Biomedical subjects
Publications and source records attributed to H E Wagner.
The occurrence of non-recurrent inferior laryngeal nerve is based on a rare embryologic vascular malformation of the aortic arches. Based on three recent cases, we discuss embryology, clinical presentation and operative technique.
A standard approach involving sequential investigations made it possible to identify a bleeding source in 98 out of 100 patients with massive lower gastrointestinal bleeding. In 5 cases the preoperative diagnosis was incorrect. Only in 2 patients was no pathology detectable. Recurrent bleeding occurred in 8 patients, 5 of whom subsequently died of hemorrhagic shock. The overall mortality was 10%, or 11% if a patient with late death due to massive rebleeding was included. 8 complications or deaths were due to diagnostic (n = 3) and therapeutic (n = 5) errors. The remaining complications with fatal outcome (n = 6) were due to the patient's associated or underlying disease. We conclude that in patients with angiographically visualized arteriovenous malformations in the coecum, a second lesion needs to be ruled out. To prevent some complications a more aggressive therapeutic approach seems necessary. On the other hand, there remain complications and deaths that cannot be prevented in view of the advanced stage of the associated or underlying disease.
We have reviewed all the records of 23 patients hospitalized in our institution from January 1981 till December 1991 and presenting a confirmed diagnosis of esophageal perforation. We have studied the aetiology, the localization, morbidity and mortality and we discuss the therapeutic management. 9 patients presented a cervical perforation, 13 patients a thoracic perforation and 1 patient an abdominal perforation. Among the patients with cervical perforation 2 patients had a local revision with drainage, 3 patients a primary suture and 4 patients were treated conservatively. No complication was found in this group. The patients with thoracic perforation have been treated as follow: 3 conservatively, 8 with thoracotomy, primary suture +/- patch, drainage, 2 patients with thoracotomy and drainage alone. All complications happened in this group: 2 gastro-intestinal bleeding, 2 ARDS, 3 mediastinitis, 1 pneumonia. 2 patients in a very poor general condition died, one with a metastatic breast carcinoma, the other after a CVI with a massive gastro-intestinal bleeding. The cervical perforations have an excellent prognosis and can be treated conservatively if they are asymptomatic and do not display a pleural lesion. The thoracic perforations can be treated surgically if they are diagnosed early before septic complications. If not, they will be better treated conservatively with drainage. The intraabdominal perforations have to be treated as every intraabdominal perforation. In this case, we perform a primary suture completed with fundoplication.
A study of ninety-four patients admitted with massive lower gastro-intestinal bleeding (LGIB) is presented using a systematic diagnostic work-up including angiography, colonoscopy and various investigations, such as scintigraphy, small bowel series and ultrasonography. The bleeding source was identified preoperatively in eighty-five patients. 9 patients had a diagnostic laparotomy and a pathology was found in additional seven. No source was identified in two patients (2.1%) at exploration and "blind" subtotal colectomy was not performed in these two cases as proposed by others. We conclude that a thorough systematic assessment of patients with LGIB is important to localize the bleeding source. Exploratory laparotomy is the final step in few cases (10%) and if no intraoperative source can be identified a "blind" colonic resection should not be performed.
In this study we used the subrenal capsule site of C57BL/6J mice to assess the tumorigenic and metastatic potential of established urothelial cell lines in a syngeneic murine model. High tumor take and subsequent removal of the primary tumor by nephrectomy resulted in the extended lifespan of the animals enabling the formation of secondary tumor growth. To test this model we have used a panel of cell lines expressing constitutively, or following transfection, ras oncogene products. All cell lines constitutively expressing ras oncogenes (K, H, or N-ras) were tumorigenic and metastatic in this assay. One non tumorigenic cell line (BBN3) and one tumorigenic but non-metastatic cell line (SH264), remained non-metastatic following transfection with the pSV2-neo gene but formed micrometastases in the lung when a ras oncogene was introduced in the same manner. Expression of altered ras proteins following transfection in these two cell lines was demonstrated using an H-ras specific antibody in Western blot analysis. This study demonstrates the value of the subrenal capsule site as a metastatic assay for bladder cancer and the potential involvement of ras oncogenes in urothelial cell metastasis.
270 patients with papillary thyroid carcinoma were retrospectively analyzed. The mean age at initial diagnosis was 43.5 years. 74% of the patients were females. 15 patients (6%) had residual tumor after initial surgery and 61 patients (24%) showed recurrent disease. The recurrence was discovered clinically, radiologically and by increasing thyroglobulin levels in 72%, 23% and 5% of the patients, respectively. Recurrent disease was located in the tumor bed, locally and metastatic and only metastatic in 61%, 23% and 16% of the patients, respectively. After a mean follow-up of 9.4 years (range 3-20 years) the overall mortality was 13%. 6% of the patients died from tumor, 3% with tumor and 4% without tumor. 46% of patients with residual tumor died from tumor progression, in contrast to 18% of patients with early recurrence (< 5 years) and 6% of patients with late recurrence (> 5 years). We conclude that papillary thyroid carcinoma has a low mortality (6%) even in an endemic area. Patients with residual tumor after initial surgery and patients with early recurrence have an increased cancer mortality.
Medical histories for the years 1978 to 1988 were reviewed to ascertain associations between colorectal cancers and extraintestinal malignancies. 61 out of 838 patients (7.3%) had an extraintestinal malignancy before the colorectal cancer. In males the rate was 5.4% and in females 10.4%. In males a high association was shown between cancers of the large bowel and urogenital cancers. In females colorectal cancer was associated with breast and gynecologic cancers. We conclude that patients with gynecologic and urologic tumors have an increased risk to develop cancers of the large bowel and that these high risk patients should undergo long-term follow-ups.
Three different systems in staging colorectal cancer (TNM3, ACPS, TNM4/Dukes) have been compared in 318 patients treated at some stage of their disease at Berne University Hospital. Simultaneously, the role of some prognostic factors for survival and relapse has been analyzed. The estimated 5 years' survival rate for all patients is 42%. After complete removal of the tumor 49% of patients relapsed. In a multivariate analysis the stage, age above 80 years and the site of the primary tumor have an influence on survival and relapse. Blood transfusions had no effect on either in this analysis. The concordance of the three staging systems is good and the resultant survival curves are similar. TNM3 puts some patients with a bad prognosis into stage I. ACPS classifies patients with residual tumor after surgery with patients with distal metastasis. It has no further advantages over TNM4. TNM4 seems at present to be the best staging system. It incorporates the advantages of the well-known Dukes classification and, with possible refinements, has the qualities to be used as a standard method.
20 patients with massive lower gastrointestinal bleeding caused by segmental or total colonic diverticular disease are presented. The bleeding source was localized by colonoscopy, angiography and intraoperatively in 5, 5 and 2 patients respectively. The hemorrhage occurred in the right colon in 9 patients and in the left colon in 3 patients. Due to ongoing bleeding 9 patients needed immediate surgery (7 right hemicolectomies, 1 left hemicolectomy, 1 sigmoidectomy). The median transfusion requirement of operated individuals was 14 units of blood. 2 (22%) patients died from postoperative complications. The remaining 7 patients had no recurrent bleeding during a median follow-up of 3.5 years (0.5-9 years). 11 patients with arrested bleeding (median transfusion requirement 3 units of blood) were treated conservatively. During a mean follow-up of 4.5 years (1.5-10 years) only one (9%) of the conservatively treated patients complained of recurrent bleeding requiring sigmoidectomy. We conclude that massive and ongoing hemorrhage (greater than 6 units of blood) occurs predominantly in right-sided colonic diverticula and requires immediate surgery. Arrested bleeding (transfusion requirements less than 6 units of blood) from colonic diverticula can be treated conservatively since operative mortality is high and recurrent bleeding is rare.
Sialyltransferase activity (EC 2.4.99.6) was measured in the microsomal fraction of colorectal cancer cell lines using an assay based on the incorporation of [14C]CMP-sialic acid into asialofetuin. In the poorly differentiated lines MIP101 and Clone A, sialyltransferase activity had a Vmax of 0.36 and 0.31 nmol/mg protein/h, respectively, while the moderately differentiated to well-differentiated cell lines HT-29, CCL188, and CX-1 had Vmaxs of 2.46, 1.05, and 1.24 nmol/mg protein/h, respectively. All cell lines tested had a Km of 15.4 (+/- 0.7)(SD) mumol/liter. The better differentiated cells had higher levels of sialyltransferase activity, which correlated with their higher levels of sialic acid and their enhanced ability to form liver metastases in the nude mouse following intrasplenic injection compared to the poorly differentiated cell lines. Treatment of the cell lines with KI-8110, a CMP-sialic acid derivative which prevents incorporation of sialic acid into glycoconjugates, resulted in reduced formation of hepatic metastases by the colorectal carcinoma cell lines in the nude mouse model. It is suggested that reduced sialylation of adhesion molecules such as carcinoembryonic antigen may change the biology of the tumor cell, one consequence of which is the prevention of implantation of the cells into distant sites, resulting in a reduced incidence of metastases.
The relationship between cellular differentiation and carcinoembryonic antigen (CEA) production by human colorectal tumor cells and their ability to form hepatic metastases was studied. Eight human colon cancer cell lines were injected into athymic mice using different routes of administration to characterize their metastatic potential. The four poorly differentiated, non or low CEA producing cell lines were poorly metastatic to the liver after intrasplenic injection. After intraperitoneal implantation the same cell lines were highly tumorigenic, and subsequently metastatic to the liver. In contrast, the four moderate to well-differentiated cell lines that produced moderate to high levels of CEA were highly metastatic to the liver following intrasplenic injection. After intraperitoneal implantation they were less tumorigenic, and metastatic to the liver. We conclude that in this system poorly differentiated non or low CEA producing colorectal cell lines have a lower metastatic capacity compared to the well-differentiated high CEA producing colorectal cell lines. These data correlate directly with the pattern of metastatic spread and clinical course observed in patients with these tumors, suggesting that degree of differentiation and level of CEA production may play a role in development of site-specific metastases.
To identify any differences in presentation among the four types of acute mesenteric ischaemia, and to correlate time between presentation and treatment with outcome, we retrospectively analysed 100 cases of acute mesenteric ischaemia at a University hospital diagnosed by radiography (n = 21), at laparotomy (n = 61), or at necropsy (n = 18). A total of 68 patients died. Mortality was 50% when the aetiology was embolic occlusion of the superior mesenteric artery and 95% when the occlusion was thrombotic; 67% when the disease was "non"-occlusive; and 30% in cases of splanchnic vein thrombosis. We conclude that early diagnosis is critical for successful management of acute mesenteric ischaemia, but outcome is also influenced by the aetiology.
10 patients with a history of systemic anticoagulation presented with an acute abdomen which proved to be due to a rectus sheath hematoma. Four patients gave a history of antecedent trauma. The prothrombin time was prolonged beyond the therapeutic range in 8 patients and therapeutic in two. The diagnosis of rectus sheath hematoma was made by non-invasive imaging (sonography [n = 8], CT-scan) in 9 patients and by operative exploration in one. 8 patients were treated non-operatively and one patient required a delayed evacuation of the infected hematoma. One patient died from myocardial infarction. We conclude that a careful history, physical examination and prothrombin time, in combination with radiologic evaluation (sonography, CT-scan) can confirm the suspected diagnosis of rectus sheath hematoma. It is important to think of this specific hemorrhagic complication induced by anticoagulation to prevent unnecessary surgery.
A study of 83 patients admitted with massive bleeding in the lower part of the gastrointestinal tract is presented using a diagnostic approach primarily of angiography and colonoscopy with the adjunctive investigations of scintigraphy, small intestine series and computed tomographic scan. The source of bleeding was identified preoperatively in 74 patients. Nine patients had a diagnostic laparotomy and the cause was found in an additional seven. A source was not identified in two patients at exploration and a blind resection was not performed. The two patients have not had recurrent bleeding four and nine years postlaparotomy. The sites of bleeding were colon in 44 patients, small intestine in 24 and the anorectum in 11. Sixty-five patients were treated operatively, two by angiographic embolization and two by endoscopic electrocoagulation. Fourteen patients were managed conservatively. The mortality rate was 10.8 percent and five patients rebled after treatment. We conclude that a thorough systematic assessment of patients with bleeding in the lower part of the gastrointestinal tract is important to localize the site of the hemorrhage. Exploratory laparotomy is the final diagnostic modality, and if a source has not been identified, a blind colonic resection should not be performed.
The influence of cellular differentiation and CEA-production by colorectal tumor cells on experimental hepatic metastases was studied. Eight human colon cancer cell lines were injected into the spleen of athymic mice. The four poorly differentiated, non or low CEA producing cell lines were poorly metastatic to the liver. In contrast, the four well-differentiated cell lines which produce moderate to high levels of CEA were highly metastatic. We conclude in this animal model that poorly differentiated, non or low CEA producing colorectal cell lines have a lower metastatic potential compared to the well-differentiated, high CEA producing tumor cells.
Recurrent disease from colorectal carcinomas is common. 25 percent of patients have apparent metastases at the time of first detection of the tumor, and at least 50% of patients die from their tumor. The aim of the postoperative follow-up of patients with carcinoma of the colon and rectum is thus to detect recurrent tumor when cure is still possible. Clinical examination and CEA-measurement is widely recommended as a reliable indicator for recurrence and metastases of colonic cancer. This may be combined with regular coloscopic surveillance for detection of anastomotic recurrences or a second colonic cancer. In case of suspicion of a recurrence or metastasis a full range of examinations should be performed to detect the site of recurrent tumor and to exclude wide spread disease. In case of a circumscribed lesion the patients may benefit from local radical resection. Patients with four or less unilateral liver metastases show a five year disease free survival reported of more than 30% and a disease free survival reported of more than 25%. Unfortunately because of wide spread misunderstanding of the potential of hepatic Rx only about 1/3 of potentially curatively resectable patients with liver metastases finally undergo liver surgery. A more active policy towards patients with colorectal disease concerning surveillance may lead to a better survival in selected cases.
It has been hypothesized that the metastatic capacity of tumors may be correlated with hypersialylation of the cell surface. We used a novel inhibitor of sialic acid incorporation, KI-8110, to determine the effect of depletion of cell surface sialic acid on the metastatic behavior of three human colorectal cancer cell lines, in which hepatic seeding was related to tumor cell differentiation. Treatment of tumor cells with KI-8110 prior to intrasplenic injection prevented liver colonization. Total cellular sialic acid was reduced, as was that of the cell surface. Secreted forms of carcinoembryonic antigen also were depleted of sialic acid by this treatment. These data show that depletion of sialic acid from cell surface glycoconjugates reduces the incidence of hepatic metastases from human colorectal primary tumors and adds to the mounting evidence of the importance of sialic acid in determining the biological behavior of tumor cells.
To determine the in vivo phenotype elicited in bladder epithelium following the expression of a ras oncogene we have introduced the HaSV ras transforming gene into transplants of normal urothelium. Stripped adult bladder mucosa incubated with HaSV, in the presence or absence of helper virus, was transplanted beneath the renal capsule of syngeneic animals and maintained for periods up to three months. Control implants, exposed to helper virus alone, formed heterotopic bladders lined by urothelium displaying focal areas of full differentiation when associated with underlying submucosal elements. Exposure of urothelium to HaSV resulted in increased proliferative potential of mucosal and submucosal elements with the appearance of a normal differentiated heterotopic bladder 10 days post-implantation. Implants left for 28 days presented a range of hyperplastic lesions (mild-severe) characterized from histological evaluation and antibody markers recognizing basal (D66) and superficial cell populations (H10) in normal bladder mucosa. Staining of mild hyperplastic lesions revealed an increased basal cell compartment and a loss of fully differentiated cells lining the lumen of the implanted bladder. In severe hyperplasia no superficial cells were observed but mucosal elements stained throughout with antibody D66. This phenotype was accompanied by an irregular laminin staining pattern associated with a disorganized basement membrane and increased blood vasculature. Similar experiments conducted with HaSV and helper virus resulted in the generation of mesenchymal lesions at 28 days with little surviving urothelium. The H-ras oncogenic protein can induce hyperplastic lesions in normal urothelium which were characteristic of preneoplastic changes identified in bladder carcinogenesis.