Cancer risk following appendectomy for acute appendicitis (Denmark)

Objective: Epidemiologic studies have not been able definitely to exclude that appendectomy carries a cancer risk. This study was conducted to clarify whether appendectomy is associated with a subsequent increase in cancer risk, since appendectomy is frequently an elective procedure. Methods: The present study included more than 82,000 persons who underwent appendectomy for acute appendicitis during 1977-89 according to the nation-wide Danish Hospital Discharge Register. During a follow-up interval of up to 17 years, cancer incidence was assessed by linkage to the Danish Cancer Registry and compared with the incidence in the general population of Denmark. Results: The total number of malignancies among appendectomized persons was 1.05 times higher than expected with 95 percent confidence intervals of 0.99-1.11. There was no clear significant excess of any specific cancer type. Conclusion: During a postsurgery period of nearly two decades, results of our study did not support the hypothesis that either appendectomy or acute appendicitis are likely to be associated with malignant neoplasms.     

Cooperative extension initiatives in marriage and couples education

Cooperative extension has a long‐term history of delivering family life education. Further, the organization has developed numerous research‐based resources and undertaken statewide initiatives in marriage and couples education. Most promising of all is the work of a group of extension specialists to create a practical, research‐based curriculum that may reach communities in the United States through the established network of extension educators and their collaborators. We review various family relationship models and describe how the design of the new couples' curriculum is based on those models.     

Primary closure of deep sternal wound infection following open heart surgery: a safe operation?

BACKGROUND: Deep median sternotomy wound infection is a significant source of morbidity and mortality after cardiac operations. Management of an infected median sternotomy incision is a subject of controversy. The aim of this study was to assess our experience with primary closure without any irrigation system for infected deep median sternotomy wound. METHODS: Between January 1994 and December 1997, 4,227 consecutive open heart procedures via a median sternotomy under cardiopulmonary bypass were performed in our department. A total of 27 (0.64%) consecutive patients with deep sternotomy wound infection were identified. The mean age of the patients was 45 years. Six were female and 21 were male. RESULTS: The incidence of deep sternal wound infection was therefore 0.64%. The mean duration between the primary operation and the onset of deep sternal wound infection was 2.5 weeks. Staphylococcus aureus and Staphylococcus epidermidis were the most common pathogen causing postoperative mediastinal infection. Out of the 27 cases, 17 were successfully treated, 8 (30%) died and 2 had a persistent fistula. The mean follow-up time was 18 months (range 4 to 52 months). The mortality in the pediatric group was 4/8 (50%) and 4/19 (21%) in the adult group. The mortality for mediastinitis presenting before one week or after 4 weeks after operation was 63%. In contrast, the mortality for mediastinitis presenting after one week but before 4 weeks after operation was 17%. CONCLUSIONS: Mediastinitis after cardiac surgical procedures remains a devastating complication. Primary closure without irrigation-suction system should only be considered in selected patients.     

Distal catheter obstruction from non-infectious cause in ventriculo-peritoneal shunted children.

In hydrocephalic children, ventriculo-peritoneal shunting is the preferred treatment with few complications. However, an obviously non-infectious peritoneal reaction to the cerebrospinal fluid (CSF) may occasionally lead to shunt malfunction. In eight hydrocephalic children, shunt malfunction with distal catheter complication was found with abdominal pseudocyst formation in seven cases and accumulation of the CSF in one. All children had a normal CSF cell count and glucose concentration, and white cell count, and C-reactive protein in peripheral blood were normal. No CSF infection could be detected despite prolonged aerobic and anaerobic cultures. After initial externalisation of the shunt and subsequent routine administration of antibiotics because infection initially was suspected, ventriculo-peritoneal shunting was attempted one to three times with identical failure before successful conversion to a ventriculo-atrial system. At laparotomy the peritoneum and intestinal serosa were hyperaemic and oedematous in all patients, five of whom also had pseudocysts and two of whom also had intra-abdominal adhesions. Four children had a revision 6-24 years after the ventriculo-atrial conversion due to short atrial catheter with distal obstruction. In three of them, the distal catheter was successfully replaced into the peritoneal cavity. The fourth child, however, developed an infectious abdominal pseudocyst with adhesions due to a then undetected Propionibacterium acnes infection. After externalisation and antibiotics, a new ventriculo-atrial shunt was inserted. At follow-up between 5 months to nearly 6 years later, the three children with peritoneal catheters did not show any signs of shunt malfunction or abdominal problems. Thus hydrocephalic children may develop shunt malfunction with distal catheter obstruction due to a still unexplained, transient, non-infectious peritoneal reaction leading to abdominal pseudocyst formation or accumulation of CSF. In some children, however, it may later be possible to replace the distal catheter into the peritoneal cavity, if no infection is involved.     

CLL family 'Pedigree 14' revisited: 1947-2004.

The notion that inherited predisposition contributes to the development of haematological malignancies is generally thought of as being a relatively new idea. However, Videbaek made a clear enunciation of such a hypothesis in 1947, from a study of tumour incidence in relatives of patients with different leukaemias. To gain further insight into inherited susceptibility to chronic lymphocytic leukaemia (CLL), we followed up the descendants of Videbaek's 'Pedigree 14' series of families. Using the Danish medical and pedigree databases, complete tracing of 222 descendants of the original 57 family members was achieved. To date, 10 family members have been diagnosed with CLL, one with T-cell lymphoma and 17 with nonhaematological cancers, including five with breast cancer. The detailed follow up of this family provides further support for inherited predisposition to CLL and illustrates the value of follow-up studies of previously published family material for genetic analyses.     

Temozolomide pharmacodynamics in patients with metastatic melanoma: dna damage and activity of repair enzymes O6-alkylguanine alkyltransferase and poly(ADP-ribose) polymerase-1.

PURPOSE: Temozolomide, a DNA methylating agent used to treat melanoma, induces DNA damage, which is repaired by O6-alkylguanine alkyltransferase (ATase) and poly(ADP-ribose) polymerase-1 (PARP-1)-dependent base excision repair. The current study was done to define the effect of temozolomide on DNA integrity and relevant repair enzymes as a prelude to a phase I trial of the combination of temozolomide with a PARP inhibitor. EXPERIMENTAL DESIGN: Temozolomide (200 mg/m2 oral administration) was given to 12 patients with metastatic malignant melanoma. Peripheral blood lymphocytes (PBL) were analyzed for PARP activity, DNA single-strand breakage, ATase levels, and DNA methylation. PARP activity was also measured in tumor biopsies from 9 of 12 patients and in PBLs from healthy volunteers. RESULTS: Temozolomide pharmacokinetics were consistent with previous reports. Temozolomide therapy caused a substantial and sustained elevation of N7-methylguanine levels, a modest and sustained reduction in ATase activity, and a modest and transient increase in DNA strand breaks and PARP activity in PBLs. PARP-1 activity in tumor homogenates was variable (828 +/- 599 pmol PAR monomer/mg protein) and was not consistently affected by temozolomide treatment. CONCLUSIONS: The effect of temozolomide reported here are consistent with those documented in previous studies with temozolomide and similar drug, dacarbazine, demonstrating that a representative patient population was investigated. Furthermore, PARP activity was not inhibited by temozolomide treatment and this newly validated pharmacodynamic assay is therefore suitable for use in a proof-of-principle phase I trial a PARP-1 inhibitor in combination with temozolomide.     

Randomized phase III study of docetaxel compared with paclitaxel in metastatic breast cancer.

PURPOSE: This randomized, controlled, multicenter, open-label, phase III study compared docetaxel versus paclitaxel in patients with advanced breast cancer that had progressed after an anthracycline-containing chemotherapy regimen. PATIENTS AND METHODS: Patients (n = 449) were randomly assigned to receive either docetaxel 100 mg/m2 (n = 225) or paclitaxel 175 mg/m2 (n = 224) on day 1, every 21 days until tumor progression, unacceptable toxicity, or withdrawal of consent. RESULTS: In the intent-to-treat population, both the median overall survival (OS, 15.4 v 12.7 months; hazard ratio [HR], 1.41; 95% CI, 1.15 to 1.73; P = .03) and the median time to progression (TTP, 5.7 months v 3.6 months; HR, 1.64; 95% CI, 1.33 to 2.02; P < .0001) for docetaxel were significantly longer than for paclitaxel, and the overall response rate (ORR, 32% v 25%; P = .10) was higher for docetaxel. These results were confirmed by multivariate analyses. The incidence of treatment-related hematologic and nonhematologic toxicities was greater for docetaxel than for paclitaxel; however, quality-of-life scores were not statistically different between treatment groups over time. CONCLUSION: Docetaxel was superior to paclitaxel in terms of OS and TTP. ORR was higher for docetaxel. Hematologic and nonhematologic toxicities occurred more frequently in the docetaxel group. The global quality-of-life scores were similar for both agents over time.     

Familial aggregation and heterogeneity of non-Hodgkin lymphoma in population-based samples.

The importance of genetic factors in the etiology of non-Hodgkin lymphoma (NHL) is suggested by case-control and cohort studies. Most previous studies have been too small to estimate accurately risks of specific categories of lymphoproliferative malignancies in relatives of NHL cases or to quantify the contribution of NHL case characteristics to familial risk. We have overcome sample size limitations and potential recall bias by using large databases from Sweden and Denmark. Diagnoses of lymphoproliferative malignancies were compared in 70,006 first-degree relatives of 26,089 NHL cases (including 7,432 with subtype information) versus 161,352 first-degree relatives of 58,960 matched controls. Relatives of NHL cases were at significantly increased risk for NHL [relative risk (RR), 1.73; 95% confidence interval (95% CI), 1.39-2.15], Hodgkin lymphoma (RR, 1.41; 95% CI, 1.0-1.97), and nonsignificantly for chronic lymphocytic leukemia (CLL; RR, 1.31; 95% CI, 0.93-1.85). No increased risk was found for multiple myeloma among case relatives. Findings with respect to siblings compared with parents and offspring or with respect to age at diagnosis of proband were inconsistent. In both populations, relatives of cases with an aggressive NHL subtype were at substantially increased risk of NHL (combined RR, 3.56; 95% CI, 1.80-7.02). We conclude that NHL has an important familial component, which is shared with Hodgkin lymphoma and CLL. We estimate that the absolute lifetime risk for a first-degree relative of an NHL case to develop NHL is 3.6% (compared with a population risk of 2.1%) and higher if the index case had an aggressive subtype of NHL.