Management of recurrent or metastatic retroperitoneal soft-tissue sarcomas.

UNLABELLED: Retroperitoneal soft tissue sarcomas remain a serious therapeutic problem. The aim of the study is to define the optimal treatment strategy of patients with locally recurrent or metastatic retroperitoneal soft tissue sarcomas. MATERIAL AND METHODS: A retrospective study was performed.Between 2001 and 2013, 89 patients with retroperitoneal soft tissue sarcomas were surgically treated in the University Hospital Queen Joanna ISUL and the Specialized Hospital for Active Treatment in Oncology Sofia. Clinicopathological data were investigated with SPSS 19. RESULTS: The mean time of onset of the first and second relapse of sarcomas was 23 and 13 months, respectively. Over 40% of the studied patients underwent more than one operation because of recurrence. Ability of radical extirpation of the tumour decreased with each subsequent relapse. The 5 year survival rate was 60% for patients with primary combined radical resection versus 28% for patients with partial resection. In the presence of metastatic lesions the 3 year survival rate was only 22%. CONCLUSION: Local recurrences, the presence of distant metastases and the ability of radical extirpation are the main long term prognostic factors.

Short versus conventional preoperative radiotherapy of rectal cancer: indications.

PURPOSE: Preoperative radiotherapy (RT) at high-dose short-course or at conventional fractions for rectal cancer has proven effect in increasing the tumor control. The aim of this study was to test the impact of 2 different preoperative RT schemes on local recurrence, distant metastasis and survival rates and to defi ne the indications for each of them. PATIENTS AND METHODS: The study included 84 patients with biopsy-proven rectal adenocarcinoma of the middle and lower third, clinically staged T2-T4, N0-2, M0. Group I patients (n=51) received a total dose of 25 Gy in 5 fractions of 5 Gy each for 5 consecutive days; operation was performed 3-5 days later. Group II patients (n=33) received a total dose of 50 Gy in 25 fractions of 2 Gy each in 5 weeks, followed by surgery after 4-5 weeks. Surgery included abdomino-perineal resection (APR) for tumors of the lower half of distal rectum, abdomino-transanal resection (ATR) for tumors of the upper half of distal rectum and anterior resection (AR) for tumors of the middle rectum. RESULTS: After a median follow-up of 53 months (range 22-84) overall survival (OS) of all patients at 4 years was 84% and the distant metastasis-free survival (DMFS) 82%. For stage II patients only, OS and DMFS was 100% in both preoperative RT groups. For stage III patients, OS in group I and II was 72% and 70%, respectively (p >0.05) and DMFS 66% and 68%, respectively (p >0.05). Local recurrence - free survival (LRFS) for all stages was 94% with 5 x 5 Gy and 25 x 2 Gy; for stage ?? only it was 100% and for stage III only 90%. However, the use of short preoperative 5 x 5 Gy scheme for tumors of the lower third of the rectum and sphincter-saving surgery was accompanied with higher rates of local recurrence: 11% after 5 x 5 Gy vs. 0% after 25 x 2 Gy. Partial tumor regression with 50 Gy of conventional RT was achieved in 79% of the cases. Such regression was not possible to assess for the 5 x 5 Gy group since surgery was performed 3-5 days after RT. No late adverse effects on normal tissues were observed with any scheme of preoperative RT. CONCLUSION: The conventional preoperative RT with 50 Gy proved more effective for advanced rectal cancer (T4 or N2) and for sphincter-saving resections for lower-lying tumors. The short scheme 5 x 5 Gy is appropriate for less advanced tumors (T2-3, N0-1), therefore requiring accurate clinical staging.

In vivo transfection and/or cross-priming of dendritic cells following DNA and adenoviral immunizations for immunotherapy of cancer--changes in peripheral mononuclear subsets and intracellular IL-4 and IFN-gamma lymphokine profile.

In order to provoke an immune response, a tumor vaccine should not only maximize antigen-specific signals, but should also provide the necessary "co-stimulatory" environment. One approach is to genetically manipulate tumor cells to either secrete lymphokines (GM-CSF, IL-12, IL-15) or express membrane bound molecules (CD80, CD86). Furthermore, patient dendritic cells can be loaded with tumor-associated antigens or peptides derived from them and used for immunotherapy. Genetic modification of dendritic cells can also lead to presentation of tumor-associated antigens. Transfection of dendritic cells with DNA encoding for such antigens can be done in vitro, but transfection efficiency has been uniformly low. Alternatively, dendritic cells can also be modulated directly in vivo either by "naked" DNA immunization or by injecting replication-deficient viral vectors that carry the tumor specific DNA. Naked DNA immunization offers several potential advantages over viral mediated transduction. Among these are the inexpensive production and the inherent safety of plasmid vectors, as well as the lack of immune responses against the carrier. The use of viral vectors enhances the immunogenicity of the vaccine due to the adjuvant properties of some of the viral products. Recent studies have suggested that the best strategy for achieving an intense immune response may be priming with naked DNA followed by boosting with a viral vector. We have successfully completed a phase I and phase II clinical trials on immunotherapy of prostate cancer using naked DNA and adenoviral immunizations against the prostate-specific membrane antigen (PSMA) and phase I clinical trial on colorectal cancer using naked DNA immunization against the carcinoembryonic antigen (CEA). The vaccination was tolerated well and no side effects have been observed so far. The therapy has proven to be effective in a number of patients treated solely by immunizations. The success of the treatment clearly depends on the stage of the disease proving to be most efficient in patients with minimal disease or no metastases. A panel of changes in the phenotype of peripheral blood lymphocytes and the expression of intra-T-cell lymphokines seems to correlate with clinical improvement.

Photodynamic therapy in lung and gastrointestinal cancers.

Twelve central bronchial carcinoma patients and two gastrointestinal (GI) tract (oesophageal and colonic) early-stage cancer patients were treated with photodynamic therapy (PDT). Haematoporphyrin (HP/5, Jacopo Monico, Italy) at a dose of 5 mg kg-1 body weight was used as photosensitizer. Laser light at 628.2-630 nm generated by two different laser systems (gold vapour laser (I.P. Optics, Sofia, Bulgaria) in lung cancer cases and an argon dye laser system (Spectra Physics, Mountain View, U.S.A.) in GI tract cancers) was used. Lung cancers were irradiated 48 h after drug administration and GI tract cancers were irradiated 72 h after infusion of the photosensitizer. Both tumour sites were treated with a total energy dose in the range 350-600 J cm-2. Efficiency of PDT in lung cancer was evaluated by X-rays and endoscopic and functional respiratory tests for bronchial de-obstruction. Complete remission after PDT of GI tract cancers was considered to be tumour eradication (histologically and cytologically proved) and a tumour-free interval of at least 12 months.

Is there an alternative approach to abdominoperineal resection for the treatment of very low lying rectal cancer? Five-year results.

PURPOSE: To investigate whether sphincter-saving surgery combined with preoperative radiotherapy and postoperative adjuvant chemotherapy can compare successfully with abdominoperineal resection in the treatment of very low lying rectal cancer. PATIENTS AND METHODS: Two groups of patients were studied. Group I included 65 patients (T2-3 N0-2 M0) with very low lying rectal cancer treated since 1995 by a sphincter- saving surgical procedure. All of them received preoperatively external radiotherapy and postoperatively adjuvant chemotherapy with 5-fluorouracil (5-FU) and folinic acid. This group was prospectively evaluated. Group II included 122 patients with the same tumor stage and location as Group I, who were treated by abdominoperineal resection and were retrospectively evaluated. The rate of local recurrence was compared between the two groups. RESULTS: In Group I patients the local recurrence rate was 13.84% (9 patients) for a period ranging from 6 months to the end of the second year after the operation. This group of patients were followed up to 60 months after the initial treatment. The local recurrence rate in Group II patients was 17.21% (21 patients; p >0.05). CONCLUSION: We consider that sphincter-preserving surgery combined with preoperative radiotherapy and postoperative adjuvant chemotherapy represents a successful alternative to abdominoperineal resection of very low lying rectal adenocarcinoma.

Different chemotherapy schedules in metastatic colorectal cancer: a response and survival analysis.

PURPOSE: To evaluate the response rate and overall survival (OS) of chemotherapy-naïve patients with metastatic colorectal adenocarcinoma treated with 4 different chemotherapy regimens. PATIENTS AND METHODS: One hundred fifty-eight patients with metastatic colorectal cancer (CRC) were included in this prospective study. The treatment regimens were as follows: a) Intraarterial (i.a.) chemotherapy: 5-fluorouracil (5-FU) 600 mg/m(2)/day by 120 hour-infusion, mitomycin C 8 mg/m(2) day 1, and epirubicin 80 mg/m(2) day 5, every 3 weeks, b) Intravenous (i.v.) chronochemotherapy: 5-FU 800 mg/m(2) i.v. infusion during 18.00 h-06.00h, leucovorin (LV) 100 mg/m(2) i.v. infusion during 18.00h-06.00h; and cisplatin 20mg/m(2) i.v. infusion, during 10.00h-18.00 h, all given on days 1-5, every 3 weeks, c) Scheme: 5-FU 500 mg/m(2) i.v. bolus, days 1-5, vincristine 1.2 mg/m(2) i.v. bolus, day 1, CCNU 120 mg/m(2) per so (p.o.), day 5, every 3 weeks. Scheme I was used as control group, d) Scheme II: 5-FU 425 mg/m(2) i.v. bolus, days 1-5, and LV 50 mg/m(2) i.v. bolus, days 1-5, every 3 weeks. The patients received 3-26 cycles of chemotherapy. The results taken were compared using the Kaplan-Meier life-table method, logrank test, Cox proportional hazard model, and Cox model with time-dependent covariates. RESULTS: Nine (26%) out of 34 patients with i.a. chemotherapy achieved complete response (CR), 8 (24%) partial response (PR), and 11 (32%) stable disease (SD). In the group of 42 patients with chronochemotherapy 4 (10%) achieved CR, 15 (36%) PR and 12 (28%) SD. In the group of 61 patients with conventional treatment with 5-FU and LV (scheme II) no CR was achieved with 11 (18%) patients responding partially. In the control group of treatment (scheme I) with 21 patients PR was observed in 2 (10%) patients. Patients with i.a. chemotherapy and chronochemotherapy achieved a similar OS, which was better than OS of scheme II. The survival was worst with scheme I. CONCLUSION: I.a. chemotherapy and chronochemotherapy showed an almost equivalent efficacy in terms of response rates, which were clearly superior to those achieved by schemes I and II. Also, OS was significantly better in the patients treated with i.a. chemotherapy and chronochemotherapy compared to patients treated with scheme II. The worst survival was seen in scheme I patients.

EPIDEMIOLOGICAL REGISTRY OF NEUROENDOCRINE TUMORS IN BULGARIA--A PILOT SURVEY.

The National registry of patients with neuroendocrine tumors (NET) in Bulgaria was established in 2013 as a joint initiative of the Bulgarian Surgical Society and the Institute for Rare Diseases. The register aims to explore the epidemiology of NET in Bulgaria, as well as the different diagnostic and treatment approaches for the disease throughout the country. This the first of its kind retrospective study of NET in the country is covering the period January 2012 - January 2013. A total of 127 patients with NET were identified. At the time of the survey the average age of patients with NET was 58.61 ± 15.59 years. The data show almost equal distribution between the genders with a slight predominance of women. The largest relative part of NET is those of NET located in the gastrointestinal tract (54.10 ± 4.51%), followed by those located in the pancreas (12.30 ± 2.97%) and in the lungs (10.66 ± 2.79%). In 72.44 ± 3.96% of the patients a immunohistochemical diagnosis was performed. The study confirmed the leading role of the surgery method of the NET management. In 65.83 ± 4.33% of the patients a radical removal of the tumor was conducted, while the relative part of the undertaken partial resection was 7.50 ± 2.40%. A statistically significant association between the type of surgical treatment and during the follow-up of patients was found. An update of the information in the register will allow a more precise determining of the distribution and management of NET in Bulgaria.

[Sexual disorders in men following radical operations on the rectum for carcinoma]. / Polovi narusheniia pri muzhe sled radikalni operatsii na rektuma zaradi kartsinom.

This is the first study in Bulgaria of postoperative sexual disorders following radical surgical operations for rectal cancer. The study group comprised 64 patients. Six months after the operation only 15 (24.4 per cent) were able to have erection. Fourty nine patients who complained of inability to have erection received long-term treatment with vitamins, tranquilizers, cholinomimetic drugs, beta-blockers and medicines increasing bladder tonus. Normal erection was re-established in 31 (63.3 per cent) of these patients. The 18 (36.7 per cent) patients unaffected by drug treatment reported of possible ejaculation. This is an indication that impairment of sympathetic innervation of the genitals after operations of the rectum is of transient nature, whereas parasympathetic damage may be definitive.

[A method for placing and using an indwelling epidural catheter for analgesia in incurable cancer patients]. / Metod za postaviane i izpolzvane na traen epiduralen katetur za obezboliavane pri inkorabilni onkobolni.

Operative technique for implantation of indwelling epidural catheter produce of the firm "Braun" (Germany) is described. During the implantation the analgesics zone is checked with Lidocaine. The catheter pouch is fixed over a bone pad in a place well visible by the patient. For permanent pain relief Dipidolor is applied twice daily one quarter of the ampoule. This catheter is implanted for pains originating from the lower extremities, the pelvis and the abdomen. The method was applied on 2 patients with very good results obtained with minimal amount of opiates.

[The diagnosis and immediate treatment results in retroperitoneal tumors]. / Diagnostika i neposredstveni lechebni rezultati pri retroperitonealnite tumori.

Immediate results of treatment of 20 patients with primary retroperitoneal tumors treated over a period of 5 years (1980-1985) at the Research Institute of Oncology in Sofia are reported. Attempt is made for anamnestic analysis, aimed at elucidating the semiotics of the disease. Analysis of the diagnostic methods serves to give recommendations for "first-rate" diagnostic procedure--computer tomography when a retroperitoneal tumor is suspected. Complex therapeutic approach consisting of radical operation and adjuvant radiation treatment is advised.

[The use of a transabdominal method in treating inguinofemoral hernia simultaneously with surgery of the rectum or sigmoid in carcinoma]. / Prilozhenie na transabdominalen metod za lechenie na ingvinofemoralni khernii ednovremenno s operatsii na rektuma ili sigmata zaradi kartsinom.

Detailed description is given of inguinofemoral herniotomy with subsequent plastic repair through transabdominal approach simultaneously with radical oncologic operation of sigmoid and rectum. The plastic repair is a two-stage procedure: The first stage consists of suturing the musculo-aponeurotic part of m. transversalis and m. obliq. internus abdominis to lig. inguinalis or lig. inguinalis to lig. Cooperi in femoral hernias. The second stage is the "ampoxen" explant, which is sutured cranially to f. transversalis, medially to the fascia behind m. rectus abdominis, downward to the public or obturator fascia and laterally to the fascia over m. iliopsoas. The explant serves as a firm "umbrella" from the internal part of the entire inguinofemoral area. The method was applied on 7 patients with very good postoperative result.

[The use of a new plastic method for consolidating a preternatural anus as prevention in paracolostomy hernias]. / Prilozhenie na nov plastichen metod za ukrepvane na protivoestestveniia anus praeter kato profilaktika na parakolostomichnite khernii.

Once the stage of extraperitoneal evasion of the sigmoid has been achieved for definitive preternatural anus, transsection is made of the aponeurosis of m. obliqu. ext. abdominis along its tendon fibers at a length of 5-6 cm. Then an aperture is made along the muscle fibers with the same length on m. obliqu. int. abdominis and m. transversus abdominis as well and finally f. transversalis is transsected. The peritoneum is intra-abdominally detached from the fascia beneath and alongside the aperture. An "Ampoxen" layer is placed around the internal aperture of the abdominal wall. The explant is sutured to the fascia and the evaded sigmoid. The latter is sutured to the aponeurosis of m. obliqu. ext. abdominis. Another Ampoxen layer is placed over this aponeurosis and sutured to the evaded intestine and in a chess-board way to the fascia. The method was applied in 22 patients with very good postoperative result.

[The results of using a new surgical method in carcinomas located in the proximal portion of the lower third of the rectum]. / Rezultati ot prilozhenieto na nov operativen metod pri kartsinomi, razpolozheni v proksimalnata chast na dolnata treta na rektuma.

A new type of abdomino-transanal resection of the rectum instead of its extirpation is being applied in tumors localized in the proximal part of the lower one third of rectum (5-6 cm from the anorectal line). For removing the whole lymph collector of the lower one third of the rectum the authors remove the levator tunnel as well. What remains intact is only the anal mucosa and the external anal sphincters. The anastomosis is realized by preliminary placing all catgut. Prophylactic transversostoma is also an obligatory procedure, so that the anal sphincters may remain at rest for 2-3 months after the operation. During this time the anal sphincters and the neorectum are fixed to the adjacent tissues and the anal tonus is fully restored. This operation was applied in 15 patients with very good result, as regards anal continence, without any case of relapse of the tumor so far.

[A combined method for treating metastases of colorectal carcinoma to the liver]. / Kombiniran metod za lechenie na metastazi ot kolorektalen kartsinom v cherniia drob.

The method is a combination of operative treatment of metastases in the liver and regional intra-arterial chemotherapy. The indications for operative treatment of the underlying tumor, the metastases in the liver and the regional chemotherapy are pointed out. Two groups of patients with colorectal cancer and remote metastases in the liver are presented: one received surgical treatment alone, the other combined therapy. It is assumed that the combined treatment of the basic tumor, the metastases in the liver plus regional intra-arterial chemotherapy is a new trend in the treatment of advanced colorectal cancer metastasized in the liver.