Biomedical subjects

Masahiko Yano

Publications and source records attributed to Masahiko Yano.

At least 19 recordsLinked to original sources

PubMed2006

Altered expression profiles of clock genes hPer1 and hPer2 in peripheral blood mononuclear cells of cancer patients undergoing surgery.

Patients undergoing surgery often develop symptoms of circadian rhythm disorders such as insomnia or delirium. However, the effect of surgery on the biological clock remains unknown. The present study examines the expression of clock genes in peripheral blood mononuclear cells (PBMCs) and measures plasma hormone concentrations in patients with esophageal cancer and early gastric cancer who underwent surgery. Six blood samples per day were collected from 9 patients with esophageal cancer before and after esophagectomy and from 9 patients with early gastric cancer before and after laparoscopy-assisted distal gastrectomy (LADG). The expression profiles of hPer1 and hPer2 mRNAs in PBMCs were determined by real-time RT-PCR. Plasma melatonin and cortisol concentrations were measured by radioimmunoassay. Plasma melatonin levels decreased in both groups throughout the day and plasma cortisol levels changed after surgery. The acrophase of clock gene expression was altered after surgery as follows: hPer1, from 6:19+/-1:50 to 13:59+/-0:59 (p=0.0003) and from 7:47+/-1:27 to 12:33+/-1:30 (p=0.0043) and hPer2, from 5:01+/-2:59 to 19:30+/-2:15 (p<0.0001) and from 6:49+/-1:59 to 13:39+/-3:06 (p=0.0171) in patients with esophageal and early gastric cancer, respectively. The post-operative phase change of hPer2 was more prominent after esophagectomy than after LADG. Our results suggest that surgical stress affects the peripheral clock as well as endogenous hormones in humans.

Cell Cycle Proteins↗

PubMed2006

Prediction of peritoneal metastasis in advanced gastric cancer by gene expression profiling of the primary site.

Peritoneal metastasis is the most common cause of tumour progression in advanced gastric cancer. Clinicopathological findings including cytologic examination of peritoneal lavage have been applied to assess the risk of peritoneal metastasis, but are sometimes inadequate for predicting peritoneal metastasis in individuals. Hence, we tried to construct a new prediction system for peritoneal metastasis by using a PCR-based high throughput array with 2304 genes. The prediction system, constructed from the learning set comprised of 30 patients with the most informative 18 genes, classified each case into a 'good signature group' or 'poor signature group'. Then, we confirmed the predictive performance in an additional validation set comprised of 24 patients, and the prediction accuracy for peritoneal metastasis was 75%. Kaplan-Meier analysis with peritoneal metastasis revealed significant difference between these two groups (P=0.0225). By combining our system with conventional clinicopathological factors, we can identify high risk cases for peritoneal metastasis more accurately.

Aged↗

PubMed2006

Advantage of pancreaticogastrostomy in detecting recurrent intraductal papillary mucinous carcinoma in the remnant pancreas: a case of successful re-resection after pancreaticoduodenectomy.

Recently there has been an increase in the number of case reports detailing the recurrence of cancer in the pancreatic remnants following surgical resection of intraductal papillary mucinous carcinoma (IPMC) of the pancreas. A case is presented here to indicate the advantage of pancreaticogastrostomy (PG) in terms of postoperative follow-up after pancreaticoduodenectomy (PD) for IPMC. A 68-year-old man underwent PD for IPMC of the pancreatic head, and the cut margin of the pancreatic duct was diagnosed as having no cancer but moderately dysplastic epithelium by an intraoperative frozen section of histology. Thus, we decided to proceed with a PG rather than pancreaticojejunostomy (PJ) in order to facilitate easier postoperative examinations. Eight years and 6 months later, during a routine follow-up examination, duct dilation of the remnant pancreas was detected by magnetic resonance imaging (MRI). Upon examination by endoscopic gastroscopy, the anastomotic site was found to be covered with a large amount of mucin from which we easily obtained both cytologic and biopsied specimens, which subsequently proved positive for cancer. In line with our diagnosis of recurrent IPMC, the patient underwent a second surgery (resection of the remnant pancreas, total pancreatectomy) and postoperative histology confirmed that indeed the patient had experienced recurrent IPMC with no nodal involvement or invasion beyond the pancreatic confines. Based on this experience, we decided to recommend PG for all patients deemed to be at high risk for the recurrence of cancer in the pancreatic remnants following PD for IPMC of the pancreatic head.

Adenocarcinoma, Mucinous↗

PubMed2006

A prospective trial for avoiding cervical lymph node dissection for thoracic esophageal cancers, based on intra-operative genetic diagnosis of micrometastasis in recurrent laryngeal nerve chain nodes.

BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate the usefulness of intra-operative genetic diagnosis of RN node micrometastasis in the decision-making of 3FL for thoracic esophageal cancers. METHODS: Eighty-nine patients with middle and lower thoracic esophageal cancer were enrolled in a prospective study, in which 3FL was performed when RN node metastasis was revealed by intra-operative histological examination and/or genetic analysis using real-time RT-PCR assay. For other cases, 2FL was performed. RESULTS: Of the 89 patients, 3FL was performed for 33 patients and 2FL for 56 patients. In the 3FL group, RN node metastasis was both histologically and genetically positive in 19 patients, histologically negative and genetically positive in 11, and histologically positive and genetically negative in 3, with cervical node metastasis being detected in 7, 3, and 0 patients, respectively. In the 2FL group, only one patient had cervical node recurrence during the follow-up period. The post-operative survival in this study was equivalent to that of the historical controls (3-year survival rates 63.9% vs. 52.3%, P = 0.1513) of 66 3FL patients when 3FL was the first choice for thoracic esophageal cancers. CONCLUSIONS: Intra-operative histological and genetic diagnosis of RN node metastasis may help avoid unnecessary cervical node resection. A Phase III trial should be done.

Aged↗

PubMed2006

Factors affecting the prognosis of patients with esophageal cancer undergoing salvage surgery after definitive chemoradiotherapy.

BACKGROUND AND OBJECTIVES: Although salvage surgery after definitive chemoradiotherapy (CRT) is common, the safety and indication has not yet been established. METHODS: We retrospectively compared the mortality and morbidity of 24 patients who underwent salvage surgery with those of historical controls treated with neoadjuvant CRT followed by planned esophagectomy during the same period, and analyzed the prognostic factor of salvage surgery. RESULTS: Preoperative serum albumin (3.7 vs. 4.1 g/dl, P = 0.0157) and lymphocyte count (763 vs. 964/mm(3), P = 0.0111) in the salvage group were significantly lower than those in the neoadjuvant group. A significant difference was also observed in operation time (567 vs. 474 min, P = 0.0381), C-reactive protein (CRP) on postoperative day 1 (11.2 vs. 8.7 mg/dl, P = 0.0021), and postoperative systemic inflammatory response syndrome (SIRS) duration (3.5 vs. 2.9 days, P = 0.0486). There were three hospital deaths in the salvage group, whereas no patient died in the neoadjuvant group. Multivariate analysis showed curability (R0 vs. R1 + R2) to be the strongest prognostic factor of salvage surgery (P = 0.0064). R1 + R2 operation was more frequently performed in the salvage group (33% vs. 13%), and the reason for all cases was unresectable T4, which had been underestimated preoperatively. CONCLUSIONS: Salvage surgery is a highly invasive and morbid operation, which is performed on immunocompromised hosts. The indication must be carefully considered, with care taken to avoid non-curative surgery.

Aged↗

PubMed2006

Clinical significance of the second cycle response to cisplatin-based chemotherapy as preoperative treatment for esophageal squamous cell carcinoma.

BACKGROUND: Repeating two cycles of cisplatin-based chemotherapy is standard protocol for preoperative treatment for advanced esophageal squamous cell carcinoma (ESCC). However, the second cycle of chemotherapy is often less effective than the first. METHODS: Forty-six patients with advanced ESCC underwent two (41) or one (5) cycle of chemotherapy, consisting of cisplatin, adriamycin, and 5-fluorouracil (5-FU), followed by surgery. RESULTS: The tumor reduction rates (RR) for the first and second cycles of chemotherapy were 33.3 +/- 22.5% versus 11.5 +/- 42.6%, with the second showing less effectiveness and larger deviation. The second cycle RR was closely correlated with the pathological findings of the surgical specimens, including the effect of chemotherapy, tumor depth, and lymph node metastases, and with postoperative survival rates, which were 75.2% and 26.8% (P = 0.0028) at 3 years for good and poor responders. The first cycle RR showed correlation with neither. The second cycle RR was the only independent prognostic factor among the preoperative parameters in multivariate analysis. CONCLUSIONS: The second cycle of cisplatin-based chemotherapy in ESCC is less effective, but more closely related with postoperative survival than the first. Treatment other than surgery should be considered for ESCC resistant to second cycle chemotherapy.

Adult↗

PubMed2006

Overexpression of hypoxia-inducible factor-1 alpha in gastric adenocarcinoma.

BACKGROUND: The transcriptional factor hypoxia-inducible factor 1alpha (HIF-1alpha) controls angiogenesis and metabolism by upregulating hypoxia-induced genes, such as the vascular endothelial growth factor (VEGF) gene and the glucose transporter (GLUT-1) gene. In addition to its regulation by oncogenes or tumor suppressor genes such as HER2, p53, VHL, and PTEN, overexpression of HIF-1alpha is induced by hypoxia. Increased HIF-1alpha expression is associated with malignant potential, and with patient prognosis and response to chemoradiotherapy in some cancer types. METHODS: We investigated the association between HIF-1alpha expression and clinicopathological characteristics, including the expression of VEGF and p53 proteins, in gastric cancer. Furthermore, we analyzed the impact of HIF-1alpha, VEGF, and p53 protein expression on resistance to chemotherapy in advanced gastric cancer. RESULTS: Among 146 specimens from patients with gastric adenocarcinoma, 89 (61.0%), 52 (35.6%), and 102 (69.9%) were positive for HIF-1alpha, p53, and VEGF expression, respectively. The increased expression of HIF-1alpha protein correlated significantly with the increased expression of p53 (P < 0.0001) and VEGF (P = 0.0007). However, overexpression of these proteins was not associated with prognosis or clinicopathological status, with the exception of infrequent distant metastases. Furthermore, overexpression of these proteins was not associated with chemosensitivity in these patients with gastric cancer. CONCLUSION: Our results indicate that overexpression of HIF-1alpha correlates significantly with p53 and VEGF protein expression in patients with gastric cancer; however, this overexpression shows no association with clinicopathological status, patient prognosis, or chemosensitivity.

Adenocarcinoma↗

PubMed2006

Risk of recurrence in a long-term follow-up after surgery in 417 patients with hepatitis B- or hepatitis C-related hepatocellular carcinoma.

OBJECTIVE: The aim of this study is to clarify the difference of risk of recurrence after hepatic resection between patients with hepatitis B- and hepatitis C-related hepatocellular carcinoma (HCC). SUMMARY AND BACKGROUND DATA: HCC is a highly recurrent carcinoma. However, consensus has not yet been reached about the relationship between hepatitis virus types and risk of recurrence in a long-term follow-up for HCC patients who underwent hepatic resection. PATIENTS AND METHODS: From the beginning of January 1990 to the end of December 1999, of 469 HCC patients who underwent curative hepatic resection, 66 (14%) patients with positive hepatitis B virus surface antigen (HBs-Ag) and negative hepatitis C virus antibody (HCV-Ab) were regarded to have B-type hepatitis (HB)-related HCC (HB-HCC) and 351 (75%) with negative HBs-Ag and positive HCV-Ab were regarded to have C-type hepatitis (HC)-related HCC (HC-HCC). A clinical follow-up was performed to assess the existence of recurrence with the median follow-up periods of 11.0 and 10.1 years for HB- and HC-HCC patients, respectively. RESULTS: The 3-, 5-, and 10-year disease-free survival (DFS) rates of HC-HCC (40%, 24%, and 12%, respectively) were significantly shorter than those of HB-HCC (57%, 54%, and 28%, respectively) (P = 0.0001). In multivariate Cox proportional hazard analysis, viral type, TNM stage, surgical margin, and Edmondson's grade were significantly associated with risk of recurrence. The risk of recurrence from the initial HCC increased to 1.93 times (95% confidence interval, 1.27-2.93) greater in HC-HCC patients than in HB-HCC patients. CONCLUSION: Hepatitis viral type is an independent factor for recurrence of HCC in a long-term clinical follow-up. This finding suggests that we may need a different strategy to control postoperative recurrence by the viral types in HCC patients.

Aged↗

PubMed2006

Clinical significance of class III beta-tubulin expression and its predictive value for resistance to docetaxel-based chemotherapy in gastric cancer.

Docetaxel, one of the most effective anticancer drugs for gastric cancer, targets beta-tubulin, the major protein in mitotic spindles. Eight isotypes of beta-tubulin, with tissue and organ-specific expression, have been identified in mammalian cells. We examined class III beta-tubulin expression in gastric cancer and assessed its relationship with sensitivity to docetaxel-based chemotherapy. A total of 115 paraffin-embedded gastric tumors were analyzed by immunohistochemistry for class III beta-tubulin expression. Twenty patients with advanced gastric cancer received preoperative docetaxel-based chemotherapy. Their biopsied specimens, obtained by endoscopy before chemotherapy were examined for class III beta-tubulin expression. The relationship between expression and chemosensitivity was assessed. Forty-two (36.4%) of 115 cases were confirmed to be positive for class III beta-tubulin expression. There was no association between clinicopathological status and prognosis. Among the patients positive for class III beta-tubulin expression, only 16.7% showed no response to chemotherapy, while 64.3% responded to the chemotherapy in the negative group. Our results suggest that class III beta-tubulin is a simple and useful predictive marker for the clinical response to docetaxel-based chemotherapy in gastric cancer.

Adult↗

PubMed2006

[A case of high-dose rate interstitial brachytherapy for locally recurrent rectal cancer].

The patient was a 55-year-old female who underwent an abdomino-perineal resection for advanced lower rectal cancer. The tumor was a well differentiated adenocarcinoma, type 2 in the Japanese classification of colorectal carcinoma, and was measured 2.3 cm in size. Histologically, the tumor was considered to be stage IIIb (mp, n3(+), P0, H0, M(-)). She received adjuvant chemotherapy with 5'-DFUR. After 13 months from the surgery, the patient developed a hip pain. After 16 months from the surgery, a pelvic MRI scan revealed a 3 cm tumor in the perineum. Biopsy from the tumor revealed adenocarcinoma. Consequently, we diagnosed local recurrence in the perineum. Chemotherapy with CPT-11 (230 mg/body) and 5'-DFUR (800 mg/body) was administered for 2 cycles. Because the tumor was enlarged, high-dose rate interstitial brachytherapy was given to the recurrent site at a total dose of 54 Gy/9 fractions/5 days. There were no severe complications. CEA was decreased within normal range from a maximum of 9.3. No progress was detected on CT and MRI, and the hip pain had disappeared. The tumor marker is within normal range for about 2 years and QOL was improved. Hence, high dose rate interstitial brachytherapy appears to be effective for locally recurrent rectal cancer.

Adenocarcinoma↗

PubMed2006

[A surgical case of solitary lymph node metastatic recurrence of hepatocellular carcinoma after hepatectomy].

The patient was a male in the sixties who received interferon therapy against hepatitis C. At first, the patient was pointed to having an increased alpha fetoprotein (AFP) level of 1104 ng/ml. Partial hepatectomy was performed against hepatocellular carcinoma (HCC) (segment 3, 44 mm in diameter) and diagnosed by further exams. The serum AFP level decreased to a normal range after hepatectomy for the time being. A rapid elevation of serum AFP level (11,293 ng/ml) was observed nine months after the surgery. No evidence of recurrence in the intra- and extra hepatic organs such as adrenal gland, lung, bone, and brain except for intra abdominal solitary lymph node metastasis was observed. Then the metastatic lymph node was removed surgically. After the removal of the lymph node, the serum AFP level decreased within a normal limit immediately. This patient currently survives without the disease for 30 months after the initial operation, and for 19 months after a resection of the meatastatic lymph node.

Biomarkers, Tumor↗

PubMed2006

[A case of apocrine adenocarcinoma suspected as an axillary lymph node metastasis from cecal cancer].

The patient was a 69-year-old male. He had a 2-year history of subcutaneous tumor in the left axilla. Biopsy of the tumor showed the features of metastatic adenocarcinoma. FDG PET to check the primary lesion revealed the collection of an ileocecal junction and left axilla. After CT scan and colonoscopy, we diagnosed cecal cancer and metastasis of the axillary lymph nodes from it. He underwent ileocecal resection and a wide local resection of the axillary tumor. Histopathological examination showed the axillary tumor was different from the cecal cancer. Axillary tumor was diagnosed not as metastasis of axillary lymph nodes from cecal cancer but apocrine adenocarcinoma.

Adenocarcinoma↗

PubMed2005

Bile acid promotes the proliferation of squamous cell carcinoma of the esophagus, independent of its inducing COX-2 expression.

BACKGROUND: We have reported G1 progression and cyclooxygenase-2 (COX-2) induction during carcinogenesis of the squamous epithelium of the esophagus. As bile acid induces COX-2 expression and promotes carcinogenesis in the digestive tract, we investigated the effect of bile acid on the proliferation of squamous cell carcinoma of the esophagus (ESCC). MATERIALS AND METHODS: MTT assay, Western blot analysis of COX-2 and cell cycle-related molecules in the G1 phase (Rb, CDC25A, cyclin D1), and CDK2 kinase assay were performed on chenodeoxycholic acid (CDCA) exposure to ESCC cell lines (TE2R, TE3, TE13, TE15). RESULTS: In the presence of gradient bile acid concentration (up to 100 microm), growth of ESCC cell lines was stimulated at a low concentration (maximally at 20-30 microm), but suppressed at a higher concentration. Only a low dose of bile acid induced the expression of cyclin D1 and CDC25A and showed high Rb phosphorylation and high CDK2 kinase activity. In contrast, bile acid progressively induced COX-2 expression in a dose-dependent manner, regardless of its biphasic effects on cell proliferation, and a COX-2 specific inhibitor (JTE-522) did not suppress growth stimulation by a low dose of bile acid. CONCLUSIONS: Bile acid at a low dose stimulates the proliferation of ESCC by inducing G1-regulating molecules. However, COX-2 expression, which is also induced by bile acid, does not affect cell proliferation. Further work is needed to elucidate its role in carcinogenesis.

Bile Acids and Salts↗

PubMed2005

Overexpression of ADAM9 enhances growth factor-mediated recycling of E-cadherin in human colon cancer cell line HT29 cells.

Growth factor-mediated stimulation of epithelial cells induces the disassembly of E-cadherin-mediated cell-cell adhesion. We found that overexpression of a disintegrin and metalloprotease 9 (ADAM9) enhanced growth factor-mediated induction of endocytosis and dynamic recycling of E-cadherin in HT29 human colon cancer cells. In addition, ubiquitination and degradation of E-cadherin were reduced in these cells. ADAM9 constitutively interacted with E-cadherin, and the two proteins co-localized at the plasma membrane of HT29 cells. Administration of a metalloprotease inhibitor or overexpression of an ADAM9 mutant lacking metalloprotease activity attenuated growth factor-dependent endocytosis and recycling of E-cadherin as well as scattering of HT29 cells. These results suggest that the metalloprotease activity of ADAM9 mediates growth factor-induced endocytosis and dynamic recycling of E-cadherin and prevents E-cadherin degradation.

ADAM Proteins↗

PubMed2005

Plasma D-dimer levels show correlation with number of lymph node metastases in patients with esophageal cancer.

BACKGROUND: Systemic activation of hemostasis and fibrolysis has been shown to be related to tumor progression in patients with malignancies such as lung cancer and colorectal cancer, but there has been no report of these clotting abnormalities in esophageal cancer. We investigated the clinical importance of measuring plasma levels of D-dimer (DD), which is a marker of the hypercoagulable stage, in preoperative patients with esophageal cancer. STUDY DESIGN: Preoperative plasma DD levels were measured in 96 patients with primary esophageal cancer who were scheduled for esophagectomy with lymphadenectomy without preoperative treatment at our hospital. Results were correlated with the clinicopathological findings. RESULTS: Significantly different plasma DD levels were found with respect to histologic T (p = 0.0015), histologic N (p < 0.0001), number of metastatic nodes (p < 0.0001), and histologic stages (p < 0.0001). The number of lymph node metastases (0/1 to 3/4 to 7/8-) was found to have the strongest association with DD level among the significant clinicopathologic factors (Spearman rank correlation 0.591, p < 0.0001). The most useful cut-off level of the plasma DD levels for diagnosis of lymph node metastasis was determined to be 0.4 microg/mL, with specificity and sensitivity for lymph node metastasis being 62.9% and 88.2%, respectively. CONCLUSIONS: Plasma DD levels are useful for assessing lymph node metastasis in patients with esophageal cancer and should be measured preoperatively.

Adult↗

PubMed2005

A genetic variant in the gene encoding the stress70 protein chaperone family member STCH is associated with gastric cancer in the Japanese population.

Association analysis, based on linkage disequilibrium between specific alleles in the candidate loci and nearby genetic markers, has been proposed to identify genes conferring susceptibility to multifactorial diseases. Using the affected sib-pair method, we previously mapped four candidate chromosomal regions, 1p32, 2q33-q35, 11p13-p14, and 21q21, for gastric cancer by linkage analysis. To identify genes involved in the disease, we performed a gene-based association analysis of 66 genes, located on 21p11-21q22, using 126 single nucleotide polymorphisms (SNPs) as genetic markers in 373 patients with 250 controls. We found a significant association of five SNPs in the stress70 protein chaperon family member STCH gene with gastric cancer, especially with the non-cardia localization subgroup (P=0.0005-0.02, odds ratio=1.44-1.72). Comparisons of haplotype frequency showed significant association between TTGGC haplotype and gastric cancer (P=0.0001, odds ratio=1.59). These results suggest that, in the Japanese population, STCH might be a new candidate for conferring susceptibility to this disease.

Alleles↗

PubMed2005

Prediction of recurrence in advanced gastric cancer patients after curative resection by gene expression profiling.

The prognosis of patients with advanced gastric cancer remains unfavorable. Even after curative resection, 40% of patients with advanced gastric cancer die of recurrence. Conventional clinicopathlogic findings are sometimes inadequate for predicting recurrence in individuals. Hence, we tried to construct a new diagnostic system, which predicts recurrence in patients with advanced gastric cancer after curative resection based on molecular analysis. Gastric cancer progression is a function of multiple genetic events that may affect the expression of large number of genes. We performed gene expression profiling with 2,304 genes in 60 advanced gastric cancer patients who underwent curative resection using a PCR array technique, a high-throughput quantitative RT-PCR technique. The diagnostic system, which was constructed from the learning set comprised of 40 patients with the most informative 29 genes, classified each case into a good-signature or poor-signature group. Then, we confirmed the predictive performance in an additional test set comprised of 20 patients, and the prediction accuracy for recurrence was 75%. Kaplan-Meier analysis revealed significant difference between the good-signature and the poor-signature group (p = 0.0125). Especially in patients with smaller tumor (< or = 5 cm), less developed LN metastasis (N(0,1)), or earlier stage (stages I and II), the prediction accuracy was high (88.9%, 84.6%, or 81.8%, respectively). Our diagnostic system based on systematic analysis of gene expression profiling can predict the recurrence at clinically meaningful level. By combining our system with conventional clinicopathologic factors, we can improve the prediction of recurrence in patients with advanced gastric cancer who underwent curative surgery.

Aged↗

PubMed2005

Correlation between histological effects on the main tumors and nodal status after chemoradiotherapy for squamous cell carcinoma of the esophagus.

BACKGROUND AND OBJECTIVES: Although the histological effectiveness of preoperative chemoradiotherapy against the main tumor is reported to be the strongest prognostic factor for patients with esophageal cancer, it remains unknown whether such chemoradiotherapy is equally effective against metastatic lymph nodes. METHODS: We studied 103 consecutive patients with esophageal cancer, who were given preoperative chemoradiotherapy followed by surgery. The histological effectiveness against the main tumor of the chemoradiotherapy was correlated with lymph mode metastasis and other clinico-pathological factors. RESULTS: The histological effectiveness against the main tumor was grade 3 in 26 patients, grade 2 in 49 and grade 1 in 28. The number of pathological node-negative patients was 21 (80.8%), 19 (38.8%), and 7 (25.0%) in those having grade 3, 2, and 1 responses of their main tumors, respectively. The average number of pathological metastatic lymph nodes was 0.19, 1.4, and 4.4 in patients with grade 3, 2, and 1 responses, respectively. Endoscopic biopsy after the chemoradiotherapy could not accurately diagnose the pathological complete response (CR) of the main tumors, with a high false negative rate (60.9%). CONCLUSIONS: The effects of chemoradiotherapy against main tumors significantly correlated with nodal status. Most patients with main tumors of pathological CR are node-negative. Patients with a grade 2 response have at most a few positive nodes. Surgery would be most beneficial for such patients.

Adult↗