Retrospective analysis of the impact of anthracycline dose reduction and chemotherapy delays on the outcomes of early breast cancer molecular subtypes.

BACKGROUND: The objective of study was to determine the effect of anthracycline dose reduction and chemotherapy delays on 5-year overall survival in patients with stage I-III breast cancer, to establish the impact of molecular subtypes on the anthracycline modification effects and to analyze reasons for such chemotherapy scheme modifications. METHODS: Medical records of patients with stage I-III breast cancer were reviewed. Inclusion criteria involved stage I- III breast carcinoma; radical surgery performed and 4 courses of AC regimen (doxorubicin and cyclophosphamide), or at least 6 courses of FAC regimen (fluorouracil, doxorubicin and cyclophosphamide) completed; no neoadjuvant chemotherapy applied; no taxane group medications administered; medical records maintain comprehensive data on treatment and follow-up. 5- year overall survival were analyzed using Kaplan-Meier and Cox proportional hazards models. RESULTS: Significant 3.17 times higher death risk at 5 year period in patients who experienced anthracycline dose reduction compared with patients who did not experience any modifications was established (HR = 3.17, 95% CI 1.7-5.9, p < 0.001). Increased death risk in patients who experienced both chemotherapy dose reduction and treatment delays compared with patients who did not experience any modifications was also established (HR = 2.76, 95% CI 1.3-5.6, p < 0.05). 5- year overall survival was affected by anthracycline dose reduction by more than 15% in ER-HER2- group (80% v. 55.6%, p = 0.015), ER + HER2- group (90.7% v. 64.9%, p < 0.01) and ER+/-HER2+ group (100% v. 84.4%, p = 0.019). 5-year overall survival was affected by chemotherapy delays more than 2 cycles in ER-HER2- group (79.2% v. 51.4%, p = 0.002), ER + HER2- group (86.3% v. 58.8%, p = 0.014) and there was no difference in ER+/-HER2+ group. Main reasons for chemotherapy scheme modifications (in decreasing order) were the following: neutropenia, modifications with no objective medical reasons, thrombocytopenia, anaemia, fatigue, infection. CONCLUSIONS: Anthracycline dose reduction in patients with stage I- III breast cancer were associated with higher mortality risk and significantly decreased 5- year absolute survival in all molecular subtypes. Chemotherapy delays alone were not associated with decreased survival only in HER2 positive subtype. The most common reason for dose reduction or chemotherapy delays was neutropenia.

Retrospective analysis of the impact of platinum dose reduction and chemotherapy delays on the outcomes of stage III ovarian cancer patients.

BACKGROUND: Ovarian cancer is a common gynaecological malignancy still remaining a challenge to treat. The objective of this study was to evaluate the impact of platinum dose reduction and chemotherapy delays on progression free survival and overall survival in patients with stage III ovarian cancer and to analyze reasons for such chemotherapy scheme modifications. METHODS: Medical records of patients with FIGO stage III ovarian cancer were reviewed. Inclusion criteria involved FIGO stage III epithelial ovarian carcinoma; cytoreductive surgery performed and 6 courses of platinum-based chemotherapy completed; no neoadjuvant chemotherapy applied; and no history of previous malignancies. Progression free survival and overall survival were analyzed using Kaplan-Meier and Cox proportional hazards models. RESULTS: Significant 3.3 times higher death risk in patients who experienced only chemotherapy delays compared with patients who did not experience any chemotherapy scheme modifications was established (HR = 3.3, 95% Cl: 1.2 - 8.5, p = 0.016). Increased death risk in patients who experienced only chemotherapy delays compared with patients who experienced both chemotherapy delays and platinum dose reduction was also established (HR = 2.3, 95% Cl: 1.1 - 4.8, p = 0.021). Main reasons for chemotherapy scheme modifications (in decreasing order) were the following: neutropenia, modifications with no objective medical reasons, renal disorders, anaemia, poor performance status, gastrointestinal symptoms and neuropathy. Overall survival in patients who experienced chemotherapy scheme modifications with no objective medical reasons was non-inferior than in patients who did not experience any chemotherapy scheme modifications. CONCLUSIONS: Chemotherapy delays in patients with FIGO stage III ovarian cancer caused lower overall survival. The most common reason for chemotherapy scheme modifications was neutropenia.

Analysis of intracorporeal knotting with invaginating suture versus endoloops in appendiceal stump closure.

INTRODUCTION: Laparoscopic appendectomy is a well-described surgical technique and has gained wide clinical acceptance. Laparoscopic appendectomy offers fewer wound infections, faster recovery and an earlier return to work in comparison to open surgery. However, concerns still exist regarding the appendiceal stump closure. AIM: The aim of this study was to compare the overall incidence and specific intraoperative and postoperative complications after application of intracorporeal knotting with invaginating suture versus endoloops for stump closure in laparoscopic appendectomy. MATERIAL AND METHODS: ONE HUNDRED FIFTY TWO CONSECUTIVE PATIENTS ACCORDING TO THE FOLLOWING INCLUSION CRITERIA WERE INCLUDED IN THE STUDY: 1. Laparoscopic appendectomy was performed during the study period; 2. Acute phlegmonous or gangrenous appendicitis without perforation was diagnosed during operation. Exclusion criteria - patients with acute perforated appendicitis and local or diffuse peritonitis. Data was grouped according to the appendiceal stump closure technique, with either endoloops - 112 patients (73.7 percent) or intracorporeal knotting with invaginating suture - 40 patients (26.3 per cent). The primary outcome measure was the rate of intraabdominal surgical-site infection, defined as post-operative intra-abdominal abscess. Secondary outcome variables were intraoperative and postoperative complications, duration of operation, hospital stay. RESULTS: There were no significant differences between the two groups in overall intraoperative and postoperative complications rate and in hospital stay. The median duration of operation was significantly shorter when the endoloop was used. The use of intracorporeal knotting with invaginating suture instead of endoloop to close the appendiceal stump decreased the total cost of laparoscopic appendectomy. CONCLUSIONS: According our study results, intracorporeal knotting with invaginating suture appendiceal stump closure technique is acceptable laparoscopic procedure, which intraoperative and postoperative results do not differ from endoloops technique. The total cost of this procedure is 80 € cheaper then endoloops technique.

CpG island methylation of the MLH1, MGMT, DAPK, and CASP8 genes in cancerous and adjacent noncancerous stomach tissues.

BACKGROUND AND OBJECTIVE. Many factors are involved in the development of gastric adenocarcinoma. The CpG island methylation of apoptosis and mismatch repair genes by the loss of their function is important in gastric adenocarcinoma. The aim of this study was to determine the methylation frequency of MLH1, MGMT, CASP8, and DAPK in cancerous and adjacent noncancerous stomach tissues, to determine possible associations with the selected clinicopathological characteristics, and to identify possible correlation between the methylation of individual genes. MATERIAL AND METHODS. The methylation status of MLH1, MGMT, DAPK, and CASP8 was investigated in 69 patients with gastric adenocarcinoma by using methylation-specific polymerase chain reaction. The associations between patients' clinical characteristics and methylation status were assessed. RESULTS. The methylation frequency of the MLH1, DAPK, MGMT, and CASP8 gene promoters in cancerous and adjacent noncancerous tissues was 31.9% and 27.5%; 47.8% and 46.4%; 36.2% and 44.9%; and 5.8% and 5.8%, respectively, but the differences were not significant. There was no significant association between the methylation status of the mentioned genes and clinicopathological characteristics, such as age, sex, tumor type by the Lauren classification, degree of differentiation G, and TNM staging. An inverse correlation between the methylation of the DAPK and MLH1 gene promoters in cancerous and surrounding noncancerous tissues was found. CONCLUSIONS. The methylation of the MLH1, MGMT, DAPK, and CASP8 genes was found to occur both in cancerous and noncancerous stomach tissues. These findings provide additional insights into gene methylation patterns in gastric adenocarcinoma.

[Early postoperative intraperitoneal chemotherapy for the treatment of advanced gastric cancer]. / Skrandzio vezio gydymas ankstyvaja pooperacine intraperitonine chemoterapija.

UNLABELLED: Surgery remains the main treatment modality for gastric cancer. Adjuvant radiochemotherapy and adjuvant chemotherapy are becoming more and more popular in the treatment of advanced gastric cancer. Early postoperative intraperitoneal chemotherapy as one of the methods of adjuvant chemotherapy is currently being extensively investigated. The aim of the present study was to evaluate the toxicity of early postoperative intraperitoneal chemotherapy and its impact on postoperative complications as well as long-term survival. MATERIAL AND METHODS: A prospective study including 46 patients with gastric cancer who underwent radical resection was carried out during 2004-2005. Fourteen patients who received early postoperative intraperitoneal chemotherapy with 5-FU (EPIC group) were compared with 32 patients not receiving intraperitoneal chemotherapy (control group). All patient, except one patient in the EPIC group, received adjuvant radiochemotherapy or adjuvant chemotherapy. The toxicity of early postoperative intraperitoneal chemotherapy was evaluated using the WHO scale, and survival was estimated by the Kaplan-Meier method. RESULTS: The rate of postoperative complications was similar in both the groups (14.3% in the EPIC group vs. 12.5% in the control group). Four patients (28.6%) in the EPIC group developed grade III toxicity. There was no difference in survival comparing the EPIC group with the control group (median survival, 30 months and 34 months, respectively; P=0.500). CONCLUSIONS: Early postoperative intraperitoneal chemotherapy with 5-fluorouracile demonstrated acceptable toxicity and was relatively simple to perform. No survival benefit was documented combining early postoperative intraperitoneal chemotherapy with adjuvant radiochemotherapy or adjuvant chemotherapy.

[Adjuvant therapy after curative resection with D2 lymphadenectomy for gastric cancer: results of a prospective clinical trial]. / Skrandzio vezio adjuvantinis gydymas po radikaliu operaciju su D2 limfadenektomija (perspektyviojo klinikinio tyrimo duomenys).

OBJECTIVE: Adjuvant chemoradiation for gastric cancer is used more frequently, but there is no general opinion about the effect of this treatment. The aim of this study was to compare adjuvant chemoradiation with adjuvant chemotherapy after radical operation for stomach cancer. MATERIAL AND METHODS: A total of 133 patients were included in this prospective study. Sixty-three patients after curative gastrectomy and D2 lymphadenectomy for gastric cancer were assigned to the chemoradiotherapy group and 70 to the chemotherapy group. The groups were identical by age, sex, and cancer stages. Toxicity was evaluated by the WHO scale, and survival was evaluated by the Kaplan-Meier method. RESULTS: Grade III and IV toxicity was found more frequently in the chemoradiation group than in the chemotherapy group (44.4% and 7.1%, respectively; P<0.0001). Treatment was not finished in 27% of patients in the chemoradiation group and 11.4% in the chemotherapy group (P=0.03). Overall survival was better in the chemotherapy group as compared with the chemoradiation group (P=0.039). Median survival for patients with stage III and IV cancer was 41 months in the chemotherapy group and 18 months in the chemoradiation group (P=0.085). Survival of patients with stage IIIA cancer in the chemotherapy group was significantly better (P=0.005). CONCLUSIONS: Median survival is shorter in the adjuvant chemoradiation group after curative gastrectomy for gastric cancer as compared with the adjuvant chemotherapy group. Adjuvant chemoradiation is more toxic and should be recommended only for patients with advanced-stage cancer.

A comparison of the effectiveness of the early enteral and natural nutrition after pancreatoduodenectomy.

SUMMARY: The role of postoperative supplementary enteral nutrition after gastrointestinal surgery is controversial. Therefore, a randomized clinical trial with attempts to address the question of plenitude of routine application of postoperative enteral feeding on rate of postoperative complications following pancreatoduodenectomy was performed. Sixty patients undergoing pancreatoduodenectomy were blindly randomized into two groups: 30 patients in the first group received early enteral nutrition (EEN), while 30 patients in the second group were given early natural nutrition (ENN). The complications were evaluated according to definition criteria. All complications were further subdivided into infectious and noninfectious complications. Our data showed that patients in EEN group gained a larger amount of energy in kcal a day during the first five days after surgery in comparison to ENN group. There was a higher rate of postoperative complications in ENN group (53.3% vs 23.3%, P=0.03). This difference occurred mainly due to the higher incidence of infectious complications in ENN group (46.7% vs 16.7%, P=0.025). There were six cases of bacteriemia in this group of patients, while only one case was observed in EEN group (6 (20.0%) vs 1 (3.3%), P=0.1). The overall risk for the development of any type of infectious complication was 1.5 times higher in ENN group. In conclusion, this study suggests that supplementary postoperative enteral nutrition helps to decrease the rate of infectious complications in patients undergoing pancreatoduodenectomy, especially in those with a plasma albumin level of less than 34.5 g/L and/or ASA class III or higher, since natural nutrition is insufficient in this case.

Etiology of bile infection and its association with postoperative complications following pancreatoduodenectomy.

UNLABELLED: Currently controversy exists whether bile infection following preoperative biliary drainage has an impact on postoperative complications and mortality rate. The objective of the study was to determine etiology of preoperative bile infection and to evaluate its influence on postoperative complications and mortality after pancreatoduodenectomy. METHODS: Data on 64 patients, undergoing pancreatoduodenectomy at Kaunas University of Medicine Hospital between 2002 and 2004 were collected prospectively. We evaluated etiology and the impact of bile infection on development of post-operative complications. Patients were divided into groups according to results of intraoperative bile culture. RESULTS: In 31 patients (48.4%) intraoperative bile cultures were negative, while in remaining 33 patients (51.6%) infected bile was documented. Both patient groups were homogenous according to demographic data, preoperative and intraoperative variables. Pancreaticoduodenectomy was performed in 21 patients after preoperative biliary drainage (endoscopic stenting, bilidigestive anastomosis or percutaneous bile drainage), others (n=43) had primary operation. Infected bile was found more often in patients who underwent biliary drainage (p<0.0001). Among 43 patients with primary pancreaticoduodenectomy 22 patients underwent endoscopic retrograde cholangiopancreatography without stenting, while remaining 21 had no preoperative endoscopic manipulation. Infected bile was present in 9 patients after endoscopic retrograde cholangiopancreatography (40.9%) and in 4 without preoperative endoscopy (19%). Enterococcus and Escherichia coli dominated in bile cultures of patients with primary pancreaticoduodenectomy, while multiple species (3 and more microorganisms) dominated following drainage procedures. Septic postoperative complications were identified in 26.6% of cases. Infected bile did not influence both overall and septic postoperative complications. Bacteria causing abdominal cavity and wound infections matched bile cultures in 7.7% of cases only. CONCLUSIONS: Our data show that infected bile is found more often after preoperative biliary drainage procedures. However, bile infection did not increase statistically significantly the number of postoperative septic complication.

[Results of the surgical treatment of periampullary cancer at the Kaunas Medical University Hospital]. / Periampulinio vezio chirurginio gydymo rezultatai Kauno medicinos universiteto klinikose.

During 1998-2000 (till October 1) 55 radical operations on the pancreas because of periampullary carcinoma were performed in Kaunas Medical University Hospital. There were 50 pancreatoduodenal resections (PDR) and 5 total pancreatectomies (PE). Age of patients ranged from 28 to 78 years, mean age was 61.9 years. Thirty six percent (36.4%) of patients were older than 70 years. Carcinoma of the head of the pancreas was diagnosed in 48 (87.3%) cases, common bile duct carcinoma in 3 (5.5%) cases, carcinoma of p. Vateri in 2 (3.6%) cases and carcinoma of duodenum in 2 (3.6%) cases. Twenty five (45.5%) patients were suffering from first or second stage cancer, 28 (50.9%)--from third stage. Stage IV was diagnosed for 2 (3.6%) patients, due to invasion to the portal, mesenteric or splenic veins. For those patients resection of portal, mesenteric or splenic veins was performed. Malignant invasion to the resection margin of the pancreas was found in 4 (7.3%) patients. Regional lymphadenectomies (D1) were performed in 23 cases and radical lymphadenectomies (D2) in 32 cases. There was no statistically significant difference in overall morbidity after the operations between those two groups. Hospital mortality in PDR group was 8% (4 pts.) and 20% (1pt.) in PE group. Actuarial survival was estimated based on data of February 1, 2001. Survival function was compared between patients who underwent radical (n = 50) and palliative (n = 43) operations. Median survival time after radical operations was 382 days, whereas after palliative operations--128 days. As postoperative morbidity is not influenced by the extent of lymphadenectomy, D2 dissection should be performed. The pancreatic resection during PDR should be performed through macroscopically normal pancreatic tissue. PE is recommended if the macroscopical invasion to distal part of the pancreas is present.