Gender-related prognostic significance of clinical and biological tumor features in rectal cancer patients receiving short-course preoperative radiotherapy.

AIM: To study the prognostic value of clinical and biological features of rectal cancer and potential gender differences in patients' overall survival (OS), local recurrence-free survival (RFS) and metastasis-free survival (MFS) after short-course preoperative radiotherapy (SCRT) with short or long interval between RT and surgery (break). BACKGROUND: The length of the interval between RT and surgery in SCRT is debatable and gender-related differences in patients survival are not established yet. MATERIALS AND METHODS: 126 patients received SCRT with 5 Gy dose per fraction during 5 days, followed by radical surgery after short break ≤17 days, and a long break >17 days. Pretreatment tumor proliferation (bromodeoxyuridine labeling index, BrdUrdLI and S-phase fraction) was evaluated by flow cytometry and proteins: CD34, Ki-67, GLUT-1, Ku70, BCL-2, P53 expression was studied immunohistochemically. RESULTS: The studied group included 84 men and 42 women. There were 33, 76, and 17 cTNM (AJCC) tumor stages I, II, III, respectively. The median follow-up time was 53.3 months (range 2-142 months). For the whole group Cox multivariate analysis revealed that tumor grade (G > 1), interval between RT and surgery >17 days, pTNM stage >1 and P53 positivity + BrdUrdLI > 7.9% were negative prognostic factors for OS. Tumor aneuploidy and MVD > 140.8 vessels/mm2 were important for RFS. pTNM stage > 1 and P53 positivity combined with BrdUrdLI > 7.9% were risk predictors for MFS. Based on tumor biological features, gender-related difference in OS, RFS, and MFS were observed. In multivariate analysis, male patients age > 62 years and break >17 days only appeared to be significant for OS. CONCLUSIONS: In male rectal patients treated with SCRT, breaks between RT and surgery >17 days should be avoided because they negatively influence patients' survival.

Gender-related significance of time interval between radiotherapy and surgery in hypofractionated preoperative radiotherapy for rectal cancer patients' survival.

AIM AND BACKGROUND: An optimal break between radiotherapy (RT) and surgery in short-course of RT (SCRT) for locally advanced rectal cancer is not clearly established. The aim of the study was to investigate the influence of the break in the preoperative SCRT and overall treatment time (OTT) for locally advanced rectal cancer patients (whole group and male/female subgroups) on patients overall survival (OS), recurrence-free survival (RFS), metastasis-free survival (MFS). MATERIALS AND METHODS: 131 patients were treated with SCRT (5 Gy/5 days), followed by surgery 3-53 days later. Break was calculated as the time interval between the end of irradiation to surgery and OTT as time interval from the beginning of RT to surgery. RESULTS: Mean break was 21.5 (range 3-53.0) days and mean OTT was 26.5 (range 7-58.0) days. In univariate analysis, a break longer than 15 days and OTT >23 days were negative prognostic factors for OS for all patients, and particularly for the male patients' subgroup. RFS was non-significantly higher (P = 0.066) for patients treated with a break ≤15 days and OTT ≤23 days (P = 0.099), irrespectively of patients' sex. Patients treated with a break longer than 15 days and OTT >23 days had non-significantly lower level of MFS than those treated with a shorter break (P = 0.269) and OTT ≤23 days (P = 0.498). CONCLUSION: In SCRT, a break in the treatment longer than 15 days, especially in the male patients subgroup, should be avoided, because it negatively affects patients' survival.

Preoperative radiotherapy does not alter pre- and early postoperative serum C-reactive protein and albumin concentrations in colorectal cancer patients.

AIM OF THE STUDY: We aimed to assess the alterations of serum C-reactive protein (CRP) and albumin levels in colorectal cancer patients who underwent preoperative radio(chemo)therapy and those who did not. MATERIAL AND METHODS: The determinations of albumin and CRP were performed before and at 2, 3, 5 and 7 days after surgery in 60 colorectal cancer patients. 25 healthy subjects served as a reference group. For each patient the modified Glasgow Prognostic Score (mGPS) was calculated. RESULTS: On the operation day CRP and albumin concentrations were not different in preoperatively treated or radiotherapy naïve patients. On postoperative day 2, 3, 5 and 7 no significant differences were observed between the two groups, with the only exception for albumin concentration, which was significantly higher on postoperative days 2 and 7 in the radiation naïve group. In all patients perioperative alterations of serum CRP level were significant at all time points (preoperatively vs. day 2, day 2 vs. day 3, day 3 vs. day 5, day 5 vs. day 7). The albumin decrease from the preoperative day to postoperative day 2 was significant, as was its increase from postoperative day 3 to 5. CONCLUSIONS: We have seen no differences in the CRP and albumin concentrations in preoperatively irradiated versus non-irradiated colorectal cancer patients on the day of surgery and on postoperative days 2, 3, 5 and 7. There were, however, significant concentration changes in the value of these two serum markers from preoperatively to postoperative day 2 and over the following postoperative week, but presumably related to the surgical trauma, not the neoadjuvant treatment.

Positive effect of single nucleotide RAD51 135G>C polymorphism and low Ku70 protein expression on female rectal cancer patients survival after preoperative radiotherapy.

BACKGROUND/AIMS: This is a retrospective analysis of 103 patients having locally advanced rectal cancer who received short-course radiotherapy (SCRT). The objective of the study was to check whether a polymorphism in the RAD51 gene (135 G>C), Ku70 protein expression, and tumor microenvironment: proliferation rate measured by BrdUrdLI and Ki-67LI, hypoxia (glucose transporter-1 expression), P53 protein expression, and DNA ploidy can influence DNA repair capacity, the factors contributing to patient overall survival (OS) and the incidence of recurrences and metastases. MATERIALS AND METHODS: RAD51 (135 G>C) polymorphism was evaluated using restriction fragment length polymorphism polymerase chain reaction, and proteins were identified using immunohistochemistry. RESULTS: There were 3 (2.9%) tumors with RAD51 CC, 75 (72.8%) with GG, and 25 (24.3%) with GC genotypes. The median follow-up time was 63.1 months (range 2-120). Patients with CC genotype survived significantly longer than those with GG and GC genotypes and did not develop any recurrences or distant metastases. Female patients with Ku70 expression (<75.1) or RAD51CC genotype (impaired DNA damage repair and radiosensitive) had significantly longer OS (p=0.013) than those with Ku70>75.1 % or RAD51GG,GC (radioresistant phenotype) and male patients in the log-rank test. In multivariate analysis, positive prognostic factors for OS in the male patients were grade=1 and <17 days break in the treatment, whereas in the female subgroup, only radiosensitive phenotype (Ku70 <75.1% or RAD51CC genotype). CONCLUSION: To the best of our knowledge, this is the first study to provide evidence for the positive effect of CC genotype of RAD51 or low Ku70 expression on OS in females with rectal cancer after SCRT.

The prevalence of HPV infection in rectal cancer - Report from South - Central Poland (Cracow region).

Some studies suggest that HPV infection may be important carcinogenic factor in development of some part of colorectal cancers. However, in the worldwide literature concerning this type of tumours, the great variability in HPV frequency is noticed. In Poland, the incidence of HPV infection in colorectal cancers was examined in five studies so far and their results are also conflicting. Therefore, the aim of the present study was to assess the HPV presence in the group of 120 patients with adenocarcinomas of rectum. HPV infection was assessed on the basis of DNA extracted from collected formalin fixed paraffin embedded tumour specimens. Viral presence was evaluated using two PCR based methods: nested PCR and quantitative PCR (qPCR) with primers specific for HPV16. All HPV positive samples were subjected to virus genotyping using AmoyDx® Human papillomavirus (HPV) Genotyping Detection Kit and P16 immunostaining. Among 120 evaluated colorectal tumours, HPV DNA was detected in 2 cancers (1.67%) by nested PCR and in 2 (1.67%) tumours by qPCR, including 1 sample diagnosed as HPV positive on the basis of both PCR variants. Two HPV positive cancers had HPV16 infection and other one HPV18. All three tumours with positivity of HPV DNA were P16 negative. In south - central Poland, HPV infection in rectal cancers probably has not influence on rectal carcinogenesis.

Bromodeoxyuridine labeling index as an indicator of early tumor response to preoperative radiotherapy in patients with rectal cancer.

PURPOSE: Assessment of tumor proliferation rate using Bromodeoxyuridine labeling index (BrdUrdLI) as a possible predictor of rectal cancer response to preoperative radiotherapy (RT). METHODS AND MATERIAL: Ninety-two patients were qualified either to short RT (5 Gy/fraction/5 days) and surgery about 1 week after RT (schedule I), or to short RT and 4-5 weeks interval before surgery (schedule II). Tumor samples were taken twice from each patient: before RT and at the time of surgery. The samples were incubated with BrdUrd for 1 h at 37 degrees C, and the BrdUrdLI was calculated as a percentage of BrdUrd-labeled cells. RESULTS: Thirty-eight patients were treated according to schedule I and 54 patients according to schedule II. Mean BrdUrdLI before RT was 8.5% and its value did not differ between the patients in the two compared groups. After RT tumors showed statistically significant growth inhibition (reduction of BrdUrdLI). As the pretreatment BrdUrd LI was not predictive for early clinical and pathologic tumor response, prognostic role of the ratio of BrdUrdLI after to BrdUrdLI before RT was considered. The ratios were calculated separately for fast (BrdUrd LI>8.5%) and slowly (BrdUrd LI

Palliative thoracic radiotherapy for patients with advanced non-small cell lung cancer and poor performance status.

OBJECTIVE: The evaluation of efficacy of palliative thoracic radiotherapy (PTR) in patients with advanced non-small cell lung cancer (NSCLC) and to compare it with efficacy of supportive care (SC) alone. MATERIALS AND METHODS: Between 2000 and 2012, 235 patients with advanced NSCLC (IIIB and IV) and Karnofsky Performance Status accounted 40-30, were qualified to PTR. In fact, 125 (53.2%) out of them were treated with PTR, and 110 (46.8%)-with SC alone, in accordance with patients expectations. There were no differences between PTR and SC group with respect to patient and tumor characteristics as well as with respect to the type and incidence of symptoms related to the local growth of NSCLC. In all 125 PTR patients the delivered tumor dose was 20Gy given in five daily fractions over five treatment days. All 110 patients who refused PTR were treated with SC in another hospital (28.2%), in a hospice (21.8%) or by general practitioners at home (50.0%). RESULTS: The 90-day overall survival rate in the group of PTR patients was 20.0%, and in the group of SC patients it was 18.2%. Median survival amounted 58 and 59 days, respectively. The efficacy of PTR and SC, relative to the symptoms associated with the local growth of NSCLC, was comparable. Tolerance of PTR was poor and early toxicity-significant. Moreover 41.6% of irradiated patients received PTR within the last 30 days of their lives and 16.0% of these patients-within the last 15 days prior to death. CONCLUSION: The life expectancy of patients with advanced NSCLC and poor performance status (Karnofsky 40-30), who presenting moderate or severe symptoms related to the local growth of cancer, is measured in days or weeks. The effective method of treatment for these patients is modern supportive care rather than PTR.

[Early results of esophagectomy and total or proximal gastrectomy without perioperative administration of total parenteral nutrition]. / Wczesne powiklania i zgony po wycieciu przelyku oraz blizszym lub calkowitym wycieciu zoladka u chorych leczonych bez stosowania calkowitego zywienia pozajelitowego.

UNLABELLED: The aim of the study was to analyse complications after radical oesophagectomy or gastrectomy in cancer patients without administration of total parental nutrition (TPN). PATIENTS AND METHODS: 45 consecutive patients underwent oesophagectomy (8 patients), proximal subtotal gastrectomy (10 patients) and total gastrectomy (27 patients). Stapler sutures were used to create anastomoses between oesophagus and stomach or oesophagus and jejunum. None patient received TPN. In all patients antropometrical and biochemical characteristics were assessed. Preoperative risk factors and type of complications were estimated. Patients with surgical complications were compared with patients without surgical complications using anthropometric and biochemical values. RESULTS: Surgical complications occurred in 10(22%) patients. The most common complication was postoperative wound infection (6 patients). Anastomotic dehiscence occurred in 4 patients and resulted in 2 deaths. Complications and deaths were observed more frequently in severely malnourished patients (BMI < 18). CONCLUSIONS: There is no justification for routine perioperative use of TPN in patients without severe malnutrition undergoing oesophageal or gastric surgery for cancer.

[Resection of the renal vein leiomyosarcoma with preservation of the kidney]. / Wyciecie miesaka gladkokomórkowego zyly nerkowej z zaoszcz dzeniem nerki.

We present a case of 75 years old woman who successfully underwent resection of the right renal vein leiomyosarcoma (LMS-VR) with preservation of the kidney. It is the first reported case in Polish and fifth in world literature. The patient is alive without recurrence 24 months after operation. The surgical resection of LMS-VR with the preservation of the kidney should always be considered when the tumour does not infiltrate the renal hilus.

Gender-related differences in pathological and clinical tumor response based on immunohistochemical proteins expression in rectal cancer patients treated with short course of preoperative radiotherapy.

BACKGROUND: Prognostic value of pretreatment expression of proteins in rectal cancer for early pathological tumor response (pTR), clinical tumor response (CTR) to preoperative radiotherapy (RT), and the potential difference between these parameters depending on patient gender is not established. MATERIAL AND METHODS: One hundred eleven patients were treated with short preoperative course of RT (SCRT) with 5 Gy dose per fraction during 5 days, followed by surgery 3 to 53 days (mean, 21 days) later. Expression of CD34, Ki-67, GLUT-1, Ku70, BCL-2, and P53 proteins was assessed immunohistochemically. RESULTS: There were 76 men and 35 women. There were 27, 69, and 15 clinical tumor-node-metastasis (cTNM) tumor stages I, II, and III, respectively. Significant differences in Ki-67, GLUT-1, Ku 70, and BCL-2 expressions between male and female tumors were observed for pathological TNM (pTNM) stage and grade. Association between proteins expression and pTNM, pTR, and CTR was analyzed separately for short (≤15 days) and long (>15 days) break between RT and surgery and males and female patients. For SCRT with short break, no protein was significantly related to pTNM; for pTR, higher Ki-67 and lower BCL-2 expression were correlated with pTR. In the male subgroup, BCL-2 overexpression was predictive. For SCRT with long break, none of the proteins was predictive for pTR, but Ki-67, Ku70 (in female subgroup), and BCL-2 expressions were positively correlated with pTNM. BCL-2 overexpression was associated with CTR in the females only. CONCLUSION: In SCRT, long break in the treatment should be avoided because correlation between Ki-67, KU70, and BCL-2 expressions and pTNM after RT might indicate tumor progression.

Multifocal colorectal adenocarcinoma with a synchronous multifocal carcinoid of the small intestine--case report and literature review.

The paper presents a case report of coexisting multifocal colorectal cancer and multifocal carcinoid of the small intestine. Our literature review did not demonstrate any report of such case. We emphasize necessity of careful inspection of abdominal cavity during any surgical procedure since small lesions, in particular in the small intestine, may be omitted--as was the case during the initial colectomy in our case. Current epidemiological data are also presented and standards of management for diagnosis and treatment of gastrointestinal carcinoid.

Gender-related differences in repopulation and early tumor response to preoperative radiotherapy in rectal cancer patients.

PURPOSE: Inhibition of tumor proliferation rate based on bromodeoxyuridine labelling index (BrdUrdLI), S-phase fraction (SPF) and MIB-1 labelling index (MIB-1 LI) as an early rectal cancer response to preoperative radiotherapy (RT). METHODS AND MATERIALS: A total of 122 patients qualified either for short RT (5 Gy/fraction/5 days) and surgery about 1 week after RT (schedule I) or for short RT and a 4-week interval before surgery (schedule II). Tumor samples were taken twice from each patient: before RT and at the time of surgery. In each sample, the BrdUrdLI, SPF and MIB-1 were calculated. Early tumor response was assessed by a biologist, a pathologist and surgeons. RESULTS: Fifty-six patients were treated according to schedule I and 66 patients according to schedule II. Mean BrdUrdLI, SPF and MIB-1 LI before RT were 8.8%, 21.0% and 53.3%, respectively, and these values did not differ between the two compared groups. After RT, tumors showed statistically significant growth inhibition based on all assessed biological markers. As pretreatment assessed parameter was not predictive for early clinical and pathologic tumor response, prognostic role of the relative value (RV), that is, the ratio of assessed parameter after RT to before RT for each of the assessed markers, was considered. The ratios were calculated separately for fast and slowly proliferating tumors and separately for male and female patients. Fast proliferating tumors were more responsive. Differences with regard to sex were visible only in slowly proliferating tumors. Accelerated cell repopulation (4.8-28%/day) was noticed in female slowly proliferating tumors about 4 weeks after RT. Only for relative MIB-1 LI it was possible to show significant correlation with pathological tumor regression. Lack of such correlation for BrdUrdLI and SPF might reflect accelerated repopulation, particularly in slowly proliferating female tumors. CONCLUSIONS: Accelerated repopulation was noticed in slowly proliferating tumors in females about 4 weeks after RT.

Gastrointestinal metastases from malignant melanoma: report of a case.

Malignant melanoma metastases in the gastrointestinal tract (GIT) are found in more than 60% of autopsies on patients who have died with disseminated melanoma; however, the rate of GIT metastases detected clinically averages only 2%. This discrepancy seems to be attributed to the nonspecific symptoms and signs of GIT involvement, which include weakness, fatigue, bleeding, anemia, and abdominal pain. Sometimes a diagnosis is only made when bowel obstruction occurs. We report a case of long-term survival after surgery for multiple melanoma metastases in the gastrointestinal tract and review the relevant literature. Both our case report and the literature review demonstrate the benefits of surgery for patients with melanoma metastases in the GIT. We also stress the need for meticulous follow-up, detailed history-taking, and rapid evaluation of any vague and unclear abdominal signs and symptoms for patients with melanoma.

Progastrin and cyclooxygenase-2 in colorectal cancer.

Colorectal cancers (CRCs) are one of the most common forms of cancer in Poland and one of the leading causes of death. The tumors have been attributed to genetic, dietary, and other environmental factors, but recently growth factors such as gastrin have also been implicated in the carcinogenesis. The relationship between plasma amidated and nonamidated gastrin in CRCs is controversial. This study was designed (1) to determine the plasma levels of progastrin and amidated gastrin in 50 CRC patients before and 3-6 months after removal of the tumor, (2) to determine the tumor concentrations of these gastrin peptides and the level of expression for gastrin mRNA and gastrin/CCK(B) receptor mRNA, (3) to examine the expression of cyclooxygenase COX-1 and COX-2 mRNA in CRC tissue, and (4) to compare the prevalence of Hp and its cytotoxic protein, CagA, and cytokines (TNFalpha, IL-1beta, and IL-8) in CRCs, before and after removal of tumor. It was found that the CRC, its resection margin, and the plasma contained severalfold higher levels of progastrin than of amidated gastrins and that the removal of the CRC tumor resulted in a marked reduction in plasma progastrin level without a significant alteration in plasma levels of amidated gastrins. Both gastrin and CCK(B)-R mRNA were detected in the cancer tissue and resection margin by RT-PCR, and similarly, COX-1 and COX-2 mRNA were expressed in these tissues of most CRCs. The seroprevalence of Hp, especially that expressing CagA, and levels of IL-1beta, but not other cytokines, were significantly higher in CRC patients than in 100 age-, gender-, and profession-matched controls and did not change significantly about 3-6 months after tumor resection. We conclude that (1) the CRC and its margin contain large amounts of progastrin and show gene expression of gastrin, CCK(B)-R, and COX-2; (2) removal of the CRC markedly reduces the plasma concentrations of progastrin; (3) the Hp infection rate is higher in CRC, and this may contribute to colorectal cancerogenesis via enhancement of progastrin and gastrin release; and (4) plasma progastrin concentrations might serve as a biomarker of CRC.