Evaluation of indocyanine green tracheobronchial fluorescence (ICG-TBF) via nebulization during minimally invasive esophagectomy.

Surgical manipulation of the tracheobronchial complex is a contributing factor in pulmonary morbidity of esophagectomy. Accurate dissection between membranous trachea and bronchi with esophagus is essential. This study tests the feasibility of delivering indocyanine green (ICG) in an aerosol form to achieve tracheobronchial fluorescence (ICG-TBF). Patients with esophageal and esophagogastric junction carcinoma (N = 37) undergoing minimally invasive esophagectomy (McKeown type) were included. ICG was aerosolized by nebulization in supine position before thoracoscopy. ICG-TBF was observed with real-time fluorescence-enabled camera. Intra- and postoperative complications related to ICG were the primary focus. ICG-TBF was identified in 94.6% (35/37) of patients with median time to fluorescence identification of 15 minutes (range 1-43). There were no airway injuries in the study. The ICU median stay was 2 (range 2-21) days. No intra- or postoperative complications attributable to ICG were observed. Grade 3 or 4 pulmonary complications were seen in total 8.1% patients. No 90-day postoperative mortality was seen. ICG delivered in aerosol form was found to be safe and effective in achieving ICG-TBF. It aided in accurate dissection of esophagus from the tracheobronchial complex. Further studies on effect of ICG-TBF in decreasing pulmonary complications of esophagectomy are needed.

Management of Epirubicin Extravasation Injuries of the Hand with Debridement and Flap Cover-A Case Series.

Chemotherapy extravasation injury is an iatrogenic injury due to extravasation of the drug from the vessel during infusion therapy. Among various chemotherapeutic drugs, DNA binding vesicants like epirubicin and doxorubicin can lead to extensive tissue necrosis following extravasation. They are commonly used in many chemotherapy regimens including those for carcinoma breast. We present our case series in the management of these wounds with aggressive debridement and regional (pedicled groin)/free flaps (superficial circumflex iliac artery perforator, lateral arm) for cover in five patients. All flaps healed well with patient returning to further treatment in 3 to 4 weeks post-surgery with preservation of hand function. Thus, early recognition of the type of drug that has extravasated is crucial. Regional and free flaps are superior to local flaps because there are no extra incisions and grafts on the limb that has already been injured.

Impact of Covid-19 on gastrointestinal cancer surgery: A National Survey.

PURPOSE: To understand the actual impact of the Covid-19 pandemic and frame the future strategies, we conducted a pan India survey to study the impact on the surgical management of gastrointestinal cancers. METHODS: A national multicentre survey in the form of a questionnaire from 16 tertiary care gastrointestinal oncology centres across India was conducted from January 2019 to June 2021 that was divided into a 15-month pre-Covid era and a similar period of active Covid pandemic era. RESULTS: There was significant disruption of services; 13 (81%) centres worked as dedicated Covid care centres and 43% reported suspension of essential care for more than 6 months. In active Covid phase, there was a 14.5% decrease in registrations and proportion of decrease was highest in the centres from South zone (22%). There was decrease in resections across all organ systems; maximum reduction was noted in hepatic resections (33%) followed by oesophageal and gastric resections (31 and 25% respectively). There was minimal decrease in colorectal resections (5%). A total of 584 (7.1%) patients had either active Covid-19 infection or developed infection in the post-operative period or had recovered from Covid-19 infection. Only 3 (18%) centres reported higher morbidity, while the rest of the centres reported similar or lower morbidity rates when compared to pre-Covid phase; however, 6 (37%) centres reported slightly higher mortality in the active Covid phase. CONCLUSION: Covid-19 pandemic resulted in significant reduction in new cancer registrations and elective gastrointestinal cancer surgeries. Perioperative morbidity remained similar despite 7.1% perioperative Covid 19 exposure.

Impact of COVID-19 on cancer care in India: a cohort study.

BACKGROUND: The COVID-19 pandemic has disrupted health-care systems, leading to concerns about its subsequent impact on non-COVID disease conditions. The diagnosis and management of cancer is time sensitive and is likely to be substantially affected by these disruptions. We aimed to assess the impact of the COVID-19 pandemic on cancer care in India. METHODS: We did an ambidirectional cohort study at 41 cancer centres across India that were members of the National Cancer Grid of India to compare provision of oncology services between March 1 and May 31, 2020, with the same time period in 2019. We collected data on new patient registrations, number of patients visiting outpatient clinics, hospital admissions, day care admissions for chemotherapy, minor and major surgeries, patients accessing radiotherapy, diagnostic tests done (pathology reports, CT scans, MRI scans), and palliative care referrals. We also obtained estimates from participating centres on cancer screening, research, and educational activities (teaching of postgraduate students and trainees). We calculated proportional reductions in the provision of oncology services in 2020, compared with 2019. FINDINGS: Between March 1 and May 31, 2020, the number of new patients registered decreased from 112 270 to 51 760 (54% reduction), patients who had follow-up visits decreased from 634 745 to 340 984 (46% reduction), hospital admissions decreased from 88 801 to 56 885 (36% reduction), outpatient chemotherapy decreased from 173634 to 109 107 (37% reduction), the number of major surgeries decreased from 17 120 to 8677 (49% reduction), minor surgeries from 18 004 to 8630 (52% reduction), patients accessing radiotherapy from 51 142 to 39 365 (23% reduction), pathological diagnostic tests from 398 373 to 246 616 (38% reduction), number of radiological diagnostic tests from 93 449 to 53 560 (43% reduction), and palliative care referrals from 19 474 to 13 890 (29% reduction). These reductions were even more marked between April and May, 2020. Cancer screening was stopped completely or was functioning at less than 25% of usual capacity at more than 70% of centres during these months. Reductions in the provision of oncology services were higher for centres in tier 1 cities (larger cities) than tier 2 and 3 cities (smaller cities). INTERPRETATION: The COVID-19 pandemic has had considerable impact on the delivery of oncology services in India. The long-term impact of cessation of cancer screening and delayed hospital visits on cancer stage migration and outcomes are likely to be substantial. FUNDING: None. TRANSLATION: For the Hindi translation of the abstract see Supplementary Materials section.

Fluorescence-guided cancer surgery-A new paradigm.

Fluorescence-guided surgery is an emerging and promising operative adjunct to assist the surgeon in various aspects of oncosurgery, ranging from assessing perfusion, identification, and characterization of tumors and peritoneal metastases, mapping of lymph nodes/leaks, and assistance for fluorescence-guided surgery (FGS). This study aims to provide an overview of principles, currently available dyes, platforms, and surgical applications and summarizes the available literature on the utility of FGS with a focus on abdomino-thoracic malignancies.

Successful Salvage of Partial Gastric Conduit Necrosis by Primary Anastomosis in a Post-Esophagectomy Patient.

Gastric conduit necrosis is a rare but severe complication of esophageal surgery, often associated with mediastinal sepsis and high morbidity and mortality rates, as well as reduced efficacy of conservative treatments. In most cases, management involves salvage therapy, including fluid resuscitation, antibiotics, aggressive debridement, drainage of infected collections, and proximal esophageal diversion. Primary anastomosis is rarely performed. We describe a successful case wherein we salvaged a patient following a McKeown esophagectomy and gastric pull-up, who developed partial full-thickness necrosis of the gastric conduit postoperatively, along with pleural and mediastinal sepsis. We managed this situation through thoracic debridement, take-down of the anastomosis, resection of the devitalized segment of the conduit, and primary esophagogastric anastomosis. Conduit perfusion was demonstrated using ICG fluorescent angiography. This case illustrates that, once debridement and sepsis control are achieved, a primary anastomosis, if feasible, can be safely performed, potentially avoiding a two-step procedure and a second laparotomy/thoracotomy.

Grossing to reporting of Wilms tumor with emphasis on proper sampling in treatment-naive and postchemotherapy specimens and their clinicopathological correlation with outcome.

Context: Emphasis on grossing to reporting for the assessment of histopathological parameters predicting outcomes in Wilms tumor. Aims: To analyze various clinicopathological parameters that effect outcomes in treatment naïve and post chemotherapy Wilms tumor specimens. Settings and Design: This was a retrospective observational study. Subjects and Methods: All patients diagnosed with Wilms tumor between 2012 and 2018 at our institute will be included with their clinical findings, laboratory reports, and radiological findings. The patients will be categorized into two groups based on treatment protocol (Society of Pediatric Oncology (SIOP) or the National Wilms Tumor Study Group/Children's Oncology Group (COG) guidelines) used. Details of Grossing and reporting protocols used for the in pre treatment and post treatment specimens will be analyzed. Follow-up till December 2020 will be analyzed. Statistical Analysis Used: Chi-square and Fisher's exact tests were used for statistical analysis. Results: A total of 36 patients with the diagnosis of Wilms tumor were included in the present study. The mean age of presentation was 3.9 ± 0.7 years, and males were more common than females. Most of them presented as abdominal mass and few with isolated hematuria. Twenty-six (72%) patients were treated under SIOP protocol with preoperative neoadjuvant chemotherapy. Ten patients underwent upfront surgery as per COG protocol. In SIOP group patients, the mean tumor size was 9.3cm. Forty percent (n = 10) we mixed histological type followed by blastemal type constituting (32%, n = 8). Regressive and epithelial histological types constituted 16% (n = 4) and 12% (n = 3), respectively. In the SIOP group 72% (n = 19) had no anaplasia and 28% (n = 7) had anaplasia. Fifty seven percent (n = 15) cases were Stage I, followed by 26.9% n = 7) and 11.5% (n = 3) being Stage II and Stage III, respectively. Ten patients underwent upfront surgery as per COG protocol. The mean tumor size among this group was 8 cm ranging from 7 cm to 11 cm. Eight (80%) cases had favorable histology and two cases showed focal anaplasia. Heterologous differentiation is seen in 3 (70%). Out of the 10 cases, one case was Stage I, six were Stage 2, one was Stage III, and two were clinical Stage IV. None of the cases showed either vessel or lymph node metastasis. All the patients received adjuvant chemotherapy postsurgery and were followed up till December 2020 for (at least 3 years). Of 25 patients in the SIOP group, 18 (72%) had complete remission with no radiological evidence of residual disease. Of the 10 patients in the COG group, 6 (70%) had complete remission. Conclusions: Histopathological evaluation of Wilms tumor is a critical aspect in the management of Wilms tumor, as tumor characteristics are different in the tumors treated under SIOP and COG protocols, which will ultimately affect the prognostic risk stratification. This necessitates the knowledge of the important grossing and reporting of these tumors under the two protocols.

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.

Use of Indocyanine Green Fluorescence Imaging in Thoracic and Esophageal Surgery.

BACKGROUND: Fluorescence imaging using indocyanine green in thoracic and esophageal surgery is gaining popularity because of the potential to facilitate surgical planning, to stage disease, and to reduce postoperative complications. To optimize use of fluorescence imaging in thoracic and esophageal surgery, an expert panel sought to establish a set of recommendations at a consensus meeting. METHODS: The panel included 12 experts in thoracic and upper gastrointestinal surgery from Asia-Pacific countries. Before meeting, 7 focus areas were defined: intersegmental plane identification for sublobar resections; pulmonary nodule localization; lung tumor detection; bullous lesion detection; lymphatic mapping of lung tumors; evaluation of gastric conduit perfusion; and lymphatic mapping in esophageal surgical procedures. A literature search of the PubMed database was conducted using keywords indocyanine green, fluorescence, thoracic, surgery, and esophagectomy. At the meeting, panelists addressed each focus area by discussing the most relevant evidence and their clinical experiences. Consensus statements were derived from the proceedings, followed by further discussions, revisions, finalization, and unanimous agreement. Each statement was assigned a level of evidence and a grade of recommendation. RESULTS: A total of 9 consensus recommendations were established. Identification of the intersegmental plane for sublobar resections, localization of pulmonary nodules, lymphatic mapping in lung tumors, and assessment of gastric conduit perfusion were applications of fluorescence imaging that have the most robust current evidence. CONCLUSIONS: Based on best available evidence and expert opinions, these consensus recommendations may facilitate thoracic and esophageal surgery using fluorescence imaging.

Blumer's Shelf on Laparoscopy.

Blumer's shelf indicates metastatic tumor deposit in rectouterine, or rectovesical pouch on digital rectal or vaginal examination, frequently from stomach, pancreatic, colon, or lung cancer. It underscores the need to carry out  a thorough clinical examination. Though it is much discussed and described in the literature, there are hardly any article or image about its appearance  on laparoscopy. We describe a case  of gastric cancer with Blumer's shelf and its appearance on laparoscopy with clinical and radiological correlation.

Thoracic Duct Lymphography by Near-Infrared Indocyanine Green Fluorescence imaging in Thoracic Surgery. A Review.

Near-infrared (NIR) fluorescence imaging with indocyanine green dye (ICG) is an emerging technology in detecting the anatomy of the thoracic duct; hence, it can be useful for the identification of the thoracic duct in real time and prevention of its injury during thoracic surgery. It helps to localize thoracic duct injury, identifying chyle leaks in difficult, recurrent, and refractory cases. This review paper provides insights regarding the current applications, advantages, and potential developments of NIR fluorescence imaging with ICG in recognizing thoracic duct during thoracic surgery.

Laparoscopic Repair of Acute Post-Esophagectomy Diaphragmatic Herniation Following Minimal Access Esophagectomy.

This study's objective was to assess the presentation, incidence, operative approach, and outcomes of acute symptomatic post-esophagectomy diaphragmatic hernia (PEDH), following minimal access esophagectomy (MAE) for esophageal and gastro-esophageal junctional cancer. Between January 2010 and December 2020, all consecutive patients undergoing esophagectomy were retrospectively analyzed. Acute symptomatic PEDH occurred in 4 patients out of 680 consecutive patients undergoing esophagectomy (0.58%) and 636 MAE (0.63%). All patients were men, with a median age of 56.5 years, and underwent minimal access transhiatal resection. The presentation was varied; 2 had restlessness, agitation, and tachycardia; one acute respiratory distress; and the last was asymptomatic but had reduced air entry over left hemithorax with unexplained hypoxia. All had transverse colon herniation into the left hemithorax. Herniated viscera were reduced with closure of hiatal defect, 3 underwent laparoscopic repair, and one needed laparotomy. Meshplasty or bowel resection was not required. The median hospital stay was 9 days with no perioperative mortality. The major complications (Clavien-Dindo grade ≥ IIIa) occurred in 2 patients. One patient was lost to follow-up, 2 died of disease after a year and 15 months post-procedure, and one is doing well at 10 months without any relapse of hernia. Acute symptomatic PEDH is a rare complication after transhiatal esophagectomy and mainly occurs in the left hemithorax. The incidence appears to be less than 1% after MAE. Laparoscopic repair is feasible in most cases. We recommend routine assessment of hiatus and tightening of hiatus to snuggly accommodate the gastric conduit.

Minimal Invasive Esophagectomy-a New Dawn of EsophagealSurgery.

Surgery is the mainstay of esophageal cancer. However, esophagectomy is a major surgical trauma on a patient with high morbidity and mortality. The intent of minimally invasive esophagectomy (MIE) is to decrease the degree of surgical trauma and perioperative morbidity associated with open surgery, and provide faster recovery and shorter hospital stay with the equivalent oncological outcome. It also allows for lesser pulmonary morbidity, less blood loss, less pain, and a better quality of life. MIE is safe and effective but has a steep learning curve with high technical expertise. Recently, it is increasingly accepted and adopted all over the globe. In this article, we discuss the safety, efficacy, short-term, and oncological outcomes of thoracoscopic- and laparoscopic-assisted minimally invasive esophagectomy and robotic surgery compared with open esophagectomy with a special focus on the Indian perspective.

The Utility of Indocyanine Green Angiography in the Assessment of Perfusion of Gastric Conduit and Proximal Esophageal Stump Against Visual Assessment in Patients Undergoing Esophagectomy: a Prospective Study.

Post esophagectomy anastomotic leakage is a crucial factor in determining morbidity and mortality. Good vascularity of the gastric conduit is essential to avoid this complication. This prospective study compares the utility of intraoperative indocyanine green (ICG) fluorescence angiography and visual assessment in assessing the vascularity of gastric conduit and proximal esophageal stump in patients undergoing esophagectomy. Thirteen consecutive patients who underwent esophagectomy for carcinoma middle, lower third esophagus or gastro-esophageal junction from August 2019 to September 2019 were included. Three patients underwent laparoscopic-assisted transhiatal esophagectomy, ten thoraco-laparoscopic-assisted esophagectomy. Reconstruction was done by gastric pull-up via posterior mediastinal route. All patients underwent assessment of perfusion of gastric conduit and proximal esophageal stump by ICG angiography and by visual assessment based on inspection of the color, the palpation of warmth, pulse, and bleeding from the edges. Visual assessment revealed the tip of the gastric conduit was dusky and ischemic in 11 patients, pink and well perfused in two. ICG fluorescence imaging showed inadequate perfusion at the tip of conduit in 12 patients, adequate in one, overall requiring revision in 12 cases. There was a discrepancy in one patient where visual inspection showed adequate perfusion, but ICG disclosed poor vascularity requiring revision of the conduit's tip. Resection of the devitalized portion of the proximal esophageal stump was needed in 5 patients both by visual and by ICG assessment. The median time to appearance of blush from the time of injection of dye was 15 s (10 to 23 s). In all the cases, the pattern of blush was simultaneous, with the concurrent appearance of ICG blush in the gastric conduit and gastro-epiploic arcade. No anastomotic leaks were noted. Visual inspection of the gastric conduit vascularity can underestimate perfusion and hence can compromise resection of the devitalized part. ICG fluorescence imaging is an accurate and promising means to ascertain the vascularity of gastric conduit during an esophagectomy. But its utility needs to be validated in randomized trials.

Flickering diaphragm sign, an indicator of laparoscopy-associated pneumothorax secondary to pleural breach.

During laparoscopic mobilisation of the oesophagus around hiatus in transhiatal oesophagectomy; commonly the pleura is breached causing iatrogenic pneumothorax. Often small breaches in pleura goes unnoticed till the attention is drawn by anaesthetist when pressures drop with building up of end-tidal CO2(etCO2) and other haemodynamic changes occur. We describe the flickering movements of the diaphragm associated with the pleural breach, a useful sign to alert the surgeon and anaesthetist to detect pneumothorax earlier than it is clinically evident.

Short-term Outcomes in Patients with Carcinoma of the Esophagus and Gastroesophageal Junction Receiving Neoadjuvant Chemotherapy or Chemoradiation before Surgery. A Prospective Study.

BACKGROUND: Neoadjuvant chemotherapy (NACT) and neoadjuvant chemoradiotherapy (NACRT) have been demonstrated to improve survival compared to surgery alone in esophageal carcinoma, but the evidence is scarce on which of these therapies is more beneficial, particularly with regard to resectability rates, postoperative morbidity and mortality, and histological responses. OBJECTIVE: This study compares the resectability, pathological response rates, and short-term surgical outcomes in patients with carcinoma of the esophagus or gastroesophageal junction receiving NACT or NACRT prior to surgery. METHODS: Patients with resectable carcinoma of the esophagus or gastroesophageal junction adenocarcinoma, squamous cell carcinoma, and adenosquamous histologies were enrolled in this well-matched prospective non-randomized study. Thirty-five patients were given NACT, and 35 NACRT. In the NACT group, 25 patients received three cycles of three-weekly carboplatin and paclitaxel, and 10 received three cycles of cisplatin/5-fluorouracil, while all the patients in the NACRT group received 41.4 Gy of radiotherapy concomitant with five cycles of weekly paclitaxel and carboplatin-based chemotherapy. RESULTS: Twenty-two patients in the NACT group and 33 patients in NACRT group had resection (P value = 0.0027). The percentage of microscopically margin-negative resection (R0 resection) was similar in both the groups (86% versus 88%). The incidences of surgical and non-surgical complications were similar in both the groups (P=0.34). There was no 30-day mortality. There was a trend toward more pathological complete regression in the NACRT group (P=0.067). The percentage of patients achieving complete tumor regression at the primary site (pT0) was significantly higher in the NACRT group. The down-staging effect on nodal status was similar in both the groups (P=0.55). There was a statistically significant reduction in tumor size in the NACRT group. The median numbers of nodes harvested and positive nodes were similar in both the groups. CONCLUSION: Patients receiving NACRT had better resectability rates and pathological response rates, but similar postoperative morbidity compared to the NACT group.

Uterine Sarcomas: Experience from a Tertiary Cancer Care Center from India.

Uterine sarcomas are uncommon and aggressive tumors comprising 3-7% of all uterine malignancies. The aim is to evaluate clinical presentation, histopathologic pattern, recurrence pattern, and outcome of patients with uterine sarcomas presenting to a tertiary care cancer center over an 8-year period. A total of 11 cases of uterine sarcoma were diagnosed. The median age of patients at presentation was 51 years (range 30-67 years). Six patients had leiomyosarcoma (54.5%), 4 had endometrial stromal sarcoma (36%), and 1 had adenosarcoma (9%). The main presenting symptoms were abnormal vaginal bleeding, low abdominal pain, and white discharge. Median follow-up was 11 months ranging from 3 to 200 months. Median survivals for leiomyosarcoma, endometrial stromal sarcoma, and adenosarcoma were 6.5, 18, and 56 months. The 3- and 5-year survival by Kaplan-Meier survival analysis of the entire cohort was 30 and 20%. The mitotic index, age, adjuvant therapy (chemotherapy, radiotherapy), and performance of pelvic nodal dissection did not impact survival significantly in the patient with leiomyosarcoma. Stage and histology had the strongest bearing on survival and leiomyosarcoma has the worst survival, whereas adenosarcoma had the best prognosis. Adequately powered prospective studies are required to define the role of radiation therapy and chemotherapy in this rare disease.

Anorectal Malignant Melanoma-Defining the Optimal Surgical Treatment and Prognostic Factors.

Patients with anorectal malignant melanoma (ARMM) have a poor prognosis. Optimal surgical treatment is not defined. The aim of the study was to define the surgical treatment for ARMM, to compare the overall survival (OS) of abdomino-perineal resection (APR) and wide local excision (WLE) and to study various prognostic factors. Thirty patients of ARMM were managed, 20 with locoregional disease, 10 metastatic. Of the 20 patients with locoregional disease, 15 underwent APR and 5 WLE. The 1-, 2-, 3-, and 4-year overall survival rates (by Kaplan-Meier survival analysis) in the APR group were 67, 40, 40, and 32%, and in WLE group were 100, 100, 67, and 67% respectively. Median survival for APR and WLE groups were 13 and 36 months and were not significant (p 0.48). Node-negative patients had better survival than node positive in the APR group (56 vs. 13 months) (p 0.017). Patients with tumor size < 2cm, lymphovascular invasion and perineural invasion negative, and margin-negative and with superficial infiltration had a trend toward better survival than their counterparts. WLE gives an equivalent oncological outcome and can be offered for patients with smaller ARMM and APR for locally advanced, larger tumors or as a salvage following recurrence after WLE.