Perioperative outcomes and platinum resistant recurrence in patients undergoing systematic, protocol-based, total parietal peritonectomy during interval cytoreductive surgery for advanced ovarian cancer: results of the TORPEDO study.

OBJECTIVE: The TORPEDO (CTRI/2018/12/016789) is the single-arm, prospective, interventional study evaluating the role of a total parietal peritonectomy (TPP) in patients undergoing interval cytoreductive surgery (iCRS). In this manuscript, we report the perioperative outcomes and platinum resistant recurrence (PRR) in 218 patients enrolled in the study. METHODS: A TPP was performed in all patients undergoing iCRS irrespective of the residual disease extent. hyperthermic intraperitoneal chemotherapy (HIPEC) was performed as per the clinician's discretion with 75 mg/m² of cisplatin. Maintenance therapy was also used at the discretion of the treating clinicians. RESULTS: From 9th December 2018 to 31st July 2022 (recruitment complete), 218 patients were enrolled at 4 medical centers in India. The median surgical peritoneal cancer index was 14 and a complete gross resection was achieved in 95.8%. HIPEC was performed in 130 (59.6%) patients. The 90-day major morbidity was 17.4% and 2.7% patients died within 90 days of surgery. Adjuvant chemotherapy was delayed beyond 6 weeks in 7.3%. At a median follow-up of 19 months (95% confidence interval [CI]=15.9-35 months), 101 (46.3%) recurrences and 19 (8.7%) deaths had occurred. The median progression-free survival was 22 months (95% CI=17-35 months) and the median overall survival (OS) not reached. Platinum resistant recurrence was observed in 6.4%. The projected 3-year OS was 81.5% and in 80 patients treated before may 2020, it was 77.5%. CONCLUSION: The morbidity and mortality of TPP with or without HIPEC performed during iCRS is acceptable. The incidence was of PRR is low. Early survival results are encouraging and warrant conduction of a randomized controlled trial comparing TPP with conventional surgery.

Subcutaneous cellular angiofibroma of arm: A case report.

ABSTRACT: Cellular angiofibroma is a rare benign mesenchymal tumor reported in genital region in middle-aged patients. We report a rare presentation of the tumor in an extragenital location-the arm of a young male patient. After biopsy, an en bloc excision of the mass was done and diagnosis was confirmed. No adjuvant treatment was required. Our patient had an unusual location for this rare tumor at an age younger than reported in literature so far. Imaging can only predict the mesenchymal nature of the tumor but histopathology and immunohistochemistry (IHC) is the cornerstone of diagnosis. Cellular angiofibroma has a good prognosis. Histopathology and IHC are needed to confirm the diagnosis, hence emphasizing the role of a good and experienced pathologist. The pathogenesis of the cellular angiofibroma is still not fully determined and current hormonal and immunotherapy suppression regimes will need further evaluation.

Long-Term Survival in Patients Treated by Cytoreductive Surgery with or Without HIPEC for Peritoneal Surface Malignancies-A report from the Indian HIPEC Registry.

A previous report from the Indian HIPEC registry showed acceptable early survival and morbidity in patients undergoing cytoreductive surgery (CRS) + / - hyperthermic intraperitoneal chemotherapy (HIPEC). The goal of this retrospective study was to evaluate the long-term outcomes in these patients. Three hundred seventy-four patients treated from December 2010 to December 2016 and enrolled in the Indian HIPEC registry were included. All patients had completed 5 years from the date of surgery. The 1-, 3-, 5- and 7-year progression-free (PFS) and overall survival (OS) and factors affecting these were evaluated. The histology was epithelial ovarian cancer in 209 (46.5%), pseudomyxoma peritonei (PMP) in 65 (17.3%) and colorectal cancer in 46 (12.9%) patients. The peritoneal cancer index (PCI) was ≥ 15 in 160 (42.8%). A completeness of cytoreduction (CC) score of 0/1 resection was obtained in 83% (CC-0-65%; CC-1-18%). HIPEC was performed in 59.2%. At a median, follow-up of 77 months (6-120 months), 243 (64.9%) patients developed recurrence, and 236 (63%) died of any cause; 138 (36.9%) were lost to follow-up. The median OS was 56 months (95% CI 53.42-61.07), and the median PFS was 28 months (95% CI 37.5-44.4). The 1-, 3-, 5- and 7-year OS was 97.6%, 63%, 37.7% and 24% respectively. The 1-, 3-, 5- and 7-year PFS was 84.8%, 36.5%, 27.3% and 22% respectively. The use of HIPEC (p = 0.03) and PMP of appendiceal origin (p = 0.01) was independent predictors of a longer OS. CRS + / - /HIPEC may achieve long-term survival in patients with PM from different primary sites in the Indian scenario. More prospective studies are needed to confirm these findings and identify factors influencing long-term survival. Supplementary Information: The online version contains supplementary material available at 10.1007/s13193-023-01727-7.

Bilateral Thoracic Cytoreductive Surgery for Pseudomyxoma Peritonei of Appendiceal Origin.

Pleural spread occurs in pseudomyxoma peritonei (PMP) in less than 10% of the patients and is treated by thoracic cytoreductive surgery with or without hyperthermic intrathoracic chemotherapy (HITOC). It is performed both for symptom palliation and disease control and includes pleurectomy and decortication and wedge and segmental lung resections. So far, only unilateral spread treated with a thoracic cytoreductive surgery (CRS) has been reported in literature. We report a patient with bilateral thoracic PMP following a complete abdominal CRS and hyperthermic intraperitoneal chemotherapy (HIPEC) who was treated with bilateral staged thoracic CRS and subsequently had a 4th CRS for abdominal disease. The staged procedure was performed as she was symptomatic due to the thoracic disease and there was disease on all pleural surfaces. HITOC was not performed. Both procedures were uneventful with no major morbidity. The patient is currently disease free nearly 84 months after the first abdominal CRS and 60 months after the second thoracic CRS. Thus, an aggressive CRS in the thorax in patients with PMP can result in a prolongation of survival while preserving the quality of life if the abdominal disease is controlled. A thorough understanding of the disease biology and surgical expertise are both essential for selecting the right patients for these complex procedures and achieving good short- and long-term outcomes.

High-Risk Peritoneal Mesothelioma: Does Metronomic Chemotherapy Have a Role?

Objective: To evaluate the feasibility, tolerance, and efficacy of OMCT (oral metronomic chemotherapy) after CRS + HIPEC for peritoneal mesothelioma in patients with poor prognostic factors: PCI > 20, incomplete CRS, poor performance status, or progression on systemic chemotherapy. Methods: A retrospective analysis of patients undergoing CRS + HIPEC for peritoneal mesothelioma and receiving OMCT for poor risk factors. Results: Sixteen patients underwent CRS + HIPEC between 2013 and 2017. The median PCI was 31.5. Complete cytoreduction (CC-0/1) was obtained in 8 patients (50%). All 16 received HIPEC except one patient with baseline renal dysfunction.Thirteen patients had PCI > 20 where only 5 had CC-0/1. Of 8 suboptimal cytoreduction (CC-2/3), 7 received OMCT (6 for progression on chemotherapy and one for mixed histology). Three patients had PCI < 20 and all had CC-0/1 clearance. Only one received OMCT for progression on adjuvant chemotherapy. Patients receiving OMCT for progression on adjuvant chemotherapy (ACT) were in poor PS.The median follow-up was 13.4 months. Five are alive with the disease (three are on OMCT). Six are alive without disease (2 are on OMCT). The mean OS was 24.3 months and the mean DFS was 18 months. Outcomes were similar between CC-0/1 and CC-2/3 groups, OMCT vs no OMCT groups.All patients receiving OMCT for progression on neoadjuvant chemotherapy had better survival (alive at 12, 20, 32, 36 months) compared to those receiving OMCT for progression on the ACT (p = 0.012). Conclusion: OMCT is a good alternative in high-volume peritoneal mesothelioma with incomplete cytoreduction and progression on chemotherapy. OMCT may improve outcomes in these scenarios when started early.

Feasibility and Safety of Taxane-PIPAC in Patients with Peritoneal Malignancies-a Retrospective Bi-institutional Study.

Taxanes have a favorable pharmacokinetic profile for intraperitoneal application. We report our initial experience with taxane-PIPAC (pressurized intraperitoneal chemotherapy) for unresectable peritoneal metastases from different primary sites in terms of safety, feasibility, response rate, and conversion to resectability. In this retrospective study, PIPAC was performed alone or in combination with systemic chemotherapy. Paclitaxel was used as a single agent, whereas docetaxel was used in combination with cisplatin-adriamycin or oxaliplatin-adriamycin. From December 2019 to December 2021, 47 patients underwent 82 PIPAC procedures (1 PIPAC in 55.3%, 2 in 29.7%, 3 in 14.8%). The most common primary sites were ovarian cancer (31.9%), gastric cancer (23.4%), and colorectal cancer (21.2%). Docetaxel-cisplatin-adriamycin was used in 33 (70.2%) patients, docetaxel-oxaliplatin-adriamycin in 12 (25.5%), and paclitaxel alone in 2 (4.2%) patients. Grade 1-2 complications were observed in 24 (51%) and grade 3-4 complications in 6 (12.7%) patients (8.5% of 82 PIPACs). 16/47 (34.0%) patients had a clinical response to PIPAC. The mean PCI was 25.9 ± 9.2 for the first PIPACs and 22.4 ± 9 for the subsequent PIPACs with an average reduction of 3.6 points [change in PCI ranged from - 14 to + 8]. The PRGS was 1/2 in 4/47 (8.5%) patients (19.0% patients with > 1 PIPAC). A reduction in ascites was observed in 35.4% presenting with ascites. Nine (19.1%) patients had conversion to operability leading to a subsequent cytoreductive surgery in 8 (17%) patients. PIPAC with docetaxel is feasible and safe. The role of PIPAC with both docetaxel and paclitaxel either alone or in combination with other drugs should be investigated in prospective studies.

Platinum resistant recurrence and early recurrence in a multi-centre cohort of patients undergoing interval cytoreductive surgery for advanced epithelial ovarian cancer.

Background: Aggressive locoregional therapies like hyperthemic intraperitoneal chemotherapy(HIPEC) and total parietal peritonectomy(TPP) have been used to delay recurrence in patients with advanced ovarian cancer undergoing interval cytoreductive surgery(CRS). The aim of this retrospective study was to evaluate the incidence of platinum resistant recurrence (PRR) and early recurrence (ER)(recurrence within 6 months and 1 year of the last dose of platinum based therapy, respectively) in patients undergoing interval CRS. The secondary goal was to study impact of each of these therapies on PRR and ER. Methods: One-hundred and fifty-three patients undergoing interval CRS from July 2018 to June 2020 were included. The surgical strategy was to perform a TPP in which the entire parietal peritoneum is resected irrespective of the disease extent or a selective parietal peritonectomy (SPP) in which only the peritoneum bearing visible residual disease is resected. The use of HIPEC was at the discretion of the treating oncologists. Results: The median surgical PCI was 15 [range, 0-37]. A CC-0 resection was obtained in 119 (77.7%) and CC-1 in 29 (18.9%) patients. Eighty-one (53%) patients had a TPP and 72 (47%) had SPP. HIPEC was performed in 98(64%) patients. Bevacizumab maintenance was administered to 31(19.6%) patients. No patients received PARP inhibitors during first-line therapy. PRR was observed in 8(5.2%) patients and ER in 30(19.6%). The respective incidences of PRR and ER were 4.9% and 16% in the TPP group, 4.1% and 23.6% in the SPP group, 9% and 20% in the no-HIPEC group and 3% and 19.3% in the HIPEC groups. On multivariate analysis, CC-0(p=0.014) resection and HIPEC(p=0.030) were independent predictors of a low ER. All patients with PR and 70% with ER had peritoneal recurrence with or without extra-peritoneal sites of recurrence. Conclusions: The incidence of PRR and ER in this cohort was low as compared to historical data. This low incidence could be attributed to the use of aggressive locoregional therapies like TPP and HIPEC. In future, studies should be conducted to confirm these findings and evaluate the potential additive benefit of TPP and HIPEC coupled together as well as their combination with maintenance therapies.

Downstaging in Advanced Rectal Cancers: A Propensity-Matched Comparison Between Short-Course Radiotherapy Followed by Chemotherapy and Long-Course Chemoradiotherapy.

BACKGROUND: Short-course radiotherapy followed by chemotherapy has not been widely evaluated as an alternative to traditional long-course chemoradiotherapy in locally advanced rectal cancer. OBJECTIVE: This study compared the oncological and short-term outcomes between short-course radiotherapy + chemotherapy and long-course chemoradiotherapy in locally advanced rectal cancer. DESIGN: This is a retrospective propensity-matched study. SETTINGS: The study was conducted in a colorectal department at a tertiary care oncology center in India. PATIENTS: There were 173 patients. Group A had 47 patients and group B had 126 patients. A 1:2.7 matching was done for age, sex, distance of tumor from the anal verge, sphincter preservation surgeries, MRI-based pretreatment T stage, and circumferential resection margin. INTERVENTIONS: The interventions performed were short-course radiotherapy + chemotherapy (group A) and long-course chemoradiotherapy (group B) in locally advanced rectal cancer. MAIN OUTCOME MEASURES: The primary measures were pathological circumferential resection margin positivity, downstaging, tumor regression grade, and postoperative complications. RESULTS: Of the patients, 52% had a positive circumferential resection margin on MRI, 57% had low rectal tumors, and 20% had T4 tumors. Distribution of rectal surgeries was similar between the 2 groups. pT downstaging and tumor regression scores were significantly better in group B ( p = 0.028 and 0.026). Pathological circumferential resection margin, distal resection margin, and nodal yield were similar. On multivariate analysis, pretreatment N status was the only independent predictive factor for pathological circumferential resection margin status. Grade 3 to 4 Clavien-Dindo complications, anastomotic leak rates, and hospital stay were similar between the 2 groups. LIMITATIONS: This was a retrospective study. Although propensity matching was performed, selection bias cannot be eliminated completely, as seen in the difference in the surgical approaches between the 2 groups. CONCLUSIONS: In a cohort containing a significant portion of MRI circumferential resection margin-positive low rectal cancers, short-course radiotherapy + chemotherapy followed by delayed surgery resulted in lower T downstaging and lower tumor regression scores compared with long-course chemoradiotherapy, but pathological circumferential margin status, distal resection margin, nodal yield, and perioperative morbidity were similar between the 2 groups. This suggests that short-course radiotherapy + chemotherapy could be a viable alternative to long-course chemoradiotherapy in locally advanced rectal cancers. See Video Abstract at http://links.lww.com/DCR/B855 . REDUCCIN DEL ESTADIO EN LOS CNCERES RECTALES AVANZADOS UNA COMPARACIN DE PROPENSIN EQUIPARADA ENTRE LA RADIACIN DE CICLO CORTO SEGUIDA DE QUIMIOTERAPIA Y LA QUIMIO RADIACIN DE CICLO LARGO: ANTECEDENTES:La radioterapia de ciclo corto seguida de quimioterapia no ha sido evaluada ampliamente como una alternativa a la tradicional quimio radioterapia de ciclo largo en el cáncer de recto localmente avanzado.OBJETIVO:Estudio que compara los resultados oncológicos y a corto plazo entre la radioterapia de ciclo corto + quimioterapia y la quimio radioterapia de ciclo largo en el cáncer de recto localmente avanzado.DISEÑO:Estudio comparado de propensión de manera retrospectiva.AJUSTE:Departamento colorrectal en un centro de atención oncológica de tipo terciario en la India.PACIENTES:Hubo 173 pacientes. El grupo A tenía 47 y el grupo B tenía 126 pacientes. Se realizó una comparación de 1: 2,7 para edad, sexo, distancia del tumor desde el margen anal, cirugías de preservación del esfínter, estadio T previo al tratamiento basada en resonancia magnética y margen de resección circunferencial (CRM).INTERVENCIONES:Radioterapia de ciclo corto + quimioterapia (grupo A) y quimio radioterapia de ciclo largo (grupo B) en cáncer de recto localmente avanzado (LARC).PRINCIPALES MEDIDAS DE RESULTADO:Positividad histopatológica de CRM, reducción del estadio tumoral, grado de regresión tumoral, complicaciones posoperatorias.RESULTADOS:El 52% de los pacientes han tenido un margen de resección circunferencial positivo en la resonancia magnética, 57% de tumores rectales bajos, 20% de tumores T4. La distribución de cirugías rectales fue similar entre los 2 grupos. Las puntuaciones de regresión tumoral y de reducción del estadio de pT fueron significativamente mejores en el grupo B ( p = 0.028 y 0.026 respectivamente). El margen de resección circunferencial patológico, el margen de resección distal y los ganglios arrojados fueron similares. En el análisis multivariado, el estadio N previo al tratamiento fue el único factor predictivo independiente para el estadio de pCRM. Las complicaciones Clavien-Dindo de grado 3-4, las tasas de fuga anastomótica y la estancia hospitalaria fueron similares entre los dos grupos.LIMITACIONES:Retrospectiva; aunque la propensión coincide, existe potencial sesgo de selección.CONCLUSIONES:En una cohorte que contenía una porción significativa de cánceres rectales bajos con margen de resección circunferencial positivo por resonancia magnética, la radioterapia de ciclo corto + quimioterapia seguida de cirugía tardía dio como resultado una mayor reducción del estadio T y de regresión tumoral en comparación con la quimio radioterapia de ciclo largo. Pero el estatus histopatológico del margen circunferencial, el margen de resección distal, el rendimiento ganglionar y la morbilidad perioperatoria fueron similares entre los dos grupos. Esto sugiere que la radioterapia de ciclo corto + quimioterapia podría ser una alternativa viable a la quimio radioterapia de ciclo largo en cánceres rectales localmente avanzados. Consulte Video Resumen en http://links.lww.com/DCR/B855 . (Traducción-Dr. Osvaldo Gauto ).

Laparoscopic versus open resection in locally advanced rectal cancers: a propensity matched analysis of oncological and short-term outcomes.

AIM: The aim was to compare oncological and short-term outcomes between open and laparoscopic surgery in locally advanced rectal cancers. METHODS: It is a retrospective analysis conducted in a high volume tertiary centre. Matching was carried out for nine variables, including preoperative factors, neoadjuvant treatment and sphincter preservation. RESULTS: Both the open and laparoscopic surgery arms had 239 patients each. The distributions of pretreatment MRI T3, T4, circumferential resection margin (CRM) positive tumours, neoadjuvant long-course chemoradiation and sphincter preservation were 80.3%, 13.6%, 50%, 89% and 56.4% respectively. The mean number of nodes harvested (12.9 vs. 12.7, P = 0.716), pathological CRM positivity (6.3% in open vs. 5.4% in laparoscopic, P = 0.697) and distal resection margins were similar. The mean blood loss was higher in open surgeries (910 ml vs. 349 ml, P < 0.001). Anastomotic leaks and Clavien-Dindo Grade 3-4 complications were higher in the open arm than in the laparoscopy arm (5.9% vs. 1.7%, P = 0.024, and 12.5% vs. 6.7%, P = 0.015 respectively). The median postoperative hospital stay was significantly shorter in the laparoscopy arm (7 vs. 6, P = 0.015). In CRM positive and threatened cases, the measured outcomes were similar between the two groups except for blood loss which was significantly higher in the open surgery (872 vs. 379, P = 0.000). CONCLUSIONS: In high volume centres, in the hands of experienced colorectal surgeons, laparoscopic rectal surgery is oncologically safe in locally advanced rectal cancers and has lesser morbidity and shorter hospital stay than open surgery. In CRM positive and threatened cases the laparoscopic surgery showed less blood loss compared to open surgery, while other outcome measures were similar to open surgery.

Patterns of peritoneal dissemination and response to systemic chemotherapy in common and rare peritoneal tumours treated by cytoreductive surgery: study protocol of a prospective, multicentre, observational study.

INTRODUCTION: Despite optimal patient selection and surgical effort, recurrence is seen in over 70% of patients undergoing cytoreductive surgery (CRS) for peritoneal metastases (PM). Apart from the Peritoneal Cancer Index (PCI), completeness of cytoreduction and tumour grade, there are other factors like disease distribution in the peritoneal cavity, pathological response to systemic chemotherapy (SC), lymph node metastases and morphology of PM which may have prognostic value. One reason for the underutilisation of these factors is that they are known only after surgery. Identifying clinical predictors, specifically radiological predictors, could lead to better utilisation of these factors in clinical decision making and the extent of peritoneal resection performed for different tumours. This study aims to study these factors, their impact on survival and identify clinical and radiological predictors. METHODS AND ANALYSIS: There is no therapeutic intervention in the study. All patients with biopsy-proven PM from colorectal, appendiceal, gastric and ovarian cancer and peritoneal mesothelioma undergoing CRS will be included. The demographic, clinical, radiological, surgical and pathological details will be collected according to a prespecified format that includes details regarding distribution of disease, morphology of PM, regional node involvement and pathological response to SC. In addition to the absolute value of PCI, the structures bearing the largest tumour nodules and a description of the morphology in each region will be recorded. A correlation between the surgical, radiological and pathological findings will be performed and the impact of these potential prognostic factors on progression-free and overall survival determined. The practices pertaining to radiological and pathological reporting at different centres will be studied. ETHICS AND DISSEMINATION: The study protocol has been approved by the Zydus Hospital ethics committee (27 July, 2020) and Lyon-Sud ethics committee (A15-128). TRIAL REGISTRATION NUMBER: CTRI/2020/09/027709; Pre-results.

Greater-omentum lesion-score (GOLS) as a predictor of residual disease in different regions of the peritoneal cavity in patients undergoing interval cytoreductive surgery for advanced ovarian cancer and its potential clinical utility.

BACKGROUND AND AIM: The greater omentum(GO) is a common site of residual disease in patients receiving neoadjuvant chemotherapy for advanced epithelial ovarian cancer. The presence of tumor in the GO could predict presence of disease in other peritoneal regions. The goal of this study was to perform a correlation between the greater-omentum lesion-score(GOLS) and presence of disease in different peritoneal regions and determine its potential utility in guiding interval cytoreductive surgery(CRS). METHODS: This prospective study included 134 patients undergoing interval CRS from July 1, 2018 to June 30, 2020. Each region of Sugarbaker's Peritobneal Cancer Index(PCI) was given a lesion score(LS) from 0 to 3 according to the diameter of the largest tumor in the region. The GOLS was recorded separately from other structures in the region. Correlation between the GOLS and surgical and pathological LS in each region was performed. RESULTS: As the GOLS increased, the incidence of disease(surgical LS) in other regions of the peritoneal cavity increased. Receiver operating characteristic(ROC) curves showed area under curve more than 80% for regions 1-2 and 7-8 indicating a high probability of disease in these regions in patients with GOLS 1-3. The positive predictive value(PPV) of preoperative imaging for GOLS was 95.7%. No cut-off of the GOLS could predict presence of disease on pathology with more than 70% accuracy. CONCLUSIONS: Presence of disease in the GO warrants performing upper abdominal exploration and/or cytoreduction and interval CRS should be planned accordingly in these patients. Imaging has a high PPV in detecting disease in the GO.

Total parietal peritonectomy performed during interval cytoreductive surgery for advanced epithelial serous ovarian cancer results in a low incidence of platinum resistant recurrence- results of a prospective multi-centre study.

BACKGROUND: The reported incidence of platinum resistant recurrence (PRR) (recurrence within 6 months of the last dose of platinum therapy) after interval debulking/cytoreductive surgery (CRS) is high compared to that after primary CRS. The goal was to study PRR following a total parietal peritonectomy (TPP), that addresses occult disease more completely. METHODS: This is a prospective multi-center study (CTRI/2018/08/015350). A TPP was performed during interval CRS following a fixed surgical protocol. Patients with a follow-up of 6 months(M) or more were included in this analysis. The incidence and patterns of PRR and factors affecting recurrence were analyzed. RESULTS: From July 2018 to October 2019, 70 patients with serous carcinoma were included. The median surgical PCI was 15 [range 5-37]. A CC-0 resection was obtained in 55 (78.5%); CC-1 in 10 (14.2%). Occult residual disease was seen in 40%. At a median follow-up of 13 months, 17 (24.2%) had developed recurrence/progression. PRR was seen in 5 (7.1%) patients. The sites of progression (>1 in 2 patients) were pleura (n = 1), visceral peritoneum (n = 2), retroperitoneal nodes (n = 2), mediastinal nodes (n = 1) and small bowel mesentery (n = 2). Overall, though the most common site of recurrence was the visceral peritoneum (N = 9), seven (>40%) patients did not develop recurrence in the visceral peritoneum. Patients with high PCI and grade 3-4 complications had a higher probability of developing recurrence. CONCLUSIONS: TPP performed during interval CRS resulted in a very low incidence of PRR. These findings need confirmation in a larger series. The benefit of TPP over conventional surgery should be evaluated in a randomized trial.

Implications of Pathologic Findings in Cytoreductive Surgery Specimens on Treatment of Colorectal Peritoneal Metastases: Results of a Prospective Multicentric Study.

BACKGROUND: A surgical peritoneal cancer index of >20 is often used to exclude patients from cytoreductive surgery for colorectal peritoneal metastases. The pathologic peritoneal cancer index in these patients may be <20. OBJECTIVE: The purpose of this study was to compare the pathologic and surgical findings and to look at potential pathologic prognostic factors. DESIGN: This is a prospective observational study including patients undergoing cytoreductive surgery. SETTINGS: The study was carried out at 3 peritoneal surface malignancy centers, 1 in France and 2 in India. PATIENTS: One-hundred patients were included from July 1, 2018, to June 30, 2019. MAIN OUTCOME MEASURES: The pathologic peritoneal cancer index, peritoneal disease distribution, pathologic response to chemotherapy, factors affecting them and their relation with surgical findings, and potential prognostic value were explored. RESULTS: Ninety percent had colonic primaries. Fifty-one percent had left-sided tumors. The median surgical peritoneal cancer index was 4 (range, 0-35). Upper regions were involved in 32% and small bowel regions in 26%, and their involvement increased with a higher peritoneal cancer index (p < 0.001). The median pathologic peritoneal cancer index was 2 (range, 0-27) and was less than the surgical peritoneal cancer index in 57%. A pathologic complete response was obtained in 25%. Patients with pathologic complete response received more antiepidermal growth factor receptor therapy (p = 0.008); more leucovorin, 5-fluorouracil, and oxaliplatin; and folinic acid, fluorouracilirin, irinotecan hydrochloride, and oxaliplatin (p < 0.001). In 7 patients with a surgical peritoneal cancer index of >20, pathologic peritoneal cancer index was <20 in 4 patients. Disease in the primary tumor/anastomotic site was found in ≈80%. LIMITATIONS: Survival outcomes are not available. CONCLUSIONS: Surgical peritoneal cancer index of >20 should not be the sole factor to exclude patients from surgery, especially in responders to systemic therapies. The pathologic peritoneal cancer index, pathologic response to systemic chemotherapy, and disease distribution in the peritoneal cavity should be meticulously documented. Correlation with survival will define their future prognostic value. The primary anastomotic site is a common site for peritoneal disease and should be carefully evaluated in all patients. See Video Abstract at http://links.lww.com/DCR/B490. IMPLICACIONES DE LOS HALLAZGOS PATOLÓGICOS EN MUESTRAS DE CIRUGÍA CITORREDUCTORA EN EL TRATAMIENTO DE METÁSTASIS PERITONEALES COLORRECTALES: RESULTADOS DE UN ESTUDIO PROSPECTIVO MULTICÉNTRICO: Una ICP quirúrgica de >20 se utiliza a menudo para excluir a los pacientes de la cirugía citorreductora por metástasis peritoneales colorrectales. La PCI patológica en estos pacientes puede ser <20.Comparar los hallazgos patológicos y quirúrgicos y observar los posibles factores pronósticos patológicos.Se trata de un estudio observacional prospectivo que incluye a pacientes sometidos a cirugía citorreductora.El estudio se llevó a cabo en tres centros de malignidad de la superficie peritoneal, 1 en Francia y 2 en India.Se incluyeron 100 pacientes desde el 1 de julio de 2018 al 30 de junio de 2019.No hubo intervención terapéutica.Se exploró la ICP patológica, la distribución de la enfermedad peritoneal, la respuesta patológica a la quimioterapia, los factores que la afectan y su relación con los hallazgos quirúrgicos y el valor pronóstico potencial.El noventa por ciento tenía lesiones primarias colónicas. El 51% tenía tumores del lado izquierdo. La mediana de la ICP quirúrgica 4 [0-35]. Las regiones superiores estuvieron involucradas en el 32% y las regiones del intestino delgado en un 26% y su participación aumentó con una ICP más alta (p <0,001). La mediana de la ICP patológica fue 2 [0-27] y fue menor que la ICP quirúrgica en el 57%. Se obtuvo respuesta patológica completa en el 25%. Los pacientes con respuesta patológica completa recibieron más terapia anti-EGFR (p = 0,008) y más FOLFOX y FOLFIRINOX (p <0,001). En 7 pacientes con una ICP quirúrgica de> 20, la ICP patológica fue menor de 20 en 4 pacientes. Se encontró enfermedad en el tumor primario/anastomósis en casi el 80%.Los resultados de supervivencia no están disponibles.La ICP quirúrgica de> 20 no debería ser el único factor para excluir a los pacientes de la cirugía, especialmente en los que responden a las terapias sistémicas. La PCI patológica, la respuesta patológica a la quimioterapia sistémica y la distribución de la enfermedad en la cavidad peritoneal deben documentarse meticulosamente. La correlación con la supervivencia definirá su valor pronóstico futuro. El sitio anastomótico primario es un sitio común de enfermedad peritoneal y debe evaluarse cuidadosamente en todos los pacientes. Consulte Video Resumen en http://links.lww.com/DCR/Bxxx. (Traducción-Dr. Gonzalo Hagerman).

Total Parietal Peritonectomy Can Be Performed with Acceptable Morbidity for Patients with Advanced Ovarian Cancer After Neoadjuvant Chemotherapy: Results From a Prospective Multi-centric Study.

BACKGROUND: Total parietal peritonectomy (TPP) removes areas of "normal-appearing" parietal peritoneum bearing microscopic residual disease and has the potential to improve survival of patients undergoing interval cytoreductive surgery (CRS) for advanced serous epithelial ovarian cancer. This report presents the morbidity outcomes for the first 50 patients enrolled in TORPEDO (CTRI/2018/12/016789), a prospective study. METHODS: All the patients underwent a TPP during interval CRS. A surgical protocol that includes a description of the boundaries for each of the five peritonectomies was followed. The common toxicology criteria for adverse events (CTCAE) classification was used to record 90-day morbidity and mortality. RESULTS: The median Peritoneal Cancer Index (PCI) for 50 patients was 15 (range, 5-37). A complete cytoreduction (CC-0 resection) was obtained in 80%, a CC-1 resection in 16%. A bowel resection was performed in 70% of the patients. Grade 3 or 4 complications were seen in 11 patients (22%), and one patient died within 90 days after surgery due to intraperitoneal hemorrhage. The most common complications were postoperative fluid collection requiring aspiration (n = 5), intraperitoneal hemorrhage (n = 2), abdominal wound dehiscence (n = 2), pseudo-obstruction (n = 1), urinary sepsis (n = 2), and ileostomy-related complications (n = 2). No bowel fistulas or anastomotic leaks occurred. Microscopic disease in 'normal appearing' peritoneum adjacent to tumor nodules was observed in 46% of the patients, and in regions given a lesion score of 0 in 34%. The parietal peritoneal regions (0-8) had a higher incidence of residual disease (p < 0.001) and occult disease (p < 0.001). CONCLUSIONS: During interval CRS, TPP can be performed with acceptable morbidity and mortality. The pathologic findings further support this therapeutic rationale. Survival outcomes should determine the future role of such a procedure in routine clinical practice.

Primary Squamous Cell Carcinoma of the Sternum.

Primary squamous cell carcinoma of the sternum is very rare. Imaging features are not specific, and a biopsy specimen may help identify the pathology. Positron emission tomography scan helps rule out a primary focus elsewhere. The treatment will be surgical management, if operable. We encountered a patient with primary squamous cell carcinoma of the sternum with an unusual presentation. After the diagnostic workup, we managed the patient surgically with resection, followed by titanium mesh reconstruction and pectoralis major flap cover. We present the case in view of its rarity and to emphasize the key surgical points.

A comparison of outcomes following total and selective peritonectomy performed at the time of interval cytoreductive surgery for advanced serous epithelial ovarian, fallopian tube and primary peritoneal cancer - A study by INDEPSO.

OBJECTIVES: To compare clinical outcomes following total and selective peritonectomy performed during interval cytoreductive surgery (CRS) for stage IIIC/IVA serous epithelial ovarian cancer. METHODS: In this retrospective study, extent of peritonectomy was classified as total parietal peritonectomy (TPP) which comprised of removal of the entire parietal peritoneum and the greater and lesser omenta or selective parietal peritonectomy (SPP) that included 1/>1 of parietal peritonectomies performed to resect sites of residual disease. A comparison of patient and disease characteristics, morbidity, mortality and survival outcomes between the two groups was made. RESULTS: From January 2013 to December 2017, 79 patients underwent CRS (TPP-30, SPP-49) with or without intraperitoneal chemotherapy (IPC). The median PCI was 14 for TPP and 8 for SPP. The 90-day grade 3-4 morbidity (23.3% for TPP, 14.2% for SPP, p = 0.58) the 90-day mortality was similar (p = 0.58). The median disease free survival (DFS) was 37 months for SPP and 33 months for TPP (p = 0.47) and median overall survival (OS) not reached for both. The 3-year OS was 95% for TPP and 70.8% for SPP (p = 0.06). The only independent predictor of OS was grade 3-4 morbidity (p = 0.01) and not TPP (p = 0.09). Microscopic residual disease was seen in 23.3% with normal looking peritoneum in TPP group. CONCLUSIONS: TPP was not associated with increased morbidity compared to SPP. There was a trend towards a longer OS in the TPP group and the finding of residual disease in 'normal looking' peritoneum' warrants prospective evaluation of the benefit of TPP in this setting.

Clinical and Radiologic Predictors of a Pathologic Complete Response to Neoadjuvant Chemotherapy (NACT) in Patients Undergoing Cytoreductive Surgery for Colorectal Peritoneal Metastases: Results of a Prospective Multi-center Study.

BACKGROUND: Patients undergoing cytoreductive surgery for colorectal peritoneal metastases who have a pathologic complete response (pCR) to neoadjuvant chemotherapy experience a significantly longer survival than those with residual disease. This response is known only after surgery. This study aimed to examine clinical and radiologic predictors of a pCR. METHODS: From July 2018 to December 2019, the study prospectively enrolled 120 patients. The clinical and radiologic findings were compared between patients with and without a pCR. A protocol for pathologic evaluation was followed. RESULTS: A pCR was observed in 34 patients (28.3%). Receiver operating characteristic (ROC) curves showed that patients with a surgical Peritoneal Cancer Index (sPCI) of 3 or lower had an 80% probability of experiencing a pCR, and that patients with a radiologic PCI (rPCI) of 2 or lower had a 70% probability of experiencing a pCR. A pCR was correctly predicted for 47% of the patients by imaging and for 44.4% of the patients by surgical evaluation. The site of primary tumor, the timing of peritoneal metastasis (PM), histology, tumor marker positivity, and mutations in known poor prognostic genes (KRAS) did not differ between the patients with and those without pCR. The primary tumor showed residual disease in 23.5% and regional nodes in 26.4% of the patients with pCR. CONCLUSIONS: The rPCI and sPCI concurred with a pCR in less than 50% of the patients. The patients with a lower PCI had greater concordance. An sPCI of 3 or lower was predictive of a pCR in 80% of the patients. The impact of KRAS mutations on pCR should be evaluated in a larger series. The predictors of pCR and response to systemic chemotherapy should be incorporated in prognostic scores used to select patients for surgery.

Distribution of residual disease in the peritoneum following neoadjuvant chemotherapy in advanced epithelial ovarian cancer and its potential therapeutic implications.

INTRODUCTION: Residual disease in 'normal appearing' peritoneum is seen in nearly 30% of the patients following neoadjuvant chemotherapy (NACT) for advanced ovarian cancer. The goal was to study the sequence of response in different regions, the commonest sites of occult residual disease, its incidence in different peritoneal regions and the potential therapeutic implications of these. METHODS: This was a prospective multi-centre study (July 2018-June 2019). Pathological evaluation of cytoreductive surgery specimens was performed according to a fixed protocol. Prevalence of residual disease in different regions was used to study patterns of response and distribution of residual disease. RESULT: In 85 patients treated between July 2018 to June 2019, microscopic disease in 'normal appearing' peritoneal regions was seen in 22 (25.2%) and in normal peritoneum around tumor nodules in 30 (35.2%) patients. Regions 4 and 8 of Sugarbaker's PCI had the highest incidence of occult disease and regions 9 and 10 the lowest. The response to chemotherapy occurred in a similar manner in over 95%- the least common site of residual disease was the small bowel mesentery, followed by upper regions (regions 1-3), omentum and middle regions (regions 0, 4, 8), lower regions (regions 5-7) and lastly the ovaries. CONCLUSIONS: During interval CRS, based on the disease mapping provided in this manuscript, regions that have a high probability of residual disease should be explored and dissected. Complete resection of involved the peritoneal region can completely address the occult disease. The role of resection of the entire region as well as 'normal appearing' parietal peritoneal regions should be prospectively evaluated.