Importance Studies on the prognostic role of hyperthermic intraperitoneal chemotherapy (HIPEC) in pseudomyxoma peritonei (PMP) are currently not available. Objectives To evaluate outcomes after cytoreductive surgery (CRS) and HIPEC compared with CRS alone in patients with PMP. Design, setting, and participants This cohort study analyzed data from the Peritoneal Surface Oncology Group International (PSOGI) registry, including 1924 patients with histologically confirmed PMP due to an appendiceal mucinous neoplasm. Eligible patients were treated with CRS with or without HIPEC from February 1, 1993, to December 31, 2017, and had complete information on the main prognostic factors and intraperitoneal treatments. Inverse probability treatment weights based on the propensity score for HIPEC treatment containing the main prognostic factors were applied to all models to balance comparisons between the CRS-HIPEC vs CRS-alone groups in the entire series and in the following subsets: optimal cytoreduction, suboptimal cytoreduction, high- and low-grade histologic findings, and different HIPEC drug regimens. Data were analyzed from March 1 to June 1, 2018. Interventions HIPEC including oxaliplatin plus combined fluorouracil-leucovorin, cisplatin plus mitomycin, mitomycin, and other oxaliplatin-based regimens. Main outcomes and measures Overall survival, severe morbidity (determined using the National Cancer Institute Common Terminology for Adverse Events, version 3.0), return to operating room, and 30- and 90-day mortality. Differences in overall survival were compared using weighted Kaplan-Meier curves, log-rank tests, and Cox proportional hazards multivariable models. A sensitivity analysis was based on the E-value from the results of the main Cox proportional hazards model. Differences in surgical outcomes were compared using weighted multivariable logistic models. Results Of the 1924 patients included in the analysis (997 [51.8%] men; median age, 56 [interquartile range extremes (IQRE), 45-65] years), 376 were in the CRS-alone group and 1548 in the CRS-HIPEC group. Patients with CRS alone were older (median age, 60 [IQRE, 48-70] vs 54 [IQRE, 44-63] years), had less lymph node involvement (14 [3.7%] vs 119 [7.7%]), received more preoperative systemic chemotherapy (198 [52.7%] vs 529 [34.2%]), and had higher proportions of high-grade disease (179 [47.6%] vs 492 [31.8%]) and suboptimal cytoreduction residual disease (grade 3, 175 [46.5%] vs 117 [7.6%]). HIPEC was not associated with a higher risk of worse surgical outcomes except with mitomycin, with higher odds of morbidity (1.99; 95% CI, 1.25-3.19; P = .004). HIPEC was associated with a significantly better overall survival in all subsets (adjusted hazard ratios [HRs], 0.60-0.68, with 95% CIs not crossing 1.00). The weighted 5-year overall survival was 57.8% (95% CI, 50.8%-65.7%) vs 46.2% (95% CI, 40.3%-52.8%) for CRS-HIPEC and CRS alone, respectively (weighted HR, 0.65; 95% CI, 0.50-0.83; P Conclusions and relevance In this cohort study, HIPEC was associated with better overall survival when performed after CRS in PMP, generally without adverse effects on surgical outcomes.

The Role of Hyperthermic Intraperitoneal Chemotherapy in Pseudomyxoma Peritonei After Cytoreductive Surgery.

Hyperthermic intraperitoneal chemotherapy (HIPEC) is performed with a wide variation in methodology, drugs, and other elements vital to the procedure. Adoption of a limited number of regimens could increase the collective experience of peritoneal oncologists, make comparison between studies more meaningful, and lead to a greater acceptance of results from randomized trials. This study aimed to determine the possibility of standardizing HIPEC methodology and regimens and to identify the best method of performing such a standardization. A critical review of preclinical and clinical studies evaluating the pharmacokinetic aspects of different HIPEC drugs and drug regimens, the impact of hyperthermia, and the efficacy of various HIPEC regimens as well as studies comparing different regimens was performed. The preclinical and clinical data were limited, and studies comparing different regimens were scarce. Many of the regimens were neither supported by preclinical rationale or data nor validated by a dose-escalating formal phase 1 trial. All the regimens were based on pharmacokinetic data and did not take chemosensitivity of peritoneal metastases into account. Personalized medicine approaches such as patient-derived tumor organoids could offer a solution to this problem, although clinical validation is likely to be challenging. Apart from randomized trials, more translational research and phases 1 and 2 studies are needed. While waiting for better preclinical and clinical evidence, the best way to minimize heterogeneity is by an expert consensus that aims to identify and define a limited number of regimens for each indication and primary site. The choice of regimen then can be tailored to the patient profile and its expected toxicity and the methodology according regional factors.

HIPEC Methodology and Regimens: The Need for an Expert Consensus.

Background: The combination of mitomycin C and cisplatin was proved to be beneficial in the treatment of lung cancer, breast cancer, anal carcinoma and human cervical cancer treatment. However, dose related toxicity happens to be one of the major concerns the treatment, leading to its discontinuation, although the patient’s response is encouraging. The aim of the present investigation was to study the protective effects of Berberis aristata (10 mg/kg body weight) on the mitochondrial dysfunction caused due to administration of mitomycin C (2 mg/kg body wt, i.p) and cisplatin (12 mg/kg body wt, i.p).
Methods: We have investigated the effects and protective effects on oxidative phosphorylation enzymes, of the electron transport system, lipid peroxidation and phospholipid composition in liver and kidney mitochondria.
Results: Co-administration of mitomycin C and cisplatin resulted in significant decrease in active respiration (State 3 Respiration), Respiratory Control Ratio (RCR) and P/O ratio’s using either succinate or glutamate plus malate as substrate. Altered enzyme activities of NADH dehydrogenase, succinate dehydrogenase, succinatecytochrome c reductase, NADH-cytochrome c reductase, cytochrome c oxidase was observed. The level of lipid peroxides was increased, and with a significant decrease in phospholipid content. Prior administration of Berberis aristata protected against observed mitochondrial dysfunction.
Conclusions: We believe that prior administration of Berberis aristata could reduce the damage to mitochondrial function, by scavenging free radicals and thereby, preventing uncoupling of oxidative phosphorylation, deactivation of enzymes of electron transport chain, generation of lipid peroxides, oxidation of phospholipids ultimately inhibiting the signaling wave propagation to the mitochondria death receptor (membrane bound cytochrome c), which generally leads to apoptosis.

/pdf/the-protective-effect-of-berberis-aristata-against-100i9xjprg.pdf

The Protective Effect of Berberis aristata against Mitochondrial Dysfunction Induced due to Co-administration of Mitomycin C andCisplatin

The 2022 PSOGI International Consensus on HIPEC Regimens for Peritoneal Malignancies: HIPEC Technologies

症例は25歳，女性．近医婦人科で月経困難症に対して子宮内避妊器具が留置された．その後のフォローの経膣超音波検査で骨盤内に腫瘤を指摘され，骨盤部MRIで8cm大の消化管由来の間葉系腫瘍が疑われた．精査加療目的に当院に紹介，腹部造影CTでS状結腸間膜由来の神経鞘腫もしくは胃腸管外間葉系腫瘍が疑われ，診断的治療を兼ねて手術の方針となった．腹腔鏡で観察を行い，被包された腫瘍はS状結腸間膜に存在し，他臓器への浸潤や腹膜播種の所見はなく，左結腸動脈分岐後の下腸間膜動脈が腫瘍に巻き込まれていた．被膜の損傷が無いように腫瘍含め腹腔鏡下S状結腸切除術を施行した．術後は合併症なく経過し，術後8日目に退院した．病理組織学的に免疫染色で，S-100蛋白陽性，c-kit陰性，CD34陰性，α-SMA陰性で神経鞘腫の診断となった．S状結腸間膜神経鞘腫は稀であり，腹腔鏡下手術を施行した症例は少なく，若干の文献的考察を加えて報告する． 

/pdf/fu-qiang-jing-xia-niqie-chu-sitaszhuang-jie-chang-jian-mo-3ttfw1j0.pdf

腹腔鏡下に切除したs状結腸間膜神経鞘腫の1例

/pdf/is-procalcitonin-a-useful-predictor-marker-in-the-diagnosis-4cpee1o3b4.pdf

Is Procalcitonin a Useful Predictor Marker in the Diagnosis of Complicated Acute Appendicitis

A Case of Breast Hemorrhage following Bicycle Handlebar Injury in an Adult

Mesenteric Schwannoma of the Small Intestine Mimicking Ovarian Tumor—A Case Report—

We have made a bibliographical study of 643 cases of gastric leiomyosarcoma in Japan for the past 11 years including 4 cases in our experience. The ratio of the males to females was 1.19:1, and the patients in 60s were the largest in number in the age distribution, being 29.2%. The sites of occurrence were: cardia -60.3%; corpus -24.5%; and antrum -7.7%, and growing patterns included exogastric type -54.8%; endogastric type -27.4%; and intramural type -5.4%. The rate of metastasis to the lymphnode was 9.8% and that to the liver was 24.2%, showing no statistical difference in site of occurrence or growing pattern. In the cases with tumors in diameters of less than 5cm, no difference was observed in the rate of metastasis to the lmyphnode, compared with those in diameters of more than 5cm, but the rate of metastasis to the liver was significantly lower. The rate of metastasis to the lymphnode in this disease was remarkably low, compared with that in gastric carcinoma, and no difference was observed by diameter of tumor. These findings, suggesting a possible difference in biological characteristics between the disease and gastric carcinoma, might offer a problem to establish an appropriate therapeutic procedure for the disease.

Leiomyosarcoma of the stomach

A new combined cancer chemotherapy regimen of mitomycin C (MMC) and cisplatin (DDP) showed synergistic antitumor activity against human gastric cancer xenografts St-40 and SC-1-NU in BALB/c nu/nu mice. The drugs were administered intraperitoneally at doses of 2 or 4 mg/kg for MMC and 3 or 6 mg/kg for DDP, respectively. To clarify the schedule-dependent antitumor activity of MMC and DDP against St-40 and SC-1-NU, different sequential therapies were conducted. Simultaneous administration of these agents showed the highest antitumor activity against SC1-NU among the three regimens used, whereas the sequence of MMC followed by DDP showed higher antitumor activity than the reverse sequence against St-40. The intratumoral concentration of platinum was significantly increased in St-40 treated with the sequence MMC to DDP, in comparison with the sequence DDP to MMC. The maximum tolerated dose (MTD) of this combination was 4 mg MMC plus 6 mg DDP per kg in all the combinations, and these MTDs were 2/3 of the corresponding values for their single use. Since this combination increased the antitumor activity of each single agent without any increase in their toxicity, it would appear to be useful clinically. © 1994 Wiley-Liss, Inc.

Synergistic antitumor activity of combination chemotherapy with mitomycin C and cisplatin against human gastric cancer xenografts in nude mice

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