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Biomedical subjects

A H Hölscher

Publications and source records attributed to A H Hölscher.

At least 19 recordsLinked to original sources

Preoperative risk analysis--a reliable predictor of postoperative outcome after transthoracic esophagectomy?

BACKGROUND AND AIMS: In patients with esophageal carcinoma, transthoracic esophagectomy is associated with high postoperative morbidity and mortality rates. The question of this study was whether an individualized preoperative risk analysis is able to predict postoperative outcome. MATERIALS AND METHODS: Based on prospectively accumulated data of 126 patients with a malignant esophageal tumor, a preoperative composite risk score using objective parameters was evaluated. All patients underwent a transthoracic en bloc esophagectomy with two-field lymphadenectomy. The risk score was correlated to the postoperative course which was classified according to the days of intensive care unit (ICU) treatment, hours of mechanical ventilation, and reoperation and readmission to the ICU. A multivariate analysis was performed to identify single risk factors. RESULTS: The overall morbidity rate was 55%, while the mortality rate was 5.6%. According to the composite risk score, 22.8% of the patients had a "low" risk, 53.2% had a "moderate" risk, and in 19% the preoperative risk was classified as "high". There was a significant correlation of the preoperative risk and the postoperative course (p<0.001). Multivariate analysis identified age, general status, and preoperative pulmonary function as independent risk factors of the postoperative outcome. CONCLUSION: Preoperative risk analysis in particular pulmonary function and general status helps to select patients for transthoracic esophagectomy to reduce postoperative morbidity.

Adenocarcinoma↗

Improved technique of heterotopic auxiliary rat liver transplantation with portal vein arterialization.

BACKGROUND AND AIMS: In acute, potentially reversible hepatic failure, auxiliary liver transplantation is a promising alternative approach. Using the auxiliary partial orthotopic liver transplantation (APOLT) method--the orthotopic implantation of auxiliary segments--most of the technical problems (lack of space for the additional liver mass, the portal vein reconstruction, and the venous outflow) are avoided, but extensive resections of the native liver and the graft are necessary. Erhard described the heterotopic auxiliary liver transplantation (HALT) with portal vein arterialization (PVA). Initial clinical results demonstrated that an adequate liver function can be achieved using this technique. We developed and improved a technique of HALT with flow-regulated PVA in the rat to perform further investigations. The aim of this paper is to explain in detail this improved experimental surgical technique. MATERIALS AND METHODS: Liver transplantations were performed in 122 male Lewis rats: After a right nephrectomy, the liver graft, which was reduced to about 30% of the original size, was implanted into the right upper quadrant of the recipient's abdomen. The infrahepatic caval vein was anastomosed end-to-side. The donor's portal vein was completely arterialized to the recipient's right renal artery in stent technique. Using a stent with an internal diameter of 0.3 mm, the flow in the arterialized portal vein was regulated to achieve physiologic parameters. The celiac trunk of the graft was anastomosed to the recipient's aorta, end-to-side. The bile duct was implanted into the duodenum. RESULTS: After improvements of the surgical technique, we achieved a perioperative survival of 90% and a 6-week survival of 80% in the last 112 transplantations. CONCLUSION: We developed a standardized and improved technique, which can be used for experiments of regeneration and inter-liver competition in auxiliary liver transplantation. Furthermore, this technique is suitable for the investigation of the influence of portal vein arterialization and portal hyperperfusion on liver microcirculation, function, and morphology.

Anastomosis, Surgical↗

[Ulcer surgery - what remains?].

Ulcer surgery today concentrates on the complications of chronic ulcer disease, especially ulcer perforation and endoscopically uncontrollable ulcer bleeding. In this case the laparoscopic or open closure of the gastroduodenal defect or local hemostasis of the bleeding ulcer by laparotomy are the main aims of surgery. Elective operations due to recurrent gastric or duodenal ulcers have become rare. An indication for gastric ulcer resistant to conservative therapy could be persisting suspicion of malignancy whereas in duodenal ulcer gastric outlet obstruction represents a reason for surgery. If these indications are confirmed the classic procedures of gastric resection like Billroth I and Billroth II are performed whereas vagotomy is no longer used. Altogether ulcer surgery has become very safe although it is practiced quite rarely.

Gastrectomy↗

Portal hyperperfusion causes disturbance of microcirculation and increased rate of hepatocellular apoptosis: investigations in heterotopic rat liver transplantation with portal vein arterialization.

Clinical results of portal vein arterialization (PVA) in liver transplantation are controversial. One reason for this is the lack of a standardized flow regulation. Our experiments in rats compared PVA with blood-flow regulation to PVA with hyperperfusion in heterotopic auxiliary liver transplantation (HALT). In group I (n = 19), the graft's portal vein was completely arterialized via the right renal artery in-stent technique, using a 0.3-mm stent, leading to a physiological average portal blood flow. In group II (n = 19), a 0.5-mm stent was used. In group II, the average portal blood flow after reperfusion was significantly elevated (group II: 6.4 +/- 1.5; group I: 1.7 +/- 0.4 mL/min/g of liver weight; P < .001). The sinusoidal diameter after reperfusion was significantly greater in group II (9.8 +/- 0.5 microm) than in group I (5.5 +/- 0.2 microm; P < .001). Red blood cell velocity in the dilated sinusoids was significantly lower in group II (171 +/- 18 microm/s) than in group I (252 +/- 13 microm/s). Stasis of erythrocytes occurred; consequently, the functional sinusoidal density was significantly reduced in group II (38 +/- 7%) compared with group I (50 +/- 3%; P < .01). Two hours after reperfusion of the portal vein, the number of apoptotic hepatocytes was significantly higher in group II than in group I (I: 0 +/- 0 vs II: 7 +/- 9 M30-positive hepatocytes/10 high-power fields). The 6-week survival rate was 9 of 11 in both groups. In group II, 6 of 9 grafts showed massive hepatocellular necroses after 6 weeks, whereas in group I, only 1 of 9 presented a slight hepatocellular necrosis. Finally, our results demonstrate negative effects of portal hyperperfusion in transplanted livers, which are correctable by adequate flow regulation.

Animals↗

High rate of lymph-node metastasis in submucosal esophageal squamous-cell carcinomas and adenocarcinomas.

BACKGROUND AND STUDY AIMS: The application of endoscopic mucosectomy in early esophageal cancer is limited by the presence of lymph-node metastasis. The aim of this prospective study was to analyze the rate of lymph-node involvement relative to the depth of mucosal or submucosal tumor penetration, comparing squamous-cell carcinomas and adenocarcinomas. PATIENTS AND METHODS: A total of 60 patients with pT1 esophageal cancer--24 with squamous-cell carcinomas (SCCs) and 36 with adenocarcinomas--were treated with transthoracic en-bloc esophagectomy with two-field lymphadenectomy (n = 50) or transhiatal esophageal resection (n = 10). An average of 30 lymph nodes were examined, and the following characteristics were evaluated: histology, mucosal infiltration, depth of submucosal wall infiltration in three thirds (sm1, sm2, sm3), grading, resection category, ratio of metastatic to resected lymph nodes, and locations of metastatic nodes. RESULTS: The rates of lymph-node metastasis were 0% for the 16 mucosal carcinomas and 45% for the 44 submucosal carcinomas (P < 0.01). There were no significant differences in the extent of lymph-node involvement between submucosal adenocarcinomas (41%) and submucosal SCCs (50%). Sm1 carcinomas were associated with a lower rate of lymph-node metastasis (SCCs 33%, adenocarcinomas 22%) than sm3 carcinomas (SCCs 69%, adenocarcinomas 78%). Two patients (9%) with submucosal SCCs and five patients (23%) with submucosal adenocarcinomas were classified as having stage pM1 lymph. The average lymph-node ratio in patients with pN1 was 0.13 for adenocarcinomas and 0.1 for SCCs (difference not significant). In the multivariate analysis, the parameters mucosal vs. submucosal (P < 0.01) and G1/G2 vs. G3 (P < 0.05) showed a significant impact in relation to metastatic lymph nodes. CONCLUSIONS: The most important factor for predicting lymph-node metastasis in early esophageal cancer is the presence of submucosal infiltration. Early adenocarcinomas and SCCs do not differ with regard to their rate of lymphatic involvement. The rate of lymph-node metastasis increases with the depth of submucosal infiltration, but metastases can already occur in sm1 lesions. Submucosal infiltration is a contraindication for endoscopic mucosectomy. Limited surgical procedures without adequate lymphadenectomy do not appear to be appropriate in the treatment of patients with submucosal esophageal carcinomas.

Adenocarcinoma↗

[Local excision with transanal endoscopic microsurgery (TEM) after endoscopic R1/R2-polypectomy of pT1 "low-risk" carcinomas of the rectum].

The transanal endoscopic microsurgery (TEM) is an adequate method for the local full-thickness excision of large rectum polyps and pT1 "low-risk" rectal carcinomas. We studied prospectively the relevance of this surgical technique concerning complete tumour excision after R1/R2-polypectomy of malignant rectal polyps. 16 patients with pT1 "low-risk" rectal carcinoma and macroscopic (R2) or microscopic (R1) incomplete endoscopic polypectomy were locally resected by TEM. In 12 patients (75 %) no residual tumour was found. In the remaining four cases (25 %), one adenoma with high-grade atypia, two pT1 "low-risk" carcinomas and one tumour infiltration in the mesorectal fat were diagnosed. The patient with the mesorectal infiltration was immediately operated on with radical resection. No further tumour cells were found in this specimen. The median follow-up was 21 months. One patient with a pT1 "low-risk" carcinoma developed a local recurrence and a single hepatic metastasis in the left liver lobe after TEM. Both were completely resected. Currently, all patients are living without evidence of tumour recurrence. Transanal endoscopic microsurgery is a suitable method for the treatment of pT1 "low-risk" rectal carcinomas after incomplete endoscopic polypectomy. In cases of a "high-risk" tumour or deeper tumour infiltration (pT> 1) after TEM radical resection must be carried out.

Adult↗

[Combined laparoscopic/endoscopic treatment of gastric stroma tumors].

INTRODUCTION: Surgical therapy of Gastrointestinal stroma tumor (GIST) is the treatment of choice. Local resection will be carried out if technically possible. We describe the technique of laparoscopic wedge resection combined with intraoperative gastroscopy in order to achieve complete tumor resection. METHOD: We report on 4 cases with gastrointestinal stroma tumors which were located in the gastric corpus (n = 2) and the cardia (n = 2). RESULTS: In all patients the tumor could be removed completely without any perioperative complications using laparoscopic wedge resection controlled by intraoperative endoscopy. The duration of hospitalisation after operation was 7 days (5-10). On the basis of the mean tumor size (mean 3.8 cm) and the low mitotic activity (mean 2.75/high power fields) the tumors belong to the group with low malignant potential. There is no evidence of recurrence after a mean follow up period of 23 (6-30) months. CONCLUSION: Combined laparoscopic/endoscopic wedge resection is a safe method for total resection of GIST of the stomach and should be preferred as alternative to open surgery.

Follow-Up Studies↗

Multiple giant leiomyomas of the esophagus and stomach.

Leiomyomas are rare esophageal disorders, although among the benign esophageal neoplasms, they are the most common. Multiple leiomyomas are distinguished from esophageal leiomyomatosis, an extremely rare condition, which is associated with Alport syndrome, showing deletions and rearrangements of the COL4A5/COL4A6 gene. There are only a few reports of diffuse multilocular lesions. A 19-year-old man presented with upper gastrointestinal bleeding and diffuse abdominal pain. On endoscopy multiple nodules covered with intact mucosa were present, the largest tumor arising from the gastro-esophageal border infiltrating the cardia. Barium swallow demonstrated narrowing of the middle and lower esophagus with the upper third of the stomach filled by the tumor. Thorax and abdominal CT scans revealed infiltration of almost the total aboral esophagus by the tumor with compression of left and right bronchi. The infiltration reached the whole lesser curvature of the stomach. Endosonography showed multiple encapsulated nodules. Due to the extended tumor growth with infiltration of the upper third of the stomach, a total esophago-gastrectomy with reconstruction by colon interposition was performed. On histopathological examination multiple esophageal leiomyomas with infiltration of the proximal third of the stomach was shown. Immunohistochemically the tumor stained positive for desmin and sm-actin and negative for CD34 and c-kit. Genetic analysis ruled out a deletion of the COL4A5/COL4A6 locus on chromosome X that is linked with Alport syndrome-diffuse leiomyomatosis. Extended mutations in the COL4A5 gene, associated with Alport syndrome, to the COL4A6 gene, are required for the development of leiomyomatosis. In young patients with diffuse multinodular infiltration by encapsulated tumors, esophageal leiomyomatosis should be considered. If the proximal third of the stomach is infiltrated by the tumor an extended resection is necessary. Reconstruction procedures include colon interposition.

Adult↗

Lewis(y) antigen (CD174) and apoptosis in gastric and colorectal carcinomas: correlations with clinical and prognostic parameters.

Lewis(y) (Le(y)), also designated CD174, represents a carbohydrate blood group antigen which is strongly expressed in neoplastic gastrointestinal tissues. Previous reports indicated an association between Le(y) expression and apoptosis. Therefore, we tried to elucidate its clinicopathological relevance in a series of 160 gastric and 215 colorectal carcinomas by immunohistochemical detection of Le(y) and visualization of apoptotic cells applying the in-situ-end labelling (ISEL) method, followed by semiquantitative scoring of the specimens. In both gastric as well as colorectal carcinomas, between 40 and 50% of the cases were Le(y) reactive. Signet-ring cell carcinomas of the stomach exhibited a significantly stronger Le(y) expression compared to other tumor types. In colorectal cancers, Le(y) was associated with increased tumor staging, showing the strongest positivity in stage IV. Further correlations with clinicopathological variables or prognosis were not observed. On the other hand, the amount of apoptotic cells was significantly reduced in mucinous adenocarcinomas of the colorectum compared to non-mucinous carcinomas. Scoring of apoptotic cells did not result in any other clinicopathologically relevant correlations. In addition, a significant association between Le(y) antigen expression and apoptosis score could not be established. Therefore, the hypothesis of a functional relationship between these two aspects of gastrointestinal tumor biology is not confirmed by our data.

Adenocarcinoma↗

Role of retinoic acid receptors in squamous-cell carcinoma in human esophagus.

BACKGROUND: Worldwide, cancer in the esophagus ranks among the 10 most common cancers. Alterations of retinoic acid receptors (e.g. RARalpha, beta, gamma, and RXRalpha, beta, gamma) expression is considered to play an important role in development of squamous-cell carcinoma (SCC), which is the most common esophageal cancer. Alcohol consumption and smoking, which can alter retinoic acid receptor levels, have been identified as key risk factors in the development of carcinoma in the aero-digestive tract. Therefore, the aim of the present study was to evaluate protein levels of retinoic acid receptors (i.e. RARalpha, beta, gamma, and RXRbeta) in esophageal SCC and surrounding normal tissue of patients with untreated SCC and controls. METHODS: All study participants completed a questionnaire concerning smoking and alcohol drinking habits as well as anthropometrical parameters. Protein levels of RARalpha, beta, gamma, and RXRbeta were determined by Western Blot in normal esophageal tissue and tissue obtained from SCC of 21 patients with newly diagnosed esophageal SCC and normal esophageal tissue of 10 controls. RESULTS: Protein levels of RARgamma were significantly lower by approximately 68% in SCC compared to normal surrounding tissue in patients with SCC that smoked and/or consumed elevated amounts of alcohol. Furthermore, RARalpha protein levels were significantly lower (approximately- 45%) in SCC in comparison to normal esophageal mucosa in patients with elevated alcohol intake. When comparing protein levels of retinoic acid receptors between normal tissue of patients with SCC and controls, RARgamma protein levels were found to be significantly higher (approximately 2.7-fold) in normal esophageal tissue of SCC patients than in esophageal tissue obtained from controls. No differences were found for RARalpha, beta, and RXRbeta protein levels between normal esophageal tissue of patients and that of controls. CONCLUSION: In conclusion, results of the present study suggest that alterations of retinoic acid receptors protein may contribute in the development of SCC in esophagus and that in some patients life style (e.g. smoking and alcohol consumption) may be a critical component in the alteration of retinoic acid receptor levels in esophagus.

Journal Article↗

Experimental bile duct protection by intraductal cooling during radiofrequency ablation.

BACKGROUND: The use of radiofrequency ablation (RFA) for liver tumours is limited by the proximity of large bile ducts to the targeted lesion. The aim of this randomized study was to evaluate intraductal cooling as a mean of protecting the bile ducts during RFA. METHODS: Twelve pigs underwent RFA adjacent to the right bile duct. After placement of an intraductal cooling catheter and a RFA probe, pigs were randomized to cooling or no cooling. Intraductal temperature was measured in all animals. The bile ducts were assessed by magnetic resonance imaging (MRI) and cholangiography 1 and 28 days after the procedure. RESULTS: Intraductal cooling abolished the increase of intraductal temperature seen in the absence of cooling. Concurrent cholangiography and MRI showed a biliary lesion in one of six pigs subjected to intraductal cooling and in five of six without cooling (P = 0.040). The biliary injuries were barely visible by MRI on day 1 but were clearly visible on day 28. CONCLUSION: Intraductal cooling can prevent biliary injury induced by RFA. The exact parameters for intraductal cooling require further investigation to establish the best compromise between bile duct protection and complete ablation of surrounding tissue.

Animals↗

[Submucosal infiltration and local recurrence in pT1 low-risk rectal cancer treated by transanal endoscopic microsurgery].

BACKGROUND: The association between submucosal infiltration and tumor recurrence was analyzed by long-term follow-up of patients with pT1 "low risk" rectal carcinoma. PATIENTS AND METHODS: Forty patients with pT1 rectal cancer of the upper and middle rectum were treated by transanal endoscopic microsurgery. All carcinomas fulfilled the low-risk criteria, and were completely resected. No further treatment was carried out. Follow-up data were available for all 40 patients, with a median follow-up of 5.4 years. RESULTS: Two patients (5.0%) developed local tumor recurrence after 14 and 18 months, respectively, and had curative rectal resection after neoadjuvant radiochemotherapy. In the histology of the initial specimens, both patients had deep submucosal infiltration (sm3). Another patient, primarily sm2 without local recurrence, developed a metachronous singular liver metastasis which was curatively resected. The risk of developing a recurrent tumor was significant for sm3 carcinomas (sm1+sm2 vs sm3, P=0.046). CONCLUSION: Transanal endoscopic microsurgery is an excellent method of treating low-risk pT1 carcinomas of the rectum. Deep submucosal infiltration (sm3) seems to be an additional high-risk factor for developing local recurrence.

Adult↗

[Correct diagnosis for indication in gastroesophageal reflux disease].

For diagnosis and quantitation of gastroesophageal reflux disease, a number of different examinations are available. The simplest are the patient's history and complaints as well as the proton pump inhibitor test; both methods have a positive predictive value of 65% to 70%. Esophagogastroduodenoscopy is the gold standard for differentiation between erosive and nonerosive reflux disease. Biopsy does not enhance the significance of endoscopy except for proof of Barrett's epithelium or malignant degeneration. Twenty-four-hour pH monitoring has the highest sensitivity and specificity for the diagnosis of gastroesophageal reflux disease. Barium swallow provides only additional information concerning hiatal hernia or stenosis. Manometry can clarify lower esophageal sphincter insufficiency or motility disorders of the tubular esophagus. However, the available studies show that manometry has no influence on postoperative outcome after fundoplication. The indication for medical therapy can primarily be based only on the history and complaints of the patient. As surgical therapy affords a high degree of diagnostic accuracy, at least endoscopy and 24-h pH monitoring are necessary for indication.

Diagnosis, Differential↗

[Preoperative evaluation of prognostic factors in esophageal squamous cell cancer].

Despite substantial improvements in the surgical therapy of esophageal squamous cell cancer, the prognosis still remains poor. This is mainly due to locally advanced tumors (T3-4, N+) or systemic metastases (M1) in the majority of patients at initial presentation. It is of the utmost importance to reliably detect relevant pretherapeutic prognostic indicators for optimal individual therapeutic strategies. Pretherapeutic prognostic indicators should therefore discriminate precisely between incurable and potentially curative disease. Preoperative or definitive multimodal treatment is increasingly being offered to patients with locally advanced tumors and opens a broad field for innovative techniques such as pretherapeutic molecular response prediction or early response detection by PET scan to further individualize and optimize treatment strategies.

Carcinoma, Squamous Cell↗

[Adenocarcinoid of the appendix vermiformis].

Adenocarcinoids are rare tumors with histological features of both carcinoid tumor and adenocarcinoma. They show a more aggressive biological behaviour than conventional carcinoids. We report a case of a 64-years-old female patient with a diffuse infiltration of the appendicular wall by an adenocarcinoid. Due to the positive surgical margin and the tumor expansion a hemicolectomy was performed. There are no precise criteria to direct the operative choice between appendectomy and hemicolectomy. It is thought that appendectomy is sufficient in case of small tumors in the tip of the appendix. Patients with diffuse appendicular involvement require a more aggressive surgical therapy.

Adenocarcinoma↗

Successful use of sirolimus in a patient with bulky ovarian metastasis of hepatocellular carcinoma after liver transplantation.

This 44-year-old woman developed multifocal hepatocellular carcinoma (HCC) within hepatitis B-induced liver cirrhosis. At the time of listing for transplantation the HCC had progressed beyond the Milan criteria. Due to her young age, high grade of histological differentiation according to biopsy, and lack of therapeutic alternatives, she was listed for transplantation. She received an organ from the Eurotransplant marginal liver list. Immunosuppression was reduced to tacrolimus monotherapy within 4 months. Five months after transplantation bilateral bulky ovarian metastases were seen on computed tomography (CT) scan. A bilateral salphingo-oophorectomy was performed and immunosuppression switched to sirolimus monotherapy. Fourteen months after this procedure and 19 months after transplantation, the patient is asymptomatic with stable liver function. She is free of recurrence as judged by CT scan, bone scan, and alpha-fetoprotein. In conclusion, radical surgical treatment and immunosuppression using sirolimus may achieve tumor-free survival in selected patients with advanced or recurrent HCC.

Adult↗

[Symptoms in patients with adenocarcinoma of the esophagus].

INTRODUCTION: Gastroesophageal reflux (GER) is the main risk factor for the development of adenocarcinoma of the esophagus (AC). The aim of our study was to evaluate symptoms of patients with AC to identify those patients with a high risk for this tumour. PATIENTS AND METHODS: 117 consecutive patients with known AC were included. Prospectively all patients were interviewed with a standardised questionnaire comprising 120 items: social status, other diseases, risk factors, therapy of the GERD and, as a main part: current symptoms and those experienced at earlier times. RESULTS: 85 % of the patients had often or sometimes reflux symptoms. 46 % of the patients with reflux symptoms had such symptoms daily. The median time span for this symptom was 20 years with a range from 1 year to 50 years. In 21 % of the patients the reflux symptoms stopped (median) three years (range two months -- 30 years) before the diagnosis of the carcinoma. Only 55 % of all patients had one or more esophago-gastroscopy examinations before the diagnosis of AC. These patients showed significantly more often earlier tumour stages than those patients without an endoscopy before diagnosis. Heartburn was treated with medication in 78 % of the patients (67 % of all patients). No patient had previously undergone antireflux surgery. CONCLUSIONS: 15 % of the patients with adenocarcinoma of the esophagus show no, and in addition 25 % only discrete, heartburn; 1. an endoscopy due to heartburn was done in half of all cases, and 2. the medications do not fulfil the therapeutic standard; 3.patients with endoscopy had significantly more frequently an earlier tumour stage.

Adenocarcinoma↗