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J H Donohue

Publications and source records attributed to J H Donohue.

At least 19 recordsLinked to original sources

Intraoperative radiotherapy for treatment of locally advanced and recurrent esophageal and gastric adenocarcinomas.

Intraoperative radiotherapy (IORT) allows delivery of radiotherapy doses in excess of those typically deliverable with conventional external beam radiotherapy. IORT has potential utility in clinical situations, such as treatment of esophageal and gastric malignancies, in which the radiation tolerance of normal organs limits the dose that can be given with conventional radiotherapy techniques. We reviewed the records of 50 patients who received IORT for locally advanced primary or recurrent gastric or esophageal adenocarcinomas deemed unresectable for cure. IORT was given as a single fraction of electron beam radiotherapy (10-25 Gy) after maximal tumor resection: R0 in 42%, R1 in 46%, and R2 in 12%. Forty-eight patients also received external beam radiotherapy (8-55 Gy), 46 received radiosensitizing chemotherapy, and nine received systemic chemotherapy after radiotherapy. Outcomes were estimated with Kaplan-Meier analysis. Median survival was 1.6 years. Overall survival at 1, 2, and 3 years was 70%, 40%, and 27%. Of 42 patients who died, 37 died from cancer progression and three from multifactorial treatment toxicity. Median survival for patients with recurrent disease versus primary disease was 3.0 years versus 1.3 years (P < 0.05), with a delay of metastatic failure in patients with recurrent tumors (P = 0.06). At 3 years, distant metastatic failure was 79%, local failure was 10%, and regional failure was 15%. IORT for locally advanced primary or recurrent gastric malignancies effectively decreases the risk of local failure. For patients with isolated local recurrences, IORT may be effective salvage therapy. However, more effective systemic therapy is needed as a component of treatment.

Adenocarcinoma↗

Single nucleotide polymorphisms (SNPs) at CDH1 promoter region in familial gastric cancer.

INTRODUCTION: Gastric cancer is the most frequent gastrointestinal malignancy in Mexico and the proportion of patients younger than 40 years is one of the highest reported in the world literature. Recently several families with familial diffuse gastric cancer have been identified at the National Institute of Medical Sciences and Nutrition. Germline mutations in the E-cadherin gene (CHD1) have been described that result in the development of diffuse hereditary gastric cancer in young patients. METHODS: The complete coding sequence at exons 1 to 16 and the promoter region of CDH1 was amplified by polymerase chain reaction in peripheral blood samples of two patients with early onset familial diffuse gastric cancer. RESULTS: No germline inactivating mutations of CHD1 were found on either patient. Single nucleotide polymorphisms -160 C->A were detected in the promoter region of CDH1 in both patients. CONCLUSIONS: The polymorphism -160 C->A theoretically confers an increased risk of developing diffuse gastric cancer. The relatives of these patients may an increased risk of gastric cancer among other tumors. There is presently not enough evidence to consider the -160 C->A polymorphism an etiologic factor of diffuse gastric cancer in these patients since the frequency and type of genetic alterations of CDH1 are largely unknown in the Mexican population. It will be necessary to conduct epidemiologic studies in the Mexican population to determine the influence that genetic alterations have on the genesis of diffuse gastric carcinoma.

Adult↗

Efficacy of bilateral prophylactic mastectomy in BRCA1 and BRCA2 gene mutation carriers.

BACKGROUND: In women with a family history of breast cancer, bilateral prophylactic mastectomy is associated with a decreased risk of subsequent breast cancer of approximately 90%. We examined the association between bilateral prophylactic mastectomy and breast cancer risk in women at high risk for breast cancer who also had mutations in BRCA1 and BRCA2 genes. METHODS: We obtained blood samples from 176 of the 214 high-risk women who participated in our previous retrospective cohort study of bilateral prophylactic mastectomy. We used conformation-sensitive gel electrophoresis and direct sequence analysis of the blood specimens to identify women with mutations in BRCA1 and BRCA2. The carriers' probabilities of developing breast cancer were estimated from two different penetrance models. RESULTS: We identified 26 women with an alteration in BRCA1 or BRCA2. Eighteen of the mutations were considered to be deleterious and eight to be of uncertain clinical significance. None of the 26 women has developed breast cancer after a median of 13.4 years of follow-up (range, 5.8-28.5 years). Three of the 214 women are known to have developed a breast cancer after prophylactic mastectomy. For two of these women, BRCA1 and BRCA2 screening was negative, and no blood specimen was available for the third. Estimations of the effectiveness of prophylactic mastectomy were performed, considering this woman as both a mutation carrier and a noncarrier. These calculations predicted that six to nine breast cancers should have developed among the mutation carriers, which translates into a risk reduction, after bilateral prophylactic mastectomy, of 89.5%-100% (95% confidence interval = 41.4% to 100%). CONCLUSIONS: Prophylactic mastectomy is associated with a substantial reduction in the incidence of subsequent breast cancer not only in women identified as being at high risk on the basis of a family history of breast cancer but also in known BRCA1 or BRCA2 mutation carriers.

Breast Neoplasms↗

Efficacy of contralateral prophylactic mastectomy in women with a personal and family history of breast cancer.

PURPOSE: To estimate the efficacy of contralateral prophylactic mastectomy in women with a personal and family history of breast cancer. PATIENTS AND METHODS: We followed the course of 745 women with a first breast cancer and a family history of breast and/or ovarian cancer who underwent contralateral prophylactic mastectomy at the Mayo Clinic between 1960 and 1993. Family history information and cancer follow-up information were obtained from the medical record, a study-specific questionnaire, and telephone follow-up. Life-tables for contralateral breast cancers, which consider age at first breast cancer, current age, and type of family history, were used to calculate the number of breast cancers expected in our cohort had they not had a prophylactic mastectomy. RESULTS: Of the 745 women in our cohort, 388 were premenopausal (age < 50 years) and 357 were post- menopausal. Eight women developed a contralateral breast cancer. Six events were observed among the premenopausal women, compared with 106.2 predicted, resulting in a risk reduction of 94.4% (95% confidence interval [CI], 87.7% to 97.9%). For the 357 postmenopausal women, 50.3 contralateral breast cancers were predicted, whereas only two were observed, representing a 96.0% risk reduction (95% CI, 85.6% to 99.5%). CONCLUSION: The incidence of contralateral breast cancer seems to be reduced significantly after contralateral prophylactic mastectomy in women with a personal and family history of breast cancer.

Adult↗

Germline E-cadherin gene mutations: is prophylactic total gastrectomy indicated?

BACKGROUND: The CDH1 gene encodes E-cadherin, an epithelial cell adhesion molecule. Germline CDH1 mutations recently were identified in families with hereditary diffuse gastric carcinoma in a pattern suggestive of autosomal dominant inheritance with incomplete penetrance. METHODS: The proband was a woman age 47 years with a strong family history of diffuse gastric carcinoma. A germline E-cadherin gene mutation was identified in this patient, her brother, and three first cousins. All five family members underwent endoscopic evaluations, which were negative for malignancy, and elected to undergo a prophylactic total gastrectomy with Roux-en-Y esophagojejunostomy. RESULTS: Pathologic examination of the proband's stomach revealed several microscopic foci of intramucosal signet ring cell adenocarcinoma in the cardia and proximal gastric body. Postgastrectomy specimens from the proband's brother and three first cousins all showed intramucosal signet ring cell adenocarcinoma in various regions of the stomach. Immunoperoxidase studies performed on gastric tissue from these five patients demonstrated diminished or absent E-cadherin reactivity in the cancerous mucosa. CONCLUSIONS: Although total gastrectomy was performed as a prophylactic intervention, occult gastric carcinoma was discovered in all five patients. Thus, total gastrectomy should be curative for gastric carcinoma in these patients. Based on their successful outcomes and the lack of efficacious surveillance methods for diffuse gastric carcinoma, prophylactic total gastrectomy may be the management of choice for germline E-cadherin gene mutation carriers. However, prophylactic total gastrectomy should be undertaken cautiously because the procedure may be associated with considerable morbidity.

Adult↗

Present status of the diagnosis and treatment of gallbladder carcinoma.

Because early carcinoma of the gallbladder causes no specific signs or symptoms, most patients with this disease are diagnosed with advanced-stage tumors. High-resolution ultrasonography and a low index of suspicion for polypoid masses or asymmetric gallbladder thickening represent the best method of early detection. Despite regular preoperative gallbladder imaging, many cancers are only detected intraoperatively or incidentally on pathologic examination. All known or suspected gallbladder cancers should be definitively treated with a laparotomy, not laparoscopic surgery. For early gallbladder cancers (Tis and T1 cancers), simple cholecystectomy is adequate therapy. More advanced-stage carcinomas without distant metastases should routinely be managed with a radical cholecystectomy, which includes partial hepatectomy and regional lymphadenectomy. Any adherent organs should be resected en bloc with the cancer. Pancreatoduodenectomy has been performed in several Japanese centers, but is rarely performed in the West for locally advanced gallbladder cancers. Most patients who undergo curative resection will develop recurrent disease, but there is currently no proven effective adjuvant therapy.

Biopsy↗

Accuracy of sentinel lymph node biopsy in patients with large primary breast tumors.

BACKGROUND: Patients with large breast tumors are increasingly undergoing neoadjuvant treatment to downstage local disease; however, accurate staging of the axilla before the initiation of chemotherapy remains problematic. In the current study, the authors report on the accuracy of sentinel lymph node (SLN) biopsy in such patients to determine the feasibility of applying this technique before induction chemotherapy. METHODS: One hundred three patients with 104 tumors classified as American Joint Committee on Cancer (AJCC) T2 (tumor >/= 2 cm but </= 5 cm) or larger were recruited at the University of Pennsylvania and the Mayo Clinic. In the majority of cases, combined blue dye and radiotracer was used for SLN identification. After SLN identification, a completion axillary lymph node dissection was performed in 87 cases. The SLN was evaluated with hematoxylin and eosin and immunohistochemistry. RESULTS: The SLN was identified in 99% of cases. The overall rate of lymph node metastasis was 59% (95% exact confidence interval [95% CI], 49-68%) (61 of 104 cases). The SLN false-negative rate was 2% (95% exact CI, < 1-11.5%) (2 patients). In 56 tumors >/= 3 cm, 1 false-negative result (2% [95% exact CI, < 1-15%]) was identified, and the rate of lymph node metastasis was 62.5% (95% exact CI, 48. 5-75%) (35 of 56 tumors). Within 30 SLN positive patients with tumors >/= 3 cm and complete axillary lymph node dissection, 3 of 8 patients (37.5% [95% exact CI, 8.5-75.5%]) with micrometastasis (</= 2 mm) to the SLN had positive non-SLN compared with 21 of 22 patients (95.5% [95% exact CI, 77-100%]) with macrometastasis (> 2 mm) to the SLN (P = 0.002). CONCLUSIONS: SLN biopsy for patients with large breast tumors is technically feasible and highly accurate. SLN biopsy should be considered for the staging of clinically negative axilla in patients scheduled to receive neoadjuvant chemotherapy.

Adult↗

Results of irradiation or chemoirradiation following resection of gastric adenocarcinoma.

PURPOSE: To evaluate the results of postoperative irradiation +/- chemotherapy for carcinoma of the stomach and gastroesophageal junction. METHODS AND MATERIALS: The records of 63 patients who underwent resection for stomach cancer were retrospectively reviewed. Twenty-five patients had complete resection with no residual disease but with high-risk factors for relapse. Twenty-eight had microscopic residual and 10 had gross residual disease. Doses of irradiation ranged from 39.6 to 59.4 Gy with a median dose of 50.4 Gy in 1.8 Gy fractions. Fifty-three of the 63 (84%) patients received 5-fluorouracil (5-FU)-based chemotherapy. RESULTS: The median duration of survival was 19.3 months for patients with no residual disease, 16.7 months for those with microscopic residual disease, and 9.2 months for those with gross residual disease (p = 0.01). The amount of residual disease also significantly impacted locoregional control (p = 0.04). Patients with linitis plastica did significantly worse in terms of survival, locoregional control, and distant control than those without linitis plastica. The use of 4 or more irradiation fields was associated with a significant decrease in the rate of Grade 4 or 5 toxicity when compared to the patients treated with 2 fields (p = 0.05). CONCLUSIONS: There was a significant association between survival and extent of residual disease after resection as well as the presence of linitis plastica. Distant failures are common and effective systemic therapy will be necessary to improve outcome. The toxicity of combined modality treatment appears to be reduced by using greater than 2 irradiation fields.

Adult↗

Results of irradiation or chemoirradiation for primary unresectable, locally recurrent, or grossly incomplete resection of gastric adenocarcinoma.

OBJECTIVE: To evaluate the results of irradiation +/- chemotherapy for patients with unresectable gastric carcinoma. MATERIALS AND METHODS: The records of 60 patients with a gastric or gastroesophageal junction adenocarcinoma and a locally advanced unresectable primary (n = 28), a local or regional recurrence (n = 21), or gross residual disease following incomplete resection (n = 11) were retrospectively reviewed. Patients were treated with external beam irradiation (EBRT) alone or external beam plus intraoperative irradiation (IOERT), and 55 of the 60 (92%) patients received 5-FU based chemotherapy. RESULTS: The median survival for the entire cohort was 11.6 months. There was no significant difference in median survival between each of the three treatment groups. In examining the extent of disease there was a significant difference in survival based on the number of sites involved. Nine patients with disease limited to a single non-nodal site appeared to represent a favorable subgroup compared to the rest of the patients (median survival of 21.8 months vs. 10.2 months,p = 0.03). In the patients with recurrent disease, the number of sites involved (p = 0.05), and total dose adding external beam dose to IOERT dose (> 54 Gy vs. < or =54 Gy, p = 0.06) were of borderline significance in regard to survival. CONCLUSIONS: In patients with either primary unresectable, locally or regionally recurrent, or incompletely resected gastric carcinoma, the overall survival is similar, and related to the extent of disease based on the number of regional sites involved. The patients with a single non-nodal site of disease represent a favorable subgroup and patients with recurrent disease may benefit from total irradiation doses > 54 Gy.

Adenocarcinoma↗

What prognostic factors are important in duodenal adenocarcinoma?

HYPOTHESIS: Survival of patients with adenocarcinoma of the duodenum depends on the ability to perform a complete resection and the tumor stage DESIGN: Retrospective case series. SETTING: Tertiary care referral center. PATIENTS: A cohort of 101 consecutive patients (mean age, 62 years), undergoing surgery for duodenal adenocarcinoma from January 1, 1976, through December 31, 1996. Patients with ampullary carcinoma were specifically excluded. Mean duration of follow-up was 4 years. INTERVENTIONS: Surgery was curative in 68 patients (67%) and palliative in 33 patients (33%). Of the curative group, 50 patients (74%) underwent radical surgery, ie, 30 (60%), pancreaticoduodenectomy; 15 (30%), pylorus-preserving pancreaticoduodenectomy; and 5 (10%), total pancreatectomy. A more limited resection procedure was used in 18 patients (26%) involving a segmental duodenal resection in 15 (83%) and a transduodenal excision in 3 (17%). patient survival, and correlation with patient and tumor variables using univariate and multivariate analysis. RESULTS: Actuarial 5-year survival for the curative group was 54%. Only 1 patient in the unresected group survived beyond 3 years. Nodal metastasis (P = .002), advanced tumor stage (P<.001), positive resection margin (P = .02), and weight loss (P<.001) had a significant negative impact on survival in multivariate analysis. Tumor grade, size, and location within the duodenum had no impact on survival. Patient age and tumor depth of invasion influenced survival in univariate analysis, but lost their prognostic significance in multivariate analysis. CONCLUSIONS: Metastasis to lymph nodes, advanced tumor stage, and positive resection margins are associated with decreased survival in patients with duodenal adenocarcinoma. An aggressive surgical approach that achieves complete tumor resection with negative margins should be pursued. Pancreaticoduodenectomy is usually required for cancers of the first and second portion of the duodenum. Segmental resection may be appropriate for selected patients, especially for tumors of the distal duodenum.

Adenocarcinoma↗

Intraoperative topical tetracycline sclerotherapy following mastectomy: a prospective, randomized trial.

BACKGROUND AND OBJECTIVES: Postoperative wound seromas are a frequent and troublesome occurrence after mastectomy. Recent reports have suggested the efficacy of topical sclerosants at reducing their formation. METHODS: A prospective, randomized, double-blinded trial was performed to examine the effect of intraoperatively administered topical tetracycline on the occurrence of postoperative mastectomy seromas. Thirty-two women were randomized to the control arm (normal saline) and 30 women to the tetracycline arm. In the treatment group, 100 ml (2 g) of tetracycline solution was administered topically to the chest wall and skin flaps prior to skin closure. The control group received an equal volume of normal saline. Patients were monitored for the development of postoperative wound seroma. RESULTS: There were no significant differences between groups regarding total volume of closed suction drainage, numbers of patients leaving hospital with drains in place, or duration of catheter drainage. Seroma formation 2 weeks postoperatively was greater in the tetracycline group than the control group (53% vs. 22%, P = 0.01). There were no differences between groups regarding the degree of postoperative pain, wound infection, or seroma formation 1 month postoperatively. CONCLUSIONS: Topical tetracycline is not effective at preventing post-mastectomy wound seromas.

Administration, Topical↗

Surgical treatment of adult primary hepatic sarcoma.

BACKGROUND: Primary sarcomas of the liver are extremely rare in adults. Optimal therapeutic approaches remain unclear. METHODS: Twenty consecutive adult patients who had surgical treatment for primary hepatic sarcomas were reviewed. Patient age ranged from 23 to 80 years. Other than one patient with primary hepatic angiosarcoma who had a history of thorium dioxide colloid (Thorotrast) exposure 23 years before diagnosis, no predisposing causes were apparent. Nineteen patients had hepatic resection and one patient had an orthotopic liver transplant. No patient received neoadjuvant chemotherapy or radiotherapy but radiotherapy was delivered intraoperatively in one patient. RESULTS: Leiomyosarcoma was the most common histological type of sarcoma diagnosed (five of 20 patients), followed by malignant solitary fibrous tumour (four) and epithelioid haemangioendothelioma (three). Fourteen tumours were high-grade sarcomas and six were low grade malignancies. Thirteen patients developed a recurrence. Distant metastases (ten patients) and intrahepatic recurrence (six) were the predominant sites of initial treatment failure. Six patients received salvage chemotherapy. Histological grade was the only factor significantly associated with overall patient survival (P= 0.03). With complete resection, patients with high-grade tumours had a 5-year survival rate of 18 (95 per cent confidence interval 5-62) per cent compared with 80 (52-100) per cent for patients with low-grade tumours. The 5-year survival rate for all 20 patients was 37 (20-60) per cent. CONCLUSION: Surgical resection is the only effective therapy for primary hepatic sarcomas at present. Better adjuvant therapy is necessary, especially for high-grade malignancies, owing to the high failure rate with operation alone.

Adult↗

A comparison of laparoscopic and open cholecystectomy in patients with compensated cirrhosis and symptomatic gallstone disease.

BACKGROUND: The purpose of this study was to compare the risks and benefits of performing open cholecystectomy (OC) and laparoscopic cholecystectomy (LC) in patients with compensated cirrhosis. METHODS: Data on 50 patients who underwent cholecystectomy for the treatment of symptomatic gallstone disease between 1990 and 1997 were collected retrospectively. These patients were divided into 2 groups: Group I included 24 patients who underwent OC, and Group II included 26 patients who underwent LC. The cohorts were well-matched for age, sex, race, clinical presentation, and Child-Turcotte-Pugh (CTP) class. Twelve patients in Group I had a concomitant surgical procedure in contrast to only 2 patients in Group II. No patient in this study had CTP Class C cirrhosis. RESULTS: There was no operative mortality. Conversion to OC was necessary in 3 patients (12%) during LC because of uncontrollable liver bed bleeding in 2 of the patients and insufficient visualization of the anatomy in 1 of the patients. Mean surgical times were significantly longer in Group I when comparing patients from both groups without concomitant surgical procedures (mean +/- SD, 177 +/- 91.3 minutes vs 116.8 +/- 42.3 minutes, P = .037). No patient in Group II required any blood component replacement in contrast to 9 patients (38%) in Group I. Intraoperative bleeding remained significantly higher in Group I when comparing patients without concomitant surgical procedures (P = .043). No patients in Group II had a wound complication, compared with 2 patients (8%) in Group I. The 12 patients without concomitant surgical procedures in Group I had significantly longer hospital stays when compared with 24 patients without concomitant surgical procedures in Group II (mean +/- SD, 6.9 days +/- 3.3 [median 6] vs 2.4 days +/- 1.8 [median 2.0]); P = .001. CONCLUSIONS: Our results demonstrate that laparoscopic cholecystectomy can be performed safely in patients with CTP Class A and B cirrhosis. It offers several advantages over open cholecystectomy, including lower morbidity, shorter operative time, and reduced hospital stay with less need for transfusions.

Blood Loss, Surgical↗

Surgical and interventional palliative treatment of upper gastrointestinal malignancies.

Malignancies of the upper gastrointestinal tract, including the oesophagus, stomach, liver, bile ducts and pancreas, are highly virulent diseases. While curative therapies relieve symptoms caused by these cancers, most of these treatments prove unsuccessful in the control of tumour due to occult residual disease. This review covers only planned palliative procedures for these conditions where patient factors (e.g. performance status or patient wishes) or tumour factors (e.g. locally advanced or known metastatic disease) prevent potentially curative intervention. For most patients, palliation of luminal obstruction, pain or other symptoms is the most worthwhile treatment that can be offered with present therapies.

Bile Duct Neoplasms↗

The incidence and clinical consequences of treatment-related bowel injury.

OBJECTIVE: To assess the frequency and clinical features of treatment-induced bowel injury in rectal carcinoma patients receiving perioperative external beam radiotherapy (EBRT). The frequency of and factors associated with treatment-induced intestinal injury have previously not been well quantified for rectal cancer patients. Postoperative adjuvant chemoirradiation is recommended for Stage II and III rectal cancers, making such data of significant interest. METHODS AND MATERIALS: The records of 386 consecutive patients undergoing radiotherapy with or without chemotherapy (CT) for rectal carcinoma between 1981-90 were reviewed. Eight-two patients were excluded for receiving nontherapeutic EBRT or modalities other than EBRT. RESULTS: Symptomatic acute treatment-related enteritis (within 30 days of EBRT +/- CT) was diagnosed in 13 patients, 3 of whom developed chronic bowel injury. Chronic treatment-related enteritis was identified in 18 patients and reoperation was required in 17 (5% of the 304 patients with complete follow-up). Chronic proctitis was documented in 38 patients, including 3 patients with small bowel injury. The probability of developing treatment-induced bowel injury at 5 years following treatment was 19%. Variables associated with an increased risk of bowel injury using multivariate analysis were transanal excision (p = 0.002), escalating radiation dose (p = 0.005), and increasing age (p = 0.01). Twenty of the affected patients required operative treatment, and 2 deaths resulted from treatment-induced enteritis. CONCLUSION: Patients with rectal carcinoma treated with EBRT +/- CT have the risk of developing treatment-induced bowel injury. The pelvic radiation dose should be limited to < or = 5040 cGy unless small bowel can be displaced. Reperitonealization of the pelvis, or other surgical methods of excluding the small intestine should be used whenever possible.

Aged↗

Sentinel lymph node biopsy with metastasis: can axillary dissection be avoided in some patients with breast cancer?

PURPOSE: Recent studies have suggested that the sentinel lymph node (SLN) biopsy is an accurate alternative staging procedure for women with breast cancer. The goal of this study was to identify a subset of breast cancer patients in whom metastatic disease was confined only to the SLN. MATERIALS AND METHODS: From two institutions, we recruited 222 women with breast cancer for SLN biopsy. A SLN biopsy was performed in each patient, followed by an axillary dissection in 182 patients. Histologic and immunohistochemical cytokeratin stains were used on all SLNs. RESULTS: The SLN was identified in 220 (97. 8%) of the 225 biopsies. Evidence of metastatic breast cancer in the SLN was found in 60 (27.0%) of the 222 patients. Of these patients, 32 (53.3%) had evidence of tumor in the SLN only. By multivariate analysis, two factors were found to be significantly associated with a higher likelihood of tumor involvement in the non-SLNs: primary tumor size larger than 2.0 cm (P =.0004) and macrometastasis (> 2.0 mm) in the SLN (P =.002). Additional analysis revealed that none (0%; 95% confidence interval, 0% to 18.5%) of the 18 patients with primary tumors < or = 2.0 cm and micrometastasis to the SLN had remaining axillary lymph node involvement. CONCLUSION: The primary tumor size and metastasis size in the SLN are independent factors in predicting the incidence of tumor in the non-SLNs. Therefore, the SLN biopsy alone may be adequate for staging and/or therapy decision making in patients with primary breast tumors < or = 2.0 cm and micrometastasis in the SLN.

Adult↗