The effect of neoadjuvant Imatinib therapy on outcome and survival after rectal gastrointestinal stromal tumour.

AIM: The study aimed to characterize the pathological and clinical response of rectal gastrointestinal stromal tumours (GISTs) to neoadjuvant Imatinib. METHOD: The medical records of patients with rectal GISTs who were diagnosed and treated in five medical centres in Israel between January 2002 and January 2009 were retrospectively examined. Twelve patients who fulfilled the inclusion criteria of nonmetastatic rectal GIST for which preoperative neoadjuvant treatment with Imatinib was considered were suitable for enrollment. RESULTS: Of the 12 patients, nine received neoadjuvant treatment with Imatinib. The three patients who had immediate surgery were excluded. There were five men and four women with a median age of 63 years and a median follow up of 32 months. All tumours were located in the lower two-thirds of the rectum. One patient had a complete clinical response, six had a partial response and two had stable disease. Seven patients subsequently underwent surgery; six had an R0 resection and one had an R1 resection. Three patients had recurrence. There was no disease-related mortality. The reduction in both tumour size and mitotic activity during preoperative Imatinib therapy was significant. CONCLUSION: Preoperative Imatinib therapy can shrink large rectal GISTs, improving the chances of successful radical surgery and decreasing the risk of considerable morbidity.

Rectal bleeding and previous anticoagulant treatment in patients with colorectal cancer do not predict outcome.

BACKGROUND: The aim of this study was to determine whether the outcome of patients with colorectal cancer who presented with bleeding and a history of anticoagulant treatment was different from those who did not have bleeding or previous anticoagulant treatment. METHODS: This was a single institution, retrospective study of patients with colorectal cancer with and without a history of rectal bleeding and treatment with anticoagulants, assessed for age, gender, tumor site, stage, recurrence rate, and survival. RESULTS: A total of 621 consecutive patients (309 men) with a mean age of 70 years (range, 36-94 years) diagnosed with colorectal cancer between 1998 and 2004 were studied. Of these, 149 patients (24%) were referred for symptoms of rectal bleeding and 161 patients (26%) had been previously treated with anticoagulants. A total of 592 patients (95%) underwent curative or palliative surgery; endoscopic polypectomy was performed in 3 cases only and in 26 patients (4%) surgery was not performed due to advanced disease or critical illness. Patients with bleeding and a history of anticoagulant treatment presented commonly with stage I cancer. In addition, tumor stage III was less common in patients with previous anticoagulant treatment irrespective of presenting signs. Disease-free and overall survival rates were similar in all groups, irrespective of bleeding at presentation or anticoagulant treatment. CONCLUSIONS: Rectal bleeding and anticoagulant treatment do not affect the outcome of newly diagnosed patients with colorectal cancer.

Combined treatment of basaloid anal carcinoma using cisplatin, 5-fluorouracil and resection of hepatic metastasis.

The combination of chemotherapy and radiotherapy with subsequent repeated local biopsy has become the standard treatment of epidermoid carcinoma. The optimal treatment of metastatic anal carcinomas is controversial. We present the case of 54-year-old woman with a diagnosis of metastatic basaloid anal carcinoma. The patient underwent resection of liver metastasis in combination with cisplatin + 5FU and local radiotherapy, without evident disease 3 years after diagnosis.

[Fournier's gangrene as a delayed complication of closed hemorrhoidectomy].

BACKGROUND: Fournier's gangrene is recognized as a synergistic necrotizing fasciitis of the perineum and abdominal wall along with the scrotum and penis in men and the vulva in women. The major sources of Fournier's Gangrene are dermatologic, anorectal and genitourinary infections. Although anorectum is remarkably rich in bacterial flora, transanal procedures are generally free of infectious or septic complications. Nevertheless, five cases of Fournier's gangrene post hemorrhoidectomy have been published. OBJECTIVE: To report a case of Fournier's gangrene as a delayed complication of closed hemorrhoidectomy and to demonstrate the management of such complication. PATIENT: A sixty-six years old male who had undergone an uncomplicated closed hemorrhoidectomy was readmitted to the hospital on postoperative day 7 for fever, perirectal erythema and tenderness accompanied by a dirty brown discharge from the wound. The patient was treated with fluid resuscitation and broad-spectrum antibiotics. Radical debridement of the perianal and scrotal region was performed accompanied by diverting colostomy. Four months later a reconstruction of the perianal area was performed by meshed split thickness skin graft and the colostomy was closed. CONCLUSIONS: Fournier's gangrene is a rare immediate or delayed complication of hemorrhoidectomy. A review of the limited available literature suggests that neither the surgical technique nor the medical history of the patient have an influence on the development of such a rare and fatal complication.

Expression of D-type cyclins in colon cancer and in cell lines from colon carcinomas.

Cyclins D1, D2 and D3 play important roles in cell proliferation and differentiation. Although their abnormal expression has been linked to cancer development and progression in a number of tissues, the expression of cyclin D2 and D3 proteins in colon cancer has not yet been characterised. In this study, we examined cyclin D1, D2 and D3 protein expression by Western blot analysis in tumour and adjacent normal colon tissues of 57 patients. In addition, we examined D-type cyclins protein expression in HT29 and LoVo39 cell lines from colon carcinomas, as a function of induced proliferation and differentiation. In both cell lines, the expression of the three D-type cyclins increased as a result of induced proliferation, whereas the expression of cyclin D3 increased as a result of induced differentiation. In colon tumours, cyclin D1 was overexpressed in 44%, cyclin D2 was overexpressed in 53% and cyclin D3 was overexpressed in 35% of the cases. We also found that in 16% of the cases, cyclin D3 protein expression was reduced in the tumour, as compared to the adjacent normal tissue. Examination of D-type cyclin protein overexpression in relation to the TNM stage of the tumours revealed that overexpression of cyclins D1 and/or D2, but not cyclin D3, is linked to colon carcinogenesis and that overexpression of cyclin D2 may be related to a higher TNM stage of the tumour.

Brachial plexus injury as a complication after colorectal surgery.

Peripheral neuropathy associated with anesthesia is a significant source of morbidity and the second most frequent cause of professional liability in anesthetic practice. Nerve injuries are a well-recognised complication of anesthesia. Brachial plexus neuropathy is a rare syndrome with an incidence of 1.6 cases per 100,000. Unfortunately, we have a limited understanding of the relations between conventional perioperative care and the genesis of peripheral neuropathy. We describe 3 cases of postoperative brachial plexus neuropathy that occurred after abdominoperineal anterior resection for rectal cancer. The symptoms resolved postoperatively in two patients by 8 weeks and in one patient by 10 weeks with conservative treatment. The differential diagnosis between brachial plexus neuropathy and other peripheral neuropathies is important, as the prognosis of brachial plexus neuropathy is generally better. The anesthetist and the surgeon should know the risks of positioning to prevent nerve injuries, and should be aware of the possibility of brachial neuropathy in order to properly make an early diagnosis.

Chronic perineal fistula as a late failure manifestation of pseudomyxoma peritonei syndrome.

Pseudomyxoma peritonei syndrome (PMP) is a rare but fascinating entity in surgical oncology. It consists of the accumulation of mucus in the peritoneal cavity, sometimes in huge amounts, in most of the cases after rupture of an appendiceal tumor. The diagnosis and management of PMP has changed significantly in the past 15 years, with the institution of an aggressive therapeutic combination: cytoreductive surgery and intraperitoneal perioperative chemotherapy. Few reports deal with the late manifestations and complications at endstage of the disease. The cases presented here are unique in that they illustrate a late 'failure' in the perianal area in three patients with long-term PMP.

Detection of abnormal proliferation in histologically 'normal' colonic biopsies using FTIR-microspectroscopy.

BACKGROUND: Abnormal crypt proliferation and development in the colon has been associated with premalignant stages of colon cancer. Conventionally, molecular markers are used to detect abnormal crypt proliferation. METHODS: In the present work, feasibility studies of FTIR-MSP to distinguish between normal and abnormal crypts from colon biopsies that show normal histopathological features have been undertaken. RESULTS: The results indicate that abnormal crypts show deviations in the pattern of absorbance in the Mid IR region along the crypt height when compared with the normal crypts. The crypts could be empirically classified into three groups such as crypts having a normal absorbance pattern for all biochemical components, crypts with abnormal absorbance pattern for some biochemical components and crypts with completely abnormal absorbance pattern along the height for all or most biochemical components studied by FTIR. The utilization of FTIR-MSP is proposed for diagnosis of abnormal metabolism at the molecular level of histologically completely normal-looking crypts, especially from those biopsies that are taken from sites far away from cancer. CONCLUSIONS: This method could give rise to a reduction in false-negative results during examination of biopsies using the conventional histopathological methods. The present method may be complementary to existing methods for precise demarcation of the zone of colostomy prior to colon cancer surgery.

Rectovaginal septal repair: case presentations and introduction of a modified reconstruction technique.

Rectovaginal fistula are a relatively rare kind of anorectal fistulas. Spontaneous healing is rare and the rectal advancement flap repair is the most popular procedure with success rates ranging between 60% and 80%. We present a new technique for repairing damage in the rectovaginal septum that consists of placing a folded polyglycolic acid mesh (Dexon) between the levator ani muscle closure area and the vaginal wall. This absorbable mesh separates the suture lines on the vaginal and rectal walls, and induces fibrosis and healing. The technique was performed in four women suffering from a rectovaginal fistula due to different causes. It was successful in all cases.

Lycopene in serum, skin and adipose tissues after tomato-oleoresin supplementation in patients undergoing haemorrhoidectomy or peri-anal fistulotomy.

Lycopene, the main carotenoid found in tomatoes and tomato-based products, has been reported to be protective against several types of cancer. Assessment of changes in plasma concentration of carotenoids following ingestion of lycopene-rich food sources does not necessarily predict changes in lycopene concentration or distribution of its isomers in other body tissues. Our aim was to determine the relationship between concentrations of lycopene and other tomato carotenoids in human serum and body tissues after tomato-oleoresin supplementation. Tomato lycopene oleoresin (30 mg/d) or a placebo was administered for 1 to 7 weeks to seventy-five volunteers undergoing elective haemorrhoidectomy or peri-anal fistulotomy. Carotenoid concentration and isomer distribution in blood and in the surgically removed skin and adipose tissues was measured by HPLC. The serum concentration of lycopene increased after supplementation from 0.26 (SD 0.12) to 0.52 (SD 0.25) micromol/l (n 35; P<0.0001). In the placebo group (n 40), lycopene serum concentration did not change significantly. Serum lycopene concentration after treatment was 2.2-fold greater in the lycopene group than in the placebo group, a slightly higher ratio than that found in skin and adipose tissue (1.6- and 1.4-fold higher than the placebo, respectively). A significant correlation between serum and tissue concentrations was found for both beta-carotene and lycopene in the placebo group, whereas in the lycopene-supplemented group the correlation between serum and tissues remained the same for beta-carotene but for lycopene was weak. Lycopene supplementation did not significantly change the proportion of all-trans v. cis isomers in the serum and tissues, despite the fact that more than 90 % of the supplemented lycopene was in the all-trans form. These results show that tomato-oleoresin supplementation increases lycopene concentrations in serum and in adipose tissue and skin. The ability to increase lycopene levels in tissues is one of the prerequisites for using it as a food supplement with health benefits.

Twelve-year survival after the diagnosis of locally advanced carcinoma of the pancreas: A case report.

The long-term survival rate of patients with carcinoma of the pancreas is low. Even more so, long-term survival of patients with metastatic pancreatic carcinoma is extremely rare. In this case report, we describe a patient with an unusual course of disease. This patient was diagnosed with locoregional carcinoma of the pancreas and therefore underwent gastroenterostomy and cholecystojeojenostomy without resection of the primary tumor. Later he was treated with radiotherapy and chemotherapy and survived 12 years, during 11 of which he had no evidence of disease. He died 12 years after the initial diagnosis from peritoneal dissemination of poorly differentiated carcinoma complicated with obstructive jaundice and sepsis. To our knowledge, this patient had the longest reported survival with locally advanced pancreas carcinoma that was not resected. The case is presented and discussed in this article.

Perianal and gluteal burns as a complication of hot water bottle treatment for anal fissure.

Contact with hot objects and surfaces often causes burns. We present a case of burns to the buttock and perineum caused by use of a hot water bottle to relieve the pain caused by an anal fissure.

Sigmoid colon carcinoma metastatic to the myometrium.

Metastases to the uterus from extragenital cancers are significantly rarer than metastases to the ovaries. Of the approximately 200 cases of metastases to the uterus from extragenital cancers that have been reported in the literature, more than half are cases of metastases from breast carcinoma and only 16 are cases of metastases from colorectal carcinoma. A case of isolated metastases restricted to the myometrium of the right uterine comu from sigmoid colon carcinoma, without involvement of the ovaries, is described. The patient who six months previously had surgery for sigmoid colon carcinoma presented with right lower abdominal pain and a palpable mass in the region of the right uterine cornu. The diagnosis of isolated metastases restricted to the myometrium of the right uterine cornu was confirmed by total abdominal hysterectomy and bilateral salpingo-oophorectomy. This case illustrates that a growing uterine mass in a patient with a history of primary extragenital cancer, regardless of whether abnormal uterine bleeding is present or absent, should alert the physician to consider the possibility of uterine metastases.

Diamond-shaped optical fiber delivery system.

OBJECTIVE: Physicians who use laser systems are looking for new fiberoptic delivery systems with better performance. We searched for a delivery system with high power and with a tip of high durability that may be reused many times. SUMMARY BACKGROUND DATA: The delivery systems currently found on the market can burn and break easily. The surgeon may either finish the surgery with a damaged delivery system, or have to switch to a new one during surgery, thus increasing the inconvenience and cost of the surgery. METHODS: Distal tips of fibers used with Nd:YAG and diode lasers have been shaped and polished according to their specific function, including excision, vaporization, and coagulation of tissue. RESULTS: We have developed several prototypes of optical fiber delivery systems, and in particular, we have developed a prototype of a delivery system, called the Diamond-Shaped Optical Fiber Delivery System, or Diamond. By making the tip of an optical fiber diamond shaped, we are able to obtain greater mechanical resistance than that of other delivery systems that were tested in our laboratory. In the Colorectal Unit, we applied it in surgical procedures such as perianal fistulectomy, hemorrhoidectomy, and excision of condilomata acuminata and pilonidal cyst and sinuses. During cutting and coagulating, the system performed well with no technical problems. CONCLUSIONS: A new delivery system (Diamond) gave satisfactory performance during surgical operations. Its main component, the diamond-shaped distal end, provided high durability and was reused many times, thus improving the quality of operations and reducing expenses greatly.

[Adjuvant therapy of colon cancer stage C MAC. Adverse effects and efficacy in the Department of Oncology, Soroka Medical Center in the years 1991-1994].

The National Institutes of Health (NIH) held a consensus conference which recommended 5-FU and levamisole as adjuvant chemotherapy for colon cancer MAC (Modified Astler Coller) stage C. From 1991-1994, 37 such patients diagnosed here were treated with 5-FU (intravenous dose of 450/mg/m2/d for 5 days and from day 29, once a week for 48 weeks) and oral levamisole (50 mg 3 times/d. for 3 days, every 2 weeks for a year), as suggested by NIH guidelines. 16 patients were males and 21 were females, mean age was 62 years and median 64. Cancer locations were: right colon (in 16, 43%), left colon (19, 51%), multiple colon primaries (2, 1%). 25 (68%) had 1-3 positive lymph nodes and 12 (32%) had 4 or more positive lymph nodes. Only 20 (54%) finished treatment as prescribed. In the others, 1 or both drugs caused side-effects for which the drugs had to be stopped. 6 patients relapsed while on treatment. The most common side-effects were diarrhea, stomatitis and bone marrow suppression. 3 were hospitalized due to neutropenic fever. 5-year actuarial survival of all patients was 61%; 5-year relapse-free survival was 61%; 5-year relapse-free survival of right versus left colon was 41% and 82%, respectively (p < 0.01). There was no significant difference in 5-year survival of those with 1-3 positive lymph nodes as compared to those with 4 or more (62% and 56%, respectively). 5-year survival in those who finished or did not finish treatment (excluding those who stopped treatment because of progressive disease) was 83% and 70%, respectively (NS). The 5-year survival of our series was similar to that of patients treated similarly elsewhere. The 5-FU and levamisole treatment was not tolerated well by our study population. It has recently been replaced in our service by a 5-FU and leucovorin regimen given for 6 months.

Double seton--a new modified approach to high transsphincteric anal fistula.

Despite the fact that complicated extrasphincteric anal fistulas have been recognized and treated for many years, there is still a lack of consensus among colorectal surgeons as to the optimum surgical approach. We have devised a modification of the seton technique, which we used in 23 patients without complications or recurrence.

Effects of oleic acid lung injury and positive end-expiratory pressure on central hemodynamics and regional blood flow.

The objective of our study was to investigate the influence on central and regional circulation of the application of positive end-expiratory pressure (PEEP=P) in a canine model of low hydrostatic pulmonary edema. Eight mongrel dogs with oleic acid-induced pulmonary edema were artificially ventilated with and without PEEP. Regional blood flow was determined using radioactive microspheres directly injected into the left ventricle. Regional blood flow to the brain was maintained under all experimental conditions, while the blood flow to the gastric fundal mucosa and to the pancreas significantly decreased following PEEP, oleic acid injection (OA) and with PEEP and oleic acid combination (P+OA). The renal blood flow decreased only during the P+OA phase. We conclude that the observed decrease in blood flow to the gastrointestinal mucosa and renal circulation in this acute low hydrostatic pressure pulmonary edema may correlate with the increased incidence of gastrointestinal and renal complications that accompany critically ill patients.