Malignant melanoma of the mucous membranes.

Primary malignant melanoma occurring in mucous membranes is uncommon. Of 410 patients with malignant melanoma, 14 (3.4%) had their primary tumour located in mucosal membranes. Five of the tumours were in the mucosal lining of the head and neck, five in the gastrointestinal tract mucosa and four in the female genitalia. Eight of the tumours were ulcerated, necrotic and deeply invasive. The most common histological subtype was acral lentiginous melanoma. Surgical resection of the primary tumour was performed in 10 patients. In the other four, surgery was not feasible, and they were treated by irradiation and immunotherapy. Six patients underwent regional lymph node dissection. In four of them, regional metastases were found. Chemotherapy was given to seven patients for widespread metastases. Nine patients (64%) died of metastatic melanoma within 2 years. The remaining five patients are alive after 3 to 8 years. It appears that mucosal membrane melanoma is a distinct variant of the disease due to both its aggressive biological behaviour and its relative inaccessibility for surgical removal, and may therefore be classified separately.

Acute left colonic obstruction: a new nonsurgical treatment.

Acute obstruction of the left side of the colon is traditionally treated by colostomy, which entails two or three surgical procedures usually in a high-risk group of patients. We present a new nonsurgical approach by which decompression of the bowel is achieved with a tube introduced proximal to the obstruction with the aid of a flexible sigmoidoscope. This procedure was successful in six of nine patients with left-sided large-bowel obstruction, thus avoiding staged surgery and allowing one definitive operation. No complications were encountered.

Effect of OKY 046, a thromboxane synthase inhibitor, on lung vascular permeability after pulmonary embolism in sheep.

OKY 046, a specific thromboxane synthase inhibitor, was used to investigate whether large pulmonary emboli, like microemboli, cause an increase in thromboxane A2 and an associated increase in vascular permeability in sheep. Nineteen sheep were anaesthetised and had cannulas inserted into the afferent lymphatic of the caudal mediastinal lymph node and pulmonary and carotid arteries. Several days later the animals were pretreated with placebo or OKY 046 0.4 mg/kg one hour before being given clotted blood 0.5 g/kg intravenously. After embolisation in the control animals mean pulmonary artery pressure (MPAP) rose from 12 to 34 mm Hg and pulmonary artery wedge pressure (PAWP) fell from 4.4 to 1.5 mm Hg; the cardiac index did not change but the physiological shunt (QS/QT) rose from 17% to 50%. One hour after embolisation the platelet count fell from 76 to 32 x 10(6)/l whereas at 15 minutes thromboxane B2 rose from 116 to 560 pg/ml in plasma and from 324 to 795 pg/ml in lymph (p less than 0.05). By 2 hours the concentration of thromboxane B2 was higher in lymph than in plasma. Lymph flow rose from 8.7 to a maximum of 27.3 ml/h at 15 minutes but despite the increase in flow the lymph:plasma (L:P) protein ratio did not fall, indicating an increased permeability of the blood vessels to protein. Pretreatment with OKY 046 inhibited the rise in plasma and lymph thromboxane B2, and limited the rise of QS/QT. The changes in MPAP, PAWP, cardiac index, platelet count, lymph flow, and L:P protein ratio, however, were no different from those in untreated sheep. These results indicate that a large pulmonary embolus leads to an increase in plasma and lung lymph thromboxane A2, which moderates the rise in QS/QT in part but not the increase in vascular permeability.

Rectoscopic decompression of acute recto-sigmoid obstruction.

Effective non-operative decompression of a low obstruction of the colon can sometimes be accomplished by inserting a tube into the rectum and threading the tip up to a point proximal to the obstruction (1). Failure of this non-surgical decompression would require emergency surgery--either a diverting colostomy or a two-stage resection. A new non-surgical treatment performed on a patient with an obstructive tumor of the recto-sigmoid is described. Decompression of the obstructed bowel was achieved with a rectal tube introduced over a flexible guide wire proximal to the obstruction with the aid of a rectoscope, following which a one-stage procedure--an anterior resection was performed in one patient, while the other was referred for oncological treatment.

Gastrointestinal anastomotic healing during treatment with perioperative 5-fluorouracil.

This clinical study examines the influence of perioperative administration of 5-fluorouracil (5-FU) on gastrointestinal anastomotic healing. Intravenous 5-FU, 10 mg/kg body weight, was started during surgery and continued for 9 days only when advanced cancer was detected. A total of 32 gastric and enteric anastomoses were performed. All 32 patients with anastomoses recovered without any clinical evidence of leakage. Side effects attributed to 5-FU appeared in five patients, usually in a mild form of diarrhea and vomiting. On the whole, the course of recovery of this group was no different than expected from patients with advanced malignancy undergoing extensive surgery. Based on this, it appears that 5-FU administration during and immediately after surgery has no deleterious effect on the gastrointestinal tract.

Endoscopic decompression of acute colonic obstruction. Avoiding staged surgery.

Colostomy is the traditional treatment for acute obstruction of the sigmoid colon. This entails two or three surgical procedures in a high-risk group of patients. Presented is a nonsurgical approach used in three patients with acute colonic obstruction. Decompression of the bowel was achieved with a tube introduced proximal to the obstruction with the aid of a flexible sigmoidoscope. In a fourth patient, in whom the obstruction was next to the splenic flecture, the procedure failed. In all instances where decompression was successful, a one-stage procedure--primary resection and anastomosis--was performed.

Intramural haematoma of the duodenum following blunt abdominal injury--the place for conservative treatment.

Two patients with intramural haematoma of the duodenum following blunt abdominal injury are presented. They responded well to conservative treatment. Complete resolution of the duodenal obstruction was demonstrated by consecutive radiological studies. Because haematomas usually resolve spontaneously, awareness and diagnosis of this rare condition are important in order to prevent unnecessary operation.

Cholelithiasis in Dubin-Johnson syndrome.

Only one instance of Dubin-Johnson syndrome associated with cholelithiasis has been reported. We present one additional patient, a 30 year old man with Dubin-Johnson syndrome in whom pancreatitis and cholecystitis, secondary to cholesterol gallstones, developed. A possible cause for the lithogenicity of the bile in the Dubin-Johnson syndrome is considered.

Mechanism of luminal alkalinization by bullfrog fundic mucosa.

Metiamide-inhibited fundic mucosa of bullfrog secreted alkali (OH-) at 0.1-0.2 mueq.cm-2.h-1.OH- was abolished by dinitrophenol (DNP) and was decreased significantly by 4,4-didsothiocyano-2,2-disulfonate stilbene (DIDS), anoxia, or HCO3(-)-free nutrient solution. In Na+ solutions, increasing nutrient, [HCO3(-)] augmented OH- and Isc linearly while resistance (R) decreased. No such changes occurred in Na+-free nutrient solution. In all experiments, delta Isc was approximately 12 X delta OH. Replacement of Cl- in the secretory solutions or in the nutrient solutions had no significant influence on OH-. When Na+-free nutrient solutions and Cl--free secretory solutions were present, OH- decreased significantly (P less than 0.01). Increasing nutrient [Cl-] in the absence of secretory Cl- significantly (P less than 0.01) augmented OH- and Isc. In the absence of secretory Cl-, OH- and Isc were linearly related to varying nutrient [Cl-]. In tissues with nutrient solutions on the secretory side and vice versa, apparent OH- was 0.4-0.5 mueq.cm-1.h-1 and was dependent on secretory [HCO3(-)] but was not affected by DNP, DIDS, or replacement of Cl- on secretory or nutrient solutions. We conclude that 1) OH- secretion is dependent on nutrient HCO3(-) and Na+ and oxidative metabolism, 2) endogenous HCO3(-) does not contribute significantly, and 3) adequate tissue Cl- must be present for normal OH-.

Acute complications of metastatic melanoma to the gastrointestinal tract.

The gastrointestinal tract is a favoured site for metastatic melanoma. Complications such as obstruction, bleeding or perforation should be alleviated by surgery in order to improve the patient's condition for further systemic therapy. Six patients with melanoma involving the gastrointestinal tract are presented: 3 were operated upon for metastatic lesions in the small bowel causing intussusception, 2 patients were treated for perforation of the small bowel and 1 patient with massive bleeding from metastatic melanoma in the stomach underwent gastrectomy. Two of the patients are alive 6 months and 4 years respectively after these operations. The other 4 survived between 6 months and 2 years.

Alkaline secretion by amphibian duodenum. II. Short-circuit current and Na+ and Cl- fluxes.

The relations among alkaline secretion, short-circuit current (Isc), and fluxes of Na+ and Cl- are examined. The Isc (1.15 +/- 0.03 microeq.cm-2.h-1) was significantly greater than the rate of alkaline secretion (1.02 +/- 0.02 microeq.cm-2.h-1). Regression analysis (n = 300) showed a highly significant correlation between alkaline secretion and Isc and indicated a residual Isc of 0.26 microeq.cm-2.h-1. In the absence of HCO3-, there was a residual Isc of 0.25 +/- 0.04 microeq.cm-2.h-1. This residual Isc is accounted for by an observed net Na+ absorption of 0.28 +/- 0.04 microeq.cm-2.h-1. Fluxes of Na+ fail to fit the flux-ratio equation and were not significantly affected by 2 X 10(-6) M ouabain, 5 X 10(-5) M amiloride, or anoxia but were significantly reduced by 2,4,6-triaminopyrimidine. The net Cl- flux was not significantly different from zero. Cl- fluxes conform to the flux-ratio equation and were reduced by anoxia or 2,4,6-triaminopyrimidine but were not affected by 4-acetamido-4'-isothiocynostilbene-2,2'-disulfonic acid (SITS). Anoxia or ouabain significantly inhibited alkaline secretion and Isc without affecting net fluxes of Na+ or Cl-, whereas amiloride or SITS had no effect on any of these parameters. There is no NaCl-coupled transport nor anion exchange, but solute-coupled Na+ absorption is demonstrated. We conclude that alkaline secretion by the duodenum involves a transcellular, energy-requiring, Na+-dependent, ouabain-sensitive, electrogenic mechanism that accounts for at least 80% of the Isc. Net Na+ absorption accounts for the residual Isc. Movements of Cl- are passive, do not contribute to Isc, and are not involved in the mechanism of alkaline secretion. Two hypothetical models of transcellular alkaline secretion are proposed.

Alkaline secretion by amphibian duodenum. I. General characteristics.

Stripped, proximal bullfrog duodenum was mounted in an Ussing chamber between HCO3--buffered nutrient (serosal) and unbuffered secretory (luminal) solutions. This preparation showed stable electrical parameters and caused alkalinization of the secretory solution at a rate of 0.95 +/- 0.03 mueq.cm-2.h-1 (mean +/- SE; n = 100). Anoxia and 2,4-dinitrophenol each reduced alkalinization by 50-60%, but acetazolamide (5 X 10(-4)M) had no effect. Removal of nutrient HCO3- and CO2 reduced alkalinization by over 90%, whereas increasing nutrient [HCO3-] at constant partial pressure of CO2 (PCO2) or increasing nutrient PCO2 at constant [HCO3-] each caused saturable increases in alkalinization, despite opposite effects on nutrient pH. Dibutyryl adenosine 3',5'-cyclic monophosphoric acid, but not dibutyryl guanosine 3',5'-cyclic monophosphoric acid, increased luminal alkalinization to 167 +/- 21% of control. Removal of nutrient, but not secretory, Na+ reduced alkalinization by 74%. Changes in the rate of alkalinization were accompanied by corresponding changes in potential difference and short-circuit current. Removal of Cl- or nutrient K+ or addition of histamine, thiocyanate, or catecholamines had no effect on electrical or secretory characteristics. We conclude that a) the amphibian duodenum transports alkali from nutrient to secretory solutions by both active and passive processes, b) there is a small secretion of endogenous HCO3-, c) alkaline secretion is electrogenic, d) Cl- does not contribute to the short-circuit current, e) alkaline secretion is partially dependent on nutrient Na+ that acts in a facilitatory, not cotransport, role, f) there is no Cl--HCO3- exchange, and g) alkaline secretion is independent of nutrient pH.

Role of nutrient HCO3(-) in protection of amphibian gastric mucosa.

In in vitro bullfrog fundic mucosa inhibited with 10(-3) M metiamide and exposed to a luminal pH of 2 a progressive slow decline in potential difference (PD) and short-circuit current (Isc) and a rise in resistance (R) were observed when the nutrient solution (N) contained 18 mM HCO3(-), but these changes were restored by an N containing 50 mM HCO3(-). Substitution of PO4(3-) or N-tris(hydroxymethyl)-methyl-2-aminoethanesulfonic acid for NHO3(-) in N caused a rapid drop in PD and Isc in inhibited tissues, changes that could be prevented by 10(-4) M histamine. Ulceration occurred more frequently in metiamide-inhibited gastric sacs exposed to artificial gastric juice with an N of 18 mMHCO3(-) than with 50 mM HCO3(-), but histamine prevented ulceration in the 18 mM HCO3(-) solution. JnetCl approximated Isc under most experimental conditions in inhibited mucosa and was reduced dramatically as were both Jn leads to sCl and Js leads to nCl when HCO3(-) was removed from N. In histamine-stimulated tissues, removal of nutrient HCO3(-) did not influence Cl- transport. Our results are consistent with the proposal that HCO3(-) in N supports normal Cl- flux and that the alkaline tide of actively secreting oxyntic cells can do the same in the absence of ambient HCO3(-).

PGE2 stimulates gastric chloride transport: possible key to cytoprotection.

Prostaglandins protect the stomach against a variety of noxious agents independently of effects on acid secretion, but the mechanism of this 'cytoprotection' is unknown. We recently proposed that gastric surface cells extrude or eliminate luminal acid by a process analogous to that described in squid axon, snail neurone, and barnacle muscle. Influxing luminal H+ combines with HCO3- which has entered the cell in exchange for intracellular chloride, probably at the nutrient membrane. Dehydration of the resulting H2CO3 into CO2 and H2O is catalysed by carbonic anhydrase, which is present in surface cells in large amounts. Interference with this chain of reactions at any point frequently causes ulceration. We have examined the effect of 16,16-dimethylprostaglandin E2 (PGE) on different segments of this protective mechanism and show here that the protective effects are intimately associated with stimulation of chloride transport. All experiments were done in vitro thus eliminating any effects of prostaglandin on mucosal circulation.