Journal of Obstetrics and Gynaecology, 2015; Early Online: 1–2 © 2015 Informa UK, Ltd. ISSN 0144-3615 print/ISSN 1364-6893 online
CASE REPORT
Infiltrating mucinous appendicular carcinoma during pregnancy. A case report and review of the literature Y. Chiverto, E. Cabezas, T. Pérez-Medina & L. Sanfrutos-Llorente
J Obstet Gynaecol Downloaded from informahealthcare.com by Yale Dermatologic Surgery on 07/27/15 For personal use only.
1Department of Obstetrics and Gynecology, University Hospital Puerta de Hierro, Madrid, Spain
DOI: 10.3109/01443615.2015.1018819 Correspondence: Dr. Yoana Chiverto, MD, Degree in Medicine and Surgery, Residency in Obstetrics and Gynecology, Department of Obstetrics and Gynecology, University Hospital Puerta de Hierro, C/ Manuel de Falla n°1, CP 28222 Majadahonda, Madrid, Spain. E-mail: [email protected]
Introduction Neoplasms of the appendix are rare; the incidence is about 1% of all appendectomy specimens and 0.5% of intestinal neoplasms (Connor et al. 1998). Carcinoid tumours are the most common, comprising over 50% of appendiceal neoplasms in most series, followed by benign tumours; primary malignant tumours are less frequent, of which adenocarcinoma comprises about 8%. Appendiceal adenocarcinomas have three separate histological types: the most common is mucinous type, less common is colonic type that mimics adenocarcinomas found in the colon, and the least common is signet ring cell adenocarcinoma, associated with a poor prognosis (Turaga et al. 2012). The average age of diagnosis is 58 years, and there is an even distribution between men and women (McCusker et al. 2002). The majority of patients present with acute appendicitis symptoms (Ito et al. 2004); others may also present with ascites, an abdominal mass or generalised abdominal pain. Less than 20% of cases are diagnosed incidentally (Cerame 1998). The prognosis is determined by the stage and histological type. In general, the optimal treatment for most appendiceal adenocarcinomas is a right colectomy (Turaga et al. 2013). Routine oophorectomy has been proposed at the time of colectomy because the ovaries are a common organ for metastases; however, no series has shown an improvement in survival with prophylactic oophorectomy, and this approach is not recommended. The role of adjuvant chemotherapy or radiation therapy is uncertain, but specific benefit from this approach is unproven; there are no published recommendations from expert groups.
Case report We report the case of a 36-year-old female, at 18 weeks’ gestation, who presented with abdominal pain that has increased during the last four days. There were no other general or obstetric symptoms. The patient has no other diseases or allergies; this is her second pregnancy, with a normal follow-up so far. Examination showed a normal obstetric examination and ultrasound, and blood test revealed leucocytosis (15.5 ⫻ 103/microL) with neutrophilia and elevated C-protein level (122.30 mg/L). Abdominal ultrasound was unable to identify the appendix, but suggested inflammatory pathology located in the right iliac fossa. Due to clinical condition, a laparoscopical examination of the abdominal cavity was proposed. An appendiceal mass was found, and procedure was converted to open surgery with McBurney incision. Appendicectomy was performed, with considerable difficulty, caused by inflammation and adhesions. During the postoperative period, intravenous antibiotics (carbapenems) were administrated, with satisfactory evolution.
The examination of the surgical specimen revealed an infiltrating mucinous appendicular carcinoma. It involved the appendiceal lumen, intestinal walls and subserosal fat, and had perforated the visceral peritoneum, but vascular infiltration was not observed. It measured at least 4 cm and preliminary classification was established as T4Nx. Inmunohistochemical study performed to evaluate microsatellites stability showed conservation of the four analysed proteins (hMLH1, MSH2, MSH6 and PMS2). The patient was informed about the findings, and she decided to terminate the pregnancy. Labour was induced with misoprostol (400 mcg/6 h, 4th dose was needed). The placenta was examined, by macroscopical and histopathological study, showing no signs of tumoural affectation. Staging images such as colonoscopy and chest, abdomen and pelvis computerised tomography (CT) scan did not show metastatic disease. Complete debulking surgery was performed, with right colectomy, exeresis of tumoural tissue and intraperitoneal heated chemotherapy (IPHC, 30-min 5-fluorouracil and oxaliplatin). The classification was T3N1M1a (stage IVb) but the Peritoneal Cancer Index (PCI) (Table I) was favourable (PCI of 6 before surgery and 0 after the cytoreductive procedure). Adjuvant chemotherapy was given during 6 months with FOLFOX (folinic acid, 5- fluorouracil and oxaliplatin). To date, after 10 months of follow-up, patient outcome has been highly satisfactory, and prognosis is hopeful.
Table I. Peritoneal Cancer Index∗ or PCI is a method of measuring the amount and distribution of metastatic tumour in the peritoneal cavity on CT scans. The index is based on tumour extent in 13 separate regions, 9 in abdomen and pelvis, and 4 in small intestine. Abdominal and pelvic regions (Divided by 4 lines) 1. Sagittal line through left midclavicular line 2. Sagittal line through right midclavicular line 3. Horizontal line through the lowest extent of the ribs (10th) 4. Horizontal line through the anterior superior iliac spines. Region Description 0 1 2 3 4 5 6 7 8 9 10 11 12 Lesion size No tumour seen Tumours ⬍ 0.5 cm Tumours ⱖ 0.5 and ⱕ 5 cm Tumours ⬎ 5 cm Confluent tumours
Central (periumbilical) Right upper Epigastrium Left upper Left flank Left lower Pelvis Right lower Right flank Upper jejunum Lower jejunum Upper ileum Lower ileum Points 0 1 2 3 3
PCI ⫽ SUM (points for all 13 regions). Interpretation: minimum score: 0 and maximum score: 39. The higher the score, the more extensive the tumour. ∗Adapated from Sugarbaker PH, Jablonski KA. Prognostic features of 51 colorectal and 130 appendiceal cancer patients with peritoneal carcinomatosis treated by cytoreductive surgery and intraperitoneal chemotherapy. Ann Surg. 1995; 221:124–132.
2
Y. Chiverto et al.
J Obstet Gynaecol Downloaded from informahealthcare.com by Yale Dermatologic Surgery on 07/27/15 For personal use only.
Discussion Tumoural disease concomitant with pregnancy is fortunately rare. The decision of the termination of the pregnancy may be based on the cancer type, weeks of gestation, stage and prognosis, and the decision of the patient. In this case, the pregnancy was still non-viable; this stage suggested an immediate treatment as best chance of cure, and the patient decided to terminate pregnancy. Preservation of the fertility may be considered, by techniques such as oocyte cryopreservation. In our case, the patient did not meet the criteria, due to the need for immediate treatment. The effects of intravenous systemic chemotherapy on future reproductive potential have been investigated; the effects of intraperitoneal chemotherapy, however, have not been specifically reported. Chemotherapeutic agents have a direct cytotoxic effect on the ovaries, which may result in premature ovarian failure and, thus, infertility. To date, very few cases of pregnancy after IPHC have been documented in literature (Kyser et al. 2006). The administration of IPHC might control growth of peritoneal disease. However, aggressive cytoreductive surgery and IPHC are less likely to produce lasting benefit for mucinous peritoneal carcinomatosis. Selection of patients is important, due to the rapid recurrence of the peritoneal surface disease that interferes with long-term benefit (Sugarbaker 2004). The most recent update of Sugarbaker’s experience with mucinous carcinoma of the appendix and IPHC included 501 patients over a 17-year period, in which peritoneal spread was present at diagnosis in 418 patients. At the time of follow-up, 236 patients remained free of disease recurrence; the overall five- and ten-year survival rates were 72% and 54%, respectively (GonzálezMoreno and Sugarbaker 2004). The utility of systemic chemotherapy for metastatic appendiceal adenocarcinoma is controversial because particularly mucinous adenocarcinomas have been considered refractory to intravenous 5-fluorouracil chemotherapy, although there are studies that suggest the opposite (Shaphiro et al. 2010; Lieu et al. 2012).
Declaration of interest: The authors report no declarations of interest. The authors alone are responsible for the content and writing of the paper.
References Cerame MA. 1988. A 25-year review of adenocarcinoma of the appendix. A frequently perforating carcinoma. Diseases of Colon and Rectum 31:145–150. Connor SJ, Hanna GB, Frizelle FA. 1998. Appendiceal tumors: retrospective clinicopathologic analysis of appendiceal tumors from 7,970 appendectomies. Diseases of Colon and Rectum 41:75–80. González-Moreno S, Sugarbaker PH. 2004. Right hemicolectomy does not confer a survival advantage in patients with mucinous carcinoma of the appendix and peritoneal seeding. The British Journal of Surgery 91:304–311. Ito H, Osteen RT, Bleday R et al. 2004. Appendiceal adenocarcinoma: long-term outcomes after surgical therapy. Diseases of Colon and Rectum 47:474–480. Kyser K, Bidus MA, Rodriguez M et al. 2006. Spontaneous pregnancy following cytoreduction with peritonectomy and hyperthermic intraperitoneal chemotherapy. Gynecologic Oncology 100:198–200. Lieu CH, Lambert LA, Wolff RA et al. 2012. Systemic chemotherapy and surgical cytoreduction for poorly differentiated and signet ring cell adenocarcinomas of the appendix. Annals of Oncology 23:652–658. McCusker ME, Coté TR, Clegg LX et al. 2002. Primary malignant neoplasms of the appendix: a population-based study from the surveillance, epidemiology and end-results program, 1973–1998. Cancer 94:3307–3312. Shapiro JF, Chase JL, Wolff RA et al. 2010. Modern systemic chemotherapy in surgically unresectable neoplasms of appendiceal origin: a single-institution experience. Cancer 116:316. Sugarbaker PH. 2004. Managing the peritoneal surface component of gastrointestinal cancer. Part 2. Perioperative intraperitoneal chemotherapy. Oncology (Williston Park) 18:207–219. Turaga KK, Pappas SG, Gamblin T. 2012. Importance of histologic subtype in the staging of appendiceal tumors. Annals of Surgical Oncology 19: 1379–1385. Turaga KK, Pappas S, Gamblin TC. 2013. Right hemicolectomy for mucinous adenocarcinoma of the appendix: just right or too much?. Annals of Surgical Oncology 20:1063–1067.
CASE REPORT
Infiltrating mucinous appendicular carcinoma during pregnancy. A case report and review of the literature Y. Chiverto, E. Cabezas, T. Pérez-Medina & L. Sanfrutos-Llorente
J Obstet Gynaecol Downloaded from informahealthcare.com by Yale Dermatologic Surgery on 07/27/15 For personal use only.
1Department of Obstetrics and Gynecology, University Hospital Puerta de Hierro, Madrid, Spain
DOI: 10.3109/01443615.2015.1018819 Correspondence: Dr. Yoana Chiverto, MD, Degree in Medicine and Surgery, Residency in Obstetrics and Gynecology, Department of Obstetrics and Gynecology, University Hospital Puerta de Hierro, C/ Manuel de Falla n°1, CP 28222 Majadahonda, Madrid, Spain. E-mail: [email protected]
Introduction Neoplasms of the appendix are rare; the incidence is about 1% of all appendectomy specimens and 0.5% of intestinal neoplasms (Connor et al. 1998). Carcinoid tumours are the most common, comprising over 50% of appendiceal neoplasms in most series, followed by benign tumours; primary malignant tumours are less frequent, of which adenocarcinoma comprises about 8%. Appendiceal adenocarcinomas have three separate histological types: the most common is mucinous type, less common is colonic type that mimics adenocarcinomas found in the colon, and the least common is signet ring cell adenocarcinoma, associated with a poor prognosis (Turaga et al. 2012). The average age of diagnosis is 58 years, and there is an even distribution between men and women (McCusker et al. 2002). The majority of patients present with acute appendicitis symptoms (Ito et al. 2004); others may also present with ascites, an abdominal mass or generalised abdominal pain. Less than 20% of cases are diagnosed incidentally (Cerame 1998). The prognosis is determined by the stage and histological type. In general, the optimal treatment for most appendiceal adenocarcinomas is a right colectomy (Turaga et al. 2013). Routine oophorectomy has been proposed at the time of colectomy because the ovaries are a common organ for metastases; however, no series has shown an improvement in survival with prophylactic oophorectomy, and this approach is not recommended. The role of adjuvant chemotherapy or radiation therapy is uncertain, but specific benefit from this approach is unproven; there are no published recommendations from expert groups.
Case report We report the case of a 36-year-old female, at 18 weeks’ gestation, who presented with abdominal pain that has increased during the last four days. There were no other general or obstetric symptoms. The patient has no other diseases or allergies; this is her second pregnancy, with a normal follow-up so far. Examination showed a normal obstetric examination and ultrasound, and blood test revealed leucocytosis (15.5 ⫻ 103/microL) with neutrophilia and elevated C-protein level (122.30 mg/L). Abdominal ultrasound was unable to identify the appendix, but suggested inflammatory pathology located in the right iliac fossa. Due to clinical condition, a laparoscopical examination of the abdominal cavity was proposed. An appendiceal mass was found, and procedure was converted to open surgery with McBurney incision. Appendicectomy was performed, with considerable difficulty, caused by inflammation and adhesions. During the postoperative period, intravenous antibiotics (carbapenems) were administrated, with satisfactory evolution.
The examination of the surgical specimen revealed an infiltrating mucinous appendicular carcinoma. It involved the appendiceal lumen, intestinal walls and subserosal fat, and had perforated the visceral peritoneum, but vascular infiltration was not observed. It measured at least 4 cm and preliminary classification was established as T4Nx. Inmunohistochemical study performed to evaluate microsatellites stability showed conservation of the four analysed proteins (hMLH1, MSH2, MSH6 and PMS2). The patient was informed about the findings, and she decided to terminate the pregnancy. Labour was induced with misoprostol (400 mcg/6 h, 4th dose was needed). The placenta was examined, by macroscopical and histopathological study, showing no signs of tumoural affectation. Staging images such as colonoscopy and chest, abdomen and pelvis computerised tomography (CT) scan did not show metastatic disease. Complete debulking surgery was performed, with right colectomy, exeresis of tumoural tissue and intraperitoneal heated chemotherapy (IPHC, 30-min 5-fluorouracil and oxaliplatin). The classification was T3N1M1a (stage IVb) but the Peritoneal Cancer Index (PCI) (Table I) was favourable (PCI of 6 before surgery and 0 after the cytoreductive procedure). Adjuvant chemotherapy was given during 6 months with FOLFOX (folinic acid, 5- fluorouracil and oxaliplatin). To date, after 10 months of follow-up, patient outcome has been highly satisfactory, and prognosis is hopeful.
Table I. Peritoneal Cancer Index∗ or PCI is a method of measuring the amount and distribution of metastatic tumour in the peritoneal cavity on CT scans. The index is based on tumour extent in 13 separate regions, 9 in abdomen and pelvis, and 4 in small intestine. Abdominal and pelvic regions (Divided by 4 lines) 1. Sagittal line through left midclavicular line 2. Sagittal line through right midclavicular line 3. Horizontal line through the lowest extent of the ribs (10th) 4. Horizontal line through the anterior superior iliac spines. Region Description 0 1 2 3 4 5 6 7 8 9 10 11 12 Lesion size No tumour seen Tumours ⬍ 0.5 cm Tumours ⱖ 0.5 and ⱕ 5 cm Tumours ⬎ 5 cm Confluent tumours
Central (periumbilical) Right upper Epigastrium Left upper Left flank Left lower Pelvis Right lower Right flank Upper jejunum Lower jejunum Upper ileum Lower ileum Points 0 1 2 3 3
PCI ⫽ SUM (points for all 13 regions). Interpretation: minimum score: 0 and maximum score: 39. The higher the score, the more extensive the tumour. ∗Adapated from Sugarbaker PH, Jablonski KA. Prognostic features of 51 colorectal and 130 appendiceal cancer patients with peritoneal carcinomatosis treated by cytoreductive surgery and intraperitoneal chemotherapy. Ann Surg. 1995; 221:124–132.
2
Y. Chiverto et al.
J Obstet Gynaecol Downloaded from informahealthcare.com by Yale Dermatologic Surgery on 07/27/15 For personal use only.
Discussion Tumoural disease concomitant with pregnancy is fortunately rare. The decision of the termination of the pregnancy may be based on the cancer type, weeks of gestation, stage and prognosis, and the decision of the patient. In this case, the pregnancy was still non-viable; this stage suggested an immediate treatment as best chance of cure, and the patient decided to terminate pregnancy. Preservation of the fertility may be considered, by techniques such as oocyte cryopreservation. In our case, the patient did not meet the criteria, due to the need for immediate treatment. The effects of intravenous systemic chemotherapy on future reproductive potential have been investigated; the effects of intraperitoneal chemotherapy, however, have not been specifically reported. Chemotherapeutic agents have a direct cytotoxic effect on the ovaries, which may result in premature ovarian failure and, thus, infertility. To date, very few cases of pregnancy after IPHC have been documented in literature (Kyser et al. 2006). The administration of IPHC might control growth of peritoneal disease. However, aggressive cytoreductive surgery and IPHC are less likely to produce lasting benefit for mucinous peritoneal carcinomatosis. Selection of patients is important, due to the rapid recurrence of the peritoneal surface disease that interferes with long-term benefit (Sugarbaker 2004). The most recent update of Sugarbaker’s experience with mucinous carcinoma of the appendix and IPHC included 501 patients over a 17-year period, in which peritoneal spread was present at diagnosis in 418 patients. At the time of follow-up, 236 patients remained free of disease recurrence; the overall five- and ten-year survival rates were 72% and 54%, respectively (GonzálezMoreno and Sugarbaker 2004). The utility of systemic chemotherapy for metastatic appendiceal adenocarcinoma is controversial because particularly mucinous adenocarcinomas have been considered refractory to intravenous 5-fluorouracil chemotherapy, although there are studies that suggest the opposite (Shaphiro et al. 2010; Lieu et al. 2012).
Declaration of interest: The authors report no declarations of interest. The authors alone are responsible for the content and writing of the paper.
References Cerame MA. 1988. A 25-year review of adenocarcinoma of the appendix. A frequently perforating carcinoma. Diseases of Colon and Rectum 31:145–150. Connor SJ, Hanna GB, Frizelle FA. 1998. Appendiceal tumors: retrospective clinicopathologic analysis of appendiceal tumors from 7,970 appendectomies. Diseases of Colon and Rectum 41:75–80. González-Moreno S, Sugarbaker PH. 2004. Right hemicolectomy does not confer a survival advantage in patients with mucinous carcinoma of the appendix and peritoneal seeding. The British Journal of Surgery 91:304–311. Ito H, Osteen RT, Bleday R et al. 2004. Appendiceal adenocarcinoma: long-term outcomes after surgical therapy. Diseases of Colon and Rectum 47:474–480. Kyser K, Bidus MA, Rodriguez M et al. 2006. Spontaneous pregnancy following cytoreduction with peritonectomy and hyperthermic intraperitoneal chemotherapy. Gynecologic Oncology 100:198–200. Lieu CH, Lambert LA, Wolff RA et al. 2012. Systemic chemotherapy and surgical cytoreduction for poorly differentiated and signet ring cell adenocarcinomas of the appendix. Annals of Oncology 23:652–658. McCusker ME, Coté TR, Clegg LX et al. 2002. Primary malignant neoplasms of the appendix: a population-based study from the surveillance, epidemiology and end-results program, 1973–1998. Cancer 94:3307–3312. Shapiro JF, Chase JL, Wolff RA et al. 2010. Modern systemic chemotherapy in surgically unresectable neoplasms of appendiceal origin: a single-institution experience. Cancer 116:316. Sugarbaker PH. 2004. Managing the peritoneal surface component of gastrointestinal cancer. Part 2. Perioperative intraperitoneal chemotherapy. Oncology (Williston Park) 18:207–219. Turaga KK, Pappas SG, Gamblin T. 2012. Importance of histologic subtype in the staging of appendiceal tumors. Annals of Surgical Oncology 19: 1379–1385. Turaga KK, Pappas S, Gamblin TC. 2013. Right hemicolectomy for mucinous adenocarcinoma of the appendix: just right or too much?. Annals of Surgical Oncology 20:1063–1067.
