A 32-year-old female patient was admitted to the emergency department of obstetrics and gynaecology department, Ren Ji Hospital, Shanghai Jiao Tong University (Shanghai, China) with an emergency admission of 11 hours for haematemesis with epigastric pain at 21 + 4 weeks of pregnancy on August 10, 2018. The patient had regular menstruation, age of menarche is 12 years old, menstrual cycle: 5–7/30, moderate volume and no dysmenorrhoea. Fertility history: 0-0-0-0. LMP: 2018-03-18, EDC: 2018-12-30. Early pregnancy ultrasound verified gestational weeks, 4 months of menopause + felt fetal movement. The patient experienced severe vomiting on May 10,2018 with pink foam in the vomitus and no concomitant symptoms such as abdominal pain, diarrhoea or melena. The patient regarded it was morning sickness and did not pay enough attention to it. Despite that, the vomiting gradually deteriorating until the patient was unable to eat normally. On August 1,2018, she was presented to one of the Maternal and Child Health Hospital and was later recommended to be referred to Renji Hospital.The patient had no family history about cancer, nor did she have a history of smoking, alcohol drinking, or toxic environment exposure. Past history: In vitro fertilization-embryo transfer (IVF-ET)
Physical examination: Vital signs were stable, with a mild anaemic appearance, a mid to lower abdominal bulge and mild epigastric pain. The patient was admitted with black vomitus. Abdominal circumference: 94 cm, fundal height: 30 cm, no contractions, fetal heart rate: 149 bpm.
Auxiliary examination: Emergency gynaecological ultrasound: singleton cephalic position, fetal heart rate and fetal movement:visible, growth meridian: 51-188-158-33
Emergency ancillary tests: Hb:95g/L; gastric fluid occult blood: positive, faecal occult blood:negative; AFP: 90.20ng/mL; CA 724:172.10U/ml, CYFRA(21 − 1):11.48ng/ml; CA242:23.5U/ml. Upper-Abdomen Enhanced MRI: Space-occupying lesion of the gastric sinus, suspicious lymph node enlargement on the lateral side of the greater curvature of the gastric sinus, scan of the pregnant uterus (Fig. 1a -c). Electron fibreoptic gastroscopy: Large ulcerated lesion of the gastric sinus, involving the four walls and the gastric angle, and the lesser curvature of the gastric body (Fig. 2); Gastroscopic diagnosis: Malignant ulcer of the gastric sinus with incomplete obstruction; Pathological diagnosis: poorly differentiated adenocarcinoma. Immunohistochemistry: Her-2(-); the tumour was classified as cTNM:cT4N + M0.
After conducting MDT discussions in Renji hospital, radical surgery for gastric cancer was recommended after termination of pregnancy. She was then induced in our Obstetrics and Gynaecology Department (22 + 1 weeks gestation), placenta-fetal membranes were sent for pathology for the presence of tumour cells. Pathology suggested: "placenta-fetal membranes", placenta membranes tissue with degeneration, no tumour tissue seen. On August 30,2018, radical surgery for gastric cancer was performed (major distal gastrectomy with remnant gastrojejunostomy RY anastomosis, anterior colon, gastric D2 lymph node dissection). Intraoperatively, The gross appearance of the resected specimen was a tumour located in the anterior wall of the gastric body and the gastric sinus, with a size of about 4*5 cm in diameter, stiff, infiltrative ulcerative type, with a central deep concave ulcer, tumour breaking through the plasma membrane layer, invading part of the transverse colonic mesentery and the pancreatic capsule, and perigastric No 6, 7, 8, 9 and 12a lymph nodes were accessible and enlarged. No obvious metastatic lesions were found in the abdominal and pelvic cavities.
Postoperative pathological examination showed " poorly differentiated adenocarcinoma (diffuse infiltrative type, 6*5*1.2cm) on the side of the lesser curvature of the gastric sinus, invading the plasma membrane, pancreatic adhesions, cancerous thrombus in the ducts, invasion of nerves, lymph nodes of the lesser curvature (5/7), lymph nodes of the greater curvature (1/5), lymph nodes of "No 7" (1/4), lymph nodes of "No 8" (1/5), and in the "transverse colonic mesentery". The "upper and lower margins", the omentum, the "hepatic ligament", the "No 4, 6 and 12a lymph nodes" were negative for fibrofatty tissue. Immunohistochemistry: CEA (+), P16 (++), Ki67 (80%), P53 (-), ER (-), PR (-), HER2 (-), PD-L1 (-, interstitial 5%), MLH1 (-), PMS2 (-), MSH2 (+), MSH6 (+) (Fig. 3a-f). According to the American Joint Committee on Cancer (AJCC) Cancer Staging Manual (Springer International Publishing, 8th Edition 2018), the tumour was classified as: pT4bN3M0, stage III C.
Unfortunately, one year postoperative follow-up revealed tumour recurrence. On August 4,2019, CT enhancement of abdomen showed soft tissue mass measuring approximately 7.5cm*5.2cm, considered tumour recurrence/metastasis with possible involvement of duodenal stump, pancreatic head capsule, adjacent transverse colon mesentery; enlarged lymph nodes in the hilar region and retroperitoneum (Fig. 4a). On August 30,2019, PET-CT similarly confirmed this result (Fig. 5). Due to the refusal of using any chemotherapy, the patient received pabrolizumab injection 100mg intravenous drip for the first time on September 3,2019.After the treatment, abdominal CTA suggusted a mass measuring approximately 6.4cm*6cm was seen on the right side of the mid-upper abdomen, which was significantly enhanced in a circular pattern with non-enhancing ground-density necrotic foci and gas shadows within, with scattered calcifications visible in the posterior superior wall and disappearance of the fatty gap with the surrounding intestinal canal (Fig. 4b).
On the day of pablizumab administration, she suffered a high fever of 39–40°C with chills, cough, dyspnea, profuse sweating, malaise, hypotension (systolic blood pressure 70 − 60 mmHg), Sp02 80–90%, WBC 19.87*10^9/L, N% 80.3%, Hepatorenal function is normal. Considering an infusion reaction or drug allergy to immunotherapy, aggressive symptomatic supportive therapy, physical hypothermia, oxygen inhalation, volume expansion and rehydration were given. 3 days later the patient's symptoms were significantly relieved and the WBC (white blood cells) are also gradually decreasing in the routine blood tests.
Then, on August 29,2019, the patient received pabrolizumab injection 100mg intravenous drip for the second time.On October 8,2019, MRI enhancement of the abdomen suggested the soft tissue mass in the right upper abdomen measuring about 6.5cm*4.0cm (Fig. 6a). On October 19,2019, the patient received pabrolizumab injection 100mg intravenous drip for the third time, the CTA for abdomen suggusted patchy shadow of duodenum and parapancreatic head in the right upper abdomen, about 5.1cm*4.0cm in diameter, the duodenum and parapancreatic head lesion is smaller than 19-10-8, multiple lymph nodes in mesentery, hilar region and retroperitoneum (Fig. 6b). During November 11,2019-February 24,2020, the patient received pabrolizumab injection 100mg intravenous drip regularly, and the lesion had shrunk to 1.7cm in diameter (Fig. 6c).
The patient developed complications such as rash and vitiligo during this period, in addition, the patient had a myocarditis which resolved after treatment in the ICU.At subsequent follow-up, whole abdomen CTA (August 23,2021) suggested that duodenal and parapancreatic head lesion reduced to 0.6 cm, full bilateral ovarian pattern, multiple lymph nodes in mesentery, hilar region and retroperitoneum (Fig. 6d).