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Page 12 of 16 Sugarbaker. J Cancer Metastasis Treat 2018;4:7 I http://dx.doi.org/10.20517/2394-4722.2017.67

of NIPS, cytoreductive surgery plus HIPEC, the grade 3 and 4 complications were 21% and mortality was 3.7%.
These morbidity and mortality statistics are approximately the same as reported for cytoreductive surgery
plus HIPEC in the absence of NIPS [65,66] .

Palliative benefits to all patients with cancerous ascites
[58]
In the publication by Canbay et al. , there was improvement in symptoms for the 78 patients who had
ascites. These benefits occurred in patients with primary gastric cancer and also in patients with recurrent
[67]
disease. Cunliffe hypothesized that peritoneal metastases are nourished via ascites as well as blood supply.
Therefore, peritoneal implants should be treated via a combined intraperitoneal and intravenous approach.
Intravenous chemotherapy has minimal effects on peritoneal metastases and intraperitoneal chemotherapy
alone has a less than 30% effect on ascites [34-36,53,54] . The bidirectional chemotherapy (intraperitoneal and
intravenous) have a response rate of 57% with 100% resolution of ascites.

Chemotherapy agents selected for NIPS
[68]
According to the study by Morgan et al. , the maximum tolerated dose (MTD) of intraperitoneal taxotere
[69]
is 125 mg/m with no grade 3 or 4 toxicities at doses below 80 mg/m . Fushida et al. showed an absence
2
2
2
of hematological toxicities after intraperitoneal taxotere at 45 mg/m given once per week. The MTD of
intraperitoneal carboplatin is 500 mg/m and 300 mg/m dose was reported as safe in Japanese ovarian cancer
2
2
2
2
patients [70,71] . This study safely used taxotere 40 mg/m and carboplatin 150 mg/m combined. The combined
use of systemic and intraperitoneal chemotherapy had no deaths and reasonable morbidity and was effective
for ascites.
In summary, NIPS should be considered in gastric cancer patients with peritoneal metastases. It has maximal
benefits for small volumes of peritoneal surface metastases and is reliable treatment for symptomatic
ascites. Bidirectional chemotherapy may be the preferred strategy for preoperative chemotherapy of gastric
carcinomatosis.

Management of primary gastric cancer with positive peritoneal cytology
The survival of primary gastric cancer patients with positive peritoneal cytology in the absence of
[72]
macroscopic peritoneal dissemination is very nearly the same . The 5-year survival rate of cytology-positive
[73]
but peritoneal metastases negative patients is 2%. Coccolini et al. performed a systematic review and
meta-analysis concerning the effects of intraperitoneal chemotherapy and peritoneal lavage on this group
[73]
of patients. Coccolini et al. concluded that 2- and 5-year overall survival in patients with free cancer cells
without carcinosis is increased by intraperitoneal chemotherapy. Peritoneal lavage further increases these
survival rates and also it further decreases the peritoneal recurrence rate.

[74]
Shimada et al. in 2001 reported in a comparative non-randomized trial about the effects of intraoperative
peritoneal lavage either associated or not with intraperitoneal chemotherapy for gastric cancer with free
peritoneal cancer cells. Patients treated by intraoperative peritoneal lavage followed by intraperitoneal
chemotherapy showed improved survival compared to patients treated by surgery alone or by surgery plus
intraperitoneal lavage.

[75]
Kuramoto et al. reported the results of a comparison between three groups of patients (total 88 patients)
with advanced gastric cancer with positive cytology at peritoneal lavage but without peritoneal metastases
undergone to surgical resection alone or surgical resection associated either to intraperitoneal chemotherapy
or to intraperitoneal chemotherapy plus peritoneal lavage. The 5-year survival rate of the patients who
had intraperitoneal chemotherapy plus peritoneal lavage was 43.8%, in the intraperitoneal chemotherapy
group was 4.6% and in the surgery alone group was 0% (P = 0.0001). The median survival time of the
intraperitoneal chemotherapy plus peritoneal lavage group, intraperitoneal chemotherapy group, and surgery
alone group were 35, 16, and 15 months, respectively. The multivariate analysis showed that the peritoneal
lavage is the only significant factor affecting the prognosis.