Histological regression of gastrointestinal peritoneal metastases after systemic chemotherapy

Objectives Peritoneal metastases (PM) are relatively resistant to systemic chemotherapy, and data on histological response to therapy is rare. The aim of this study was to quantify the treatment response of PM after systemic chemotherapy. Methods Retrospective monocentric cohort study of 47 consecutive patients with PM from gastrointestinal origin undergoing surgery (cytoreduction: CRS + Hyperthermic IntraPEritoneal Chemotherapy [HIPEC] or Pressurized IntraPeritoneal Aerosol Chemotherapy [PIPAC]) after prior systemic chemotherapy from 1.2015 to 3.2019. Tumor response was assessed using the 4-scale Peritoneal Regression Grading System (PRGS) (4: vital tumor to 1: complete response). Results Patients had a median of 2 (range: 1–7) lines and 10 (3–39) cycles of prior systemic chemotherapy. A median of four biopsies (range: 3–8) was taken with a total of 196 analyzed specimens. Twenty-four biopsies (12%) showed no histological regression (PRGS4), while PRGS 3, two and one were diagnosed in 37 (19%), 39 (20%), and 69 (49%) specimens, respectively. A significant heterogeneity was found between peritoneal biopsies in 51% patients. PRGS correlated strongly with peritoneal spread (PCI, p<0.0001), and was improved in patients with more than nine cycles of systemic chemotherapy (p=0.04). Median survival was higher in patients with PRGS < 1.8 (Quartiles one and 2) than higher (Q3 and Q4), but the difference did not reach significance in this small cohort. Conclusions PRGS is an objective too to describe histological response of PM of GI origin after systemic chemotherapy. This response differs significantly between patients, allowing to distinguish between chemosensitive and chemoresistant tumors.

Targeting Leader Cells in Ovarian Cancer as an Effective Therapeutic Option

Majority of ovarian cancers are diagnosed at advanced stages with intra-peritoneal spread as the most common mode of disease metastasis. The formation of cancer spheroids is essential for the collective migration process, where shed tumour cells from the primary tumour form aggregates rather than disseminating as individual cells and seed within the peritoneal cavity. These cancer spheroids consist of leader cells (LC) and follower cells (FC), with the LC subset as key drivers of cellular movement and invasion. LCs have stem cell-like properties and are highly chemo-resistant with a specific survival addiction to several cell signalling pathways, such as the PI3K/AKT/mTOR pathway. We explore in this book chapter, the evidence supporting the role of LC in OC metastasis and the suppression of LC as an attractive therapeutic option for the treatment of advanced OC.

CO-STAR: Surgical conversion feasibility trial of sintilimab (PD-1 inhibitor) combined with Nab-PTX, S-1 and apatinib for the first-line treatment of stage IV gastric cancer (GC).

e16041 Background: Chemotherapy and PD-1 inhibitor have shown significant clinical benefits in first-line treatment of GC, overall survival was still dismal. The surgical intervention with curative or life prolonging intention was evaluated as feasible for stage IV GC from clinical trials and retrospective cohorts. Our previous study of cytotoxic chemotherapy (S-1 & PTX) in combination with multi-targets anti-angiogenic TKIs illustrated increased response and R0 resection rate. Given the enhanced response from chemo, PD-1 and TKIs regimens, this trial was designed to assess the feasibility of surgical conversion from this combination in stage IV GC. Methods: This is a prospective, single-arm, single-center, phase II trial. Eligible criteria were treatment naïve, histopathologically confirmed stage IV (AJCC8th) and ECOG PS 0-1 GC adenocarcinoma. Pts were given with sintilimab (200mg, iv, d1) combined with Nab-PTX (w/o peritoneal spread: 260 mg/m2, iv, d1; w/ peritoneal spread: 180 mg/m2, iv, d1 and 80 mg/m2, ip, d1), S-1 (60mg, po, bid, d1-14), and apatinib (250mg, po, qd) every 3 wks. Tumor response was assessed every 2-4 cycles by radiologic imaging and MDT was employed to determine surgical feasibility. Safety run-in was employed in the first 3+3 pts by DLTs to determine the tolerability. The primary endpoint was ORR and R0 surgical conversion rate. Results: 42 pts were enrolled up to 2/2021. The median follow-up was 3.5m (range 0.7-11.3). The median age was 56 yrs (range 31-72), male was 47.6%, and PS 1 was 31.0%. The metastatic factors were characterized as No.16 lymph nodes 54.8% (23), liver 23.8% (10), peritoneum 40.5% (17), Krukenberg 2.4% (1), and extensive metastases (≥2 organs) 42.9% (18). No DLT occurred in initial 6 pts. Of 36 evaluable pts, ORR was 61.1% and DCR was 97.2%. Surgical conversion was currently identified in 18 pts with 94.4% (17) R0 resection, and the R0 surgical conversion rate was 47.2% (17/36). Median treatment cycle in converted pts was 4. 22.2% (4/18) pts achieved pathological complete response (TRG 0), and 27.8% (5/18) pts had major response (TRG 0-1). The most common AEs were grade 1-2, and 1 SAE of hemorrhage grade 4 occurred. No increase of anastomotic leakage, hemorrhage, and abdominal infection, and no surgery caused death and complication caused second operation occurred. The median postoperative length of stay was 9.5d (range 6-16). Conclusions: These preliminary results showed favorable tumor response and acceptable tolerability for potential surgical resection. Sintilimab, doublet chemotherapy, and apatinib might offer an opportunity of cure for stage IV gastric cancer. Trial ID: NCT04267549. Clinical trial information: NCT04267549. [Table: see text]

Gastric cancer with repeated metastasis in the colonic lumen: a case report and multi-surgical experience

Poorly differentiated gastric adenocarcinoma is commonly associated with lymph node metastasis, peritoneal spread, and liver metastasis but rarely with intraintestinal metastasis. Most patients with metastatic gastric carcinoma are unable to undergo surgical treatment and have a poor prognosis. A 42-year-old man with hunger-related abdominal pain was diagnosed as having gastric cancer. After the first surgery (distal partial gastrectomy) and the second surgery (gastric stump carcinoma (GSC) resection), the patient suffered repeated multiple intracolonic metastases and underwent three additional resection operations. The patient survived for 154 months after the first operation. In patients with gastric carcinoma that metastasizes to the colonic lumen, radical resection, if possible, can extend survival. Once patients develop extensive extraintestinal metastasis, radical resection cannot be performed, and patients often exhibit a poor prognosis.

Ovarian Cancer as Random Finding in Laparoscopy

Laparoscopy can be used for almost all gynecological procedures and is considered as the indicated method for specific procedures. This is especially true for adnexal surgery. Of course, while it is considered a method of choice for the treatment of benign ovarian tumors, the same does not apply to malignant ones, although treatment of ovarian cancer either at an early or even at a more advanced stage is feasible with laparoscopy. Finding malignancy, when not suspected, during laparoscopic treatment of an ovarian cyst is a situation raising several issues, depending on whether the identification of malignancy is intra- or post-operative, which involve inadequate surgical staging, peritoneal spread of cancer cells, intraoperative rupture of a malignant ovarian cystic tumor, and port site metastasis. This chapter analyzes the possible adverse events related to the use of laparoscopy in the treatment of adnexal masses considered as benign but turn out to be malignant, and how they can be mitigated with careful preoperative patient selection and with adequate surgical experience.

PIPAC – overview of the method and first use in the Czech Republic

PIPAC is a new technique for intra-abdominal administration of aerosol chemotherapy in a gaseous environment (capnoperitoneum). It can be indicated for peritoneal spread of various origins, most commonly ovarian cancer, stomach cancer and colorectal cancer. Due to its mini-invasiveness, the application can be repeated. The article provides a brief overview of current views of PIPAC and describes the first experience with PIPAC in the Czech Republic.

Management of Low-Grade Appendiceal Mucinous Neoplasm with Extensive Peritoneal Spread Diagnosed during Pregnancy: Two Case Reports and Literature Review

Background. Clinical decisions in patients with peritoneal dissemination of low-grade appendiceal mucinous neoplasms (LAMN) diagnosed during pregnancy are challenging. However, their slow progression and favorable prognosis allow deferring definitive treatment until after spontaneous delivery, a reasonable period of breastfeeding, and fertility preservation. Case Presentation. Two pregnant patients were incidentally diagnosed with LAMN and extensive peritoneal spread at 20 weeks gestation and at cesarean section. Treatment with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in both cases was delayed until spontaneous delivery at term and breastfeeding in the first patient and breastfeeding and fertility preservation in the second patient. Both patients remain disease-free for over 5 years, and their children are healthy. The literature review highlights the challenges that physicians face in treating pregnant patients with stage IV appendiceal tumors. Conclusion. Pregnancy management decisions in patients with peritoneal spread from mucinous appendiceal tumor should be based on understanding the tumor biology and prognosis. Definitive treatment in pregnant patients with favorable tumors, such as LAMN, may be delayed until spontaneous delivery without compromising maternal survival.