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Biomedical subjects

P Watanapa

Publications and source records attributed to P Watanapa.

At least 19 recordsLinked to original sources

Liver fluke-associated cholangiocarcinoma.

BACKGROUND: Infection with liver flukes has been reported to be associated with bile duct malignancy. METHODS: The review is based on a literature search (Medline) and, in some cases, direct contact with authors or principal investigators. RESULTS: A large body of evidence indicates that Opisthorchis viverrini is a definite cause of human cholangiocarcinoma, whereas Clonorchis sinensis is a probable cause. The evidence regarding Opisthorchis felineus is insufficient to assess its role in carcinogenesis. Possible mechanisms of carcinogenesis include chronic irritation, nitric oxide formation, intrinsic nitrosation and activation of drug-metabolizing enzymes. Early detection of bile duct malignancy is difficult and not clinically available at present, although cholangiocarcinoma-associated soluble antigen has been reported in an experimental study to be a useful early marker of cancer development. Long-term survival after surgical treatment of liver fluke-associated cancer is similar to that reported in patients without liver fluke infestation. CONCLUSION: Liver fluke-associated cholangiocarcinoma is still a health problem in developing countries. Mechanisms of carcinogenesis should be explored further in order to reduce the impact of this disease.

Animals↗

The observation of immunosuppressor(s) derived from cultured tumor cells and its partial neutralization with OK-432.

Malignant tumors such as brain tumors have been reported to be associated with immunosuppression caused by certain tumor-secreted cytokines. The reversion of tumor-derived immunosuppression has not been described. The use of OK-432, an immunomodulatory agent prepared from Su-strain of Streptococcus pyogenes A3, to activate peripheral blood mononuclear cells from a patient with glioblastoma multiforme has demonstrated a sharp rise in proliferative response. This proliferative response was compromised in the presence of living and irradiated autogeneic cancer cells. The conditioned media from cultured cells of glioblastoma multiforme, astrocytoma, and cholangiocarcinoma were tested for immunosuppressive ability. We found that conditioned media from 3 of 4 cases of glioblastoma, all 3 cases of astrocytoma, and 1 case of cholangiocarcinoma exhibited immunosuppressive activity toward the proliferative response of allogeneic peripheral blood mononuclear cells to phytohemagglutinin. This is the first report that cholangiocarcinoma produces soluble immunosuppressor(s). Our finding suggested that soluble substance(s) as well as direct cell-cell contact between tumor cells and mononuclear cells play roles in the observed tumor-derived immunosuppression.

Adjuvants, Immunologic↗

Solitary rectal ulcer syndrome: two case reports.

Owing to its rarity, solitary rectal ulcer syndrome (SRUS) is often misdiagnosed as malignant ulcer, or ulcer in association with inflammatory bowel disease. We present two adult females with anorectal symptoms (i.e. pain, tenesmus and bowel habit changes). Both had normal levels of serum carcinoembryonic antigen. Barium enema revealed irregular mucosa with stricture of the lower rectum. An ulcer, 2.7 cm in diameter, was found in one patient but not the other. Rectal biopsy under sigmoidoscopy demonstrated non-specific inflammation, without evidence of malignancy. Because of the intractable symptoms and the inability to discriminate between malignant and benign conditions, exploratory laparotomy was performed, followed by low anterior resection of the rectum. Histological examination of both specimens showed submucosal rectal fibrosis with a non-specific ulceration in one. These findings were compatible with SRUS. The patients' symptoms improved dramatically after the resection and they remain well, five months and one year after surgery. Awareness of this rare anorectal condition is necessary for appropriate management particularly to avoid unnecessary abdomino-perineal resection.

Adult↗

Cholangiocarcinoma in patients with opisthorchiasis.

Cholangiocarcinoma is very common in areas endemic for the liver fluke Opisthorchis viverrini. Survival after surgical treatment of cholangiocarcinoma associated with opisthorchiasis was studied prospectively in 30 patients, all of whom resided in an endemic area. The median age was 52 (range 32-69) years and twenty-five patients were men. Seven patients had their tumours removed, four with concomitant liver resection. Twenty-two patients underwent palliative biliary bypass procedures to a segmental duct. Laparotomy with biopsy of metastatic lesions was undertaken in one patient with multiple lymph node metastases and peritoneal seedlings. No patient received postoperative chemotherapy or radiation treatment. Patients were followed for 2 years or until death. The 1-year survival rate after tumour resection was 86 per cent and the 2-year survival rate 43 per cent. After palliative procedures the 1-year survival rate was 26 per cent; no patient reached 2 years and the median survival time was 8 months. Survival after surgical treatment of cholangiocarcinoma in patients with opisthorchiasis is broadly similar to that reported for cholangiocarcinoma without liver fluke infestation.

Adult↗

Recovery patterns of liver function after complete and partial surgical biliary decompression.

BACKGROUND: Recovery patterns of liver function after surgical drainage of obstructing biliary system have not been studied properly, particularly after a single-lobe biliary decompression where atrophic-hypertrophic changes of the liver may affect the recovery of liver functions. PATIENTS AND METHODS: Thirty patients with malignant obstructive jaundice had their liver functions evaluated biochemically both 1 week and 1 day preoperatively, and at 4 points postoperatively: 3 days, 1 week, 3 weeks, and 6 weeks. Half of them underwent complete biliary drainage procedures, whereas the remaining half had partial drainage (decompression of the left lobe only by means of segment III duct-enteric bypass). RESULTS: For those with complete drainage, serum alkaline phosphatase (AP) and gamma glutamyl transpeptidase (GGT) were 40% to 50% of preoperative levels 3 days after surgery (P<0.005), and were about twice the norm at 6 weeks. Their serum total and direct bilirubins (TB, DB) were approximately 60% reduced 1 week after the drainage (P<0.05). For partial drainage, serum AP and GGT decreased by 50% at 1 week (P<0.05), but were still very high 6 weeks after the drainage. The TB and DB decreased significantly 1 week postoperatively, and were three times the norm at 6 weeks. Serum albumin decreased sharply at 3 days and returned to normal levels 3 weeks after either complete or partial biliary drainage. Aminotransferase enzymes responded differently between the two groups. The levels dramatically declined one week after complete drainage and were slightly higher than normal thereafter. Following partial drainage, the enzyme levels were unchanged throughout the study period. CONCLUSION: Complete biliary drainage can nearly normalize the liver functions by 6 weeks, and biliary drainage of one lobe of the liver can effectively recover the liver functions.

Adult↗

The potential role of intraoperative ultrasonography in the surgical treatment of hilar cholangiocarcinoma.

The role of intraoperative ultrasonography (IOU) in the surgical treatment of hilar cholangiocarcinoma was explored in twenty-two patients, 17 males and 5 females. The mean age was 55 years (range 36-78 years). Preoperative imaging studies included abdominal ultra-sonography and/or CT scan, and visceral angiography. Operations performed were segment III bypass in 18 patients, local resection of tumour in 2 and resection of tumour en bloc with left hepatectomy in 2. Interpretation of IOU in terms of vascular involvement by the tumour (as compared to angiography or operative findings) was correct in 21 patients; no vascular invasion in 20 and portal vein invasion in the remainder. One false negative result occurred in a patient whose IOU failed to show right hepatic artery encasement by the tumour. When compared to postoperative cholangiography or surgical specimen, IOU correctly demonstrated location and extent of the tumours in all but one patient who had incomplete tumour resection. IOU was also helpful in locating segment III duct for biliary bypass. The mean time used for IOU was 15.1 min (range 10-20 min.), and there was no procedure-related complication. When supplemented with operative exploration, IOU seems to be very useful in the assessment of the resectability of hilar cholangiocarcinoma.

Adult↗

Beware the anomalous portal vein.

Portal vein thrombosis is an unusual potential complication of liver resection. In our case it was due to ligation of the right branch of the portal vein during right hepatectomy in a patient without portal vein bifurcation. Hepatic angiography can delineate this abnormality and influence the choice of surgical management.

Cholangitis↗

A 31P and 1H-NMR investigation in vitro of normal and abnormal human liver.

Spectral changes in human hepatic tumours and possible systemic effects of tumour on host liver were assessed by 31P and 1H in vitro NMR spectroscopy. The 1H and 31P spectra from liver tumour biopsies showed significant elevation in phosphoethanolamine, phosphocholine, taurine, citrate, alanine, lactate and glycine, and significant reduction in GPE (glycerophosphoethanolamine), GPC (glycerophosphocholine), creatine and threonine compared to histologically normal tissue. 31P-NMR spectra obtained from histologically normal tissue within tumour-bearing livers showed significant elevation in phosphoethanolamine and phosphocholine compared to data from liver biopsies from nontumour-bearing patients (pancreatitis). These results suggest that alterations in membrane metabolism in host liver can be detected by 31P-NMR.

Biopsy↗

Effect of luminal growth factor preservation on intestinal growth.

Intestinal atrophy contributes to the clinical difficulties of patients who cannot eat normally. Atrophy is prevented by luminal food proteins but not by the equivalent aminoacids. This observation is not explained by current theories of intestinal physiology. Epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha) are secreted into the gut lumen. We speculated that these are digested by pancreatic enzymes in fasting juice, but preserved when food proteins block the active sites of these enzymes. Studies based on molecular size and bioactivity confirmed that fasting human jejunal juice destroys EGF and TGF alpha. EGF, but not TGF alpha, was preserved when the milk protein casein or an enzyme inhibitor were present; elemental diets were ineffective. Diversion of pancreatic juice to the mid point of the small intestine in rats significantly increased luminal EGF-like bioactivity and all variables of growth in the proximal enzyme-free segment. Our findings support a novel mechanism of control of intestinal growth, which has important clinical implications. The addition of enzyme-inhibiting proteins such as casein to elemental diets may preserve intestinal integrity and function.

Animals↗

Single-loop biliary and gastric bypass for irresectable pancreatic carcinoma.

Twenty-five patients with irresectable carcinoma of the pancreatic head received a modified type of palliative bypass in which the transected bile duct and the gastric antrum were anastomosed to the same Roux loop of jejunum. There were 13 women and 12 men with a median age of 54 (range 35-74) years. All but three patients were jaundiced and 11 underwent preoperative biliary decompression. In 18 patients jaundiced at the time of operation, the median preoperative serum bilirubin level was 287 (range 57-804) mumol/l. The median operative time was 4.0 (range 2.5-6.0) h. There were no hospital deaths. Minor postoperative complications occurred in nine patients and the median hospital stay after operation was 13 (range 7-49) days. The median postoperative survival was 4.8 (range 1.5-11.5) months. This operation provides good palliation safely in selected patients with irresectable pancreatic carcinoma.

Adult↗

Inhibitory effect of a cholecystokinin antagonist on pancreatic carcinogenesis after pancreatobiliary diversion.

The role of cholecystokinin (CCK) has been explored in pancreatic carcinogenesis following pancreatobiliary diversion (PBD), using the specific CCK receptor antagonist CR-1409. Male Wistar rats (n = 80) weighing 70-100 g were given weekly i.p. injections of azaserine (30 mg kg-1 week-1) for 3 consecutive weeks. One week later animals were randomised to receive either PBD or sham PBD and thereafter to receive s.c. injections of either saline or CR-1409 (10 mg kg-1 day-1, 5 days a week). Six months after operation surviving rats were killed as follows: sham + saline 20, PBD + saline 19, sham + CR-1409 14, PBD + CR-1409 11. Cardiac blood was taken for CCK assay and the pancreas was excised for wet weight measurement and quantitative estimation of atypical acinar cell foci (AACF), the precursor of carcinoma. PBD reduced median body weight (3-20% less than shams) but trebled the absolute and relative pancreatic weights (P < 0.001). CR-1409 blunted this adaptive response to PBD, reducing absolute pancreatic weight by 35% (P < 0.005). PBD quadrupled circulating CCK concentrations, regardless of the antagonist treatment. Acidophilic AACF occurred only in rats with PBD. CR-1409 markedly reduced the number of observed acidophilic AACF by 90% (P < 0.001) and the number of foci per pancreas by 93% (P < 0.001). Moreover, CR-1409 reduced the mean focal diameter of each lesion by 18% (P < 0.005), the mean focal volume by 58% (P < 0.05) and the percentage of pancreas occupied by acidophilic foci by 95% (P < 0.001). PBD enhances pancreatic carcinogenesis by causing hypercholecystokininaemia, and CR-1409 largely inhibits this enhancement.

Animals↗

Experimental pancreatic hyperplasia and neoplasia: effects of dietary and surgical manipulation.

Several studies carried out during the past two decades have investigated the effect of dietary and surgical manipulation on pancreatic growth and carcinogenesis. Diets high in trypsin inhibitor stimulate pancreatic growth and increase the formation of preneoplastic lesions and carcinomas in the rat pancreas. Cholecystokinin (CCK) is the key intermediary in this response, since both natural and synthetic trypsin inhibitors increase circulating levels of the hormone and CCK antagonists largely prevent these changes. Fatty acids enhance pancreatic carcinogenesis in both rats and hamsters, whereas protein appears to have a protective role in the rat, but to increase tumour yields in the hamster. Several surgical operations affect the pancreas. Pancreatobiliary diversion and partial gastrectomy stimulate pancreatic growth and enhance carcinogenesis, probably by means of increased CCK release. Complete duodenogastric reflux has similar effects on the pancreas but the gut peptide involved is gastrin. Although massive small bowel resection increases pancreatic growth, the marked reduction in caloric absorption probably explains its failure to enhance carcinogenesis. CCK and enteroglucagon might work in concert to modulate the tropic response of the pancreas to small bowel resection. In the pancreas, as in the large intestine, hyperplasia appears to precede and predispose to neoplasia.

Animals↗

Severe subcellular damage in the rat exocrine pancreas after pancreatobiliary diversion.

Cholecystokinin (CCK) may contribute to the genesis of both pancreatic carcinoma and acute pancreatitis. By transposing a long segment of jejunum to lie between the pylorus and the duodenal papilla, pancreatobiliary diversion (PBD) causes a persistent increase in circulating CCK levels, as the normal feedback inhibition of jejunal CCK release by pancreatic juice is evaded. A number of morphological, physiological, and acinar cytokinetic changes ensue. This investigation has examined the ultrastructural changes in pancreatic acinar cells after PBD in the presence and absence of CR1409 (lorglumide), a CCK receptor antagonist. After 14 days there was degranulation and vacuolation of acinar cells with involvement of the enzyme acid phosphatase. The presence of morphologically distinct extracisternal acid phosphatase indisputably predisposed acinar cells to severe damage. Treatment with CR1409 largely prevented degranulation after PBD, but vacuolation of acinar cells still occurred, indicating a possible toxic effect of the receptor antagonist. This is the first report of CCK itself, rather than one of its analogues, causing in vivo pancreatic damage that is generally considered as a forerunner to acute pancreatitis. This is of fundamental importance to the understanding of the earliest stages of the disease.

Acid Phosphatase↗

Surgical palliation for pancreatic cancer: developments during the past two decades.

Improvements in pancreatic imaging over the past 20 years have revolutionized the preoperative diagnosis and assessment of resectability in patients with suspected pancreatic cancer. This review highlights the resultant trends in the surgical treatment of ductal carcinoma of the pancreas, comparing series reported between 1981 and 1990 with those from the previous decade. Small but worthwhile gains have been achieved both in overall resection rate and in the survival rate from such resections. Nevertheless, 80 per cent or more of affected patients are still unsuitable for resection because of the extent of their disease. Laparotomy retains a crucial role in the management of carcinoma of the pancreatic head, although percutaneous and endoscopic stents provide a useful alternative for palliation of malignant obstructive jaundice in elderly patients or those with carcinomatosis. Operation provides the chance to confirm the nature and full extent of the tumour, to circumvent duodenal obstruction and to abolish pain, besides relieving jaundice without the need for tubes (with their potential to block). By contrast, operative treatment generally has much less to offer in patients with carcinoma of the pancreatic body, unless diagnosis and irresectability remain in doubt. In combination, radiotherapy and 5-fluorouracil may achieve more as adjuncts to palliative surgery than either agent alone. The increasing safety of pancreaticoduodenectomy raises the possibility of palliative resection in younger patients with limited but incurable disease.

Cholestasis, Extrahepatic↗