Efficacy and safety of an Aron Alpha method in managing giant ovarian tumors

Highlights

• •Pathological misdiagnosis of giant ovarian masses as malignant tumors can occur.
• •Intraoperative rupture of a malignant tumor increases the risk of up-stage disease.
• •Intraoperative rupture of the tumor capsule increases the risk of recurrence.
• •The Aron Alpha method is a useful procedure for the removal of giant ovarian tumors.

Abstract

Background

Giant malignant tumors have an increased risk of intraoperative rupture, which might lead to a worse disease condition and tumor recurrence. We performed a clinical study on patients with a giant ovarian mass who underwent laparoscopy combined with an Aron Alpha method.

Methods

This retrospective clinical study spanned from January 2016 to September 2022 and included 23 patients with giant ovarian tumors treated with an Aron Alpha method.

Results

The mean age of the subjects was 47.6 ± 17.8 years, mean tumor diameter 20.4 ± 5.8 cm, mean surgical duration 87.2 ± 33.1  min, and mean hemorrhage volume 94.1 ± 92.2 mL. No patient experienced intraoperative tumor rupture or surgery-related symptoms. Histopathology of excised samples revealed serous cyst adenoma and mucinous cystadenoma, mucinous cystadenoma of borderline malignancy and mature cystic teratoma, and endometriotic cyst adenoma in 6, 4, and 3 patients, respectively. The mean hospitalization period was 6.0 ± 1.2 days, and the hospitalization period was not extended in any subject.

Conclusion

The Aron Alpha method allows tumor resection without capsular rupture and is a useful, minimally invasive surgical method for resecting giant ovarian tumors in which malignancy cannot be ruled out.

1. Introduction

For preoperative diagnosis, reference is made to diagnostic imaging and tumor markers. However, it is occasionally diffuicult to determine whether a giant ovarian mass is benign or malignant preoperatively. A final pathological diagnosis of a malignant tumor may also be made. Intraoperative tumor rupture can occur with chemical peritonitis, gliomatosis peritonei, pseudomyxoma peritonei, and malignant ovarian tumors. Intraoperative tumor rupture increases the risks of worsening disease and malignant ovarian tumor recurrence (Ben-Ami et al., 2010, Fortt and Mathie, 1969, Gocht et al., 1995, Hong et al., 2012, Kondo et al., 2010, Poncelet et al., 2006, Rutgers and Scully, 1988, Whiteside and Keup, 2009). Thus, it is important to prevent intraperitoneal leakage of intratumoral fluid. However, excising giant ovarian tumors without intraoperative rupture presents problems, such as increased surgical wound size and invasiveness, when conventional approaches are used.

To remove giant ovarian tumors, the authors recently combined laparoscopy and an Aron Alpha method. The technique, which incorporates mini-laparotomy and Aron Alpha, was minimally invasive.

The present study is a retrospective evaluation of the efficacy and safety of the Aron Alpha method in treating relatively large ovarian masses at our hospital.

2. Materials and methods

The Aron Alpha method was selected when malignancy could not be ruled out, and the patient and/or their family members provided informed consent for treatment. Between January 2016 and September 2022, the Aron Alpha method was performed on 23 patients with giant ovarian tumors. In this study, ovarian tumors are tumors with a maximum diameter of at least 15 cm on preoperative magnetic resonance imaging or pelvic X-ray computed tomography.

The surgical method involved initiating surgery in the lithotomy position under general anesthesia. The abdomen was opened, and a 10-mm laparoscope was inserted at the navel area. The presence of adhesions and intraperitoneal lesions was assessed laparoscopically, and the intraperitoneal cavity was observed. Subsequently, ascitic fluid was collected, and cytology was performed (Fig. 1A). After observing the intraperitoneal cavity, a 3–6 cm incision was made in the center of the lower abdomen, and a Gosset retractor (Natsume Seisakusho Co., Ltd., Tokyo, Japan) was attached (Fig. 1B). Gauze was placed around the tumor beforehand to prevent Aron Alpha A “Sankyo”® (Daiichi Sankyo Co., Ltd., Tokyo, Japan; referred to below as “Aron Alpha”) from dripping into surrounding tissues and causing unwanted adhesion (Fig. 1C). Aron Alpha was applied to the tumor surface in a lattice pattern, and a sterilized plastic bag was placed on the tumor. We manually compressed the tumor for a few minutes with a hand placed inside the plastic bag, to ensure that the bag had firmly adhered to the tumor (Fig. 1D). Afterward, a cross-shape incision was made with a sharp blade from inside the plastic bag. To prevent leakage of tumor contents into the abdominal cavity and ensure complete adhesion between the ovarian tumor and bag, the tumor and bag were grasped with a Kocher clamp, and intratumoral fluid was aspirated from inside the bag (Fig. 1E). After aspirating some intratumoral fluid, the tumor was pulled outward and more intratumoral fluid was aspirated. Subsequently, the tumor was lifted out of the body (Fig. 1F). The suspensory ligament of the ovary and the proper ovarian ligaments of the diseased side were ligated and severed after confirming the route of the ureter. The ovary and fallopian tube on the diseased side were excised. Following this, the intraperitoneal cavity was washed with a physiological saline solution, and surgery was completed by implanting a pleated drainage tube (MD-45408S; Akita Sumitomo Bakelite Co., Ltd., Akita, Japan) in the Douglas pouch.

Fig. 1.

Surgical findings. A: The intraperitoneal cavity was observed laparoscopically, and ascitic fluid was collected for cytology tests (⇒). B: After intraperitoneal observation, a 3–6 cm incision was made in the center of the lower abdomen and a Gosset retractor was attached. C: To prevent Aron Alpha from dripping into the surrounding tissues, the area surrounding the tumor was padded with gauze (⇒⇒). D: Aron Alpha was applied to the tumor surface in a lattice pattern, and a sterilized plastic bag was fitted tightly over the ovarian tumor and stuck to it (⇒⇒⇒). E: After confirming the adhesion of the ovarian tissue and bag, the plastic bag was pierced with a sharp blade, and the intratumoral fluid was aspirated using a tube (⇒⇒⇒⇒). F: After intratumoral fluid aspiration, the tumor was guided out of the patient’s body and more intratumoral fluid was aspirated. The tumor was then lifted out of the body. After checking the route of the ureter, the pelvic funnel ligament was ligated and severed, and the appendages were excised.

Age, pregnancy and delivery histories, comorbidities, surgical duration, hemorrhage volume, postoperative complications, histopathological diagnosis, and hospitalization duration were retrospectively determined for each patient from medical records. Numerical data are presented as mean ± standard deviation.

This study was approved by the Ethics Committee of the International University of Health and Welfare Hospital on November 16, 2022 (approval no. 22-B-32). Additionally, information about the procedure for opting out was published on the homepage of the International University of Health and Welfare Hospital.

3. Results

The participants’ backgrounds are presented in Table 1. Their mean age was 47.6 ± 17.8 years (range: 19–87 years). The following comorbidities were found: hypertension (3 subjects), hyperlipidemia (2 subjects), and angina, cholelithic cholecystitis, and varicose veins in the leg (1 subject each). Nine subjects were nulliparous and 14 were parous. The mean body mass index (BMI) was 22.6 ± 3.4 (14.6 to 30.2). The mean tumor diameter was 20.4 ± 5.8 cm (15.0–32.0 cm). Surgical results are presented in Table2. The mean surgical duration was 87.2 ± 33.1  min (36–150 min), and the mean hemorrhage volume was 94.1 ± 92.2 mL (range: 10–270 mL). None of the patients experienced intraperitoneal rupture. Ascitic fluid cytology results were negative for all subjects. Histopathology results for excised tissue samples indicated serous cyst adenoma and mucinous cystadenoma in six subjects each, mucinous cystadenoma of borderline malignancy and mature cystic teratoma in four subjects each, and endometriotic cyst adenoma in three subjects. No accidental surgery-related symptoms were observed. The mean hospitalization duration was 6.0 ± 1.2 days (5–8 days), and hospitalization was not extended for any subject. After hospital discharge, neither decreased activities of daily living nor cognitive impairment was found in any subject.

Table 1.

Subject background.

Case	Age (years)	BMI (kg/m2)	Number of pregnancies (count)	Number of deliveries (count)	Comorbidities	Maximum tumor diameter (mm)
1	19	23	0	0		150
2	36	21.8	1	0		150
3	78	19.7	5	3	Varicose veins of lower extremities	150
4	35	27.4	4	4		180
5	31	29.4	1	1		150
6	34	19.8	3	2		170
7	45	23.2	1	0		150
8	67	23.4	5	3	Hyperlipidemia, hypertension	280
9	22	20.7	0	0		300
10	33	23.2	4	2		160
11	48	21.4	1	1		320
12	53	24.5	0	0		300
13	68	21.1	5	2	Calculous cholecystitis, hypertension	192
14	53	21.3	3	1		166
15	47	25.3	0	0		240
16	57	22.7	1	1		260
17	27	21	0	0		150
18	49	19.5	0	0		190
19	32	14.6	0	0		214
20	87	24.5	4	3	Angina pectoris, hypertension	200
21	64	30.2	2	2	Hyperlipidemia	280
22	50	20.8	3	3		200
23	59	20.8	3	3	Hyperlipidemia	150

BMI, body mass index.

Table 2.

Surgical outcomes.

Case	Operation time (minutes)	Blood loss (mL)	Ascitic fluid cytology	Histopathological examination	Hospitalization period (days)
1	136	60	Class I	Mature cystic teratoma	5
2	74	10	Class I	Mature cystic teratoma	5
3	99	10	Class I	Mature cystic teratoma	7
4	95	200	Class I	Serous cyst adenoma	5
5	121	200	Class I	Endometric cyst	5
6	48	10	Class I	Serous cyst adenoma	5
7	88	10	Class I	Serous cyst adenoma	5
8	80	60	Class I	Mucinous cyst adenoma	5
9	91	180	Class I	Mucinous cyst adenoma	5
10	147	250	Class I	Endometric cyst	6
11	74	10	Class I	Mucinous cystadenoma of borderline malignancy	8
12	36	10	Class I	Mucinous cyst adenoma	7
13	113	150	Class I	Mucinous cystadenoma of borderline malignancy	8
14	58	150	Class I	Mucinous cyst adenoma	7
15	36	20	Class I	Mucinous cystadenoma of borderline malignancy	7
16	116	270	Class I	Mucinous cystadenoma of borderline malignancy	7
17	92	195	Class I	Mature cystic teratoma	5
18	40	10	Class I	Serous cyst adenoma	5
19	92	170	Class I	Serous cyst adenoma	5
20	65	10	Class I	Mucinous cyst adenoma	7
21	150	150	Class I	Endometric cyst	8
22	90	20	Class I	Mucinous cyst adenoma	7
23	65	10	Class I	Serous cyst adenoma	5

4. Discussion

Determining whether a giant ovarian tumor is malignant or benign before surgery is challenging. For preoperative diagnosis, reference is made to diagnostic imaging, tumor markers, and, if necessary, cytology tests and rapid histopathology tests. However, in many cases, the possibility of malignancy or borderline malignancy cannot be ruled out, and occasionally, the final pathological diagnosis is a malignant tumor. For malignant ovarian tumors, if the tumor capsule ruptures intraoperatively, there would be intraperitoneal leakage of tumor contents. The leakage would increase the risk of a worse disease condition (Whiteside and Keup, 2009) and disease recurrence (Poncelet et al., 2006, Rutgers and Scully, 1988). Therefore, excising the tumor without intraperitoneal leakage of intratumoral fluid is important. However, to overcome this challenge, conventional surgical methods require increased wound size and surgical invasiveness, which is also problematic.

The present authors recently combined laparoscopy and Aron Alpha for tumor resection without intraperitoneal leakage of tumor contents. Aron Alpha for medical purposes and a plastic bag were used, and a mini-laparotomy was performed with a 3–6 cm incision. A key point in the successful application of this method is that absolute adhesion must be achieved between the tumor surface and plastic bag. Thus, it is important to dry the ovarian tumor surface as much as possible using gauze. Additionally, the glue should be applied on the tumor surface in a lattice pattern to increase the area in contact with air and promote polymerization, hardening, and adhesion strength.

Further, after adhesion of the sterilized plastic bag to the tumor, a cross-shaped tumor incision should be made from inside the bag. Subsequently, the tumor wall and plastic bag should be grasped with a Kocher clamp at four points in the incision region. If the adhesion between the tumor and plastic bag is firm, after the tumor contents are aspirated and the tumor shrinks, the tumor would be easily extracted from the body. Thus, this method allows tumor excision without intraperitoneal leakage of intratumoral fluid and reduces surgical invasiveness and duration.

In recent years, in connection with the aging population, there have been more occasions to perform ovarian surgery in elderly people. In the present study, five of the subjects were over 65 years old. Elderly people have decreased general physiological functions, including organ reserve capacity, wound-healing capacity, and immunity. Moreover, they often have comorbidities, such as hypertension and diabetes, and decreased cardiopulmonary and other organ function. Thus, elderly people have higher rates of postoperative complications, which are associated with increased hospitalization and increased risk of postoperative surgery-related death (Meyerhardt et al., 2008, Pavelka et al., 2006). Therefore, minimally invasive surgery is recommended in this population.

In our hospital, normal laparotomy requires a 10-day hospitalization period, which spans from the day before surgery to the 8th day after surgery. However, in our Aron Alpha method, the patient is hospitalized the day before surgery and discharged 3–4 days later, totaling 5–6 days. In the present study, no patient experienced postoperative complications, decreased activities of daily living, or increased hospitalization, and all patients were discharged on the scheduled date. Additionally, the low invasiveness of this method is an advantage.

Finally, the combination of the gluing with laparoscopy is important for several reasons: (i) the presence or absence of adhesion between the abdominal wall and tumor can be confirmed; (ii) ascitic fluid can be collected as a blood admixture; and (iii) the entire intraperitoneal cavity, including the upper abdomen, can be observed; this facilitates biopsy, partial resection, or histopathological diagnosis of peritoneal lesions. In addition, the surgical technique was easy and the Aron Alpha and plastic bags are inexpensive, making the technique a useful method for resecting large ovarian tumors when malignancy cannot be ruled out.

We plan to verify the efficacy and safety of this surgical procedure based on a larger number of cases of giant ovarian tumors.

5. Conclusion

The Aron Alpha method enables ovarian tumor excision with minimal invasiveness and no intraperitoneal leakage of intratumoral fluid. This method is useful for resecting giant ovarian tumors when malignancy cannot be excluded.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

CRediT authorship contribution statement

Toshiyuki Kakinuma: Methodology, Software, Validation, Formal analysis, Writing – original draft, Writing – review & editing, Visualization, Supervision, Project administration. Kaoru Kakinuma: Investigation, Resources, Data curation. Takumi Shinohara: Investigation, Resources, Data curation. Ayano Shimizu: Investigation, Resources, Data curation. Rora Okamoto: Investigation, Resources, Data curation. Ayaka Kaneko: Investigation, Resources, Data curation. Nobuhiro Takeshima: Investigation, Resources, Data curation. Kaoru Yanagida: Investigation, Resources, Data curation. Michitaka Ohwada: Investigation, Resources, Data curation.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.