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Background. A randomized trial was undertaken comparing the Western R1 resection with limited N1-level lymphadenectomy and the Japanese R2 resection with extended lymphadenectomy, including the N2-level for curative resection of gastric cancer patients. After 389 patients were entered in the trial, protocol deviations were observed that reduced the intended distinction between the two types of lymphadenectomy: noncompliance, i.e., no substantiation of lymphadenectomy by nodal yields at indicated stations, and contamination, i.e., extension of lymphadenectomy outside the allocated level of nodal clearance. Methods. To identify factors underlying these protocol deviations, the authors analyzed the influence of six patient-, tumor, and treatment-related characteristics on the magnitude of deviations per patient, and on the incidence of deviations per lymph node station. Results. Protocol deviations were influenced by the following station-specific factors: (1) the number of nodes per station; (2) the clarity of anatomical station definition; (3) the location of stations; (4) local conventions on the type of gastrectomy; and (5) technical features to allow complete en bloc dissection. Furthermore, nonspecific factors such as inadequate retrieval of nodes, incomplete dissection, and careful selection of clinically overt metastases outside the allocated level of nodal clearance were randomly distributed over stations, and they, too, contributed to the deviations. Conclusions. Based on the findings, the authors took additional steps to preserve the distinction between limited and extended lymphadenectomy and to improve the accuracy of nodal staging. These factors should be considered when standardization of both surgicopathologic trials and clinical protocols for the treatment of gastric cancer is pursued. Cancer 1994; 73:1544-51. Key words: randomized controlled trial, stomach neoplasms, quality control, lymph node excision, neoplasm staging.

The purposes of this study were 1) to investigate the feasibility of using providers’ administrative systems for the assessment of healthcare utilization in economic evaluations performed alongside multicenter studies, 2) to assess the convergent validity of patients’ and providers’ reports of care, and 3) to investigate whether differences between providers’ and patients’ reports are related to age, gender, health, recall period, and volumes of care.

The outcome after surgery for rectal cancer differs markedly between patient series regarding local recurrence rates and survival. A high incidence of local recurrence is associated with conventional, nonstandardized procedures. To improve results of surgery, various additional treatments, such as radiotherapy, chemotherapy, and immunotherapy, have been tested. The Swedish Rectal Cancer Trial (SRCT) was the first trial to show that better local control achieved with preoperative radiotherapy resulted in improved survival. In recent years local control and survival have been further improved by the introduction of standardized total mesorectal excision (TME) surgery. A major problem of published studies on adjuvant therapy is that surgery was not standardized in these studies. Furthermore, quality control of the surgical technique by standardized pathological examination of the specimen is absent in most studies. In Europe, TME has become the preferred standard of operative management for rectal cancer. Adjuvant therapy studies should now be reexamined based on a platform of standardized, optimal surgery and pathology. We studied the European trials in which TME surgery is intentionally performed. Most of these trials are still in progress, with follow-up too short for definitive results, apart from interim analyses. However, the Dutch TME trial has already shown that performing a large, multicenter trial with quality control of both surgery and pathology is feasible. Semin. Surg. Oncol. 19:350–357, 2000. © 2000 Wiley-Liss, Inc.

The prognosis of patients with irresectable liver metastases derived from colorectal cancer is invariably poor; unfortunately, these tumours show only minor responses to conventional anticancer agents. The best responses have been obtained by fluoropyrimidines delivered as continuous infusion into the hepatic artery (HAI): their rapid uptake and detoxification by liver cells results in relatively low systemic drugs levels. This approach increases mean survival duration from 17 to 26 months and, in few patients, causes “down-staging” that may result in resectability. To improve opportunities for chemotherapy, the technique of 1-hour recirculating perfusion of the vascularly isolated liver (isolated hepatic perfusion, IHP) was developed. If leakage to the systemic circulation is negligible—and the compounds used do not readily cause hepatotoxicity—IHP allows usage of drug doses that would be fatal if delivered systemically. Because alkylating agents generally have steep dose-response curves, mitomycin C (MMC) and melphalan (L-PAM) entered phase I/II studies on IHP. Using these drugs, IHP was performed in principle as a single procedure in 60 otherwise untreated patients at our institution. However, despite preliminary data that indicate impressive clinical responses are obtained, improvement over HAI will probably be minor. Because IHP is a complicated way of drug delivery, one could argue that its use is justified only when it has the potential to kill all tumour cells in the liver. We critically discuss the possibilities of IHP and/or the use of gene therapy in an IHP setting. Semin. Surg. Oncol. 14:262–268, 1998. © 1998 Wiley-Liss, Inc.

A syngeneic rat liver metastasis model, the CC531 colon carcinoma cell line in Wag rats, was used to study the homing properties and anti-tumor effects of adoptively transferred, interleukin-2 (IL-2)-activated, cultured natural killer (A-NK) cells. To identify the route of administration that gives the highest tumor infiltration, 1.5 × 10⁸ A-NK cells were dyed with fluorescent rhodamine and injected via 4 different routes into rats, bearing subcapsularly induced (day 10) liver metastases. The routes chosen were: jugular vein, portal vein, hepatic artery and directly into the peritoneal cavity (i.p). The rats were sacrificed 20 hr after administration of A-NK cells. The highest (p < 0.05) infiltration of tumors by A-NK cells was found both at the tumor border and in the tumor center after injection via the hepatic artery: 65 ± 7 A-NK cells/mm² at the tumor border and 26 ± 14 A-NK cells/mm² in the center of the tumor (jugular vein infusion: 32 ± 10 and 9 ± 5 A-NK cells/mm², respectively; portal vein infusion: 36 ± 13 and 7 ± 4 A-NK cells/mm², respectively). No A-NK cells were detected in the liver after i.p. injection. Rats bearing day 5 tumors were injected with 1.5 × 10⁸ A-NK cells via the hepatic artery or via the jugular vein (n = 5 and n = 6 respectively). Regional administration of A-NK cells via the hepatic artery resulted in a significant (p < 0.05) lower weight (35 ± 23 mg) of tumors than did systemic administration (70 ± 10 mg). Our results suggest that both the level of tumor infiltration by adoptively transferred A-NK cells and the therapeutic outcome depend on the route of administration. Int. J. Cancer 75:233–238, 1998. © 1998 Wiley-Liss, Inc.

The incidence of breast cancer increases with age. The frequency of this cancer is increasing among older women because of the changing demographics and increased life expectancy. In addition to the classic tumor-related factors for predicting prognosis, individual patient characteristics may be associated with disease-specific mortality and other breast cancer outcomes. Data from observational studies in patients with breast cancer suggest an age-specific association with mortality.