Factors predicting microinvasion in Ductal Carcinoma in situ.

BACKGROUND: Whether sentinel lymph node biopsy (SLNB) should be performed in patients with pure ductal carcinoma in situ (DCIS) of the breast has been a question of debate over the last decade. The aim of this study was to identify factors associated with microinvasive disease and determine the criteria for performing SLNB in patients with DCIS. MATERIALS AND METHODS: 125 patients with DCIS who underwent surgery between January 2000 and December 2008 were reviewed to identify factors associated with DCIS and DCIS with microinvasion (DCISM). RESULTS: 88 patients (70.4%) had pure DCIS and 37 (29.6%) had DCISM. Among 33 DCIS patients who underwent SLNB, one patient (3.3%) was found to have isolated tumor cells in her biopsy, whereas 1 of 14 (37.8%) patients with DCISM had micrometastasis (7.1%). Similarly, of 16 patients (18.2%) with pure DCIS and axillary lymph node dissection (ALND) without SLNB, none had lymph node metastasis. Furthermore, of 20 patients with DCISM and ALND, only one (5%) had metastasis. In multivariate analysis, the presence of comedo necrosis [relative risk (RR)=4.1, 95% confidence interval (CI)=1.6-10.6, P=0.004], and hormone receptor (ER or PR) negativity (RR=4.0, 95%CI=1.5-11, P=0.007), were found to be significantly associated with microinvasion. CONCLUSIONS: Our findings suggest patients presenting with a preoperative diagnosis of DCIS associated with comedo necrosis or hormone receptor negativity are more likely to have a microinvasive component in definitive pathology following surgery, and should be considered for SLNB procedure along with patients who will undergo mastectomy due to DCIS.

Videoendoscopic single-port nipple-sparing mastectomy and immediate reconstruction.

PURPOSE: Single-incision videoendoscopic surgery has recently become popular as a result of the ongoing search for less invasive procedures. The aim of this study was to evaluate the safety and efficacy of endoscopic single-port nipple-sparing mastectomy, axillary lymphadenectomy, and immediate reconstruction in patients with breast cancer. PATIENTS AND METHODS: From May 14, 2012 through January 23, 2013, 10 patients underwent videoendoscopic single-port nipple-sparing mastectomy and axillary dissection via a single, limited incision and immediate prosthetic reconstruction. Patient charts were reviewed, and demographic data, operative time, complications and pathology results were analyzed. RESULTS: In all patients, videoendoscopic surgery was performed successfully. Of 10 patients, 7 were diagnosed as having invasive ductal carcinoma, 2 had a ductal carcinoma in situ, and 1 underwent bilateral prophylactic mastectomy. The weight of the resected gland was 300-650 g, with a mean of 420 g. There were no operative complications, and the mean operative time was 250 minutes (range, 160-330 minutes). One-stage reconstruction with implants was performed on 4 patients, whereas expanders were placed in the remaining 6. Surgical margins of all cases were pathologically negative, and there were no recurrences observed during the early follow-up period. CONCLUSIONS: Videoendoscopic single-port nipple-sparing mastectomy is technically feasible even in larger breasts, enabling immediate reconstruction with good cosmetic outcomes. However, further studies with larger clinical series and long-term follow-up are required to compare the safety and efficacy of the technique with those of the standard nipple-sparing mastectomy.

Incremental value of magnetic resonance imaging for breast surgery planning.

PURPOSE: The aim of this study was to evaluate the effect of breast magnetic resonance imaging (MRI) on preoperative or intraoperative surgical planning. METHODS: One hundred and sixty females with breast cancer were enrolled in the study. The contribution of MRI compared to MMG and USG, their histopathological concordance, and their impact on surgical treatment were evaluated prospectively. RESULTS: In 48 (30.0%) of the patients, MRI identified suspicious lesions that were not detected by MMG and USG. The diagnosis by MRI was accurate in 17 (10.6%) of them, while in remaining 31 patients (19.4%) the additional lesions found by MRI and interpreted as malignant were found not to be malignant. The pathological accordance of MRI and MMG compared with USG were 69.3 and 70.0%, respectively, whereas individually, MMG and USG were in accordance with the pathological examination in 52.9 and 67.9% of the cases, respectively. CONCLUSIONS: Assessment of the tumor size, multifocality, multicentricity, and presence of ductal carcinoma in situ by MRI may lead to misinterpretations in the majority of patients. The surgical approach should not be changed based solely on MRI findings. An accurately interpreted MMG combined with USG may be sufficient in most cases.

Clinical importance of micrometastasis in sentinel lymph nodes.

INTRODUCTION: We evaluated the incidence of micrometastasis and nonsentinel lymph node metastasis as well as local and axillary recurrence rates after level I-II axillary lymph node dissection. MATERIALS AND METHODS: Patients (n=760) with early-stage breast cancer underwent sentinel lymph node biopsy, and 45 patients (6.0%) with micrometastasis (0.2-2.0mm) were included in this study. Data concerning tumor, patients' characteristics and adjuvant treatments were recorded. RESULTS: The median age was 46 (26-67) years, median breast tumor size was 20 (1-50) mm, and median number of excised sentinel lymph nodes were 2 (1-5). All patients with micrometastasis underwent further level I-II axillary lymph node dissection. Eleven of 45 (24.4%) patients with micrometastasis in their sentinel lymph node biopsy had nonsentinel lymph node metastasis after an axillary lymph node dissection. There was no factor related to nonsentinel lymph node metastasis. Stage migration occurred in 4 of 45 patients (8.8%) due to the detection of micrometastases or macrometastases in nonsentinel lymph nodes. DISCUSSION: The classical treatment after detection of micrometastasis in sentinel lymph nodes is further axillary dissection. However, nonrandomized, nonprospective studies with 4-5 years follow up showed 0.6% axillary recurrence without further axillary lymph node dissection, although we still need the results of randomized controlled studies.

Metastatic lymph node ratio is an independent prognostic factor in gastric cancer.

BACKGROUND/AIMS: The metastatic status of the regional lymph node is the most significant prognostic factor for gastric cancer. However, diverse prognoses are evident even among the same N classifications of the current tumor-node-metastasis system. The aim of this study is to evaluate the prognostic significance of the ratio of metastatic to examined lymph nodes (N ratio) for identifying a high-risk subgroup of patients with gastric cancer. METHODOLOGY: The postoperative survival of 264 consecutive patients with operable gastric cancer was analyzed with regard to its N ratio and current N classification. Survival was determined by the Kaplan-Meier method and differences were assessed by the log-rank test. Multivariate analysis was performed using the Cox proportional hazards model in forward stepwise regression. RESULTS: The lymph node ratio was classified as follows N ratio 1, 1 to 10, N ratio 2, 11 to 25; and N ratio 3, >25. The 5-year survival rates stratified by N ratio were N ratio 1, 81%; N ratio 2, 49%; N ratio 3, 25%. The rates of survival were significantly different according to the N ratio in pN1 and pN2 classification of the UICC/TNM classification (p<0.05). Cox regression analysis revealed that N ratio was sensitive prognostic factor in these surgically treated patients, which were also significantly correlated with extent of lymph node dissection and pathologic tumor stage (p<0.05). CONCLUSIONS: N ratio can be recommended as an applicable parameter for lymph node involvement of gastric cancer. It is a more effective and precise indicator for prognostic stratification of patients with lymph node positive gastric cancer than the current N classification of the tumor-node-metastasis system.

Breast cancer risk factors in Turkish women--a University Hospital based nested case control study.

BACKGROUND: Breast cancer has been increased in developing countries, but there are limited data for breast cancer risk factors in these countries. To clarify the risk for breast cancer among the Turkish women, an university hospital based nested case-control study was conducted. METHODS: Between January 2000 and December 2006, a survey was prospectively conducted among women admitted to clinics of Istanbul Medical Faculty for examination and/or treatment by using a questionnaire. Therefore, characteristics of patients diagnosed with breast cancer (n = 1492) were compared with control cases (n = 2167) admitted to hospital for non-neoplastic, non-hormone related diseases. RESULTS: Breast cancer risk was found to be increased in women with age (> or = 50) [95% confidence interval (CI) 2.42-3.18], induced abortion (95% CI 1.13-1.53), age at first birth (> or = 35) (95% CI 1.62-5.77), body mass index (BMI > or = 25) (95% CI 1.27-1.68), and a positive family history (95% CI 1.11-1.92). However, decreased breast cancer risk was associated with the duration of education (> or = 13 years) (95% CI 0.62-0.81), presence of spontaneous abortion (95% CI 0.60-0.85), smoking (95% CI 0.61-0.85), breast feeding (95% CI 0.11-0.27), nulliparity (95% CI 0.92-0.98), hormone replacement therapy (HRT) (95% CI 0.26-0.47), and oral contraceptive use (95% CI 0.50-0.69). On multivariable logistic regression analysis, age (> or = 50) years (OR 2.61, 95% CI 2.20-3.11), induced abortion (OR 1.66, 95% CI 1.38-1.99), and oral contraceptive use (OR 0.60, 95% CI 0.48-0.74) were found to be associated with breast cancer risk as statistically significant independent factors. CONCLUSION: These findings suggest that age and induced abortion were found to be significantly associated with increased breast cancer risk whereas oral contraceptive use was observed to be associated with decreased breast cancer risk among Turkish women in Istanbul.

Increased lymph node positivity in multifocal and multicentric breast cancer.

BACKGROUND: Multifocal and multicentric (MF/MC) breast cancers have been reported to be associated with increased lymph node metastases. The limited data on this issue prompted us to investigate the pathologic and clinical differences between unifocal and MF/MC breast cancer. STUDY DESIGN: Between 1990 and 2002, 1,322 patients with operable invasive breast cancer underwent a definitive operation at our Breast Clinic. Patients with MF/MC breast cancer (n=147, 11%) were compared with patients with unifocal breast cancer (n=1,175; 89%) in terms of pathologic and clinical characteristics. RESULTS: Patients with MF/MC were found to have a higher frequency of lymph node metastases when the largest diameter was used as a tumor size estimate for MF/MC cancer (unifocal T1 and T2, 35% and 49%, respectively, versus MF/MC T1 and T2, 48% and 67%, respectively; p=0.05 and p=0.003, respectively). When the combined diameter assessment was used, the frequency of lymph node positivity was similarly higher in MF/MC patients versus unifocal patients (unifocal T1 and T2, 35% and 49%, respectively, versus MF/MC T1 and T2, 49% and 61%, respectively; p=0.08 and p=0.046, respectively). At a median followup of 55 months (range 12 to 153 months), 5-year disease-free survival (DFS; unifocal, 88% versus MF/MC, 82%, p=0.14) and overall survival (OS) rates (unifocal, 92% versus MF/MC, 93%, p=0.43) did not show any significant difference between two groups. CONCLUSIONS: Our data suggest that breast tumors with multiple foci have a different biology, with an increased metastatic potential to axillary lymph nodes, regardless of tumor size, that reflects an advanced stage. The clinical relevance of the currently used TNM classification system, which uses the diameter of the largest nodule, is supported by our findings.

Impact of laparoscopic surgery on bladder and sexual function after total mesorectal excision for rectal cancer.

BACKGROUND: Bladder and sexual dysfunction are well-documented complications of rectal cancer surgery. This study aimed to determine whether laparoscopy can improve the outcome of these dysfunctions or not. METHODS: The study included 63 of the 116 patients who underwent surgery for rectal cancer between 2002 and 2006. Bladder and male sexual function were studied by means of a questionnaire on the basis of the International Prostatic Symptom Score (IPSS) and International Index of Erectile Function (IIEF). In addition, bladder function was determined by means of postvoid residual urine measurement and uroflowmetry. Postoperative functions were compared with the preoperative data to detect subjective functional deterioration. Outcomes were compared between patients who underwent open (group 1, n = 29) and laparoscopic (group 2, n = 34) total mesorectal excision. RESULTS: Only minor disturbances of bladder function were reported for one patient (3%) in group 1 and three patients (9%) in group 2 (p > 0.05). Impotency after surgery was experienced by 6 of 17 preoperatively sexually active males (29%) in group 1 and 1 of 18 males (5%) in group 2 (p = 0.04). Similarly, 5 of 10 women (50 %) in group 1 and 1 of 14 women (7%) in group 2 felt that their overall level of sexual function had decreased as a result of surgery (p = 0.03). CONCLUSIONS: Open rectal cancer resection is associated with a higher rate of sexual dysfunction, but not bladder dysfunction, compared with laparoscopic surgery. Laparoscopic rectal cancer surgery offers a significant advantage with regard to preservation of postoperative sexual function and constitutes a true advance in rectal cancer surgery compared with the open technique. The proposed advantages can be attributed to improvement in visibility by the magnification feature of laparoscopic surgery.

Is the thymidine labeling index a good prognostic marker in breast cancer?

BACKGROUND: The aim of the present study was to determine the prognostic relevance of thymidine labeling index (TLI) in patients with breast cancer. METHODS: TLI of the primary tumor was measured in 268 patients at the time of the surgical biopsy by an in vitro method. RESULTS: Fifty-four patients had stage I disease, and 138 patients had stage II disease, and 76 patients had stage III disease. One hundred-four patients were found to have low TLI-index (<3%), and 164 patients had high TLI-index (>/=3%). The median follow-up was 71.5 months (range, 6-138 months). The 5-year overall survival (OS) and disease free survival (DFS) rates was 84% and 74%, respectively. Lymph node involvement, tumor size more than 2 cm, high nuclear grade and estrogen receptor negativity were found to be associated with poorer DFS and OS rates. On subgroup analysis, however, the 5-year OS rate was significantly higher in the low TLI-group than in the high TLI-group in patients with stage I disease (100% vs 76%, p = 0.05). CONCLUSION: Our findings suggest that the prognostic significance of TLI appears to be limited to early breast cancer that might help to distinguish patients who need more aggressive adjuvant treatment.

The value of combined peritumoral and subdermal injection techniques for lymphoscintigraphy in detection of sentinel lymph node in breast cancer.

PURPOSE: The aim of this study was to evaluate the success rate of combined peritumoral and subdermal injection techniques based on our previous experience on different injection techniques for lymphoscintigraphy. PATIENTS AND METHODS: Fifty-nine women with early breast cancer (mean tumor size, 20.5 mm) were prospectively studied. On the morning of the operation, each patient had 2 injections, one peritumoral (PT) medial to the lesion and one subdermal (SD) into the skin over the tumor quadrant. Each injection consisted of 20 MBq (540 mCi) Tc-99m rhenium sulfide colloid. Early dynamic and delayed static images were obtained up to 4 hours after injections. An intraoperative gamma probe was used to explore the axillary sentinel lymph nodes (SLN). All surgical specimens were evaluated histopathologically. RESULTS: Forty patients had breast-preserving surgery and 19 had modified radical mastectomy. Thirty-eight patients had axillary dissection. All but 4 patients showed axillary lymphatic drainage. Twelve of 59 patients (20%) showed extraaxillary drainage with lymphoscintigraphy. Combined injection technique yielded a 93.2% success rate in detecting axillary SLN. In 2 of 4 patients with no drainage on lymphoscintigraphy, intraoperative gamma probe revealed SLN during the surgery. Twenty patients (33%) had positive axillary lymph nodes. In 14 of them, the SLN was the only positive node. A false-negative rate was found 1.6% (one of 59 patients). CONCLUSION: This results suggest that a combination of both PT and SD techniques increases the success rate of visualization SLN and enhances the visualization of extraaxillary nodes for further treatment planning.

Malignant phyllode tumor metastatic to the duodenum.

Phyllode tumor (PT) is extremely rare tumor of the breast. Distant metastasis occurs in 10%-20% of patients with malignant phyllode tumor. The most common sites of metastases are the lungs and bones. Although theoretically any organ may have metastasis, an isolated duodenum metastasis has not been documented as yet in the English-language literature. We report herein a case with a isolated duodenal metastasis from PT of breast in a 31 year-old-woman who underwent right mastectomy 4 years before because of the recurrent malignant PT. She presented to our hospital with massive upper gastrointestinal bleeding. Clinical evaluation revealed a huge mass originated from duodenum. Urgent laparotomy and pancreaticoduodenectomy were carried out in order to remove the bleeding duodenal mass. The pathologic examination of the resected specimen showed a malignant spindle cell tumor consistent with metastatic malignant PT. Our case of gastrointestinal bleeding due to an isolated duodenal metastasis as a result of hematogenous spread from malignant phyllode tumor of breast is unique in the English literature and pancreaticoduodenectomy is a curative treatment for patients with isolated duodenal involvement.

Feasibility of surgical management in patients with granulomatous mastitis.

Granulomatous mastitis (GM) is a rare inflammatory breast disease of unknown etiology. Although it usually presents with sinus formation and abscesses, it may mimic the clinical characteristics of breast cancer. The aim of this study was to identify the clinical, radiologic, and pathologic characteristics of patients with GM and to show the results of surgical treatment in these patients. A chart review was performed for patients that were treated with a diagnosis of GM at the Breast Unit, Department of Surgery, Istanbul Medical Faculty, University of Istanbul, between September 1998 and January 2003. Eighteen patients were eligible for this study. The median age was 41.5 years (range 16-80 years). Seventeen patients were evaluated by both ultrasonography and mammography; whereas one young patient only had ultrasonography. Three patients were further examined with color Doppler ultrasonography and magnetic resonance imaging (MRI). Fourteen patients (78%) presented with a mass as the chief symptom, with a median size of 3.9 cm (range 1-8 cm), whereas four patients presented with fistula in their breasts. None of the radiologic techniques distinguished benign disease from cancer in any of the 14 patients that presented with a mass except one patient with normal mammography findings. Ultrasonography was only helpful to localize the abscess associated with a fistula tract in one patient. Therefore fine-needle aspiration biopsy (FNAB) was performed in six patients, followed by surgical excisional biopsy. The remaining eight patients with a clinical suspicion of malignancy underwent wide surgical excision with frozen section analysis under general anesthesia. All of the FNAB and frozen section evaluations revealed benign findings. All of the 18 patients underwent a wide excisional biopsy and had a definitive histopathologic diagnosis of GM. The median follow-up was 36 months (range 6-60 months). Only one patient had a recurrent disease, which was diagnosed at 12 months. GM is a rare breast disease that mimics cancer in terms of clinical findings. Preoperative radiologic diagnosis might be difficult. Complete surgical excision is the treatment of choice.

Does the early ligation of the splenic artery reduce hemorrhage during laparoscopic splenectomy?

The aim of this study was to investigate whether early ligation of the splenic artery before splenic lysis has an effect on the amount of intraoperative bleeding and conversion rate during laparoscopic splenectomy. Laparoscopic splenectomy was performed in 34 patients with hematological diseases or splenic cysts between January 1993 and January 2003. The splenic artery was ligated before manipulation of the spleen in 22 patients (group 1) and laparoscopic splenectomy was performed with no previous ligation of the splenic artery in 12 patients (group 2). Prospective data was collected and the groups compared regarding intraoperative blood loss, platelet count, operative time, hospital stay, and conversion rate. Laparoscopic splenectomy was successfully completed in 30 (88%) patients. One patient in group 1 (5%) and 3 patients in group 2 (25%) required conversion due to bleeding. Estimated average blood loss was 161 mL (range 70-450 mL) in group 1, and 292 mL (range 100-700 mL) in group 2 (P < 0.001). The average operative time was 140 minutes (range 80-240) in group 1, and 155 minutes (range 80-200) in group 2 (P > 0.05). There were no statistically significant differences between the two groups comparing splenic size, conversion rate, hospital length of stay and platelet count. Early ligation of the splenic artery is feasible, safe and effective and may provide easy dissection and manipulation of the spleen during laparoscopic splenectomy with decreased intraoperative blood loss and no extension of the operative time.

Does the complication rate increase in laparoscopic cholecystectomy for acute cholecystitis?

BACKGROUND: Laparoscopic cholecystectomy (LC) has replaced open cholecystectomy for the treatment of gallbladder disease. Despite the well-accepted success of LC in chronic cholecystitis, the efficacy of this technique has been subject to some debate in acute cholecystitis (AC). This study was designed to evaluate our institution's experience with LC for AC and chronic symptomatic calculous cholecystitis (CC), based on complication and conversion rates to open surgery. PATIENTS AND METHODS: The records of 1158 patients with LC from September 1991 to December 2001 were analyzed. The parameters of age, gender, early and late complication rates, and conversion rates from LC to open cholecystectomy were compared in patients with AC and CC. RESULTS: During the study period, LC was performed in 1158 patients. Of these, 162 patients had AC (group 1) and 996 patients had CC (group 2). The conversion rates were 4.3% (7/162) in group 1 and 2.4% (24/996) in group 2. The complication rates were not significantly different (5.6% in group 1, 5.1% in group 2, P > 0.05). Difficulty in dissection around Calot's triangle and obscure anatomy were the main reasons for conversion to conventional open surgery. The mortality rate was 1.2% in group 1 and 0.01% in group 2. CONCLUSION: LC appears to be a reliable, safe, and effective treatment modality for AC and CC. The surgical approach should be performed carefully because of the spectrum of potential hazards of the laparoscopic procedure. Conversion and complication rates are similar in both AC and CC groups, and improve as surgeons gain experience.

Inflammatory breast cancer: results of antracycline-based neoadjuvant chemotherapy.

Twenty-three patients with inflammatory breast cancer treated with a combined modality approach including anthracycline-based induction chemotherapy-surgery-chemotherapy-radiotherapy were reviewed. Twelve patients (52.2%) received FAC (5-fluorouracil, adriamycin, cyclophosphamide) and 11 patients (47.8%) were treated with FEC (5-fluorouracil, epirubicin, cyclophosphamide) induction chemotherapy for three cycles every 3 weeks. Surgery was followed by the initial chemotherapy or second-line chemotherapy for an additional six cycles to complete nine cycles and radiotherapy, respectively. The median overall survival (OS) time was 27 months and the median disease-free survival (DFS) was 13 months. Furthermore, patients treated with FAC induction chemotherapy have been found to have longer median OS and DFS periods compared to patients with FEC induction chemotherapy in both univariate and multivariate analysis. In conclusion, the superiority of doxorubicin-containing chemotherapy over epirubicin-containing chemotherapy should be established in larger randomized studies and more effective chemotherapeutic agents such as taxans are required for better survival rates in inflammatory breast cancer patients.

Increased false negative rates in sentinel lymph node biopsies in patients with multi-focal breast cancer.

There are few data about the reliability of sentinel node biopsy in patients with multi-focal breast cancer. The aim of this study was to determine the factors affecting the identification and accuracy of the sentinel node, comparing multifocality with other variables, using peritumoral isosulfan blue dye injection technique alone. Between 1998 and 2001, 122 patients with clinically negative nodes from a single institute were eligible for sentinel lymph node biopsies (SLNBs). All patients underwent conventional axillary lymph node dissection (ALND). SLNs were identified in 111 of 122 (91%) cases, and analyzed by hematoxylin and eosin. Twenty-one patients with multifocal breast cancer were determined by clinical or pathologic examination (gross or microscopic). Success in locating the sentinel node was unrelated to patient's age, tumor size, type, location, histological or nuclear grade, multifocality, or a previous surgical biopsy. SLNBs accurately predicted the status of the axilla in 104 of the 111 patients (93.7%), while 18 of the 21 patients with multi-focal breast cancer (85.7%) had successful lymphatic mapping. The false negative (FN) rate was 11.3% among patients with successful SLNBs. Multifocality and tumor size (>2 cm) were associated significantly with decreased accuracy and increased FN rates (for multifocality, p = 0.007 and p = 0.006, and for tumor size >2 cm, p = 0.04 and p = 0.05, respectively) in binary logistic regression analysis, whereas excisional biopsy, tumor location in the upper outer quadrant and patient's age did not significantly affect the accuracy and FN rates in univariate analysis. These results suggest sentinel lymph node biopsy using peritumoral isosulfan blue injection method alone can accurately predict axillary status in patients with clinically negative nodes, but patients with multi-focal disease and large tumor size may not be ideal candidates.

An ultrasensitive tumor enriched flow-cytometric assay for detection of isolated tumor cells in bone marrow of patients with breast cancer.

BACKGROUND: An ultrasensitive tumor enriched flow-cytometric assay was used to determine its feasibility in detection of isolated tumor cells (ITC) in bone marrow (BM) of patients with breast cancer. METHODS: Epithelial cells were removed by magnetic microbeads conjugated with an anti-cytokeratin 7/8 monoclonal antibody to enrich tumor cells in BM samples. A specific gate for MCF-7 breast cancer cells (gate(MCF-7 cells)) was also taken into consideration in addition to a gate including all enriched BM cells (gate(enriched BM cells)) in flow-cytometric analysis to enhance the specificity of the method. RESULTS: Nineteen patients with stage I/II were evaluated. Ten patients (53%) were found to have cytokeratin positive (CK(+)) cells according to the gate(enriched BM cells) whereas 6 patients (32%) had CK(+) cells when the gate(MCF-7 cells) was taken into account. CONCLUSIONS: New strategies in nonmorphological ultrasensitive techniques might be useful to categorize patients with ITCs having different tumor morphology and characteristics.