Assessing the suitability of gastric carcinoma for limited resection: histologic differentiation of endoscopic biopsy

Histologically differentiated adenocarcinoma satisfies one of the criteria for limited surgery for mucosal carcinoma of the stomach: however, the histology of the endoscopic biopsy specimen is often different from that of the resected specimen. The medical records of 1018 early gastric carcinomas were retrospectively analyzed to investigate the relation between the histologies of biopsy and resected specimens. Regression analysis showed that the histologies of biopsy specimens were significantly related to those of resected specimens (r = 0.677, n = 5, p = 0.0288) for the mucosal carcinomas, but their relation was not significant for the submucosal carcinomas (r = 0.677, n = 5, p = 0.2091). By analyzing the 344 differentiated mucosal carcinomas, moderately differentiated tubular adenocarcinomas were seen to be frequently less differentiated at resection. The histology of the biopsy specimens from mucosal carcinoma of the stomach grossly satisfies one of the criteria for limited surgery, but moderately differentiated adenocarcinoma may not be suitable for this treatment.     

Axillary lymph node metastases of bronchogenic carcinoma

BACKGROUND: Metastasis of bronchogenic carcinoma to axillary lymph nodes is rare. The pathways and possible significance of axillary lymph node metastasis from bronchogenic carcinoma were investigated. METHODS: Seventeen patients with probable axillary lymph node metastases from bronchogenic carcinoma were identified by computed tomography. There were 15 nonsmall cell lung cancers and 2 small cell lung cancers. Axillary lymph node metastasis was proven by biopsy in six cases. Metastases were presumed because of an increase in the size of axillary lymph nodes compared with prior studies in six patients and enlarged axillary lymph nodes associated with biopsy-proven ipsilateral supraclavicular lymph node metastasis in five patients. RESULTS: Four of 10 right-sided lung cancers had ipsilateral and six had contralateral axillary lymph node metastases. Six of seven left-sided cancers had ipsilateral and one had contralateral axillary lymph node metastases. Patients with ipsilateral lymph node disease had chest wall involvement and/or supraclavicular and mediastinal lymph node metastases. All seven patients with contralateral axillary lymph node metastases had supraclavicular and/or mediastinal lymph node metastases. CONCLUSION: Bronchogenic carcinoma may involve ipsilateral axillary lymph nodes via either chest wall invasion or retrograde spread from supraclavicular lymph nodes. Contralateral axillary lymph node involvement requires involvement of contralateral mediastinal and supraclavicular lymph nodes with retrograde spread to the axillary lymph nodes.     

Axillary lymph node metastases from bronchogenic carcinoma

BACKGROUND: Axillary lymph node metastases (ALNMs) from bronchogenic carcinoma are rare and their significance may be questioned. A surgical approach may allow a better understanding of the mechanism of their occurrence. METHODS: A retrospective study of 1,486 cases of surgically removed non-small cell lung carcinoma was performed. Twenty-two patients (1.5%) had extrathoracic nodal metastases. Nine of them were ALNMs (<1%). These cases form the basis of this study. RESULTS: In 1 patient ipsilateral ALNM was removed during a lung operation. It was a left non-small cell lung carcinoma invading the chest wall (T3 N2). In the other patients (n = 8) ALNMs were observed during postoperative follow-up; 4 underwent ALNM resection, 2 had radiotherapy, and 2 had symptomatic treatment only. For these 8 patients, in the TNM classification performed after an initial bronchogenic carcinoma operation, the lymph node status was, respectively, N0 in four cases, N1 in three cases, and N2 in one case. Survival ranged from 1 to 10 months, except for one patient who is still alive after more than 5 years. In this case, the ALNM was discovered 4 months after a right lower lobectomy for a T2 N0 adenocarcinoma. CONCLUSIONS: Axillary lymph node metastases may be involved through direct chest wall invasion of bronchogenic carcinoma or retrograde spread from supraclavicular lymphnode block. However, another mechanism seems to be the systemic vascular route.     

Papillary thyroid carcinoma: justification for total thyroidectomy and management of lymph node metastases

Papillary thyroid carcinoma (PTC) is the most common epithelial thyroid tumor and comprises approximately 80% of all thyroid cancers. In this article, the authors discuss the data showing that total thyroidectomy is the treatment of choice of clinically significant PTC, and review an algorithm for the management of lymph node metastases. Although the prognosis for patients with PTC is generally good, appropriate surgical management (total thyroidectomy plus 131I and life-long TSH suppression) can further reduce recurrence and cancer death rates significantly.     

Microcirculation of the lymph node with metastases

Microangiographic and histologic examination of the popliteal lymph node was performed on 49 rabbits 3 to 55 days after V2 tumor implantation into the hind paw. Control animals received subcutaneous tissue extract from normal rabbit donors. During the first 10 days after the tumor implant from an allogeneic animal donor, the draining lymph node exhibited a hypervascular response which after 2 weeks gradually subsided. Subsequently, during the early stages of lymph node metastasis there was still hypervascularity adjacent to the metastatic deposit. In about 4 weeks the metastases became more established and surrounded by layers of plasma cells. The hypervascular changes of the surrounding lymph node subsided by this time. In lymph node metastases the microvasculature could be an indicator of the immunologic activity of the host.     

Systematic sextant biopsies improve preoperative prediction of pelvic lymph node metastases in patients with clinically localized prostatic carcinoma

PURPOSE: An algorithm including the results of systematic sextant biopsies was statistically developed and evaluated to predict the probability of pelvic lymph node metastases in patients with clinically localized carcinoma of the prostate. MATERIALS AND METHODS: Clinical stage, serum prostate specific antigen concentration, Gleason score, number of positive biopsies, number of biopsies containing any Gleason grade 4 or 5 cancer and number of biopsies predominated by Gleason grade 4 or 5 cancer were recorded in 345 patients undergoing pelvic lymph node dissection and correlated with the incidence of lymph node metastases. Multivariate logistic regression, and classification and regression trees analyses were performed. RESULTS: In univariate analysis all variables had a statistically significant influence on lymph node status. Logistic regression showed that the amount and distribution of undifferentiated Gleason grade 4 and 5 cancer in the biopsies were the best predictors of lymphatic spread followed by serum prostate specific antigen. Classification and regression trees analysis classified 79.9% of patients who had 3 or fewer biopsies with Gleason grade 4 or 5 cancer and no biopsies predominated by undifferentiated cancer as a low risk group. In this group positive lymph nodes occurred in only 2.2% (95% confidence interval 0.8 to 4.7%). CONCLUSIONS: Including the results of systematic sextant biopsies substantially enhances the predictive accuracy of algorithms that define the probability of lymph node metastases in prostatic cancer. Patients thus defined as having no lymphatic spread could potentially be spared pelvic lymph node dissection before definitive local treatment.     

Mechanism of lymph node metastases: current concepts

Advances in head and neck surgical techniques with aggressive adjuvant treatment have reduced the incidence of locoregional failure in many types of head and neck cancer. Failure to control distant disease, however, remains of the most frustrating aspects in the care of these patients. A strong foundation in the biology of invasion and metastasis is necessary to understand more clearly the reasons for the development of distant and locally recurrent disease. This article focuses on basic mechanisms of invasion and metastasis in head and neck squamous cell carcinoma.     

Effect of lymph node dissection on survival of gastric carcinoma

We investigated microbial contamination of in-use antiseptics at a hospital. No microbial contamination was observed in 70 samples of 0.02% benzalkonium chloride solution (500-ml volume), 70 samples of 1% titratable I2 povidone-iodine solution (250-ml volume), or 15 samples of 0.1% ethacridine lactate solution (500-ml volume) during use in reduced amounts. Nor was any microbial contamination observed in 70 samples of cotton balls soaked in 1% titratable I2 povidone-iodine solution in canisters or cotton gauze soaked in 70% (w/v) ethanol solution in canisters. However, among 70 samples of cotton balls soaked in 0.02% benzalkonium chloride solution in canisters, 6 (8.6%) were contaminated with 10(4) to 10(6) viable cells/ml. The microbial species detected were glucose non-fermentative bacilli such as Alcaligenes xylosoxidans and Pseudomonas putida. The contaminants obtained from cotton balls soaked in 0.02% benzalkonium chloride solution did not proliferate in that solution or in distilled water but showed rapid growth in the cotton balls soaked in either of these liquids. These findings suggested that benzalkonium chloride solution tends to become contaminated when cotton balls are immersed. Therefore, cotton balls soaked in benzalkonium chloride solution are not recommended as an antiseptic. When no other choice is available, the cotton balls should be soaked in benzalkonium chloride solution at the time of usage.     

Tumor recurrence following resection for early gastric carcinoma and its implications for a policy of limited resection

Some patients suffer postoperative recurrence after curative resection of early gastric carcinoma. This study reviewed consecutive patients with a single primary lesion and analyzed the relation between the pathologic findings and recurrence of early gastric carcinomas for determining indications for limited surgery. Among the 1585 consecutive patients with a solitary primary lesion of an early gastric carcinoma who had undergone curative surgery between 1963 and 1989 at one general hospital, pathologic findings relating to recurrence were analyzed according to Japan's General Rules for Gastric Cancer Study in Surgery and Pathology. Of these carcinomas, mucosal carcinomas comprised 701 (44.2%) and submucosal ones 884 (55.8%). The total recurrence rate in this series was 1.0%. Submucosal carcinomas (1.6%) were significantly (p < 0.02) more recurrent than mucosal ones (0.29%). Of the 16 patients with recurrence, 10 (62.5%) died within 5 years after surgery, frequently because of blood-borne metastasis. Macroscopically elevated components, the degree of histologic differentiation, and lymph node metastasis significantly contributed to the postoperative recurrence. After detailed analysis of submucosal carcinomas, it is strongly suspected that carcinomas with a macroscopically elevated component were significantly associated with nodal involvement and microvessel invasion, and that these abnormalities lead to recurrence. Among the early gastric carcinomas, differentiated submucosal carcinomas with a macroscopically elevated component, lymph node metastasis, or both have the most potential of recurrence after surgery. Mucosal carcinomas must be restricted to limited surgery, but, blood-borne metastasis should be carefully avoided.     

Significance of CT in the detection of regional lymph node metastases in colorectal carcinoma

PURPOSE: For preoperative staging of colorectal cancer a CT scan is frequently performed. This report examines the sensitivity of CT for regional lymph node metastasis of colorectal cancer using different criteria. MATERIALS AND METHODS: Preoperative CT scans of 153 patients with colorectal cancer were analyzed using different criteria for N1. The results were then compared to the postoperative histological findings. RESULTS: For N1 = lymph nodes (LN) > 1 cm the sensitivity was 47%. For N1 = LN > 1 cm or an increased number of LN < 1 cm the sensitivity was 71%. In patients with a primary tumor seen on CT, sensitivity rose to 87%. DISCUSSION: Evidence of regional nodal metastatic disease is only relevant for rectal cancer, colon polyps, and for locally excised tumors when considering present surgical concepts for the treatment of colorectal cancer. In these cases CT analysis using the broadened criteria for N1 proposes a valuable argument regarding possible preoperative radiotherapy or an operative revision.     

Factors affecting prognosis of papillary thyroid carcinoma with bilateral cervical lymph node metastases

One hundred thirty nine cases of papillary thyroid carcinoma with bilateral lymph node metastases were reviewed. They were surgically treated at the Cancer Hospital of Shanghai Medical University in the years from 1956 through 1990. There were 73 men and 66 women with a median age of 35 (range 11-70) years. The median follow-up period was 11 years. Kaplan-Meier survival curves were calculated for the population. The overall survival rate was 94.7% at 5 years, 85.9% at 10 years, and 82.3% at 15 years. In univariate analysis, factors influencing prognosis are age at diagnosis, tumor size, extrathyroidal invasion, residual tumor and thoroughness of excision. When Cox proportional risk model was applied to analyze the survival data, factors of survival significance are the age at diagnosis and thoroughness of excision.     

Nuclear medicine approaches for detection of axillary lymph node metastases

Rhopalosiphum padi virus (RhPV) is an aphid virus that has been considered a member of the Picornaviridae based on physicochemical properties. The 10,011-nt polyadenylated RNA genome of RhPV was completely sequenced. Analysis of the sequence revealed the presence of two open reading frames (ORFs). The predicted amino acid sequence of ORF1, representing the first 6600 nt of the RhPV genome, showed significant similarity to the nonstructural proteins of several plant and animal RNA viruses. Direct sequence analysis of the RhPV capsid proteins showed that ORF2, which represents the last 2900 nt, encodes the three structural proteins (28, 29, and 30 kDa). The predicted amino acid sequence of ORF2 is very similar to the corresponding regions of Drosophila C virus, Plautia stali intestine virus, and to a partial sequence from the 3' end of the cricket paralysis virus genome. The site of initiation of protein synthesis for ORF2 could not be determined from the amino acid and nucleotide sequences. ORF1 is preceded by 579 nt of noncoding RNA and the two ORFs are separated by more than 500 nt of noncoding RNA. Like picornaviruses, these regions may function to facilitate the cap-independent initiation of translation of the two ORFs. These data suggest that RhPV, Drosophila C virus, Plautia stali intestine virus, and probably cricket paralysis virus are members of a unique group of small RNA viruses that infect primarily insects.     

Prospective randomized evaluation of preoperative endoscopic vital staining using CH-40 for lymph node dissection in gastric cancer

BACKGROUND: CH-40 is a suspension of activated carbon particles that was developed in Japan to carry anticancer drugs to regional nodes and peritoneal seedings of gastric cancer. METHODS: Forty-five consecutive patients who had surgical resection and D2 lymph node dissection for gastric cancer over a 2-year period were randomly assigned to preoperative endoscopic submucosal injection of CH-40 (group A) or no staining (group B). A total of 21 patients in group A and 24 in group B were available for analysis. RESULTS: The number of resected nodes per patient was significantly higher (t = 6.06; 40 df; P < .0001) in group A (mean+/-S.E. = 35.3+/-1.24) than in group B (mean+/-S.E. = 25.5+/-1.02). The rate of metastatic nodes resected was significantly higher (chi2 = 6.903 ; 1 df; P = .009) in stained (22.5%) than in non-stained (14.7%) nodes of group A and also (chi2 = 6.906; 1 df; P = .009) in stained nodes of group A than in group B (15.8%). CONCLUSIONS: Preoperative endoscopic vital staining with CH-40 proved to be rapid, safe, and effective in all cases in this series. Its use allowed surgeons to resect a higher number of lymph nodes. and to identify and examine more metastatic nodes. It also permitted identification of nodal micrometastases on routine histopathologic examination.     

Gamma-probe-guided resection of the sentinel lymph node in breast cancer

Regional lymph node metastases in patients with breast cancer have fundamental staging, prognostic, and treatment implications. Classically, axillary lymph node sampling requires a dissection under general anesthesia. The concept that a primary, or sentinel, lymph node is the first node to receive drainage from a tumor has been established in patients with malignant melanomas using radiolabeled tracers and vital dyes. This study proposed two hypotheses: (1) radiolabeled sentinel lymph nodes can be identified in most patients with breast cancer, and (2) radiolabeled sentinel lymph node biopsy accurately predicts axillary lymph node metastases in those patients. Patients with operable breast cancer had Tc-99 sulphur colloid injected around their breast tumors 1-6 hours preoperatively. Patients underwent gamma probe identification of sentinel lymph nodes that were biopsied. All patients underwent axillary lymphadenectomy in conjunction with lumpectomy or mastectomy. Fifty female patients ages 26 to 90 years underwent lumpectomies with axillary dissections (40 patients) or modified radical mastectomies (10 patients). Sentinel lymph nodes were identified in 42 of 50 patients (84%). Eight patients (16%) had metastases to the axillary lymph nodes. In 7 patients, sentinel lymph nodes correctly predicted the status of the axillary nodes. There was one false negative result. A total of 550 lymph nodes were resected for an average of 11.2 nodes per patient. Sentinel lymph node scintigraphy and biopsy accurately predicted the axillary lymph node status in 41 of 42 patients (98%). Scintigraphy can identify sentinel lymph nodes in a large majority of patients. Sentinel lymph node biopsy is an accurate predictor of axillary lymphatic metastases.     

Surgical treatment of gastric adenocarcinoma: the role of lymph node dissection

In this retrospective study, 652 patients who had curative resections for gastric cancer from 1977 to 1991 were reviewed to evaluate improvements in gastric cancer surgery and the influence of the extent of lymphadenectomy on survival. The patients were grouped into three time periods: 1977 to 1981, 1982 to 1986 and 1987 to 1991. The percentage of patients with early gastric cancer increased from 17.7% during 1977 to 1981, to 24.3% during 1987 to 1991. The average number of dissected lymph nodes was 7.5 +/- 8.1 during 1977 to 1981 and 16.4 +/- 10.3 during 1987 to 1991, when more radical lymphadenectomy was adopted. Total gastrectomies increased from 10.9% to 25.9% in the same time periods while combined visceral resections increased from 26.7% to 38.1%. Operative mortality decreased from 5.0% to 1.7%. The overall 5-year survival rate increased from 34.8% to 59.4%. In subgroup analysis, significant improvement of the 5-year survival rate was noted in the following groups: patients with stage I, II and III tumors but not stage IV; both proximal and distally located tumors; tumors with or without lymph node metastases; T1 and T2 but not in T3 and T4 (cancer invasion beyond the serosa). The decreased surgical mortality in recent years suggests that curative resection with extensive lymph node dissection can now be safely performed. Radical gastrectomy with extended lymphadenectomy may be adopted in gastric cancer resection for better control of regional disease.     

Histopathologic validation of the sentinel lymph node hypothesis for breast carcinoma

BACKGROUND AND OBJECTIVE: The sentinel node hypothesis assumes that a primary tumor drains to a specific lymph node in the regional lymphatic basin. To determine whether the sentinel node is indeed the node most likely to harbor an axillary metastasis from breast carcinoma, the authors used cytokeratin immunohistochemical staining (IHC) to examine both sentinel and nonsentinel lymph nodes. METHODS: From February 1994 through October 1995, patients with breast cancer were staged with sentinel lymphadenectomy followed by completion level I and II axillary dissection. If the sentinel node was free of metastasis by hematoxylin and eosin staining (H&E), then sentinel and nonsentinel nodes were examined with IHC. RESULTS: The 103 patients had a median age of 55 years and a median tumor size of 1.8 cm (58.3% T1, 39.8% T2, and 1.9% T3). A mean of 2 sentinel (range, 1-8) and 18.9 nonsentinel (range, 7-37) nodes were excised per patient. The H&E identified 33 patients (32%) with a sentinel lymph node metastasis and 70 patients (68%) with tumor-free sentinel nodes. Applying IHC to the 157 tumor-free sentinel nodes in these 70 patients showed an additional 10 tumor-involved nodes, each in a different patient. Thus, 10 (14.3%) of 70 patients who were tumor-free by H&E actually were sentinel node-positive, and the IHC lymph node conversion rate from sentinel node-negative to sentinel node-positive was 6.4% (10/157). Overall, sentinel node metastases were detected in 43 (41.8%) of 103 patients. In the 60 patients whose sentinel nodes were metastasis-free by H&E and IHC, 1087 nonsentinel nodes were examined at 2 levels by IHC and only 1 additional tumor-positive lymph node was identified. Therefore, one H&E sentinel node-negative patient (1.7%) was actually node-positive (p < 0.0001), and the nonsentinel IHC lymph node conversion rate was 0.09% (1/1087; p < 0.0001). CONCLUSIONS: If the sentinel node is tumor-free by both H&E and IHC, then the probability of nonsentinel node involvement is <0.1%. The true false-negative rate of this technique using multiple sections and IHC to examine all nonsentinel nodes for metastasis is 0.97% (1/103) in the authors' hands. The sentinel lymph node is indeed the most likely axillary node to harbor metastatic breast carcinoma.     

Papillary thyroid carcinoma: MR diagnosis of lymph node metastasis

We investigated the in vitro antifungal activity of amphotericin B, alone and in combination with rifabutin, an inhibitor of bacterial RNA polymerase, against 26 clinical isolates of Aspergillus and 25 clinical isolates of Fusarium. Synergy or additivism between these drugs was demonstrated against all isolates tested. Amphotericin B MICs were reduced upon combination with rifabutin from a mean of 0.65 microg/ml to a mean of 0.16 microg/ml against Aspergillus, and from a mean of 0.97 microg/ml to a mean of 0.39 microLg/ml against Fusarium (P < 0.000001 for both). Similarly, the MICs of rifabutin were reduced upon combination with amphotericin B from a mean of >32 microg/ml to a mean of 1.1 microg/ml against both fungi (P < 0.000001 for both). These positive interactions were corroborated by a colony count study with two Fusarium isolates, for which treatment with the combination of subinhibitory concentrations of amphotericin B (at concentrations 2- and 4-fold less than the MIC) and rifabutin (at concentrations ranging from 4- to 64-fold less than the MIC) resulted in 3.2-log reductions in colony counts compared to those after treatment with either drug alone. Inhibition of RNA synthesis was shown to be the mechanism of antifungal activity. These results suggest that inhibition of fungal RNA synthesis might be a potential target for antifungal therapy.