Cytoreductive Surgery With or Without HIPEC in the Management of Peritoneal Dissemination from Rare Histological Subtypes of Ovarian Cancer - a Retrospective Study by INDEPSO.

The aim of this study was to evaluate the potential role of optimal cytoreductive surgery with or without HIPEC in the management of peritoneal dissemination from rare histological subtypes of ovarian cancer and to report the prognostic factors affecting survival. In this retrospective multicentric study, all patients with diagnosis of locally advanced ca ovary with histology other than high-grade serous carcinoma and those having undergone cytoreductive surgery (CRS) with or without hyperthermic intraperitoneal chemotherapy for the same were included. Factors affecting survival were evaluated in addition to studying the clinicopathological features. In the period from January 2013 to December 2021, 101 consecutive patients of ovarian cancer with rare histology underwent cytoreductive surgery with or without HIPEC. The median OS was not reached (NR), and the median PFS was 60 months. On evaluation of factors affecting overall survival (OS) and progression-free survival (PFS), PCI > 15 was associated with not only a decreased PFS (p = 0.019) but also a decreased OS (P = 0.019) on univariate and multivariate analysis. With respect to histology, the best OS and PFS were seen with granulosa cell tumor, mucinous tumors for which median OS and median PFS were NR respectively. Cytoreductive surgery can be performed with an acceptable morbidity in patients with peritoneal dissemination from ovarian tumors of rare histology. The role of HIPEC and impact of other prognostic factors on the treatment and survival outcome need further evaluation in larger series of patients. Supplementary Information: The online version contains supplementary material available at 10.1007/s13193-022-01640-5.

Gastric Cancer With Peritoneal Metastasis-A Comprehensive Review of Current Intraperitoneal Treatment Modalities.

The treatment of patients with peritoneal metastasis from gastric cancer continues to evolve. With various forms of intraperitoneal drug delivery available, it is now possible to reach the sites of peritoneal metastases, which were otherwise sub-optimally covered by systemic chemotherapy, owing to the blood peritoneal barrier. We conducted a narrative review based on an extensive literature research, highlighting the current available intraperitoneal treatment options, which resulted in improved survival in well-selected patients of peritoneally metastasized gastric cancer. Intraperitoneal chemotherapy showed promising results in four different treatment modalities: prophylactic, neoadjuvant, adjuvant, and palliative. It is now possible to choose the type of intraperitoneal treatment/s in combination with systemic treatment/s, depending on patients' general condition and peritoneal disease burden, thus providing individualized treatment to these patients. Randomized controlled trials for the different treatment modalities were mainly conducted in Asia and lack further validation in the other parts of the world. Most recent application tools, such as pressurized intraperitoneal aerosol chemotherapy, seem promising and need to pass the ongoing clinical trials.

Closing the Cancer Care Gap in India.

Cancer burden in India is increasing. Cancer treatment today is multi-disciplinary requiring the coordination of many specialists for best outcomes. Bringing such expertise together to the district level is the greatest challenge for cancer care in any country, moreover in India. This article focuses on the step-wise journey to make comprehensive cancer care center in a small city.

First Report of a Low-Grade Pseudomyxoma peritonei Originating from Gall Bladder.

Pseudomyxoma peritonei (PMP) refers to accumulation of mucinous ascites with or without neoplastic cells in the peritoneal cavity. It most commonly originates from a low or a high grade primary appendiceal mucinous neoplasm. Though adenocarcinoma of gall bladder has been reported to give rise to PMP, to the best of our knowledge, this is the first report of a PMP arising from a low grade mucinous tumour of the gall bladder. A 72-year-old patient was diagnosed with PMP 1.5 years after a cholecystectomy. After initial oral TS1 (combination of tegafur, gimeracil and oteracil) and later intraperitoneal (IP) chemotherapy with docetaxel and cisplatin, the patient was operated with the goal of tumour debulking, including removal of 5.5 L of mucinous ascites, an appendectomy, and ovariectomy. The histopathologic report showed a normal appendix and metastasis of PMP to the right ovary. After the exclusion of the 2 most common sites of origin (appendix and ovary), the specimen of the cholecystectomy was reviewed. It showed low grade mucinous tumour in the gall bladder, with immuno-histochemical markers (IHCs) suggestive of CK7, CDX2, MUC 2 positive and CK20, MUC5AC negative. MIB-1 index was 12%. The pathologic report of cytoreductive surgery performed after 7 cycles of IP chemotherapy confirmed the diagnosis of PMP originating from low grade mucinous tumour of the gall bladder. Our case report illustrates a rare disease and highlights that, though peritoneal metastasis from gall bladder cancers are known to have a poor prognosis, the peritoneal dissemination from a low grade mucinous neoplasm of gall bladder (PMP) has a significantly better prognosis due to a better disease biology and improved treatment options currently available for the treatment of PMP.

Intraperitoneal chemotherapy in the treatment of gastric cancer peritoneal metastases: an overview of common therapeutic regimens.

Peritoneal metastasis (PM) have an incidence of 10-20% in patients with gastric cancer (GC), and even up to 40% in patients with UICC Stage III GC. Due to the aggressive characteristic of adenocarcinoma of the stomach, GC is the third leading cause of cancer deaths worldwide. For GC with PM, the treatment of choice is according to national and international guidelines systemic chemotherapy, combined with biologic therapy against specific receptor antigen in with overexpression, such as HER-2. Multimodal treatment regimens including intraperitoneal application of chemotherapy and cytoreductive surgery (CRS) have been investigated and established all over the world. Driven by pharmacological studies and thoughts considering the increased benefits of cytotoxic agents used in the abdominal cavity, several drugs and drug combinations are widely used. In order to standardize treatment protocols, it is crucial to differentiate between normothermic and hyperthermic intraperitoneal chemotherapy (NIPEC, HIPEC). The requirements of an ideal cytotoxic drug different obviously dependent on its application method. Because of their high molecular weight and lipophilic structure, taxanes, such as paclitaxel or docetaxel have a long intraperitoneal retention time and are commonly used in NIPEC, while platin derivates, such as carboplatin or oxaliplatin are known for their synergistic effect to heat and are chosen in HIPEC. This review aims to explore and summarize different intraperitoneal treatment regimens strictly evaluated by supporting evidence in an effort to consolidate many regimens to a few evidence-based treatment protocols that deserve further investigation and distribution. This analysis included all studies focusing on intraperitoneal chemotherapy: Phase II, Phase III trials and non-randomized retrospective trials of larger cohorts of patients with GC and established PM or risk of PM. Interestingly, the protocols for NIPEC are quite uniform, with less variation between the therapeutic components in contrast to the different HIPEC protocols. This difference might be explained by the divergent evolution of NIPEC and HIPEC, as the former exclusively originated in Japan, while HIPEC experienced a more multicentric evolution and distribution in the United States, Asia, Europe, and worldwide utilization today.

Retrospective Analysis of Patients with Signet Ring Subtype of Colorectal Cancer with Peritoneal Metastasis Treated with CRS & HIPEC.

Signet ring cell subtype (SRC) of colorectal cancer (CRC) is a rare subtype and occurs in approximately 1% of all patients with CRC. Patients with peritoneal metastasis (PM) of SRC have a poor prognosis, and this subtype is frequently considered as a contra-indication for extensive surgical treatment. This retrospective study from two dedicated peritoneal surface malignancy centers in Japan included all patients treated with CRS ± hyperthermic intraperitoneal chemotherapy (HIPEC) between July 1994 and December 2017 from a prospectively maintained database. Preoperative, operative, and postoperative parameters were recorded, including complication rates and follow-up. Sixty of the 320 patients treated with CRS due to CRC were diagnosed with SRC subtype. The mean age of the patients was 51.4 years, and the mean peritoneal carcinomatosis index (PCI) was 13.1. Complete cytoreduction was achieved in 61.7% of cases. The postoperative morbidity rate was 25% and the mortality rate was 1.7%. The median overall survival (OS) was 14.4 months. Cox regression analysis revealed small bowel PCI > 2 (hazard ratio (HR) 6.5; p = 0.008) as the most important factor for OS. With accurate patient selection (e.g., PCI ≤ 12 or small bowel PCI ≤ 2), even patients with PM of CRC with SRC subtype may benefit from CRS and HIPEC, with median OS from 17.8 to 20.8 months and 5-year OS of 11.6%.

Neoadjuvant Intraperitoneal Chemotherapy in Patients with Pseudomyxoma Peritonei-A Novel Treatment Approach.

Neoadjuvant intravenous chemotherapy in patients with pseudomyxoma peritonei (PMP) has not shown convincing results. The effectiveness of neoadjuvant intraperitoneal (IP) chemotherapy has never been reported. This prospective, non-randomized phase II study included patients with PMP treated between May 2017 and December 2018, who were not considered suitable for primary cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The majority of patients were treated with laparoscopic HIPEC (oxaliplatin 200 mg/m2, 60 min, 43 °C). IP chemotherapy was started 2 weeks after docetaxel 40 mg/m2 + cisplatin 40 mg/m2, accompanied by oral S1 (tegafur, gimeracil, and oteracil) (50 mg/m2) for 14 days, followed by one week rest. Clinical parameters and complications were recorded. In total, 22/27 patients qualified for CRS and HIPEC after neoadjuvant treatment. A complete cytoreduction (Completeness of cytoreduction Score 0/1) could be achieved in 54.5%. The postoperative morbidity rate was 13.6% and mortality was rate 4.5%. In total, 20/22 patients had major pathological tumor responses. The mean drop in CEA was 28.2% and in the peritoneal carcinomatosis index (PCI) was 2.6. Positive or suspicious cytology turned negative in 69.2% of patients. Thus, for PMP patients who were not amenable for primary surgery, the majority received complete cytoreduction after treatment with neoadjuvant IP chemotherapy, with satisfying tumor regression and with low complication rates. The oncological benefit in terms of survival with this new treatment regimen needs to be proven.

The Pathologic Peritoneal Cancer Index (PCI) Strongly Differs From the Surgical PCI in Peritoneal Metastases Arising From Various Primary Tumors.

BACKGROUND: The surgical peritoneal cancer index (sPCI) is calculated based on a subjective evaluation of the extent of peritoneal disease during surgery. The pathologic PCI (pPCI) may be a more accurate and objective method for determining the PCI. This study aimed to compare the sPCI and pPCI and to study the potential pitfalls and clinical implications of using the pPCI. METHODS: This prospective study (July to December 2018) included all patients undergoing cytoreductive surgery (CRS). The pPCI was calculated for each patient and compared with the sPCI. The impact of potential confounding factors on the difference between pPCI and sPCI was evaluated. RESULTS: Among 191 patients undergoing CRS at four centers, the pPCI and sPCI were concordant for 37 patients (19.3%). The pPCI was lower than the sPCI for 125 patients (65.4%) and higher for 29 patients (15.1%). The concordance between the two groups was maximum for gastric cancer (38.8%) and colorectal cancer (27.6%) and least for mesothelioma (6.7%) and rare primary tumors (5.6%) (p = 0.04). The difference was 0 to 3 points for 119 patients (62.3%), 4 to 5 points for 27 patients (14.1%), and more than 5 points for 45 patients (23.5%). The rate of concordance was not influenced by the use of neoadjuvant chemotherapy (NACT) (p = 0.4), but the difference was greater when NACT was used (p = 0.03). CONCLUSIONS: The pPCI strongly differs from the sPCI for patients undergoing CRS for peritoneal disease and may provide a more accurate evaluation of the peritoneal disease extent. Further studies are needed to determine its prognostic value compared with sPCI, and consensus guidelines are needed for calculating it.

Long Term Survival after Cytoreductive Surgery Combined with Perioperative Chemotherapy in Gastric Cancer Patients with Peritoneal Metastasis.

The present study demonstrated prognostic factors for long-term survival in patients after a comprehensive treatment (CHT) for peritoneal metastasis (PM) from gastric cancer (GC). MATERIALS AND METHODS: Among 419 patients treated with neoadjuvant intraperitoneal/systemic chemotherapy (NIPS), 266 (63.5%) patients received complete resection (CC-0) of the macroscopic tumors. In total, 184 (43.9%) patients were treated with postoperative systemic chemotherapy. RESULTS: All patients treated who received incomplete cytoreduction (CC-1) died of GC within 6 years. In contrast, 10- year survival rates (-YSR) of CC-0 resection were 8.3% with median survival time (MST) of 20.5 months. Post-NIPS peritoneal cancer index (PCI) ≤11, and pre-NIPS PCI ≤13 were the significant favorable prognostic factors. Patients with numbers of involved peritoneal sectors ≤5 survived significant longer than those with ≥6. Both negative pre- and post-NIPS cytology was associated with significant favorable prognosis. Multivariate analyses identified pre-PCI (≤13 vs. ≥14), and cytology after NIPS (negative cytology vs. positive cytology) as independent prognostic factors. Ten year-survivors were found in patients with involvement of the greater omentum (9%), pelvic peritoneum (3%), para-colic gutter (13.9%), upper jejunum (5.6%), lower jejunum (5.5%), spermatic cord (21.9%), rectum (9.5%), ureter (6.3%), ovary (6.7%), and diaphragm (7.0%) at the time of cytoreduction. Twenty-one patients survived longer than 5 years, and 17 patients are still alive without recurrence. CONCLUSIONS: GC-PM should be removed aggressively, in patients with PCI after NIPS ≤11, PCI before NIPS ≤13, mall bowel PCI ≤2, and complete cytoreduction should be performed for metastasis in ≤5 peritoneal sectors.

Target region resection in patients undergoing cytoreductive surgery for peritoneal metastases-is it necessary in absence of visible disease?

BACKGROUND: The aim was to study the patterns of target region (greater omentum, lesser omentum, falciform and umbilical round ligament) involvement in patients undergoing cytoreductive surgery (CRS) from various primary tumors, factors affecting involvement and implications on surgical practice. METHODS: All patients undergoing CRS from July 2018 to December 2018 were included in this prospective study. The incidence of target region involvement in presence and absence of visible disease and the impact of primary tumor site, PCI and other variables on target region involvement was evaluated. RESULTS: In 191 patients, greater omentum was involved in over 15% of patients irrespective of the primary tumor type and in 15.7% in absence of visible disease. 75% of these had PCI <20. The involvement of the other three target regions was higher than 20% in ovarian cancer, appendiceal tumors and peritoneal mesothelioma. Involvement of these 3 regions was associated with a higher PCI (p < 0.001 for all) and omental involvement (p < 0.001for all). 2.1% of colorectal cancer patients had umbilical round ligament involvement, 4.2% had falciform ligament involvement and none had lesser omentum involvement. CONCLUSIONS: Target region involvement varies according to primary tumour site and disease extent. Resection of the greater omentum should be performed during CRS for PM arising from all primary sites. Resection of other target organs may be performed for selected patients with ovarian cancer, peritoneal mesothelioma and mucinous appendiceal tumors in absence of visible disease. For other patients, it should be done only in presence of visible disease.

Pathological assessment of cytoreductive surgery specimens and its unexplored prognostic potential-a prospective multi-centric study.

BACKGROUND AND AIM: The grade/histological subtype is one of the most important prognostic markers in patients undergoing cytoreductive surgery (CRS). Our aim was to study other potential prognostic information that can be derived from the pathological evaluation of CRS specimens and provide a broad outline for evaluation of these. METHODS: This prospective study (July to December 2018) included all patients undergoing cytoreductive surgery (CRS). A protocol for pathological evaluation was laid down which was based on existing practices at the participating centers and included evaluation of the pathological PCI, regional node involvement, response to chemotherapy, morphology of peritoneal metastases (PM) and distribution in the peritoneal cavity. RESULTS: In 191 patients undergoing CRS at 4 centers, the pathological and surgical PCI differed in over 75%. Nodes in relation to peritoneal disease were positive in 13.6%. Disease in normal peritoneum adjacent to tumor nodules was seen in >50% patients with ovarian cancer and mucinous apppendiceal tumors. 23.8% of evaluated colorectal PM patients had a complete response and 25.0% ovarian cancer patients had a near complete pathological response to chemotherapy. CONCLUSIONS: Pathological evaluation of extent and distribution of peritoneal disease differs from the surgical evaluation in majority of the patients. Lymph node involvement in relation of peritoneal disease is common. The morphological presentation of PM in ovarian cancer and mucinous appendiceal tumors merits evaluation of more extensive resections in these patients. Standardized methods of synoptic reporting of CRS specimens could help capture vital prognostic information that may in future influence how these patients are treated.

Effects of Cytoreductive Surgery Combined with Perioperative Chemotherapy on Long-Term Survivals of Colorectal Cancer Patients with Peritoneal Metastasis, with Special Reference to the Involved Peritoneal Sectors and Organs.

Peritoneal Surface Oncology Group International(PSOGI)proposed a novel treatment, named comprehensive treatment for peritoneal metastasis(PM)from colorectal cancer(CRC). The present study demonstrated the efficacies of the treatment regarding the peritoneal sectors and organs involved with PM from CRC. MATERIALS AND METHODS: Among 365 patients received laparotomy, 278 CRC patients with PM underwent complete cytoreductive surgery(CC-0). RESULTS: After CC-0 resection Grade 3, Grade 4, and Grade 5 postoperative complication were found in 20(7.2%), 26(9.3%), and 6(2.2%). Five- and 10-year survival rate(YSR)of CC-0 resection were 24.5%, and 11.6% with median survival time(MST)of 42.0 months. Regarding the peritoneal cancer index(PCI)of small bowel(SB-PCI), all patients of PCI B3 died of the disease. In contrast, 10-YSR of patients with SB-PCI of 0, 1, and 2 were 26.1%, 19.5%, and 6.2%, respectively. Ten-YSR of patients with the number of involved peritoneal sectors C9 ranged from 6.9% to 29.8%. MST of patients with PM in each peritoneal sector(sector 0 to sector 8)ranged from 26.4 months to 49.2 months, and 10-YSR ranged from 4.2%to 17.2%. Ten-YSR of patients with involvement of rectum, stomach, liver capsule, seminal vesicle, ureter, uterus, or ovary ranged from 0% to 16.9%. CONCLUSIONS: From the present data, PM should be removed aggressively to achieve complete cytoreduction, when the patients with PCIC26, involved peritoneal sectorsC9 and SB-PCIC2 are supposed to receive complete cytoreduction of PM.

Re-excision after unplanned resection of nonmetastatic nonrhabdomyosarcoma soft tissue sarcoma in children: Comparison with planned excision.

BACKGROUND: It is not exceptional to come by children with initial unplanned surgical intervention for nonrhabdomyosarcoma soft tissue sarcomas (NRSTS). The aim of this study was to evaluate the presence of residual disease in these patients after re-excision and compare the treatment outcomes with patients who had planned upfront excision. METHODS: The data of patients with primary nonmetastatic NRSTS with initially unplanned excision who underwent re-excision between March 2006 and December 2014 were analyzed and the results compared with patients having planned upfront excision in the similar period. RESULTS: Of the 84 patients, 40 (48%) had an unplanned excision elsewhere; 35 of these patients had a re-excision. Twenty-one of the remaining 44 patients underwent upfront planned excision. A residual tumor was present in 16 (45.7%) patients. There was no significant difference in the local recurrence, distant metastases, or deaths in patients with re-excision or planned excision. The 5-year overall, disease-free survival and local control rates were, respectively, 93.5%, 90.2% and 96.6% for the re-excision group and 84.9%, 65.2% and 88.5% in the planned excision group (p=NS). CONCLUSIONS: The probability of residual disease following unplanned excision of NRSTS is high. The outcomes following re-excision are similar to that with planned excision. PROGNOSIS STUDY: Level II evidence.

Pseudoaneurysms Masquerading as Malignant Bone Tumours.

Swelling around the knees can be due to both neoplastic as well as non neoplastic aetiology. One of the rare cause for the same is pseudoaneurysm. Pseudoaneurysms can mimic a bone tumor or a soft tissue sarcoma. Pseudoanuerysms result because of the gradual growth occurring due to constant arterial pressure and development of a reactive fibrous capsule. Inappropriate diagnosis and management of these lesions may result in major morbidity and rarely mortality. We present two cases of pseudoaneurysms around the knees which were misdiagnosed as osteogenic sarcomas. These cases also stress on the importance of multidisciplinary care, in preventing avoidable morbidity, mortality and providing safe and optimal care to the patients.

Pancreatoblastoma masquerading as hepatoblastoma: A diagnostic dilemma.

Clinicoradiological and histopathological differentiation of pancreatoblastoma from hepatoblastoma can often be a challenge in clinical practice owing to their peculiar resemblance. We report a case of a 4-year-old boy with a right hypochondriac region mass, which was diagnosed as hepatoblastoma on the basis of imaging, raised tumor marker, and biopsy; however, pancreatic origin of the mass was ascertained on exploration and pancreatoblastoma was confirmed on histopathology.

Disseminated histoplasmosis mimicking laryngeal carcinoma from central India--a case report.

A 58 year old male, chronic smoker, with diabetes mellitus (Type II), residing in Madhya Pradesh presented with dysphagia, hoarseness, odynophagia and significant weight loss. Microlaryngoscopy showed reddish ulcerated area involving valleculae, and pharyngo-epiglottic fold. Histopathological examination showed foamy macrophages containing Histoplasma capsulatum. Patient initially responded to Azoles, relapsed three months after stopping the treatment and presented with oral lesions. Biopsy showed H. capsulatum, histologically as well as on culture. The mycelial phase converted to yeast phase on B.H.I.A. at 37 degrees C confirming the isolate as H. capsulatum. The patient responded well to amphotericin B.