Splenectomy before tumor inoculation prolongs the survival time of cachectic mice.

The effects of splenectomy on the development of cachexia, tumor growth and animal survival were studied in tumor-bearing CDF1 mice. Mice were inoculated with two subclones of colon 26 adenocarcinoma, clone 20 (with a potent capacity to induce cachexia) and clone 5 (without such activity), and underwent splenectomy before or after tumor inoculation. Splenectomy significantly prolonged the survival of mice bearing clone 20 when it was performed prior to tumor inoculation, although the progression of cachexia and tumor growth were not affected. The survival rate was higher in splenectomized than it was in nonsplenectomized mice 20-40 days after tumor inoculation. Such effects on survival were not observed, however, in mice splenectomized after inoculation with clone 20 or in mice that underwent splenectomy either before or after inoculation with clone 5. The decrease of peripheral blood lymphocyte count observed in mice bearing clone 20 was magnified when splenectomy was performed before tumor inoculation, but the serum levels of tumor necrosis factor and interleukin-6 were comparable. These results indicate that cancer death from cachexia is not directly attributable to enhanced catabolism. The mechanism by which splenectomy ameliorates the survival of cachectic mice remains to be studied, although several changes observed in the splenectomized mice after inoculation, including decreases in the peripheral blood L3T4+ cells and Lyt-2+ cells on the 9th day and 15th day respectively, and increase in the L3T4+/Lyt-2+ cell ratio on the 15th day suggest the involvement of the modified host's immune response.

Manifestations of cancer cachexia induced by colon 26 adenocarcinoma are not fully ascribable to interleukin-6.

In order to further clarify the role of interleukin 6 (IL-6) in the pathogenesis of cachexia, recombinant human IL-6 (hIL-6) was administered s.c. by osmotic pump for 9 days at a dose of 1 or 10 micrograms/day into CDF1 mice inoculated with a non-cachexia-inducing subclone of colon 26 adenocarcinoma (clone 5), or with a cachexia-inducing subclone (clone 20) of this malignancy. The serum level of IL-6 in non-cachectic mice with clone-5 tumors was 35% lower than in cachectic mice bearing clone 20 of colon 26 adenocarcinoma on the 19th day after tumor inoculation. IL-6 administration induced anemia, thrombocytosis and visceral organ hypertrophy not only in mice with clone-5 tumors but also in control mice with no tumor burden. Lipolysis and proteolysis became conspicuous when a large dose (10 micrograms/day) of IL-6 was infused into mice with clone-5 tumors. However, IL-6 supplementation did not induce loss of body weight, a decline in food intake or lymphocytopenia, which were characteristically observed in cachectic mice with clone-20 tumors. In conclusion, IL-6 appears to be a permissive factor for the development of cachexia but, while it can induce some of the symptoms typical of cachexia, it cannot in itself induce the full cachectic syndrome.

Minute malignant islet cell tumor of the pancreas: report of a case.

We present herein the case of a 73-year-old Japanese man in whom a minute malignant islet cell tumor, 7 mm in maximal diameter, was discovered. The patient was admitted to our hospital to undergo a gastrectomy for gastric cancer, at which time preoperative ultrasonography (US) revealed a minute hypoechoic mass located in the head of the pancreas. Endoscopic retrograde pancreatography, angiography, computed tomography, and magnetic resonance imaging failed to reveal the features or location of the tumor; however, these details were obtained by endoscopic and intraoperative US. Although intraoperative fine-needle aspiration cytology of the tumor enabled a diagnosis of islet cell tumor to be made, it failed to provide enough material to evaluate the grade of malignancy, which was confirmed by histologic examination of the enucleated tumor, allowing the appropriate surgical procedure to be decided.

Characterization of mice bearing subclones of colon 26 adenocarcinoma disqualifies interleukin-6 as the sole inducer of cachexia.

A subclone (clone 20) of chemically induced, murine colon adenocarcinoma with a potent ability to induce cachexia and another subclone (clone 5) without such an activity were transplanted to syngeneic mice (CDF1) and their tissue weights, blood components and cytokine levels in sera were compared. Mice transplanted with clone 20 showed a profound body-weight loss by 15 days after inoculation when the tumor accounted for less than 1% of the body weight, along with marked reduction of food and water intakes. Thereafter, they transiently gained in body weight with restoration of food and water intakes. Thus, the change in body weight was biphasic and not proportional to the tumor size. Body fat was lost preferentially, accompanied with a decrease in plasma triglyceride levels. The thymus contracted remarkably, and the peripheral lymphocyte count decreased extensively. Mice transplanted with clone 5, in contrast, did not show any of these changes characteristic of cachexia. Serum concentration of interleukin-6, which has been proposed as the principal inducer of cachexia in mice with colon 26, increased in mice with clone 5 to levels comparable to those in mice with clone 20. The changes in mice bearing clone 20 could not all be explained in terms of known biological activities of interleukin-6. Additional unknown factors, therefore, are presumed to contribute to cachexia in mice with clone 20. Identification of them should be helpful in the care of cachectic patients.

A newly developed fine-caliber endoscope for peroral cholangiopancreatoscopy.

We have developed a new fine-caliber (2.09 mm outer diameter) endoscope for peroral cholangiopancreatoscopy. The endoscope contains one image transmission fiber, 12 light guide fibers (the transmitter of light from the light source) and a working channel (a lumen for the guide wire and rinsing). The working channel, whose bore is 0.72 mm, is located centrally within the endoscope. The endoscope can be introduced reliably into the bile and pancreatic ducts using the same techniques as those for endoscopic nasobiliary drainage through the instrumental channel of a duodenoscope for examination without pretreatment of the papilla of Vater. Two patients with lesions of the pancreatic duct and seven patients with lesions of the bile duct suspected or detected by endoscopic retrograde cholangiopancreatography (ERCP) were examined. Direct inspection of the biliopancreatic duct not only provided enough information to make a definite diagnosis, but also revealed lesions that were not detectable by ERCP or other examinations.

Transient rise in serum interleukin-8 concentration during acute myocardial infarction.

OBJECTIVE: To determine whether interleukin-8 (IL-8, a potent activator of neutrophils) is involved in tissue injury during ischaemia and reperfusion in patients with acute myocardial infarction. SETTING: Teaching hospital. SUBJECTS: Five consecutive patients with acute Q-wave myocardial infarction, two patients with stable angina who underwent elective percutaneous transluminal coronary angioplasty, and 10 normal controls. MAIN OUTCOME MEASURE: Serum IL-8 concentration measured by enzyme linked immunosorbent assay (ELISA) over time (every four, eight or 12 hours for 36-72 hours). RESULTS: All five patients with acute myocardial infarction had a transient but significant rise in serum IL-8 concentration (13-1100 ng/l) within 22 hours after the onset of symptoms, whereas IL-8 was not detected in any of the samples from patients with angina pectoris or normal controls. One patient who died of pump failure and two patients who had mild congestive heart failure showed the highest values (1100, 920, and 190 ng/l respectively). CONCLUSIONS: Serum IL-8 concentration showed a transient rise during the very early phase of acute myocardial infarction. In combination with several recent lines of evidence indicating the importance of injurious activities of neutrophils as a cause of tissue damage in acute myocardial infarction and the potent stimulation of neutrophils by IL-8, these results strongly suggest that IL-8 is important in the development of myocardial injury in acute myocardial infarction.

Effects of newly introduced chemotherapeutic agents on a cytogenetically highly malignant neuroblastoma, xenotransplanted in nude mice.

A human neuroblastoma xenograft, designated TNB9, was used in this experiment. This xenograft is known to have a homogeneously staining region (HSR) on chromosome 20 and to exhibit 60- to 100-fold amplification of clones 8, G21 and N-myc, and showed a rapid tumor weight doubling time of 5.9 days; it represents one of the most malignant strains of human neuroblastoma. The effects of nine different chemotherapeutic agents on this xenograft were studied according to the standard Battelle Columbus Laboratories protocol, and the in vivo chemotherapeutic sensitivity assessment disclosed that Mitomycin C, Ifosfamide, and Carboplatin were highly effective against it, while VP-16, NK-171, 5-Fluorouracil, and THP-Adriamycin were ineffective. Cytogenetic and molecular-cytogenetic analyses suggest that the present data may accurately predict the clinical results with these chemotherapeutic agents in treating patients in advanced stages, as did those from our previous studies. Inclusion of Mitomycin C, Ifosfamide, and/or Carboplatin into a new chemotherapeutic protocol may be recommended.

Lidocaine metabolite formation as a measure of perioperative liver function.

In order to determine whether lidocaine metabolism, as the formation of monoethylglycinexylidide (MEGX), could be used as a quantitative index of perioperative liver function, serum levels of MEGX in 31 surgical patients were measured and compared with the results of conventional liver function tests. A significant correlation was found between the values of MEGX and ICGR15 in 20 of the 31 patients. The values of ICGR15 were lower than 20% in patients whose MEGX values were above 60 ng/ml and 20% or higher in those with MEGX values of lower than 60 ng/ml. There was also a significant correlation between MEGX values and antithrombin III values, and between MEGX values and the postoperative maximum levels of aspartate aminotransferase. However, no correlation was found between MEGX values and other preoperative conventional liver function tests in any of the 31 patients. We suggest that a cut-off MEGX value of 60 ng/ml be used as an indicator for satisfactory preoperative liver function. MEGX formation could be a useful prognostic index for patients who have undergone surgical procedures for liver disease, and employed as a quantitative assessment of perioperative liver function.

[A multicenter comparative study in patients with liver metastasis to compare tegafur in new forms with existing drugs. SF-RC.SF-SP Comparative Study Group].

A multicenter comparative study was carried out in 101 patients with liver metastasis to compare tegafur in a new oral form (Sunfural S) and tegafur in a new soft-capsule suppository form (Sunfural Rectal Capsules) with existing drugs. Sunfural S showed a tendency toward high plasma and tissue levels as compared to existing drugs, and clinically, Sunfural S produced survival times that surpassed those of existing drugs. Liver metastasis at the present time has few effective treatments, but we expect that anticancer effects will be obtained through the administration of new drugs with improved bioavailability.

[A case of multiple aneurysms originated from the superior mesenteric artery branch, and a review of literature].

A case of multiple aneurysm of superior mesenteric artery (SMA) branch is presented. A 54-year-old man with sudden onset of back pain was admitted to our hospital. Severe abdominal pain was developed and he fell into shock. Selective angiography of the SMA demonstrated aneurysm of the accessory middle colic artery to splenic flexure. Laparotomy disclosed much intraperitoneal blood and a large clot under the pancreatic body with a gushing hemorrhage. The bleeding vessel was ligated and sutured. The postoperative course was uneventful, but the subsequent angiography revealed another aneurysm of SMA branch, which was not able to be seen in the previous angiography because of overlapping with main SMA trunk. Resection of the aneurysm was done. The etiology of the latter aneurysm was suggested to be medial degeneration histologically. Fourty-nine cases of SMA aneurysm from the Japanese literature were reviewed and discussed. Emphasis is placed on early diagnostic laparotomy for appropriate management and the role of angiography in confirmation of bleeding site in case of spontaneous intraabdominal hemorrhage.

Factors influencing insulin secretion after pancreatoduodenectomy.

Preoperative patients with periampullary cancer had a higher mean sigma IRI value than that of normal controls, and also had a delayed pattern of insulin response and a lower insulinogenic index during oral-GTT. sigma IRI levels after pancreatoduodenectomy were similar to those of normal controls when the pancreatic remnants were histologically intact at the time of surgery. Postoperative sigma IRI levels could not be predicted based on the extent of histological fibrosis of the distal pancreas at the time of surgery. Patency of pancreatojejunostomy was obtained with the modified Warren's method in 39 out of 40 patients, and sigma IRI levels were maintained up to 5 years postoperatively. No significant difference was found in sigma IRI levels between pancreatoduodenectomised patients with the conventional Roux-en-Y procedure and those with the inverted Roux-en-Y with jejunal interposition. The mean insulin peak value and sigma IRI level were higher in pancreatoduodenectomised patients than in normal controls, and higher in gastrectomised patients than in pancreatoduodenectomised patients. Pancreatoduodenectomy with superior mesenteric arterial dissection resulted in remarkably low sigma IRI levels.

Splenic arteriovenous fistula formation due to angiodysplasia in a splenic aneurysm of a patient with liver cirrhosis--a report of a case.

A 53 year-old Japanese woman with liver cirrhosis manifested massive hematemesis due to ruptured esophageal varices. Celiac angiography demonstrated an aneurysm of the splenic hilus and arteriovenous fistula around the aneurysm. She underwent splenectomy, proximal gastrectomy, distal esophageal devascularization and pyloroplasty. Histological examination of the aneurysm revealed arterial dysplasia with a focal medial gap. Microscopic tissue clefts at the site of a medial gap were considered to be the source of the angiographic arteriovenous fistula.

[Mixed ductal and acinar cell cancer of the pancreas head; report of a case].

A 63 year old Japanese man was admitted in Feb. 1983, with his chief complaint of upper abdominal pain. Physical examination showed only resistance in the right hypochondrium on palpation, but no icteric conjunctiva and skin. A large global tumor of the pancreas head was visualised as a hyperechoic mass with irregularly shaped cystic cavity in ultrasonography, as a hypervascular mass with lucent area in celiac arteriography, and as a mass lesion with low density area in body computerized tomography. Cancer cells were histologically confirmed on specimens taken by fine needle aspiration biopsy under ultrasonic guidance. Cancer of 6.5 X 6.0 X 4.0 cm in size was resected by pancreaticoduodenectomy. Four months after operation, two liver metastatic nodules were resected by right hepatic lobectomy. Histologically, tumor was composed of two characteristic patterns, acinar cell cancer and duct cell cancer, which were confirmed by immunohistochemical techniques. The patient is doing well 3 years and 3 months postoperatively without evidence of recurrent cancer. To our best knowledge, this case is the seventh of mixed ductal and acinar cancer in the world, but the previous 6 cases were reported on autopsy specimens.

[A resected case of recurrent carcinoma of the right colon ten years after the initial operation].

A 59 year-old female complained of right lower abdominal mass. She underwent radical operation 10 years ago for the right colonic cancer staged Dukes C. She had passed 10 years without any sign or symptom of recurrence. She noticed a egg-sized tumor in the right lower abdomen unexpectedly one month ago when she got a bruise on that region, and then the tumor grew rapidly. Preoperative examinations, including barium enema, abdominal computerized tomography and so on, suggested a extraluminal tumor with infiltration to the colon. Laparotomy revealed that the tumor originated from the right paracolic gutter. The tumor sized 18 X 11 X 8 cm was resected and histological diagnosis was adenocarcinoma with the similar structural pattern to the initial specimen. On the basis of both operations and histological findings, we concluded that free tumor cells might be implanted in the large raw surface of the right dorsolateral abdominal wall, which was created by surgical incision at the initial operation, and subsequently appeared as a local recurrence after 10 years interval.

Clinicopathological study on cystadenocarcinoma of the pancreas.

Although rare, mucinous cystadenocarcinoma of the pancreas is an established pathological entity. However, its characteristic features on diagnostic imaging have not yet been defined. Based upon clinicopathological studies on 5 cases, two subgroups of mucinous cystadenocarcinoma of the pancreas are proposed: the endophytic and the exophytic types. The former consist of large well-demarcated cystic tumors with numerous inward-growing cauliflower-like excrescences in mucinous material, which were characteristically demonstrated either by CT or ultrasonography. Tumors of this subtype were visualized as hypervascular masses in the capillary phase of angiography. Areas of malignant tissue were well-demarcated without capsular invasion, and tumors were free from lymph node or distant metastasis. Though cystic, the exophytic subtype had negligible inward-growing papillary projections. Corresponding to their macroscopic features, these tumors were demonstrated as cystic lesions lacking papillary projections on ultrasonography or CT. No tumor stains could be demonstrated by angiography. Despite of their smaller size than the former subtype, cancerous growth penetrated through the cyst wall and metastasized to lymph nodes, causing poorer prognosis than in the former.

Endocrine and exocrine pancreatic functions following partial pancreatectomy + partial hepatectomy.

Comparative studies were performed on changes in endocrine and exocrine responses of the pancreas after partial hepatectomy, partial pancreatectomy or combination of these procedures in rats, in order to clarify the effect of the combined operation on the remnant pancreatic parenchyma. Three days after partial (60%) pancreatectomy with partial (70%) hepatectomy, endocrine function was better preserved than after partial pancreatectomy alone, suggesting that hypersecretion of insulin initiated by partial hepatectomy may ameliorate the defective glucose-induced insulin secretion following partial pancreatectomy. Further, exocrine function in terms of amylase output was relatively well maintained 3 days after partial pancreatectomy + partial hepatectomy as compared with partial pan after partial pancreatectomy + partial hepatectomy as compared with partial pancreatectomy alone.