Human gastrin- releasing peptide receptor expression in women with uterine cervix cancer.

Introduction: 212Pb-DOTAM-GRPR1 is a pharmaceutical radioimmunoconjugate consisiting of an α-particle-emitting radionuclide lead-212 (212Pb), a metal chelator DOTAM (1,4,7,10-tetrakis(carbamoylmethyl)-1,4,7,10-tetraazacyclododecane), and a gastrin-releasing peptide receptor (GRPR)-targeted antagonist currently being evaluated as therapy in uterine cervix and other cancer types. Previous studies have revealed that a variable proportion of uterine cervix cancer tumors overexpress the radiopharmaceutical target GRPR when assessed by cell proportion and staining intensity immunoreactive scores (IRS). Tumor response to 212Pb-DOTAM-GRPR1 strongly associates with GRPR overexpression, and therefore, it seems reasonable to assess uterine cervix cancer GRPR immunoreactivity for greater insight into the feasibility of using 212Pb-DOTAM-GRPR1 as a radiopharmaceutical treatment. Methods: We examined a series of 33 uterine cervix cancer paraffin-embedded tumors in order to establish whether this tumor type overexpresses GRPR at an IRS score of 6 or higher, as 212Pb-DOTAM-GRPR1 is currently being evaluated in clinical trials against tumors showing such a level of expression. Results: The results show that five of five (100%) primary adenocarcinomas and 10 of 16 (63%) primary squamous cell tumors overexpress GRPR at an IRS score of 6 or higher. Discussion: The frequency of overexpression in this study suggests that 212Pb-DOTAM-GRPR1 radiopharmaceutical treatment may be useful in the management of persistent, recurrent, or metastatic uterine cervix cancer patients. A phase I clinical trial involving patients with metastatic uterine cervix cancer is currently underway (NCT05283330).

Targeted α-Emitter Therapy with 212Pb-DOTAMTATE for the Treatment of Metastatic SSTR-Expressing Neuroendocrine Tumors: First-in-Humans Dose-Escalation Clinical Trial.

Peptide receptor radiotherapy with somatostatin analogs has been successfully used for years as a treatment for somatostatin-overexpressing tumors. Treatment of neuroendocrine tumors (NETs) with the ß-particle emitter 177Lu-DOTATATE is currently considered the standard of care for subjects with gastroenteropancreatic NETs. Despite the success of 177Lu-DOTATATE, there remains significant room for improvement in terms of both safety and efficacy. Targeted α-emitter therapy with isotopes such as 212Pb has the potential to improve both. Here, we present the preliminary results of the phase 1 first-in-humans dose-escalation trial evaluating 212Pb-DOTAMTATE (a bifunctional metal chelator [DOTAM] and the SSTR-targeting peptide [TATE]) in patients with somatostatin receptor-positive NETs. Methods: Twenty subjects with histologically confirmed NETs, prior positive somatostatin analog scans, and no prior history of 177Lu/90Y/111In peptide receptor radiotherapy, with different primary sites of the disease, were enrolled. Treatment began with single ascending doses of 212Pb-DOTAMTATE, with subsequent cohorts receiving an incremental 30% dose increase, which was continued until a tumor response or a dose-limiting toxicity was observed. This was followed by a multiple ascending dose regimen. The recommended phase 2 dose regimen consisted of 4 cycles of 2.50 MBq/kg (67.6 µCi/kg) of 212Pb-DOTAMTATE administered at 8-wk intervals, intravenously. Results: Ten subjects received the highest dose, 2.50 MBq/kg/cycle (67.6 µCi/kg/cycle). Treatment was well tolerated, with the most common treatment-emergent adverse events being nausea, fatigue, and alopecia. No serious treatment-emergent adverse events were related to the study drug, and no subjects required treatment delay or a dose reduction. An objective radiologic response of 80% was observed for the first 10 subjects treated at the recommended phase 2 dose. Conclusion: Targeted α-therapy with 212Pb-DOTAMTATE has been shown to be well tolerated. Preliminary efficacy results are highly promising. If these results are confirmed in a larger, multicenter clinical trial, 212Pb-DOTAMTATE would provide a substantial benefit over currently Food and Drug Administration-approved therapies for patients with metastatic or inoperable SSTR-expressing NETs regardless of the grade and location of the primary tumor.

Robotic pelvic and aortic lymphadenectomy for endometrial cancer: the console surgeon's perspectives on surgical technique and directing the assistant.

OBJECTIVE: Our purpose is to describe and demonstrate basic console dissection techniques in robotic hysterectomy, aortic and pelvic lymphadenectomy for endometrial carcinoma, and efficient methods to direct the assistant. METHODS: The operating room and patient are prepared as previously detailed. Adequate exposure is the key to a successful procedure, and a skilled bedside assistant is essential in developing the dissection. Clear communication between the console surgeon and assistant plays a critical role. In addition, proper use of the robotic fourth arm allows additional retraction and permits smooth case progression. RESULTS: We have completed more than 120 robotic hysterectomies, pelvic-aortic lymphadenectomies for endometrial cancer with these key steps. CONCLUSIONS: A systematic routine and effective use of the bedside assistant is essential for successfully completing robotic hysterectomy and aortic and pelvic lymphadenectomy. This manuscript and video illustrates our method emphasizing an efficient and comprehensive technique for this procedure.

Tying a loop-to-strand suture: is it safe?

OBJECTIVE: This study was undertaken to evaluate the integrity of the loop-to-strand knot when tied with square and nonidentical sliding knots. STUDY DESIGN: The synthetic absorbable monofilament suture poliglecaprone 25 in 0 and 2-0 suture gauges was used in this experiment. For each suture gauge, 3 groups of knots were tested: (1) single strand-to-single strand, flat square knot, (2) loop-to-single strand, flat square knot, and (3) loop-to-single strand, nonidentical sliding knot. All knots were tied with 6 throws. The proportion of knots becoming untied was compared among the 3 groups for each suture gauge. Ultimate load required to untie or break knots within each group was also evaluated. RESULTS: The loop-to-strand knot performed well in both suture gauges tested as long as it was tied with a flat square knot. The loop-to-strand knot tied with a nonidentical sliding knot had an unacceptably high failure rate. CONCLUSION: The loop-to-strand termination of a continuous suture may be acceptable when tied with a 6-throw flat square knot but not acceptable if tied with sliding knots.

The effect of number of throws on knot security with nonidentical sliding knots.

OBJECTIVE: The study was undertaken to test the integrity of nonidentical sliding knots made with 3 throws compared with those made with 6 throws with monofilament and braided absorbable suture. STUDY DESIGN: The 3 throw nonidentical sliding knot was compared with the 6 throw nonidentical sliding knot in 4 different suture groups. The groups were 0-0 polydioxanone, 2-0 polydioxanone, 0-0 polyglactin 910, and 2-0 polyglactin 910. Knots were tested to failure with a tensiometer. The proportion of 3 throw knots becoming untied was compared with the 6 throw knot within each group. Ultimate load required to break tied knots within each suture group was also evaluated. RESULTS: The 3 throw knots had very high rates of knot failure and untied significantly more often than the 6 throw knots. CONCLUSION: The 6 throw nonidentical sliding knot demonstrates superior knot integrity compared with the 3 throw knot with both monofilament and braided absorbable suture.