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H W Tilanus

Publications and source records attributed to H W Tilanus.

At least 55 records · Page 3Linked to original sources
PubMed2001

Indications and long-term outcome of treatment for benign hepatic tumors: a critical appraisal.

HYPOTHESIS: The natural history and clinical behavior of benign hepatic tumors during long-term follow-up may not justify primary surgical treatment. DESIGN: Retrospective study. SETTING: Tertiary referral center. PATIENTS: Two hundred eight patients diagnosed as having a benign liver tumor between January 1, 1979, and December 31, 1999. INTERVENTION: Seventy-four patients underwent hepatic surgery and 134 were managed conservatively by radiological follow-up. MAIN OUTCOME MEASURES: Symptoms and complications were assessed during management and follow-up. RESULTS: In the surgically treated population, the liver lesion was symptomatic in 47 patients (64%) and an incidental finding in 27 (36%). The operative morbidity and mortality were 27% (20 of 74 patients) and 3% (2 of 74 patients), respectively. Overall, 28 (80%) of 35 patients with complaints were asymptomatic after surgery. During observation of the tumor in the conservatively managed group, 39 (87%) of 45 patients who presented with complaints were asymptomatic during a mean follow-up of 45 months; 6 patients had mild abdominal pain considered to be unrelated to the tumor. CONCLUSIONS: Conservative management of solid benign liver lesions such as focal nodular hyperplasia and hemangioma can be performed safely, irrespective of their size. We only advise surgery for liver lesions when there is an inability to exclude malignancy or in the case of severe complaints related to the tumor. Resection is always advocated in the case of a large hepatocellular adenoma (>5 cm) to reduce the risk of rupture and malignant degeneration.

Adenoma, Liver Cell↗
PubMed2001

A comparison of the costs and effects of liver transplantation for acute and for chronic liver failure.

Little is known about costs and cost-effectiveness of liver transplantation (LTx) for acute liver failure compared to costs and cost-effectiveness of LTx for chronic liver failure. In this study, costs of acute and of chronic LTx patients were determined in a retrospective study. Files of 100 consecutive patients who underwent LTx in 1993-1997 were studied. Costs up to 1 year after LTx were Euro 107,675 (chronic liver failure) and Euro 90,792 (acute liver failure). The difference was mainly caused by higher hospitalisation costs and higher personnel costs for chronic liver failure. Medication costs for acute liver failure were higher, due to a high administration rate of expensive anti-HBs immunoglobulin therapy in patients with viral hepatitis B. LTx for chronic liver failure is more costly and seems to be more cost-effective than LTx for acute liver failure, since 1-year survival is higher in patients who underwent transplantation for chronic liver failure.

Acute Disease↗
PubMed2001

Establishment of cell lines from adenocarcinomas of the esophagus and gastric cardia growing in vivo and in vitro.

The aim of this study was to establish cell lines of adenocarcinomas of the gastro-esophageal junction(GEJ), which grow in vivo and in vitro. Primary esophageal and gastric cardia adenocarcinomas and corresponding lymph node metastases were xenografted subcutaneously to immunodeficient nude mice. In addition, tumor tissue was also used for in vitro culture. Xenografting of 70 primary adenocarcinomas and 17 metastases resulted in the initial growth of 22 and 6 tumors, respectively (total 32%). Upon retransplantation, six long-term xenografts [esophageal adenocarcinoma (OAC)P33X, OACP47X, OACP56X, OACP58X, OACP67X, OACP76X] from primary tumors and three (OACM2.1X, OACM30X, OACM53X) from metastases were obtained. In vitro culture attempts of 34 primary tumors and nine metastases resulted in the establishment of three (7%) permanent in vitro growing cell lines. From one patient, a cell line from the primary tumor (OACP4 C) and from a lymph node metastasis (OACM4.1 C) was established. The third cell line (OACM5.1 C) was also derived from a lymph node metastasis. The in vivo and in vitro cell lines were characterized using immunocytochemistry and microsatellite analysis to verify their epithelial and human tumor origin, respectively.

Adenocarcinoma↗
PubMed2001

Molecular cytogenetic evaluation of gastric cardia adenocarcinoma and precursor lesions.

Analyses of cancer incidence data in the United States and Western Europe revealed steadily rising rates over the past decades of adenocarcinomas of the esophagus and gastric cardia. Genetic information on gastric cardia adenocarcinoma and its preneoplasias is sparse. We have used comparative genomic hybridization to obtain a genome-wide overview of 20 archival gastric cardia adenocarcinomas and 10 adjacent preneoplastic lesions (4 metaplasias, 1 low-grade dysplasia, 5 high-grade dysplasias). Multiple genetic alterations were discriminated in all adenocarcinomas. Frequent loss (> or =25% of all tumors) was detected, in decreasing order of frequency, on 5q, 18q, 4q, 3p, 9p, 2q, 11q, 14q, 21q, 4p, 9q, 16q, 1p, and 8p. Frequent gain (> or =25% of all tumors) was disclosed, in decreasing order of frequency, on 20q, 7p, 8q, 1q, 7q, 20p, 17q, 13q, Xp, 6q, 8p, 19q, 5p, 6p, and Xq. Loss of the Y chromosome was found in 60% of male cases. High level amplification was frequently (>10% of all tumors) detected on 7q21, 8p22, 12p11.2, 17q12-q21, and 19q13.1-q13.2. The precursor lesions showed multiple aberrations in all high-grade dysplasias, whereas few genetic changes were discerned in LGD and metaplasias. High level amplifications were also found in high-grade dysplasias, ie, on 7q21, 8p22, and 17q12-q21. Moreover, the percentage of aberrations was not significantly different for invasive carcinomas or high-grade dysplasias. Approximately 70% of the precursor aberrations were also present in the adjacent carcinoma. Minimal overlapping regions in the preneoplasias included loss on 18q12-q21 and gains on 8q23 and 17q12-q21, suggesting involvement of genes residing in these regions. In conclusion, we have (i) created a map of genetic alterations in gastric cardia adenocarcinomas and (ii) provided evidence for the presence of a metaplasia-dysplasia-carcinoma sequence in this poorly understood type of cancer.

Adenocarcinoma↗
PubMed2001

In vitro cytokine production of TNFalpha and IL-13 correlates with acute liver transplant rejection.

Individuals may differ in their capacity to produce cytokines. Since cytokines play a key role in allograft rejection, we investigated whether inter-individual differences in cytokine production by in vitro stimulated PBMC are related to the occurrence of acute liver transplant rejection. Our study group comprised 49 liver transplant recipients and 30 healthy individuals. Rejection, which occurred within one month after liver transplantation, was defined in 22 patients ("rejectors") as biopsy-proven rejection, treated with high dose prednisolone. Patients who never experienced rejection episodes were termed as "nonrejectors" (n=27). PBMC of healthy individuals and of liver transplant recipients, collected late after transplantation (mean 3.5 years), were cultured in the presence and absence of Concanavalin A. The production of TNF-alpha, IFN-gamma, IL-10, and IL-13 was measured in supernatant after 1, 2, 3, 4, and 7 days of cell culture. In cell culture, stimulated PBMC of rejectors were found to produce significantly higher levels of TNF-alpha, while there was a trend towards higher production of IFN-gamma and IL-10 as compared to nonrejectors. After grouping patients into high or low cytokine producers based upon reference levels of the healthy individuals using multivariate analysis it was found that occurrence of acute liver transplant rejection correlated to high production of TNF-alpha and low production of IL-13. After stimulated cell culture PBMC of liver transplant recipients show a differential production of TNF-alpha and IL-13 which is correlated with the occurrence of acute liver transplant rejection.

Acute Disease↗
PubMed2001

Major liver resection results in a changed plasma amino acid pattern as reflected by a decreased Fischer ratio which improves by bactericidal/permeability increasing protein.

BACKGROUND/AIMS: Major liver resection results in a high morbidity and mortality, and endotoxin plays a role in post-resection hepatic failure. Severe hepatic failure as seen in hepatitis and cirrhosis may be accompanied by hepatic encephalopathy and is characterized by a typical plasma amino acid pattern reflected by a decreased Fischer ratio. This study was performed to evaluate the plasma amino acid pattern in patients undergoing major liver surgery receiving placebo or the endotoxin-neutralizing agent bactericidal/permeability-increasing protein (rBPI21). PATIENTS AND METHODS: Forty-eight patients were randomized in this phase II, dose escalation, multicenter trial. Plasma amino acid profiles were determined preoperatively, and on the first (day 1) and third (day 3) postoperative day. RESULTS: In the placebo group the Fischer ratio decreased significantly on both postoperative days. Administration of rBPI21 also resulted in a decreased Fischer ratio on day 1, but not on day 3. Highly elevated alanine plasma levels were observed on day 1 in placebo-treated patients, whereas rBPI21 prevented this elevation. Plasma alanine levels on day 1 correlated with the duration of post-resection hepatic failure. CONCLUSIONS: Major liver resection results in a decreased Fischer ratio and a rise in plasma alanine levels. Plasma levels of alanine on the first postoperative day correlated with the duration of the post-resection hepatic failure. rBPI21 improved the Fischer ratio and prevented the rise of plasma alanine levels.

Adult↗
PubMed2001

Randomized clinical trial of patient-controlled versus fixed regimen feeding after elective abdominal surgery.

BACKGROUND: Although studies have shown that early oral feeding after abdominal surgery is feasible, many surgeons still advocate a careful, slow introduction of postoperative oral feeding. This study was conducted to investigate whether patient-controlled postoperative feeding is possible in patients undergoing colonic or aortic surgery. METHODS: A randomized clinical trial compared patient-controlled postoperative oral feeding (PC group) with a fixed regimen (FR group). Patients in the PC group (n = 56) received oral feeding when they requested it; patients in the FR group (n = 49) started a normal diet on day 5. Endpoints were time to tolerance of a diet similar to the preoperative diet, reinsertion of a nasogastric tube, complications and duration of hospitalization. RESULTS: Median time to resumption of a normal diet was 3 days in the PC group and 5 days in the FR group (P < 0.001). Reinsertion of a nasogastric tube was required in nine patients in each group (P not significant). The incidence of complications was similar in both groups: 12 of 56 in the PC group and 13 of 49 in the FR group. There was no significant difference in duration of hospital stay between the groups. CONCLUSION: Most patients tolerate a normal diet on the third day after operation. Patient-controlled postoperative feeding is safe and leads to earlier resumption of a normal diet.

Aged↗
PubMed2001

Treatment of ruptured hepatocellular adenoma.

BACKGROUND: As the morbidity and mortality rates associated with emergency resection in patients with a ruptured hepatocellular adenoma are high, the authors have favoured initial non-operative management in haemodynamically stable patients. METHODS: A retrospective study was performed to evaluate the treatment of ruptured hepatocellular adenoma. RESULTS: Over a 21-year interval, 12 patients presented with a ruptured hepatocellular adenoma. Haemodynamic observation and support was the initial management in all 12 patients. Three underwent urgent laparotomy and gauze packing because of haemodynamic instability; no emergency liver resection was necessary. Eight patients had definitive surgery; three developed postoperative complications but none died. Regression of the tumour was observed in three of four patients treated conservatively. CONCLUSION: The initial management of a ruptured hepatocellular adenoma should be haemodynamic stabilization. Definitive resection is required for rebleeding or for tumours exceeding 5 cm in diameter. A conservative approach may well be justified in case of regression of an asymptomatic adenoma.

Adenoma, Liver Cell↗
PubMed2001

Prospective analysis of the diagnostic yield of extended en bloc resection for adenocarcinoma of the oesophagus or gastric cardia.

BACKGROUND: The extent of lymph node dissection can affect tumour node metastasis staging. The resulting 'stage migration' might hamper stage-by-stage comparison between different forms of oesophageal resection. The aim of this study was to assess the diagnostic impact of extended en bloc lymphadenectomy in staging (adeno)carcinoma of the mid/distal oesophagus or gastric cardia. METHODS: This was a prospective study of 74 patients (67 men and seven women; median age 63 (range 40-78) years) who underwent extended oesophagectomy between 1994 and 2000. RESULTS: A median of 31 (range 15-78) lymph nodes was resected (and identified), with a median of 5 (range 0-31) positive nodes. Twenty-seven patients (36 per cent) had tumour-positive nodes in extended fields: 15 patients (20 per cent) in the abdomen and 15 patients (20 per cent) in the mediastinum. Subcarinal nodes were most affected (19 per cent). Extended resection led to tumour upstaging in 17 patients (23 per cent); two patients had isolated positive subcarinal nodes and 15 other tumours became M1a owing to positive nodes near the coeliac axis, hepatic artery or splenic artery. Tumour positivity in paratracheal or aortopulmonary nodes occurred in 8 per cent of patients, without influencing staging. CONCLUSION: Extended en bloc lymphadenectomy altered staging in 17 of 74 patients (23 per cent) with adenocarcinoma of the oesophagus or cardia, mainly into M1a owing to positive coeliac nodes (20 per cent).

Adenocarcinoma↗
PubMed2001

Self-expanding metal stents for complicated and recurrent esophagogastric cancer.

BACKGROUND: Fewer complications are encountered with the use of self-expanding metal stents compared with semirigid prostheses in the palliation of patients with malignant esophagogastric obstructions. Metal stents can also be used to treat patients with complicated and/or recurrent esophagogastric carcinoma. METHODS: Covered metal stents were placed in 57 patients for the following reasons: esophagorespiratory fistula (n = 16), recurrent carcinoma in a gastric tube interposition (n = 21), recurrent carcinoma after partial (n = 4) or total (n = 6) gastrectomy, or a carcinoma near the upper esophageal sphincter (n = 10). RESULTS: The procedure was technically successful in 55 of 57 (96%) patients. Dysphagia score improved from a mean of 3.6 to 1.6 (p < 0.001). Major complications occurred in 13 (23%) patients. In all cases, esophagorespiratory fistulas were occluded. Tumor recurred in 5 of 16 patients with a fistula, 8 of 21 patients after gastric tube interposition, 3 of 10 patients after gastrectomy, and 2 of 10 patients with a tumor immediately distal to the upper esophageal sphincter. Median survival was 61 days. Prior radiation, chemotherapy, or both increased the risk of specific stent-related complications in relation to the (neo)esophagus (6 of 16 [38%] versus 4 of 41 [10%]: odds ratio, 5.5: 95% CI [1.3, 24], p = 0.018). CONCLUSIONS: Self-expanding metal stents are effective and relatively safe for palliation of patients with malignancy and dysphagia caused by fistula formation, postoperative recurrence, and tumors near the upper esophageal sphincter. Placement should be considered at an early stage in these conditions.

Aged↗
PubMed2001

Partial liver transplantation.

Since the introduction of the split-liver transplantation procedure 15 years ago a variety of partial liver transplantations have been developed. The earliest form of split-liver transplantation consisted of reduction of a whole liver graft to just the left lateral segment or the left liver lobe, which was then small enough to transplant to a young child. The rest of the liver was discarded. This method partially solved the great need for liver grafts for children but as the remaining part of the liver was discarded the method was in fact detrimental for adults on the waiting list. Further surgical development resulted in splitting of the liver ex vivo into two transplantable partial grafts: the left part to a child and the right lobe to an adult. This procedure was successfully introduced but the complicated logistics resulted in prolonged cold ischemia times for the grafts. In order to keep the cold ischemia time as short as possible, the in situ split-liver technique was developed, in which the liver was split in the post-mortem donor. Refinement of this operation led to results which were superior to those obtained with the ex vivo method; moreover, it opened the door to living-donor liver transplantation. The first successful procedure was performed from a mother to a child, who received the mother's left liver segment. The introduction of this technique resulted over the years in a decrease in the pediatric waiting list to almost zero. As the demand for organs increases every year and the number of donors remains constant in Western countries, the right-lobe living-donor liver transplantation for adults has been introduced. Introduction of all forms of partial liver transplantation has relieved the pressure on waiting lists, especially for children but also for adults. There are, however, serious concerns regarding the high morbidity and mortality rates associated with the living-donor donation procedure.

Adult↗
PubMed2001

Molecular biology of Barrett's adenocarcinoma.

OBJECTIVE: To review the current knowledge on the genetic alterations involved in the development and progression of Barrett's esophagus-associated neoplastic lesions. SUMMARY BACKGROUND DATA: Barrett's esophagus (BE) is a premalignant condition in which the normal squamous epithelium of the esophagus is replaced by metaplastic columnar epithelium. BE predisposes patients to the development of esophageal adenocarcinoma. Endoscopic surveillance can detect esophageal adenocarcinomas when they are early and curable, but most of the adenocarcinomas are detected at an advanced stage. Despite advances in multimodal therapy, the prognosis for invasive esophageal adenocarcinoma is poor. A better understanding of the molecular evolution of the Barrett's metaplasia to dysplasia to adenocarcinoma sequence may allow improved diagnosis, therapy, and prognosis. METHODS: The authors reviewed data from the published literature to address what is known about the molecular changes thought to be important in the pathogenesis of BE-associated neoplastic lesions. RESULTS: The progression of Barrett's metaplasia to adenocarcinoma is associated with several changes in gene structure, gene expression, and protein structure. Some of the molecular alterations already showed promise as markers for early cancer detection or prognostication. Among these, alterations in the p53 and p16 genes and cell cycle abnormalities or aneuploidy appear to be the most important and well-characterized molecular changes. However, the exact sequence of events is not known, and probably multiple molecular pathways interact and are involved in the progression of BE to adenocarcinoma. CONCLUSIONS: Further research into the molecular biology of BE-associated adenocarcinoma will enhance our understanding of the genetic events critical for the initiation and progression of Barrett's adenocarcinoma, leading to more effective surveillance and treatment.

Adenocarcinoma↗
PubMed2001

Phase II study of the combination cisplatin, etoposide, 5-fluorouracil and folinic acid in patients with advanced squamous cell carcinoma of the esophagus.

The objective of this study was to determine the toxicity and the efficacy of the combination of cisplatin, etoposide, 5-fluorouracil (5-FU) and folinic acid in the treatment of patients with advanced squamous cell carcinoma of the esophagus. Patients received cisplatin 80 mg/m(2) i.v. on day 1, etoposide 125 mg/m(2) i.v. on day 1 and etoposide 200 mg/m(2) p.o. on days 3 and 5, 5-FU 375 mg/m(2)/day continuously i.v. combined with folinic acid 30 mg p.o. 6 times per day on days 1--4. Courses were repeated every 4 weeks until progression or up to a maximum of 6 courses. Patients were evaluated for response after every two courses. Sixty-nine patients received a total of 291 courses (median 4, range 1--6). The hematological toxicity consisted of leukocytopenia grade 3 or 4 in 17 and 16% of patients, respectively. Leukocytopenic fever was seen in 19% of patients. Thrombocytopenia grade 3 or 4 was seen in 13 and 7% of patients, respectively. Non-hematological toxicity consisted of nausea/vomiting grade 3 in 32%, diarrhea grade 3 in 6% and mucositis grade 3 or 4 in 23% of patients. The overall response rate was 34% (complete response 4%, partial response 30%) and the median time to progression was 7 months in 13 patients who received no additional treatment. The median survival for all patients was 9.5 months with a 1-year survival rate of 36%. Ten patients with initially locally unresectable disease (N=2) or celiac or supraclavicular lymph node metastases (N=8) who received additional treatment (esophageal resection in seven patients and radiotherapy in three patients) after they had responded to chemotherapy had a 3-year survival of 50%. We conclude that the combination cisplatin and etoposide combined with 5-FU and folinic acid is a safe and active regimen for patients with advanced squamous cell carcinoma of the esophagus. Mucositis is the most prevalent toxicity.

Adult↗
PubMed2001

Coagulopathy following major liver resection: the effect of rBPI21 and the role of decreased synthesis of regulating proteins by the liver.

This prospective study investigated the role of reduced hepatic synthesis of regulating proteins in coagulopathy after partial hepatectomy (PH) compared with major abdominal surgery (MAS) without involvement of the liver. Furthermore, we studied the effect of rBPI21, an endotoxin-neutralizing agent, on coagulopathy after PH was studied. Compared with MAS, PH resulted in significantly elevated levels of thrombin-antithrombin-III and plasmin-alpha2-antiplasmin complexes. Levels of antithrombin-3, alpha2-antiplasmin, fibrinogen, plasminogen, alpha2-macroglobulin (alpha2-M), and C1-inhibitor remained lower following PH. Treatment with rBPI21 led to significantly lower levels of tissue-type plasminogen activator (t-PA). Post-operative disseminated intravascular coagulation (DIC) was associated with significantly higher bilirubin and t-PA plasma levels and significantly lower levels of alpha2-M. This study indicates that PH induced hepatic failure results in decreased synthesis of hepatic regulating plasma proteins and subsequent activation of coagulation and fibrinolysis. Prevention of t-PA release by rBPI21 may have important clinical implications. Decreased availability of alpha2-M may be a factor in post-operative DIC.

Abdomen↗
PubMed2000

[Treatment of non-resectable liver tumors with percutaneous interstitial laser coagulation while interrupting blood circulation to the liver].

OBJECTIVE: To evaluate, in patients with hepatocellular carcinoma or colorectal carcinoma disseminated to the liver, treatment with interstitial laser coagulation (ILC) during temporary occlusion of vascular inflow in the liver: feasibility, complications and initial tumour response. DESIGN: Prospective, descriptive. METHODS: Patients were included if their tumours were surgically irresectable and smaller than 4 cm in diameter and did not exceed a number of 3. ILC was performed under general anaesthesia, basically via a percutaneous approach. Vascular inflow was occluded during laser treatment. Twenty-four hours after ILC a triphasic spiral CT was performed to assess the result of the treatment. RESULTS: In 10 patients 14 hepatic tumours were lasered in 12 treatment sessions (10 percutaneous and 2 at laparotomy). After 5 treatment sessions, complications were observed of which pain at the insertion site of the catheters was the most frequent. For 6 out of the 10 patients with percutaneous procedures, discharge was within 24 hours after ILC. Nine out of the 14 tumours (65%) were completely coagulated. CONCLUSION: ILC with vascular inflow occlusion is a safe and feasible technique that can be performed during a short hospital stay. Initial tumour response is 65% and these results justify determination of duration of response in a larger group of patients.

Aged↗
PubMed2000

Importance of portal flow diversion in experimental auxiliary partial orthotopic liver transplantation.

BACKGROUND: Auxiliary partial orthotopic liver transplantation (APOLT) has successfully been performed in patients with noncirrhotic metabolic diseases. It remains, however, unclear if intervention in the portal venous inflow is necessary to ensure adequate portal blood flow to graft and host liver. In this experimental study we evaluate the hepatic flow during APOLT. METHODS: Left lateral/medial segmental grafts were transplanted from beagle to dalmatian dogs. Vascular structures were anastomosed end-to-end. The effect of diversion of the portal flow was studied in three groups: in the ligation group (n=3) the host portal vein was tied off, the free flow group (n=6) had random flow to both livers. In the banding group (n=11) the host portal vein was banded with a adjustable strapband to restore the pretransplantation flow distribution. RESULTS: After reperfusion the blood flow through the common portal vein decreased from 49 to 36 ml/kg/min (P<0.03) in all animals. Flow through the left portal vein decreased from 26 to 5 ml/kg/min (P<0.0001). Banding restored the flow in the left portal vein to 12 ml/kg/min, although the flow in the free-flow group remained 4 ml/kg/min. In the ligation group the total portal flow was forced toward the graft leading to the highest perfusion: 24 ml/kg/min (P<0.005). Adverse effect of this ligation was the development of portal hypertension. CONCLUSIONS: This experimental study confirms that diversion of the portal flow is necessary for adequate graft perfusion in APOLT. Banding can restore the pretransplantation flow distribution, without compromising the flow in the common portal vein.

Animals↗
PubMed2000

Genetic alterations involving exon 3 of the beta-catenin gene do not play a role in adenocarcinomas of the esophagus.

Beta-catenin has been identified as an oncogene. Phosphorylation of sites encoded by exon 3 of the beta-catenin gene facilitates degradation of this protein by the adenomatous polyposis coli (apc) gene product. Mutations in these sites or inactivation of apc lead to stabilization of beta-catenin, which then translocates to the nucleus where it modulates the transcription of genes involved in tumor formation. To explore the role of beta-catenin mutations in adenocarcinomas of the esophagus, we screened for genetic alterations in exon 3 in 69 tumor samples. We detected no mutations in exon 3 by PCR-SSCP analysis nor did we find large interstitial deletions involving exon 3. beta-catenin immunostaining on 54 tumors showed focal nuclear staining in 7 tumors and homogeneous nuclear staining in 3 tumors; in the latter; no mutations in the mutation cluster region of apc were detected. These results show that genetic alterations of exon 3 of the beta-catenin gene do not occur and therefore do not contribute to the pathogenesis of esophageal adenocarcinomas. The abnormal cytoplasmic and nuclear localization of beta-catenin indicates that other mechanisms leading to elevated free beta-catenin in these cancers must be involved.

Adenocarcinoma↗