End-to-side duct-to-mucosa pancreaticojejunostomy after pancreaticoduodenectomy A comparison trial of small versus larger jejunal incision. A single center experience.

AIM: The rates of post-operative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD) are between 5% and 30%. Nowadays, pancreaticojejunostomy (PJ) represents the most common type of reconstruction after PD, but the ideal technique is still debated. Our randomized trial was conceived with the intent to evaluate if two variants of PJ could influence the post-operative outcome in term of early complications. MATERIAL AND METHODS: Forty-eight consecutive patients treated with PD were randomized into 2 groups (Group 1 or Large Jejunal Incision or LJI group and Group 2 or Small Jejunal Incision or SJI group). Outcome measures were the operative time, postoperative complications, length of postoperative hospital stay, amylase content in drains. RESULTS: wenty-two patients were enrolled in the LJI and 26 in the SJI group. Median operative times did not differ between the 2 groups. The groups were homogeneous in respect to the median age of patients, the clinical presentation of jaundice and the presence of percutaneous biliary drainage (PBD). POPF developed in 3/22 (13.6%) and 1/26 (4%) patients among the LJI and SJI group respectively (3 grade B and 1 grade C respectively) (p=0.341). PPH occurred in 8/22 (36%) and 2/26 (8%) patients among the LJI and SJI group, respectively (p=0.018). The Amylase content in the drainage fluid measured at the 5th postoperative day showed a higher value in patients who underwent LJI anastomosis compared to those with SJI anastomosis [LJI group: 26.5 (6-254) U/l vs SJI group: 7 (0-38) U/l; p=0.051]. Delayed Gastric Emptying (DGE) was not different. The multivariate logistic regression analysis demonstrated both LJI anastomosis and DGE as independent predictors for pancreatic fistula (DGE: OR=20.04, CI 95%=1.92-208.83, P=0.012; LJI anastomosis: OR=24.58, CI 95%=1.71-354.32, P=0.019) and PPH (DGE: 30.5, CI 95%=3.02-308.16, P=0.004; LJI anastomosis: OR=12.71, CI 95%=1.23-131.55, P=0.033). CONCLUSIONS: Based on the present results, we suggest to adopt what a "pancreas duct-oriented" approach: if pancreas duct is large a SJI-PJ is recommended; if the duct is < than 3 mm, a LJI must be preferred. Our conclusion is that the association of some surgeons to perform always the techniques with them are more confident is a concept of the past: recent data suggest that the pancreatic surgeon must have the different techniques in his "armamentarium" and varying the technique depending on local characteristic of the pancreas to allow a tailored approach to the patient. KEY WORDS: Pancreaticojejunostomy, Pancreatic fistula, Surgical Sutcome.

Extracorporeal versus intracorporeal anastomosis after laparoscopic right hemicolectomy: cost-effectiveness analysis.

AIM: The cost effectiveness of the laparoscopic right hemicolectomy is still debated, and the current literature does not allow to be drawn certain conclusion. Our study compared direct clinical costs and outcomes for laparoscopic right hemicolectomy with the two most used type of anastomosis, such as ExtraCorporeal Anastomosis (ECA) and IntraCorporeal Anastomosis (ICA). MATERIAL AND METHODS: In this retrospective study, all patients who underwent laparoscopic right hemicolectomy with intracorporeal and extracorporeal anastomosis between January 2016 and April 2018 were evaluated. Patients were divided into two groups according to the type of anastomosis: ECA or ICA. RESULTS: Thirty ECA and twenty-nine ICA patients were included in the study. Operative time was significantly longer in ICA group than ECA group (p < 0.001). No significant differences between the groups were seen in terms of timeto- first flatus, postoperative complications and re-admission rate. ICA group showed a shorter hospitalization (5 vs 6; p < 0.022). In the ICA group, considering only the surgical tools were more expensive than in ECA (1435.6 € vs 72 €). Nevertheless, the total cost of the two procedures in similar (14451.36 € in ECA group vs 14631.04 € in ICA group). CONCLUSION: ECA and ICA are comparable in terms of postoperative outcomes. ICA requires much more expensive charges, compared to a minor hospitalization. The ECA seems to be less expensive in terms of surgical supplies but the longer recovery determines an increase in the total cost resulting in a non-inferiority of one compared to the other technique. KEY WORDS: Cost-analysis, ExtraCorporeal Anastomosis, IntraCorporeal Anastomosis, Laparoscopy, Right Hemicolectomy.

How we do it: totally laparoscopic complete mesocolon excision for splenic flexure cancer.

BACKGROUND: Splenic flexure (SF) cancer is not a common condition and its treatment is still under discussion. Although laparoscopic surgery is well accepted for the treatment of colon cancer at any stage, complete mesocolon excision (CME) with selective vascular ligation using the laparoscopic approach for SF cancer remains technically demanding and represents a real challenge for surgeons. METHODS: We present a single-institution experience of laparoscopic CME for SF cancer. Intra-operative, pathologic, and post-operative data of patients who underwent laparoscopic SF resection were reviewed to assess the technical feasibility and oncologic safety. Technical features, histopathology, morbidity, and mortality were evaluated. RESULTS: From February 2015 to October 2017, a minimally invasive approach was proposed to 17 patients (M/F 14/3) affected by splenic flexure cancer. In all patients, the procedure was completed by laparoscopy. The anastomosis was completed intra-corporeally in 89% of cases. The distal margin was 3.1 ± 2.6 cm and the proximal margin was 6.5 ± 3.3 cm from the tumor site. The number of mean harvested nodes was 13.9 ± 7. The mean operative time was 215.5 ± 65 min, and blood loss was 80 ± 27. In one case, a laparoscopic partial gastrectomy was associated due to tumor invasion. The mean post-operative stay was 6.7 ± 3.3 days. Readmission was necessary for two patients. No major morbidity was recorded. CONCLUSIONS: Despite the wide spread and increasing confidence in laparoscopic colectomy, SF resection remains one of the most challenging procedures in colorectal surgery with a complex learning curve. SF resection with CME and CVL is feasible and safe for the treatment of early-stage and locally advanced SF cancer.

A surgical department for intensified care.

PURPOSE: The growing pressure to rationalize costs in the healthcare system demands the development of new healthcare models aimed at allowing patients to receive the best treatment, without ignoring the rising costs. METHODS: In the Healthcare Unit 2 located in the Abruzzo region in Italy, a new model of intensified care surgical department was designed in January 2013. The department was based on the selection of the degree of patient disease. Patients requiring a medium-low degree surgery were treated in the peripheral unit, in the Ortona hospital, while more complex surgical procedures, most cancer cases (including stomach, liver, pancreas, colon-rectum or multi-organ resections), were performed in the central unit in the Chieti hospital. RESULTS: The value of production at the peripheral unit, in Ortona, increased by 299.4% along with an increase in discharges of 112.6%, with an average DRG weight from 1.02 to 1.45. At the central unit, in Chieti, the average DRG weight produced was 3.328. In relation to quality assessment, pancreatic surgery morbidity was 27.0% and mortality was 1.7 % due to resection and 2.2% for other causes. Likewise, for colon-rectal surgery, a global morbidity of 35.0% and anastomotic leakage of 3.9% was seen. CONCLUSIONS: The 24-month preliminary results show that new models of intensified care surgical departments can be created. In addition, results clearly show that such model significantly improves both services and surgical results. This original model allows optimal use of resources favouring both service quality and patient satisfaction.

Borderline resectable pancreatic cancer and the role of neoadjuvant chemoradiotherapy.

Borderline resectable pancreatic cancer is now recognized as a distinct clinical entity. In these cases, neoadjuvant treatment could maximize the potential for an R0 resection and avoid R1/R2 resections. In fact, by analyzing, the current literature is evident that approximately one-third of initially borderline resectable pancreatic tumors may undergo successful resection following neoadjuvant therapy. However, the enormous difficulties in achieving a consensus and the variability in therapeutic algorithms have delayed progress in establishing strong evidence-based practices for diagnosis and treatment. In addition, the absence of a unique definition of borderline resectable pancreatic cancer remains a great obstacle for planning a therapeutic strategy and surgical decision-making. If on the one hand, we can finally say that the presence of only few prospective trials generates no strong data to support a specific neoadjuvant therapy regimen in borderline resectable pancreatic cancer, on the other hand, there are many studies on patients with borderline resectable pancreatic cancer who receive neoadjuvant therapy that can enjoy an R0 resection with similar outcomes to up-front resectable disease.

Influence of preoperative biliary drainage on surgical outcome after pancreaticoduodenectomy: single centre experience.

PURPOSE: Controversy prevails on the impact of preoperative biliary drainage (PBD) on postoperative complications and clinical outcome of pancreatic cancer. We determined whether PBD is associated with increased morbidity and mortality rates after pancreaticoduodenectomy. METHODS: A total of 131 consecutive patients who underwent pancreaticoduodenectomy (93 jaundiced, 38 with no jaundice) were included in this study. Overall, 57 % of jaundiced patients underwent PBD, while 43 % were not drained. The impact of PBD on postoperative morbidity and mortality was evaluated by means of logistic regression analysis. The Kaplan-Meier method was applied to determine the effect of PBD on survival of patients with malignant lesions. RESULTS: Mortality and morbidity rate was 3 % and 54.6 %, respectively. PBD was demonstrated to be the unique predictor of complications (odds ration [OR] = 10.18; 95 % confidence interval [CI], 3.65-28.39, p < 0.001). The jaundiced patients who were drained exhibited high frequencies of wound infection (p < 0.001), post-pancreatectomy haemorrhage (p = 0.0185) and hyperglycaemia (p < 0.001). In addition, an increased frequency of pancreatic fistula emerged among drained patients compared to those who were not drained (p = 0.036). PBD did not affect survival of patient with malignant lesions. CONCLUSIONS: With the exception of the classical indications, PBD should be carefully evaluated in patients with resectable pancreatic cancer.

Substance P and neprilysin in chronic pancreatitis.

BACKGROUND/AIMS: We aimed to analyze substance P (SP) and neprilysin (NEP), the membrane metallopeptidase that degrades SP, in chronic pancreatitis (CP). METHODS: SP and NEP mRNA levels were analyzed by qRT-PCR in tissue samples from 30 patients with CP and 8 organ donors. In addition, SP serum levels were determined before and after surgery in the same patients, by means of a competitive ELISA assay. Genetic and epigenetic analyses of the NEP gene were also performed. RESULTS: SP mRNA expression levels were higher in CP tissues compared to controls (p = 0.0152), while NEP mRNA showed no significant differences between CP and healthy subjects (p = 0.2102). In CP patients, SP serum levels correlated with those in tissue, and after surgical resection SP serum levels were reduced compared to the preoperative values. Failure of NEP to overexpress in CP tissues was associated with significant miR-128a overexpression (p = 0.02), rather than with mutations in the NEP coding region or the presence of hypermethylation sites in the NEP promoter region. CONCLUSION: Tissue and serum levels of SP were increased in CP, while NEP levels remained unaltered. In an SP/NEP-mediated pathway, it would appear that NEP fails to provide adequate surveillance of SP levels. Failure of NEP to overexpress could be associated with miRNA regulation.

Neuroimmune interactions in patients with inflammatory bowel diseases: disease activity and clinical behavior based on Substance P serum levels.

BACKGROUND AND AIM: The neuropeptide Substance P, plays a key role in modulating neuroimmune interactions in patients with inflammatory bowel diseases. We analyzed Substance P serum levels in patients with ulcerative colitis and Crohn's disease, to detail the involvement of the neuropeptide in the pathophysiology of these disorders. METHODS: Serum samples were collected from 61 patients with ulcerative colitis (24 with active and 37 with inactive disease), 66 patients with Crohn's disease (29 with active and 37 with inactive disease) and 45 healthy subjects, enrolled into the study. Neuropetide serum levels were measured by means of an ELISA/EIA. Associations with disease activity and patients clinical features were also taken into account. RESULTS: Compared to controls, Substance P serum levels were significantly increased in both patients with ulcerative colitis and Crohn's disease, (p<0.001). In patients with ulcerative colitis, levels paralleled disease activity (p=0.014), and the amount of the neuropeptide was considerably decreased during clinical and endoscopic remission of the disease, (p=0.025). Conversely, median Substance P levels did not differ between patients with active and inactive Crohn's disease. However, levels of the neuropeptide were more often elevated in patients with inactive and stricturing/fistulizing Crohn's disease, (p=0.002). CONCLUSIONS: Data underline that Substance P might exerts important immunomodulatory functions in inflammatory bowel disease. This study suggests a potential role for Substance P serum levels in monitoring intestinal inflammation in patients with inflammatory bowel disease.

A modified fast-track program for pancreatic surgery: a prospective single-center experience.

OBJECTIVE: The objective of this study is to evaluate the impact of a fast-track protocol in a high-volume center for patients with pancreatic disorders. BACKGROUND: The concept of fast-track surgery allowing accelerated postoperative recovery is accepted in colorectal surgery, but efficacy data are only preliminary for patients undergoing major pancreatic surgery. We aimed to evaluate the impact of a modified fast-track protocol in a high-volume center for patients with pancreatic disorders. METHODS: Between February 2005 and January 2010, 145 subjects had resective pancreatic surgery and were enrolled in the program. Essential features of the program were no preanaesthetic medication, upper and lower air-warming device, avoidance of excessive i.v. fluids perioperatively, effective control of pain, early reinstitution of oral feeding, and immediate mobilization and restoration of bowel function following surgery. Outcome measures were postoperative complications such as pancreatic fistula, delayed gastric emptying, biliary leak, intra-abdominal abscess, post-pancreatectomy hemorrhage, acute pancreatitis, wound infection, 30-day mortality, postoperative hospital stay, and readmission rates. RESULTS: On average, patients were discharged on postoperative day 10 (range 6-69), with a 30-day readmission rate of 6.2%. Percentage of patients with at least one complication was 38.6%. Pancreatic anastomotic leakage occurred in seven of 101 pancreatico-jejunostomies, and biliary leak in three of 109 biliary jejunostomies. Postoperative hemorrhage occurred in ten (6.9%) patients and wound infection in nine (6.2%) cases. In-hospital mortality was 2.7%. Fast-track parameters, such as normal food and first stool, correlated significantly with early discharge (<0.05). At multivariate analysis, lack of jaundice, and resumption of normal diet by the 5th postoperative day were independent factors of early discharge. CONCLUSION: Fast-track programs are feasible, easy, and also applicable for patients undergoing a major surgery such as pancreatic resection.

Reciprocal modulation of circulating CD4+CD25+bright T cells induced by extracorporeal photochemotherapy in cutaneous T-cell lymphoma and chronic graft-versus-host-disease patients.

The mechanisms of action of extracorporeal photochemotherapy (ECP) in cutaneous T-cell lymphoma (CTCL) are poorly understood. Recently, ECP has been shown to induce an increase in regulatory T cell (Treg) expression and functional activities in Graft-versus-host-disease (GvHD), whereas no data are available in CTCL patients. The aim of this study is to evaluate whether ECP is able to modulate the expression levels of the circulating CD4+CD25+bright subset in CTCL patients and whether these modifications are related to the disease course. The patient population included 43 CTCL and 15 chronic GvHD patients treated by ECP at our institutions since 1992. The expression of the circulating CD4+CD25+bright subset was analysed at baseline and sequentially during treatment by flow-cytometry. Fifty healthy donors were used as controls. The baseline circulating CD4+CD25+bright percentage values in CTCL (median: 4.3 percent) were similar to those of healthy donors, whereas GvHD showed significantly lower values (median: 1.5 percent; p<0.001). During treatment, CTCL patients were characterised by an early decrease (from 4.3 percent to 2.4 percent median after 6 months). The CD4+CD25+bright decrease was associated to the disease course, as it occurred in 91.3 percent of responding but in only 25 percent of PD patients (p=0.0001). On the other hand, a significant increase of CD4+CD25+bright cells was observed in GvHD. ECP induces a reciprocal modulation of the circulating CD4+CD25+bright cells in CTCL and GvHD, with a downregulation in CTCL potentially associated with the response mechanisms.

The ECM proteoglycan decorin links desmoplasia and inflammation in chronic pancreatitis.

BACKGROUND: Recurrent inflammation in chronic pancreatitis (CP) is not well understood. AIMS: To investigate whether decorin, an extracellular matrix (ECM) proteoglycan with macrophage modulating activity, is a pathogenic factor allowing diseased pancreatic stroma to sustain inflammation by affecting the cytokine profile of accumulating inflammatory cells. METHODS: Decorin was examined in 18 donors and 32 patients with CP by quantitative reverse transcription polymerase chain reaction (QRT-PCR), western blotting, and immunohistochemistry of pancreatic specimens. QRT-PCR was used to assess cytokine expression in donor peripheral blood mononuclear cells (PBMC), exposed or not to decorin in vitro, and to compare it with the cytokine profile of circulating and resident mononuclear cells (MNC) of patients with CP. RESULTS: In CP, desmoplasia is associated with overexpression of decorin in the growing ECM and enlarged pancreatic nerves. In culture, exposure of MNC to decorin stimulated expression of the MNC recruiting chemokine MCP-1. In biopsies, MNC infiltrates in decorin rich CP tissue showed a 300-fold upregulation of MCP-1 compared with decorin free peripheral blood, whereas no difference was found in basal MCP-1 expression in PBMC of patients versus donors. This effect was specific for MCP1-other inflammatory cytokines, such as interleukin 1beta and tumour necrosis factor alpha, were not affected. CONCLUSION: Decorin is a molecular marker of desmoplasia in CP, and excessive decorin may allow fibrotic masses to nourish and protract inflammation by deregulating the process of MNC accumulation and activation. These data provide a molecular basis for surgical resection of diseased tissue as a treatment option in CP.

Vanilloids in pancreatic cancer: potential for chemotherapy and pain management.

BACKGROUND: Success of chemotherapy and alleviation of pain are frequently less than optimal in pancreatic cancer patients, leading to increasing interest in new pharmacological substances, such as vanilloids. Our study addressed the question of whether vanilloids influence pancreatic cancer cell growth, and if vanilloids could be used for pain treatment via the vanilloid 1 receptor (VR1) in pancreatic cancer patients. METHODS: In vitro, the effect of resiniferatoxin (vanilloid analogue) on apoptosis and cell growth in pancreatic cancer cells--either alone, combined with 5-fluorouracil (5-FU), or combined with gemcitabine--was determined by annexin V staining, FACS analysis, and MTT assay, respectively. VR1 expression was evaluated on RNA and protein level by quantitative polymerase chain reaction and immunohistochemistry in human pancreatic cancer and chronic pancreatitis. Patient characteristics--especially pain levels--were registered in a prospective database and correlated with VR1 expression. RESULTS: Resiniferatoxin induced apoptosis by targeting mitochondrial respiration and decreased cell growth in pancreatic cancer cells without showing synergistic effects with 5-FU or gemcitabine. Expression of VR1 was significantly upregulated in human pancreatic cancer and chronic pancreatitis. VR1 expression was related to the intensity of pain reported by cancer patients but not to the intensity of pain reported by patients with chronic pancreatitis. CONCLUSIONS: Resiniferatoxin induced apoptosis in pancreatic cancer cells indicates that vanilloids may be useful in the treatment of human pancreatic cancer. Furthermore, vanilloid might be a novel and effective treatment option for neurogenic pain in patients with pancreatic cancer.

Dermal suspension flaps for McKissock's vertical bipedicle flap vs. classical McKissock's technique: comparison of aesthetic results and patient satisfaction.

McKissock's vertical bipedicle flaps technique is a common technique used in reduction mammaplasty. This technique includes a well-vascularised dermal-parenchymal pedicle for safe nipple-areola transposition, but it has been criticised as resulting in a flat breast with inadequate projection after long-term follow-up. Various techniques in which dermal suspension flaps are used have demonstrated decreased secondary ptosis. We used a dermal suspension flap technique for the vertical bipedicled flap of the McKissock's breast reduction and compared it with classical McKissock's technique by review of the patient charts, photographic analysis and patient-satisfaction questionnaire. Evaluations and measurements with postoperative photographs for the dermal brassiere group compared with the classical McKissock breasts were found to be statistically different. There were no differences in complication rates and patient satisfaction between the groups. McKissock's technique with dermal suspension flap is an easy and uncomplicated modification that provides additional advantages for prevention of the secondary ptosis of the reduced breasts in the long term.

Evaluation of alloderm and autologous skin in quadriceps muscles of rats for injection laryngoplasty.

There are three surgical methods utilized in treating glottic insufficiency: laryngeal framework surgery, reinnervation procedures and injection medialization. The trend towards the use of less invasive procedures led us to focus on injection medialization in this study. The advantages of vocal fold injection are that the procedure requires no external incisions, is easily applicable and can be applied in an office setting. Furthermore, injection medialization is applicable in cases of atrophic vocal fold and vocal fold scarring. In developing injection medialization, laryngologists are in search of an "ideal material" that should be biocompatible and resistant to resorption. In the initial applications of this method, synthetic materials were used. In the past 2 decades, however, researchers have become more and more interested in the advantages of biological materials. In our animal study, we investigated the behavior of AlloDerm and autologous skin injected in the quadriceps muscles of rats. The materials were easily injected. Histopathological and volumetric analyses were done; the rats were sacrificed the 1st day post-injection and subsequently in the 1st, 3rd and 6th months. AlloDerm's absorption levels were generally high, and its inflammation and fibrosis levels were low and medium. In the 6th month, histiocytic foreign body reaction was observed. The mean graft yield was 4.5%. Autologous skin results for inflammation and fibrosis levels were similar to those of AlloDerm. However, no foreign body reaction was observed in AS injected muscle. The graft yield was 74.6%. The growth of keratin cysts had an effect on the results of the graft yield.

Chronic pancreatitis: the perspective of pain generation by neuroimmune interaction.

Chronic pancreatitis (CP) is an inflammatory, often painful, disease of the exocrine pancreas which leads to exocrine insufficiency. The pathophysiology of pain in CP is incompletely understood. Several hypotheses have been advanced, including pancreatic and extrapancreatic causes. Here, the different pain hypotheses are discussed and evidence is presented that neuroimmune interactions are significant in the pathogenesis of pain generation and inflammation in CP. A better understanding of the complex cellular and molecular mechanisms of neuroimmune interactions should offer possibilities for innovative therapy and long term disease prevention.

Beneficial effects of Batimastat (BB-94), a matrix metalloproteinase inhibitor, in rat experimental colitis.

BACKGROUND AND AIMS: Matrix metalloproteinases (MMPs) represent a group of enzymes that regulate cell-matrix composition playing a major role in the inflammatory response. In the present study we evaluated the ability of the MMP inhibitor Batimastat (BB-94) to modify the course of experimental colitis induced in the rat by trinitrobenzensulfonic acid (TNB). METHODS: Colitis was induced in 40 rats by intracolonic administration of TNB. Animals were divided into four groups of ten rats each: group 1 received only intracolonic TNB, group 2 received TNB+5 mg/kg intraperitoneal BB-94, group 3 TNB+10 mg/kg BB-94 and group 4 TNB+20 mg/kg BB-94. The MMP inhibitor was administered 30 min before induction of colitis and twice daily until death. Ten rats receiving only intracolonic 0.9% saline served as controls. Animals were killed after seven days; segments of colon were removed and used for histological score of inflammation and myeloperoxidase (MPO) activity. RESULTS: Rats receiving only intracolonic 0.9% saline showed no evidence of colitis. The inflammation score was 0.9, MPO activity 0.235 U/mg. Group 1 (TNB-treated rats) exhibited a high inflammation score (12.4) and MPO activity (0.715 U/mg). Conversely, BB-94-treated rats showed, compared to the TNB group, a significantly lower inflammation score and MPO activity in a dose-dependent fashion. Group 2: inflammatory score 10.1, MPO activity 0.474 (p < 0.05 vs. TNB); group 3: inflammatory score 8.3, MPO activity 0.287 (p < 0.01 vs. TNB); group 4: inflammatory score 5.0, MPO activity 0.256 (p < 0.01 vs. TNB). CONCLUSIONS: Treatment with BB-94 has dose-dependent beneficial effects on the inflammatory alterations in rat experimental colitis. Thus, the inhibition of MMPs may represent a novel therapeutic approach for treatment of intestinal inflammation.

Connective tissue growth factor in human liver cirrhosis.

BACKGROUND: Connective tissue growth factor (CTGF) belongs to a family of factors that regulate fibrogenesis and wound healing. While the significance of transforming growth factor beta (TGF-beta) in liver fibrosis is well established, the role of CTGF in fibrosing hepatopathy is still unknown. METHODS: CTGF was analyzed in 10 normal and in 16 cirrhotic liver tissue samples. Northern blot analysis was used to examine the concomitant expression of CTGF and TGF-beta1 mRNAs, and the cellular localization of CTGF mRNA was studied by in situ hybridization. For identification of myofibroblasts and activated hepatic stellate cells, alpha-smooth muscle actin (alpha-SMA) immunohistochemistry was used. RESULTS: Northern blot analysis showed 6.5-fold enhanced expression of CTGF mRNA and 7.8-fold enhanced expression of TGF-beta1 mRNA in liver cirrhosis in comparison with normal controls (p<0.01). By in situ hybridization, CTGF mRNA was detectable in only a few spindle cells in the portal tracts in normal liver samples. In contrast, there was strong expression of CTGF mRNA in fibroblasts and myofibroblast-like cells present in fibrous septa surrounding the cirrhotic nodules, in stellate cells, in endothelial cells and in mesenchymal cells around ductular proliferations, and in ductular epithelial cells. There was a strong correlation between CTGF mRNA and TGF-beta1 mRNA as well as the degree of fibrosis (p<0.01). CONCLUSIONS: Overexpression of CTGF in liver cirrhosis, especially in fibroblasts/myofibroblasts and stellate cells, suggests that this novel factor may play an important role in hepatic fibrosis.