Randomized controlled trials of the efficacy of lung cancer screening by sputum cytology revisited

BACKGROUND:

Two randomized controlled trials of lung cancer screening initiated in the 1970s, the Johns Hopkins Lung Project and the Memorial Sloan‐Kettering Lung Study, compared 1 arm that received annual chest X‐ray and 4‐monthly sputum cytology (dual‐screen) to a second arm that received annual chest X‐ray only. Previous publications from these trials reported similar lung cancer mortality between the 2 groups. However, these findings were based on incomplete follow‐up, and each trial on its own was underpowered to detect a modest mortality benefit.

METHODS:

The authors estimated the efficacy of lung cancer screening with sputum cytology in an intention‐to‐screen analysis of lung cancer mortality, using combined data from these trials (n = 20,426).

RESULTS:

Over ½ of squamous cell lung cancers diagnosed in the dual‐screen group were identified by cytology; these cancers tended to be more localized than squamous cancers diagnosed in the X‐ray only arm. After 9 years of follow‐up, lung cancer mortality was slightly lower in the dual‐screen than in the X‐ray only arm (rate ratio [RR], 0.88; 95% confidence interval [CI], 0.74‐1.05). Reductions were seen for squamous cell cancer deaths (RR, 0.79; 95% CI, 0.54‐1.14) and in the heaviest smokers (RR, 0.81; 95% CI, 0.67‐1.00). There were also fewer deaths from large cell carcinoma in the dual‐screen group, although the reason for this is unclear.

CONCLUSIONS:

These data are suggestive of a modest benefit of sputum cytology screening, although we cannot rule out chance as an explanation for these findings. Cancer 2009. © 2009 American Cancer Society.     

Liver pathology following hepatic arterial infusion chemotherapy. Hepatic toxicity with FUDR

The authors reviewed the liver histopathology and the clinical features of eight patients with liver metastases from colorectal cancer who were treated by hepatic arterial infusion chemotherapy (HAIC) via an implantable pump (Infusaid). Before HAIC, these patients had no evidence of hepatitis, and results of liver biopsies performed on three patients showed only minor morphologic alterations. All the liver tumors responded to HAIC, but all patients developed hepatitis. Clinical findings included nausea, vomiting, abdominal pain and jaundice. Serum transaminases, alkaline phosphatase and bilirubin levels were increased. Clinical observations suggested that 5-fluoro-2'-deoxyuridine (FUDR), the predominant drug given, was the hepatotoxic agent. Toxic effects were hepatocyte necrosis, steatosis, cholestasis, central vein sclerosis, and alterations in the portal triad. In addition, central vein lesions like those in veno-occlusive disease, and micronodular cirrhosis resembling that induced by alcohol, were encountered. Although individual susceptibility to FUDR appeared to vary, portal triad fibrosis was present in all eight cases and, together with central vein sclerosis and cirrhosis, appeared to be related to the dose and duration of HAIC.     

Non-sentinel lymph node involvement in a patient with an atypical Spitz tumor and a positive sentinel node. Report of a case and review of the literature

We report a 20-year-old male patient with an atypical Spitz tumor, located in the dorsal aspect of his left hand, and a positive sentinel axillary lymph node. After lymphadenectomy, 1 of 23 non-sentinel lymph nodes excised was found to contain small multiple deposits of large spindle atypical melanocytes. Reviewing the pertinent literature, 5 of 29 patients with atypical Spitz tumors and positive sentinel nodes who had undergone lymphadenectomy have shown non-sentinel node involvement (17.2%), a proportion similar to that reported in melanoma patients. The exact nature of atypical Spitz tumors and the interpretation of cell deposits detected in sentinel nodes are still debated; data regarding the non-sentinel lymph node involvement in patients with atypical Spitz tumors may contribute to better understand the real biological potential of such tumors.     

Molecular methods for the study of the genetic determinants of nephropathy in type 1 (insulin-dependent) diabetes

Recently, evidence has accumulated that genetic factors may contribute to the development of diabetic nephropathy in patients with type 1 (insulin-dependent) diabetes mellitus. To identify variation at a gene locus, newly developed methods are introduced which employ denaturing gradient gel electrophoresis (DGGE) to study sequence differences in polymerase chain reaction (PCR)-amplified DNA fragments as well as in genomic DNA. These techniques are illustrated with studies of the angiotensinogen gene and the insulin receptor gene. In preliminary data from a comparison between individuals with and without diabetic nephropathy, we found no DNA sequence difference in the part of the angiotensinogen gene coding for angiotensin I. We did find, however, different distributions of a DNA polymorphism detected with the probe corresponding to exons 7 and 8 of the insulin receptor gene inRsaI DGGE blots in a comparison of patients with slow and fast progressing nephropathy. The interpretation of this finding and the need for further studies are discussed. In conclusion, the advent of methods of molecular genetics makes possible studies on genetic determinants of diabetic nephropathy. However, more clinical and epidemiological data are needed to find out how many genes are involved and how they interact with exposure to diabetes. Foremost, DNA from families with two or more siblings with diabetic nephropathy must be collected so that genetic studies will be possible.