The road to tailored adjuvant chemotherapy for all four non-pancreatic periampullary cancers: An international multimethod cohort study.

BACKGROUND: Despite differences in tumour behaviour and characteristics between duodenal adenocarcinoma (DAC), the intestinal (AmpIT) and pancreatobiliary (AmpPB) subtype of ampullary adenocarcinoma and distal cholangiocarcinoma (dCCA), the effect of adjuvant chemotherapy (ACT) on these cancers, as well as the optimal ACT regimen, has not been comprehensively assessed. This study aims to assess the influence of tailored ACT on DAC, dCCA, AmpIT, and AmpPB. PATIENTS AND METHODS: Patients after pancreatoduodenectomy for non-pancreatic periampullary adenocarcinoma were identified and collected from 36 tertiary centres between 2010 - 2021. Per non-pancreatic periampullary tumour type, the effect of adjuvant chemotherapy and the main relevant regimens of adjuvant chemotherapy were compared. The primary outcome was overall survival (OS). RESULTS: The study included a total of 2866 patients with DAC (n = 330), AmpIT (n = 765), AmpPB (n = 819), and dCCA (n = 952). Among them, 1329 received ACT, and 1537 did not. ACT was associated with significant improvement in OS for AmpPB (P = 0.004) and dCCA (P < 0.001). Moreover, for patients with dCCA, capecitabine mono ACT provided the greatest OS benefit compared to gemcitabine (P = 0.004) and gemcitabine - cisplatin (P = 0.001). For patients with AmpPB, no superior ACT regime was found (P > 0.226). ACT was not associated with improved OS for DAC and AmpIT (P = 0.113 and P = 0.445, respectively). DISCUSSION: Patients with resected AmpPB and dCCA appear to benefit from ACT. While the optimal ACT for AmpPB remains undetermined, it appears that dCCA shows the most favourable response to capecitabine monotherapy. Tailored adjuvant treatments are essential for enhancing prognosis across all four non-pancreatic periampullary adenocarcinomas.

Differences in Lymph Node Metastases Patterns Among Non-pancreatic Periampullary Cancers and Histologic Subtypes: An International Multicenter Retrospective Cohort Study and Systematic Review.

BACKGROUND: Standard lymphadenectomy for pancreatoduodenectomy is defined for pancreatic ductal adenocarcinoma and adopted for patients with non-pancreatic periampullary cancer (NPPC), ampullary adenocarcinoma (AAC), distal cholangiocarcinoma (dCCA), or duodenal adenocarcinoma (DAC). This study aimed to compare the patterns of lymph node metastases among the different NPPCs in a large series and in a systematic review to guide the discussion on surgical lymphadenectomy and pathology assessment. METHODS: This retrospective cohort study included patients after pancreatoduodenectomy for NPPC with at least one lymph node metastasis (2010-2021) from 24 centers in nine countries. The primary outcome was identification of lymph node stations affected in case of a lymph node metastasis per NPPC. A separate systematic review included studies on lymph node metastases patterns of AAC, dCCA, and DAC. RESULTS: The study included 2367 patients, of whom 1535 had AAC, 616 had dCCA, and 216 had DAC. More patients with pancreatobiliary type AAC had one or more lymph node metastasis (67.2% vs 44.8%; P < 0.001) compared with intestinal-type, but no differences in metastasis pattern were observed. Stations 13 and 17 were most frequently involved (95%, 94%, and 90%). Whereas dCCA metastasized more frequently to station 12 (13.0% vs 6.4% and 7.0%, P = 0.005), DAC metastasized more frequently to stations 6 (5.0% vs 0% and 2.7%; P < 0.001) and 14 (17.0% vs 8.4% and 11.7%, P = 0.015). CONCLUSION: This study is the first to comprehensively demonstrate the differences and similarities in lymph node metastases spread among NPPCs, to identify the existing research gaps, and to underscore the importance of standardized lymphadenectomy and pathologic assessment for AAC, dCCA, and DAC.

The Five Periampullary Cancers, not Just Different Siblings but Different Families: An International Multicenter Cohort Study.

BACKGROUND: Cancer arising in the periampullary region can be anatomically classified in pancreatic ductal adenocarcinoma (PDAC), distal cholangiocarcinoma (dCCA), duodenal adenocarcinoma (DAC), and ampullary carcinoma. Based on histopathology, ampullary carcinoma is currently subdivided in intestinal (AmpIT), pancreatobiliary (AmpPB), and mixed subtypes. Despite close anatomical resemblance, it is unclear how ampullary subtypes relate to the remaining periampullary cancers in tumor characteristics and behavior. METHODS: This international cohort study included patients after curative intent resection for periampullary cancer retrieved from 44 centers (from Europe, United States, Asia, Australia, and Canada) between 2010 and 2021. Preoperative CA19-9, pathology outcomes and 8-year overall survival were compared between DAC, AmpIT, AmpPB, dCCA, and PDAC. RESULTS: Overall, 3809 patients were analyzed, including 348 DAC, 774 AmpIT, 848 AmpPB, 1,036 dCCA, and 803 PDAC. The highest 8-year overall survival was found in patients with AmpIT and DAC (49.8% and 47.9%), followed by AmpPB (34.9%, P < 0.001), dCCA (26.4%, P = 0.020), and finally PDAC (12.9%, P < 0.001). A better survival was correlated with lower CA19-9 levels but not with tumor size, as DAC lesions showed the largest size. CONCLUSIONS: Despite close anatomic relations of the five periampullary cancers, this study revealed differences in preoperative blood markers, pathology, and long-term survival. More tumor characteristics are shared between DAC and AmpIT and between AmpPB and dCCA than between the two ampullary subtypes. Instead of using collective definitions for "periampullary cancers" or anatomical classification, this study emphasizes the importance of individual evaluation of each histopathological subtype with the ampullary subtypes as individual entities in future studies.

Different Periampullary Types and Subtypes Leading to Different Perioperative Outcomes of Pancreatoduodenectomy: Reality and Not a Myth; An International Multicenter Cohort Study.

This international multicenter cohort study included 30 centers. Patients with duodenal adenocarcinoma (DAC), intestinal-type (AmpIT) and pancreatobiliary-type (AmpPB) ampullary adenocarcinoma, distal cholangiocarcinoma (dCCA), and pancreatic ductal adenocarcinoma (PDAC) were included. The primary outcome was 30-day or in-hospital mortality, and secondary outcomes were major morbidity (Clavien-Dindo 3b≥), clinically relevant post-operative pancreatic fistula (CR-POPF), and length of hospital stay (LOS). Results: Overall, 3622 patients were included in the study (370 DAC, 811 AmpIT, 895 AmpPB, 1083 dCCA, and 463 PDAC). Mortality rates were comparable between DAC, AmpIT, AmpPB, and dCCA (ranging from 3.7% to 5.9%), while lower for PDAC (1.5%, p = 0.013). Major morbidity rate was the lowest in PDAC (4.4%) and the highest for DAC (19.9%, p < 0.001). The highest rates of CR-POPF were observed in DAC (27.3%), AmpIT (25.5%), and dCCA (27.6%), which were significantly higher compared to AmpPB (18.5%, p = 0.001) and PDAC (8.3%, p < 0.001). The shortest LOS was found in PDAC (11 d vs. 14-15 d, p < 0.001). Discussion: In conclusion, this study shows significant variations in perioperative mortality, post-operative complications, and hospital stay among different periampullary cancers, and between the ampullary subtypes. Further research should assess the biological characteristics and tissue reactions associated with each type of periampullary cancer, including subtypes, in order to improve patient management and personalized treatment.

Pheochromocytoma associated with neurofibromatosis type 1: concepts and current trends.

BACKGROUND: Neurofibromatosis Type 1(NF-1) has autosomal dominant inheritance with complete penetrance, variable expression and a high rate of new mutation. Pheochromocytoma occurs in 0.1%-5.7% of patients with NF-1. CASE PRESENTATION: We present the case of a 37-year-old patient with laparoscopically resected pheochromocytoma. He was investigated for hypertension, flushing and ectopic heart beat. Abdominal CT and MRI revealed a mass measuring 8 x 4 cm in the right adrenal gland. The diagnosis of pheochromocytoma was confirmed by elevated 24-hour urine levels of VMA, metanephrines and catecholamines as well as positive MIBG scan. The patient presented with classic clinical features of NF-1, which was confirmed by pathologic evaluation of an excised skin nodule. The patient underwent laparoscopic right adrenalectomy through a transabdominal approach and was discharged on the second postoperative day, being normotensive. The patient is normotensive without antihypertensive therapy 11 years after the procedure. CONCLUSION: Nowadays in the era of laparoscopy, patients with pheochromocytoma reach the operating theatre easier than in the past. Despite, the feasibility and oncological efficacy of the laparoscopic approach to the adrenals, continued long term follow-up is needed to establish the minimally invasive technique as the preferred approach. Furthermore, these patients should be further investigated for other neoplasias and stigmata of other neurocutaneous syndromes, taking into account the association of the familial pheochromo-cytoma with other familial basis inherited diseases.

Functional results of speech and swallowing after oral microvascular free flap reconstruction.

PURPOSE: To study speech and swallowing in patients who underwent microvascular free flap reconstruction after major surgery of the oral cavity. PATIENTS AND METHODS: Twenty patients, 17 men and 3 women, with a mean age of 58.5 years (range 27-79 years) were included in the study. Squamous cell carcinoma was the most common malignancy. Swallowing assessment was performed through videofluoroscopy, using three consistencies of barium meal. The recorded swallows were assessed for the ability to hold the bolus during the oral phase, lip seal, tongue movement, residue in the floor of the mouth, laryngeal penetration and aspiration. Speech function regarding intelligibility and articulation was objectively assessed. RESULTS: Fifteen out of 20 patients (75%) had a good lip seal. Fourteen patients (73.6%) had adequate control of bolus, while in 89.4% the neotongue motility was satisfactory. Vallecular residue was noted in 25% of patients, laryngeal penetration in two (10%), while three patients (15%) continued to have significant aspiration, which necessitated continuous feeding through a gastrostomy. Postoperative speech intelligibility and articulation was satisfactory in 75 and 62.5% of the patients, respectively. CONCLUSIONS: Microvascular free flap reconstruction of major defects after oral resections rehabilitates the functions of swallowing and speech in acceptable levels, improving quality of life in these patients.

Gastrointestinal Seed Bezoars: A Systematic Review of Case Reports and Case Series.

Seed bezoars are a distinct subcategory of phytobezoars, caused by indigestible vegetable or fruit seeds. The aim of our study was to present a comprehensive review on seed bezoars, focusing on epidemiology, symptomatology, diagnosis and treatment options. A systematic review of the English literature (1980-2018) was conducted, using PubMed, Embase and Google Scholar databases. Fifty-two studies fulfilled the inclusion criteria, with a total of 153 patients, the majority of whom (72%) came from countries around the Eastern Mediterranean and the Middle East. Patients complained primarily about constipation (63%), abdominal/rectal pain (19%) or intestinal obstruction (17%). Most seed bezoars were found in the rectum (78%) and the terminal ileum (16%). Risk factors were recognised in 12% of cases. Manual disimpaction under general anaesthesia was the procedure of choice in 69%, while surgery was required in 22% of cases. Seed bezoars appear to represent a different pathophysiological process compared to fibre bezoars. Seeds usually pass through the pylorus and ileocaecal valve, due to their small size, and accumulate gradually in the colon. Seed bezoars are usually found in the rectum of patients without predisposing factors, causing constipation and pain. History and digital rectal examination are the mainstay of diagnosis, with manual extraction under general anaesthesia being the procedure of choice.

Solitary fibrous tumor of the liver expressing CD34 and vimentin: a case report.

A case of a successfully treated solitary fibrous tumor (SFT) of the liver is reported. An 82-year-old female presented with left upper abdominal discomfort, a firm mass on palpation, and imaging studies revealed a large tumor, 15 cm in diameter, arising from the left lobe of the liver. A formal left hepatectomy was performed. Microscopic evaluation showed spindle and fibroblast-like cells within the collagenous stroma. Immunohistochemistry disclosed diffuse CD34 and positive vimentin, supporting the diagnosis of a benign SFT. The patient remained well 21 months after surgery. SFT of the liver is a very rare neoplasm of mesenchymal origin. In most cases it is a benign lesion, although some may have malignant histological features and recur locally or metastasize. With less than 30 reported cases in the literature, little can be said regarding its natural history or the benefits of adjuvant radiochemotherapy. Complete surgical resection remains the cornerstone of its treatment.

Primary malignant melanoma of the duodenum: aggressive management and long-term survival of an unusual oncologic entity.

Primary malignant melanoma originating in the small bowel is extremely rare. We report the case of a 55-year-old man who presented with a preoperative bleeding duodenal tumor. A standard pancreaticoduodenectomy was performed. Histopathological examination ascertained the diagnosis of a duodenal malignant melanoma with locoregional lymphatic spread. A thorough postoperative investigation did not reveal any primary melanotic lesions. Thus, the diagnosis of a primary melanoma originating from the duodenum was suggested. Fourteen months after surgery, the patient had no evidence of recurrence. Primary malignant melanoma of the duodenum is an existing, though unusual, oncologic entity. Aggressive surgery remains the treatment of choice offering both symptom palliation and long-term survival.

Burn wound angiogenesis is increased by exogenously administered recombinant leptin in rats.

BACKGROUND: Leptin is a potent direct angiogenic factor that stimulates endothelial cell migration and activation in vitro and angiogenesis in vivo. In addition, leptin has been discussed to play an important role in angiogenesis, as it promotes the formation of new blood vessels. PURPOSE: The effect of exogenously administered leptin on the healing process of a full tissue burn wound model. METHODS: Sixty-three Sprague-Dawley male rats were used. Full tissue burn wound was created by electrocautery. The width of the pin was 0.3 cm; its length was 2 cm and was used at the "cut" modulation. Rats were divided into seven groups of nine animals each. Burn wounds were injected with murine recombinant leptin and the rats were sacrificed 3, 7 and 9 days after surgery. Every group had obtained three animals for the three different days of sacrifice. Three different leptin doses of 250 pg/ml, 500 pg/ml and 1000 pg/ml were used in different animal groups (A, B and C). For every one of the three leptin doses used, another animal group was evaluated by using the combined injection of leptin and antileptin (A1, B1, and C1), in order to study the inhibitory effect to the leptin factor. Nine rats were served as controls. These were injected with 0.3 ml water for injection solution and sacrificed at the same time intervals. After sacrifice of the animals, the skin was grossly determined by its appearance, colour and texture. Full thickness burn wounds were dissected for histological examination. A qualitative analysis of angiogenesis in the burn wound was conducted following a standard hematoxylin and eosin stain. The wound tissue samples from each experimental group underwent immunohistochemical evaluation of microvessel density by endothelial cell staining with mouse anti-rat CD 34 monoclonal antibody. RESULTS: The most impressive growth of new blood vessels appeared seven and nine days after treatment with the highest leptin doses. There were no significant differences in microvessel density between the seventh and the ninth postoperative day among different groups treated with leptin. All wounds from the control group, as well as those from animal groups treated with the combined injection of leptin and antileptin did not develop any new vessels. CONCLUSION: Exogenous administration of recombinant leptin increases early tissue angiogenesis in the burn wound level of an experimental animal model.

Synchronous Colonic Adenocarcinoma and Metastatic Lobular Carcinoma in a Colectomy Specimen: A Rare Finding.

Invasive lobular carcinoma is the second-most-common subtype of invasive breast carcinoma. Its metastatic pattern is different compared to invasive carcinoma-no special type. It metastasizes more often to the gastrointestinal tract, peritoneum, pleura, and ovaries. The extrahepatic gastrointestinal tract metastases occur mostly in the stomach and small intestine and less often in the colon and rectum. We present a case description of an 87-year-old woman admitted to our hospital with hematochezia, abdominal discomfort, fatigue, and weight loss. A colonoscopy revealed an exophytic tumor of the sigmoid colon. Metastatic disease was not found in imaging studies. A low anterior resection was performed. The pathologic examination revealed a collision tumor consisting of a poorly differentiated adenocarcinoma of the colon and metastatic lobular carcinoma. The diagnosis was challenging due to the lack of a previous history. Also, the diffuse architectural pattern and signet ring cells found may be in primary signet ring carcinoma of the colon as well as in carcinomas from other anatomical sites. Immunohistochemistry was helpful in making the diagnosis. A review of the literature revealed that this is the fourth case of metastatic breast carcinoma coexisting with colonic adenocarcinoma.

Pre-operative chemoradiotherapy with oral capecitabine in locally advanced, resectable rectal cancer.

PURPOSE: The aim of the study was to evaluate the efficacy and tolerance of pre-operative chemoradiotherapy with oral capecitabine in Greek patients with locally advanced, resectable rectal cancer. MATERIALS AND METHODS: Thirty patients, 16 men and 14 women with a median age of 58 years (range, 21-75 years), with potentially resectable T3NO (30%), T3N1 (53%) and T4NO-1 (17%) rectal cancer, were treated with capecitabine (825 mg/m(2), twice daily for 7 days/week) and concomitant radiotherapy (50.4 Gy/28 fractions) for 5.5 weeks. Patients underwent surgery with total mesorectal excision 4-6 weeks later followed by 4-months of post-operative treatment with capecitabine. The primary end-point was to determine the clinical and pathological response, safety profile, preservation of the sphincter mechanism and rate of peri-operative complications. RESULTS: The median distance of rectal tumors from the anal verge was 7 cm. All patients had curative resection. Downstaging rate was 84% (25/30) on endorectal ultrasonography and 75% (22/30) on pathology findings. Pathological complete response rate was 23% (7/30). No patient had grade 4 toxicity. Grade 3 toxicity occurred in 3 patients (10%) and consisted mainly of leucopenia (6%) and hand-foot syndrome (4%). Mild or moderate toxicity was frequent, but always reversible. Twenty-four patients (80%) received sphincter-preserving surgical procedures. Peni-operative complications were seen in 6 (20%) patients and included mechanical ileus (3%), delayed wound healing (7%), wound infection (7%) and anastomotic leakage (3%). CONCLUSION: Pre-operative chemoradiotherapy with oral capecitabine in locally advanced, resectable rectal cancer achieves significant rates of tumor downstaging and sphincter preservation with a favorable safety profile.

Mechanical deterioration underlies malignant behavior of aneurysmal human ascending aorta.

OBJECTIVE: The human ascending aorta becomes markedly prone to rupture and dissection at a diameter of 6 cm. The mechanical substrate for this malignant behavior is unknown. This investigation applied engineering analysis to human ascending aortic aneurysms and compared their structural characteristics with those of normal aortas. METHODS: We measured the mechanical characteristics of the aorta by direct epiaortic echocardiography at the time of surgery in 33 patients with ascending aortic aneurysm undergoing aortic replacement and in 20 control patients with normal aortas undergoing coronary artery bypass grafting. Six parameters were measured in all patients: aortic diameter in systole and diastole, aortic wall thickness in systole and diastole, and blood pressure in systole and diastole. These were used to calculate mechanical characteristics of the aorta from standard equations. Aortic distensibility reflects the elastic qualities of the aorta. Aortic wall stress reflects the disrupting force experienced within the aortic wall. Incremental elastic modulus indicates loss of elasticity reserve. RESULTS: Aortic distensibility falls to extremely low levels as aortic dimension rises toward 6 cm (3.02 mm Hg(-1) for small aortas versus 1.45 mm Hg(-1) for aortas larger than 5 cm, P < .05). Aortic wall stress rises to 157.8 kPa for the aneurysmal aorta, compared with 92.5 kPa for normal aortas. For 6-cm aortas at pressures of 200 mm Hg or more, wall stress rises to 857 kPa, nearly exceeding the known maximal tensile strength of human aneurysmal aortic wall. Incremental elastic modulus deteriorates (1.93 +/- 0.88 MPa vs 1.18 +/- 0.21 MPa, P < .05) in aneurysmal aortas relative to that in normal aortas. CONCLUSION: The mechanical properties of the aneurysmal aorta deteriorate dramatically as the aorta enlarges, reaching critical levels associated with rupture by a diameter of 6 cm. This mechanical deterioration provides an explanation in engineering terms for the malignant clinical behavior (rupture and dissection) of the aorta at these dimensions. This work adds to our fundamental understanding of the biology of aortic aneurysms and promises to permit future application of engineering measurements to supplement aneurysm size in clinical decision making in aneurysmal disease.

Intravascular papillary endothelial hyperplasia (Masson's hemangioma) presenting as a soft-tissue sarcoma.

Intravascular papillary endothelial hyperplasia (Masson's hemangioma) is an unusual benign, non-neoplastic, vascular lesion characterized histologically by papillary fronds lined by proliferating endothelium. It may appear as a primary or pure form developing in a distended vessel, or it can be associated with hemangiomas, pyogenic granulomas, or lymphagiomas. Nearly all lesions are intimately associated with a thrombus in various stages of organization. The main significance of intravascular papillary endothelial hyperplasia is its clinical and histological resemblance to soft-tissue sarcoma and possible misinterpretation as such. A case of intravascular papillary endothelial hyperplasia clinically diagnosed and treated as a low-grade angiosarcoma, in a 60-year-old man, presenting with a mass in the left thigh, is reported.

Immunohistochemical testing for Helicobacter pylori infection in ascending aortic aneurysms and penetrating aortic ulcers.

Evidence implicating Helicobacter pylori (H. pylori) in coronary artery disease and aneurysmal lesions is controversial. No published data have related H. pylori infection to ascending aortic aneurysms and penetrating ulcers, although both of these lesions may have an infectious components in their initiating process. We sought to investigate possible H. pylori infection in 54 human specimens of 42 aortic aneurysms and 12 penetrating ulcers. No evidence of H. pylori was found in these specimens.

Revascularization alone (without mitral valve repair) suffices in patients with advanced ischemic cardiomyopathy and mild-to-moderate mitral regurgitation.

BACKGROUND: Whether or not to perform adjunctive mitral repair in patients undergoing coronary artery bypass grafting (CABG) for advanced ischemic cardiomyopathy with moderately severe mitral regurgitation (MR) remains controversial. METHODS: We examine the clinical and echocardiographic outcome after isolated CABG in 49 patients with ischemic cardiomyopathy and 1+ to 3+ MR undergoing surgical revascularization. The patients were identified for analysis of mitral valve-related issues from a larger series of 183 patients with ischemic cardiomyopathy (MUGA ejection fraction < or = 30%) undergoing CABG by a single surgeon from 1986 to 1996. Patient age was 66.3 years (mean, range 45 to 83 years). There were 5 women (10.2%) and 44 men (89.8%). Mean ejection fraction was 22.4% with a range of 10% to 30%. Thirty-four patients had preoperative congestive heart failure (70%) and 12 (25%) had pulmonary edema. Number of grafts was 2.8 (mean, range 1 to 5). The MR was 1+ in 18 patients (37.5%), 2+ in 26 (52%) and 3+ in 5 patients (10.5%). RESULTS: Hospital mortality was 2.0% (1 of 49 patients). Ejection fraction improved from 22.0% to 31.5% (p < 0.05) after CABG. Mean degree of MR improved with CABG alone from 1.73 to 0.54 (p < 0.05) as measured at a mean interval of 36.9 months from CABG. New York Heart-Association congestive heart failure class improved from 3.3 to 1.8 (p < 0.05). Long-term survival was 88%, 65%, and 50% at 1, 3, and 5 years postoperatively. No patient required subsequent mitral valve operation or heart transplantation in long-term follow-up. CONCLUSIONS: We conclude that, in patients with advanced ischemic cardiomyopathy and mild-to-moderate MR, isolated CABG (without mitral valve, repair) suffices, producing dramatic improvement in ejection fraction, in congestive heart failure, and in degree of MR, with excellent (relative) long-term survival. The improvement in MR likely results from improved left ventricular function and size consequent upon revascularization.

Early bioprosthetic mitral valve "pseudostenosis" after complete preservation of the native mitral apparatus.

An advantage of bioprosthetic mitral valve replacement in patients with normal sinus rhythm is avoidance of the need for long-term anticoagulation. Bioprosthetic valve thrombosis is a rare complication, supporting this approach. This case report represents an example of porcine mitral valve stenosis, likely secondary to thrombosis, in which all of the native mitral valve apparatus was left intact. This was successfully treated with standard anticoagulation therapy. This complication should be considered in patients in whom retention of the mitral valve apparatus has been performed. Such patients may benefit from long-term anticoagulation treatment to obviate this event.

Brief tamoxifen pretreatment enhances the chemosensitivity of gastric carcinoma cells to 5-fluorouracil in vitro.

BACKGROUND: Estrogen receptors (ERs) have been detected in gastric carcinoma cells in vivo and in vitro. Several in vitro and in vivo studies examining the potential beneficial effects of adjuvant Tamoxifen (Tmx) have shown contradictory experimental and clinical results. MATERIALS AND METHODS: We examined the effects of a brief Tmx pretreatment on the chemosensitivity to 5-FU of two gastric carcinoma cell lines. One of these cell lines was ER(+) and the other ER(-). Tmx was administered for 24 hours before chemotherapy. RESULTS: We observed a significant increase in the cytotoxic action of 5-FU in both gastric carcinoma cell lines in the order of 100-155%. This increase in 5-FU cytotoxicity was not mediated by either the ER cell status or through TGF-beta 1 secretion. CONCLUSION: Brief Tmx pretreatment increases the chemosensitivity of gastric carcinoma cells to 5-FU in vitro.

Tissue microarray detection of matrix metalloproteinases, in diseased tricuspid and bicuspid aortic valves with or without pathology of the ascending aorta.

OBJECTIVE: The degeneration of bicuspid aortic valve and its frequent association with ascending aortic pathology, point to a still unidentified genetic tissue defect with unknown mediators. Metalloproteinases (MMPs) are lytic enzymes that have been strongly implicated in aneurysm formation. The purpose of this study was to detect the presence of these enzymes in aortic valvular tissue in healthy and diseased aortic valves with or without the presence of synchronous ascending aortic pathology. METHODS: Aortic valve specimens from 26 aortic valve replacement patients as well as 4 healthy control tricuspid aortic valves were included. 10 patients had bicuspid aortic valves, and 16 had tricuspid aortic valves. Half of our patient population had a concomitant aortic procedure for aortic pathology. The study detected MMPs 1,2 and 9 as well as their Tissue inhibitors (TIMPs) 1 and 2. MMP and TIMP detection was accomplished with the construction of a tissue micro array and immunohistochemistry. CONCLUSIONS: MMP-9 expression was significantly higher in bicuspid aortic valves compared to normal valves (P<0.05). When compared to the tricuspid valve group, MMP-9 mean value was significantly higher in bicuspid valves (P<0.05). When the entire rest of the valve group (n=4+16, i.e. control and tricuspid valve groups) was compared to the bicuspid valve group, bicuspid valves had significantly higher MMP-2, and MMP-9 (P<0.01) expression. TIMP expression also changed in diseased valves, among different patient groups. This increased proteolytic presence in bicuspid aortic valves may attribute to the observed decreased elastin and collagen content, and their resultant functional failure.