Perioperative outcomes of esophagectomy preceded by the laparoscopic transhiatal approach for esophageal cancer.

This study was designed to determine the efficacy of esophagectomy preceded by the laparoscopic transhiatal approach (LTHA) with regard to the perioperative outcomes of esophageal cancer. The esophageal hiatus was opened by hand-assisted laparoscopic surgery, and carbon dioxide was introduced into the mediastinum. Dissection of the distal esophagus was performed up to the level of the tracheal bifurcation. En bloc dissection of the posterior mediastinal lymph nodes was performed using LTHA. Next, cervical lymphadenectomy, reconstruction via a retrosternal route with a gastric tube and anastomosis from a cervical approach were performed. Finally, a small thoracotomy (around 10 cm in size) was made to extract the thoracic esophagus and allow upper mediastinal lymphadenectomy to be performed. The treatment outcomes of 27 esophageal cancer patients who underwent LTHA-preceding esophagectomy were compared with those of 33 patients who underwent the transthoracic approach preceding esophagectomy without LTHA (thoracotomy; around 20 cm in size). The intrathoracic operative time and operative bleeding were significantly decreased by LTHA. The total operative time did not differ between the two groups, suggesting that the abdominal procedure was longer in the LTHA group. The number of resected lymph nodes did not differ between the two groups. Postoperative respiratory complications occurred in 18.5% of patients treated with LTHA and 30.3% of those treated without it. The increase in the number of peripheral white blood cells and the duration of thoracic drainage were significantly decreased by this method. Our surgical procedure provides a good surgical view of the posterior mediastinum, markedly shortens the intrathoracic operative time, and decreases the operative bleeding without increasing major postoperative complications.

New technique of laparoscopic colectomy with the LAP DISC and a 5-mm flexible scope.

PURPOSE: We devised a new method for the safe introduction of the first trocar and induction of pneumoperitoneum for laparoscopic excision of the large intestine. METHODS: With this method, a small laparotomy is first conducted according to the size of the exposed affected intestinal tract or tumor size, prior to the application of a LAP DISC (LD) to the wound and introduction of a 12-mm trocar for the establishment of pneumoperitoneum. The method is advantageous in that organ injury and vessel injury are avoided when the small laparotomy is conducted first, and prompt transition to a conventional laparotomy is possible. The diaphragm of the iris bulb can be controlled in a non-stepwise manner. In addition, trocars, the stapler, and other instruments, can be inserted under the pneumoperitoneum. Furthermore, the use of a 5-mm flexible scope allows surgical maneuvers, except for application of LD, to be conducted via 5-mm trocars. In addition, the 5-mm scope can be inserted through any trocar, allowing multidirectional avoidance of dead space and intraperitoneal observation. When only 5-mm trocars are used, it is not necessary for the sites of trocar puncture to be closed by sutures, and this minimizes the risk of adhesions and port-site herniation. The method is also considered to be excellent from the point of view of esthetics. RESULTS: We employed this surgical approach in 50 patients with colorectal cancer at our hospital. None of the patients developed any traumatic complications associated with the insertion of trocars, and none of the patients, even those with a past history of abdominal operation, required conversion to conventional laparotomy. CONCLUSIONS: Based on these results, this method involving a small laparotomy prior to the application of an LD and introduction of a 12-mm trocar for establishing pneumoperitoneum, with the efficient use of a 5-mm flexible camera, is considered to be safe and useful for laparoscopic excision of the large intestine.

Repeated hepatic resection for recurrent hepatocellular carcinoma in eighteen cases.

BACKGROUND: Although intrahepatic recurrence after hepatic resection for hepatocellular carcinoma is the most significant cause of death, very few reports are available for hepatic re-resection as a radical treatment for recurrence. METHODS: Eighteen patients who underwent repeated hepatic resections for hepatocellular carcinoma were evaluated. Most of the patients regularly received measurement of alpha-fetoprotein level once a month and examination by ultrasonography and/or computed tomography scanning once every 3 to 4 months. RESULTS: No operative deaths occurred. The alpha-fetoprotein levels of 9 of the 18 patients were within the normal range. Most patients underwent limited hepatic resection to maintain the remaining hepatic function. The 1-, 3-, and 5-year cumulative survival rates after repeated resection were 88%, 37%, and 37%, respectively. The 3-, 5-, and 7-year survival rates after the first resection were 88%, 68%, and 45%, respectively. These showed no significant difference from the survival rates of patients with no recurrences after hepatic resection. CONCLUSIONS: Careful follow-up examinations after hepatic resection are needed for early detection of recurrences, and efforts should be made for repeated hepatic resection, which leads to satisfactory outcome.

Effects of intravenous perilla oil emulsion on nutritional status, polyunsaturated fatty acid composition of tissue phospholipids, and thromboxane A2 production in streptozotocin-induced diabetic rats.

The effects of a perilla oil (PO) emulsion rich in alpha-linolenic acid, administered by intravenous infusion, on nutritional status, fatty acid composition, and thromboxane A2 production were compared with those of a soybean oil (SO) emulsion in streptozotocin-induced diabetic rats given a fat-free diet for 7 days. The PO emulsion improved body weight gain and nitrogen balance compared with the SO emulsion and reduced thromboxane A2 production by platelets. The PO emulsion also increased the proportion of eicosapentaenoic acid, but decreased that of arachidonic acid, in liver and serum phospholipids. Plasma insulin concentrations and blood biochemical indices were similar in the two groups. An intravenously infused PO emulsion effectively reduces thromboxane A2 production through changes in the fatty acid composition of liver and serum phospholipids, as with oral administration, and improves the nutritional status of diabetic rats.

Degradation kinetics of L-alanyl-L-glutamine and its derivatives in aqueous solution.

The degradation kinetics of five glutamine dipeptides in aqueous solution, i.e. glycyl-L-glutamine (Gly-Gln), L-alanyl-L-glutamine (Ala-Gln), L-valyl-L-glutamine (Val-Gln), L-leucyl-L-glutamine (Leu-Gln) and L-isoleucyl-L-glutamine (Ile-Gln), were studied. Stability tests were performed using a stability-indicating high-performance liquid chromatographic assay. Two different Ala-Gln degradation routes, i.e. the cleavage of a peptide bond and the deamination of an amide group, were observed. The degradation was adequately described by pseudo-first-order kinetics. The maximum stability of Ala-Gln was obtained at an approximate pH of 6.0. The pH-rate profile described by specific acid-base catalysis and hydrolysis by water molecules agreed with the experimental results. The activation energy of Ala-Gln at pH 6.0 was determined to be 27. 1kcal mol-1, and the shelf-life (90% remaining) at 25 and 40 degrees C was predicted to be 5.3 years and 7.1 months, respectively. The rate constants of the glutamine dipeptides were influenced by the N-terminal amino acid residue and decreased in the order: Gly-Gln, Ala-Gln, Leu-Gln, Val-Gln and Ile-Gln.

Preparation of fine emulsified fat particles without glycerol for intravenous nutrition.

A method of preparing fine emulsified fat particles without glycerol for intravenous nutrition was investigated. The factors assessed were the oil phase ratio, the glucose level of the aqueous phase and the temperature of high-pressure homogenization. The particle size decreased with an increase in the oil phase ratio and it went below 250 nm only in the emulsion with a 50% oil phase ratio. The weight-weighted particle size (dw)/number-weighted particle size (dn) value reflected the particle size distribution. The emulsion with a 50% oil phase ratio had a very narrow distribution of particle sizes and the dw/dn value was below 1.1. With the use of glucose solutions for the aqueous phase, smaller particle sizes and narrower distributions were obtained with increasing glucose concentrations. The controlled temperature of 50 degrees C was appropriate for high-pressure homogenization, producing particles below 160 nm. The rate of the layer separation was a function of particle size. The particle sizes below 180 nm can be expected to suppress the separation of the formulation which consisted of 10.0% soybean oil, 1.2% phospholipids and 5.0% glucose. The stability studies were conducted at 40 degrees C for 3 months and the fat emulsion was stable during storage. These investigations contribute to the preparation of a new caloric source for peripheral parenteral nutrition.

Degradation kinetics of L-glutamine in aqueous solution.

The degradation kinetics of L-glutamine (Gln) in aqueous solution was studied as a function of buffer concentration, pH and temperature. Stability tests were performed using a stability-indicating high-performance liquid chromatographic assay. The degradation product of Gln was 5-pyrrolidone-2-carboxylic acid. The reaction order for Gln in aqueous solution followed pseudo-first-order kinetics under all experimental conditions. The maximum stability of Gln was observed in the pH range from 5.0 to 7. 5. The pH-rate profile described by specific acid-base catalysis and hydrolysis by water molecules agreed with the experimental results. Arrhenius plots showed the temperature dependence of Gln degradation, and the apparent activation energy at pH 6.41 was determined to be 9.87 x 10(4) J mol(-1).

[Intravenous chronic toxicity of lentinan in rats: 6-month treatment and 3-month recovery (author's transl)].

Chronic toxicity of lentinan was studied in male and female JCL : SD rats. Lentinan was given intravenously into tail vein. Dosage levels employed were 0 (5% mannitol), 0.01, 0.1, 1 (with or without dextran), and 10 mg/kg/day for 6 months in a volume of 1 ml/100 g body weight. After 6 months, the treatment was discontinued and a recovery study was performed for 3 months. Rats receiving 10 mg/kg had redness and necrosis of the tail, the treatment was stopped at week 5, and the rats were sacrificed. Rats receiving 1 mg/kg showed redness of the ear, tail, and scrotum, which was remarkable in the 2nd and 3rd months. Body weight gains were not adversely affected. Laboratory examinations revealed an increase in leukocyte count, decreases in differential eosinophil count and platelet count, and an increase in serum beta-globulin level in drug-treated rats. At autopsy after 6 months, rats from the drug-treated groups had pulmonary hemorrhage and enlargements of the spleen and mesenteric lymph nodes. Histologic changes attributable to treatment included (1) activation of reticulo-endothelial system such as small epithelioid cell nodule in the liver, spleen, and mesenteric lymph nodes, and mobilization of Kupffer cells; (2) arteritis in various organs, especially notable in the spleen, testis, and epididymis ; (3) hemorrhage in the lung; and (4) hypospermatogenesis. All these changes described above had a propensity to recover. The maximum no effect level was estimated to be less than 0.01 mg/kg in the present study in male and female rats.

Effect of a new amino acid solution on nutritional status and nitrogen metabolism in rats with chronic renal failure undergoing hyperalimentation.

We studied the effects of the new amino acid solution MRX-III on the nutritional status and nitrogen metabolism of rats with chronic renal failure (CRF) in comparison with those of a general amino acid solution (MPR-F). The essential amino acids/non-essential amino acids ratio was 3.21 for MRX-III and 1.09 for MPR-F. Rats with CRF, induced by 7/8 renal ablation, were divided into 6 groups of 8 rats each receiving total parenteral nutrition (TPN) containing MRX-III or MPR-F at a non-protein calorie/nitrogen ratio (Cal/N) of 300, 600 or 900 for 7 d. The rats were infused with test solutions containing the same amounts of non-protein calories. The cumulative nitrogen balance, as a nutritional index, in the MRX-III group was significantly higher than that in the MPR-F group at the Cal/N of 600 or 900, and the plasma albumin level at the Cal/N of 300. The plasma transferrin levels at the Cal/N of 900 in the MRX-III groups were significantly higher than those in the corresponding MPR-F groups. At all Cal/N, the MRX-III groups showed low levels of blood urea nitrogen and urinary excretion of ammonia and urea nitrogen as compared with the MPR-F groups at the same Cal/N. The plasma amino acid concentration profiles in the MRX-III groups after TPN showed greater similarity to that in the Normal group as compared with the profiles in the corresponding MPR-F groups. No aggravation of renal failure was observed in any TPN groups during TPN. These results indicate that, in rats with CRF undergoing hyperalimentation, the effects of MRX-III on the nutritional status and nitrogen metabolism are superior to those of the general amino acid solution, MPR-F. It is suggested that MRX-III could safely provide adequate amounts of nitrogen during hyperalimentation.

Tumor growth inhibition and nutritional effect of D-amino acid solution in AH109A hepatoma-bearing rats.

We examined the inhibitional and nutritional effects of total parenteral nutrition (TPN) containing D-amino acids (D-phenylalanine, D-Phe; D-valine, D-Val; D-leucine, D-Leu; D-methionine, D-Met) on tumor growth in AH109A hepatoma-bearing rats. Five experimental groups were examined: a control amino acid solution group (control group), D-Phe group, D-Val group, D-Leu group and D-Met group. The analysis of tumor volume and weight revealed significant tumor growth inhibition in the D-Val group as compared with the control group. In the D-Val group, decreases of DNA and protein contents in the tumor tissues were also observed. The D-Leu and D-Met groups showed a tendency toward tumor growth inhibition. The protein content in the liver tissues of these two groups was significantly higher as compared with the control group. The DNA content in the liver tissue was also significantly higher in the D-Met group. The body weight including the tumor (on the final day of TPN) was significantly lower in the D-Val group as compared with the control group, but there was no significant difference in the groups for body weights not including tumors (carcass body weight). The hematocrit and hemoglobin values, indicators of anemia, were significantly higher in the D-Val group as compared with the control group. From these results, regarding tumor growth inhibition, the D-Val solution had the strongest inhibitory effect with no negative influence on the host, and improvement of nutritional status was also suggested in the rats that received the D-Leu or D-Met solutions.

Comparison of glucose and fat as energy sources in peripheral parenteral nutrition in rats.

Glucose is usually chosen as the energy source for total parenteral nutrition. However, the optimal glucose:fat ratio for peripheral parenteral nutrition has not been examined sufficiently. We compared glucose:fat ratios in hypocaloric nutrition. Male SD rats were given hypocaloric parenteral nutrition (approx. 190 kcal/kg/d) for 5 d after laparotomy. The hypocaloric solutions used contained 0, 33, 50, 67 or 100% of the non-protein energy in the form of fat. Body weight change, nitrogen balance, organ weights, and hepatic, splenic and plasma biochemistries were assessed. Body weight increase in the 67 and 100% fat groups was significantly greater than that in the 0% fat group. Nitrogen balance was the same in all groups. Hepatic glycogen content was significantly lower in the 100% fat group than that in the 0% fat group. The weight of epididymal fat deposits was significantly lower in the 0% fat group than in the 50 and 67% fat groups. On the other hand, tissue triglyceride content and plasma lipid levels in the 100% fat group were significantly higher than in the 0% fat group, and were also higher than in the control group. It is suggested that combinations of glucose and fat have sparing effects on body fat and hepatic glycogen. Combinations of glucose and fat as non-protein energy sources were superior to glucose or fat alone for hypocaloric parenteral nutrition.

Correlation between intravenously supplied energy level and zinc metabolism in laparotomized rats.

We investigated the relationship between intravenous energy loading and zinc status in laparotomized rats. One of three test solutions consisting of 3% amino acid, the same amount of electrolytes (excluding zinc) and different concentrations of glucose were infused through the jugular vein for 5 d. The total energy was 109, 191 and 273 kcal/kg/d, respectively. Significantly positive correlations were observed between infusion energy and rat body weight changes (% of initial value) and between infusion energy and cumulative nitrogen balance. Regarding the zinc status, a negative correlation was found between infusion energy and plasma zinc concentration, and a positive correlation was observed between infusion energy and urinary zinc excretion. There was no significant relationship between infusion energy and hepatic zinc content. These results indicate that the zinc requirement might be increased when infusion energy is elevated and the nutritional status is improved. Zinc supplementation in the post-operative period should be considered in light of not only catabolism but also anabolism. Anabolism may be more important than catabolism in regard to zinc metabolism under relatively mild stress.

Significance of magnetic resonance image and blood manganese measurement for the assessment of brain manganese during total parenteral nutrition in rats.

In this study, we report on the influence of trace elements (TE) on signal intensities of nuclear magnetic resonance images (MRI), both in vivo and in vitro. Optimal parameters for the assessment of Mn concentration in the brain of rats on total parenteral nutrition were established. For the in vitro study, Mn and trace element solutions, one containing Zn, Cu, Fe, and I (TE-4) and another containing the above elements plus Mn (TE-5), were diluted with physiological saline or with rat brain homogenate and used to measure signal intensities in MRI. Concentration-dependent signal hyperintensity was observed in both cases in the Mn and the TE-5 solutions, but no effect was observed with the TE-4 solution. The signal increase was greater for brain tissue homogenates. In the in vivo study, the experimental animals were maintained under total parenteral nutrition (TPN) with a standard clinical dose of TE-5 and/or with 10-fold the clinical dose of TE-4 and TE-5 for 1 wk. Only rats that were receiving the increased TE-5 dose showed signal hyperintensity on MRI. Positive correlations were observed among the signal hyperintensity, the blood Mn concentrations, and that of the rat brain. Our results suggest that Mn in TE preparations may be the cause of signal hyperintensity on MRI in a concentration-dependent fashion, and that MRI and measurement of blood Mn may be used to estimate Mn accumulation in brain tissue.

Magnetic resonance image and blood manganese concentration as indices for manganese content in the brain of rats.

Neurological disorders similar to parkinsonian syndrome and signal hyperintensity in brain on T1-weighted magnetic resonance (MR) images have been reported in patients receiving long-term total parenteral nutrition (TPN). These symptoms have been associated with manganese (Mn) depositions in brain. Although alterations of signal intensity on T1-weighted MR images in brain and of Mn concentration in blood are theoretically considered good indices for estimating Mn deposition in brain, precise correlations between these parameters have not been demonstrated as yet. Male Sprague-Dawley rats received TPN with 10-fold the clinical dose of the trace element preparation (TE-5) for 7 d. At 0, 2, 4, 6, and 8 wk post-TPN, the cortex, striatum, midbrain, and cerebellum were evaluated by MR images, and Mn concentration in blood and Mn content in these brain sites were measured by atomic absorption spectrometry. Immediately after TPN termination, signal hyperintensity in brain sites and elevated Mn content in blood and brain sites were observed. These values recovered at 4 wk post-TPN. A positive correlation was observed between either the signal intensity in certain brain sites or Mn content in blood and the relevant brain sites. Our observations suggest that the Mn concentration in blood and signal intensity in the brain sites on T1-weighted MR images are reliable indices for monitoring Mn contents in brain.

Effect of enrichment of infusion solutions with branched chain amino acids in parenteral nutrition of rats.

The effect of enrichment of the branched chain amino acids (BCAAs) leucine, isoleucine and valine on total parenteral nutrition was studied in rats. Experimental infusion solutions with a sufficient, marginal or deficient level of glucose contained either the conventional amino acid composition (22.6% BCAAs) or a BCAA-enriched amino acid composition (36% BCAAs). Rats were infused with experimental solutions for 4 days and several parameters of protein metabolism were evaluated in various tissues. Under conditions of sufficient energy supply, BCAA-enriched and conventional groups showed similar body weight gains and muscle protein degradations as measured by urinary 3-methylhistidine excretion. Polysome profiles in the liver and gastrocnemius muscle of the BCAA-enriched group were more heavily aggregated than those of the conventional group. Under the conditions of marginal or deficient energy supply, beneficial effects of BCAA enrichment over the conventional amino acid composition became more evident in terms of better body weight retention, higher RNA/DNA ratio and heavier polysome profile in both liver and muscle, and reduced protein catabolism in muscle. The present study suggests that enrichment of BCAAs, particularly valine and isoleucine, may be useful for nutritional support under hypercatabolic or stressed conditions.

[Effects of various Ringer's solutions on acid-base balance in rats in hemorrhagic shock and with hepatic dysfunction].

We investigated the effects of bicarbonated Ringer's solution (BR) on arterial blood acid-base balance, and compared these with the effects of lactated Ringer's solution (LR) and acetated Ringer's solution (AR) in rats in hemorrhagic shock. Rats underwent 70% reduction of hepatic blood flow and blood shedding of 1.5% of body weight. Each solution was infused through the femoral vein at a rate of shed blood volume x 8.hr-1 for 30 min under urethane anaesthesia. After the blood shedding, arterial blood pH and HCO3-decreased but plasma lactate concentration increased. These parameters improved significantly in the BR group compared with those in the LR group. However, the LR group showed the lowest blood pH and the highest plasma lactate concentration among the groups. These results suggest that BR has superior effects on the arterial blood acid-base balance and glucose metabolism in rats in hemorrhagic shock and with hepatic dysfunction.

[Strategy for the treatment of hepatocellular carcinoma].

Hepatocellular carcinoma is a refractory cancer for the following two reasons: the tumor characteristics, including formation of tumor thrombus in the portal vein, metastasis within the liver and multicentricity of growth; and liver function disturbance due to cirrhotic change by B- or C-type viral infection. The most desirable treatment is hepatic resection, the only method producing a disease-free condition. However, there are not many cases that meet the indications for hepatic resection, since they have advanced lesions and/or liver dysfunction. If one cannot perform a hepatic resection, other suitable therapies should be selected, including transcatheter arterial embolization, percutaneous ethanol injection therapy, ligation of hepatic artery, irradiation, chemotherapy from hepatic artery via reservoir and so on. Combined therapy may sometimes be necessary for satisfactory efficacy. For long-term survival it is very important to do a close follow-up study over a long period. This encourages us to detect new lesions earlier and then perform suitable therapy again. Notifying patients of the disease and obtaining informed consent are needed for this long-term follow-up and treatment. When patients were examined who had first undergone hepatic resection and then hepatic re-resection for recurrence, we found that their survival rate was not different from that in the non-recurrent cases. This result indicates that overcoming refractory hepatocellular carcinoma requires a multidisciplinary treatment in which hepatic resection is the main means.

[Establishment of alpha-fetoprotein producing human rectal cancer cell line (RKK-YK) and its features].

We succeeded in establishing a rectal cancer cell line RKK-YK from the primary lesion in a patient with rectal cancer. It took 36.2 hours for duplication. We were able to transplant the RKK-YK cell line to nude mice at a transplantation rate of 50%. The transplanted tumor exhibited histological features similar to those of the primary lesion. Cancer cells with two different degrees of differentiation, in which features of moderately differentiated adenocarcinoma and well-differentiated adenocarcinoma were observed together, were established. The levels of the tumor markers (CEA, CA19-9 and AFP) were elevated in the supernatant of the culture solution and the serum of the nude mice over time course. In the immunohistological examination of the transplanted tumor, anti-CEA, anti-CA19-9 and anti-AFP antibodies were positively stained. Molecular biological analysis revealed nor point mutation or deletion in K-ras gene exon 1 and 2, p53 gene exon 5 to 11 or MCC.