Clinical Outcomes in Patients With Krukenberg Tumors From Colorectal Cancer.

INTRODUCTION: Ovarian metastases from gastrointestinal cancers such as colorectal cancer, also known as Krukenberg tumors (KTs), present unique challenges in management due to diagnostic uncertainty, decreased responsiveness to systemic therapies compared to other sites of metastasis, and associated debilitating symptomatology. Thus, we sought to characterize our institutional outcomes in metastatic colorectal cancer (mCRC) patients with KTs. METHODS: A retrospective single-institution study was performed identifying adult, female patients from 2012 to 2021 with a diagnosis of mCRC. Patient demographics and clinicopathologic characteristics were collected and analyzed. Descriptive statistics, univariate and multivariable analyses, and Kaplan-Meier survival analyses were performed. RESULTS: Of 235 mCRC patients, 45 (19.1%) had KTs, 41 (91.1%) of whom had KTs in conjunction with other metastatic sites. Other initial sites of metastasis included the liver (n = 93, 39.6%), lung (n = 28, 11.9%), and peritoneum (n = 18, 7.7%). In the KT cohort, the median age was 48 y, 53.3% were non-Hispanic White, 100% had microsatellite stable tumors, 33.3% had Kristen Rat Sarcoma Virus (KRAS) mutations, and 6.7% had V-raf Murine Sarcoma Viral Oncogene Homolog B (BRAF) mutations. Fifty five point six percent of KT patients underwent cytoreductive surgery (CRS), 24.4% underwent palliative debulking, and 20% underwent no surgical intervention. Reasons for not undergoing CRS were disease-related (n = 14, 70%), due to poor performance status (n = 1, 5%), or both (n = 5, 25%). Five-year overall survival was 48.2% in KT patients who underwent CRS. Poor tumor grade was an independent predictor of mortality (hazard ratio 10.69, 95% confidence interval 1.20-95.47, P = 0.03). CONCLUSIONS: Almost 90% of our patient cohort with KTs from mCRC experience additional sites of metastasis. Around half of KT patients who underwent CRS were alive at 5 y.

Invasive micropapillary carcinoma of the breast and bilateral ovarian mature cystic teratoma with benign Brenner tumor in a postmenopausal woman - An uncommon occurrence.

The synchronous occurrence of bilateral ovarian tumors and breast malignancy often raise the suspicion of a Krukenberg tumor or a hereditary breast and ovarian cancer syndrome, both of which are uncommon in clinical practice. A 58-years-old postmenopausal woman had a right breast lump and was diagnosed as infiltrating duct carcinoma, no special type, and incidentally detected bilateral adnexal mass with the clinical suspicion of Krukenberg tumor. However, following the radical surgical excision of the right breast and bilateral ovaries, the right breast showed invasive micropapillary carcinoma (IMPC) while the ovaries showed mature cystic teratoma (MCT) with benign Brenner tumor. IMPC of the breast along with bilateral ovarian MCT with benign Brenner tumor is an unusual clinical occurrence in a postmenopausal female and thus worthy of documentation. It should be categorized as a non-hereditary synchronous tumor. The histomorphology augmented by immunohistochemistry and appropriate clinical context is pivotal in rendering a correct diagnosis.

Krukenberg Tumors in Young Women: Computed Tomography and Magnetic Resonance Imaging Diagnosis.

INTRODUCTION: The purpose of this report was to present the computed tomography (CT) and magnetic resonance imaging (MRI) features of Krukenberg tumors and to review the pertinent clinical data about the rising incidence of this malignancy among young women. MATERIAL AND METHODS: This series included 8 women who ranged in age from 24 to 44 years (mean, 36.3 years). They were diagnosed to have Krukenberg tumors during a 5-year period (2011-2016). All patients were evaluated by abdominal CT and pelvic or transvaginal sonography. Five of them also had MRI of the abdomen, and 3 had positron emission tomography scans. RESULTS: The primary cancer was located in the stomach of 7 patients and in the colon in 1. The initial presentation was due to large pelvic mass and abdominal distention by ascites in 3 patients, gastrointestinal symptoms in 4, and small bowel obstruction by carcinoma of the ascending colon in 1 woman. Ovarian metastases were demonstrated on the initial imaging examination of 5 patients and developed as metachronous lesion during follow-up in 3 cases. Six women died 3 to 23 months (mean, 11 months) after the diagnosis. One has survived for 6 years after extensive surgery, and 1 was lost to follow-up. CONCLUSIONS: Krukenberg tumors are being diagnosed with an increasing frequency because of well-documented rising incidence of gastric and colorectal carcinomas among young women. Therefore, those presenting with gastrointestinal cancer should have careful imaging of their ovaries for possible metastases, and conversely, the clinical or sonographic detection of bilateral ovarian masses would require evaluation by CT or MRI of the abdomen in search for a potential primary gastrointestinal cancer. This report highlights the CT and MRI features of this neoplastic process and reviews the current concepts about its development and management.

Cd44v6 acts as a directional responding factor in the process of transcoelomic metastasis from gastric carcinoma to Krukenberg tumor.

INTRODUCTION: Due to the limited number of studies focusing on the optimal treatment of multiple Krukenberg tumor (KT)-gastric carcinoma (KT - GC), it is necessary to conduct large-scale studies to confirm the definite role of serum tumor markers in the diagnosis and prognosis of KT. Moreover, the clinical significance of variant 6 of CD44 (CD44v6) in transcoelomic metastasis should be considered. AREAS COVERED: This review covers molecular pre-cancer diagnosis, gastric carcinoma metastasis, and anti-cancer treatments. Additionally, gastrointestinal cancer metastasis is a key area for improvement. EXPERT OPINION: The detection of CD44v6 differs in the World Health Organization Classification of Gastric Adenocarcinoma, the Lauren Classification of Gastric Adenocarcinoma, and the anatomic location of gastric adenocarcinoma. The results were compared among the three groups. The mechanism of gastric adenocarcinoma metastasis still requires further elucidation. CD44v6 molecular detection helps clarify the pre-cancer diagnosis of KT before seeding. If subsequent studies confirm its role as a signaling molecule, it could pave the way for new research directions in clinical practice; however, additional academic confirmation is necessary.

Incidental Diagnosis of Ovarian Torsion Due to a Krukenberg Tumor Originating from Gastric Cancer: A Case Report.

BACKGROUND: Benign lesions cause ovarian torsion more commonly than malignant ovarian tumors. Further, Krukenberg tumors have rarely been reported to cause ovarian torsion. CASE PRESENTATION: Herein, we present the case of a patient with an incidentally discovered ovarian mass, which was finally diagnosed as a Krukenberg tumor accompanying ovarian torsion with primary stomach cancer. We further review the clinical, imaging, and histological features of Krukenberg tumors. CONCLUSION: Radiologists should be aware of Krukenberg tumors that may present with ovarian torsion.

Clinicopathologic Review of Metastatic Breast Cancer to the Gynecologic Tract.

Metastatic spread is the single most significant predictor of poor survival in breast cancer. Some of the most common metastatic sites are the bones, lungs, liver, brain, and peritoneal cavity. Clinically metastatic breast cancer to the gynecologic tract is usually asymptomatic and diagnosed as an incidental finding during a histologic examination of gynecologic specimens resected for other reasons. Cases of metastatic breast cancer to gynecologic organs diagnosed from August 1995 to January 2021 were retrieved from our institution's pathology databases, and their clinicopathologic features were reviewed. The most common site of metastasis was the ovary which was involved in about 79% (22 of 28 cases) of metastases to the gynecologic tract. Clinically, only 8 cases (36%) presented with ovarian mass detected in imaging studies and the rest of the cases were all incidental findings. Among ovarian metastasis, 59% of cases were invasive lobular carcinoma and 41% were invasive ductal carcinoma. In 5 cases, metastatic breast cancer was found in the endometrium, including 2 cases with endometrial metastasis only and 3 cases with multiple gynecologic organs involved. Metastatic breast cancer rarely involved the lower gynecologic tract, with only 7% vaginal metastasis and 4% found in the vulva. The absolute majority of metastatic breast cancer outside of the ovaries were lobular carcinoma (88%). Most of the metastatic breast carcinomas were positive for estrogen receptor on immunohistochemistry (27 of 28 cases, 96%). Her-2/neu immunostaining was positive in 4 cases only (14%). Metastatic breast cancer needs to be distinguished from gynecologic primary neoplasms and metastatic tumors from adjacent urinary and GI tracts. A careful review of the patient's history and adequate immunohistochemistry panel are helpful to render the diagnosis.

Tumor to Tumor Metastasis: A Case Report of Metastatic Angiosarcoma to an Ovarian Brenner Tumor and Review of the Literature.

While angiosarcoma metastatic to the ovary is rare, metastatic angiosarcoma to an ovarian tumor has never been reported in the literature, so far. We report a case of a 61-yr-old postmenopausal woman with history of breast cancer, presenting with metastatic angiosarcoma to an ovarian Brenner tumor. Initially at the frozen section examination, on limited sampling, and without knowledge of the patient's history, a diagnosis of at least proliferating Brenner tumor was rendered. Upon review of permanent sections, an intermixed angiosarcoma component was identified within Brenner tumor. Tumor to ovarian tumor metastasis is a rare phenomenon, with only 18 cases reported in the last 50 yr. It poses diagnostic challenges during sampling and histopathologic interpretation. Detailed clinical history, careful gross examination and sampling are important to recognize the separate tumor components.

Krukenberg Tumor Presentation of Recurrent Gallbladder Cancer After a Decade.

BACKGROUND: Krukenberg tumors are among rare cases of metastatic ovary cancers. They are presented as a solid mass which generally has bilateral and sometimes cystic components and is also known through symptoms related to the mass effect and/or hormonal imbalance. However, they may present findings before the primary tumor or remain asymptomatic for a long time. CASE REPORT: We presented a patient, who was diagnosed with gallbladder cancer nine years ago and whose adjuvant treatment was completed, applied to the outpatient clinic with the complaint of vaginal bleeding. Surgery was recommended to the patient and the patient was diagnosed with metastatic signet ring cell gallbladder cancer. The patient was started on gemcitabine-capecitabine treatment after surgery. CONCLUSION: The case is important both due to the rareness of metastasis of gall bladder cancer on the ovaries and also the detection of metastasis following the nine-year recurrence-free period. This case shows that routine controls including a careful gynecological examination in a patient primarily detected to have gastrointestinal malignity are important for recognizing late metastases.

[Laparoscopic Resection of a Liver and Ovarian Metastasis of Transverse Colon Cancer-A Case Report].

A 60s woman was diagnosed to transverse colon cancer and she underwent laparoscopic right hemicolectomy. Localized peritoneal dissemination surrounding tumor was detected during surgery. She was administrated to chemotherapy due to a hepatic metastasis in S2/3 postoperatively. Subsequently, PET-CT revealed a left ovarian metastasis in addition to a liver metastasis during chemotherapy. Laparoscopic hepatic left lateral segmentectomy and bilateral adnexectomy was performed at 1 year and 9 months after the first surgery and histopathological examination showed a metastasis of transverse colon cancer. The growth of liver and lung metastases and peritoneal disseminations was detected at 6 months later after the second surgery and the patient is currently receiving palliative treatment. Previous literatures described that ovarian metastasis of colon cancer showed bilateral metastasis and resistance to chemotherapy frequently and ruptured in some cases. We should consider to resect bilateral ovary even if unilateral metastasis alone was detected by imaging examination.

[Long-Term Survival of an Adolescent and Young Adult Patient with Unresectable Advanced Gastric Cancer in Whom Multidisciplinary Treatment Was Effective].

We report the case of a long-term-surviving adolescent and young adult patient with unresectable advanced gastric cancer for whom multidisciplinary treatment was effective. A 29-year-old woman was referred to our hospital for further examination following a diagnosis of gastric cancer by a local physician. Esophagogastroduodenoscopy showed a deep ulcerated lesion in the lower third of the stomach, and analysis of biopsy specimens revealed an adenocarcinoma. Abdominal contrast- enhanced computed tomography showed gastric wall thickening in the lower third of the stomach. The patient underwent distal gastrectomy with lymph node dissection, including resection of localized peritoneal metastases, followed by Roux-en- Y reconstruction. The pathological diagnosis was serosa-invading poorly differentiated adenocarcinoma with 1 lymph node metastasis measuring 6.0×5.5 cm in the posterior wall of the lower third of the stomach and negative immunohistochemical staining for human epidermal growth factor receptor 2. The patient received postoperative chemotherapy with S-1 and oxaliplatin. She developed bilateral ovarian metastases measuring 13.0 cm and 7.8 cm after 17 months. The patient presented with severe lower abdominal pain and underwent an emergency bilateral ovarian metastasectomy, which revealed torsion of the right ovarian tumor, which had twisted twice on its pedicle, and a left ovarian mass. After the operation, 41 courses of ramucirumab with nab-paclitaxel were administered as a second-line treatment, and she received systemic drug treatment. Sixty months after the gastrectomy, the patient developed left hydronephrosis due to peritoneal metastases and was treated with nivolumab after ureteral stent replacement. No effective treatment was proposed in cancer multigene panel testing, and she died 66 months after the initial treatment because of disease progression. Comprehensive multidisciplinary treatment, including surgical and local therapy for peritoneal dissemination based on drug therapy for unresectable advanced gastric cancer, may result in long-term survival. Further research and accumulation of such cases would lead to the development of novel treatments.

Complementary anti-cancer pathways triggered by inhibition of sideroflexin 4 in ovarian cancer.

DNA damaging agents are a mainstay of standard chemotherapy for ovarian cancer. Unfortunately, resistance to such DNA damaging agents frequently develops, often due to increased activity of DNA repair pathways. Sideroflexin 4 (SFXN4) is a little-studied inner mitochondrial membrane protein. Here we demonstrate that SFXN4 plays a role in synthesis of iron sulfur clusters (Fe-S) in ovarian cancer cells and ovarian cancer tumor-initiating cells, and that knockdown of SFXN4 inhibits Fe-S biogenesis in ovarian cancer cells. We demonstrate that this has two important consequences that may be useful in anti-cancer therapy. First, inhibition of Fe-S biogenesis triggers the accumulation of excess iron, leading to oxidative stress. Second, because enzymes critical to multiple DNA repair pathways require Fe-S clusters for their function, DNA repair enzymes and DNA repair itself are inhibited by reduction of SFXN4. Through this dual mechanism, SFXN4 inhibition heightens ovarian cancer cell sensitivity to DNA-damaging drugs and DNA repair inhibitors used in ovarian cancer therapy, such as cisplatin and PARP inhibitors. Sensitization is achieved even in drug resistant ovarian cancer cells. Further, knockout of SFXN4 decreases DNA repair and profoundly inhibits tumor growth in a mouse model of ovarian cancer metastasis. Collectively, these results suggest that SFXN4 may represent a new target in ovarian cancer therapy.

TWIST1 induces proteasomal degradation of ß-catenin during the differentiation of ovarian cancer stem-like cells.

Ovarian cancer (OC) is one of the leading gynecologic cancers worldwide. Cancer stem-like cells are correlated with relapse and resistance to chemotherapy. Twist1, which is involved in ovarian cancer stem-like cell differentiation, is positively correlated with CTNNB1 in different differentiation stages of ovarian cancer cells: primary epithelial ovarian cancer cells (primary EOC cells), mesenchymal spheroid-forming cells (MSFCs) and secondary epithelial ovarian cancer cells (sEOC cells). However, the expression of ß-catenin is inversed compared to CTNNB1 in these 3 cell states. We further demonstrated that ß-catenin is regulated by the protein degradation system in MSFCs and secondary EOC but not in primary EOC cells. The differentiation process from primary EOC cells to MSFCs and sEOC cells might be due to the downregulation of ß-catenin protein levels. Finally, we found that TWIST1 can enhance ß-catenin degradation by upregulating Axin2.

Characteristics and clinicopathological features of patients with ovarian metastasis of endometrial cancer: a retrospective study.

There are no criteria for patient selection for ovarian-preserving surgery for endometrial cancer (EC). In this study, intraoperative findings of ovarian swelling (OvS) and the clinicopathological features of patients with EC with or without ovarian metastasis were analysed to identify risk factors for ovarian metastasis. Patients who underwent surgery for EC between 2012 and 2019 at our hospital were enrolled. In univariate analysis, all features were significantly higher in metastasis(+) cases. In multivariate analysis, lymphatic space invasion (LSI), cervical stromal involvement (CSI), peritoneal dissemination, and OvS were significant risk factors. In univariate analysis in stage I and II cases classified without adnexal pathological factors, type 2 histologic type, LSI, CSI, and OvS were significantly higher in metastasis(+) cases. LSI, CSI, and OvS were significant risk factors in multivariate analysis. Patients with type 1 histologic type EC without myometrial invasion ≥1/2, CSI and extrauterine lesions are appropriate for ovarian preservation. IMPACT STATEMENTWhat is already known on this subject? The number of premenopausal patients with endometrial cancer (EC) is increasing. Bilateral oophorectomy for EC results in surgical primary ovarian insufficiency, and thus, surgery with ovarian preservation has been examined. However, there are few reports on risk factors for ovarian metastasis of EC and no established criteria for patient background or pathological factors to determine suitability for ovarian preservation surgery.What do the results of this study add? In univariate analysis, all pathological findings suggestive of disease progression were more frequent in cases with ovarian metastases. In multivariate analysis, lymphatic space invasion (LSI), cervical stromal involvement (CSI), peritoneal dissemination, and ovarian swelling (OvS) were identified as significant risk factors for ovarian metastasis. In an analysis of stage I and II cases classified without adnexal pathological factors, type 2 histologic type, LSI, CSI, and OvS were significantly more common in cases with ovarian metastasis, and LSI, CSI, and OvS emerged as significant risk factors for ovarian metastasis in multivariate analysis.What are the implications of these findings for clinical practice and/or further research? Patients with type 1 histologic type EC without depth of myometrial invasion ≥1/2, CSI, or extrauterine lesions may be appropriate cases for ovarian preservation.

Frequency and therapeutic strategy for patients with ovarian metastasis from gastric cancer.

PURPOSE: This study aimed to analyze the clinicopathological features and treatment outcomes of ovarian metastasis from gastric cancer. METHODS: This study included 155 female patients with unresectable advanced or recurrent gastric cancer at the Kochi Medical School between January 2007 and December 2021. A review of patients with ovarian metastasis was conducted, and their clinicopathological information and survival outcomes were compared with respect to ovarian metastasis. RESULTS: Fifteen patients were diagnosed with ovarian metastasis from gastric cancer with a median age of 54 years (range: 30-87 years) and an incidence of 9.7%. The median age of patients who developed ovarian metastasis was significantly lower those without ovarian metastasis (54 years vs. 71 years, P = 0.014). The median survival time (MST) for 15 patients with unresectable advanced gastric cancer who developed ovarian metastasis was 21.4 months (range: 0.2-41.4 months). The MST for 15 patients who underwent surgical resection and systemic drug treatment including chemotherapy to ovarian metastasis was significantly higher than those who received systemic drug treatment alone (28.1 months vs. 10.0 months; P = 0.021). CONCLUSION: Ovarian metastasis was found in 9.7% of female patients with unresectable advanced or recurrent gastric cancer and in younger patients than in those without ovarian metastasis. Multidisciplinary treatment, including surgical resection and systemic drug treatment for ovarian metastasis from gastric cancer, may benefit selected patients.

Decision-making in postoperative chemotherapy for ovarian metastasis from colorectal cancer: a retrospective single-center study.

BACKGROUND: Ovarian metastases from colorectal cancer are relatively uncommon, and no consensus has been reached regarding resection of metastases or chemotherapy before and after surgery. We evaluated the clinicopathological characteristics of ovarian metastases from colorectal cancer and the impact of metastatic resection. We also performed a comparative analysis to clarify the prognostic impact of metastatic resection and the choice of chemotherapy before and after surgery. METHODS: Between 2006 and 2014, 38 patients at our institution underwent resection of ovarian metastases from colorectal cancer. Clinicopathological data were extracted from the patients' records and evaluated with respect to the long-term outcome. For 15 patients with metachronous ovarian metastases who received chemotherapy until immediately before resection, we compared the prognosis with and without changes in the regimen after resection. RESULTS: The 5-year overall survival rate was 19.9%, and the median survival duration was 27.2 months. The survival rate in the R0 resection group (n = 8) was significantly better than that in the R1/2 resection group (n = 30) (P = 0.0004). Patients without peritoneal dissemination (n = 15) or extra-ovarian metastases (n = 31) had a significantly better prognosis than those with peritoneal dissemination (n = 23) or extra-ovarian metastases (n = 7) (P = 0.040 and P = 0.0005, respectively). The progression-free survival and median survival times of patients who resumed chemotherapy after resection without a change in their preoperative regimen were 10.2 months and 26.2 months, respectively, while those among patients with a change in their regimen before resection versus after resection were 11.0 months and 18.1 months, respectively. The difference between the two groups was not statistically significant (progression-free survival time and median survival time: P = 0.52 and P = 0.48, respectively). CONCLUSIONS: Patients who underwent R0 resection of ovarian metastases clearly had a better prognosis than those who underwent R1/2 resection. Additionally, a poor prognosis was associated with the presence of peritoneal dissemination and extra-ovarian metastases. The data also suggested that resumption of chemotherapy without changing the regimen after resection could preserve the next line of chemotherapy for future treatment and improve the prognosis.

Krukenberg tumor in pregnancy: a rare case and review of the literature.

Krukenberg's tumor diagnosed in pregnancy is an uncommon situation that raises both diagnosis and medical management issues. We performed a review of the existing literature regarding this pathology, diagnostic means and therapeutic approaches, motivated by a case in our own practice. A 35-year-old primigravida was diagnosed with an adnexal mass during the first trimester prenatal ultrasound. Ultrasound revealed a 10 cm right adnexal mass with multiple septae, richly vascularized, whose presence and characteristics were confirmed by magnetic resonance imaging. Due to the progressively increasing tumor size, laparoscopy was performed with right adnexectomy and peritoneal biopsies. Histopathology diagnosed a metastatic ovarian tumor from a mucinous colorectal adenocarcinoma. After delivery the patient was further investigated and diagnosed with sigmoid cancer. Even though ovarian cancer in pregnancy is rare, adnexal ultrasound is mandatory when scanning during the first trimester to rule out the presence of associated fallopian or ovarian masses.

Clinical, Morphologic, and Molecular Features Associated With Ovarian Metastases From Pattern A Endocervical Adenocarcinomas.

Ovarian metastases from endocervical adenocarcinomas (EAs) are rare but well-described. Silva Pattern A tumors have been reported to pose essentially no risk of lymph node metastases or recurrence. We describe a cohort of patients with Silva Pattern A EAs with ovarian metastases, as well as involvement of other sites. Eight pattern A EAs with ovarian metastases (4 synchronous, 4 metachronous) were identified from our institution's pathologic archives (2008-2021). Clinicopathologic and molecular features for each case were recorded. All patients were treated by hysterectomy; in each case, the entire tumor was submitted for histologic evaluation. The synchronous metastases were all clinically suspected to be ovarian primary tumors; EAs with metachronous ovarian involvement were confined to the uterus at initial diagnosis, with ovarian metastasis occurring 5 to 171 months after hysterectomy. Morphologically, all tumors were predominantly gland-forming, 5/8 (63%) displayed prominent mucinous differentiation, and 5/8 (63%) involved the corpus. All EAs were either noninvasive (exophytic/papillary/more complex than adenocarcinoma in situ) or showed nondestructive cervical stromal invasion to a depth of 5 mm or less. In the 5 tumors tested by next-generation sequencing, ARID1A, GNAS, and KRAS mutations were detected in 2 (40%), 3 (60%), and 4 (80%) cases, respectively. All 6 patients with follow-up (range, 32 to 181 mo; median, 99.5 mo) had at least 1 recurrence. All but one are without evident disease at last clinical assessment. In an otherwise typical Silva Pattern A EA, corpus involvement, mucinous differentiation, and certain gene mutations may be associated with risk for synchronous or metachronous ovarian metastases.