Intraosseous carcinoma of the anterior maxilla identified as the occult primary tumour of carcinoma of unknown primary.

Carcinoma of unknown primary (CUP) is defined as lymph node metastasis without a detectable origin until after the initial treatment has been performed. The most common occult primary site in the head and neck, as revealed by a review of the published literature, is the oropharynx. An occult primary site in the oral region is extremely rare. We report a rare case of head and neck CUP (HNCUP) in a 69-year-old female patient, wherein the occult primary lesion was a primary intraosseous carcinoma (PIOC) invading the anterior maxilla. During the course of the initial diagnostic workup, no primary lesion could be identified; however, cervical lymph node metastasis to left levels IB and IIA were observed in the patient. A neck dissection followed by adjuvant radiotherapy was performed. However, the PIOC of the anterior maxilla was identified 6 months after neck treatment and was confirmed as the occult primary tumour of the HNCUP. This case is quite rare and required a comprehensive workup to guide optimal treatment. Careful follow-up or active biopsy should be considered if osteolytic changes are observed in the jaw.

[A case of advanced gastric cancer with multiple liver metastases in an elderly patient that responded dramatically to UFT therapy].

An 88-year-old female patient suffering from Borrmann type 3 advanced gastric cancer complicated by multiple hepatic metastases underwent a total gastrectomy. A small dose of 200 mg/day of UFT was administered orally every day postoperatively. At postoperative month 6, a marked diminishment of the hepatic metastatic lesions was noted. Resection of the primary lesion with a regimen of a small oral dose of UFT was remarkably effective in this elderly gastric cancer patient with complications from multiple hepatic metastases.

In vivo subcellular elemental dynamics in liver graft: With special reference to effect of non-selective endothelin receptor antagonist, TAK-044, on the graft injury.

Background: No data are available concerning the in vivo subcellular dynamics of elements in liver grafts and the effect of endothelin receptor antagonist, TAK-044, against graft injury. Methods: Liver transplantation was performed in porcine under active veno-venous bypass. The grafts stored in chilled preservation solution were recirculated following reflush with lactated Ringer's solution with or without TAK-044 (10 mg/kg). Cold and warm ischemic times of the grafts were comparable between the two groups. Elements (Na, K, Cl, Ca, P and S) were measured in three fractions of cytoplasm, mitochondria and nucleus by electron probe X-ray microanalysis for the graft biopsy specimens obtained at various time from donor laparotomy to 1 week after liver grafting. Liver functions also were compared between the two groups. Results: In both groups, concentration of each element changed in parallel among the three subcellular fractions and their changes were less marked in the nucleus. In the control group, there were significant increases in cytoplasmic Na and Cl after portal reperfusion and in cytoplasmic and mitochondrial Ca after hepatic artery reperfusion. These were accompanied by K and mitochondrial S decreases without a statistical significance. In the TAK group, such postreperfusion elemental alterations were significantly suppressed and early deterioration of the liver functions was alleviated, as compared with the control group. Conclusion: A supplemental use of TAK-044 in a rinse solution before reflush contributed to stability of subcellular elements after reperfusion and better preservation of early graft function.

Highly efficient kinetic resolution of beta-halohydrins catalyzed by a chiral 1,2-diamine.

Kinetic resolution of racemic beta-halohydrins has been achieved by reaction with benzoyl chloride in the presence of a catalytic amount (0.3 mol%) of a chiral diamine combined with diisopropylethylamine to afford the corresponding benzoates and unreacted beta-halohydrins in good to excellent enantioselectivities. The benzoate can be converted to the corresponding allylic benzoate without loss of optical purity by treatment with (1,5-diazabicyclo[4.3.0]non-5-ene).

Laparoscopic surgery assisted by a transvaginal approach.

We used laparoscopic surgery assisted by a transvaginal approach for gastrointestinal diseases. In the first case, a huge submucosal tumor enucleated laparoscopically from the minor curvature of the stomach was extracted through the vagina. In the second case, partial resection of the rectum to treat rectal endometriosis was performed laparoscopically with the assistance of manual handling inserted transvaginally. Although it can be applied only to female patients, especially to multipara, the vagina as an access point to the abdominal cavity can be widely used for various purposes in laparoscopic surgery.

Progression of hepatocellular carcinoma as reflected by nuclear DNA ploidy and cellular differentiation.

BACKGROUND/AIMS: Intratumor heterogeneity of DNA ploidy within a single hepatocellular carcinoma is not well understood. The present study was designed to examine the histologic distribution of intratumor DNA ploidy in hepatocellular carcinomas of different growth types in relation to cell differentiation. METHODS: Twenty patients (16 men and four women; mean age, 60.2 years) with hepatocellular carcinoma (mean diameter, 4.3 cm) were studied. One hundred and twenty-seven samples from different sites of each tumor were analyzed by determination of the nuclear DNA content and histological examination. RESULTS: The DNA ploidy was heterogeneous in nine (45%) of the 20 tumors. Five tumors had a mixture of diploid and aneuploid regions, and the remaining four consisted of aneuploid regions with different DNA indices. There was no significant difference in patient characteristics between the heterogeneous and homogeneous groups. A significant correlation was found between tumor growth type and the incidence of heterogeneity. Only 16% of single nodular carcinomas without intratumor septal formation exhibited heterogeneity, while single nodular tumors with septal formation or confluent multinodular tumors were associated with high incidences of different DNA ploidy patterns or DNA indices. There was no aneuploidy in well-differentiated foci, while aneuploidy was frequently found in moderately or poorly differentiated foci (incidences of 67% and 74%, respectively). CONCLUSIONS: Heterogeneity of DNA ploidy may develop along with changes in growth pattern and cell dedifferentiation or by confluence of nodules originating from different tumor cell clones.

Thoracoscopic parasternal lymph node dissection for the staging of breast cancer.

With the advent of advanced thoracoscopic techniques, new applications have been expanding their roles in thoracic surgery. The aim of this paper is to introduce our new thoracoscopic approach in performing parasternal lymph node dissection of advanced breast cancer for its staging. This technique does not need the removal of any costal cartilage which is usually done in the conventional classical technique after radical mastectomy. Thoracoscopic procedure, in which wide and complete parasternal lymph node dissection is done, is minimally invasive and easy to perform. Therefore, the thoracoscopic technique may be a suitable alternative to the conventional approach in the future.

Factors regulating tumor pressure in hepatocellular carcinoma and implications for tumor spread.

This study was performed to investigate factors determining tumor pressure (TP) in hepatocellular carcinoma (HCC) and a correlation of pressure gradient between TP and portal vein pressure (PVP) with tumor spread. TP and hepatic tissue pressure (HTP) were measured in 70 patients who underwent hepatic resection for HCC. Changes in TP after hepatic artery occlusion (HAO) or portal vein occlusion (PVO) were observed. HTP was elevated with worsening chronic liver disease, and exhibited a significant positive correlation with PVP. The TP was significantly higher in the encapsulated and the nonnecrotic HCCs. The pressure gradient (TP-PVP) was significantly greater in the encapsulated HCCs, especially in those with microscopic portal vein invasion (vp) or intrahepatic metastasis (im). HAO caused a greater decrease in TP than did PVO, with the decrease being particularly marked in the encapsulated HCCs. The TP of HCC was found to be regulated mainly by the presence or absence of a tumor capsule or necrosis, and partly by the hepatic arterial flow and PVP. Our study suggests that TP increases with capsule formation and that the pressure gradient between TP and PVP may be a causal factor in the dispersement of tumor cells into the portal vein.

Hepatoprotective effect of a nonselective endothelin receptor antagonist (TAK-044) in the transplanted liver.

This study was designed to investigate whether or not a novel nonselective endothelin A/B (ETA/ETB) receptor antagonist (TAK-044) provides hepatoprotection during porcine liver transplantation. The grafts were stored in chilled Euro-Collins solution and recirculated following reflush with lactated Ringer's with (TAK group) or without (control group) TAK-044 (10 mg/kg). Intracellular (cytoplasma, mitochondria, and nucleus) calcium (Ca) concentrations were measured in the hepatic biopsy materials obtained serially at varying time point from donor laparotomy to recipient closure using an electron probe X-ray microanalyzer. Liver function tests also were determined. The cold and warm ischemia times of the grafts were comparable between the two groups. The peak endothelin-1 T-1) concentration after recirculation was significantly higher in the TAK group than in the control group (129 +/- 30 pg/ml vs 26 +/- 6.5 pg/ml). However, release of liver enzymes, increases in total bile acid, and deterioration of indocyanine green retention rate were significantly suppressed in the TAK group. In the control group, the intracellular Ca concentrations, especially in the mitochondrial fraction, were elevated markedly following recirculation of the hepatic arterial flow. In the TAK group, this effect was suppressed. Thus, the supplementary use of the nonselective ETA/ETB receptor antagonist TAK-044 via a rinse route may alleviate an early postreperfusion microcirculatory disturbance of the liver grafts without adverse effects by the increased ET-1 on the systemic circulation.

Thoracoscopic treatment of esophagobronchial fistula with esophageal diverticulum.

Thoracoscopic fistulectomy and diverticulectomy for esophagobronchial fistula with esophageal diverticulum were performed on a 49-year-old-woman. The neck of the diverticulum and the fistula were divided with endo-stapling technique. Intraoperative esophagoscopy was found to be useful for the definite localization and complete excision of the fistula and the diverticulum and the avoidance of stenosis of the esophagus. To avoid the recurrence of fistula, a pedicle of viable mediastinal pleura was interposed between esophageal and bronchial closures. Postoperative course was uneventful, and the complete relief of symptom was experienced for a period of 10 months after the operation. It is to be considered that the present thoracoscopic procedure with intraoperative esophagoscopy can be used as a standard operative procedure for esophagobronchial fistula with esophageal diverticulum.

Intrahepatic metastases in hepatocellular carcinoma: the role of the portal vein as an efferent vessel.

The mechanism and pathogenesis of the high frequency of intrahepatic metastasis in hepatocellular carcinoma (HCC) has not yet been elucidated. Two hundred and thirty one tumors (< or = 5 cm in diameter) of resected specimens of HCC were examined for the relationship between mode of tumor spread and tumor size. Efferent vessels in HCC were identified by direct injection of radiopaque material into the tumor in 23 resected liver specimens selected at random from the 231 tumors. The most frequent site for tumor spread in HCC was capsular invasion followed by extracapsular invasion, vascular invasion, and finally intrahepatic metastasis. There was a strong statistical correlation between the presence of intrahepatic metastasis and the frequency of vascular invasion (correlation coefficient = 0.998). Radiopaque material injected directly into 23 resected tumors entered only the portal vein in 17 tumors and into both the portal and hepatic veins in six tumors. In all eight patients with unresectable lesions, radiopaque media injected percutaneously into tumor nodules flowed only into the portal vein. These findings suggest that tumor spread in HCC progresses from capsular invasion to intrahepatic invasion and that the portal vein may act as an efferent tumor vessel.

Microwave coagulonecrotic therapy for hepatocellular carcinoma.

The present study reports on the usefulness of microwave coagulonecrotic therapy (MCT) as a treatment option for hepatocellular carcinoma (HCC) with poor hepatic reserve. From June 1992 to March 1995, MCT using a microwave electrode was employed on 8 patients using laparoscopic control and 19 with the open method, and wedge resection (Hx) was applied to the 23 patients. All patients had HCC with poor hepatic reserve. Radiation output was 100 watts with a mean radiation duration of about 30 minutes. The severity of liver dysfunction and the regional characteristics of the tumor (tumor size, multiplicity, portal invasion, tumor depth) were comparable between the MCT and Hx groups. The operative time was significantly shorter for the MCT group than the Hx group. The mean blood loss was 1570 ml in the Hx group but negligible in the MCT group. There was no operative mortality in the MCT group in contrast to 4.3% (1 of 23) in the Hx group. Complications were observed in 11.1% (3 of 27) and 34.8% (8 of 23), respectively, for the MCT and Hx groups. The postoperative total bilirubin had lower values and the start of diet was earlier in the MCT group than the Hx group. The 3-year crude and disease-free survival rates were 86% and 44%, respectively, for patients who underwent MCT, which were comparable to 75% and 14% for those with Hx. MCT can achieve long-term results equivalent to those obtained by wedge resections, but it is less invasive and technically easier. Therefore it can be an alternative option in place of limited resection for HCC with poor hepatic reserve.

Intrahepatic metastases in hepatocellular carcinoma: evidence for spread via the portal vein as an efferent vessel.

BACKGROUND: The mechanism and pathogenesis of the high frequency of intrahepatic metastasis in hepatocellular carcinoma (HCC) has not yet been elucidated. METHODS: Two hundred thirty-one tumors ( < or = 5 cm in diameter) of resected specimens of HCC were examined for the relationship between mode of tumor spread and tumor size. Efferent vessels in HCC were identified by direct injection of radiopaque material into the tumor in 23 resected liver specimens selected from the 231 tumors. RESULTS: The most frequent site for tumor spread in HCC was capsular invasion followed by extracapsular invasion, vascular invasion, and finally intrahepatic metastasis. Radiopaque material injected directly into 23 resected tumors entered the portal vein in only 17 tumors and entered into both the portal and hepatic veins in six tumors. CONCLUSIONS: These findings suggest that tumor spread in HCC progresses from capsular invasion to intrahepatic invasion and that the portal vein may act as an efferent tumor vessel.

Pathologic and radiographic studies of intrahepatic metastasis in hepatocellular carcinoma; the role of efferent vessels.

The efferent vessel of hepatocellular carcinoma (HCC) and the mechanism and pathogenesis of the high frequency of intrahepatic metastasis in HCC has not yet been clarified. Three hundred ninety-three resected specimens of HCC were examined for tumor thrombosis in the portal vein and the hepatic vein: 231 tumors < or = 5 cm in diameter were examined for the relationship between mode of tumor spread and tumor size. Efferent vessels in HCC were identified by direct injection of radiopaque material into the tumor in 23 resected liver specimens and by percutaneous infusion of radiopaque media into tumor nodules in 8 patients. The mode of tumor spread in HCC progressed from capsular invasion to extracapsular invasion, then to vascular invasion, and finally to intrahepatic metastasis. There was a strong statistical correlation between the presence of intrahepatic metastasis and portal vein thrombosis (p < 0.05, R = 0.998). Radiopaque material injected directly into 23 resected tumors entered only the portal vein in 17 tumors and into both the portal and hepatic veins in 6 tumors. In all 8 patients with unresectable lesions, radiopaque media injected percutaneously into tumor nodules flowed only into the portal vein. These findings suggest that intrahepatic invasion by HCC may occur through the portal vein as an efferent tumor vessel.

Laparoscopic microwave coagulonecrotic therapy for hepatocellular carcinoma.

The present study reports on the usefulness of laparoscopic microwave coagulonecrotic therapy as a new option in the treatment of hepatocellular carcinoma. Five patients with liver tumors associated with cirrhosis were treated from July 1993 to March 1994 with a microwave electrode (output 100 W, 3 to 4 cm long) devised for laparoscopic use. The tumors, all with diameters less than 3 cm and superficially located, were coagulated for a total radiation period of 20 to 30 min under laparoscopic, intraoperative ultrasonographic control. Postoperative complications were negligible, and laboratory values (glutamate-pyruvate transaminase, bilirubin, prothrombin time, platelet count) returned to preoperative levels within 7 days. Complete necrosis, including the surrounding liver tissue, was confirmed by a follow-up dynamic computed tomography scan during the follow-up period of 6 to 17 months (mean, 13 months). Laparoscopic microwave coagulonecrotic therapy can exert an effect on tumor equivalent to that obtained from a wedge resection but is noninvasive and may represent a new option for unresectable liver cancers.

Clinicopathologic spectrum of resected extraductal mass-forming intrahepatic cholangiocarcinoma.

BACKGROUND: The mode of tumor growth of intrahepatic cholangiocarcinoma (CC) varies considerably from patient to patient. This study describes the clinicopathologic variety of the extraductal mass-forming type of CC. METHODS: Patients with CC characterized by an extraductal mass (n = 26) who underwent hepatectomy from 1976 through 1992 were clinicopathologically classified into three types: Type I (n = 7), no biliary stricture; Type II (n = 13), biliary stricture without jaundice; and Type III (n = 6), biliary stricture with jaundice. RESULTS: Type I included three patients with microductular-trabecular arrangement and behavior reminiscent of hepatocellular carcinoma (high association with chronic liver disease, mild positivity for alpha-fetoprotein [AFP], no lymph node metastasis, but frequent intrahepatic metastasis), in contrast to the other typical cholangiocarcinoma. Hepatolithiasis was associated only with Type II CC: The serum positivity for AFP and carcinoembryonic antigen was much higher in Type I CC, whereas positivity of CA 19-9 was highest in Type III. Involvement of the portal vein, hepatic artery, or hepatic duct was most frequent in Type III CC, which necessitated resection of the extrahepatic bile duct and hepatectomy. CONCLUSION: The clinicopathologic behavior of intrahepatic CC differs considerably according to the presence or absence of stricture of the biliary tree. Thus, CC without biliary stricture behaves more like hepatocellular carcinoma, whereas CC with biliary stricture is more like hilar or extrahepatic bile duct carcinoma.

Hepatic resection under in situ hemihepatic hypothermic perfusion with hepatoprotective agents.

Hepatectomy was performed under in situ right lobar hypothermic perfusion combined with hepatoprotective agents in six patients who had hepatocellular carcinoma and coexisting liver disease. Following occlusion of the right hepatic vein and the right portal pedicle, in situ cold perfusion was initiated using chilled Ringer's lactate infused through a cannula placed in the right main portal vein. The right superior segments were resected in a bloodless field. The liver was cooled to 22-26 degrees C for 40 to 80 minutes with no significant changes in systemic hemodynamics or body temperature. Postoperative liver functions showed no marked derangement; the mean peak GPT was 221 U and the mean peak total bilirubin 2.3 mg d/l. Local cooling minimizes the risk of ischemia/reperfusion injury in this very vulnerable population, yet gives the surgeon adequate time to perform a challenging resection in a bloodless field.

A prediction scoring system to select the surgical treatment of liver cancer. Further refinement based on 10 years of use.

OBJECTIVE: This study reports further refinement of a prediction scoring system, which was established in 1980 as a guide to determine a safe limit for hepatectomy, based on 10 years of use. SUMMARY BACKGROUND DATA: In the past, whether major resection was safe was judged empirically from the net resection volume or the residual hepatic volume combined with the patient's liver function. However, such judgment was not based on objectively defined criteria. METHODS: Patients with hepatocellular carcinoma (HCC; n = 376) and metastatic cancer (n = 58) who had hepatectomy at some time from 1981 through 1990 were entered into this study. A prediction score (PS) was computed using a multiple regression equation that consists of computed tomographic scan-estimated resection rate, indocyanine green retention rate, and the patient's age. A PS greater than 55 was classified as a risky zone, a PS of 45 to 55 was considered borderline and a PS less than 45 was a safe zone. RESULTS: With HCC and chronic liver disease, all patients in the risky zone died, whereas 33% in the borderline zone died and 7.3% died who were in the safe zone. With metastatic cancer with normal liver, all patients in the risky zone died, whereas no patient in either the borderline or safe zones died. The major cause of death in the risky zone was liver failure due to excessive resection. In the borderline and safe zones, liver failure developed primarily after abdominal sepsis or pulmonary infection, particularly for those with adverse prognostic factors such as disturbed glucose tolerance, lower platelet count, and higher indocyanine green retention rate. CONCLUSION: Prediction scores can eliminate deaths related to excessive resection for patients with normal or injured livers. When patients have adverse prognostic factors, careful surgery and postoperative management is mandatory to avoid liver failure triggered by intra- or extra-abdominal sepsis, even if the score remains in a borderline or safe zone.