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Sugarbaker. J Cancer Metastasis Treat 2018;4:7 I http://dx.doi.org/10.20517/2394-4722.2017.67 Page 7 of 16

[49]
as an important tool to detect disease below a size threshold of approximately 1 cm . If a gastric cancer
patient is found to have macronodular small bowel disease or would otherwise not be able to be completely
cytoreduced, HIPEC would not be warranted, and the morbidity of exploratory laparotomy could be avoided.
Laparoscopy may establish that patients have very limited peritoneal metastases (PCI ≤ 6) and should be
considered for CRS and HIPEC [50,51] . Recent randomized trials suggest that neoadjuvant chemotherapy
[52]
should be used for gastric cancer patients free of peritoneal disease . Laparoscopy may exclude patients
with peritoneal metastases who would not benefit from aggressive neoadjuvant chemotherapy that is unlikely
to improve their survival.

NEOADJUVANT INTRAPERITONEAL AND SYSTEMIC CHEMOTHERAPY
In medically fit patients with gastric cancer with peritoneal metastases systemic chemotherapy may be
recommended. Chemotherapy can provide palliation, improve survival, and improve quality of life compared
to best supportive care in patients with metastatic disease. However, the benefits of systemic chemotherapy
in gastric cancer patients with peritoneal metastases may be reduced when compared to metastatic disease at
[53]
other sites. Preusser et al. demonstrated that an aggressive systemic chemotherapy regimen can have a 50%
response rate in advanced gastric cancer, however this less effective in patients with peritoneal metastases.
[54]
Ajani et al. used neoadjuvant chemotherapy and reported the failure of the regimen was most common in
patients with peritoneal metastases. Systemic chemotherapy alone for primary gastric cancer with peritoneal
metastases is a disappointing plan of management.

Neoadjuvant chemotherapy for gastric cancer can be modified for patients with peritoneal seeding by
combining systemic and intraperitoneal chemotherapy. Chemotherapy may gain access to small peritoneal
cancer nodules via the systemic circulation and by diffusion from a chemotherapy solution within the
[55]
peritoneal cavity. Yonemura et al. proposed a prospective phase II study to establish the efficacy and
assess toxicities of NIPS chemotherapy in patients with gastric cancer with peritoneal metastases. They
identified patients with peritoneal metastases by laparoscopy, laparotomy with biopsy or cytology from
ascites. To qualify for NIPS, patients must have: (1) proven peritoneal seeding by histology or cytology; (2)
no hematogenous or remote lymph node metastases; (3) be less than or equal to 65 years; (4) have an Eastern
Clinical Oncology Group score of 2 or less; (5) adequate bone marrow, liver, cardiac, and renal function; and
(6) no other severe medical comorbidities or synchronous malignancies.

Qualifying patients had a peritoneal port system (Bard Port, C.R. Bard Inc., USA) inserted into the
abdominal cavity under local anesthesia with the tip placed within the cul-de-sac of Douglas.

Chemotherapy regimen
Prior to administration of chemotherapy, 500 mL of saline was instilled into the peritoneal cavity and
fluid was removed for cytology. Taxotere 40 mg and carboplatin 150 mg were used for intraperitoneal
2
chemotherapy in addition to 1000 mL of saline over 30 min. Methotrexate 100 mg/m and 5-fluorouracil
2
600 mg/m in 100 mL of saline over 15 min were administered intravenously the same day. This regimen was
administered weekly for two cycles. After the second cycle, peritoneal wash cytology was again performed.
If cytology was positive, neoadjuvant chemotherapy was continued for 2 more cycles. Peritoneal cytology
testing is repeating after the fourth cycle and the process is continued as long as cytology is positive.

If cytology became negative, upper endoscopy, laparoscopy and computed tomography scan was performed.
If tumors showed no demonstrable change, then 2 more cycles were administered. The number of NIPS
chemotherapy cycles was controlled by the effect on the primary cancer and peritoneal cytology. Complete
cytoreduction was required for prolonged survival in prior studies that examined peritoneal metastases.
Therefore, the goal of the NIPS regimen was complete or near complete response of metastases on small
bowel surfaces [Figure 5].