BACKGROUND.Peritoneal carcinoma has been regarded as a uniformly lethal clini-

SUMMARY:The mechanism by which the immune system of a tumor-bearing host acquires tolerance toward tumor antigens is still elusive. Antigen-presenting cells (APCs) are critical regulators of the decision between immune response and tolerance. APCs that express the tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO) have been found to inhibit T-cell responses both in vitro and in vivo. We hypothesized that malignant tumors exploit this mechanism by recruiting IDO-expressing APCs to the tumor-draining lymph nodes. To test this hypothesis, archival tissues and records of 26 cases of lymph node dissection for invasive cutaneous melanoma were obtained. IDO immunohistochemistry was performed on 14 cutaneous tumors and 328 regional lymph nodes. Abnormal accumulations of IDO-positive cells with a monocytoid or plasmacytoid morphology were identified in the perisinusoidal regions of draining lymph nodes in 45% of nodes studied. Recruitment of IDO-positive cells was seen in nodes with and without malignancy. We hypothesize that these IDO-positive APCs may contribute mechanistically to acquired tolerance to tumor antigens. Immunostaining of tumor-draining lymph nodes for abnormal accumulation of IDOexpressing cells might thus constitute an adverse prognostic factor and could contribute to the decision process and the appropriate care of patients with this deadly disease. (Lab Invest 2003, 83:1457-1466.

There have been rare reports of glomerulopathies developing in patients with Bartter syndrome (BS) and its milder variant, Gitelman syndrome (GS). We present the first case of C1q nephropathy (C1qN) in an African American child with GS. This child was diagnosed with GS at 9 years of age and subsequently developed nephrotic range proteinuria 3 years later. Renal biopsy revealed mesangial hypercellularity and focal segmental glomerulosclerosis (FSGS). The segmental lesions were generally located at the vascular pole. Dominant C1q (2+) staining along with IgG (1-2+) was demonstrated in the mesangium, which correlated with scattered electron dense mesangial deposits demonstrated by electron microscopy. Treatment with an angiotensin-converting enzyme inhibitor led to an improvement in proteinuria to near-normal values (urine protein/creatinine ratio down to 0.5), but the creatinine clearance declined to approximately 58 ml/min/1.73 m(2). This case highlights the possible association between the milder hypokalemic tubulopathy, GS, and glomerular disease, including C1qN. Prompt evaluation of proteinuria with renal biopsy in these patients is recommended to detect significant glomerular pathology. Further research is needed to define risk factors for this complication.

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The purpose of this study was to determine the effect of proximal gastric distension on interdigestive patterns of canine gastrointestinal motility and to examine the role of extrinsic nerves in regulating such an effect. Serosal electrodes were placed on the antrum, duodenum, and jejunum. Animals were studied before and after transthoracic vagotomy or after neural isolation of the entire jejunoileum (extrinsic denervation). Proximal gastric distension for 5 h was provided by inflating with air a thin complaint bag placed into the proximal stomach after the onset of phase III of the migrating motor complex (MMC). Four volumes (0, 1.5, 12.5, and 25 ml/kg) were each tested four times in each animal. In neurally intact animals, gastric distension with volumes of 12.5 and 25 ml/kg consistently abolished the MMC in the antrum (100%), duodenum (96%), and proximal jejunum (greater than or equal to 62%), but less often in distal jejunum (greater than or equal to 25%). After vagotomy, gastric distension did not inhibit cycling of the MMC in the antrum, duodenum, or proximal or distal jejunum. After extrinsic denervation of the jejunoileum, gastric distension inhibited the MMC in the antrum and the duodenum but had no effect in the proximal or distal jejunum. These findings suggest that nonnutrient proximal gastric distension may contribute to postprandial changes in patterns of myoelectric activity in the upper gastrointestinal tract and that this effect is mediated by the vagus nerves.

Failure of surgical treatment for gastrointestinal cancers is often caused by recurrence of the tumor in traumatized peritoneal surfaces. This study examined the effect of intraperitoneal administration of doxorubicin and recombinant tissue plasminogen activator (rt‐PA), a fibrinolytic agent, on incidence and volume of postoperative tumor implants in peritoneal wounds. Prior to randomization, a surgical wound was created on the right parietal peritoneum of 110 BDIX rats and 6 × 105 DHD/K12 colon cancer cells were inoculated intraperitoneally (ip). The control group was given an intraperitoneal injection of saline. Five groups received 1 mg/kg of ip doxorubicin at different times postoperatively: at the end of surgery (DO), 3 hr after surgery (D + 3), postoperative day 1 (Dl), postoperative day 3 (D3), and postoperative day 7(D7). In a second set of experiments, five groups of rats received, in addition to postoperative doxorubicin, 5 mg/kg of intraoperative ip rt‐PA. Incidence and volume of tumor implants in peritoneal wounds were assessed for each group 20 days after the tumor inoculation. All rats of the control group (incidence = 100%) developed tumor implants in peritoneal wounds. Mean (SD) volume was 16.2 (4.7) mm3. When administered at DO, D + 3, and Dl intraperitoneal doxorubicin reduced significantly the incidence and volume of tumor implants in wounds. Postoperative administration of doxorubicin at D3 and D7 did not affect significantly the incidence and the volume of tumor implants in peritoneal wounds. When rt‐PA was administered intraoperatively, ip injection of doxorubicin at any postoperative timing decreased significantly the incidence and volume of tumor implants. In conclusion, ip doxorubicin administered before postoperative D3 may act on tumor cell implanted in peritoneal wounds. Delayed (D3, D7) ip administration of doxorubicin does not prevent the development of tumor implants in peritoneal wounds. Intraoperative administration of rt‐PA may significantly increase the efficacy of delayed ip chemotherapy. © 1996 Wiley‐Liss, Inc.

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