Prevalence and localization of nodal metastases in squamous cell carcinoma of the oral cavity: role and extension of neck dissection

Lymph node (LN) metastases represent the most important negative prognostic factor in squamous cell carcinoma (SCC) of the oral cavity, even though controversies still exist regarding their management. The aim of this study was to retrospectively analyze our experience in surgical management of SCC of the oral cavity with particular focus on the prevalence and localization of lymph nodal metastases and recurrences. The clinical records of 89 consecutive patients treated from 1983 to 2002 by concomitant surgery on both the T and N sites, excluding those undergoing salvage surgery, were reviewed. A total of 119 neck dissections (ND) were performed. Survival outcomes were calculated by the Kaplan–Meier method, while univariate comparisons by the log-rank and non-parametric tests were performed between different groups of patients. Five-year overall and determinate survivals were 50 and 57%, respectively. LN metastases were observed in 52% (56% of these showing extracapsular spread) and their presence strongly correlated with determinate survival (p < 0.0001). The prevalence of clinical and occult nodal disease was not related to the pT status. Neck levels II (59%) and I (56%) were most frequently involved. Metastases to level IV accounted for 15% of positive LN, even though 28% of them turned out to be skip metastases. Five neck recurrences were observed, only one of which was salvaged by surgery. The high prevalence of clinical and occult LN metastases in this setting suggests that ND should be performed on a nearly routine basis, even for lesions with a low-T category and a cN0 neck. Moreover, ND should always encompass level IV due to the possibility of skip metastases, particularly in tumors involving the oral tongue. In patients with a cN+ neck, levels from I to V should be addressed, particularly in the presence of metastases at levels III and IV.     

INDICATIONS FOR ENDOSCOPIC MUCOSAL RESECTION FOR EARLY COLORECTAL CANCER: SHOULD THEY BE STRICT OR SHOULD THEY BE EXPANDED?

Endoscopic technologies have been developed greatly. As for early gastric cancer, the indications for endoscopic mucosal resection for early colorectal cancer have been widened recently. Technological advances can support wider and deeper resections using endoscopy but the remaining problem for the endoscopic management of cancer is lymph node metastasis. I discuss here the indication for endoscopic mucosal resection for early colorectal cancer to bring into focus the risk factors for metastasis to lymph nodes.     

Nodular hyperplasia surrounding fibrolamellar carcinoma

We report a case of acetaminophen-induced liver necrosis in a 14-year-old girl. At autopsy, a 9 cm subcapsular nodule was present in the right lobe of the liver which showed distinct zonation: a central greyish white area of fibrolamellar carcinoma with a peripheral fleshy, tan-coloured rim ranging from 1 to 2 cm in thickness. This peripheral zone consisted of nodular, hyperplastic parenchyma resembling the changes seen in focal nodular hyperplasia, and stood out from the adjacent necrotic parenchyma. The sparing of this zone from the deleterious effects of acetaminophen provides indirect evidence of a predominantly arterial rather than portal blood supply to this region. The arterial supply was most probably derived from the tumour vasculature and may explain the parenchymal hyperplasia sometimes reported adjacent to a fibrolamellar carcinoma. Awareness of this phenomenon is essential when evaluating a needle biopsy, as sampling of this region may lead to a false negative diagnosis.     

Lymphoid tissues induce NGF-dependent and NGF-independent neurite outgrowth from rat superior cervical ganglia explants in culture

Induction of neurite outgrowth from superior cervical ganglia (SCG) by rat lymphoid tissues was studied using a tissue culture model. Neonatal rat SCG were cultured with 6–12-week-old rat thymus, spleen, or mesenteric lymph node (MLN) explants in a Martrigel layer, in defined culture medium without exogenous nerve growth factor (NGF). SCG were also co-cultured with neonatal rat heart (as positive control) or spinal cord (SC; as negative control). To determine whether inflammation affects the ability of lymphoid tissues to induce neurite outgrowth, we also examined MLN at various times after infecting rats with Nippostrongylus brasiliensis (Nb-MLN). In one series of experiments, a single lymphoid tissue explant was surrounded by four SCG at a distance of 1 mm. The extent of neurite outgrowth was determinded by counting the number of neurites 0.5 mm away from each ganglion at several time points. Adult thymus and, to a lesser extent, spleen had strong stimulatory effects on neurite outgrowth from SCG after 12 hr or more in culture. For thymus tissue, this was similar to the positive control heart explants. MLN from normal rats had minimal effect on neurite outgrowth; however, Nb-MLN showed a time-dependent enhancement of the neurite outgrowth, maximal at 3 weeks after infection. The relative efficacy of neurite outgrowth induction (heart ≥ thymus ≥ Nb-MLN ≥ spleen ≥ MLN ≥ SC) was confirmed in a second series of experiments where one SCG was surrounded by three different tissue explants. We then examined the role of 2.5S NGF, a well-known trophic factor for sympathetic nerves, in the lymphoid tissue-induced neurite outgrowth. Anti-NGF treatment of co-cultures of SCG and heart almost completely blocked the neurite outgrowth. Anti-NGF also significantly inhibited thymus- and spleen-induced neurite outgrowth, but not as effectively as heart-induced neuritogenesis (93,80, and 77% inhibition at 24 hr; 86,70, and 68% inhibition at 48 hr for heart, thymus, and spleen, respectively). On the other hand, anti-NGF inhibited only 8% of neurite outgrowth induced by 3-week post-infection Nb-MLN at 24 hr, and 41% at 48 hr. These data show that several adult rat lymphoid tissues exert neurotrophic/tropic effects. The predominant growth factor in thymus and spleen is NGF, while Nb-MLN produces factor(s) which is (are) immunologically distinguishable from NGF. These neurotrophic/tropic factors are produced during the reactive lymphoid hyperplasia that forms part of the inflammatory response against the nematode, N. brasiliensis. This suggests the possibility that cytokines produced by lymphocytes or other inflammatory cells may stimulate sympathetic neurite outgrowth in vivo. © 1994 Wiley-Liss, Inc.     

Modulators of growth in primary culture of rat proximal tubular cells II

Summary: The present studies assessed the effects of manipulating extracellular sodium (Na) concentration and Na transport on cellular hypertrophy and hyperplasia in primary culture of rat proximal tubular cells. A concentration-dependent effect on thymidine incorporation and protein content was observed with cell culture media Na concentration of 130, 140 and 150 mmol/L. This effect was independent of osmolality (matched with mannitol) and no stimulatory effect occurred if choline was substituted for Na. Cells derived from sham-operated (Sx) animals exposed to a higher media concentration of Na (150 vs 140 mmol/L) had both stimulated thymidine incorporation to 186.8 ± 35.41% (P<0.05) and enhanced cell protein content to 134.7 ± 135% (P<0.05). This effect was more pronounced in cell cultures derived from unilaterally nephrectomized (Nx) animals, being 212.8 ± 31.5% (P<0.01) for thymidine incorporation (P<0.05 vs cells from sham-operated animals grown in high Na media) and 114.4 ± 3.2% (P<0.001) for protein content (P=0.11 vs sham-operated cells grown in similar conditions). the addition of 10^?4 mmol/L ethylisopropyl amiloride hydrochloride (EIPA) to Nx cells in a normal or high Na concentration media resulted in a decrease in cellular protein content to 82.6 ± 6.8% (P<0.05) and 85.5 ± 0.2% (P<0.0001) compared to respective controls. 10^?4 mol/L EIPA in media supplemented with insulin-like growth factor (IGF-1) blocked the proliferative response normally seen in response to this growth factor from 156.6 ± 13.7 to 27.5 ± 3.1% (P<0.0001) compared to control. However, the presence of EIPA did not abrogate the hypertrophic response elicited by IGF-1 (cell protein content 128.1 ± 13.1% of control with IGF-1 vs 124.9 ± 12.5 with IGF-1 and EIPA; P= n.s.). Addition of 10^?4 mol/L EIPA to 10% serum derived from either Sx or Nx animals blocked the growth response to the sera, limiting the cellular protein content to 76.6 ± 5.5% (P<0.0001) and 89.7 ± 4.4% (P<0.0001) and thymidine incorporation to quiescent levels of 0.2 ± 0.1% (P<0.0001) and 0.4 ± 0.1% (P<0.0001) compared to respective controls. In summary, rat renal proximal tubular cell growth is influenced by Na concentrations in the cell culture environment and inhibited in the presence of EIPA. This supports a role for altered epithelial transport in the cellular growth response to a number of stimuli.     

Colonic pseudolipomatosis, microscopically classified into two groups

Background: Colonic pseudolipomatosis is rare and the pathogenesis is controversial. The purpose of the present paper was to clarify endoscopic and histological characteristics of colonic pseudolipomatosis and to discuss the etiology. Methods: A total of 15 lesions from 14 patients was reviewed. They were able to be histologically classified into two groups on the basis of variety in size of the vacuoles: Group A, the ratio of largest vacuole to smallest vacuole in size is less than three, Group B, the ratio is more than four. Results: Four of 15 lesions were group A, and were endoscopically polypoid or flat lesions covered with normal‐looking mucosa. They were microscopically characterized by (i) predominant location in the upper portion of the lamina propria; (ii) no submucosal involvement; (iii) less variation in vacuolar size; and (iv) no association with lymph follicles. The vacuoles of group A contained proteinaceous materials in two of four lesions. Group B (11 lesions) had small elevated mucosa with normal‐looking surface or non‐elevated reddish mucosa. Microscopically, the lesions were mainly located in the lower portion of the lamina propria, occasionally also in the submucosa, had variable‐sized vacuoles, and were related to lymph follicles. Conclusion: It is suggested that the vacuoles in group A contain fluid, and may indicate an abnormal stagnation of interstitial fluid. Microscopic appearance of group B is essentially similar to that of pneumatosis coli. It is thought that group B probably results from penetration of gas from the crypts into the mucosa during colonoscopy. It is unclear why group B had a preference for ileocecal valve and an association with lymph follicles.     

Changes in hepatic lymph vessels in endotoxaemia.

This study was undertaken into rats to investigate changes in the hepatic lymph vessels and the space of Disse in endotoxaemia and to examine their relationship with the development of endotoxin-induced hepatic injury. Lymph stasis, namely dilatation of the lymph vessels and oedema, developed rapidly in the medium-sized portal canals, the large portal canals, and the liver hilum after endotoxin injection, but not in the small portal canals. Such changes reached their maximum 4-8 h after endotoxin injection and had recovered markedly by 16 h after the injection. The space of Disse remained within normal limits during this period. These findings suggest that the intrahepatic lymph stasis in endotoxaemia may be caused by a reduction in the pumping activity of the extrahepatic and the intrahepatic large lymph vessels rather than by an increase of lymph formation in the liver lobules. There was no evidence suggesting a direct relationship between the disturbance of hepatic lymph flow and the development of hepatic injury in endotoxaemia.