Multicenter randomized controlled trial and registry study to assess the safety and efficacy of the NanoKnife® system for the ablation of stage 3 pancreatic adenocarcinoma: overview of study protocols.

BACKGROUND: Irreversible electroporation (IRE) is a local ablation technique utilizing high voltage, low energy direct current to create nanopores in cell membrane which disrupt homeostasis and leads to cell death. Previous reports have suggested IRE may have a role in treating borderline resectable and unresectable Stage 3 pancreatic tumors. METHODS: Patients with Stage 3 pancreatic ductal adenocarcinoma (PDAC) will be enrolled in either a randomized, controlled, multicenter trial (RCT) or a multicenter registry study. Subjects enrolled in the RCT must have no evidence of disease progression after 3 months of modified FOLFIRINOX (mFOLFIRINOX) treatment prior to being randomization to either a control or IRE arm. Post-induction and post-IRE treatment for the control and IRE arms, respectively, will be left to the discretion of the treating physician. The RCT will enroll 528 subjects with 264 per arm and include up to 15 sites. All subjects will be followed for at least 24 months or until death. The registry study will include two cohorts of patients with Stage 3 PDAC, patients who received institutional standard of care (SOC) alone and those treated with IRE in addition to SOC. Both cohorts will be required to have undergone at least 3 months of SOC without progression prior to enrollment. The registry study will enroll 532 patients with 266 patients in each arm. All patients will be followed for at least 24 months or until death. The primary efficacy endpoint for both studies will be overall survival (OS). Co-primary safety endpoints will be 1) time from randomization or enrollment in the registry to death or new onset of Grade 4 adverse event (AE), and (2 high-grade complications defined as any AE or serious AE (SAE) with a CTCAE v5.0 grade of 3 or higher. Secondary endpoints will include progression-free survival, cancer-related pain, quality of life, and procedure-related pain for the IRE arm only. DISCUSSION: These studies are intended to provide Level 1 clinical evidence and real-world data demonstrating the clinical utility and safety of the use of IRE in combination with chemotherapy in patients with Stage 3 PDAC. TRIAL REGISTRATION: Clinicaltrials.gov NCT03899636 and NCT03899649. Registered April 2, 2019. Food and Drug Administration (FDA) Investigational Device Exemption (IDE) trial G180278 approved on May 3, 2019.

Survival rates for breast cancers detected in a community service screening mammogram program.

BACKGROUND: This single-institution long-term prospective study was performed in the setting of community service screening mammography to evaluate the association between the methods of breast cancer detection and survival rates. METHODS: From 1994 through 2001, data on 1237 patients with breast cancer were collected concurrent with definitive surgical treatment and entered into a comprehensive database. RESULTS: Mammography was the sole method of detection for 517 (44%) of 1179 Tis-T2 breast cancers. Fifty-seven percent of invasive cancers detectable by mammography alone were less than 1 cm in diameter. For 1049 patients with invasive cancers, the 5-year overall observed survival rates were 94% for 372 whose cancers were detectable by mammogram alone and 87% for 677 whose cancers were detectable by palpation (alone or in combination with mammography) (P = .0002). CONCLUSIONS: Most of the contribution to breast cancer mortality reduction is from the detection of small nonpalpable cancers, not from adjuvant therapy.

Upstaging of atypical ductal hyperplasia after vacuum-assisted 11-gauge stereotactic core needle biopsy.

BACKGROUND: Nonpalpable mammographic abnormalities are frequently evaluated by means of a stereotactic core needle biopsy. This technique is a very sensitive indicator of invasive cancer, but is less reliable to discriminate between ductal carcinoma in situ and atypical ductal hyperplasia (ADH). The objective of this study was to determine the correlation of the 11-gauge vacuum-assisted core needle biopsy to open biopsy when a diagnosis of ADH is obtained. HYPOTHESIS: The use of 11-gauge vacuum-assisted stereotactic core needle biopsy does not conclusively diagnose ADH. DESIGN: Retrospective analysis. SETTING: University-affiliated teaching hospital. PATIENTS: Mammographic findings were evaluated with an 11-gauge vacuum-assisted stereotactic core biopsy in 1750 patients. Seventy-seven patients were diagnosed as having ADH; of these, 65 underwent excisional biopsy. MAIN OUTCOME MEASURES: Pathological upstaging rate. RESULTS: Of the 65 patients who underwent excisional breast biopsy, 11 (17%) had their condition upstaged to a breast cancer diagnosis. These patients had presented at a later age than those who retained a benign diagnosis after excisional biopsy. The number of cores taken did not correlate with diagnostic accuracy. CONCLUSIONS: Of the 65 patients who underwent open biopsy for ADH in this series, only 83% had an accurate diagnosis. A diagnosis of ADH by stereotactic core needle biopsy should be followed by an open excisional biopsy.

Failure of sentinel lymph node mapping in patients with breast cancer.

BACKGROUND: Lymphatic mapping with sentinel lymphadenectomy (SL) has become more widely used as an alternative to axillary dissection for the staging of breast cancer. This study was conducted to evaluate the potential associations of patient and tumor characteristics with the lymphatic mapping failure rate. STUDY DESIGN: Between September 1996 and April 2003, 1,094 breast cancer patients participated in a single-institution prospective SL protocol, which was conducted using technetium 99 m sulfur colloid alone to identify sentinel lymph nodes. During the validation phase, consisting of the first 80 patients, all patients had SL followed by axillary dissection. Beginning with the 81st patient, the standard technique consisted of radiolabeled colloid injection in a peritumoral distribution 16 to 24 hours before the operation, followed by SL alone for node-negative patients. RESULTS: Of 1,094 consecutive patients, 62 (5.7%) did not map. Patients having more than 10 involved lymph nodes had a significantly higher incidence of mapping failure (40.9%) than those who were node-negative (5.3%) (odds ratio = 9.19, p = 0.002). Age was a factor predictive of mapping failure for node-negative patients 70+ years of age (odds ratio = 3.14, p = 0.018). Biopsy technique, tumor size, tumor location, cell type, and surgeon experience were not predictors of mapping failure, regardless of node status. CONCLUSIONS: The lymphatic mapping failure rate was associated with both anatomic and pathologic factors. Patients with extensive nodal involvement had a significantly greater chance of mapping failure. Among node-negative patients, those who were older were more likely to have mapping failure than those who were younger, suggesting that decreased breast density in postmenopausal women might provide an anatomic explanation for nonmapping.

Coil embolization of a lumbar artery to control vascular injury during intradiscal surgery.

STUDY DESIGN: Case study. OBJECTIVE: To emphasize the role that interventional radiology can perform in stemming bleeding to vascular structures injured during spine surgery without altering patient position. SUMMARY AND BACKGROUND DATA: Injury to the lumbar artery or aorta may occur during lumbar disc surgery. Occasionally the site of bleeding may not be readily identifiable or accessible through the surgical incision. Interventional radiology techniques may be employed to help locate and stop these difficult to locate vascular structures without changing a patient position. METHODS: A 48-year-old woman undergoing L4-L5 lumbar hemilaminectomy and discectomy secondary to a herniated disc sustained an injury to a right L3 lumbar artery. Several liters of blood were lost in an attempt to surgically locate and repair the injury to the lumbar artery. A literature search identified the potential severity and treatment options. RESULTS: An interventional radiologist was called for and he was able to angiographically locate the source of bleeding and stem its source using coil embolization of the lumbar artery. CONCLUSION: Whenever there is bleeding from an inaccessible site, consultation with an interventional radiologist to perform an intraoperative coil embolization of the injured vessel should be done especially if a resort to an anterior abdominal approach would permit uncontrolled bleeding.

The effects of hormone replacement therapy on postmenopausal breast cancer biology and survival.

BACKGROUND: The goal of this study was to compare the characteristics of breast cancers and survival rates in HRT users versus nonusers. METHODS: Data were analyzed for 1055 patients > or = 50 years of age who had definitive therapy for breast cancer from 1994 through 2002. RESULTS: There were 471 (45%) HRT users. The median age at diagnosis was 61.0 years for HRT users and 68.0 years for HRT nonusers (P < .001). HRT users more often had tumors that were <1 cm (P = .007), node negative (P = .033), and grade I (P = .016). HRT users had a decreased risk of death versus nonusers (hazard ratio = .438, 95% confidence limit = .263 to .729, P = .002). CONCLUSIONS: HRT users developed breast cancer at a younger age than nonusers; HRT use was associated with the development of biologically more favorable cancers than those that developed in nonusers; and overall and disease-free survival rates were higher in HRT users than nonusers.

Effect of hospital volume on margin status after pancreaticoduodenectomy for cancer.

BACKGROUND: The volume-outcome relationship has been repeatedly demonstrated for pancreatectomy, but identifying underlying reasons for this association has been challenging. Some have suggested that differences in surgical technique may affect longterm survival, but it is unknown whether margin-positive resection rates vary by hospital volume. Our objective was to evaluate the effect of hospital pancreatectomy volume on margin status. STUDY DESIGN: Patients who underwent pancreaticoduodenectomy for localized pancreatic adenocarcinoma were identified from the National Cancer Data Base (1998 to 2004). Regression modeling adjusting for patient, tumor, and hospital factors was used to assess predictors of margin involvement and to evaluate the effect of margin status on survival. Volume quintiles were based on average annual hospital pancreatectomy volume. RESULTS: Of 12,101 patients, 24.4% had positive resection margins (14.6% microscopic/R1; 9.8% macroscopic/R2). From 1998 to 2004, there was not a significant change in margin-positive resection rates (p=0.43). On multivariable analysis, patients were more likely to have a margin-positive resection if they had a higher T classification or nodal involvement, were uninsured or living in lower-income areas, or underwent resection at lowest-volume hospitals compared with highest-volume hospitals (25.9% versus 22.6%, p < 0.0001; odds ratio, 1.21; 95% confidence interval, 1.01 to 1.43). On multivariable analysis, margin involvement was associated with a higher risk of longterm mortality compared with margin-negative resections (p < 0.0001). CONCLUSIONS: Involved resection margins are a poor prognostic factor after a pancreaticoduodenectomy. Patients undergoing pancreaticoduodenectomy at low-volume centers are more likely to have margin-positive resections. Standardization of pathologic evaluation for pancreatectomy specimens is needed.

Axillary recurrence after sentinel node biopsy.

BACKGROUND: Sentinel node biopsy (SNB) has evolved as the standard of care in the surgical staging of breast cancer. This technique is accurate for surgical staging of axillary nodal disease. We hypothesized that axillary recurrence after SNB is rare and that SNB may provide regional control in patients with microscopic nodal involvement. METHODS: With institutional review board approval, SNB was performed with peritumoral injection of 99mTc-labeled sulfur colloid. From 1996 to 2003, 1167 patients were entered into a prospective cancer database after surgical therapy; 916 patients consented to long-term follow-up. Fifty-two patients (5.7%) did not map successfully and were excluded, leading to a study population of 864 patients. The median follow-up was 27.4 months (range, 1-98 months). RESULTS: The median number of sentinel nodes harvested was 2, and 633 (73%) patients had negative sentinel nodes. Thirty (4.7%) of those sentinel node-negative patients underwent completion axillary dissection, whereas 592 (94%) patients were followed up with observation. A total of 231 (27%) had positive sentinel nodes: 158 (68%) of these patients underwent completion axillary dissection, and 73 (32%) were managed with observation alone. Two (.32%) patients who were sentinel node negative had an axillary recurrence; one of these patients had undergone completion axillary dissection. No patient in the observed sentinel node-positive group had an axillary recurrence (odds ratio, .37; P = .725). CONCLUSIONS: On the basis of a median follow-up of 27.4 months, axillary recurrence after SNB is extraordinarily rare regardless of nodal involvement, thus indicating that this technique provides an accurate measure of axillary disease and may impart regional control for patients with node-positive disease.

Tumor volume as a prognostic factor for sarcomatosis.

BACKGROUND: The appropriate therapeutic interventions for sarcomatosis, or sarcoma characterized by intraabdominal dissemination, remain unclear. The authors performed a retrospective analysis of their recent experience with patients diagnosed with sarcomatosis to determine the overall survival and the effects of clinicopathologic features on survival rates at two and four years. METHODS: A query of the authors' prospective soft tissue sarcoma database identified 51 patients with a diagnosis of sarcomatosis who were evaluated at the authors' institution between June 1996 and June 1999. Clinical and pathologic factors were evaluated, and survival was calculated using a Kaplan-Meier survival analysis. Disease was categorized as low or high volume based on findings at surgical exploration or computed tomography scan evaluation. Disease was classified as low/intermediate grade or high grade based upon histologic examination. RESULTS: Twenty five patients were male and 26 were female. The median time from the initial diagnosis of sarcoma to the development of sarcomatosis was 0.9 years (range, 0-26 years). Thirty nine patients were treated with surgery, whereas 32 received primarily nonsurgical treatment. Histology revealed gastrointestinal stromal tumor (GIST) in 33 patients and other histologies in 18 patients. The two year overall survival rate of patients with GIST was similar to that of patients with other types of sarcoma (38% versus 42%, respectively, P = 0.77). Patients with low volume disease had an overall two year survival rate of 82%, compared with only 24% for patients with high volume disease (P = 0.008). There was no difference in the overall survival rates of patients with low grade (n = 18) versus high grade tumors (n = 33, P = 0.29). With a median followup of 2.7 years (range, 0.5-26.4 years), the median time from sarcomatosis to death was 13 months (range, 4-42 months). CONCLUSIONS: Evaluating volume of disease at the time of diagnosis permits stratification of patients into prognosis based subsets. We found no significant difference in two or four year survival rates in patients with GIST and those with non-GIST sarcomatosis.