Treatment of anal fistulas with Obsidian RFT®: just another autologous compound platelet-rich fibrin foam?

BACKGROUND: Sphincter-preserving techniques like autologous compound platelet-rich fibrin foam have gained popularity, offering potential for better functional outcomes in anal fistula treatment. The present study aimed to evaluate the efficacy and safety of Obsidian RFT®. METHODS: The study conducted a retrospective analysis from January 2018 to December 2022 on patients who received anal fistula closure with Obsidian RTF® at the Department of General Surgery, Medical University of Vienna. Clinical diagnosis, complemented by radiographic imaging, was employed to confirm inconclusive cases. Demographic and fistula characteristics and postoperative data were collected from electronic records following STROCSS criteria. RESULTS: Fifteen patients received Obsidian RFT® treatment for anal fistulas. We found no intra- and postoperative complications. The median hospital stay was 3 days. After a median follow-up of 32 months, a closure rate of 53.3% was detected. Non-significant differences were observed in various variables, yet trends emerged, indicating associations between abscess presence and non-healing fistulas. A distinct age threshold (≥ 42.7 years) served as an indicator for an inability to achieve anal fistula cure. CONCLUSION: Obsidian RFT® represents a safe, minimally invasive operative procedure. Approximately half the patients experienced healing, with better outcome in a younger population. TRIAL REGISTRATION: Ethical Approval number Medical University of Vienna (#1258/2018). This study was registered retrospectively in ClinicalTrials.gov (NCT06136325).

Allogeneic expanded adipose-derived stem cells in the treatment of rectovaginal fistulas in Crohn's disease.

AIM: Crohn's disease (CD)-related rectovaginal fistulas (RVFs) are rare, challenging to treat and associated with a high morbidity. Due to a significant lack of data, we aimed to analyse the safety and feasibility of allogeneic adipose-derived stem cells (ASCs) in the treatment of CD-related RVF. METHOD: Four consecutive patients with CD-related RVF underwent treatment with expanded allogeneic ASCs extracted from a healthy donor in a tertiary referral centre in 2019. None of the patients had an intestinal diversion at the time of the treatment. Follow-up was performed 6 months postoperatively. RESULTS: The median operation time was 45 min with a median hospital stay of 3 days. No intra-operative complications occurred. Three patients (75%) developed recurrent RVF after a median follow-up of 19 days. Two patients required surgical treatment including loose seton drainage due to discharge and pain. One patient developed recurrence of symptoms after 10 days, but refused further surgical therapy. Only one patient (25%) showed healing of the RVF, with re-epithelialization of both the vaginal and rectal opening and absence of clinical symptoms. CONCLUSION: Expanded allogeneic ASC therapy represents a novel safe treatment option for CD-associated RVF. Although efficacy appears limited, further controlled studies are required to draw robust conclusions.

Mesenteric granulomas independently predict long-term risk of surgical recurrence in Crohn's disease.

AIM: The risk factors that predict surgical recurrence in Crohn's disease (CD) remain controversial. Postoperative anti-tumour necrosis factor (anti-TNF) therapy might lower recurrence rates whilst the presence of mesenteric granulomas has been postulated to increase the risk. We hypothesized that mesenteric granulomas indicate disease severity and might predict the risk of surgical recurrence, irrespective of immunosuppressive therapy. METHOD: We performed a retrospective review of all consecutive patients undergoing operations for CD between January 2000 and December 2014 at a single tertiary referral centre and assessed the perioperative factors and histological findings at the time of surgery. Surgical recurrence rates and the immunosuppressive regimen were assessed through retrospective chart review and telephone interviews. RESULTS: A total of 274 patients were eligible for analysis. Median follow-up was 8.54 (5.48-14.42) years. A total of 63 patients (23.0%) underwent surgery for recurrent CD after a median of 4.75 (2.10-7.96) years. In final histology, 35 (12.8%) patients had mesenteric granulomas. TNF inhibitors were administered postoperatively in 104 (38.0%) and thiopurines in 137 (50.0%) patients. In univariate analysis, only the presence of mesenteric granulomas [hazard ratio (HR) 1.95; 95% CI 1.05-3.62; P = 0.035] significantly increased the risk for recurrent surgery while postoperative anti-TNF (HR 0.85; 95% CI 0.49-1.50; P = 0.581) or thiopurine therapy (HR 1.03; 95% CI 0.61-1.73; P = 0.916) did not. In multivariate analysis, only the presence of mesenteric granulomas significantly influenced the risk of surgical recurrence (HR 1.94, 95% CI 1.04-3.60; P = 0.037). CONCLUSION: Intestinal and mesenteric granulomas should be differentiated in pathology reports, because mesenteric, but not intestinal, granulomas may be associated with an increased risk of surgical recurrence.

Effect of pathologist's dedication on lymph node detection rate and postoperative survival in colorectal cancer.

AIM: As adjuvant chemotherapy in colorectal cancer relies on the identification of lymph node metastases, the pathologist's dedication may have a considerable influence on postoperative survival. METHOD: The aim of this retrospective study was to assess the impact of the pathologist's dedication on lymph node detection rate and postoperative survival in patients operated on by a single experienced colorectal surgeon within a 5-year period. We assessed 229 patients undergoing total mesorectal excision or complete mesocolic excision by the senior author between 1 January 2009 and 31 December 2013. Pathologists were grouped as 'general pathologist' or 'dedicated pathologist' depending on their dedication/specialization. RESULTS: Dedicated pathologists found statistically significantly more lymph nodes in colorectal specimens than general pathologists [23 (interquartile range 24) vs 14 (interquartile range 11), respectively; P < 0.001]. The detection rate of ≥ 12 lymph nodes per specimen was significantly higher in the dedicated pathologist group [65/74 (87.8%) vs 105/155 (67.7%); P = 0.016]. However, postoperative survival did not differ in the respective subgroups. In the multivariable analysis by Cox proportional hazard model, International Union against Cancer Stage IV was the only factor associated with decreased disease-specific survival (hazard ratio 28.257; 95% CI 3.850-207.386; P = 0.001). CONCLUSION: In our centre, the pathologist's dedication has an impact on lymph node detection rate but does not influence postoperative disease-specific survival.

The type of loose seton for complex anal fistula is essential to improve perianal comfort and quality of life.

AIM: The use of a loose seton for complex anal fistulae can cause perianal discomfort and reduced quality of life. The aim of this study was to assess the impact of the novel knot-free Comfort Drain on quality of life, perianal comfort and faecal continence compared to conventional loose setons. METHOD: Forty-four patients treated for complex anal fistula at a single institution between July 2013 and September 2014 were included in the study. A matched-pair analysis was performed to compare patients with a knot-free Comfort Drain and controls who were managed by conventional knotted setons. The 12-item Short Form survey (SF-12) questionnaire was used to assess quality of life. Additionally, patients reported perianal comfort and faecal incontinence using a Visual Analog Scale (VAS) and the St Mark's Incontinence Score. RESULTS: The Comfort Drain was associated with improved quality of life with significant higher median physical (P = 0.001) and mental (P = 0.04) health scores compared with a conventional loose seton. According to the VAS, patients with a Comfort Drain in situ reported greater perianal comfort with significantly less burning sensation (P < 0.001) and pruritus (P < 0.001). Faecal continence was similar in each group. CONCLUSION: The Comfort Drain offers improved perianal comfort and better quality of life compared with a conventional loose seton and therefore facilitates long-term therapy in patients with complex fistula-in-ano.

Surgical recurrence after primary ileocolic resection for Crohn's disease.

BACKGROUND: The current study was conducted to assess long-term outcomes after primary ileocolic resection for Crohn's disease (CD) and to identify factors associated with surgical relapse in the era of immunosuppressive medications. METHODS: Data were collected retrospectively on 116 consecutive patients, who underwent primary ileocolic resection for CD at a tertiary referral center between 1997 and 2006. Medical records were reviewed, and the use of immunomodulators was noted. The cumulative probability for a second operation due to recurrent CD was described by Kaplan-Meier curves. RESULTS: Ten patients (8.6 %) developed surgical recurrence after a mean follow-up period of 8.1 (±2.6) years. The percentage of patients not requiring further surgery was 96.5% and 88.0 % at 5 and 10 years, respectively. An urgent indication for surgery was significantly associated with the necessity of repeated intestinal resection (hazard ratio 5.6, 95 % confidence interval 1.2-27.0, p = 0.0145). In addition, postoperative exposure to azathioprine/6-mercaptopurine for more than 3 months decreased the probability of surgical recurrence significantly (hazard ratio 2.5, 95 % confidence interval 0.6-9.9, p = 0.0349). CONCLUSIONS: In contrast to previous studies, we observed a significant low surgical recurrence rate after primary ileocolic resection. Additionally, maintenance treatment with azathioprine/6-mercaptopurine after surgery may reduce the necessity for repeat surgical intervention.

Sexual function and quality of life after surgical treatment for anal fistulas in Crohn's disease.

BACKGROUND: The aim of this study was to assess sexual function and quality of life (QoL) in patients after surgery for perianal Crohn's disease. METHODS: Eighty-eight consecutive patients with perianal Crohn's disease, operated on at the Medical University of Vienna, completed a self-administered questionnaire including the International Index of Erectile Function (IIEF), Female Sexual Function Index (FSFI), Short Form-12 Health Survey (SF-12), and the Inflammatory Bowel Disease Questionnaire (IBDQ). Patients with a current stoma were excluded from further analysis. The median follow-up time was 104 months (range 3-186 months). Healthy subjects served as controls for each case and were matched by age (±6 years) and gender. Forty-seven (68 %) female and 22 male patients with a median age of 46.5 years (range 18-64 years) were analyzed. Eleven (16 %) patients had simple and 58 (84 %) complex anal fistulas. RESULTS: The median SF-12 physical health score of the patients was significantly lower (47.9 (range 25.5-57.2)) than that of the controls (54.3 (range 34.6-61.8); p = 0.03). Not surprisingly, the median total sore of the IBDQ of the controls was significantly better than that of the patients (controls: 188.5 (range 125-206.5), patients: 157 (range 60-199.5); p < 0.0001). Analysis with the multiple logistic regression test showed that type of operation, >1 perianal fistula opening, and active Crohn's disease were independent risk factors for a worse IBDQ (p = 0.03, p = 0.015 and p < 0.0001). Interestingly, the median FSFI and IIEF score were not found to be significant different in any domain. CONCLUSIONS: QoL but not sexual function is significantly influenced by surgery for perianal Crohn's disease.

Effect of preoperative fever-range whole-body hyperthermia on immunological markers in patients undergoing colorectal cancer surgery.

BACKGROUND: Previous studies have demonstrated beneficial immunological effects of fever-range whole-body hyperthermia (FR-WBH) as an adjunct to non-surgical cancer therapy. We conducted a study of preoperative FR-WBH in patients undergoing colorectal cancer surgery to evaluate perioperative, hyperthermia-induced immunomodulation. METHODS: The trial was conducted as a subject-blinded, controlled, randomized study. Subjects in the FR-WBH group (n=9) were treated with FR-WBH before operation under propofol sedation; the target core temperature was 39 (0.5)°C with 1 h warming and 2 h plateau phase. Subjects in the control group (n=9) were treated with propofol sedation only. Blood samples were acquired before and after treatment, after operation, and 24, 48 h, and 5 days after the end of surgery. The following parameters were measured: lipopolysaccharide (LPS)-induced tumour necrosis factor (TNF)-α, procalcitonin (PCT), interleukin (IL)-6/10, heat shock proteins (HSPs) 60, 70, and 90, human leucocyte antigen-DR (HLA-DR), and LPS-binding protein (LBP). RESULTS: HSPs were increased in the FR-WBH group after treatment [HSP60, 48 h postop: 143 (41)% vs 89 (42)%, P=0.04; HSP90, postop: 111 (33)% vs 64 (31)%, P=0.04; HSP70: P=0.40; FR-WBH vs control, P-values for area under the level/time curve]. TNF-α levels were elevated after surgery in the control group and remained near baseline in the FR-WBH group [24 h postop: 73 (68)% vs 151 (72)%, P=0.04]. PCT increased in both groups 24 h after surgery; in the control group, this increase was significantly higher (P=0.02). There were no significant differences for IL, HLA-DR, or LBP. CONCLUSIONS: The immune system to react to surgical stress, as measured by a panel of laboratory indicators, might be improved by preoperative FR-WBH.

Incidental appendectomy--standard or unnecessary additional trauma in surgery for colorectal cancer? A retrospective analysis of histological findings in 380 specimens.

BACKGROUND: Incidental appendectomy is a frequent but non-standard procedure during surgery for colorectal cancer. Incidental appendectomy during colorectal resections is performed at the discretion of the operating surgeon. METHOD: This retrospective study used data from 1352 consecutive patients who underwent surgery for colorectal cancer between 1993 and 2009 at the Medical University of Vienna. The authors evaluated histopathological results of appendices removed incidentally. In addition, complications and costs of the additional intervention were analyzed. RESULTS: Appendectomy had been performed in 314 (23.22%) patients because of appendicitis. Incidental appendectomy had been performed in 380 (28.11%) patients: 86 (22.63%) had a histologically completely normal appendix, a pathologic alteration was found in 289 (76.05%) and a neoplasm was found in seven (1.84%). No complications occurred from the additional surgical procedure. The costs and time effort were negligible. CONCLUSION: Incidental appendectomy is a safe procedure and can be integrated into surgery for colorectal carcinoma to avoid future complications. Pathological findings of the appendix, including neoplasm, are frequent but the clinical relevance remains questionable.

Repeat endorectal advancement flap after flap breakdown and recurrence of fistula-in-ano--is it an option?

AIM: Endorectal advancement flaps are an established treatment for high transsphincteric and suprasphincteric fistulae. The outcome of a repeat procedure in the case of flap breakdown and fistula recurrence remains unclear. The aim of the study was to analyse the outcome of repeat endorectal advancement flaps. METHODS: We retrospectively analysed patients with a repeat endorectal advancement flap procedure after flap breakdown and recurrence of fistula-in-ano of cryptoglandular origin who had been treated in our unit between 1994 and 2010. RESULTS: In all, 97 patients underwent an endorectal advancement flap procedure for fistula-in-ano and, of these, nine patients (five men, four women, 9.3%) subsequently underwent a repeat procedure due to flap breakdown. Median age was 40 years (range 25-60). Median follow-up time was 85 months (range 26-136). Seven full-thickness and two mucosal flap repeat procedures were performed because of eight transsphincteric and one suprasphincteric fistulae. The repeat procedure was successful in seven (78%) patients. In one of the two patients with repeat flap failure, a third flap procedure failed again. Disturbances of postoperative faecal incontinence were observed in five (55%) patients. Overall, the median postoperative Vaizey faecal incontinence score was 1 (range 0-4). CONCLUSION: Repeat endorectal advancement flap procedures are feasible and associated with a low recurrence rate and mild postoperative faecal incontinence. Therefore, a repeat procedure is a viable option in the case of a flap breakdown and fistula recurrence.

Haemorrhoids, constipation and faecal incontinence: is there any relationship?

AIM: Little is known about the association of haemorrhoids and anorectal function. Moreover, available data on the impact of constipation on the presence of haemorrhoids are conflicting. The present study aimed to assess any potential relationship between haemorrhoids and anorectal dysfunction. METHOD: All participants who attended the Austrian nationwide healthcare programme for colorectal cancer screening at four medical institutions were enrolled prospectively between 2008 and 2009. A colonoscopy and detailed anorectal examination were performed on all patients. Haemorrhoids were classified according to an international grading system. Faecal incontinence was defined as the involuntary loss of solid stool, liquid stool or gas, at least once a month. Constipation was recorded by a constipation scoring system. RESULTS: Of 976 participants, 380 (38.9%) were found to have haemorrhoids. There was an association between healthy individuals, patients with symptomatic and patients with asymptomatic haemorrhoids and incontinence of liquid stool. No association was found regarding incontinence for solid stool and gas. The median constipation score was significantly higher in those patients with haemorrhoids (grade I-IV) compared with patients without haemorrhoids (2.5 points (range, 0-19) and 3 points (range, 0-19); P = 0.0113). 'Painful evacuation effort' and 'assistance for defaecation (stimulant laxatives, digital assistance or enema)' showed a significant correlation with haemorrhoids (P = 0.0394 and P = 0.0143). CONCLUSION: Although the median constipation score was low in both groups, there was a significant association between constipation and haemorrhoids in adult patients.

Treatment of perianal sepsis and long-term outcome of recurrence and continence.

AIM: The study investigated the fate of patients with perianal sepsis of cryptoglandular origin. METHOD: All patients treated for perianal sepsis between January 1994 and December 2000 were retrospectively analysed regarding recurrence and faecal incontinence. Data collection was conducted by chart review and by telephone questionnaire using the Vaizey incontinence score. RESULTS: One hundred seventy-three (58%) of 300 patients were available for follow-up at a median period of 121 (77-171) months. Fistula-in-ano was diagnosed in 156 (90%) patients. After a single surgical procedure, 55 (32%) patients had no recurrence of perianal sepsis. In 118 (68%), recurrence required multiple procedures (median 3, range 2-19). If only a single incision and drainage was performed (n = 10, 6%), no faecal incontinence occurred. Drainage with fistulotomy (n = 45, 26%) induced mild incontinence in 9% and severe incontinence in 4%. After multiple procedures that were required in 118 (68%) patients, mild and severe faecal incontinence was found in 16% and 4% of them, respectively. CONCLUSION: Treatment of anal sepsis is associated with a high recurrence rate and a substantial risk of faecal incontinence.

Haemorrhoids and quality of life.

AIM: There are few studies into the quality of life of patients with haemorrhoids. The aim of this study was to assess the quality of life of patients with haemorrhoids in an adult general population. METHOD: Participants, who attended the Austrian nationwide healthcare programme for colorectal cancer screening at four medical institutions, were enrolled prospectively between 2008 and 2009. A colonoscopy was performed in all patients. Haemorrhoids were classified according to an international grading system and defined as symptomatic in cases with bleeding, itching, soiling or pain. Quality of life was measured by the Short Form-12 Health Survey. RESULTS: Of 976 participants, 380 patients (39%) had haemorrhoids. The median physical health score was 52.6 (range 20.6-61.3) in the symptomatic and 53.2 (range 16.2-61.3) in the asymptomatic group (P = 0.7993). The median mental health score showed also no significant difference between both groups [symptomatic group, 52.8 (range 12.4-62.6); asymptomatic group, 54.8 (range 18.7-67.2); P = 0.0738]. CONCLUSION: Haemorrhoids, irrespective of their degree, do not influence quality of life measured by the Short Form-12 Health Survey.

Endo-sponge assisted treatment of anastomotic leakage following colorectal surgery.

AIM: Endo-sponge assisted treatment (endo-sponge) represents a novel approach to treat patients with anastomotic dehiscence following anterior resection for rectal cancer. Yet, limited data are available to predict success, compatibility with radiotherapy and/or chemotherapy as well as acceptance by the patients. METHOD: Between September 2007 and June 2008, nine patients suffering from anastomotic leakage after anterior rectal resection (n = 6) or suffering from leakage of rectal stump following Hartmann's procedure (n = 3) were treated by endo-sponge. We recorded clinical outcome and patient's comfort using a 10-point visual analogue scale (VAS). RESULTS: Median time of endo-sponge treatment was 3 weeks (range: 2-8). There were no minor or major complications. In 6 (66.6%) patients, the anastomotic leakage healed successfully. Three patients showed no response and needed further surgical intervention. The lack of success was due to complexity of the leakages, which comprised either more than 270 degrees of the circumference or consisted of two distant fistulas. Formation of granulation tissue was unaffected by chemotherapy. For the question 'alteration in daily life activity', a median score of 5 (range: 1-9) was found. Measuring 'pain sensation' during endo-sponge treatment patients scored a median of 3 (range: 0-6). CONCLUSIONS: Endo-sponge treatment can be recommended as an alternative approach to treat pelvic sepsis following anastomotic dehiscence or rectal stump insufficiency. Extended leakages should be treated by different approaches having little probability of successful healing, but can lead to discomfort for the patient. Radiochemotherapy does not cause a problem for application of the endo-sponge.

Short-term complications of wide-lumen stapled anastomosis after ileocolic resection for Crohn's disease: who is at risk?

AIM: There is growing evidence that stapled anastomoses are similarly effective compared to hand-sewn anastomoses in Crohn's patients. This study was designed to assess safety and limitations of wide-lumen stapled ileocolic anastomoses. METHOD: All patients with ileocolic resections for Crohn's disease perfomed between 1998 and 2006 were studied. A stapled anastomosis was constructed whenever possible. Potential risk factors for postoperative complications were recorded, retrospectively. Univariate and multivariate analyses were performed. RESULTS: In 209 out of 220 cases (95%, 132 primary operations) stapled anastomoses were performed. Eleven patients underwent a hand-sewn anastomosis owing to massive bowel dilatation (n = 7) or increased wall thickness (n = 4). There were 10 major (4.5%; surgical: 8, medical: 2) complications including two anastomotic leaks and one anastomotic bleed (all from stapled anastomoses) and one death not related to the anastomosis. Minor complications occurred in 25 patients. In multivariate analysis, major surgical postoperative complications were significantly associated with a low level of albumin (P = 0.0113) and previous resections for Crohn's disease (P = 0.0144). CONCLUSION: Stapled ileocolic anastomosis was safe in the majority of Crohn's patients. The most important limitation was technical impracticability. A low level of albumin and a history of previous resection increased the risk of postoperative complications.

Improvement of a dendritic cell-based tumour vaccine by an influenza virus.

BACKGROUND: Induction of cytotoxic T cells by dendritic cells (DCs) is a promising approach to tumour-immunotherapy. A standardized effective preparation of DCs remains a challenge for clinical application. MATERIAL AND METHODS: We assessed whether influenza A partial NS1 deletion (NS1-124) - or complete NS1 deletion (delNS1) vaccine viruses can be employed to enhance monocyte-derived dendritic cell (MODC)-based T-cell stimulation directed against malignant cells in vitro. RESULTS: Infection of cultures containing human MODCs and CD3(+) T cells with NS1 deletion viruses led to an increased induction of type I interferons and IL-6 compared with infection with wild-type virus. This correlated with the fact that infection of MODCs with NS1 deletion viruses but not with wild type virus led to stimulation of a cytotoxic T-cell (CTL) response against the Panc-1 cells, which were used as cell lysate to prime the MODCs. Moreover, stimulation of MODCs with Panc-1 tumour cell lysate obtained via lysis with the complete deletion virus delNS1, but not with the partial NS1 deletion virus also enhanced the CTL response against the tumour cells. Induction of function CTL response in those assays correlated with an increased proliferation of CD8(+) T cells. CONCLUSIONS: The pro-inflammatory capacity of influenza NS1 deletion vaccine viruses could serve as an adjuvant-like agent to improve preparations of MODC-based anti-cancer vaccines. The complete NS1 deletion virus appears to be more potent as adjuvant when used for production of tumour lysates.

Postoperative course and long term follow up after colectomy for slow transit constipation--is surgery an appropriate approach?

OBJECTIVE: Patients with slow transit constipation who do not respond satisfactorily to common medical treatment are considered candidates for colectomy. The present observational long term study was designed to assess outcome after surgery. METHOD: Twenty consecutive patients were treated by colectomy for slow transit constipation between 1996 and 2004. Preoperative and postoperative data were reviewed by using our institutional database. A questionnaire including validated scoring systems and questions about complications and subsequent surgical interventions was sent to all available patients. RESULTS: Three patients (15%) died perioperatively. Median long term follow up was 84 months. Ten patients (50%) needed further operations after colectomy: Three patients (15%) had surgery during the early postoperative period, seven patients (35%) during follow up. A total of 31 operations had to be performed in these patients. Twelve patients (86%) responded to the questionnaires. Their median Wexner constipation score was 11.5 (range 8-23). Six patients fulfilled the Rome II criteria for constipation. The median Vaizey incontinence score was 7.5 (range 0-22). The median GIQLI showed 80 points (range 32-129). CONCLUSION: Morbidity and mortality rate after colectomy were inadmissibly high. Taking into account the poor functional results, we cannot recommend colectomy for slow transit constipation.

Dendritic cell-based vaccination in solid cancer.

PURPOSE: Dendritic cell (DC)-based immunotherapy is rapidly emerging as a viable tool in cancer treatment. This approach has been used mostly in patients in the presence of defined tumor antigens such as melanoma. In this study, cancer patients with advanced disease that lacks defined tumor antigens were vaccinated with tumor lysate-pulsed DCs. PATIENTS AND METHODS: Twenty patients (pancreatic, hepatocellular, cholangiocellular, and medullary thyroid carcinoma) with stage IV disease were enrolled in the study. In 3-week intervals, freshly isolated autologous CD14 magnetic bead-selected monocytes were cultured in granulocyte-macrophage colony-stimulating factor and interleukin-4 to obtain immature DCs. These cells were pulsed with autologous tumor lysate and matured with tumor necrosis factor alpha. Mature DCs were applied into a groin lymph node, under ultrasound guidance. Adjuvant interleukin-2 (20,000 U/kg) was given subcutaneously daily, for 12 days, after each vaccination. Toxicity, tumor marker profile, immune response, and clinical response were determined. RESULTS: Vaccination was well tolerated. No physical signs of autoimmunity were detected. DC vaccination induced delayed-type hypersensitivity reactivity in 18 patients. Tumor marker responses were observed in eight patients. In addition, in three patients the generation of interferon gamma-positive T cells was induced during the vaccination. Objective changes in measurable lesions or tumor markers were evident in seven of 20 assessed patients. None of the patients was found to meet the criteria for partial or complete responses. CONCLUSION: These data indicate that vaccination with autologous tumor-pulsed DCs generated from peripheral blood is safe and can induce tumor-specific cellular cytotoxicity. Clinical responses are achievable, even in patients with advanced disease.