A novel method for treatment of chronic anal fissure: adipose-derived regenerative cells - a pilot study.

AIM: The purpose of this study was to investigate the safety and feasibility of autologous adipose-derived regenerative cells (ADRC) in the treatment of chronic anal fissure. METHOD: A prospective pilot study was conducted in six patients with chronic anal fissures at the First Surgical Clinic, Clinical Center of Serbia and at the BelPrime Clinic, Belgrade, Serbia. All patients were candidates for surgical treatment. The average duration of symptoms was 24 months. Pain assessment was quantified using a visual analogue scale and bowel continence was assessed using the Wexner incontinence score. Both were assessed before treatment and during each postoperative outpatient visit. Liposuction was performed under local or general anaesthesia. Extraction of ADRC was achieved with a closed automated medical device. The fat and ADRC were injected subcutaneously into the edge of the fissure. The rest of the pellet was infiltrated into the internal anal sphincter. The study has been registered at ClinicalTrials.gov (NCT02628522). RESULTS: Complete healing of the anal fissure and the disappearance of symptoms was achieved in all patients. The average time to complete pain cessation was 33.7 ± 15.0 days. All fissures healed after 3 months and remained healed 12 months after the procedure. There were no complications related to the procedure. CONCLUSION: The application of ADRC may be an alternative to lateral sphincterotomy and a reliable procedure which avoids faecal incontinence.

Matrix Metalloproteinase-2 and -9, Lactate, and Malate Dehydrogenase and Lipid Peroxides in Sera of Patients with Colorectal Carcinoma.

Matrix metalloproteinases (MMPs) are involved in tumour invasion and metastasis of colorectal carcinoma. Oxidative stress represents one of the possible mechanisms that activate inactive MMPs. Oxidative stress increases lipid peroxidation, which causes impaired membrane permeability and leakage of lactate dehydrogenase (LDH) and malate dehydrogenase (MDH) into circulation. Our aim was to assess the activity of MMP-2 and MMP-9 and its relation to the parameters of oxidative stress and membrane damage markers in patients with different TNM (tumour, lymph nodes, metastasis) stages of colorectal carcinoma. MMP-2 and -9 activities were evaluated by gelatin zymography. Oxidative stress was examined by quantifying serum malondialdehyde (MDA) concentration. LDH and MDH activities were determined spectrophotometrically. The activities of MMP-2 and -9 were significantly higher in the sera of colorectal carcinoma patients when compared to healthy subjects. There was a stage-dependent increase in relative MMP-2 activity compared to the overall serum gelatinolytic activity. The activity of MMP-9 was the highest in TNM III. The MDA concentration and the LDH and MDH activities were significantly higher in colorectal carcinoma patients than in controls, while LDH and MDH activities were stage dependent. There was significant correlation between serum MMP-2 and LDH activity in TNM II, III and IV patients. A stage-dependent increase of LDH and MDH activity was observed. We highlight here that MMP-9 could be a 100% sensitive marker of TNM stage III of colorectal carcinogenesis. In this study it was shown for the first time that gelatinolytic activity in colorectal carcinoma is associated with redox imbalance.

Mucinous adenocarcinoma of the urinary bladder after long-term duodeno-renal and colovesical fistula--case report.

Primary adenocarcinoma of the urinary bladder is a rare neoplasm. It accounts for 1-2% of all bladder carcinomas and sometimes may be found in the bladder diverticula. Fistula between duodenum and renal pelvis is another rarity while colovesical fistula is not so uncommon. We present a case of a 40 years old man who had surgery for colovesical and duodenorenal fistula and subsequently developed adenocarcinoma of the urinary bladder.

Sacral schwannoma found incidentally--report of a case.

Sacral schwannoma is a rare retrorectal tumor in adults. Postoperative sacral neurological deficit is difficult to avoid. Currently, there is no established consensus regarding best treatment options. We present a case of a 33 years old patient with atypical discomfort in lower abdomen and no neurological complaints who was diagnosed with a pelvic mass by abdominal ultrasound. CT, MRI and MSCT showed an inhomogeneous presacral mass involving right S1 sacral foramen. Although there were no neurological complaints, EMG and ENG showed a minor chronic lesion of L5 root bilaterally, more on the right side, affecting the fibers to the small muscles of the feet. We treated this patient with total extirpation of the mass without additional curretage. No radiotherapy was applied and postoperative neurological functions were preserved.

Function after intersphincteric resection for low rectal cancer and its influence on quality of life.

AIM: The aim of the study was to investigate function and quality of life after different types of intersphincteric resection (ISR). METHOD: Between January 2006 and February 2008, 45 patients (34 men and 11 women) with distal third rectal cancer underwent curative ISR. Function was evaluated using the Memorial Sloan Kettering Cancer Center bowel function questionnaire and Wexner score, anal manometry and measurements of rectal capacity were also performed. Quality of life was assessed using the Serbian version of the European Organisation for Research and Treatment of Cancer, quality of life questionnaire (EORTC QLQ-C30) and the translated version of the fecal incontinence quality of life scale (FIQL). RESULTS: There were no postoperative deaths. Partial ISR was performed in 22 (48.9%) patients, subtotal ISR was performed in 19 (42.2%) patients and total ISR was performed in four (8.9%) patients. Anastomotic leakage occurred in nine (20%) patients. Five (11.1%) of 45 patients had major (complete) incontinence and a further six (13.3%) patients had continuing frequent faecal leakage 12 months after ileostomy reversal. There was no significant difference in quality of life between the groups in the EORTC QLQ-C30 scale, but this was significantly altered by internal anal sphincter resection in two of the FIQL scales (coping/behaviour and depression/self-perception). CONCLUSION: Although ISR does not affect quality of life in general, the extent of internal anal sphincter resection has a negative impact on symptom-specific quality of life owing to faecal incontinence.

The role of pelvic MRI in assesment of combined surgical and infliximab treatment for perianal Crohn's disease.

AIM: To evaluate the role of pelvic MRI in diagnosis and assesment of combined surgical and infliximab treatment of perianal Crohn's disease (PACD). METHOD: 24 patients with signs of PACD were prospectively evaluated. They were previously treated with azathyoprin for a period of 6 months to 7 years and antibiotics and than started on Infliximab 5 mg/kg (IFX) at 0, 2 and 6 weeks induction protocol. Luminal CD activity was assesed by colonoscopy. Perianal Disease Activity Index (PDAI) was calculated to evaluate perianal fistulae activity. Surgical examination under anesthesia (EUA) was performed and non-cutting seton placed where appropriate. Pelvic MRI was performed in each patient before Infliximab treatment, and in half of the patients after IFX. MRI criteria were used to asses activity and remission of PACD. RESULTS: 14/24 (58.5%) patients had ileocolitis, 10/24 (41.5%) colitis, and in 22/24 (91.7%) rectum was affected. Median disease duration was 5.5 +/- 2.5 years. MRI revealed simple fistula in 4/24 (16.7%) and complex fistula in 20/24 (83.3%) patients. Abscess was present in 19/24 (79%) patients. Enterocutaneous and recto-vaginal fistula was found in 2 (8.3%) and 3 (12.5%) patients, respectively. Median PDAI before and 8 weeks after IFX treatment was 8.3 +/- 2.08 and 3.5 +/- 1.03, respectively (p = 0.00064). Incomplete response (reduction fistulae drainage by 50%) was found in 10/24 (42%) patients, complete response (no drainage) in 11/24 (46%) patients, while in 3/24 (12.5%) new fistula opened. Control pelvic MRI was performed in 13/24 (54%) patients. Of those, 9/13 (69%) had complete remission according to MRI criteria. Seton was removed after second IFX dose in 15/24 (62.5%) patients and placed again in 2/24 (8%) patients 4 months after completion of IFX treatment. CONCLUSION: In patients with PACD, pelvic MRI before and after IFX treatment is an important diagnostic tool to asses fistula tract localisation, reveal abscess, planning adequate treatment approach and assess the effect of treatment. Surgical decision to remove seton was in accordance with MRI criteria for remission in PACD.

[Penetrant injuries of colon--our experience].

In attemption to determine the place of primary repair in management of colon injuries, an open, non randomized clinical study was performed. Retrospective (RS) group of 62 patients according to exclusion criteria by Stone (S/F) and Flint (F1) was managed by one or two stage surgical procedure. Prospective (PR) group of 34 patients was managed using one stage repair non-selectively: two stage procedures were performed in 3 cases of advanced peritonitis and multi-segmental lacerations with impaired circulation of colon. In RS group 36 patients were managed by primary repair and in PR group, 31 were managed by primary repair. Both groups were of similar age/sex. Indexes of trauma severity were similar (TS, ISS, PATI). The latent time was shorter in PR group. Associated injuries to other body regions and abdominal organs were similar in both groups. S/F criteria and Flint grading in both (RS vs. PR) groups were similar. Comparison of attempted and successful primary repairs justifies the more liberal use of primary repair in early management of colon injuries.

Noncolonic cancer stem cells in bone marrow of colorectal cancer patients.

OBJECTIVE: To investigate whether preoperative noncolonic cancer stem cells in bone marrow (BM) of R0 colorectal cancer (CRC) patients are cancer cells and impact on liver metastases (LM) rates. METHOD: Prospective data on continuous CRC patients were collected from five centres. Bone marrow aspirates, taken at laparotomy, were sent to a single lab. Noncolonic cancer stem cells were defined according to UICC. A quantity of 3 x 10(6) BM cells per patient was processed with monoclonal antibodies against cytokeratin 20. APC or p53 gene mutation and microsatellite instability (MSI) were assessed in primary tumours (PT) by single-strand conformation polymorphism. Noncolonic cancer stem cells in BM of PT mutation or MSI-positive patients were isolated with immunobeads coated with magnetically labelled anti-human epithelial antigen antibody and DNA-screened for mutations. RESULTS: Although 199 patients were enrolled, 162 patients were available for analysis. No patients were lost to follow-up. Twenty-five (2-170) noncolonic cancer stem cells were found in BM of 40 patients. Twenty-two patients developed LM at 36-month follow-up. Adenomatous polyposis coli (APC) or p53 gene mutation or MSI were identified in the PT of 78 patients. The same gene mutations or MSI were not found in noncolonic cancer stem cells of the BM of these patients. After adjustment, there was no significant effect of confounding factors. Noncolonic cancer stem cells in BM had no impact on LM rates, cancer-specific death rates, or all death rates. CONCLUSIONS: Preoperative noncolonic cancer stem cells in BM of R0 CRC patients were not cancer cells and had no impact on LM rates.

Is there a future role for immunoscintigraphy in the diagnosis of colorectal carcinoma?

Immunoscintigraphy combines the advances in immunology and nuclear medicine to target tumor sites. Visualization of colorectal carcinomas is based on different monoclonal antibodies and their fragments against tumor-associated antigens labeled with gamma emitting radionuclides which accumulate in the tumor tissue due to their interaction with corresponding antigens. Available data on the role of immunoscintigraphy in detection of recurrence and metastases of colorectal carcinomas are reviewed. Despite a variety of investigations related to the application of immunoscintigraphy in diagnostics of colorectal cancer, using different radiolabeled immunoreactive agents and imaging methods there has not been a consensus among the investigators regarding the best modality of the method, including the specific radiopharmaceutical for this purpose. Some general conclusions concerning potentials of immunoscintigraphy in such diagnostics, including expectancy of the newly developed SPECT/CT systems, are suggested. The possibilities of PET imaging of colorectal carcinomas using monoclonal antibodies labeled with positron emitting radionuclides, as well as of the radioimmunoguided surgery and radioimmunotherapy are also discussed. Key words: Immunoscintigraphy, colorectal cancer, recurrences, metastases, radioimmunoguided surgery, SPECT/CT.

Influence of long-term radiotherapy on symptoms and signs of locally advanced primary rectal cancer of distant localisation.

This study is a part of a clinical trial in preoperative radiotherapy of low rectal cancer, conducted as a prospective and partly retrospective clinical study. It was designed to estimate the influence of long-term radiotherapy on symptoms of locally advanced rectal cancer. We included 49 patients with T3/4 stage adenocarcinoma (diagnosis confirmed by clinical, pathological and CT examinations) of the lower two thirds of the rectum, who were treated with long-term radiotherapy (45 Gy in 20-25 fractions) and questioned for the presentation of symptoms before and after the treatment. The chief complaints of these patients were the presence of blood in stool, abdominal and pelvic pain, straining (tenesmus) and the alteration in bowel movement. We found a significant decrease in symptoms and signs of the illness after the radiotherapy as well as the improvement of the quality of life.

Closure of loop ileostomy after low anterior rectal resection and restorative proctocolectomy.

OBJECTIVE: Low pelvic anastomoses are associated with a high leak rate. Loop ileostomies are commonly performed during ileoanal and coloanal anastomoses. This study was undertaken to review our experience with loop ileostomy closure after low anterior rectal resection and restorative proctocolectomy. PATIENTS AND METHODS: One hundred sixty five patients undergoing loop ileostomy closure at a single institution after coloanal and ileoanal anastomoses for rectal carcinoma (n = 148) ulcerative colitis (n = 9) and FAP (n = 8) from January 2003 to December 2006. Fecal diversion was maintained for a mean 13,5 weeks. RESULTS: Of the 165 patients, 100 were male and 65 female with mean age 59 (range 23-83 years). Overall, complication rate was 10,9 per cent. The common complication were sub occlusion six patients, occlusion three patients, wound infection eight patients and abdominal sepsis one patient. Complications required operative management in four cases. There was no mortality related to ileostomy. CONCLUSION: The study shown that ileostomy closure is a safe and effective with generally minor complications and should be considered as a safe alterative for fecal diversion.

Isolated splenic metastases of colorectal carcinoma--case report and review of literature.

It is very rare situation when surgeon can virtually expect a curative operation after revealing distal metastases of colorectal carcinoma. In case of isolated splenic metastases, splenectomy can result with good five year survival rate. There are no more than 15 cases of isolated splenic metastases publish in English speaking literature. This article reveals our case along with a literature review and brief discussion of diagnostic and therapeutic options.

Ischaemic colitis--review.

Colonic ischaemia, commonly referred to as ischaemic colitis, is the most common type of intestinal ischaemia. The term "ischaemic colitis" was used by Marston (1966) with three typical patterns of injury described: transient reversible ischaemia, ischaemic ulcers with stricturing, and gangrenous ischaemic colitis. Dominant presenting symptoms were colicky abdominal pain, vomiting, bloody diarrhea, and hematochezia. Patients often have minimal signs on clinical examination. Most patients were diagnosed at colonoscopy. Two regions that are believed to be anatomically vulnerable to ischemic disease are "Griffith's point", at the splenic flexure and "Sudeck's critical point", of the Drummond marginal artery. Clinically, ischaemic colitis is classified as non-gangrenous or gangrenous. Non-gangrenous ischaemic colitis involves the mucosa and submucosa and accounts for 80-85 percent of all cases of ischaemic colitis. Non-gangrenous ischaemic colitis is further subclassified into transient, reversible ischaemic colitis with a less severe form of injury and chronic, non-reversible ischaemic colitis, which includes chronic colitis and stricture and has a more severe form of injury. Gangrenous ischaemic colitis accounts for the remaining 15-20 percent of cases and manifests as the most seve-re form of injury. It includes acute fulminant ischaemia with transmural infarction that may progress to necrosis and death. Specific indications for operation include peritonitis, perforation, recurrent fever or sepsis, clinical deterioration in patients refractory to me-ical management. Relative indications include fulminant colitis, massive hemorrhage, chronic protein losing colopathy, and symptomatic ischemic stricture.

Non-Hodgkin's lymphomas of the large bowel-clinical characteristics, prognostic factors and survival.

The aims of this study were to review the clinical presentation of non-Hodgkin's lymphomas of the large bowel, to analyze the prognostic factors using univariate and multivariate methods, as well as the overall survival. We identified 24 cases at our clinic between 1991 and 2005, based on pathohistological analysis and standard diagnostic criteria established by Dawson et al. They accounted for 1.2% of all cases of the large bowel malignancies (24/2021) during this period. The following clinical information such as age, gender, symptoms, tumor localization, operation performed, histology grade, stage of disease, and adjuvant chemotherapy was obtained. Survival function was expressed by Kaplan-Meier curve and Log-rank test was performed for the difference in survival between two patient groups. Multivariate analysis was carried out using the Cox proportional hazard model. Overall mean survival time was 41.91 months. According to the univariete analysis, the factors influencing overall survival rate was operation type (elective and emergent). Tumor stage and operation type were independent prognostic factors for survival, as determined by multivariate analysis. Our results showed that tumor stage and operation type should be considered as the most important prognostic factors in patients with primary non-Hodgkin's lymphomas of the large bowel.

Molecular characterization of hsp90 isoforms in colorectal cancer cells and its association with tumour progression.

A key role of hsp90 in the activity of various oncogenic proteins and pathways is currently of intense interest. To clarify the molecular basis of biological behaviour of colorectal cancers we analysed the expression characteristics of hsp90 in cytosolic, nuclear and plasma membranous fractions of cancer cells. As determined by Western blot assay all hsp90 isoforms studied, alpha (84 kDa), beta (86 kDa) and hsp90N (75 kDa), were up-regulated and differentially expressed in various stages of colorectal carcinoma. The inducible hsp90alpha isoform is a component of invasive phenotype of cancer cells thus pointing to the importance of hsp90alpha for metastasis generation. The expression of hsp90beta is definitely higher in poorly-differentiated carcinomas than in well-differentiated cancers, suggesting an involvement of hsp90beta in the inhibition of cancer cell differentiation. Especially, the expression of cytosolic hsp90N isoform in malignant cells points to the possibility that induction or overexpression of hsp90N might be causally related to tumour formation. Hsp90N is the plasma-membrane-associated protein in poorly-differentiated colorectal cancers with metastasis. This suggests that the expression of hsp90N is elevated with progressive dedifferentiation often associated with advanced cancer stages. Hsp90 was exclusively localized in the invasive front in a majority of metastatic cancers as visualized by immunohistochemical study. Consistent with these facts, the frequent expression of hsp90alpha and hsp90N on the surface of colorectal cancer cells may enable hsp90 to act as a mediator of metastasis generation. The above results indicate more complex roles for hsp90 in colorectal tumourigenesis. In this way, the hsp90 would be at the crossroads of both signalling and cell migration events.

Bimonthly 24 h infusion of high-dose 5-fluorouracil vs EAP regimen in patients with advanced gastric cancer. A randomized phase II study.

BACKGROUND: To investigate the activity and toxicity of high dose (HD) infusional 5-FU in comparison to EAP regimen as first-line chemotherapy in patients with advanced gastric cancer. PATIENTS AND METHODS: Histologically confirmed measurable advanced gastric cancer, age < 72 yr, ECOG performance status 0-2, no prior chemo- and radiotherapy, adequate organ functions. TREATMENT: EAP arm: doxorubicin (40 mg/m(2)), etoposide (360 mg/m(2)), and cisplatin (80 mg/m(2)) every 28 d; HD 5-FU arm: 5-FU 2.6 g/m(2) 24 h infusion, biweekly. RESULTS: Sixty patients were randomized. Patient characteristics (arms EAP/HD 5-FU): Median age 57/55 yr, median PS 1/1, LAD (patients) 3/8, M1 (patients) 27/22. Median number of cycles (range): EAP arm 4 (2-8), HD 5-FU arm 2 (1-8). Worst toxicity per cycle (grade 3 and 4 in%): Neutropenia 20/3, thrombocytopenia 9/0, anemia 9/13, diarrhea 3/10, nausea 17/7, vomiting 10/0 for EAP and HD 5-FU arms, respectively. All patients were eligible for response in both arms. Confirmed response rate (95%CI): EAP arm 34% [16-50%]/HD 5-FU arm 10% (0-21%), no change: 46/40%, progression of disease: 20/50, respectively. Overall survival (range): EAP arm A 7 mo [3-27], HD 5-FU arm 6 mo (4-25). CONCLUSIONS: Infusional HD 5-FU showed a low incidence of severe toxicity. But given the low efficacy of 5-FU in the dosage we applied in the study, it cannot be recommended as a single treatment for further studies. Assessment of higher dose intensity and/or dose density of 5-FU, with introduction of other active drugs in combination, could be an option for further studies.

Allantoic remnants presenting as a giant retroperitoneal cyst.

Urachal anomalies are usually found in early childhood or just after birth. These usually involve patent ductus urachus, urachal cyst, umbilical-urachal sinus or vesicourachal diverticulum. Very rarely are urachal anomalies found in adults, usully as an infected urachal cyst. We are presenting a case of surgically removed giant urachal retroperitoneal cyst that was found by chance during the abdominal ultrasound examination of a 22 year old man who was initially treated for idiopathic hypertension.

Endoanal ultrasonography in establishing the diagnosis of fecal incontinence.

Visualisation of the rectum, rectoanal junction and adjacent structures is very demanding and challenging both with technical and medical side. Local staging of rectal and anal tumor and perianal neoplasm by conventional and sibgle slice CT or by barium enema study is not so valuable. These methods can not visualise fistulous communication in inflamatory bowel diseases and have not any role in evaluation of fecal incontinence. During last decade, endoscopic ultrasound and magnetic resonance imaging have been recognised as methods of choice in establishing diagnosis of rectal, perirectal, anal and perianal diseases. The aim of this article is to review the possibilities of endoanal ultrasound in evaluation of fecal incontinence.