Enhanced recovery after surgery in cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: national survey of peri-operative practice by Indian society of peritoneal surface malignancies.

Objectives: The Enhanced recovery after surgery (ERAS) program is designed to achieve faster recovery by maintaining pre-operative organ function and reducing stress response following surgery. A two part ERAS guidelines specific for Cytoreductive surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) was recently published with intent of extending the benefit to patients with peritoneal surface malignancies. This survey was performed to examine clinicians' knowledge, practice and obstacles about ERAS implementation in patients undergoing CRS and HIPEC. Methods: Requests to participate in survey of ERAS practices were sent to 238 members of Indian Society of Peritoneal Surface malignancies (ISPSM) via email. They were requested to answer a 37-item questionnaire on elements of preoperative (n=7), intraoperative (n=10) and postoperative (n=11) practices. It also queried demographic information and individual attitudes to ERAS. Results: Data from 164 respondents were analysed. 27.4 % were aware of the formal ERAS protocol for CRS and HIPEC. 88.4 % of respondents reported implementing ERAS practices for CRS and HIPEC either, completely (20.7 %) or partially (67.7 %). The adherence to the protocol among the respondents were as follows: pre operative (55.5-97.6 %), intra operative (32.6-84.8 %) and post operative (25.6-89 %). While most respondents considered implementation of ERAS for CRS and HIPEC in the present format, 34.1 % felt certain aspects of perioperative practice have potential for improvement. The main barriers to implementation were difficulty in adhering to all elements (65.2 %), insufficient evidence to apply in clinical practice (32.4 %), safety concerns (50.6 %) and administrative issues (47.6 %). Conclusions: Majority agreed the implementation of ERAS guidelines is beneficial but are followed by HIPEC centres partially. Efforts are required to overcome barriers like improving certain aspects of perioperative practice to increase the adherence, confirming the benefit and safety of protocol with level I evidence and solving administrative issues by setting up dedicated multi-disciplinary ERAS teams.

Bowel Anastomosis After or Before HIPEC: A Comparative Study in Patients Undergoing CRS+HIPEC for Peritoneal Surface Malignancy.

BACKGROUND: Anastomotic leak after cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) remains a dreaded complication. There is no consensus statement regarding the optimal timing for bowel anastomoses to perform after or before HIPEC. METHODS: Patients who underwent CRS+HIPEC and had at least one bowel anastomosis were retrospectively analyzed to evaluate if timing of anastomosis done after or before HIPEC had an impact on bowel complication rates (anastomotic leak and perforation). RESULTS: From 2013 to 2019, 214 of 370 patients underwent CRS+HIPEC and had at least one bowel anastomosis. Of these 214 patients, 104 and 110 patients had anastomosis after and before HIPEC, respectively. A total of 324 anastomoses were performed, with a mean of 0.87 anastomoses per patient (range 1-4). The incidence of anastomotic leaks was comparable between the pre- and post-HIPEC groups (3.6% vs. 4.8%; p > 0.05), as was the bowel complication rate (7.6% vs. 7.2%). After multivariate analysis, prior surgical score >1 (odds ratio [OR] 4.3), recurrent cancers (OR 7.4), and more than two anastomosis (OR 3.8) were considered independent risk factors for bowel complications. CONCLUSION: Anastomosis of the bowel performed after or before HIPEC does not affect bowel complication rates (leak/perforation). Higher prior surgical score, surgery for recurrent cancers, and more than two bowel anastomosis are independent risk factors for predicting bowel complications. Prehabilitation, standardization of steps, immediate attention and repair of serosal tears, and thorough inspection of the bowel before closure helps to decrease bowel complications. The timing of anastomosis can be at the discretion of the surgeon.

Adaptations and Safety Modifications to Perform Safe Minimal Access Surgery (Minimally Invasive Surgery: Laparoscopy and Robotic) during the COVID-19 Pandemic.

It is inevitable that some patients with suspected or confirmed COVID-19 may require urgent surgical procedures. The objective of this review was to discuss the modifications required in the operating room during COVID-19 times for minimal access, laparoscopy, and robotic surgery, especially with regard to minimally invasive surgical instruments, buffalo filter, trocars with smoke evacuator, and special personal protection equipment. We have discussed the safety measures to be followed for the suspected or confirmed COVID-19 patient. In addition to surgical patients, health care workers should also protect themselves by following the guidelines and recommendations while treating these patients. Although there is little evidence of viral transmission through laparoscopic or open approaches, we recommend modifications to surgical practice such as the use of safe smoke evacuation and minimizing energy device use to reduce the risk of exposure to aerosolized particles to the health care team. Therefore, hospitals must follow specific protocols and arrange suitable training of the health care workers. Following well-established plans to accomplish un-deferrable surgeries in COVID-19-positive patients is strongly recommended.

Prospective Study Comparing Clinical vs Indocyanine Green Fluorescence-Based Assessment of Line of Transection in Robotic Rectal Cancer Surgery-Indian Study.

Anastomotic leakage continues to be the most feared postoperative complications in rectal surgery with negative impact on both short- and long-term outcomes. Fortunately, new surgical strategies have helped to offset this complication and improve surgical outcomes. Traditionally, perfusion is assessed by intraoperative visual judgment by the surgeon. These subjective methods lack predictive accuracy resulting in either excess or insufficient colonic resection. Indocyanine green (ICG) fluorescence has shown promise in identifying the adequacy of perfusion. After injection of ICG, the system projected high-resolution near-infrared real-time images of blood flow in mesentery and bowel wall. This novel imaging method is used intraoperatively for taking real-time informed decisions. We conducted a single institutional prospective study to identify the feasibility of ICG identification of vascularity of anastomotic site and its impact on the change of plan of surgical management in robotic rectal cancer surgery. Between September 2017 and April 2019, fifty patients undergoing robotic rectal cancer surgery were included in the study. The aim was to analyze the feasibility and clinical benefit of intraoperative near-infrared fluorescence imaging in determining the line of transection in comparison with the traditional method. Line of proximal transection of the bowel subjectively assessed by the surgical team was marked point B and that after ICG injection was marked point A if moved proximally and point C if moved distally. The vascular anatomy was clearly identified with no intraoperative or injection-related adverse effects. Of the 50 patients, the line of transaction remained the same in 6 patients (12%). Based on the fluorescence imaging, the surgical team opted for further proximal change of the transection line up to an "adequate" fluorescent portion in 3 patients (6%) and distally in 41 patients (82%). ICG-based infrared image-guided localization gives a real-time image of colon vascularity possibly affecting anastomotic leak. The ICG fluorescence imaging system is a simple, safe, and useful technique, performed within a short time, and it enables visual evaluation of the blood flow in the intestinal tract prior to anastomosis. Larger studies are needed before this can become the standard of care.

Robotic Surgery for Rectal Cancer: Hype or Hope? (Indian Experience).

The primary goal to achieve cure in oncology is to reduce recurrence, maximize disease-free survival, maintain function, and optimize quality of life. Surgery remains the mainstay treatment modality in rectal cancer. The current trend is to perform least invasive method of doing complex surgeries while not compromising in the oncological of functional outcomes of patients. Total mesorectal excision (TME) for rectal cancer surgery entails removal of the rectum with its fascia as an intact unit while preserving surrounding vital structures. The procedure is technically challenging because of the narrow and deep pelvic cavity housing the rectum encased by fatty lymph vascular tissue within the perirectal fascia, distally the anal sphincter complex, and an intimate surrounded by vital structures like ureter, vessels, and nerves. Robotic technology enables overcoming these difficulties caused by complex pelvic anatomy. This system can facilitate better preservation of the pelvic autonomic nerve and thereby achieve favorable postoperative sexual and voiding functions after rectal cancer surgery. The nerve-preserving TME technique includes identification and preservation of the superior hypogastric plexus nerve, bilateral hypogastric nerves, pelvic plexus, and neurovascular bundles.

Practice patterns, attitudes, and knowledge among clinicians regarding hyperthermic intraperitoneal chemotherapy and pressurized intraperitoneal aerosol chemotherapy: a national survey by Indian society of peritoneal surface malignancies (ISPSM).

OBJECTIVES: Perception of cytoreductive surgery (CRS), hyperthermic intraperitoneal chemotherapy (HIPEC), and pressurized intraperitoneal aerosol chemotherapy (PIPAC) for treating peritoneal surface malignancies (PSM) differ widely among physicians. METHODS: This on-site survey performed during a major oncology congress in 2019 evaluated the current opinion, perceptions, knowledge and practice of HIPEC and PIPAC among oncologists in India. RESULTS: There were 147 respondents (gynecologists (30%), surgical oncologists and gastrointestinal surgeons (64%), and medical oncologists (6%)). Whereas most respondents considered CRS and HIPEC an appropriate therapeutic option, 25% would not recommend CRS and HIPEC. The main barriers to referral to an expert center were inaccessibility to such a center (37.8%), non-inclusion of CRS and HIPEC in clinical practice guidelines (32.4%), and a high morbidity/mortality (21.6%). Variations were found in the various practice patterns of CRS/HIPEC like eligibility criteria, HIPEC protocols and safety measures. Although PIPAC awareness as a novel therapeutic option was high, only a limited number of centers offered PIPAC, mainly because of non-access to technology and missing training opportunities (76.2%). CONCLUSIONS: Lack of widespread acceptance, poor accessibility and low utilization presents a significant challenge for HIPEC and PIPAC in India. There is a need to raise the awareness of curative and palliative therapeutic options for PSM. This might be achieved by the creation of expert centers, specialized training curricula and of a new sub-speciality in oncology.

Minimally Invasive Surgery and Surgical Smoke, Decoding Fear and Ensuring Safety: Adaptations and Safety Modifications During COVID Pandemic.

The most fearful word starting from C, Cancer has now been replaced with COVID-19 owing to its associated physical, emotional and financial hardships as well as its social stigma. Never before we as medical fraternity been challenged to take care of patients and at the same time consider the safety of ourselves, family members and our fellow healthcare workers. Emotions and fear-driven treatments that are otherwise inefficacious may contribute to a false sense of security, unwarranted side-effects, divert resources and delay research into treatments that may actually work. Decoding fear with available evidence i.e. practicing evidence-based medicine will guide us in better handling of situations in this pandemic. The objective of this review is to discuss the modifications required in the operating theatre during COVID-19 times for minimal access, laparoscopy and robotic surgery, especially with regard to the handling of surgical smoke, minimally invasive surgical instruments, trocars with smoke evacuator and special personal protection equipment. Although there is no evidence of viral transmission through laparoscopic or open approaches, we recommend modifications to surgical practice such as the use of safe smoke evacuation and minimizing energy device use. We have come up with Rule of 20 for 2020 pandemic in operation theatres and modification of trocar for safe handling of surgical smoke in MIS which can be used in resource-limited settings. Hospitals must follow specific protocols and arrange suitable training of the healthcare workers. We believe that "Fears are educated into us, and can, if we wish, be educated out".

Impact of extent of parietal peritonectomy on oncological outcome after cytoreductive surgery and HIPEC.

BACKGROUND: In peritoneal surface malignancy (PSM), in spite of optimal cytoreductive surgery (CRS), majority of recurrences that occur are intraperitoneal. In patients with PSM, studies employing fluorescent imaging and microscopic examination have shown normal looking peritoneum may harbor active disease. This study was done to assess the recurrence pattern, oncological outcomes, and morbidity and mortality of the extent of peritonectomy in patients who underwent total parietal peritonectomy (TPP) or involved field peritonectomy (IFP) as a part of the procedure during CRS and hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: This was a retrospective analysis of prospectively collected data, from February 2013 to December 2017. A total of 163 patients with PSM underwent TPP or IFP with CRS plus HIPEC. Their oncological outcomes, recurrence pattern, postoperative morbidity and mortality were analyzed. RESULTS: Of the 163 cases, the primary organs of origin were ovary, colorectal, appendicular pseudomyxoma, stomach, mesothelioma and others (67.4%, 16.5%, 6.1%, 4.9%, 2% and 2%), respectively. TPP was performed in 70 patients and IFP in 93 patients. TPP group had higher mean PCI (16 vs. 14), longer duration of surgery (11 vs. 9 h), and more blood loss (1,243 vs. 675 mL). Overall G3-G4 morbidity was comparable in both groups (42.8% vs. 33.3%) as was mortality (5.7% vs. 4.4%). Kaplan-Meier analysis showed that with a median follow-up of 45 months, TPP group had a recurrence-free survival (RFS) of 26 months and overall survival (OS) was yet to be achieved, whereas the IFP group had a RFS and OS of 21 and 43 months, respectively. CONCLUSIONS: Performing TPP reduces the chance of missing the microscopic disease, therefore can minimize local recurrence, and better oncological outcomes. TPP can be performed with acceptable morbidity and mortality, at the cost of increased duration of surgery and higher blood loss.

Pressurized IntraPeritoneal Aerosol Chemotherapy vs. intravenous chemotherapy for unresectable peritoneal metastases secondary to platinum resistant ovarian cancer - study protocol for a randomized control trial.

BACKGROUND: Despite optimal surgery and appropriate first-line chemotherapy, ∼70-80 % of patients with epithelial ovarian cancer will develop disease relapse. The prognosis is poor especially for women with Platinum resistant ovarian cancer. The standard treatment for these groups of patients is non-platinum-containing chemotherapy like taxanes, anthracyclines, gemcitabine, topotecan, and trabectedin. These drugs in various combinations and sequences provide modest survival or symptomatic benefit but with significant side effects. Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) is a minimally-invasive drug-delivery technique specifically addressing limited tissue penetration and poor drug distribution with promising results. PIPAC is a novel method of delivering normothermic chemotherapy into the abdominal cavity as an aerosol under pressure. This concept seems to enhance the effectiveness of intra peritoneal chemotherapy by taking advantage of the physical properties of gas and pressure by generating an artificial pressure gradient and enhancing tissue uptake and distributing drugs homogeneously within the closed and expanded peritoneal cavity. Thus, due to the high local bioavailability during PIPAC, the chemotherapy dosage can be reduced which in turn largely prevents systemic side effects and organ toxicity. METHODS: The study aims to investigate the therapeutic efficacy measured as objective tumour response according to Response Evaluation Criteria in Solid Tumours (RECIST) criteria, of PIPAC in comparison with conventional Intravenous chemotherapy for women with recurrent platinum resistant ovarian cancer with peritoneal metastasis (PM). Consecutive patients diagnosed with PM secondary to platinum-resistant ovarian cancer will be randomized to PIPAC group or IV chemotherapy group. The primary objective of this study is to determine the efficacy after three cycles of PIPAC with cisplatin and doxorubicin in comparison with six cycles of systemic chemotherapy. The secondary outcome measures include morbidity and mortality, overall survival and disease specific survival. Analysis is by intention to treat. AIM: Assess the objective tumour response of PIPAC in comparison with systemic intravenous chemotherapy for women with platinum-resistant ovarian cancer. STUDY TYPE: Prospective randomized control intervention trial. INTERVENTION MODEL: IV Chemotherapy group (Control group) PIPAC group (Experimental group). MASKING: Open label. PRIMARY PURPOSE: Treatment. SAMPLE SIZE: Calculated sample size is 97 and rounded to 100. For each treatment group sample size of 50 will be considered. PRIMARY OUTCOME CRITERIA: Objective tumour response according to Response Evaluation Criteria in Solid Tumours (RECIST) criteria version 1.1.Secondary outcome criteria: Morbidity;Disease-specific survival (months between inclusion and death due to ovarian cancer);OS (months between inclusion and death due to any cause);CA 125 levels. DISCUSSION: PIPAC in women with platinum resistant ovarian PM has good response owing to superior tissue penetration and better drug distribution. The procedure is safe and well tolerated owing it to its minimal invasiveness. Typical side-effects of systemic chemotherapy, such as alopecia, peripheral neurotoxicity, nausea and myelosuppression are absent. We expect reduction of ascites with symptomatic relief and CA 125 levels. PIPAC is a novel technique for selected patients with platinum resistant ovarian PM and further investigation in comparative clinical trials with conventional chemotherapy will establish its role as a good palliative treatment option. ETHICS COMMITTEE APPROVAL: Obtained. STATUS: Recruiting. TRIAL REGISTRATION NUMBER: REF/2018/08/021223 Registered on Clinical Trials Registry - India (CTRI); www.ctri.nic.in.

Watson for Oncology and breast cancer treatment recommendations: agreement with an expert multidisciplinary tumor board.

Background: Breast cancer oncologists are challenged to personalize care with rapidly changing scientific evidence, drug approvals, and treatment guidelines. Artificial intelligence (AI) clinical decision-support systems (CDSSs) have the potential to help address this challenge. We report here the results of examining the level of agreement (concordance) between treatment recommendations made by the AI CDSS Watson for Oncology (WFO) and a multidisciplinary tumor board for breast cancer. Patients and methods: Treatment recommendations were provided for 638 breast cancers between 2014 and 2016 at the Manipal Comprehensive Cancer Center, Bengaluru, India. WFO provided treatment recommendations for the identical cases in 2016. A blinded second review was carried out by the center's tumor board in 2016 for all cases in which there was not agreement, to account for treatments and guidelines not available before 2016. Treatment recommendations were considered concordant if the tumor board recommendations were designated 'recommended' or 'for consideration' by WFO. Results: Treatment concordance between WFO and the multidisciplinary tumor board occurred in 93% of breast cancer cases. Subgroup analysis found that patients with stage I or IV disease were less likely to be concordant than patients with stage II or III disease. Increasing age was found to have a major impact on concordance. Concordance declined significantly (P ≤ 0.02; P < 0.001) in all age groups compared with patients <45 years of age, except for the age group 55-64 years. Receptor status was not found to affect concordance. Conclusion: Treatment recommendations made by WFO and the tumor board were highly concordant for breast cancer cases examined. Breast cancer stage and patient age had significant influence on concordance, while receptor status alone did not. This study demonstrates that the AI clinical decision-support system WFO may be a helpful tool for breast cancer treatment decision making, especially at centers where expert breast cancer resources are limited.

Randomized control trial comparing quality of life of patients with end-stage peritoneal metastasis treated with pressurized intraperitoneal aerosol chemotherapy (PIPAC) and intravenous chemotherapy.

BACKGROUND: Peritoneal metastasis (PM) is a common occurrence in gynaecological and gastrointestinal cancers and is associated with poor survival. Patients typically present with ascites, abdominal pain, malnutrition, nausea, emesis, and bowel obstruction which significantly compromise the quality of life (QoL). The treatment remains a particular challenge, with palliative systemic chemotherapy being the standard of care. However, the efficacy of systemic chemotherapy is poor but with high potential for side effects and complications. QoL plays an important role in patients with PM and is deteriorating continuously until death. Thus, there is an obvious medical need for better therapeutic options in PM for prolonging survival and preserving QoL by reducing both disease-related symptoms and therapy side effects. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel technique for delivering pressurized normothermic chemotherapy into the abdominal cavity as an aerosol. This concept seems to enhance the effectiveness of intraperitoneal chemotherapy by taking advantage of the physical properties of gas and pressure by generating an artificial pressure gradient and enhancing tissue uptake and distributing drugs homogeneously within the closed and expanded peritoneal cavity. METHODS: The primary objective of this study is to assess QoL and symptoms in a consecutive cohort of patients with PM treated with PIPAC procedure in comparison with conventional systemic intravenous chemotherapy. QoL is assessed prospectively using European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30(Version 3.0) questionnaire. QLQ-C30 is a 30-question self-administered questionnaire inquiring about global health status, 9 individual symptoms, and 5 functional scales. Baseline QoL is measured using the global physical health functional score, and symptom scores derived from EORTC QLQ30 questionnaire before starting therapy, followed by at 60, 120, and 180 days after the first intervention. Calculated sample size is 119 and rounded to 120. For each treatment group, sample size of 60 will be enrolled; Intervention model: IV chemotherapy group (control group) and PIPAC group (experimental group); Study type: prospective randomized control intervention trial. DISCUSSION: All consecutive patients diagnosed with advanced end-stage PM are randomized to be treated with PIPAC or IV chemotherapy. The primary objective of this study is to determine the QoL after three cycles of PIPAC in comparison with six cycles of systemic chemotherapy. The secondary outcome measures include morbidity and mortality. Analysis is by intention to treat. RESULTS: The effect of systemic chemotherapy remains limited on the peritoneum due to poor vascularization and low penetration. Side effects after systemic chemotherapy for PM are relatively frequent. QoL plays an important role in these patients and is deteriorating continuously due to the disease or therapy related. Thus, there is need for better therapeutic options for prolonging survival and preserving QoL by reducing both disease-related symptoms and therapy side effects. PIPAC is a novel minimally invasive repeatable treatment modality which demonstrated potentially encouraging tumour response and only minimal toxicity in patients with PM of various origins. It can optimize local drug delivery and improve clinical outcome due to superior pharmacological properties as compared to systemic chemotherapy. TRIAL REGISTRATION: REF/2018/08/021225 Registered on Clinical Trials Registry-India (CTRI); www.ctri.nic.in.

Idiopathic granulomatous mastitis: diagnostic and therapeutic challenges to general surgeon.

BACKGROUND: Idiopathic granulomatous mastitis, four decades since its first description still remains a disease of dilemma. Correct diagnosis with exclusion of various causes and appropriate treatment with surgery, antibiotics and steroids are the keys to overcome the persisting challenge that lies in management of this dilemmatic disease. MATERIAL: We report 4 cases of idiopathic granulomatous mastitis that were treated in Kannur medical college hospital. CONCLUSION: Idiopathic granulomatous mastitis is uncommon benign breast disease that can be confused with two of the very common breast conditions, breast carcinoma and breast abscess. The management of IGM needs a holistic approach with the surgeon, pathologist and radiologist working in unison to unravel the difficulties that lie in treating this disease and bringing back the smile on patients face.