinomas fueron sometidos a resección curativa, y del 100% en 3 años en los 16 pacientes en quienes se resecó un tumor de menos de 5 cm de diámetro. Ochenta y cuatro pacientes sobrevivieron la ligadura de la arteria hepática; en 50 de éstos se consideró que el área de isquemia incluía las lesiones neoplásicas contenidas en el hígado. La tasa de supervivencia de estos 50 pacientes fue superior a la de los pacientes que fueron sometidos a resección hepática no curativa.Nuestra conclusión es que la detección precoz y la resección curativa son la mejor manera de superar los resultados a largo plazo en pacientes cirróticos con carcinoma hepatocelular y que la ligadura de la arteria hepática es superior a la resección incompleta (no curativa).

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Résumé De 1973 à 1982 les auteurs ont opéré 226 malades qui présentaient un cancer hépatocellulaire, 103 par hépatectomie et 93 par ligature de l'artère hépatique. La majorité des patients présentaient une cirrhose ou des lésions hépatiques, un tiers étaient porteurs de varices oesophagiennes. Comme dans les autres séries japonaises ou asiatiques, les résultats à long terme chez les 90 malades qui avaient subi une hépatectomie furent décevants par comparaison avec les séries occidentales concernant les sujets indemnes de cirrhose. Cependant la survie actuarielle à 3 ans fut de 90% chez les opérés qui présentaient un cancer d'un diamètre inférieur à 3 cm (n=18). Le taux de survie à 5 ans fut de 70,8% chez 25 malades qui avaient subi une résection à but curatif, et le taux de survie à 3 ans fut de 100% chez 16 opérés qui avaient subi une résection pour une tumeur d'un diamètre inférieur à 5 cm. Quatrevingt-quatre malades ont survécu à la ligature de l'artère hépatique; chez 50 d'entre eux la zone ischémique provoquée par la ligature intéressait la totalité de la région hépatique occupée par les lésions néoplasiques. Le taux de survie de ces 50 malades fut toujours supérieur à celui de ceux qui n'avaient pu être l'objet d'une résection hépatique.De cette étude, on peut retenir les conclusions suivantes: le diagnostic précoce et la résection à but curatif du cancer hépatocellulaire chez les cirrhotiques représentent des conditions favorables à l'obtention de résultats à long terme satisfaisants; les résultats de la ligature de l'artère hépatique sont supérieurs à ceux de la résection incomplète (résection à but non curatif).

     

A case of advanced breast cancer markedly responding to chemo-endocrine therapy with only slight alopecia

We report a case of good response to chemo-endocrine therapy with slight alopecia. A 55-year-old woman was diagnosed as advanced breast cancer with T4c, N3, M1, Stage IV, who was left cervical node-positive. She received 4 cycles of CTF (cyclophosphamide 100 mg/body/day 1-14, THP 30 mg/body/days 1,8, and 5-FU 750 mg/body/days 1, 8 4 wq) therapy in addition to oral tamoxifen (20 mg/body) administration. After this treatment, the primary tumor was markedly reduced (PR), and only slight alopecia was observed. Generally, 3 cycles of CAF (CEF) therapy induced severe alopecia (grade 3). But this CTF regimen caused grade 1 alopecia. Most women have strong resistance to alopecia. It seems that the quality of life for breast cancer patients was affected by the extent of the alopecia. Therefore, CTF therapy should be considered effective for advanced breast cancer patients while reducing the extent of alopecia.     

Local recurrence of pancreatic cancer successfully treated with gemcitabine

We report a patient for whom systemic chemotherapy using gemcitabine was effective against local recurrence of pancreatic cancer. A 58-year-old man underwent pancreatoduodenectomy for a pancreatic head cancer. The diagnosis was Stage IVb poorly-differentiated tubular adenocarcinoma, scirrhous type, pT4, PL (+), P0, H0, pN2. However, after 21 months, gastrointestinal bleeding occurred. Gastroscopy and CT examination revealed a mass at the cut-end of the pancreas invading the stomach. The serum CA19-9 level was found to be elevated. Systemic chemotherapy was performed with a regimen of gemcitabine 1,000 mg/m2/week for 2 weeks, followed by a week rest. The recurrent tumor in the stomach disappeared, and the mass at the cut-end of the pancreas became small. The serum CA 19-9 level regained the normal value. Two years after the diagnosis of recurrence, he returned to work, and his chemotherapy is being continued as an outpatient.     

Interleukin-8, Cyclo-oxygenase-2, and Trefoil Factor Family 1 Gene Expression and Their Association with Helicobacter pylori Infection in the Remnant Stomach

Purpose The risk factors for secondary stomach carcinogenesis after distal gastrectomy have not been evaluated in detail. Methods Using gastrointestinal endoscopy, we examined 112 patients who had undergone gastrectomy. Biopsy specimens were taken from the stoma and the upper corpus mucosa in the remnant stomach to examine the associations among Helicobacter pylori (H.pylori) infection, bile reflux, and the expressions of interleukin-8 (IL-8), cyclo-oxygenase-2 (COX-2), and trefoil factor family 1 (TFF1) genes in the stomach mucosa. Results The IL-8 levels in the corpus mucosa were significantly higher in the H.pylori-positive patients than in the H.pylori-negative patients (P = 0.015). The IL-8 levels were significantly higher in the stomal mucosa than in the corpus mucosa in the H.pylori-positive patients (P = 0.047). The COX-2 levels in the corpus mucosa tended to be higher in the H.pylori-positive patients, but these levels were not significantly different in the stoma mucosa. The COX-2 levels in the corpus were significantly higher after Billroth II (BII) anastomosis than after Billroth I (BI) anastomosis (P = 0.041). TFF1 expression in the stoma was higher in the H.pylori-positive patients than in the H.pylori-negative patients, but the difference was not significant. Conclusions Both H.pylori infection and bile reflux increased IL-8 levels after BI anastomosis. Furthermore, COX-2 levels were higher after BII than after BI anastomosis. These indicators will become useful not only as biomarkers to predict the degree of inflammation in the stomach mucosa, but also as surrogate biomarkers to predict the risk of secondary stomach carcinogenesis in the remnant stomach mucosa.     

Differences in infarct evolution between lipopolysaccharide-induced tolerant and nontolerant conditions to focal cerebral ischemia

OBJECT: Although brain tissue may be protected by previous preconditioning, the temporal evolution of infarcts in such preconditioned brain tissue during focal cerebral ischemia is largely unknown. Therefore, in this study the authors engaged in long-term observation with magnetic resonance (MR) imaging to clarify the difference in lesion evolution between tolerant and nontolerant conditions. METHODS: Bacterial lipopolysaccharide (LPS; 0.9 mg/kg) was administered intravenously to induce cross-ischemic tolerance. Focal cerebral ischemia was induced 72 hours later in spontaneously hypertensive rats. Serial brain MR images were obtained 6 hours, 24 hours, 4 days, 7 days, and 14 days after ischemia by using a 7.05-tesla unit. Lesion-reducing effects were evident 6 hours after ischemia in the LPS group. Preconditioning with LPS does not merely delay but prevents ischemic cell death by reducing lesion size. Lesion reduction was a sustained effect noted up to 14 days after ischemia. Reduction of local cerebral blood flow (ICBF) in the periinfarct area was significantly inhibited in the LPS group, which was correlated with endothelial nitric oxide synthase (eNOS) expression. CONCLUSIONS: Significant preservation of ICBF in the periinfarct area, which is relevant to sustained upregulation of eNOS, could be a candidate for the long-term inhibiting effect on infarct evolution in the LPS-induced tolerant state.     

Localization of radioactive125I-Labelled botulinus toxin at the neuromuscular junction of mouse diaphragm

Summary Autoradiography at the light microscopic level demonstrated that the¹²⁵I-labelled neurotoxin fromClostridium botulinum type A crystalline toxin binds specifically to the neuromuscular junction of the mice diaphragm.     

Prolonged renal parenchymal retention of 99mTc mercaptoacetyltriglycine after nephron-sparing surgery

OBJECTIVE: Nephron-sparing surgery is a treatment in which a part of a diseased kidney is resected and some parenchyma of the kidney is spared. Impairment of spared renal parenchyma after the surgery may cause prolonged prarenchymal retention in renal scintigraphy with Tc mercaptoacetyltriglycine (Tc-MAG3). The aim of this study was to determine whether or not parenchymal retention of Tc-MAG3 is prolonged after nephron-sparing surgery. METHODS: Twenty-two patients underwent a total of 29 Tc-MAG3 studies within 1 year after nephron-sparing surgery. In 17 patients (23 examinations) who had bilateral kidneys, the presence of diffuse prolongation of parenchymal retention was determined for the operated kidney. In all patients, the presence of regional prolongation around the surgical margin was assessed. RESULTS: Diffuse prolongation was observed in four of 10 examinations performed within 1 month after surgery and in none of 13 examinations performed later than 1 month after surgery. Regional prolongation was shown in 10 of 14 examinations performed within 1 month after surgery and in three of 15 examinations performed later than 1 month after surgery. In five patients who were studied both prior to and later than 1 month after surgery, regional prolongation was noted on the first study. On the second study, regional prolongation was improved and initial renal uptake around the surgical margin was intensified. CONCLUSIONS: Renal parenchymal retention of Tc-MAG3 is frequently prolonged in the early period after nephron-sparing surgery. Renal scintigraphy with Tc-MAG3 may aid in characterizing acute renal damage after nephron-sparing surgery.     

Proximal-type epithelioid sarcoma in a 36-year-old man: closer immunoelectron-microscopic resemblance of the tumor cells to epithelial cells than to mesenchymal cells

Proximal-type epithelioid sarcoma (PES) is a rare neoplasm. We report a case of PES that arose in the perineal subcutis of a 36-year-old Japanese man who died within 4 months of the first clinical sign, probably due to massive pulmonary metastases. In the present study, we analyzed the tumor obtained at surgery, immunohistochemically, immunoelectron-microscopically and genetically. Although the tumor cells in the patient expressed both cytokeratin and vimentin immunohistochemically, they showed epithelial characteristics immunoelectron-microscopically because they had tonofilaments constructed of cytokeratin, not vimentin. In addition, the cytokeratins expressed on the tumor were glandular-type keratins. These findings indicate that PES may be a form of carcinoma in soft tissue. To ascertain the possible origin of the tumor, we compared the tumor immunohistochemically with fetal tissues. Although notochord and fetal peritoneal mesothelium were similar to the tumor antigenically, we could not confirm the specific origin of the tumor. Furthermore, the p53-WAF1 pathway did not contribute to tumorigenesis in the patient because the tumor had no mutation in exons 5-8 of the p53 gene and was immunohistochemically positive for WAF1.