Laparoscopic insertion of pelvic tissue expander prior radiotherapy for sacral metastasis of alveolar maxillary rhabdomyosarcoma to prevent radiation enteritis.

INTRODUCTION: Rhabdomyosarcoma is the most common soft tissue sarcoma seen in childhood and adolescence. The most frequent sites are head and neck. PRESENTATION OF CASE: A young female with maxillary rhabdomyosarcoma involving region of maxillary sinus with skeletal metastases was primary treated acccording to RMS 2005 protocol. She received 9 cycles of chemotherapy. Primary tumor of maxillary sinus was surgicaly removed after 4 cycles of chemotherapy, with 6th cycle of chemotherapy a radical radiotherapy of primary tumor location and metastasis in spinal vertebras, ribs, pelvic bone and left femoral bone started what leads to complete regression of skeletal metastases. In course of maintenance therapy MRI scan showed 12 × 28 × 23 mm lesion in sacrum in the vicinity of right sacroiliacal joint with caracteristics of metastasis. Because the region of right sacroiliacal joint with bowel was already included in primary radiation treatment, tissue expander was laparoscopicaly inserted in lower pelvis to displace bowel loops from radiation field to prevent radiation enteritis. After external beam radiotherapy to her sacrum, a good response without any side effects was achieved. DISCUSSION: Laparoscopic insertion of pelvic tissue expander prior EBRT and it's subsequent removal after EBRT is safe and effective method for displacing loops of bowel out of the pelvis. With minimal morbidity converts untreatable disease to treatable by allowing delivering high doses of radiation to the patient. CONCLUSION: After 2 years of follow up the disease is in remission and the patient without any major complaint.

Influence of concurrent capecitabine based chemoradiotherapy with bevacizumab on the survival rate, late toxicity and health-related quality of life in locally advanced rectal cancer: a prospective phase II CRAB trial.

Background Few studies reported early results on efficacy, toxicity of combined modality treatment for locally advanced rectal cancer (LARC) by adding bevacizumab to preoperative chemoradiotherapy, but long-term data on survival, and late complications are lacking. Further, none of the studies reported on the assessment of quality of life (QOL). Patients and methods After more than 5 years of follow-up, we updated the results of our previous phase II trial in 61 patients with LARC treated with neoadjuvant capecitabine, radiotherapy and bevacizumab (CRAB study) before surgery and adjuvant chemotherapy. Secondary endpoints of updated analysis were local control (LC), disease free (DFS) and overall survival (OS), late toxicity and longitudinal health related QOL (before starting the treatment and one year after the treatment) with questionnaire EORTC QLQ-C30 and EORTC QLQ-CR38. Results Median follow-up was 67 months. During the follow-up period, 16 patients (26.7%) died. The 5-year OS, DFS and LC rate were 72.2%, 70% and 92.4%. Patients with pathological positive nodes or pathological T3-4 tumors had significantly worse survival than patients with pathological negative nodes or T0-2 tumors. Nine patients (14.8%) developed grade 33 late complications of combined modality treatment, first event 12 months and last 87 months after operation (median time 48 months). Based on EORTC QLQ-C30 scores one year after treatment there were no significant changes in global QOL and three symptoms (pain, insomnia and diarrhea), but physical and social functioning significantly decreased. Based on QLQ-CR38 scores body image scores significantly increase, problems with weight loss significantly decrease, but sexual dysfunction in men and chemotherapy side effects significantly increase. Conclusions Patients with LARC and high risk factors, such as positive pathological lymph nodes and high pathological T stage, deserve more aggressive treatment in the light of improving long-term survival results. Patients after multimodality treatment should be given greater attention to the regulation of individual aspects of quality of life and the occurrence of late side effects.

Validation of The Slovenian Version of the Low Anterior Resection Syndrome Score for Rectal Cancer Patients after Surgery.

PURPOSE: The purpose of this study was to translate the low anterior resection syndrome (LARS) score into Slovenian and to test its validity on Slovenian patients who underwent low anterior rectal resection. METHODS: The LARS score was translated from English into Slovenian and then back-translated following international recommendations. The Slovenian version of the LARS questionnaire was completed by patients who underwent low anterior rectal resection between 1 January 2006 and 31 December 2010 at the University Medical Centre Ljubljana. An anchor question assessing the impact of bowel function on lifestyle was included. To assess test-retest reliability, some of the patients answered the LARS score questionnaire twice. RESULTS: A total of 100 patients (66.7%) of the 150 patients who were contacted for participation, were included in the final analysis. A total of 58 patients reported major LARS score. The LARS score was able to discriminate between patients who received radiotherapy and those who did not (p<0.001), and between total and partial mesorectal excision (p<0.001). Age was not associated with a greater LARS score (p=0.975). There was a perfect fit between the QoL category question and the LARS score in 66.0% of cases and a moderate fit was found in 24.0% of the cases, showing good convergent validity. Test-retest reliability of 51 patients showed a high intraclass correlation coefficient of 0.86. CONCLUSIONS: The Slovenian translation of the LARS score is a valid tool for measuring LARS.

Total neoadjuvant treatment of locally advanced rectal cancer with high risk factors in Slovenia.

Background In the light of a high rate of distant recurrence and poor compliance of adjuvant chemotherapy in high risk rectal cancer patients the total neoadjuvant treatment was logical approach to gaining acceptance. We aimed to evaluate toxicity and efficiency of this treatment in patients with rectal cancer and high risk factors for local or distant recurrence. Patients and methods Patients with rectal cancer stage II and III and with at least one high risk factor: T4, presence of extramural vein invasion (EMVI), positive extramesorectal lymph nodes or mesorectal fascia (MRF) involvement were treated with four cycles of induction CAPOX/FOLFOX, followed by capecitabine-based radiochemotherapy (CRT) and two consolidation cycles of CAPOX/FOLFOX before the operation. Surgery was scheduled 8-10 weeks after completition of CRT. Results From November 2016 to July 2018 66 patients were evaluable. All patients had stage III disease, 24 (36.4%) had T4 tumors, in 46 (69.7%) EMVI was present and in 47 (71.2%) MRF was involved. After induction chemotherapy, which was completed by 61 (92.4%) of patients, radiologic downstaging of T, N, stage, absence of EMVI or MRF involvement was observed in 42.4%, 62.1%, 36.4%, 69.7% and 68.2%, respectively. All patients completed radiation and 54 (81.8%) patients received both cycles of consolidation chemotherapy. Grade 3 adverse events of neoadjuvant treatment was observed in 4 (6%) patients. Five patients rejected surgery, 3 of them with radiologic complete clinical remissions. One patient did not have definitive surgery of primary tumor due to unexpected cardiac arrest few days after sigmoid colostomy formation. Among 60 operated patients pathological complete response rate was 23.3%, the rate of near complete response was 20% and in 96.7% radical resection was achieved. Pathological T, N and stage downstaging was 65%, 96.7% and 83.4%, respectively. Grade ≥ 3 perioperative complications were anastomotic leakage in 3, pelvic abscess in 1 and paralytic ileus in 2 patients. The rate of pathologic complete response (pCR) in patients irradiated with 3D conformal technique was 12.1% while with IMRT and VMAT it was 37% (p < 0.05). Hypofractionation with larger dose per fraction and simultaneous integrated boost used in the latest two was the only factor associated with pCR. ConclusionsTotal neoadjuvant treatment of high risk rectal cancer is well tolerated and highly effective with excellent tumor and node regression rate and with low toxicity rate. Longer follow up will show if this strategy will improve distant disease control and survival.

Small gastrointestinal stromal tumour of the duodenum causing a life-threatening bleeding - A case report and review of the literature.

INTRODUCTION: Duodenal gastrointestinal stromal tumors (DGISTs) are mesenchymal tumors. Main presenting symptoms are gastrointestinal bleeding and non-specific abdominal pain. Surgical treatment is golden standard for treatment of DGISTs. Tumour location and size determine the surgical strategy. Recurrence rate depends on tumour location and completeness on removal. PRESENTATION OF CASE: 75 years old male fell ill with hematemesis, hemohesia and dizziness. Oesophagogastroduodenoscopy (EGD) did not reveal the source of bleeding. Upon admission, a second EGD was performed due to loss of consciousness and anaemia, which revealed only approximate source of bleeding in the third portion of the duodenum. The exact bleeding spot could not be reached and bleeding could not be controlled endoscopically. Patient was transferred to the operating room for an emergency explorative laparotomy. After extensive mobilisation of the duodenum a 2 × 2 cm intraluminal tumour with central bleeding ulceration was found in D3. The diseased part of the duodenum was excised and the duodenotomy was closed with interrupted sutures. Final pathohistological report confirmed gastrointestinal stromal tumour, pT1. Postoperative period was uneventful. DISCUSSION: Gastrointestinal stromal tumours are most common in males aged 60-65 years. Surgical treatment is a golden standard. Surgical approach depends upon tumor location and size. In case of major bleeding surgical procedure is lifesaving and diagnostics for staging purposes are omitted. CONCLUSION: Gastrointestinal stromal tumors are a potential source of life-threatening bleeding. In such cases an emergency operation is often indicated with aim to remove the tumour en bloc and achieve hemostasis as soon as possible.

Induction chemotherapy, chemoradiotherapy and consolidation chemotherapy in preoperative treatment of rectal cancer - long-term results of phase II OIGIT-01 Trial.

Background The purpose of the study was to improve treatment efficacy for locally advanced rectal cancer (LARC) by shifting half of adjuvant chemotherapy preoperatively to one induction and two consolidation cycles. Patients and methods Between October 2011 and April 2013, 66 patients with LARC were treated with one induction chemotherapy cycle followed by chemoradiotherapy (CRT), two consolidation cycles, surgery and three adjuvant capecitabine cycles. Radiation doses were 50.4 Gy for T2-3 and 54 Gy for T4 tumours in 1.8 Gy daily fraction. The doses of concomitant and neo/adjuvant capecitabine were 825 mg/m2/12h and 1250mg/m2/12h, respectively. The primary endpoint was pathologic complete response (pCR). Results Forty-three (65.1%) patients were treated according to protocol. The compliance rates for induction, consolidation, and adjuvant chemotherapy were 98.5%, 93.8% and 87.3%, respectively. CRT was completed by 65/66 patients, with G ≥ 3 non-hematologic toxicity at 13.6%. The rate of pCR (17.5%) was not increased, but N and the total-down staging rates were 77.7% and 79.3%, respectively. In a median follow-up of 55 months, we recorded one local relapse (LR) (1.6%). The 5-year disease-free survival (DFS) and overall survival (OS) rates were 64.0% (95% CI 63.89-64.11) and 69.5% (95% CI 69.39-69.61), respectively. Conclusions In LARC preoperative treatment intensification with capecitabine before and after radiotherapy is well tolerated, with a high compliance rate and acceptable toxicity. Though it does not improve the local effect, it achieves a high LR rate, DFS, and OS.

Prognostic Significance of Tumor Regression in Locally Advanced Rectal Cancer after Preoperative Radiochemotherapy.

BACKGROUND: The majority of rectal cancers are discovered in locally advanced forms (UICC stage II, III). Treatment consists of preoperative radiochemotherapy, followed by surgery 6-8 weeks later and finally by postoperative chemotherapy. The aim of this study was to find out if tumor regression affected long-term survival in patients with localy advanced rectal cancer, treated with neoadjuvant radiochemotherapy. PATIENTS AND METHODS: Patients with rectal cancer stage II or III, treated between 2006 and 2010, were included in a retrospective study. Clinical and pathohistologic data were acquired from computer databases and information about survival from Cancer Registry. Survival was estimated according to Kaplan-Meier method. Significance of prognostic factors was evaluated in univariate analysis; comparison was carried out with log-rank test. The multivariate analysis was performed according to the Cox regression model; statistically significant variables from univariate analysis were included. RESULTS: Two hundred and two patients met inclusion criteria. Median follow-up was 53.2 months. Stage ypT0N0 (pathologic complete response, pCR) was observed in 14.8% of patients. Pathohistologic stage had statistically significant impact on survival (p = 0.001). 5-year survival in patients with pCR was>90%. Postoperative T and N status were also found to be statistically significant (p = 0.011 for ypT and p < 0.001 for ypN). According to multivariate analysis, tumor response to neoadjuvant therapy was the only independent prognostic factor (p = 0.003). CONCLUSIONS: Pathologic response of tumor to preoperative radiochemotherapy is an important prognostic factor for prediction of long-term survival of patients with locally advanced rectal cancer.

The Influence of the Distal Resection Margin Length on Local Recurrence and long- term Survival in Patients with Rectal Cancer after Chemoradiotherapy and Sphincter- Preserving Rectal Resection.

BACKGROUND: Low recurrence rates and long term survival are the main therapeutic goals of rectal cancer surgery. Complete, margin- negative resection confers the greatest chance for a cure. The aim of our study was to determine whether the length of the distal resection margin was associated with local recurrence rate and long- term survival. PATIENTS AND METHODS: One hundred and nine patients, who underwent sphincter-preserving resection for locally advanced rectal cancer after preoperative chemoradiotherapy between 2006 and 2010 in two tertiary referral centres were included in the study. Distal resection margin lengths were measured on formalin-fixed, pinned specimens. Characteristics of patients with distal resection margin < 8 mm (Group I, n = 27), 8-20 mm (Group II, n = 31) and > 20 mm (Group III, n = 51) were retrospectively analysed and compared. Median (range) follow-up time in Group I was 89 (51-111), in Group II 83 (57-111) and in Group III 80 (45-116) months (p = 0.326), respectively. RESULTS: Univariate survival analysis showed that distal resection margin length was not statistically significantly associated with overall survival or local recurrence rate (p > 0.05). In a multiple Cox regression analysis, after adjusting for pathologic T and N stage (yT, yN), distal resection margin length was still not statistically significantly associated with overall survival. CONCLUSIONS: Our study shows that close distal resection margins can be accepted as oncologically safe for sphincter-preserving rectal resections after preoperative chemoradiotherapy.

Acute Toxicity and Tumor Response in Locally Advanced Rectal Cancer After Preoperative Chemoradiation Therapy With Shortening of the Overall Treatment Time Using Intensity-Modulated Radiation Therapy With Simultaneous Integrated Boost: A Phase 2 Trial.

BACKGROUND AND PURPOSE: This phase 2 study investigated the efficacy and safety of preoperative intensity modulated radiation therapy with a simultaneous integrated boost (IMRT-SIB) without dose escalation, concomitant with standard capecitabine chemotherapy in locally advanced rectal cancer. METHODS AND MATERIALS: Between January 2014 and March 2015, 51 patients with operable stage II-III rectal adenocarcinoma received preoperative IMRT with pelvic dose of 41.8 Gy and simultaneously delivered 46.2 Gy to T2/3 and 48.4 Gy to T4 tumor in 22 fractions, concomitant with capecitabine, 825 mg/m2/12 hours, including weekends. The primary endpoint was pathologic complete response (pCR). RESULTS: Fifty patients completed preoperative treatment according to the protocol, and 47 underwent surgical resection. The sphincter preservation rate for the low rectal tumors was 62%, and the resection margins were free in all but 1 patient. Decrease in tumor and nodal stage was observed in 32 (68%) and 39 (83%) patients, respectively, with pCR achieved in 12 (25.5%) patients. There were only 2 G ≥ 3 acute toxicities, with infectious enterocolitis in 1 patient and dermatitis over the sacral area caused by the bolus effect of the treatment table in the second patient. CONCLUSIONS: Preoperative IMRT-SIB without dose escalation is well tolerated, with a low acute toxicity profile, and can achieve a high rate of pCR and downstaging.

Thrombosis of pancreatic arteriovenous malformation induced by diagnostic angiography: case report.

BACKGROUND: We report on a case of pancreatic arteriovenous malformation (PAVM) that obliterated shortly after diagnostic angiography (DSA). PAVM is a rare anomaly that presents with upper abdominal pain, signs of acute pancreatitis and massive gastrointestinal bleeding. The management of PAVM is rather complex, with complete treatment usually accomplished only by a total extirpation of the affected organ or at least its involved portion. DSA prior to treatment decisions is helpful for characterizing symptomatic PAVM, since it can clearly depict the related vascular networks. In addition, interventional therapy can be performed immediately after diagnosis. CASE PRESENTATION: A 39-old male was admitted due to recurring upper abdominal pain that lasted several weeks. Initial examination revealed the absence of fever or jaundice, and the laboratory tests, including that for pancreatic enzymes, were unremarkable. An abdominal ultrasound (US) showed morphological and Doppler anomalies in the pancreas that were consistent with a vascular formation. A subsequent DSA depicted a medium-sized nidus, receiving blood supply from multiple origins but with no dominant artery. Coil embolization was not possible due to the small caliber of the feeding vessels. In addition, sclerotherapy was not performed so as to avoid an unnecessary wash out to the non-targeted duodenum. Consequently, the patient received no specific treatment for his symptomatic PAVM. A large increase in pancreatic enzymes was noticed shortly after the DSA procedure. Imaging follow-up by means of CT and MRI showed small amounts of peripancreatic fluid along with a limited area of intra-parenchymal necrosis, indicating necrotizing pancreatitis. In the post-angiography follow-up the patient was hemodynamically stable the entire time and was treated conservatively. The symptoms of pancreatitis improved over a few days, and the laboratory findings returned to normal ranges. Long-term follow-up by way of a contrast-enhanced CT revealed no recanalization of the thrombosed PAVM. CONCLUSION: The factors associated with the obliteration of PAVM during or after DSA are poorly understood. In our case it may be attributed to the low flow dynamics of PAVM, as well as to the local administration of a contrast agent. Asymptomatic PAVM, as diagnosed with non-invasive imaging techniques, should not be evaluated with DSA due to the potential risk of severe complications, such as acute pancreatitis.

Neoadjuvant capecitabine, radiotherapy, and bevacizumab (CRAB) in locally advanced rectal cancer: results of an open-label phase II study.

BACKGROUND: Preoperative capecitabine-based chemoradiation is a standard treatment for locally advanced rectal cancer (LARC). Here, we explored the safety and efficacy of the addition of bevacizumab to capecitabine and concurrent radiotherapy for LARC. METHODS: Patients with MRI-confirmed stage II/III rectal cancer received bevacizumab 5 mg/kg i.v. 2 weeks prior to neoadjuvant chemoradiotherapy followed by bevacizumab 5 mg/kg on Days 1, 15 and 29, capecitabine 825 mg/m2 twice daily on Days 1-38, and concurrent radiotherapy 50.4 Gy (1.8 Gy/day, 5 days/week for 5 weeks + three 1.8 Gy/day), starting on Day 1. Total mesorectal excision was scheduled 6-8 weeks after completion of chemoradiotherapy. Tumour regression grades (TRG) were evaluated on surgical specimens according to Dworak. The primary endpoint was pathological complete response (pCR). RESULTS: 61 patients were enrolled (median age 60 years [range 31-80], 64% male). Twelve patients (19.7%) had T3N0 tumours, 1 patient T2N1, 19 patients (31.1%) T3N1, 2 patients (3.3%) T2N2, 22 patients (36.1%) T3N2 and 5 patients (8.2%) T4N2. Median tumour distance from the anal verge was 6 cm (range 0-11). Grade 3 adverse events included dermatitis (n = 6, 9.8%), proteinuria (n = 4, 6.5%) and leucocytopenia (n = 3, 4.9%). Radical resection was achieved in 57 patients (95%), and 42 patients (70%) underwent sphincter-preserving surgery. TRG 4 (pCR) was recorded in 8 patients (13.3%) and TRG 3 in 9 patients (15.0%). T-, N- and overall downstaging rates were 45.2%, 73.8%, and 73.8%, respectively. CONCLUSIONS: This study demonstrates the feasibility of preoperative chemoradiotherapy with bevacizumab and capecitabine. The observed adverse events of neoadjuvant treatment are comparable with those previously reported, but the pCR rate was lower.

Preoperative prediction of lymph node status in gastric cancer patients with the help of computer analysis.

INTRODUCTION: An optimal management of gastric cancer should be stage-oriented with the main criterion of lymph node status. Nodal status can be assessed preoperatively with modern radiological imaging techniques, sentinel node biopsy, molecular or genetic markers of tumor and computer analysis. The aim of this study was to evaluate the feasibility and accuracy in preoperative prediction of lymph node status with the help of computer analysis. METHODS: The computer model was constructed with data from patients with gastric cancer treated at the University Medical Centre Ljubljana between 1993 and 2003. Prediction of the computer model was then tested on 110 patients treated between 2004 and 2005 in the same manner as patients from the database. The goal of the study was to compare prediction for lymph node status in the control group by the computer program with real data collected after surgery. RESULTS: Accuracy of computerized preoperative predictions of N0/N1 status is 86% (sensitivity 91% and specificity 79%) and of N1/N2 status is 89% (sensitivity 87% and specificity 90%). CONCLUSION: Results of accuracy of preoperative predictions of nodal status are very high and allow in each individual case to guide stage-appropriate therapy. Best applicability is obtained with implementation of this new approach with standard diagnostic methods.

Computer-guided surgery for gastric carcinoma.

Lymphadenectomy offers the only hope for cure when lymph nodes are involved. In gastric cancer, three approaches have been pursued to preoperatively predict node status in individual patients, modern radiological imaging techniques, sentinel node and technique that uses a computerized database of information to convert a large amount of information and experience to a treatment decision for an individual patient. The aim of this study was to evaluate accuracy in preoperative prediction of lymph node status in selected patients with the help of computer analysis for stage-appropriate surgery. With the help of computer programs Win Estimate and Microsoft Access, we constructed an artificial neural network that calculated a statistical prediction of nodal status in an observed patient with preoperatively gathered data. In 110 patients who have undergone R0 resection with D2 lymphadenectomy, the differences between the individual results generated by artificial neural network calculation and the actual data were compared. The accuracy of computerized predictions of N0 stage for study group is 91%, sensitivity 94% and specificity 87%. The results of accuracy of computerized preoperative prediction of N2 stage are 88%, with sensitivity 94% and specificity 88%. Preoperative analyses of patient data and tumour characteristics offers a rational approach to individualizing tumour therapy where the extent of lymph node dissection is tailored to the type, site, and stage of the tumour, thereby minimizing the disadvantages associated with the extensive operative procedure.

Role of computer analysis in gastric cancer surgery: evaluation of the WinEstimate v. 2.5 computer program.

To identify the group of patients with gastric cancer who can benefit from extensive lymphadenectomy and to offer a rational approach to lymph node dissection, it is important to know the incidence of metastases at each lymph node station. A computer program was developed for assessment of lymph node involvement and survival time in each individual case according to preoperative variables. In patients who have undergone R0 resection with D2 lymphadenectomy, differences between the individual results generated by the computer and the actual data were compared. A cutoff point of 10% in the prediction of metastases was used as a positive result. The computer program made false predictions in 9% of patients for the pN status (3% lower and 6% higher than the actual status). Computerized prediction of 5-year survival was close to the rate calculated by the Kaplan-Meier method (55.5% vs 56.1%). Preoperative computer analysis of patient data and tumor characteristics offers a rational approach to individualizing tumor therapy] where the extent of lymph node dissection is tailored to the type, site, and stage of the tumor, thereby minimizing the disadvantages (morbidity, mortality) associated with the extensive operative procedure.