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Open research questions in Intraperitoneal and Appendiceal Malignancies

82 gap statements mined from Intraperitoneal and Appendiceal Malignancies papers in our 4.5M-paper local library, which holds 477 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.

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What the literature leaves open

  • One of the major challenges is the substantial morbidity associated with CRS+HIPEC. Another challenge is the need for specialized centers and experienced surgeons to perform the procedure.

    Evaluation of the Impact of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) on Long-Term Survival and Morbidity Profile: A Systematic Review of the Peritoneal Carcinomatosis Management · 2026 · DOI

  • There is a need for further research to determine the optimal selection criteria for patients undergoing CRS+HIPEC. The review highlights the importance of tumor biology and disease burden in determining the outcome of CRS+HIPEC.

    Evaluation of the Impact of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) on Long-Term Survival and Morbidity Profile: A Systematic Review of the Peritoneal Carcinomatosis Management · 2026 · DOI

  • The relationship between osteosarcopenia and PCI is not well understood. The impact of osteosarcopenia on major postoperative complications is not well established.

    Impact of Osteosarcopenia on Peritoneal Cancer Index and Major Complications in Patients with Peritoneal Carcinomatosis · 2026 · DOI

  • There is conflicting data about appendiceal neoplasm risk in CAP versus UCAP. The reported increase in the incidence of ANs has yet to be attributed to a specific cause, and it remains uncertain if the mortality rate of ANs is following a similar trend.

    Incidental serrated lesions of the appendix: analysis of 2,137 appendectomy specimens · 2026 · DOI

  • The rarity of appendiceal neoplasms and the lack of awareness among clinicians may contribute to delayed or incidental diagnosis.

    A Rare Appendiceal Neoplasm Presenting as Chronic Appendicitis in an Elderly Female: A Case Report · 2026 · DOI

  • There is a need for research into new methods of treating pseudomyxoma peritonei in high-risk patients for whom cytoreduction with HIPEC is not feasible.

    An 80-year-old female with pseudomyxoma peritonei due to mucinous cancer of unknown origin — molecular characterization and diagnostic challenges · 2026 · DOI

  • Malignant pleural diseases are a significant clinical challenge, with limited treatment options. The development of effective treatment strategies for malignant pleural diseases is a major challenge. The optimization of HITHOC treatment protocols is a technical challenge.

    EVALUATION OF THE EFFICACY AND SAFETY OF HYPERTHERMIC INTRATHORACIC CHEMOTHERAPY IN MALIGNANT PLEURAL DISEASES · 2026 · DOI

  • Further studies are needed to fully understand the efficacy and safety of HITHOC in patients with malignant pleural diseases. Research should focus on optimizing the treatment protocol and identifying patient subgroups that may benefit most from HITHOC. The development of novel treatment strategies based on HITHOC may be an area of future research.

    EVALUATION OF THE EFFICACY AND SAFETY OF HYPERTHERMIC INTRATHORACIC CHEMOTHERAPY IN MALIGNANT PLEURAL DISEASES · 2026 · DOI

  • There is a lack of awareness among gastrointestinal surgeons about the possibility of IDD-lymphomas in patients with autoimmune diseases using immunosuppressant drugs. There is a need for early consideration of minimally invasive treatments or postoperative chemotherapy.

    Small Bowel Perforation as an Initial Manifestation of Immune Deficiency and Dysregulation-Associated Lymphoma in a Patient With Rheumatoid Arthritis: A Case Report · 2026 · DOI

  • The concentration of all 11 biopsy-proven foregut malignancies in the discordant group is an unexpected finding that warrants further investigation.

    Foregut malignancy after discordant fecal immunochemical test: A cohort study at a United States safety-net hospital · 2026 · DOI

  • Lack of standardized H&E morphological criteria for diagnosing presacral neoplasms. High misdiagnosis rate due to non-specific clinical manifestations and deep anatomical location. Need for a practical pathological diagnostic system to improve clinical oncological practice.

    Key H&E morphologic features associated with preoperative misdiagnosis of presacral neoplasms: a retrospective slide re−review study · 2026 · DOI

  • Funding Despite encouraging preliminary results, evidence supporting ctDNA and ptDNA in appendiceal cancer remains limited, consisting primarily of retrospective case series, small institutional cohorts, and mixed gastrointestinal cancer populations.

    Circulating tumor DNA in appendiceal malignancies: a comprehensive review of clinical applications and limitations · 2026 · DOI

  • The efficacy of locoregional therapy with intraperitoneal (IP) drug delivery plus systemic chemotherapy for peritoneal carcinomatosis is understudied.

    Efficacy of Bidirectional Paclitaxel plus Capecitabine or Nilotinib for Peritoneal Carcinomatosis: A Single Institution Analysis of Two Phase II Clinical Trials · 2026 · DOI

  • However, the extent to which systemic therapy alters the PCI and whether such changes are reflected in PCI dynamics remains insufficiently understood.

    Systemic Chemotherapy in Patients with Synchronous Peritoneal Metastasis from Gastric and Esophagogastric Junction Cancers Has No Uniform Effect on the Peritoneal Cancer Index · 2026 · DOI

  • One challenge is the complex interaction between tumor intrinsic features and the unique anatomical and immune environment of the peritoneal cavity. Another challenge is the limited understanding of the molecular mechanisms that drive peritoneal metastasis, including the role of metabolic reprogramming and extracellular vesicles.

    Peritoneal metastasis in pancreatic cancer: molecular mechanisms, microenvironmental remodeling, and emerging intraperitoneal interventions · 2026 · DOI

  • This case highlights the diagnostic challenges of PPCCC and offers valuable insights into the clinical and pathological spectrum of this underrecognized malignancy.

    Primary peritoneal clear cell carcinoma with metastasis mimicking ovarian carcinoma: a case report and literature review · 2026 · DOI

  • KRAS is the most commonly mutated gene in AA and a promising therapeutic target, but its preclinical and translational relevance in AA remains unclear.

    KRAS inhibition is an effective therapy for appendiceal adenocarcinoma · 2026 · DOI

  • The survival benefit of hyperthermic intraperitoneal chemotherapy (HIPEC) has been well defined at the time of interval cytoreductive surgery, but the role of HIPEC remains uncertain for patients with newly diagnosed advanced ovarian cancer in the upfront setting.

    Hyperthermic intraperitoneal chemotherapy after upfront cytoreductive surgery for stage III epithelial ovarian cancer: Follow‐up of long‐term survival · 2025 · DOI

  • Although 2016 consensus guidelines defined high-grade appendiceal mucinous neoplasms (HAMNs) as a distinct histologic entity, their clinical course and optimal management remain poorly characterized.

    Clinicopathologic and Molecular Characteristics of High-Grade Appendiceal Mucinous Neoplasms · 2025 · DOI

  • These results establish foundational insights into PM biology, though future PM tissue profiling is warranted to overcome primary tumor bias in genomic data.

    Pan-cancer clinicopathological and genomic characteristics of peritoneal metastasis · 2025 · DOI

  • Peritoneal metastasis (PM) poses a significant clinical challenge, yet the patient characteristics and genomic drivers underlying PM remain poorly characterized.

    Pan-cancer clinicopathological and genomic characteristics of peritoneal metastasis · 2025 · DOI

  • Distal pancreatic resection during cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is rare, with limited knowledge available.

    Is the tail of the pancreas always tumor-infiltrated when macroscopically affected during cytoreductive surgery? A clinicopathological study and experience from a high-volume center · 2025 · DOI

  • Natural killer (NK) cells exhibit rapid responsiveness in anti-tumor immunity; however, NK cells' dynamic evolution and clinical significance in MPM remain unclear.

    Dynamic evolution of NK cells and immune remodeling mediated by CRS + HIPEC: prognostic mechanisms and therapeutic implications for malignant peritoneal mesothelioma · 2025 · DOI

  • The exact pathogenesis of PPC remains uncertain, but mounting evidence supports two main theories: (1) the Müllerian metaplasia hypothesis, which proposes that pluripotent mesothelial cells undergo Müllerian transformation into serous epithelium capable of malignant transformation; and (2) the tubal origin hypothesis, suggesting that serous tubal intraepithelial carcinoma (STIC) cells from the fimbrial end…

    Primary Peritoneal Low-Grade Serous Carcinoma in a 16-Year-Old Female: A Case Report · 2026 · DOI

  • Developing precision-targeted interventions against peritoneal metastasis in pancreatic cancer - Integrating emerging locoregional treatment strategies…

    Peritoneal metastasis in pancreatic cancer: molecular mechanisms, microenvironmental remodeling, and emerging intraperitoneal interventions · 2026 · DOI

Most-cited papers in Intraperitoneal and Appendiceal Malignancies

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Open questions raised by papers listed on this page include: (1) There is a need for further research to determine the optimal selection criteria for patients undergoing CRS+HIPEC (“Evaluation of the Impact of Cytoreductive Surgery and Hyperthermic…”, 2026); (2) The relationship between osteosarcopenia and PCI is not well understood (“Impact of Osteosarcopenia on Peritoneal Cancer Index and Major Complications in…”, 2026); (3) The rarity of appendiceal neoplasms and the lack of awareness among clinicians may contribute to delayed or incidental diagnosis (“A Rare Appendiceal Neoplasm Presenting as Chronic Appendicitis in an Elderly…”, 2026); (4) There is a need for research into new methods of treating pseudomyxoma peritonei in high-risk patients for whom cytoreduction with HIPEC is not feasible (“An 80-year-old female with pseudomyxoma peritonei due to mucinous cancer of…”, 2026); (5) Further studies are needed to fully understand the efficacy and safety of HITHOC in patients with malignant pleural diseases (“EVALUATION OF THE EFFICACY AND SAFETY OF HYPERTHERMIC INTRATHORACIC…”, 2026). 82 gap statements have been mined from Intraperitoneal and Appendiceal Malignancies papers in our 4.5M-paper local library, which holds 477 papers on the topic; the gaps come from whichever of those papers state one. They are mostly the research gaps the authors state and the papers' abstracts, plus future-work, limitations and challenges passages. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one, so you can read the original claim in context.

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