Biomedical subjects

Fumio Matsuzuka

Publications and source records attributed to Fumio Matsuzuka.

At least 19 recordsLinked to original sources

PubMed2006

Clinical significance of metastasis to the central compartment from papillary microcarcinoma of the thyroid.

We previously demonstrated that for papillary microcarcinoma (PMC), (1) patients with lateral lymph node metastasis detected on preoperative ultrasonography (US) are more likely to develop recurrence, and (2) dissection of the lateral compartment does not improve the prognosis of patients without US-detectable lateral metastasis. In this study, we focused on metastasis from PMC to the central compartment. We investigated the clinical significance of lymph nodes in the central compartment using the same series of 600 patients as used in the previous study. Ultrasound-diagnosed central node metastasis could be found in 30 patients (20.0%). Although the specificity of US for detecting central node metastasis was 99.1%, sensitivity was only 10.9%. Neither US-diagnosed nor pathologically confirmed central node metastasis affected the disease-free survival (DFS) rate of PMC patients. Furthermore, in cases where PMC was located only in one lobe, central node dissection in the contralateral lobe did not improve the DFS rate. These findings suggest that, for PMC, (1) US is an insensitive technique for detecting the central node metastasis, (2) the presence of central node metastasis is unrelated to DFS of patients, and (3) when performing lobectomy for PMC involving only one lobe, dissection of the central compartment in the contralateral lobe is optional.

Adult↗

PubMed2006

Prognostic significance of extrathyroid extension of papillary thyroid carcinoma: massive but not minimal extension affects the relapse-free survival.

OBJECTIVES: Extrathyroid extension has been recognized as a prognostic factor in papillary thyroid carcinoma. In the most recent version of the UICC TNM classification system, extrathyroid extension has been classified into two grades, minimal extension (extension to sternothyroid muscle or perithyroid soft tissues) and massive extension (extension to subcutaneous soft tissue, larynx, trachea, esophagus, or recurrent laryngeal nerve). In this study, we investigated the prognostic significance of each of the two types of extension. PATIENTS AND METHODS: One thousand and sixty-seven patients with papillary thyroid carcinoma without distant metastasis at surgery, who underwent surgical treatment in Kuma hospital between 1990 and 1995 and had been followed postoperatively for 60 months or more, were enrolled in this study. The grading of extrathyroid extension was based on both pathological findings and intraoperative surgical findings. RESULTS: In univariate analysis, although patients with massive extension showed a significantly worse relapse-free survival (RFS) rate than those with no or minimal extension (P < 0.0001), there was no difference in the RFS rate between patients with no extension and those with minimal extension. Among patients with massive extension, the RFS rate tended to be worse in those with posterior extension than in those with anterior extension (P = 0.0562). Furthermore, the RFS rate of patients with massive posterior extension only to the recurrent nerve demonstrated a better RFS rate than those with extension to other posterior organs (P = 0.0052). Multivariate analysis demonstrated that massive extrathyroid extension is recognized as an independent prognostic factor for RFS (P = 0.0003). CONCLUSIONS: These findings suggest that (1) upgrading of T category for tumors with massive extension is appropriate, whereas that for tumors with only minimal extension is not, and (2) careful surgical treatment and postoperative follow-up are required for tumors with massive extension to posterior organs other than the recurrent laryngeal nerve.

Adenocarcinoma, Papillary↗

PubMed2006

Sensitivity and specificity of intraoperative recurrent laryngeal nerve stimulation test for predicting vocal cord palsy after thyroid surgery.

INTRODUCTION: Recurrent laryngeal nerve (RLN) palsy after thyroidectomy, although infrequently encountered, can decrease quality of life. In addition to the hoarseness that occurs with unilateral RLN palsy, bilateral RLN palsy leads to dyspnea and often to life-threatening glottal obstruction. Therefore, intraoperative awareness of the nerve's status is of great importance. This study examined the sensitivity and specificity of a palpation technique to detect contraction of the posterior cricoarytenoid muscle (PCA) through the posterior hypopharyngeal wall while the RLN was being stimulated with a disposable nerve stimulator during thyroid surgery (the laryngeal palpation test) to predict postoperative RLN deficits. METHODS: A total of 2197 RLNs in 1376 patients were identified to be at risk of injury during thyroidectomy performed between July 2003 and August 2004. Postoperative RLN integrity was assessed using direct laryngoscopy or laryngofiberoscopy to visualize vocal fold mobility. RESULTS: Altogether, 76 RLNs failed to elicit a PCA contraction in response to nerve stimulation, and 80 cases of temporary vocal cord palsy and 21 cases of permanent vocal cord palsy were recognized on postoperative evaluation. For postoperative vocal cord palsy, the sensitivity and specificity of the laryngeal palpation test were 69.3% and 99.7%, respectively, with a positive predictive value of 92.1% and negative predictive value of 98.5%. For permanent vocal cord palsy, the sensitivity and specificity were 85.7% and 97.3%, respectively, with a positive predictive value of 23.7% and negative predictive value of 99.8%. CONCLUSIONS: The laryngeal palpation test is not a particularly useful method for predicting the level of RLN function after thyroidectomy. All patients must be examined postoperatively by direct laryngoscopy or laryngofiberoscopy to check vocal cord mobility. Even if there is no contraction of the PCA and we detect vocal cord palsy immediately after surgery, vocal cord palsy often recovers within 1 year when visual preservation of RLN is successful.

Adolescent↗

PubMed2006

A prophylactic infusion of calcium solution reduces the risk of symptomatic hypocalcemia in patients after total thyroidectomy.

BACKGROUND: Several risk factors have been associated with post-operative transient hypocalcemia after thyroid surgery. However, there are no studies evaluating preventive measures to avoid symptomatic postoperative hypocalcemia. Although intravenous infusion of calcium improves hypocalcemic symptoms, it is unknown whether prophylactic infusion prevents symptoms of postoperative hypocalcemia. PATIENTS AND METHODS: Five hundred and forty-seven patients underwent total thyroidectomy. Two groups were identified: group A (n = 243) received prophylactic intravenous drip infusion of 78-156 mg of calcium solution at 3-8 hours after operation, and group B (n = 304) received no prophylactic treatment. Prophylactic infusion was used only once if the patients did not have symptoms of hypocalcemia. Serum calcium (Ca) levels, intact parathyroid hormone (i-PTH) levels on the first postoperative day (1st POD), and the prevalence of symptoms of hypocalcemia were prospectively analyzed. RESULTS: The serum Ca levels at the 1st POD in group A patients (7.91 +/- 0.49 mg/dl, mean +/- SD) was significantly higher than group B patients (7.65 +/- 0.54, P < 0.0001), while the serum i-PTH levels were not significantly different between the two groups. The prevalence of numbness and/or tetany before noon on the 1st POD was significantly lower in group A patients. Prophylactic infusion of calcium solution reduced the prevalence of tetany from 8.6% to 2.1%. CONCLUSION: A prophylactic infusion of calcium solution after total thyroidectomy may be useful in reducing the development of symptomatic hypocalcemia and reduces the patients' risk of having discomfort and anxiety due to hypocalcemia.

Calcium↗

PubMed2006

Clinical significance of lymph node metastasis of thyroid papillary carcinoma located in one lobe.

BACKGROUND: Previous studies have shown that lymph node metastasis can be of prognostic value. In this study, we investigated the clinical significance of node metastasis focusing on metastasis in the central compartment for patients with papillary carcinoma located in one lobe. PATIENTS AND METHODS: We investigated the frequency of lymph node metastasis in 759 patients with papillary carcinoma to determine whether and how such metastasis affects disease-free survival (DFS). RESULTS: Central node metastasis was observed in 63% of patients, and the frequency was increased in relation to tumor size. The frequency of lateral node metastasis was 62.0%, which was also directly related to tumor size. On multivariate analysis of cases showing tumor larger than 1 cm, central node metastasis was recognized as an independent prognostic factor of DFS. The frequency of metastasis to the paratracheal nodes contralateral to the tumor was drastically elevated for tumors larger than 1 cm, but metastasis to this region did not independently predict worse DFS. CONCLUSION: Central node metastasis independently predicts a worse DFS for patients with papillary carcinoma larger than 1 cm.

Adult↗

PubMed2006

Minimal extrathyroid extension does not affect the relapse-free survival of patients with papillary thyroid carcinoma measuring 4 cm or less over the age of 45 years.

PURPOSE: In the most recent version of the UICC TNM classification system for thyroid carcinoma, tumors with minimal extrathyroid extension were classified as T3. In this study, we investigated whether this upgrading is appropriate for papillary thyroid carcinoma. METHODS: We investigated the difference in the relapse-free survival (RFS) rate between patients with tumors having no, minimal, and massive extrathyroid extension in a series of 502 patients over the age of 45 years. RESULTS: Patients with tumors showing massive extension showed a worse RFS rate except for those with tumors measuring 1 cm or less. However, there was no significant difference in RFS between tumors measuring 4 cm or less showing no or minimal extension. In an investigation of 409 patients without any clinically apparent node metastasis, the RFS of patients with tumors larger than 4 cm with massive extension was significantly worse than those with tumors measuring 4 cm or less, while the RFS of patients with tumors with either no or minimal extension did not depend on the tumor size. CONCLUSIONS: These findings suggest that tumors with minimal extension should be classified to have the same T grade as those without such extension, and upstaging of such tumors is therefore not appropriate.

Aged↗

PubMed2006

Delta Np73 expression in thyroid neoplasms originating from follicular cells.

AIMS: p73, a homologue of p53, is known as a negative regulator of tumour progression. However, delta Np73, an isoform of p73 lacking the NH2-terminal transactivation domain plays an oncogenic role by interfering with the activity of p53 and TA (full-length transactivating isoforms) p73. In this study, we investigated the expression of delta Np73 in human thyroid neoplasms originating from follicular cells. METHODS: We immunohistochemically investigated delta Np73 expression in 223 thyroid neoplasms. Delta Np73 expression level was evaluated as the sum of positivity score and intensity score. RESULTS: Normal follicular cells did not express delta Np73, but 27.3% of follicular adenoma, 85.4% of follicular carcinoma, 99.2% of papillary carcinoma, and 95.7% of anaplastic carcinoma were positive for the transcript. Delta Np73 expression level did not differ between widely invasive and minimally invasive follicular carcinomas. In papillary carcinoma, the level was inversely linked to tumour size, extrathyroid extension, and clinically apparent metastasis. Furthermore, in anaplastic carcinoma, delta Np73 expression level was significantly lower than that in papillary carcinoma. CONCLUSIONS: Our findings indicate that delta Np73 plays a role predominantly in the early phase of papillary carcinoma progression.

Adenocarcinoma, Follicular↗

PubMed2006

Needle tract implantation of follicular neoplasm after fine-needle aspiration biopsy: report of a case.

We herein report a 28-year-old woman with a follicular neoplasm showing subcutaneous needle tract implantation. One month after fine-needle aspiration biopsy (FNAB) for a tumor measuring 2.5 cm, the patient became aware of a subcutaneous nodule measuring about 1 cm at the needle insertion site. FNAB smear of this nodule showed poorly cohesive clusters of follicular cells with nuclear crowding, overlapping and resetting with some microfollicular architecture. Total thyroidectomy and resection of the subcutaneous nodule were performed. Although there was no capsular or vascular invasion of the nodule, the lesion was diagnosed as follicular carcinoma because of the subcutaneous seeding. Ki-67 labeling indices of the thyroid nodule and implanted tumor were higher than 5%. Furthermore, although galectin-3 was completely negative in the thyroid nodule, it was heterogeneously positive in the implanted tumor. It is therefore suggested that high cell proliferating activity as a characteristic of the original nodule and the subsequently obtained invasive characteristic of the implanted tumor contributed to this event. To date, there has not been any recurrence of the implanted lesion. Because implanted follicular carcinoma can be surgically removed, this complication should not impair the usefulness of FNAB.

Adult↗

PubMed2006

Usefulness of ultrasonography for diagnosis of malignant lymphoma of the thyroid.

BACKGROUND: Recent developments in ultrasonography (US) and the prevalence of ultrasound-guided fine needle aspiration biopsy (US-FNAB) has enabled physicians to detect and diagnosis thyroid diseases, including thyroid malignant lymphoma, much more easily. METHODS: We describe our diagnostic strategy for malignant lymphoma on US screening. We screened possible malignant lymphoma patients by US characteristics such as enhanced posterior echoes. RESULTS: Among 170 patients suspected of malignant lymphoma between 2000 and 2004, 74 (43.5%) were also diagnosed as having or suspected of lymphoma by US-FNAB. Five patients dropped out, and 67 of 69 patients who underwent surgical examination were pathologically diagnosed as having lymphoma. Finally, 79 (47.9%) of 165 US-suspected patients were confirmed as having lymphoma. Only 21.5% of lymphoma patients complained of rapidly growing goiter. CONCLUSION: US screening for goiters contributes markedly to diagnosis of lymphoma at an early phase, facilitating early initiation of therapy.

Adult↗

PubMed2006

Tensin3 is a novel thyroid-specific gene.

Thyroid-specific genes, such as thyroid peroxidase, thyroglobulin, Na+/I- symporter and thyroid-stimulating hormone receptor, play fundamental roles in thyroid function and relate to many pathological conditions. Using sequence specific-differential display, we detected three genes that showed higher expression levels in normal thyroid tissues than in thyroid tumor tissues. After subcloning and sequencing analysis, one of the genes was revealed to be tensin3. The expression level of tensin3 was examined with real-time quantitative PCR analysis. Its expression levels were more depressed in thyroid tumor tissues than in normal thyroid tissues. The decrease was even more evident in two anaplastic carcinomas. High and moderate levels of tensin3 mRNA expression were observed in the thyroid and placenta respectively. Tensin3 mRNA was expressed only in low levels in other tissues, such as the brain, heart, lung, liver, pancreas, kidney, skeletal muscle, white blood cells and prostate. These results show that tensin3 is a novel thyroid-specific gene and further investigations may reveal its relation to thyroid function or thyroid disease.

Humans↗

PubMed2005

Expression of cdc25B and cdc25A in medullary thyroid carcinoma: cdc25B expression level predicts a poor prognosis.

Cdc25B and cdc25A phosphatases are prominent stimulators of cell cycle progression and have been suggested to play oncogenic roles. In this study, we immunohistochemically investigated the expression of these phosphatases in medullary thyroid carcinoma. Cdc25B was positive in 35.8% of cases examined. Its positivity was linked only to patient age. However, patients with cdc25B-positive tumors showed a significantly worse disease-free survival rate (P=0.0210) than those with cdc25B-negative tumors. Cdc25A was positive in only 17.2% of cases and was not related to clinicopathological parameters or prognosis. These findings suggest that cdc25B can be regarded as having prognostic significance and as a novel marker of biologically aggressive characteristics in this carcinoma.

Adolescent↗

PubMed2005

Papillary microcarcinomas of the thyroid with preoperatively detectable lymph node metastasis show significantly higher aggressive characteristics on immunohistochemical examination.

OBJECTIVES: We recently demonstrated that papillary microcarcinomas with preoperatively detectable node metastasis in the lateral compartment on ultrasonography (clinically apparent metastasis) show worse postoperative relapse-free survival than those with no metastasis or metastasis that could not be detected preoperatively, but was confirmed by pathological examination after surgery (occult metastasis). In this study, we investigated difference in the aggressive characteristics of microcarcinoma of this type from various perspectives. MATERIALS AND METHODS: We immunohistochemically examined the expression of cell proliferating markers, Ki-67, cyclin D1, p27, and retinoblastoma gene product (pRb), apoptotic markers, single-strand DNA (ssDNA), and metastatic suppressor, kangai-1 (KAI-1) for 19 microcarcinoma patients with clinically apparent metastasis, 14 patents with occult metastasis, and 22 patients without metastasis. RESULTS: Cases of clinically apparent metastasis showed increased cyclin D1 expression together with decreased p27 expression and higher levels of pRb and Ki-67 expression. Furthermore, ssDNA expression was higher and bcl-2 expression was lower in these cases, while KAI-1 expression was significantly reduced. There was no significant difference in the expression of these proteins between cases demonstrating no and occult metastases. CONCLUSION: These findings suggest that cases of clinically apparent metastasis show significantly higher growth based on cell proliferating activity, apoptosis, and expression of metastatic suppressor than those demonstrating no or occult metastases.

Adult↗

PubMed2005

Phosphorylation and inactivation of Tob contributes to the progression of papillary carcinoma of the thyroid.

Tob, a member of the Tob/BTG family, is a novel anti-proliferative protein, but it becomes inactive when phosphorylated. In this study, we investigated whether Tob is phosphorylated and inactive in various thyroid neoplasms in order to elucidate how this event plays a role in their progression. Tob phosphorylation was only occasionally seen in normal follicular cells. A high level of Tob phosphorylation was observed in 42.1% of follicular adenoma, 14.3% of follicular carcinoma. In papillary carcinoma, the Tob phosphorylation level was elevated more frequently than that in follicular carcinoma, and 39.7% of specimens were classified in the high group. Tob phosphorylation level in papillary carcinoma was directly linked to tumor size, lymph node metastasis, extrathyroid extension and the presence of poorly differentiated lesion. In anaplastic carcinoma, surprisingly, Tob phosphorylation was not observed in any cases, but the deficiency of Tob expression was also observed in all these cases. These results suggest that (1) Tob phosphorylation contributes to the progression of papillary carcinoma especially in the later phase through cancellation of its anti-proliferative function, and (2) the deficiency of Tob expression is attributable to the lack of Tob phosphorylation in anaplastic carcinoma.

Adenoma↗

PubMed2005

Usefulness of thyroglobulin measurement in fine-needle aspiration biopsy specimens for diagnosing cervical lymph node metastasis in patients with papillary thyroid cancer.

The diagnosis of lymph node metastasis in patients with papillary thyroid cancer is an important factor when deciding to perform neck dissection at the initial surgery, as well as for evaluating the lymph node swelling after surgery. Ultrasound (US)-guided fine-needle aspiration biopsy cytology (FNAB-C) is the most useful technique for diagnosing lymph node metastasis. Recently, however, measurement of thyroglobulin in the wash-out of the needle (FNAB-Tg) has been proposed for early detection of neck lymph node metastasis in patients with differentiated thyroid cancer. The purpose of this study was to evaluate the usefulness of FNAB-Tg in detecting lymph node metastasis prior to initial or reoperative thyroid surgery. US-guided FNAB-C was performed on 129 enlarged lymph nodes of 111 patients before surgery. All of them were later histologically confirmed to contain metastasis. Immediately after obtaining an FNAB-C specimen, the needle was rinsed with 0.5 ml of normal saline solution, and the wash-out was subjected to measurement of the Tg level (FNAB-Tg). If the FNAB-Tg level was higher than the serum Tg of the patient, we diagnosed the lymph node as positive (metastatic lymph node). FNAB-Tg sensitivity was 81.4%, and FNAB-C sensitivity was 78.0%. Altogether, 4 (36.4%) of 11 cases judged "benign" and 6 (37.5%) of 16 cases judged "inadequate" by FNAB-C were positive by the FNAB-Tg measurement. Thyroglobulin measurement in fine-needle aspiration biopsy wash-out is thus a useful technique for diagnosing lymph node metastasis of papillary thyroid cancer.

Biopsy, Fine-Needle↗

PubMed2005

Needle tract implantation of papillary thyroid carcinoma after fine-needle aspiration biopsy.

Although fine-needle aspiration biopsy (FNAB) is a useful tool for diagnosing thyroid carcinoma, there are some risks of complications. In this study, we investigated tumor implantation by FNAB of papillary carcinoma. We compared the characteristics of the main tumors and implanted tumors of patients showing FNAB implantations. Between 1990 and 2002, 4912 patients underwent FNAB and were diagnosed as having papillary carcinoma. We encountered 7 cases of needle tract implantation, which account only for 0.14%. We reviewed these 7 cases as well as 3 other patients who underwent FNAB in other hospitals. The intervals between FNAB and detection of the implanted tumor ranged from 2 to 131 months. For these 10 patients, the main tumors in 6 were diagnosed as poorly differentiated carcinoma, and 7 showed extrathyroid extension. Five showed the development of implanted tumor after comparatively shorter intervals (2-68 months), and we classified these as the short interval group. The remaining 5 were classified as the long interval group, because tumor development occurred after 87-131 months. All 5 cases in the short interval group involved preoperatively detectable lymph node metastasis; those in the long interval group did not. The MIB-1 labeling index of the implanted tumor was high in 4 cases in the short interval group, but it was low in all cases in the long interval group. The implanted tumors could be surgically removed without recurrence at the focal sites. These findings indicate that, although high growth activity in the metastatic lesions may be a risk factor of FNAB, inducing the growth of implanted tumors along the needle tract within a short interval after the procedure, FNAB remains the most useful technique for diagnosing thyroid carcinoma. The incidence of implantation was low, and when it did occur, the tumors could be surgically removed without recurrence.

Aged↗

PubMed2005

Stretching exercises to reduce symptoms of postoperative neck discomfort after thyroid surgery: prospective randomized study.

Patients who undergo thyroid surgery frequently suffer from unpleasant symptoms such as a stretching, choking, or pressing feeling or discomfort in the neck for a long time. The usefulness of rehabilitation (i.e., a stretching exercise) for reducing these symptoms after surgery has never been studied. In the present study, attempts were made to evaluate the usefulness of the stretching exercise in reducing disagreeable postoperative symptoms in the patients who had undergone thyroid surgery. A total of 409 patients, including 234 thyroid cancer patients, were randomly divided into a stretching group (n = 204) and a control group (n = 205). Patients in the stretching group were instructed that the stretching exercise was to be performed three times a day beginning the morning following surgery. A questionnaire survey was performed before surgery and then 1 week, 1 month, 6 months, and 1 year after surgery. Total symptom scores obtained from the questionnaire survey from the control group and the stretching group were compared. The use of analgesics was also investigated. Postoperative neck symptoms declined gradually over the course of a year, and the total symptom scores were significantly (p < 0.001) lower in the stretching group than in the control group at all points throughout the year (1 week, 1 month, 6 months, and 1 year). The mean requirement for the use of analgesics during hospitalization was significantly (p < 0.0001) less in the stretching group (1.6 +/- 2.3 tablets, mean +/- SD) than in the control group (3.1 +/- 3.8 tablets). The stretching exercise had effectively reduced postoperative neck symptoms and also reduced the use of analgesics after thyroid surgery.

Adolescent↗

PubMed2005

Ultrasonographically and anatomopathologically detectable node metastases in the lateral compartment as indicators of worse relapse-free survival in patients with papillary thyroid carcinoma.

The recent prevalence of ultrasonography has made it easier to detect lymph node metastasis in the lateral compartment of patients with thyroid carcinoma. In this study, we investigated the prognostic impact of lateral node metastasis preoperatively detectable by ultrasonography (US) and metastasis diagnosed by pathology examination but not detected on preoperative US [anatomopathologically (AP)-detectable metastasis] in 560 patients with papillary carcinoma >1 cm in diameter, who underwent thyroidectomy with modified radical neck dissection at our hospital. Patients with US-detectable metastasis (US+ patients) showed a significantly worse relapse-free survival (RFS) rate than those with no metastasis (US-/AP- patients) or AP-detectable metastasis (US-/AP+ patients) regardless of tumor size. Furthermore, the RFS of US-/AP+ patients with tumors >2 cm was worse than that of US-/AP- patients with tumors >2 cm or US-/AP+ patients with tumors measuring 1.1-2.0 cm. There was no significant difference in RFS between US-/AP+ and US-/AP- patients with tumors measuring 1.1-2.0 cm. These findings suggest that US-detectable lateral metastasis predicts a worse RFS for patients regardless of tumor size, and AP-detectable metastasis affects the RFS of patients with tumors >2 cm.

Adenocarcinoma, Papillary↗

PubMed2005

Ill-defined edge on ultrasonographic examination can be a marker of aggressive characteristic of papillary thyroid microcarcinoma.

We have previously demonstrated that, although most papillary thyroid microcarcinomas (PMC) do not grow or grow only slowly, cases showing lateral node metastasis diagnosed by ultrasonography (US) show an aggressive characteristic associated with poor disease-free survival. In this study, we focused on two prominent U.S. features: tumor, edge definition and strong echoes. We investigated whether these findings reflect aggressive characteristics of PMC in a series of 155 cases. Poor edge definition was observed in 21.5% of patients, all of who showed worse disease-free survival (p = 0.0477) than those with a well-defined edge. Furthermore, this finding was directly linked to US-diagnosed lateral node metastasis (p = 0.0001). Strong echoes were observed in 63.9% of the cases, and fine strong echoes were seen in 25.2%. Cases demonstrating fine strong echoes tended to frequently show recurrence (p = 0.0902), and this finding was also significantly linked to US-diagnosed lateral node metastasis (p = 0.0494). These findings suggest that an ill-defined tumor edge is an important US feature of biologically aggressive PMC. We should carefully follow such patients, regardless of the therapeutic strategy, observation, or surgical treatment chosen.

Adenocarcinoma, Papillary↗