Part 2 book “Gynecologic oncology clinical practice and surgical atlas” has contents: Perioperative and critical care, targeted therapy and immunotherapy, integrative oncology, quality of life, and supportive care, surgical instrumentation and sutures, uterine procedures, cervical procedures,… and other contents.
Metastases to the Gynecologic Tract S Diane Yamada and Nita K Lee Metastases to the genital tract may occur as a result of recognizable widely disseminated disease from another site or as an isolated lesion In the latter case, it may be difficult to distinguish between a primary tumor of the gynecologic tract or metastases to the gynecologic tract from a nongynecologic site Because treatment planning and appropriateness of surgery may be dictated by the primary site of the tumor, it is important to make the distinction between primary and metastatic disease This chapter focuses on common sites of metastases to the gynecologic tract, characteristic clinical presentations, and radiologic and pathologic considerations that may be clinically helpful in treatment planning EPIDEMIOLOGY Key Points Metastatic disease to the gynecologic organs most commonly arises from colorectal, breast, gastric, and appendiceal primary malignancies Within the reproductive tract, the ovaries and vagina are the organs most commonly affected by metastatic disease Malignant masses or lesions in the gynecologic organs should be considered as potential sites of metastases if an established primary malignancy is of advanced stage or demonstrates poor prognostic factors Metastatic disease to the genital tract from nongenital tract malignancies is relatively uncommon but is influenced by geographic differences in cancer incidence For instance, in Asian countries where gastric cancer is more common, metastatic disease to the genital tract is more prevalent In Japan, 18% to 29% of tumors found in the reproductive organs may be non-gynecologic in origin; in Thailand, where cholangiocarcinoma is quite prevalent, 7% of all metastases to the genital tract may arise from the gallbladder or extrahepatic biliary tract.1 A single-institution review from the United States of 445,000 accessioned cases identified 325 metastatic tumors to the genital tract over a 32year time period; 149 (45.8%) were from extragenital sites including the colon and rectum, breast, stomach, and appendix Additional primary sites included the bladder, ileum, and cutaneous melanoma The remaining sites of metastases originated from other areas within the genital tract such as the endometrium.2 The ovaries and vagina are, by far, the structures most commonly involved with nongenital tract metastases Although percentages may vary by geographic area, the most common primary sites of disease metastatic to the ovaries typically arise from the gastrointestinal (GI) tract (large intestine and stomach, pancreas, biliary tract, and appendix) and breast These sites comprise 50% to 90% of the metastatic cancers to the ovaries (Table 17-1) Although the histology of a metastatic breast cancer may look uniquely like breast cancer, metastases from other sites, such as the pancreas and appendix, are mucinous and can be difficult to distinguish from a primary mucinous tumor of the ovary Endometrioid-appearing histologies in the ovary can arise from metastatic colon cancer, and clear cell histology can be confused with signet ring cells from a gastric cancer or a metastatic clear cell renal carcinoma In the case of breast cancer, metastases to the ovary may remain completely occult and are detected only at autopsy or when they become symptomatic to the patient or identified on examination by her physician With mucinous tumors, the metastases in the ovary can become quite large, leading to significant symptoms and typically dominating the clinical picture for the patient and the clinician Table 17-1 Metastatic Tumor to the Ovaries Reproductive tract lesions are most likely to reflect metastatic disease when there is an established nongynecologic primary malignancy, especially if the primary tumor is advanced or has poor prognostic factors This is true of metastatic breast, pancreatic, and colon cancer In the case of some metastatic GI tract malignancies, however, the primary tumor may not be found for many years after the metastasis The classic signet ring cell adenocarcinoma of the ovary is called a Krukenberg tumor, which represents fewer than 6% to 7% of all ovarian tumors in Western countries The signet ring morphology was initially described in 1896 by a German pathologist and gynecologist, Friedrich Krukenberg However, the extragenital origin of the Krukenberg tumor was not described until years later The stomach is the primary site of malignancy in 70% of cases of Krukenberg tumor The route of spread to the ovaries is believed to be lymphatic due to the copious lymphatic plexus surrounding the gastric mucosa and submucosa This lymphatic plexus, which communicates with the lymphatics along the ovarian vessels, provides a direct conduit for even small gastric cancers to spread to the hilum and cortex of the ovary.3 Primary appendiceal neoplasms, including low-grade mucinous neoplasms, signet ring adenocarcinomas, and mucinous carcinoid tumors, also may remain occult until they present with symptomatic ovarian masses or disseminated mucin consistent with pseudomyxoma peritonei The rupture site of a primary low-grade appendiceal neoplasm may be small and contained with fibrotic mucus.4 When this occurs, the resulting ovarian metastases are frequently bilateral and occur as a result of implantation of tumor cells and mucin on the surface of the ovaries, which can then invade into the stroma If there is unilateral involvement of the ovary, it is more frequently on the right side, adjacent to the appendix.5 Most patients with colorectal cancer, similar to those with breast cancer, will have their primary malignancy detected before the diagnosis of metastatic disease to the ovaries In colorectal cancers, only 3% of patients initially present with an ovarian mass In general, the majority of primary colon cancers occur distally in the sigmoid or rectum In patients who develop ovarian metastases, most have a primary lesion in the colon that has full-thickness invasion of the bowel wall, direct invasion into adjacent structures, multiple positive lymph nodes, and/or involvement of other non-ovarian sites such as the omentum or liver.6 Although ovarian involvement can occur by direct extension, other processes such as angio-genesis and stromal cell–cancer cell interaction have been proposed for the predilection of colorectal cancer to metastasize to the ovaries In patients with pancreatic cancer, 4% to 6% will have ovarian metastases during the course of their disease.4 In a small series of patients with metastatic pancreatic cancer, all patients had other sites of intraperitoneal disease, such as the omentum and bowel mesentery, when the ovarian involvement was detected.7 Carcinomas of the extrahepatic bile ducts and gallbladder are far more common in Asian countries Ovarian metastases may present in a heterogenous manner, with nearly equal number of patients presenting at the time of primary tumor diagnosis and before or after detection of the primary tumor site The vast majority of metastases are bilateral and mucinous, but the tumor may be infiltrative or primarily present on the surface of the ovaries and can be cystic, solid, or mixed in morphology.8 After the gastrointestinal tract, breast cancer is the most common site of origin of metastatic disease, especially to the ovaries Because there are genetic mutations in BRCA1, BRCA2, and the DNA mismatch repair genes that predispose women to develop ovarian cancer, distinguishing a primary ovarian malignancy from a metastatic breast or colon cancer in women who harbor these genetic mutations may create a diagnostic dilemma Nearly 10% of women who develop breast cancer before the age of 50 years will harbor a mutation in BRCA1 or BRCA2 that will place them at risk for ovarian cancer.9 Distinguishing advanced primary ovarian cancer from metastatic breast cancer is critical in providing recommendations for the appropriateness of cytoreductive surgery, chemotherapy, or hormonal therapy In a review of 79 women with a history of breast cancer who presented with carcinomatosis and underwent surgery, the majority of patients (75%) were diagnosed with primary ovarian, tubal, or peritoneal cancers.10 Although not statistically significant, the authors suggested a trend favoring a new primary ovarian cancer in women with longer intervals since their breast cancer diagnosis and higher CA-125 values In autopsy studies, 10% of patients with breast cancer have ovarian metastases.11 The most significant risk factor for ovarian involvement is advanced-stage breast cancer In a series of 31 patients with stage IV breast cancer who underwent laparoscopy for either an adnexal mass or therapeutic bilateral salpingo-oophorectomy, 21 patients (68%) were diagnosed with metastatic breast cancer.12 Conversely, women diagnosed with early-stage breast cancer are more likely to have benign adnexal disease than metastatic disease in their ovaries In a series of 129 women with breast cancer who underwent surgery for an adnexal mass, 88% were found to have benign ovarian cysts; of the remaining patients with malignant lesions, the majority were primary ovarian cancers rather than metastatic breast cancer.10 Metastatic melanoma and renal cell carcinoma frequently pose diagnostic problems When metastatic to the ovaries or uterus, the majority of patients with melanoma have disseminated disease in other areas The ovaries represent the majority (75%) of metastases Usually, there is a history of removal of a cutaneous lesion or an ocular lesion The time span to the development of metastatic disease that involves the ovaries and becomes clinically significant may be many years Metastases to the uterus, cervix, vagina, and vulva are exceedingly rare, with individual reports scattered throughout the literature Primary sites that can metastasize to the uterine corpus or cervix include breast, stomach, colon, rectum, melanoma, lung, and kidney.13 In patients with a history of breast cancer, distinguishing between a primary uterine malignancy and metastatic breast cancer can be challenging if the patient has received hormonal therapy for her breast cancer Tamoxifen is associated with known uterine pathology, including hyperplasias, highly irregular polyps, and primary endometrial cancers, all of which may also present with vaginal bleeding In general, women with metastatic breast cancer to the uterus have a poor prognosis, as the uterus is rarely the only site of disseminated disease.14 Isolated metastases to the vagina have been described in breast, renal, pancreatic, biliary tract, and colon cancer Reports of metastases to the vulva are even more unusual DIAGNOSIS Key Points Metastatic lesions to the reproductive organs typically present with similar symptoms of primary gynecologic cancers and include abnormal bleeding, pelvic pain, and bloating Ultrasound imaging may identify solid and bilateral ovarian masses that are suggestive of metastatic disease In women with pelvic masses or vaginal lesions, elevated serum markers, such as carcinoembryonic antigen (CEA) or CA–19-9, may suggest a nongynecologic primary malignancy Whenever a patient has a history of cancer and presents with a mass or lesion in the gynecologic tract, metastatic disease must be considered in the differential Patients with metastatic disease to the ovaries are frequently younger than patients with primary ovarian cancer On average, patients with Krukenberg tumors are in the 40- to 50-year age range.15 Symptoms associated with ovarian involvement can include abdominal bloating, abdominal or pelvic pain, and weight loss Gastric cancers, because of luteinization of the ovarian stroma, may produce virilization or, on occasion, irregular vaginal bleeding.16 Occasionally, the patient may be asymptomatic and have a mass discovered on routine physical examination.17 This can occur with metastatic breast cancer In 30% of cases of metastatic disease to the ovaries, the mass may be the initial presenting feature before the diagnosis of the actual primary tumor site.16 Any metastatic tumor that involves the uterus, cervix, vagina, or vulva may lead to symptoms of irregular or postmenopausal bleeding, discomfort due to the presence of a mass, or pain Symptoms or the finding of an unexplained mass in the reproductive tract should trigger a diagnostic work-up in the form of imaging and appropriate laboratory studies Ultrasound or CT is usually the initial imaging study performed Features of ovarian tumors on ultrasound that suggest a metastatic origin include bilateral involvement of the ovaries, a solid appearance, and a differential in the size of the ovaries These features occur in 80% of patients of Krukenberg tumor When there is a combined solid and cystic component, or cystic features only, distinction from a primary ovarian cancer becomes challenging (Figure 17-1) On CT scan or MRI, many of the same features found on ultrasound will be present, including a primarily solid component or solid and cystic components with septations (Figure 17-2) In the face of bilateral cystic ovarian masses and copious fluid on imaging studies, a low-grade appendiceal neoplasm resulting in pseudo-myxoma peritonei should be suspected FIGURE 17-1 Transvaginal ultrasound of Krukenberg tumor involving the left ovary, metastatic cholangiocarcinoma FIGURE 17-2 CT scan, Krukenberg tumor involving ovaries, metastatic colorectal carcinoma CT scan may identify the primary site of disease if a suspicious mass is found elsewhere in the GI tract In addition, a radiographic abnormality on upper GI series may suggest an underlying gastric cancer However, tumors in the gastric mucosa may be quite small when they metastasize and remain undetected for many years Endoscopic examination may miss a small tumor that has extensively infiltrated into the submucosa Tumors arising from the pylorus may also be difficult to detect given their location Serum markers may help to distinguish the primary site of disease CA-125 is elevated in 70% of advanced-stage ovarian cancers Although CA-125 may be elevated in a patient with a Krukenberg tumor, it may not be elevated to the degree of epithelial ovarian cancers.18 CEA is a marker for colon, appendiceal, and gastric cancers, whereas CA–19-9 can be a marker for pancreatic cancer A CA-125 to CEA ratio of greater than 25 has also been used to help distinguish ovarian from metastatic colorectal cancer with an overall test accuracy of 94%.19 Metastatic lesions to the ovary from the breast frequently present as solid masses or generalized ovarian enlargement in postmenopausal women This occurs more frequently in women who have stage IV breast cancer When the masses are cystic and solid, however, differentiating a primary ovarian cancer from a metastasis is more difficult Positron emission tomography (PET)-CT, which is often used in breast cancer staging and restaging, can detect incidental lesions in the pelvis that require further investigation The sensitivity and specificity of PET for metastatic lesions to the ovary is not well established Although the standardized uptake value (SUV) is higher in breast cancer metastases to the ovaries compared with GI cancers, these results are based on very limited numbers of patients with overlapping SUV levels and should not be used to distinguish primary cancers from metastatic disease at this time.20 PATHOLOGY Key Points Mucinous adenocarcinomas of the ovary may represent metastases from a primary malignancy in the gastrointestinal tract or pancreas Krukenberg tumors are characteristically bilateral, solid, and exhibit a bosselated outer surface Immunohistochemical profiling, including CK7, CK20, CDX2, and S100, may distinguish a primary gynecologic malignancy from metastatic disease The majority of primary ovarian cancers are of papillary serous histology In any instance where the ovarian cancer is a mucinous or endometrioid histology, it may be challenging to distinguish a primary malignancy of the ovary from a metastatic tumor Metastatic colorectal cancers can mimic primary endometrioid ovarian carcinomas, whereas metastatic appendiceal and pancreatic cancers can be confused with primary mucinous or mucinous borderline tumors of the ovary Frequently, however, primary mucinous or endometrioid cancers of the ovary are unilateral, not bilateral When the tumor is bilateral, or small (< 10 cm) and unilateral, metastatic disease should be suspected The classic Krukenberg tumor has pathologic criteria defined by the World Health Organization to include the presence of mucin-producing signet ring cells, stromal involvement, and ovarian stromal sarcomatoid proliferation.21 The intracytoplasmic mucin of the signet ring cells typically stains with mucicarmine or a periodic acid-Schiff stain Although Krukenberg tumors have typically been classified as metastatic gastric cancers, more recently the term has been applied to all metastatic GI cancers and can include colon or pancreatic cancers as well as metastatic tumors of any nongenital tract origin When they result from metastatic gastric cancer, they are grossly solid with a smooth nodular or bosselated outer surface (Figure 17-3A) When cut, the surface is white or tan with areas of red or brown discoloration and a firm or gelatinous appearance (Figure 17-3B) Histologically, the tumors have an infiltrative, irregular growth pattern with single-cell invasion, signet ring cells, and surface mucin (Figure 17-4A, 4B).22 Metastatic mucinous cancers tend to have a multinodular growth pattern that involves the ovarian surface The presence of necrotic debris or “dirty necrosis,” a higher degree of nuclear atypia in the well-formed glands, and desmoplasia are features of metastatic colon cancer and can be used to distinguish a metastatic lesion from a primary mucinous or endometrioid cancer (Figure 17-5A-C).11 The size of the ovarian metastasis does not seem to be a distinguishing factor in metastatic colorectal cancer, as the lesions can get quite large (> 10 cm) and be unilateral.6 radiation therapy, 150–151 surgery, 147–148, 147f for uterine serous carcinoma (USC), early-stage, 123 for vaginal cancer, 191–196 chemotherapy with radiotherapy, 192–193 endodermal sinus tumor, 196 melanoma, 195–196 radiation technique for, 193–195, 193f, 194f, 195f radiotherapy, 192 sarcoma, 196 surgery, 192, 192f verrucous carcinoma, 196 for vaginal dysplasia, 80–81 for vulvar cancer, 177–180 of advanced disease, 180 of early-stage disease, 178–180, 179t of metastatic lymph nodes, 180 of microinvasive disease, 178 of poor surgical candidates, 180, 181f for vulvar dysplasia, 80–81 Trichomonas vaginalis, genital dysplasia and, 68 TRUS See Transrectal ultrasound TSGs (tumor suppressor genes), 24 Tubo-ovarian abscess (TOA), 204 Tumor growth, 407 Tumor markers, 45–47 in adnexal mass, 207–208, 208t in cervical cancer, 45 in endometrial cancer, 45–46 for germ cell tumors, 258, 259t of ovarian cancers, 10 in ovarian and fallopian tube cancers, 46–47, 47t in vulvar and vaginal cancers, 47 Tumor-infiltrating lymphocytes (TILs), 430, 430f with Lynch syndrome, 28 Tumor suppressor genes (TSGs), 24 Turner syndrome, germ cell tumors and, 258 TVUS See Transvaginal ultrasound Type 1 endometrial carcinoma biology of, 26, 108–109 genetics of, 27 immunohistochemistry of, 44 pathogenesis of, 108 pathology of, 26–27 type 2 compared with, 26 Type 2 endometrial carcinoma biology of, 26, 108–109 genetics of, 27 p53, p16, and IMP3 expression in, 44 pathogenesis of, 108 pathology of, 26–27 type 1 compared with, 26 Type 1 ovarian cancer genetics of, 31–32 origins of, 32–33, 32f, 33f, 34f pathology of, 30–31 type 2 compared with, 30, 30t Type 2 ovarian cancer genetics of, 31–32 origins of, 32–33, 32f, 33f, 34f pathology of, 30–31 type 1 compared with, 30, 30t U UFH See Unfractionated heparin Ultrasonic instruments, 473–474, 474f Ultrasound, 39–40 See also Doppler ultrasonography of adnexal mass, 205–206, 205f, 205t for breast cancer, 282f, 284 for cervical cancer, 47–48 for endometrial cancer, 52–53, 110 for germ cell tumors, 258, 258f for gestational trophoblastic disease (GTD), 54, 159–160, 160f of metastases to gynecologic tract, 335, 336f for ovarian cancer, 55–56, 220 for salpingo-oophorectomy preparation, 484 for sex cord-stromal tumors, 267 for uterine sarcomas, 141 for vulvar cancer, 58 Underlying event rate, 15 Undifferentiated endometrial sarcoma, pathology of, 140t, 144 Unequal randomization, 14 Unfractionated heparin (UFH), 350, 364–365 Unilateral salpingo-oophorectomy (USO) See Salpingo-oophorectomy Unopposed estrogen therapy, endometrial cancer and, 106, 106t Upper vaginectomy, 552–553, 553f Ureter, in salpingo-oophorectomy, 483 Ureter mobilization, in radical abdominal hysterectomy, 518, 520f Ureteral dissection, in laparoscopic radical hysterectomy, 525–526, 526f, 527f Ureteral isolation, in laparoscopic radical hysterectomy, 525 Ureteral mobilization, for urinary diversion, 635–636 Ureteroileal anastomoses, 637–639, 638f Urinary diversions, 634–647 determination of type of, 635 operative procedure for, 635–639 re-establish intestinal continuity, 639, 640f small bowel segment isolation, 636 stoma creation, 636–637, 637f ureteral mobilization, 635–636 ureteroileal anastomoses, 637–639, 638f postoperative care for, 639–641 preoperative preparation and indications for, 634–635 right colon continent, 641–647 operative procedure for, 641–645, 642f, 643f, 644f, 645f postoperative care for, 645–647 preoperative preparation for, 641 procedure overview for, 641 Urinary tract symptoms, 463 USC See Uterine serous carcinoma Usual ductal hyperplasia (UDH), 287 Uterine adnexae, 203 Uterine artery ligation for abdominal hysterectomy, 497–498, 498f in laparoscopic radical hysterectomy, 525–526, 526f, 527f in modified radical abdominal hysterectomy, 513, 514f in radical abdominal hysterectomy, 518, 519f Uterine cancer See also High-grade serous carcinomas computed tomography (CT) of, 51f magnetic resonance imaging (MRI) of, 52f Uterine corpus cancer epidemiology of, 3–6 endometrial cancer, 3–5 Lynch syndrome, 5, 5t uterine sarcomas, 5–6 histopathology of, 112 Uterine manipulator positioning for laparoscopic hysterectomy, 506–507, 507f for laparoscopic radical hysterectomy, 524 Uterine procedures, 493–528 abdominal hysterectomy, 493–500 laparoscopic hysterectomy, 505–511 laparoscopic radical hysterectomy, 523–528 modified radical abdominal hysterectomy, 511–516 radical abdominal hysterectomy, 516–523 vaginal hysterectomy, 500–505 Uterine sarcomas, 139–154 diagnosis of, 140–142 epidemiology of, 5–6, 139–140, 140t, 141t future directions for, 154 pathology of, 140t, 142–146 adenosarcoma, 140t, 145 carcinosarcoma, 140t, 144–145, 145f endometrial stromal nodule, 140t, 144 endometrial stromal sarcoma, 140t, 143–144, 144f FIGO staging, 146, 146t leiomyosarcoma, 140t, 142–143, 143f undifferentiated endometrial sarcoma, 140t, 144 recurrence of, 153 special management issues, 153–154 ovarian conservation with, 153 rapidly enlarging leiomyomata, 153–154 survival and prognosis of, 151, 151f, 152t, 153t treatment for, 146–151, 147f chemotherapy, 148–150 radiation therapy, 150–151 surgery, 147–148, 147f Uterine serous carcinoma (USC), 112, 113t, 114f treatment of advanced or recurrent, 126 early-stage, 123 Uterine vessel division, for laparoscopic hysterectomy, 509, 509f Utero-ovarian ligament transection for abdominal hysterectomy, 496, 497f modified radical abdominal hysterectomy, 513 in radical abdominal hysterectomy, 518 in salpingo-oophorectomy, 485, 486f Uterosacral resection in modified radical abdominal hysterectomy, 514 in radical abdominal hysterectomy, 519, 521f Uterosacral transection, in laparoscopic radical hysterectomy, 526–527, 527f Uterus, lymphatic network of, 115, 115t V VAC See Vacuum-assisted closures; Vincristine, actinomycin D, and cyclophosphamide Vaccines for cancer, 431, 431t antibody response with, 434 cancer-testis antigen, 433–434 dendritic cell-based, 434–435 whole tumor antigen, 435 for human papilloma virus (HPV), 81 Vacuum-assisted closures (VAC), 681–683, 682f Vaginal bleeding, 189 Vaginal brachytherapy, 388f for vaginal cancer, 192, 193 for vaginal intraepithelial neoplasia (VAIN), 81 Vaginal cancer, 187–199, 188f diagnosis of, 188–189, 189t epidemiology of, 13, 187–188 extramammary Paget disease, 13 future directions for, 199 imaging for, 59 magnetic resonance imaging (MRI), 59 positron emission tomography (PET), 59 pathology of, 189–191, 189f, 190f FIGO staging, 191, 191t metastatic spread patterns, 191 recurrence of, 199 special management problems with, 199 survival and prognosis for, 196–198, 196f, 197f advanced-stage disease, 197 early-stage disease, 197, 198t rare tumors, 197–198 treatment for, 191–196 chemotherapy with radiotherapy, 192–193 endodermal sinus tumor, 196 for melanoma, 195–196 radiation technique for, 193–195, 193f, 194f, 195f radical vaginectomy, 553–556, 555f, 556f radiotherapy, 192, 402–403 sarcoma, 196 surgery, 192, 192f verrucous carcinoma, 196 tumor markers in, 47 vaginal intraepithelial neoplasia (VAIN) and, 188 Vaginal dysplasia See also Vaginal intraepithelial neoplasia diagnosis of, 72 incidence of, 67 treatment for, 80–81 upper vaginectomy, 552–553, 553f Vaginal hysterectomy, 500–505 operative procedure for, 501–504 anesthesia and patient positioning, 501 dividing lateral ligaments and vessels, 502–504, 503f, 504f entering anteriorly, 502, 502f, 503f entering posteriorly, 501, 502f final steps, 504 oophorectomy, 504, 504f vaginal cuff closure, 504 vaginal wall incision, 501 postoperative care for, 505 preoperative preparation for, 500 procedure overview for, 500 Vaginal intraepithelial neoplasia (VAIN) human papilloma virus (HPV) and, 13 incidence of, 67 treatment for, 80–81 upper vaginectomy, 552–553, 553f vaginal cancer and, 188 Vaginal melanoma, 190, 190f, 191 prognosis for, 198 treatment for, 195–196 Vaginal reconstruction, 648–665 classification of, 648–649, 649t–650t indications for, 648, 648t positioning and planning for, 651 preoperative preparation for, 649–651 for type I vaginal defects, 651–654 full-thickness skin grafts, 653–654, 654f mesh or allograft omental flaps, 654 skin grafts with omental flap, 651 split-thickness skin grafts, 651–653, 653f for type II vaginal defects, 654–665 bilateral gracilis myocutaneous flap, 657–661, 659f, 660f, 661f bulbocavernosus myocutaneous flap, 657, 658f pudendal thigh fasciocutaneous flap, 655–657, 656f skin flap classification for, 654–655 vertical rectus abdominis myocutaneous (VRAM) flap, 661–665, 663f, 664f vaginal defect classification for, 648, 649f Vaginectomy See Radical vaginectomy; Upper vaginectomy VAIN See Vaginal intraepithelial neoplasia Vascular endothelial growth factor (VEGF) bevacizumab for, 442–444, 443f, 443t, 444f in stromal ovarian tumors, 269 targeted therapy for, 129, 129t, 441–445, 442f Vascular endothelial growth factor receptor (VEGFR), targeted therapy for, 129, 129t VEGF See Vascular endothelial growth factor VEGFR (vascular endothelial growth factor receptor), 129, 129t Venous thromboembolism (VTE), 463 prophylaxis for, 362–366, 363f, 363t, 364f, 365f Ventilator support, 354 Verrucous carcinomas cervical, 88 vaginal, 191 treatment for, 196 Vertical rectus abdominis myocutaneous (VRAM) flap, for vaginal reconstruction, 661–665, 663f, 664f Vesicouterine fold incision, for vaginal hysterectomy, 502, 503f Vessel sealant devices, 471 See also Ultrasonic instruments Villoglandular adenocarcinomas, cervical, 91 VIN See Vulvar intraepithelial neoplasia Vinblastine, 415 See also Methotrexate, vinblastine, doxorubicin, and cisplatin for sex cord-stromal tumors, 271 Vinca alkaloids, 415 in pregnancy, 307 Vincristine, 415 for germ cell tumors, 263 Vincristine, actinomycin D, and cyclophosphamide (VAC) for germ cell tumors, 262 for sex cord-stromal tumors, 271 Vinorelbine, 415 Vomiting with chemotherapy, 422 management of, 460–461, 461t VRAM flap See Vertical rectus abdominis myocutaneous flap VTE See Venous thromboembolism Vulva, immunohistochemistry in, 43 Vulvar cancer, 173–185 diagnosis of, 174–175, 174t, 175f, 176f epidemiology of, 13, 173–174 extramammary Paget disease, 13 FIGO staging for, 176, 176t imaging for, 58–59 magnetic resonance imaging (MRI), 58 positron emission tomography (PET), 59 ultrasound, 58 pathology of, 175–177, 176t, 177t recurrence of, 182 special management problems with, 182–185 Paget disease of vulva, 183–185 postoperative complications, 182–183, 183f vulvar melanoma, 183, 184f survival and prognosis of, 180–182, 181t treatment for, 177–180 of advanced disease, 180 of early-stage disease, 178–180, 179t inguinofemoral lymphadenectomy, 548–551, 548f, 549f, 550f of metastatic lymph nodes, 180 of microinvasive disease, 178 of poor surgical candidates, 180, 181f radiation therapy, 180, 402, 403f–404f radical vulvectomy, 545–548, 545f–546f, 547f simple and skinning vulvectomy, 543–544, 544f tumor markers in, 47 Vulvar dysplasia See also Vulvar intraepithelial neoplasia diagnosis of, 72–73, 72f human papilloma virus (HPV) and, 173–174 incidence of, 67 pathogenesis of non-human papilloma virus (HPV), 68–69, 69f pathology of, 76–77, 76f, 77f treatment for, 80–81 Vulvar intraepithelial neoplasia (VIN) differential diagnosis of, 77 grading system for, 76–77 histologic diagnosis of, 76–77, 76f, 77f human papilloma virus (HPV) and, 13 incidence of, 67 p16 and p53 expression in, 43 recurrence of, 82 treatment for, 80–81 types of, 43 variants of, 77 vulvar cancer and, 173 Vulvar melanoma, 183, 184f melanoma, 175, 176t Vulvar procedures, 543–552 inguinofemoral lymphadenectomy, 548–551, 548f, 549f, 550f radical vulvectomy, 545–548, 545f–546f, 547f sentinel lymph node dissection, 551–552, 551f simple and skinning vulvectomy, 543–544, 544f Vulvar reconstruction, 548, 665–671 gracilis myocutaneous flap for, 668 indications for, 665 Martius flaps for, 668 myocutaneous flaps for, 668–671, 670f perioperative considerations for, 665 pudendal thigh flap, 668 rhomboid transposition flap for, 666, 667f split-thickness skin grafts (STSGs) for, 665–666, 665f tensor fascia lata flap for, 668–671, 670f, 671f Y-V advancement flap for, 666–668, 669f, 670f Vulvectomy See Partial radical vulvectomy; Radical vulvectomy; Simple vulvectomy; Total radical vulvectomy W WART See Whole abdominal radiotherapy Warty carcinoma, cervical, 88 Warty variant, of vulvar intraepithelial neoplasia, 77 Wavelength, 374 Whole abdominal radiotherapy (WART) for endometrial cancer, advanced-stage or recurrent, 125 for ovarian cancer, 402 Whole tumor antigen vaccines, 435 Wound management, 681–683, 682f Wound/stoma care, 366 X X-linked inheritance, 25 Y YKL-40, 46 Yolk sac tumor See also Endodermal sinus tumors tumor markers of, 10 in vagina, 191 Y-V advancement flap, for vulvar reconstruction, 666–668, 669f, 670f ... between ovarian and colorectal adenocarcinomas Tumour Biol 19 92; 13:18 -26 20 Kitajima K, Suzuki K, Senda M, et al FDG PET/CT features of ovarian metastasis Clin Radiol 20 11;66 :26 4 -26 8 21 Serov SF, Scully RE... mucinous carcinomas of the ovary: gross and histologic findings in 50 cases Am J Surg Pathol 20 03 ;27 :28 1 -29 2 23 Falchook GS, Wolff RA, Varadhachary GR Clinicopathologic features and treatment strategies for patients with pancreatic adenocarcinoma and ovarian metastases... survivors J Clin Oncol 20 10 ;28 (27 ): 421 4- 422 0 10 Simpkins F, Zahurak M, Armstrong D, et al Ovarian malignancy in breast cancer patients with an adnexal mass Obstet Gynecol 20 05;105:507-513 11 Young RH