Microscopic Lymphatic Invasion Research Articles

Tumor desmoplasia outperforms preoperative serum calcitonin as surgical biomarker in sporadic medullary thyroid cancer.

Conceptually, thyroid tumor desmoplasia may be better suited for excluding node metastases in sporadic MTC than preoperative serum calcitonin levels. This analysis included 181 patients with unilateral sporadic MTC graded on the 7-grade desmoplasia scale after thyroidectomy and neck dissection. When thyroid tumor desmoplasia reached 1% and ≥50%, node metastases increased from 0% to 7% (median of 0 metastases) and 83% (median of 7.5 metastases), microscopic lymphatic invasion from 0% to 3% and 35%, extrathyroid extension from 0% to 5% and 22%, and extranodal growth from 0% to 0% and 44%, whereas biochemical cure declined from 100% to 95% and 25%. Thyroid tumor diameters and basal calcitonin overlapped widely among the seven desmoplasia groups, precluding differentiation by thyroid tumor size or serum calcitonin levels. Thyroid tumor desmoplasia, unlike serum calcitonin levels, discriminates extremely well between node-negative and node-positive sporadic MTC, opening new avenues for precision surgery.

Prognostic factors for aggressiveness in subcentimeter papillary thyroid carcinoma: impact of tumor size and lymph node metastases.

Subcentimeter papillary thyroid carcinoma (sPTC), also known as papillary thyroid microcarcinoma, is associated with a good prognosis and low mortality risk. However, some sPTCs exhibit biologically aggressive characteristics. The aim of this study was to identify factors affecting the prognosis and aggressiveness of sPTC by considering the demographic characteristics of patients with sPTC and the pathologic characteristics of the tumors. The study included 255 patients aged ≥ 18 years who were operated on at Ondokuz Mayis University, Faculty of Medicine (Samsun, Turkey) between June 2008 and December 2021. All patients had histopathologic confirmation of sPTC (≤10 mm) and underwent regular follow-up for at least 36 months. The tumors had a mean size of 5 mm (0.1-10 mm) and were multifocal in 53.7% of patients. Capsular invasion was observed in 9% of patients. Vascular invasion, lymphatic invasion, and extrathyroidal invasion were present in 2%, 5.5%, and 0.8% of patients, respectively. Metastatic cervical lymph nodes were observed in 9.4% of patients. On multivariate logistic regression analysis, tumor size (odds ratio [OR] 1.380, 95% confidence interval [CI] 1.106-1.722, p = 0.004) and sex (OR 4.233, 95% CI 1.355-13.226, p = 0.013) were the main predictive factors influencing lymph node metastasis. Tumors > 5 mm, compared with tumors ≤ 5 mm, had higher rates of multifocality (p = 0.009), parenchymal invasion (p = 0.008), calcifications (p = 0.001), microscopic lymphatic invasion (p = 0.002), and presence of metastatic lymph nodes (p < 0.001). The findings of this study highlight important factors to consider in making decisions about prophylactic central compartment neck dissection in patients with sPTCs, particularly those with clinically node-negative tumors.

Metastatic risk profile of microscopic lymphatic and venous invasion in papillary thyroid cancer.

The aim of this study was to define the suitability of microscopic lymphatic and venous invasion for prediction of lymph node and distant metastases in papillary thyroid cancer. Stratification by microscopic lymphatic and venous invasion, and multivariable analyses on lymph node and distant metastases including microscopic lymphatic and venous invasion as independent variables. Tertiary referral centre. 422 patients who had ≥5 lymph nodes removed at initial thyroidectomy. Lymph node and distant metastases. Patients with microscopic lymphatic invasion had larger primary tumours than patients without and more often revealed microscopic venous invasion, multifocal tumour growth and lymph node metastases. Patients with microscopic venous invasion exhibited larger primary tumours than patients without and more commonly had microscopic lymphatic invasion, poor tumour differentiation, lymph node metastases and distant metastases. Prediction of lymph node metastases by microscopic lymphatic invasion was better than prediction of distant metastases by microscopic venous invasion regarding sensitivity (61.0 vs. 33.3%) and positive predictive value (92.6 vs. 20.9%), comparable regarding specificity (89.6 and 93.4%), and worse regarding negative predictive value (51.9 vs. 95.3%) and accuracy (70.1 vs. 87.7%). On multivariable logistic regression analysis, microscopic lymphatic invasion was associated with lymph node metastasis (odds ratio [OR] 11.1) and multifocal tumour growth (OR 2.4), whereas primary tumour size (OR 5.8 for tumours >40mm relative to tumours ≤20mm) and multifocal tumour growth (OR 3.1) were associated with distant metastasis. Stricter histopathological criteria are warranted to enhance the utility of microscopic vascular invasion for prediction of distant metastases in papillary thyroid cancer.

Preoperative percutaneous needle lung biopsy techniques and ipsilateral pleural recurrence in stage I lung cancer.

A recent meta-analysis of individual patient data revealed that preoperative percutaneous transthoracic needle lung biopsy (PTNB) was associated with an increased risk of ipsilateral pleural recurrence in stage I lung cancer. This study aimed to examine whether particular PTNB techniques reduced the risk of pleural recurrence. We retrospectively included 415 consecutive patients with stage I lung cancer who underwent preoperative PTNB and curative resection from 2009 through 2016. Detailed information was collected, including clinical, PTNB technique, radiologic, and pathologic characteristics of lung cancer. Cox regression analyses were performed to identify risk factors for pleural recurrence before and after propensity score matching. The overall follow-up period after PTNB was 62.1 ± 23.0months, and ipsilateral pleural recurrence occurred in 40 patients. Before propensity score matching, age (p = 0.063), microscopic pleural invasion (p = 0.065), and pathologic tumor size (p = 0.016) tended to be associated with pleural recurrence in univariate analyses and subsequently were matched using a propensity score. After propensity score matching, multivariate analysis revealed that ipsilateral pleural recurrence was associated with a larger target size on computed tomography (hazard ratio [HR] = 1.498; 95% CI, 1.506-2.125; p = 0.023) and microscopic lymphatic invasion (HR = 3.526; 95% CI, 1.491-8.341; p = 0.004). However, no PTNB techniques such as needle gauge, biopsy, or pleural passage numbers were associated with a reduced risk of recurrence. No particular PTNB techniques were associated with reduced pleural seeding after PTNB in stage I lung cancer. Regardless of the technique, PTNB needs to be cautiously applied when early lung cancer is suspected, followed by curative treatment. • Age, microscopic pleural invasion, and pathologic tumor size tended to be associated with pleural recurrence in stage I lung cancer before propensity matching. • After propensity matching, pre-biopsy CT target size and microscopic lymphatic invasion were associated with pleural recurrence. • No particular PTNB techniques were associated with reduced pleural seeding in stage I lung cancer before and after propensity matching.

Metastatic Risk Profile of Microscopic Lymphatic and Venous Invasion in Medullary Thyroid Cancer.

The metastatic risk profile of microscopic lymphatic and venous invasion in medullary thyroid cancer is ill-defined. This evidence gap calls for evaluation of the suitability of microscopic lymphatic and venous invasion at thyroidectomy for prediction of lymph node and distant metastases in medullary thyroid cancer. In this study of 484 patients with medullary thyroid cancer who had≥5 lymph nodes removed at initial thyroidectomy, microscopic lymphatic and venous invasion were significantly associated with greater primary tumor size (27.6 vs. 14.5 mm, and 30.8 vs. 16.2 mm) and more frequent lymph node metastasis (97.0 vs. 25.9%, and 85.2 vs. 39.5%) and distant metastasis (25.0 vs. 5.1%, and 32.8 vs. 7.3%). Prediction of lymph node metastases by microscopic lymphatic invasion was better than prediction of distant metastases by microscopic venous invasion regarding sensitivity (97.0 vs. 32.8%) and positive predictive value (58.4 vs. 39.2%); comparable regarding negative predictive value (98.5 vs. 90.5%) and accuracy (80.4 vs. 85.1%); and worse regarding specificity (74.1 vs. 92.7%). On multivariable logistic regression, microscopic lymphatic invasion predicted lymph node metastasis better (odds ratio [OR] 65.6) than primary tumor size (OR 4.6 for tumors>40 mm and OR 2.7 for tumors 21-40 mm, relative to tumors≤20 mm), whereas primary tumor size was better in predicting distant metastasis (OR 8.3 for tumors>40 mm and OR 3.9 for tumors 21-40 mm, relative to tumors≤20 mm) than microscopic venous invasion (OR 3.2). These data show that lymphatic invasion predicts lymph node metastases better in medullary thyroid cancer than venous invasion heralds distant metastases.

Risk of pleural recurrence after percutaneous transthoracic needle biopsy in stage I non-small-cell lung cancer.

To determine whether percutaneous transthoracic needle biopsy (PTNB) increased the risk of pleural recurrence in stage I non-small-cell lung cancer (NSCLC). In this retrospective study, we reviewed 830 consecutive patients with stage I NSCLC who underwent curative resection between 2004 and 2010. Cox regression analyses with propensity score matching were performed to identify risk factors for pleural recurrence. Of 830 patients, 540 (65.1%) underwent PTNB before surgery, while 290 (34.9%) underwent preoperative bronchoscopic biopsy or intraoperative wedge resection for a pathological diagnosis. Concomitant pleural recurrence occurred in 42 patients (5.1% [95% CI, 3.8-6.8]; 34 [6.3%] PTNB patients and eight [2.8%] non-PTNB patients) and isolated pleural recurrence took place in 26 patients (3.1% [95% CI, 2.1-4.6]; 20 [3.7%] PTNB patients and 6 [2.1%] non-PTNB patients). On multivariate analysis after matching, only visceral pleural invasion was associated with concomitant pleural recurrence (hazard ratio [HR]=3.367; 95% CI, 1.262-8.986; p=0.015) and isolated pleural recurrence (HR=3.216; 95% CI, 1.037-9.978; p=0.043), while PTNB was associated with neither concomitant nor isolated pleural recurrence (p=0.605 and p=0.963, respectively). Among 540 patients undergoing PTNB, the transfissural approach did not have a significant association with pleural recurrence (p=0.539 and p=0.313, respectively); instead, visceral pleural invasion and microscopic lymphatic invasion were significantly associated with concomitant pleural recurrence, and microscopic lymphatic invasion was associated with isolated pleural recurrence (p<0.05). PTNB did not significantly increase the risk of pleural recurrence in stage I NSCLC, whereas visceral pleural invasion was responsible for pleural recurrence. • PTNB did not significantly increase the risk of pleural recurrence in stage I NSCLC, whereas visceral pleural invasion was responsible for pleural recurrence. • The transfissural approach in PTNB did not increase the risk of pleural recurrence. • PTNB can be performed for the confirmatory diagnosis of peripheral stage I lung cancer without concern for the risk of pleural recurrence.

Long-term survival and cure model following liver resection for breast cancer metastases

IntroductionLong-term survival is still rarely achieved with current systemic treatment in patients with breast cancer liver metastases (BCLM). Extended survival after hepatectomy was examined in a select group of BCLM patients.Patients and methodsHepatectomy for BCLM was performed in 139 consecutive patients between 1985 and 2012. Patients who survived < 5 years were compared to those who survived ≥ 5 years from first diagnosis of hepatic metastases. Predictive factors for survival were analyzed. Statistically cured, defined as those patients who their hazard rate returned to that of the general population, was analyzed.ResultsOf the 139, 43 patients survived ≥ 5 years. Significant differences between patient groups (< 5 vs. ≥ 5 years) were mean time interval between primary tumor and hepatic metastases diagnosis (50 vs. 43 months), mean number of resected tumors (3 vs. 2), positive estrogen receptors (54% vs. 79%), microscopic lymphatic invasion (65% vs. 34%), vascular invasion (63% vs. 37%), hormonal therapy after resection (34% vs. 74%), number of recurrence (40% vs. 65%) and repeat hepatectomy (1% vs. 42%), respectively. The probability of statistical cure was 14% (95% CI 1.4–26.7%) in these patients.ConclusionsHepatectomy combined with systemic treatment can provide a chance of long-term survival and even cure in selected patients with BCLM. Microscopic vascular/lymphatic invasion appears to be a novel predictor for long-term survival after hepatectomy for BCLM and should be part of the review when discussing multidisciplinary treatment strategies.

Ipsilateral pleural recurrence after diagnostic transthoracic needle biopsy in pathological stage I lung cancer patients who underwent curative resection

ObjectivesThe relationship between transthoracic needle biopsy (TTNB) and pleural recurrence of cancer after curative lung resection remains unclear. We aimed to assess whether TTNB increases the ipsilateral pleural recurrence (IPR) rate and identify other potential risk factors for pleural recurrence after surgery. Materials and methodsThis retrospective study included 392 patients with p-stage I non-small cell lung cancer with solid or part-solid nodules after curative lung resection in 2009–2010. Imbalances among the characteristics were adjusted using an inverse probability-weighted method based on propensity scoring. Multivariate Cox’s regression analysis and the Kaplan-Meier method were used to determine independent risk factors for IPR. ResultsA total of 243 (62%) patients received TTNB, while 149 (38%) underwent an alternate, or no, diagnostic technique. IPR was significantly more frequent in the TTNB group (p=0.004), while total recurrence was similar between the groups (p=0.098). After applying the weighted model, diagnostic TTNB (hazard ratio [HR], 5.27; 95% confidence interval [CI], 1.49–18.69; p=0.010), microscopic visceral pleural invasion (HR, 2.76; 95% CI, 1.08–7.01; p=0.033) and microscopic lymphatic invasion (HR, 3.25; 95% CI, 1.30–8.10; p=0.012) were associated with an increased frequency of IPR. Among patients who received TTNB, microscopic lymphatic invasion was a risk factor for IPR (HR, 2.74; 95% CI, 1.10–6.79; p=0.030). ConclusionsThe diagnostic TTNB procedure is associated with pleural recurrence but may be unrelated to overall recurrence-free survival in early lung cancer. Moreover, microscopic lymphatic invasion could be a risk factor for pleural recurrence. TTNB should be carefully considered before lung resection and close follow-up to detect if pleural recurrence is needed.

Clinical characteristics of papillary thyroid carcinoma arising from the pyramidal lobe.

PurposePapillary thyroid carcinoma (PTC) arising from the pyramidal lobe is rare; therefore, clinicopathologic evaluation is lacking. In addition, the rate of occult malignancy in the pyramidal lobe after thyroid surgery is unclear. This study is to evaluate the clinical characteristics of PTCs that involve the pyramidal lobe.MethodsThe study enrolled 1,107 patients who underwent thyroid surgery for PTC at Seoul National University Hospital from 2006 to 2015. Pyramidal lobe status in pathologic reports was clear in all cases. “Pyramidal lobe-dominant PTC” was defined as single pyramidal lobe cancer or multifocal cancer with larger pyramidal lobe tumor. “Incidental pyramidal lobe PTC” was defined as occult cancer identified after thyroidectomy or as multifocal cancer with smaller pyramidal lobe tumor.ResultsTen patients were included in the pyramidal lobe-dominant PTC group. The mean age was 58 ± 12.5 years, and the mean tumor size was 0.7 ± 0.7 cm. Cervical lymph node metastasis was found in 5 patients (50%). Three patients had microscopic lymphatic invasion, and 7 had advanced American Joint Comitee on Cancer (AJCC) stage disease (5 with stage III and 2 with stage IV). Compared with conventional PTC (n = 1,058), pyramidal lobe-dominant PTC was significantly associated with lymphatic invasion (P = 0.031) and advanced AJCC stage (P = 0.022). The prevalence of incidental pyramidal lobe PTC was 3.56%.ConclusionPyramidal lobe PTC is relatively small in size; however, the rate of extrathyroidal extension and lymph node metastasis is high. Preoperative evaluation of nodal status is important, and the extent of surgery should be determined in accordance with the preoperative diagnosis.

Cholangiocarcinoma with intraductal tubular growth pattern versus intraductal papillary growth pattern

Intraductal neoplasms of the bile duct are macroscopically characterized by exophytic or polypoid growth patterns and have a favorable prognosis. Although some tumors with a predominantly tubular microscopic pattern have been reported, they have not been well characterized clinicopathologically. The purpose of the present study was to compare the newly recognized cholangiocarcinoma with an intraductal tubular growth pattern and cholangiocarcinoma with an intraductal papillary growth pattern and to investigate the pathological and prognostic significance of the former. This study analyzed 161 patients with tumors with exophytic or polypoid growth patterns from a large series of 733 cholangiocarcinoma cases surgically resected from January 1998 to May 2013. The study patients were divided into two groups: those whose tumors showed a predominantly tubular growth pattern (n=52) and those whose tumors exhibited a predominantly papillary growth pattern (n=109). Tubular growth pattern was associated with combined vascular resection and the absence of macroscopic mucin. Several histological indexes were significantly higher for the tubular growth pattern than the papillary one, including tubular adenocarcinoma, depth of invasion, microscopic lymphatic invasion, venous invasion, perineural invasion, and necrosis. Although the survival curves overlapped (P=0.693), the rate of liver metastasis was significantly higher for the tubular growth pattern than for the papillary one (P=0.012). Genomic DNA analysis focusing on somatic mutations in codons 12 and 13 of KRAS and codon 600 of BRAF revealed only one (4%) KRAS and no BRAF mutation among the 25 tubular cases examined. In conclusion, the tubular growth pattern exhibited differences in some histologic indexes, in addition to a higher hepatic metastasis rate and a lower KRAS mutation frequency, compared with the papillary growth pattern, but no difference in prognosis was observed. The distinctiveness of this tubular neoplasm should be further examined in the future.

Standardized Uptake Values in the Primary Lesions of Non-Small-Cell Lung Cancer in FDG-PET/CT Can Predict Regional Lymph Node Metastases.

Maximum standardized uptake values (SUVmax) at the primary lesions of non-small-cell lung cancer in (18)F-fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG-PET/CT), and the microscopic local extension of tumors were examined to develop reliable criteria to determine candidates for sublobar resection. We retrospectively analyzed 209 patients who underwent lobectomy, bilobectomy, or pneumonectomy with systematic lymph node dissection. Preoperative SUVmax at the primary lesion, microscopic lymphatic, venous, and pleural invasion in addition to lymph node metastases in the resected specimens were examined. Receiver operating characteristic analyses were used to predict an optimal cutoff for lymph node metastases. With receiver operating characteristic analysis, the areas under the curve for SUVmax and tumor size were 0.693 and 0.545, respectively, suggesting SUVmax superiority for prediction of lymph node metastases with a cutoff of 2.9. When a tumor was ≤2.0 cm (n = 41, 19.6 %), the percentages of microscopic lymphatic invasion, venous invasion, pleural invasion, and lymph node metastases were 12.2, 7.3, 4.9, and 17.1 %, respectively. When SUVmax was <3.0 (n = 91, 43.5 %), these percentages were 15.4, 3.3, 7.7, and 8.8 %, showing that SUVmax could efficiently exclude nodal metastases in more cases than tumor size. The postoperative 5-year survival rate was 86.6 % in patients with SUVmax < 3.0 and 58.1 % in patients with SUVmax ≥ 3.0 (p < 0.001). (18)F-FDG uptake value was more useful than tumor size for selecting patients with non-small-cell lung cancer suitable for intentional sublobar resection.

MicroRNA-21 ISH analysis to predict DFS in pancreatic cancer patients undergoing adjuvant gemcitabine after curative surgery.

234 Background: Overexpression of microRNA-21(miR-21) in pancreatic cancer has been reported to be associated with tumor cell proliferation, invasion, and also resistance to gemcitabine (GEM) chemotherapy. The aim of this study was to evaluate whether miR-21 expression, determined by microRNA ISH, was associated with clinical outcomes of pancreatic cancer patients who underwent adjuvant gemcitabine chemotherapy after curative surgery. Methods: Expression levels of miR-21 were semi quantitatively analyzed for staining intensity and distribution of positive tumor cells, by microRNA ISH in formalin-fixed paraffin embedded tissue arrays from 41 pancreatic cancer patients who underwent adjuvant GEM chemotherapy after curative resection at Kanagawa Cancer Center. The staining intensity for the miR-21 was assigned a score from 1 to 3 based on staining with1+: weakly, 2+: moderately, and 3+: strongly positive. The percentage of positive tumor cells was scored as follows, 1+: &lt; 50% positive cells, 2+: 50-80% positive cells, and 3+: ³a 81% positive cells. A composite score was obtained by calculating the sum of these two scores. Results: 27 patients were assigned to low miR-21 expression group (score &lt;4) and 14 patients to high miR-21 group (score 4,5,6). High miR-21 expression group had a significantly shorter DFS (P = 0.039, by log-rank test). The median DFS was 9.8 months (95% CI, 6.9-12.6) in the low miR-21 group, and 7.9 months (95% CI, 6.1-9.8) in the high miR-21 group. The median OS was 19.6 months (95% CI, 6.3-32.8) in the low miR-21 group, and 15.1 months (95% CI, 11.7-18.5) in the high miR-21 group, but was not significant. Multivariate analysis including miR-21 expression, microscopic lymphatic invasion and microscopic perineural invasion, indicated that miR-21 expression (p = 0.024) and microscopic lymphatic invasion (p = 0.035) were the independent predictor for DFS. Conclusions: A high level of miR-21 expression in pancreatic cancer was significantly associated with shorter DFS in patients who received adjuvant GEM after curative resection. miR-21 ISH analysis may serve as a significant predictor for GEM resistance in adjuvant setting.

090 * SIGNIFICANT INCREASE IN CIRCULATING TUMOUR CELLS IN PULMONARY VENOUS BLOOD DURING SURGICAL MANIPULATION IN PATIENTS WITH PRIMARY LUNG CANCER

Objectives: Circulating tumour cells (CTCs) are tumour cells shed from primary tumour which circulate in peripheral blood after passing through the drainage vein. This prospective study was conducted to assess changes in CTCs in the drainage pulmonary vein (PV) during lung cancer surgery. Methods: A total of 30 consecutive peripheral-type primary lung cancer patients who underwent lobectomy via thoracotomy (adenocarcinoma 73.3%; pathologic stage I 60%) were included. For each patient, 2.5 ml blood was sampled from the lobar PV of the primary tumour site before and after surgical manipulation for lobectomy. CTCs were quantitatively examined with the CellSearch system. Results: Before surgical manipulation, CTCs were detected in PV blood in the majority of patients (22/30, 73%), whereas CTCs were detected in peripheral blood in only two patients. The median number of CTCs in PV blood before manipulation (prePV-CTCs) was 4.0 (cells/2.5 ml), and there was no significant difference in prePV-CTCs according to any clinico-pathological characteristics including tumour size, progression, or histologic type. After manipulation, that is at the time of completion of lobectomy, PV-CTCs significantly increased (median postPV-CTCs 60.0, P < 0.001). Increase in postPV-CTCs was associated with microscopic lymphatic invasion. PV-CTCs significantly increased in tumours with lymphatic invasion (pre and postPV-CTCs, 4.0 and 90.5, respectively; P = 0.006), but not in tumours without lymphatic invasion (pre and postPV-CTCs, 3.5 and 7.0, respectively). Conclusions: We documented a significant increase in CTCs in drainage PV after surgical manipulation, especially in tumours with lymphatic invasion. We are awaiting survival data with 5-year follow-up, which may provide insight into the clinical significance of PV-CTCs.

Improving prediction of lateral node spread in low rectal cancers—multivariate analysis of clinicopathological factors in 1,046 cases

This study aims to search for independent predictors of lateral node metastasis in low rectal cancers. We analyzed 1,046 patients who underwent curative resection for lower rectal cancer in our prospectively collected database. All lymph nodes were dissected from the fresh specimen, and their locations were documented prospectively according to the classification by the Japanese Society of Cancer of the Colon and Rectum. More than 35% of the patients had demonstrated upward nodal metastasis in the direction of the inferior mesenteric vessels, while 11% demonstrated lateral node metastasis, which was present in 17.3% of patients with T3 and T4 lesions. Multivariate analysis revealed five factors to be statistically significant independent predictors of lateral node metastasis: female sex, tumors that were not well differentiated, pathological T3 and above, positive microscopic lymphatic invasion, and positive mesorectal nodes. Using the variables sex, differentiation, T stage, and mesorectal nodes as risk factors, because these could be elucidated preoperatively, the presence of lateral node metastasis was then analyzed according to the number of positive risk factors. When there were fewer than three positive factors, the risk of lateral nodal spread was low (4.5%). When three or more risk factors were positive, the odds of lateral node metastasis were more than 7.5 times higher (p < 0.001). The findings of this study provide a scoring system that can be used to guide the clinician to the presence of lateral node metastasis in low rectal cancers.

Clinical significance of lymph node dissection in renal cell carcinoma

To identify the role of lymph node dissection in renal cell carcinoma (RCC). A total of 100 patients (66 males, 34 females) were enrolled in the study. The mean age and tumor size were 61.4 years and 5.8 cm, respectively. A total of 41 patients (41%) had tumors <4 cm in diameter. The pathological status was pT1, pT2 and pT3 in 60, 11 and 29 patients, respectively. In total, lymph node metastases were found in seven cases (7%). Of 40 patients with pT1a tumors (tumor size <4 cm), one (2.5%) had lymph node metastasis. Patients with lymph node metastases had significantly larger tumors than those without (8.9 vs 5.5 cm; p<0.05). Regarding patient outcome, 33 (33%) had tumor progression (alive with disease, n=14; disease-specific death, n=19) after a median follow-up period of 54.0 months. In univariate analysis, 15/18 prognostic markers [tumor size, tumor grade, pT, pN and M categories, stage, microscopic venous invasion (V category), microscopic lymphatic invasion (Ly category), pathological tumor infiltration pattern (INF category), plasma fibrinogen, C-reactive protein, immunosuppressive acidic protein, alpha-2 globulin and erythrocyte sedimentation rates at 1 and 2 h] were common significant predictors of tumor progression. A Cox hazard model revealed tumor size, tumor grade and pathological stage to be independent prognostic factors. Tumor size is a crucial prognostic factor for tumor progression, and lymph node dissection may be omitted in T1a tumors.

Prognostic factors for gastric cancer in the elderly

Gastric cancer is one of the major causes of death from constructing a Kaplan–Meier survival curve. Univariate analysis was performed to evaluate significant malignant disease in Japan. An increasing number of elderly patients are presenting with this disease as the relationships between clinicopathologic features and patient survival. The results of the analysis are size of the geriatric population in Japan increases. The purpose of the present study was to determine the summarized in Table 1(a). Unfavourable prognostic factors included tumours factors affecting the prognosis of elderly patients suffering from gastric cancer. The prognosis of gastric cancer in located throughout the entire stomach, presence of lymph-node metastasis, capillary microinvasion, the elderly was examined in a study of 923 consecutive patients treated in the Department of Surgery, Sendai infiltrative and scirrhous histologic pattern and cancer invasion beyond the subserosal layer. Multivariate analysis National Hospital, Sendai, Japan in the 10-year period from 1985 to 1995. The macroscopic and microscopic using Cox’s proportional hazards regression model showed lymph-node metastasis, depth of invasion, classifications of gastric cancer were based on the general rules for Gastric Cancer Study in Japan. The patients lymphatic invasion and tumour location to be significantly correlated with 5-year survival (Table 1(b)). were divided into two age groups: group 1 (over 70 years of age) consisting of 273 patients aged 70–87 years Oohara et al. reported that gastric cancer in the aged (>70 years) was characterized by a large tumour, deep (average age, 75 years) and group 2 consisting of 650 patients aged 23–69 years (average age, 56 years). There cancer cell invasion, advanced stage and poor prognosis. However, some previous studies have suggested that the was no significant difference between the two groups with respect to gender, location, depth of invasion, long-term prognosis for gastric cancer in the elderly is favourable. In a study of 22 patients over 65 years of cancer–stromal pattern, infiltrative pattern, mode of lymph node metastasis, microscopic lymphatic invasion age presenting with gastric cancer in Mount Sinai Medical Center, Edelman et al. suggested that such patients have and type of operation, but there were significant differences with respect to tumour size, macroscopic the same morbidity and mortality rates following surgery for gastric cancer as do younger patients. Adachi et al. appearance, histologic pattern and microscopic vascular permeation. found that the patient’s age was not related to tumour size and depth of invasion, lymph-node metastasis or Survival curves were calculated by the Kaplan–Meier method, and comparisons were made using the log-rank histologic stage. They showed that elderly patients (>80 years) could be successfully treated with a good clinical test. The overall survival rate of patients in group 1 was similar to that of patients in group 2. The relationship outcome and that post-operative complications were between clinicopathologic variables and 5-year survival not serious. rate in group 1 patients was then determined by

Clinical characteristics and proliferating activity of intrahepatic cholangiocarcinoma.

To assist in the development of new approach to the palliation and treatment of intrahepatic cholangiocarcinomas, we classified tumours into mass-forming (MF), peri-ductal extension (PD), and spicula-forming (SF) types in 14 subjects who underwent surgical treatment. Lymph node metastasis and microscopic lymphatic invasion were pronounced in the PD and SF types. Furthermore, in SF type tumours the incidence of microscopic vascular and perineural invasion was high. The proliferating cell nuclear antigen labelling index, a reflection of the proliferation rate of tumour cells, was significantly higher in PD and SF types than in the MF type. The prognosis associated with the MF type tended to be better than that of the other two types. For the MF type, liver resection with tumour free margins must be performed, whereas for the PD and SF types, aggressive treatment, that is a combination of extensive liver resection, lymph node dissection, and effective adjuvant anti-cancer therapy should be provided to aim at life-long cure.

High Incidence of Nuclear Accumulation of p53 Protein in Gastric Cancer

The accumulation of p53 protein in the nuclei of cancer cells is known to correlate well with the presence of mutations in the p53 gene. We therefore investigated the immunohistochemical reactivity of the anti-p53 antibody, PAb1801, in specimens taken from 149 cases of primary gastric cancer and processed by acetone fixation, in order to elucidate the incidence and clinicopathological significance of p53 alterations in gastric cancer. Thirty-four out of 99 (34%) advanced gastric cancers and 11 out of 50 (22%) early gastric cancers showed positive reactions in the nuclei. The nuclei of non-cancerous cells, including gastric glandular epithelial cells, however, were not stained. Histopathologically, a nuclear accumulation of p53 protein was seen frequently in papillary adenocarcinoma, well- to moderately-differentiated tubular adenocarcinoma and poorly-differentiated adenocarcinoma with solid nests or focal tubular structures (43/101, 43%), but was rarely seen in signet-ring cell carcinoma, mucinous adenocarcinoma or poorly-differentiated adenocarcinoma growing in a scattered manner (2/48, 4%). There was no correlation between stainability of p53 protein and clinicopathological features such as depth of tumor invasion, microscopic lymphatic invasion, microscopic venous invasion, nodal involvement and clinicopathological stage in papillary adenocarcinoma, well- to moderately-differentiated tubular adenocarcinoma and poorly-differentiated adenocarcinoma with solid nests or focal tubular structures. The results suggest papillary adenocarcinoma, well- to moderately-differentiated tubular adenocarcinoma and poorly-differentiated adenocarcinoma with solid nests or focal tubular structures to share a common carcinogenetic pathway in which mutation of the p53 gene has an important role to play at a relatively early stage. Additionally, we showed the applicability of immunohistochemical detection of p53 protein in endoscopic biopsy material routinely formalin-fixed. The current method may be of some help in routine practice in discriminating between normal, precancerous and cancer cells in the stomach.

Radical Resection for Carcinoma of the Ampulla of Vater

One hundred four consecutive patients who underwent radical resection for ampullary cancer between 1965 and 1989 were retrospectively reviewed. Frequent clinical findings included jaundice (67%), significant (greater than 10%) weight loss (42%), and anemia (27%). Eighty-seven patients (84%) underwent a subtotal pancreatectomy, and 17 patients (16%) underwent a total pancreatectomy. The postoperative mortality was 5.7% (six patients), and reoperation for postoperative complications was required in six patients. The 5- and 10-year survival rates were 34% and 25%, respectively. Eight patients died of tumor recurrence more than 5 years after resection. Patient survival was significantly impaired by microscopic lymphatic invasion, regional nodal metastasis, tumor grade, and the epithelium of origin. In a multivariate analysis, only microscopic lymphatic invasion significantly reduced patient survival. Radical resection for ampullary cancer can be performed with a low morbidity and mortality and should remain the procedure of choice for ampullary carcinoma.