Efficacy of combined anti-TNF-alpha and surgical therapy in perianal and enterocutaneous fistulizing Crohn's disease--clinical observations from a tertiary Eastern European center.

BACKGROUND AND AIMS: Recently, anti-TNF-alpha therapy has increasingly been used in the treatment of perianal Crohn's disease (PCD), but there is only limited data regarding its short- and long-term efficacy. MATERIAL AND METHODS: The medical records of 68 patients treated with anti-TNF-alpha for PCD were assessed retrospectively. Rate of complex fistulas was 75%. Every patient received induction therapy, but in 20 cases the treatment was discontinued before week 52 due to funding regulations, an allergic reaction, or compliance problems. On week 12, the luminal activity decreased in more than 80% of the cases and the complete remission (CR) rate was about 60%; by the end of the first year, this ratio did not change substantially. Complete fistula closure was achieved in 26 cases (38.3%) and 53 patients (51.5%) showed a partial response during the 1-year period. Regarding both perianal and luminal activities, CR rate was achieved in 23 cases (33.8%). However, after the biological therapy was discontinued, recurrence of fistulas could be detected in every second patient. Additional surgical intervention was performed in 45% of patients during the 1-year period (seton drainage of fistulas and abscess drainage). CONCLUSION: The anti-TNF-alpha therapy combined with surgery is an effective treatment of PCD. Approximately every third patient revealed complete fistula closure, while half of the other cases showed a partial response. Due to the high rate of fistula recurrence after stopping the biological therapy, more than 1 year of anti-TNF-α treatment may be beneficial.

[Efficacy of tumor necrosis factor-alpha inhibitors in fistulising perianal Crohn's disease]. / A tumornekrózis-faktor-alfa-gátlók hatékonysága perianalis fisztulázó Crohn-betegségben.

INTRODUCTION: Tumor necrosis factor-alpha inhibitors are increasingly used in the treatment of severe Crohn's disease. AIM: The aim of the authors was to assess retrospectively the short and long term efficacy of tumor necrosis factor-alpha inhibitors in fistulising Crohn's disease. METHOD: Responses to therapy was determined using Crohn's Disease Activity Index, Perianal Disease Activity Index, the rate of complete fistula closure and the additional surgical procedures during biological therapy. RESULTS: After 12 weeks the perianal activity was decreased in more than 80% of the cases, and the complete remission rate was about 60%. After one year of therapy about one third of the patients had fistula closure, but after cessation of the biological therapy recurrence of fistulas was detected in every second patient. In most cases additional immunosuppressive therapy was necessary during biological treatment. During the one-year therapy period additional surgical treatments were performed in 45% of patients; seton insertion and abscess drainage were the most frequent procedures. CONCLUSIONS: Tumor necrosis factor-alpha inhibitor therapy is effective in the treatment of perianal Crohn's disease, however, additional immunosuppressive drugs and rectum sparing surgical procedures were necessary during the one-year treatment period. Because of the high rate of fistula recurrence, long term tumor necrosis factor-alpha treatment may be useful.

[Clinical and histopathological results after the neo-adjuvant treatment of advanced rectal tumors]. / Klinikai és hisztopatológiai eredmények elorehaladott rectumtumorok neoadjuváns kezelése után.

The role of the surgical intervention is decisive in treating colorectal tumors. The neo-adjuvant radio-chemotherapy has improved the efficacy of the treatment of advanced rectum tumors. In order to decrease the size and stage of advanced rectal carcinoma and to increase the rate of resecability, we introduced neoadjuvant radio-chemotherapy. We carried out neo-adjuvant and surgical treatment in case of 67 patients with rectal adenocarcinoma (T 2-4 N 1-2 M 0 ) between June 1, 2005 and July 31, 2008. The average age of the patients was 61.2 years, the division according to sex was 44 males/23 females. Regarding the local stage of the rectal process or the proximity to the sphincter, we applied radio-chemotherapy (radiotherapy 25 times altogether 45 Gy and on the first and last week for 5-5 days they received 350 mg/m 2 /day 5-FU and 20 mg/m 2 /day leucovorin chemotherapy, recently complemented with 3 x 1.8 Gy advanced boost radiation aiming at the macroscopic tumor site with security zone). Patients underwent surgery 8 weeks on average after restaging examinations. Thirty-eight patients underwent anterior rectal resection with double stapler procedure; there were 18 abdominoperineal rectal extirpations, 7 Hartmann operations and 4 per annum excisions. Compared to the preoperative staging, the histological evaluation of the resected specimens showed total remission (pT 0 N 0 ) in 11% and partial remission in 43%. The morbidity necessitating reoperation was 5.9%, without mortality and suture insufficiency. The long-term neo-adjuvant oncological treatment led to down-staging of rectal tumors in most cases and increased the resecability and rate of resection operations.

[The first molecular analysis of a Hungarian HNPCC family: a novel MSH2 germline mutation]. / Az elsó magyar hereditaer nem polypoticus colorectalis carcinoma család molekuláris vizsgálata: az MSH2 gén uj mutációja.

BACKGROUND: Hereditary nonpolyposis colorectal cancer is an inherited disease characterized by onset at an early age, an excess of synchronous and metachronous large bowel tumors and a variety of extracolorectal malignancies. Basal and squamous cell carcinomas of the skin are not customarily included in the tumor spectrum of the syndrome. The disease is caused by a germline mutation in one of the DNA mismatch repair genes, most commonly MSH2 or MLH1, and typically presents with microsatellite instability and frequent loss of mismatch repair protein expression in the tumor tissue. PATIENT: The case of a 62-year old woman who had a history of colon cancer at the age of 46 years, endometrial cancer at the age of 56 years, baso-squamous, and squamous cell cancer of the face at the ages of 53, 54, 62 and 58 years, respectively, and rectal cancer at 60 is reported. Her family fulfills the Amsterdam criteria for the diagnosis of hereditary nonpolyposis colorectal cancer. The baso-squamous cell, the squamous cell, the endometrial and the rectal cancers were assessed for the microsatellite instability status and the expression of the MSH2 and MLH1 mismatch repair proteins, and the p53 tumor suppressor protein by immunohistochemistry. Mutational screening using an automated capillary DNA sequencer was performed by the direct genomic sequencing of 17 fragments of the MSH2 gene, which covers promoter, all exons and flanking intronic regions. RESULTS: All cancers displayed microsatellite instability and were positive for the p53 protein. The immunohistochemical staining in the baso-squamous cell, the squamous cell, the rectal and endometrial cancers were negative for MSH2 and positive for MLH1 proteins. DNA sequencing analysis revealed a mutation c.2292G > A in exon 14 of the MSH2 gene, which is altering the 764. amino acid, the tryptophan to STOP codon (p.W764X). Thus the MSH2 protein is presumably truncated by 171 aminoacids. CONCLUSION: To the best of authors' knowledge, this is the first molecular characterization of a Hungarian hereditary nonpolyposis colorectal cancer family. According to the Human Mutation Database and International Collaborative Group of HNPCC Database, this mutation is novel, has not been reported previously. Cutaneous baso-squamous and squamous cell cancers may present as part of the HNPCC phenotype. Detection of the loss of mismatch repair protein expression and mismatch repair gene mutation mapping, represents a significant improvement of the diagnosis of this syndrome in Hungary. These examinations identify the mutation carriers who are at an increased risk of developing cancers.

[Multiple organ resections for the surgical treatment of locally advanced colorectal cancer infiltrating the urinary tract]. / Kiterjesztett (multivisceralis) mûtétek a vizeletelvezetô rendszert érintô elôrehaladott colorectalis carcinomák ellátására.

The authors present data on 13 patients operated on for the treatment of locally advanced colorectal cancer infiltrating the adjacent parts of the urinary tract. Based on prior diagnostic evidences, every surgical intervention has been indicated as an expected curative resection. All patients of this study underwent a curative resection. The origin of the advanced cancer was in 9 cases the sigmoid colon, in 3 cases the rectum and in 1 case the ascending colon. Beside the resection of the tumorous colon or rectum, a resection of the urinary bladder has been performed in 9, a nephrectomy in 3 and the resection of the ureter in 2 cases. An additional gynecological resection was made in 4 cases for tumors infiltrating the female internal genitals. No mortality and no serious complication needing reoperation occurred in these series. Based on their experiences of a series of 13 radically operated cases, the authors suggest extended multiple organ resection for the treatment of advanced colorectal cancer infiltrating the urinary tract.

[Causes of local recurrence after curative surgery for rectal cancer]. / A lokális recidíva okai a végbélrák radikális mûtétei után.

The rate of local recurrence (LR) has been 20-40% after resective surgery for rectal cancer by the traditional - Miles or Dixon - operative technics. The authors performed curative resection in 358 patients with rectal cancer in a 10 year period (01.01.1990 - 31.12.2000) in the Surgical Department of Szeged University. Since 01.01.1996 the authors changed this type of surgery for the Heald technics (total mesorectal excision - TME - with sharp dissection, using the UltraCision device) for the surgical treatment of middle or lower third rectal cancer. To compare the results of the two procedures, the authors analysed their material in two periods: Period I: 01.01.1991 - 31.12.1992: 62 patients operated on with the traditional operative technics; LR 15% within 2 years after surgery. Period II: 01.01.1997 - 31.12.1998: 78 patients operated on with the Heald technics (TME with sharp dissection); LR 6.4% within 2 years after surgery. Based on their results, the authors found that the modern operative technics by Heald, used in the second period of the study, was a relevant factor decreasing LR from 15% to 6.4%, while the gender, age of the patients, ratio of the abdominoperineal extirpation versus anterior resection (APRE/AR) and the free margin of more than 3 cm proved to be irrelevant.

[Subtotal colectomy for the treatment of obstructive left colon cancer. Follow-up results]. / Szubtotális colectomia a bal colonfél obstruktív vagy stenotizáló tumorainak primer ellátására. Utánvizsgálati eredményeink.

AIM: Subtotal colectomy (STC) involves an extended resection of the large bowel over the splenic flexure. In a period of 8 years, a total of 72 subtotal colectomies (STC) were performed for the treatment of large bowel obstructions or symptomatic stenosis caused by cancer of the left colon. A primary ileocolic latero-terminal anastomosis was made in each case. The aim of study was to evaluate the late results of procedure. PATIENTS AND METHODS: In a non-prospective, non-randomized study of 23 of the total of 72 STC cases, authors investigated the postoperative quality of life, the changes in the intestinal bacterial flora, and signs of a nutritional deficiency or of an accelerated bowel transit. METHODS: 1) H2 excretion test, 2) UDCA-PABA and 3) Schilling test for contaminated small bowel syndrome and bowel transit time, studied by means of a 4) barium meal and 5) radiopaque marker passage, and 6) registration of the number of defecations/day. RESULTS: The laboratory findings were in the normal range in each case. The daily number of defecations gradually decreased during the 3 months after the operation (mean 1.9/day). The lack of an ileocoecal valve did not result in bacterial overgrowth in the small bowel and the investigations did not reveal contaminated bowel syndrome. The oro-anal transit time was reduced in only four cases. Three months postoperatively, no patient had a deteriorated quality of life. CONCLUSIONS: STC offers 1) one-stage treatment for colonic obstruction in emergency surgery, 2) tumour removal with sufficient oncological radicality, and 3) primary reconstruction of the digestive tract, with a safe ileocolic anastomosis even in emergency cases. The follow-up study of 23 of the patients proved that loss of 60-80% of the colon did not cause any symptomatic disturbance of the digestive functions. The quality of life after surgery was normal, the slightly increased number (mean 1.9) of daily defecations was acceptable, and bacterial colonization of the small bowel did not occur.