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Vipul D Yagnik,1,* Baljit Kaur,2 Sushil Dawka,3 Aalam Sohal,4 Geetha R Menon,5 Pankaj Garg6,7,* 1Department of Surgical Gastroenterology, Nishtha Surgical Hospital and Research Center, Patan, Gujarat, India; 2Department of Radiology, SSRD Magnetic Resonance Imaging Institute, Chandigarh, India; 3Department of Surgery, SSR Medical College, Belle Rive, Mauritius; 4Department of Internal Medicine, University of California San Francisco (UCSF), Fresno, CA, USA; 5Department of Statistics, Indian Council of Medical Research, New Delhi, India; 6Department of Colorectal Surgery, Indus International Hospital, Mohali, Punjab, India; 7Department of Colorectal Surgery, Garg Fistula Research Institute, Panchkula, Haryana, India*These authors contributed equally to this workCorrespondence: Pankaj Garg, Department of Colorectal Surgery, Indus International Hospital, Mohali, Punjab, India, Email drgargpankaj@yahoo.comBackground: Definitive management of acute fistula-abscess (anal fistulas associated with acute abscess) is gaining popularity against the two-staged approach (early abscess drainage with deferred fistula management). However, locating an internal opening (IO) in acute fistula-abscess can be difficult. A recent protocol (Garg protocol) has been shown to be effective in managing anal fistulas with non-locatable IO.Purpose: To test the efficacy of the Garg protocol in managing acute fistula-abscess with non-locatable IO.Methods: Patients with acute fistula-abscess operated by a definitive procedure were included. A preoperative MRI was done in all patients. Patients in whom the IO was non-locatable after clinical, MRI, and intraoperative examination were managed by the three-step Garg protocol. Garg protocol: 1) Reassessment of MRI; 2) In non-horseshoe fistulas, the IO was assumed to be at the point where the fistula tract reached closest to the sphincter-complex; 3) In horseshoe fistulas, the IO was assumed to be located in the midline (anterior or posterior as per the horseshoe location). Low fistulas were treated by fistulotomy and high fistulas by a sphincter-sparing procedure. The long-term healing rate and change in continence (Vaizey scores) were evaluated.Results: A total of 201 patients with acute fistula-abscess were operated over six years, and 19 were lost to follow-up. A total of 182 patients (154-males) were followed up (median-37 months). The IO was locatable in 133/182 (73.1%) (control group) and was non-locatable in 49/182 (26.9%) (study group). The study group was managed as per the Garg protocol. The age, sex-ratio, and fistula parameters were comparable in both groups. The long-term healing rate was 112/133(84.2%) in the IO-locatable group and 43/49 (87.8%) in the IO-non-locatable group (p=0.64, not-significant). The objective continence scores did not change significantly after surgery in both groups.Conclusion: Acute fistula-abscess with non-locatable IO can be managed successfully by the Garg protocol without any risk of incontinence.Keywords: anal fistula, fistulotomy, incontinence, surgery, recurrence, abscess

Pankaj Garg,1,2 Vipul D Yagnik,3 Sushil Dawka,4 Baljit Kaur,5 Geetha R Menon6 1Department of Colorectal Surgery, Indus Super Specialty Hospital, Mohali, Punjab, India; 2Department of Colorectal Surgery, Garg Fistula Research Institute Surgery, Panchkula, Haryana, India; 3Department of Surgical Gastroenterology, Nishtha Surgical Hospital and Research Centre, Patan, Gujarat, India; 4Department of Surgery, SSR Medical College, Belle Rive, Mauritius; 5Department of Radiology, SSRD MRI Imaging Centre, Chandigarh, Haryana, India; 6National Institute of Medical Statistics, Indian Council of Medical Research, New Delhi, IndiaCorrespondence: Pankaj Garg, Department of Colorectal Surgery, Indus Super Specialty Hospital, Mohali, Punjab, 140507, India, Fax +91 9501011000, Email drgargpankaj@yahoo.comBackground: Anal fistulas cause great uncertainty and anxiety in patients and surgeons alike. This is largely because of the inability to accurately confirm postoperative fistula healing, especially long-term healing. There is no scoring system available that can objectively assess cryptoglandular anal fistulas for postoperative healing and can also accurately predict long-term healing.Methods: Several parameters that could indicate anal fistula healing were assessed. Out of these, six parameters (four MRI-based and two clinical) were finalized, and a weighted score was given to each parameter. A novel scoring system (NSS) was developed. A minimum possible score (zero) indicated complete healing whereas the maximum weighted score (n = 20) indicated confirmed non-healing. Scoring was done with postoperative MRI (at least 3 months post-surgery), then compared with the actual healing status, and subsequently correlated with the final long-term clinical outcome.Results: The NSS was validated in 183 operated cryptoglandular fistula-in-ano patients over a 3-year period in whom 283 MRIs (preoperative plus postoperative) were performed. The postoperative follow-up was 12– 48 months (median-30 months). The NSS was found to have a very high positive predictive value (98.2%) and moderately high negative predictive value (83.7%) for long-term fistula healing. Additionally, its sensitivity and specificity in predicting healing were 93.9% and 94.7%, respectively.Conclusion: Thus, this new scoring system is highly accurate and would be a useful tool for surgeons and radiologists managing anal fistulas. By objectivizing the assessment of postoperative healing, it can both ease and streamline management. Moreover, reliable prediction of recurrence-free long-term healing will greatly allay the apprehensions associated with this dreaded disease.Keywords: anal fistula, MRI, postoperative, scoring system, internal opening, healing

Pankaj Garg,1 Baljit Kaur,2 Vipul D Yagnik,3 Sushil Dawka4 1Indus Super Specialty Hospital, Mohali, India; 2Department of Radiology, SSRD MRI Centre, Chandigarh, India; 3Nishtha Surgical Hospital and Research Centre, Patan, Gujarat, India; 4SSR Medical College, Belle Rive, MauritiusCorrespondence: Pankaj GargIndus Super Specialty Hospital, Mohali, 140607, IndiaFax +91-9501011000Email drgargpankaj@yahoo.comBackground: In the anal sphincter complex, the intersphincteric space between the internal and external sphincters is the only conventionally recognized pathway for the spread of sepsis. However, there is another unrecognized space discovered on MRI, the “outer-sphincteric space”, between the external anal sphincter and its lateral fascia along which pus can spread. An abscess in the intersphincteric space is easily drained into the rectum via the transanal route and is more likely to spread into the supralevator space. Conversely, an abscess in the outer-sphincteric space is difficult to drain transanally into the rectum and is more likely to become a transsphincteric abscess/fistula.Methods: The MRIs of anal fistula patients operated over four years on intersphincteric abscesses were analyzed. The pattern of spread into the ischiorectal fossa and/or supralevator space and ease of drainage into the rectum through the transanal route were studied.Results: Thirty-six patients were operated on to drain their intersphincteric abscesses through the anal canal. Two distinct patterns were noted. Twenty patients had abscesses in the intersphincteric space, which were easily drained into the rectum. Of them, 6/20 had supralevator extension, while only 1/20 had spread to the ischiorectal fossa. In 16/36 patients, the abscess was in the outer-sphincteric space and could not be drained into the rectum. In 9/16 of these patients, pus spread into the ischiorectal fossa but supralevator spread did not happen in any patient.Conclusion: Apart from the intersphincteric space, there is perhaps another unrecognized anatomical space – the outer-sphincteric space – discovered on MRI, through which pus can spread in anal fistulas or abscesses.Keywords: anal fistula, intersphincteric, MRI, supralevator, ischiorectal fossa, outer-sphincteric

Pankaj Garg,1,2 Baljit Kaur,3 Konica Singla,2 Geetha R Menon,4 Vipul D Yagnik5 1Department of Colorectal Surgery, Indus International Hospital, Mohali, India; 2Department of Colorectal Surgery, Garg Fistula Research Institute (GFRI), Haryana, India; 3Department of Radiology, SSRD Imaging Centre, Chandigarh, India; 4Department of Biostatistics, Indian Council of Medical Research, New Delhi, India; 5Department of Surgical Gastroenterology, Nishtha Surgical Hospital and Research Centre, Patan, Gujarat, IndiaCorrespondence: Pankaj GargGarg Fistula Research Institute (GFRI), H.no- 1042, Sector-15, Panchkula, Haryana, 134113, IndiaFax +91 9501522000Email drgargpankaj@yahoo.comPurpose: In some anal fistulas, the internal/primary opening cannot be located even after examination and assessment on MRI or transrectal ultrasound. The efficacy of a simple new protocol to manage such therapeutically challenging fistulas was tested.Patients and Methods: All anal fistula patients operated consecutively over 7 years were included in the study. A simple two-step protocol was followed for fistulas in which the internal opening was not locatable after clinical examination and MRI assessment. First, the MRI was reassessed. The site where the fistula was closest to the internal sphincter was noted. It was assumed that the internal-opening was located at that position and the fistula was treated accordingly. Second, in horseshoe anal fistulas with no apparent internal opening, it was assumed that the internal opening was located in the midline. Low fistulas were treated by fistulotomy and high fistulas by a sphincter-sparing procedure. Incontinence was evaluated by objective incontinence scores (Vaizey scores).Results: A total of 757 patients were operated (median follow-up-33 months). Of these, 57 patients were excluded due to short or inadequate follow-up. In 154/700 (22%) patients, the internal opening could not be located while in 546/700 (78%), the internal opening was found. Both the groups were similar in all parameters. In the “internal-opening found” group, the fistula healed completely in 486/546 (89%) and in the ‘internal-opening not found group’, the fistula healed in 140/156 (90.9%) (p=1.01). The objective continence scores did not change significantly after surgery in both the groups.Conclusion: This new protocol seems effective as a high cure rate could be achieved in ‘internal-opening not found’ fistulas which was comparable to fistula healing in the ‘internal-opening found’ group.Keywords: anal fistula, internal opening, horseshoe, MRI, recurrence, fistula-in-ano

Rolf F Barth,1 Gong Wu,1 W Hans Meisen,2 Robin J Nakkula,1 Weilian Yang,1 Tianyao Huo,1 David A Kellough,1 Pravin Kaumaya,3–5 Claudia Turro,6 Lawrence M Agius,7 Balveen Kaur2 1Department of Pathology, 2Department of Neurological Surgery, 3Department of Obstetrics and Gynecology, 4Department of Molecular and Cellular Biochemistry, 5Department of Microbiology, 6Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH, USA; 7Department of Pathology, Mater Dei Hospital, University of Malta Medical School, Msida, Malta Abstract: The aim of this study was to evaluate four different platinated bioconjugates containing a cisplatin (cis-diamminedichloroplatinum [cis-DDP]) fragment and epidermal growth factor receptor (EGFR)-targeting moieties as potential therapeutic agents for the treatment of brain tumors using a human EGFR-expressing transfectant of the F98 rat glioma (F98EGFR) to assess their efficacy. The first two bioconjugates employed the monoclonal antibody cetuximab (C225 or Erbitux®) as the targeting moiety, and the second two used genetically engineered EGF peptides. C225-G5-Pt was produced by reacting cis-DDP with a fifth-generation polyamidoamine dendrimer (G5) and then linking it to C225 by means of two heterobifunctional reagents. The second bioconjugate (C225-PG-Pt) employed the same methodology except that polyglutamic acid was used as the carrier. The third and fourth bioconjugates used two different EGF peptides, PEP382 and PEP455, with direct coordination to the Pt center of the cis-DDP fragment. In vivo studies with C225-G5-Pt failed to demonstrate therapeutic activity following intracerebral (ic) convection-enhanced delivery (CED) to F98EGFR glioma-bearing rats. The second bioconjugate, C225-PG-Pt, failed to show in vitro cytotoxicity. Furthermore, because of its high molecular weight, we decided that lower molecular weight peptides might provide better targeting and microdistribution within the tumor. Both PEP382-Pt and PEP455-Pt bioconjugates were cytotoxic in vitro and, based on this, a pilot study was initiated using PEP455-Pt. The end point for this study was tumor size at 6 weeks following tumor cell implantation and 4 weeks following ic CED of PEP455-Pt to F98 glioma-bearing rats. Neuropathologic examination revealed that five of seven rats were either tumor-free or only had microscopic tumors at 42 days following tumor implantation compared to a mean survival time of 20.5 and 26.3 days for untreated controls. In conclusion, we have succeeded in reformatting the toxicity profile of cis-DDP and demonstrated the therapeutic efficacy of the PEP455-Pt bioconjugate in F98 glioma-bearing rats. Keywords: cisplatin, F98EGFR rat glioma, molecular targets, peptides, monoclonal antibodies

Placental Site Trophoblastic Tumor (PSTT) is a rare malignancy that often presents with extensive disease and can be resistant to traditional treatments. We present the case of a woman with stage IV PSTT who was initially managed with neoadjuvant chemotherapy followed by tumor debulking. Adjuvant therapy was guided by further pathologic analysis that revealed high levels of staining for PD-L1 as well as the presence of tumor infiltrating lymphocytes (TILs). Subsequently, the patient was treated with traditional chemotherapy with the EP/EMA regimen with the addition of pembrolizumab. The patient's treatment course was complicated by the development of pulmonary arteriovenous malformations, autoimmune thyroiditis thought to be secondary to immunotherapy, and significant tinnitus secondary to platinum agents. Currently the patient is in follow up and remains in a complete remission.

This paper describes a way to simulate and visualise 3D representations of the resultant electric field vector propagation for plane, circular and elliptically polarised waves. These polarisation states are obtained by the superposition of two coherent linearly polarised waves oscillating in two mutually perpendicular directions. The required data to obtain the simulations for these representations is generated by programming an Excel spreadsheet for polarisation equations and varying the process parameters such as phase difference and amplitude of the superimposing waves. The obtained data are then linked with Origin Pro 8.5 software to draw 3D vector plots which provide a visual aid to understanding the propagation of the electric field vector with space and time. The method can be used as an easy and effective way to understand the concept of polarisation.

This paper presents a comprehensive exploration of shock waves in a dusty plasma, incorporating the dynamics of inertial dust and ions with Maxwellian distributed electrons. By deriving the Korteweg-de Vries-Burgers (KdV-B) equation and by using its standard solution we analyze the characteristics of the shock front under varying parameters. Furthermore, we conduct a phase plane analysis to elucidate the system's behavior and dynamics by tuning in the parameters that provide various types of perturbation in the system. The investigation sheds light on the intricate behavior of shock waves in dusty plasmas and contributes valuable insights to the understanding of plasma dynamics. [ABSTRACT FROM AUTHOR]

This paper presents the usage of an Excel spreadsheet for studying charged particle dynamics in the presence of uniform electric and magnetic fields. The equation of motion of the charged particle is developed under different conditions and the data is obtained in an Excel spreadsheet under variation of parameters such as the velocity of charged particle, applied field strength and direction. For visualizing the change in trajectory of the charged particle 2D and 3D plots are further obtained by using Excel and Origin Pro8.5 graphical software's, respectively.

Excel spreadsheets are used as an excellent tool in physics laboratory experiments related to wave optics. This paper presents a simple way to simulate diffraction of waves through a slit using Excel spreadsheets without any tedious programming. These simulations are used to visualize the effect of variation of different parameters such as number of slits, wavelength of incoming light, slit width and slit separation on Fraunhofer diffraction pattern.