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MBBS, MD (Pathology),
Sanjay Gandhi institute of trauma and orthopedics,
Bengaluru.
On Aug 2018




Dr. Mamta Gupta,
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Reviewing articles is no less a pain staking process and requires in depth perception, knowledge about the topic for review. It requires time and concentration, yet I enjoy doing it. The JCDR website especially for the reviewers is quite user friendly. My suggestions for improving the journal is, more strict review process, so that only high quality articles are published. I find a a good number of articles in Obst. Gynae, hence, a new journal for this specialty titled JCDR-OG can be started. May be a bimonthly or quarterly publication to begin with. Only selected articles should find a place in it.
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Dr. Mamta Gupta
Consultant
(Ex HOD Obs &Gynae, Hindu Rao Hospital and associated NDMC Medical College, Delhi)
Aug 2018




Dr. Rajendra Kumar Ghritlaharey

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Salient features of the JCDR: It is a biomedical, multidisciplinary (including all medical and dental specialities), e-journal, with wide scope and extensive author support. At the same time, a free text of manuscript is available in HTML and PDF format. There is fast growing authorship and readership with JCDR as this can be judged by the number of articles published in it i e; in Feb 2007 of its first issue, it contained 5 articles only, and now in its recent volume published in April 2011, it contained 67 manuscripts. This e-journal is fulfilling the commitments and objectives sincerely, (as stated by Editor-in-chief in his preface to first edition) i e; to encourage physicians through the internet, especially from the developing countries who witness a spectrum of disease and acquire a wealth of knowledge to publish their experiences to benefit the medical community in patients care. I also feel that many of us have work of substance, newer ideas, adequate clinical materials but poor in medical writing and hesitation to submit the work and need help. JCDR provides authors help in this regards.
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Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
E-mail: drrajendrak1@rediffmail.com
On May 11,2011




Dr. Shankar P.R.

"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
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Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."



Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
E-mail: ravi.dr.shankar@gmail.com
On April 2011
Anuradha

Dear team JCDR, I would like to thank you for the very professional and polite service provided by everyone at JCDR. While i have been in the field of writing and editing for sometime, this has been my first attempt in publishing a scientific paper.Thank you for hand-holding me through the process.


Dr. Anuradha
E-mail: anuradha2nittur@gmail.com
On Jan 2020

Important Notice

Case report
Year : 2022 | Month : August | Volume : 16 | Issue : 8 | Page : XD01 - XD04 Full Version

Co-existence of Head and Neck Squamous Cell Carcinoma with Sinonasal Mucormycosis: Therapeutical Challenges


Published: August 1, 2022 | DOI: https://doi.org/10.7860/JCDR/2022/53093.16776
Nitin Sharma, Dushyant Mandlik, Purvi Patel, Aditya Joshipura, Kaustubh Patel

1. Consultant, Department of Head and Neck and Endoscopic Skullbase Surgery, HCG Cancer Centre, Ahmedabad, Gujarat, India. 2. Consultant, Department of Head and Neck and Skullbase Surgery, HCG Cancer Centre, Ahmedabad, Gujarat, India. 3. Consultant, Department of Head and Neck and Endoscopic Skullbase Surgery, HCG Cancer Centre, Ahmedabad, Gujarat, India. 4. Consultant, Department of Head and Neck and Skullbase Surgery, HCG Cancer Centre, Ahmedabad, Gujarat, India. 5. Head, Department of Head and Neck and Endoscopic Skullbase Surgery, HCG Cancer Centre, Ahmedabad, Gujarat, India.

Correspondence Address :
Dr. Nitin Sharma,
First Floor opd Tower, HCG Cancer Centre, Sola, Ahmedabad, Gujarat, India.
E-mail: nitinentkota@yahoo.com

Abstract

Pandemic was new experience for entire humanity. Medical fraternity was no exception. The cases of mucormycosis were on the rise during the second wave of the pandemic. Presented here are two cases which were combination of two diseases, one of which was squamous cell carcinoma of head and neck region (49-year-old male) and other one was sinonasal mucormycosis (56-year-old male). Both patients were diabetics and had history of Coronavirus Disease-2019 (COVID-19) infection in past. Our literature search doesn’t reveal any previously reported cases of this rare combination. There were certain challenges in management. Both diseases were lethal and treatment of one cannot be prioritised over other. Challenges in managing those cases were, reconstruction planning, perioperative management and postsurgery adjuvant therapy. In absence of previous experience to treat this combination or any literature available new treatment protocol were formulated. Cases were discussed in multidisciplinary team meetings and treatment plans were formulated. Mucormycosis and oral squamous cell carcinoma both were operated and reconstructed in same sitting. In one patient revision endoscopic debridement had to be done. Amphotericin B was started once diagnosis was confirmed. Patients were followed-up on weekly basis during first month and imaging was done every 15 days. Both patients had satisfactory recovery without any sign of progression of mucormycosis. Adjuvant radiation was given in both cases at appropriate time. At follow-up both patients were free from disease for six months. From these unique experiences it can be recommended that combination of sinonasal mucormycosis and squamous cell carcinoma of head and neck is very rare. Both diseases can be treated simultaneously. excision and reconstruction can be done in single sitting. There is no need to delay or avoid adjuvant radiation. Multidisciplinary team approach is the key for treatment.

Keywords

Amphotericin B, Oral squamous cell carcinoma, Reconstruction planning

Case Report

Case 1

A 49-year-old male patient presented to Department of Head and Neck Surgery with complaints of swelling at the left angle of the mandible for the last one month. His swelling was progressively increasing in size and was absolutely painless. He was chronic tobacco chewer. Diabetes Mellitus was diagnosed three months back and the patient was on antidiabetic medication. He also had history of COVID-19 infection three months back. Family history was insignificant. On examination, there was a swelling at level Ib on the left side of neck. Swelling was 4×4 centimetres in size. It was solid, hard with irregular edges, and fixed to underlying muscles. Skin over swelling was normal. Nothing abnormal was found in oral cavity.

The patient underwent Positron Emission Tomography and Computed Tomography (PET-CT) scan which was suggestive of Fluorodeoxyglucose (FDG) avid mass at left level Ib, level II, and level III. The mass was adherent to tail of parotid gland, sternocleidomastoid muscle, and submandibular gland. There was inflammatory mucosal thickening in left maxillary sinus with an unexplained defect in medial wall of left maxillary sinus and non FDG avid fullness in left pterygopalatine fossa (Table/Fig 1),(Table/Fig 2). Provisional diagnosis of squamous cell carcinoma of nasal cavity with cervical node metastasis was made. Differential diagnosis included co-existing inverted papilloma or sinonasal mucormycosis with separate cervical pathology like metastatic neck disease, tubercular lymphadenitis, lymphoma.

His Fine Needle Aspiration Cytology (FNAC) from left side of neck showed few clusters and singly dissociated atypical squamous cells and hyperchromatic nuclei suggesting keratinising squamous cell carcinoma metastatic type.Treatment plan was to do superficial parotidectomy with left extended radical neck dissection for metastatic squamous cell carcinoma. Multiple samples were to be taken for frozen section and direct microscopy from suspected areas of left nasal cavity. If the microscopy suggested malignant then maxillectomy would be done. If mucormycosis was positive then endoscopic nasal debridement, if inverted papilloma then medial maxillectomy would be done.

The patient underwent left superficial parotidectomy with left extended radical neck dissection. Multiple endoscopic biopsies were taken from medial wall of maxillary sinus, maxillary sinus mucosa, and pterygopalatine fossa. Light microscopic examination of tissue from medial wall of left maxillary sinus was reported as “aseptate fungus” which was suggestive of mucormycosis. Tissue from pterygopalatine fossa and mucosa from maxillary sinus were reported negative. Endoscopic nasal debridement including medial maxillectomy, pterygopalatine fossa clearance anterior and posterior ethamoidectomy was done to complete the procedure. Reconstruction of neck was done with pectoralis major myocutaneous flap. Separate instruments were used for both procedures. During postoperative period nasal saline nasal wash was given every two hourly.

On postoperative day two histopathology (Table/Fig 3) and culture both confirmed the invasive mucormycosis infection. Patient was started with liposomal Amphotericin B from the second day onwards and was discharged after five postoperative days in stable condition to another multispecialty hospital for further antifungal treatment. He was followed-up clinically every week for one month and monthly thereafter. Imaging was done every 15 days for 45 days then on sos basis later. His final histopathology was suggestive of sinonasal mucormycosis with metastatic moderately differentiated squamous cell carcinoma (Table/Fig 4) with extra nodal extension T0N3B. Later clinical followed-up was done on monthly basis. He received 30 fractions and 60 grays of radiation. Chemotherapy was not given to avoid the combined side-effects of amphotericin B and chemotherapy. After adjuvant treatment patient was followed-up on monthly basis. Imaging was done after six months which was reported normal (Table/Fig 5),(Table/Fig 6).

Case 2

A 56-year-old male patient presented at Department of Head and Neck Surgery with complaint of non healing ulcer in oral cavity for three months. The patient gave history of pain at right infraorbital region for two days. Ulcer was progressively increasing in size and was associated with trismus. The patient gave history of COVID-19 infection two months back. Diabetes mellitus and hypertension were two associated co-morbidities for last 6 and 7 years, respectively and was on medication for both. He had habit of tobacco chewing for last 25 years. Family history was not significant. He was diagnosed as moderately differentiated squamous cell carcinoma right buccal mucosa on the basis of the biopsy done two months back. Two cycles of neoadjuvant chemotherapy was given elsewhere (carboplatin, 5 flurouracil, paclitaxal).

On examination there was a proliferative lesion at right buccal mucosa which was involving skin of cheek with palpable IB node. Right infra orbital region was tender. Blackish brown necrotic material in right nasal cavity at inferior turbinate was noticed on diagnostic nasal endoscopy. Nasal tissue was sampled and sent for histopathological examination, direct microscopy and fungal culture.

He underwent contrast enhanced MRI scan with gadolinium contrast which was reported 52×40×41 millimetres (mms) lesion at right buccal mucosa, lower gingivo-buccal sulcus (GBS) with erosion of mandible. There were multiple enlarged right IB and level II nodes. 34×15×13 mms irregular non enhancing area was seen involving right ethmoid sinus, nasal septum, and inferior turbinate (Table/Fig 7).

Provisional diagnosis of sinonasal mucormycosis with squamous cell carcinoma righ buccal mucosa with metastatic neck disease was given. Differential diagnosis included inverted papilloma, angiofibroma, squamous cell carcinoma and rhinosporidiosis of nasal cavity with squamous cell carcinoma of the right buccal mucosa with metastatic neck disease.

Direct microscopy and histopathology both confirmed presence of aseptate fungus which was suggestive of mucormycosis (Table/Fig 8).

Treatment plan was surgery followed by medical management with amphotericin B with appropriate adjuvant treatment.

He underwent right composite resection (full thickness right buccal mucosa, right segmental mandibulectomy with limited Infra Temporal Fossa (ITF) clearance with right supra omohyoid neck dissection with sinonasal debridement and medial maxillectomy and antero-lateral thigh flap reconstruction under general anaesthesia. Liberal saline wash was given to avoid cross contamination and separate instruments were used for both procedures.

On the next day he was started with liposomal amphotericin B under supervision of a physician. During postoperative period nasal wash was given every two hourly.

On postoperative day two he complained of severe right infra orbital pain which was not responsive to analgesics. On third postoperative day revision endoscopic debridement was performed. His pain subsided after the second surgery. His postoperative period of seven days was uneventful and was transferred to the Government medical hospital for liposomal amphotericin B later. He was kept on weekly follow-up. Contrast enhanced MRI was advised every 15 days for three times. His postoperative follow-ups were normal and MR studies remained static. Final histopathology was reported as moderately differentiated squamous cell carcinoma right buccal mucosa (Table/Fig 9) with sinonasal mucormycosis. Multiple positive nodes at Ib and level 2 (T4aN3b AJCC).

This patient was also a candidate for chemoradiation. Joint discussion with a medical and radiation oncologist was done. To avoid combined side-effects of amphotericin B and chemotherapy finally he received 60 grays and 30 fractions of Intensity Modulated Radiation Therapy (IMRT) instead of concurrent chemoradiation. He was being followed clinically on monthly basis and imaging was done after six months which was reported normal postsurgical status without any active disease (Table/Fig 10).

Discussion

Squamous cell carcinoma of the oral cavity is very common in India, especially in the central or western part of the country (1). Surgery at an early stage of disease is one of the prime factors which determines prognosis (2). So it is recommended that surgery should be done as soon as possible. On the other hand, mucormycosis is a life-threatening condition characterised by rapid progression and high mortality from 50-100% (3). Mucormycosis is caused by various fungi from order mucorales. Sign and symptoms of sinonasal mucormycosis includes nasal discharge/crusting, facial pain, proptosis and loss of vision (4). Mucormycosis occurs in two forms: invasive which is fulminant and the other one non invasive. Patients with leukaemia, neutropenia, diabetes mellitus, acute renal failure, antineoplastic medication and immunocompromised states are more at risk (5).

Literature search didn’t yield any previous papers or case reports where both diseases were found in one patient at the same time. Sinonasal mucormycosis and squamous cell carcinoma are individually rare diseases. Combination of these two diseases is rarer. Countrywide vaccination, infrastructure development, understanding of pathogenesis of development of mucormycosis has enabled us to prevent future COVID-19 outbreaks and mucormycosis. Because of the same reason we may not find this rare combination in future.

The challenges were:

• No guidelines available to manage simultaneous occurrence of sinonasal mucormycosis and oral squamous cell carcinoma.
• Should treatment of one is to be prioritised over other or simultaneous treatment possible?
• Can mucormycosis infection cause destruction of reconstructive surgery? Should we postpone the Reconstruction to the second stage?

commencement of treatment (7). Similarly biopsy/direct microscopy or fungal culture is required to start amphotericin B treatment (8). Once radiologist suspected, samples were taken to prove the synchronous occurrence of squamous cell carcinoma and sinonasal mucormycosis.

Counselling and Consent for Treatment

In the light of the present knowledge, we can assume presence of mucormycosis with squamous cell carcinoma may increase the chances of failure of flap (9), requirement of recurrent debridements and prolonged hospital stay. Proper counselling was paramount. Both cases were counselled at every step which resulted in satisfied patient and relatives at the end of treatment.

Which One is to be Treated First?

Neither published literature nor guidelines are available for synchronous occurrence of mucormycosis and oral squamous cell carcinoma. Both diseases were lethal as well as progressive. Availability of endoscopic skull base surgeon, head and neck surgeon, reconstructive team, necessary infrastructure and multidisciplinary team made it easy to plan both surgeries in one sitting.

Extra Surgical Care

Squamous cell carcinoma was excised via intra-oral/cervical approach while mucormycosis debridement was done endoscopically via transnasal approach. Since surgery resulted in common oro-nasal cavity in both cases, liberal saline wash was given to avoid contamination. Instruments of both the cases were kept separate. Operating surgeon descrubbed and rescrubbed again while switching from one procedure to another. Frequency of oral nasal wash was raised upto 2 hourly in day and every 4 hrs at night till completion of treatment.

Reconstruction should be Delayed or Done Simultaneously?

In one case microvascular reconstruction was done while in the other Pectoralis Major Myocutaneous (PMMC) flap was done. Both flaps survived. Diabetes was a risk factor for progression of mucormycosis. Invasive mucormycosis has a tendency to spread in surrounding areas. Diabetes Mellitus was also an independent risk factor of vascular failure in microvascular reconstruction (10). There might be increased total risk of flap compromise in presence of both diseases (9),(10). To manage diabetes mellitus strict blood sugar monitoring was done. From this experience it can be recommended that reconstruction can be done in same sitting. Revision debridement was done in one patient as he developed pain in the right periorbital area. Pain subsided after revision surgery. Both patients were discharged on the fifth postoperative day. Both patients were shifted to another multispeciality unit for further medical management.

Follow-up Protocol

Both patients were kept on regular weekly follow-up as usually done in routine patients with oral squamous cell carcinoma. Initially, MRI scan every 15 days is recommended. After three consecutive MRI studies remained static it was decided to get imaging at the time of appearance of new symptoms.

Can Adjuvant Treatment be Administered with Amphotericin B?

As per final histopathology report, both patients should be considered for chemoradiation. As there were no guidelines these cases were discussed with radiation and medical oncologists. In the view of the need of amphotericin B treatment for mucormycosis and there was risk of increased nephrotoxicity in simultaneous administration of amphotericin B and chemotherapy (11) it was decided to avoid chemotherapy.

Liposomal amphotericin B was started from 2nd postoperative day and continued with adjuvant chemotherapy. At the time of completion of treatment both patients were asymptomatic. Till follow-up both patients had completed disease free six months.

Conclusion

Synchronous occurrence of both mucormycosis is rare and never reported. There are no guidelines available. From this rare experience it can be recommended that both diseases can be treated simultaneously. With careful and vigilant approach reconstruction can be done in same sitting. There is no need to compromise in management of either squamous cell carcinoma or mucormycosis. No need to delay or avoid adjuvant radiation. Multidisciplinary institutional management is a key to success.

References

1.
Sharma S, Satyanarayana L, Asthana S, Shivalingesh KK, Goutham BS, Ramachandra S. Oral cancer statistics in India on the basis of first report of 29 population-based cancer registries. J Oral Maxillofac Pathol. 2018;22(1):18-26. Doi: 10.4103/jomfp.JOMFP_113_17. PMID: 29731552; PMCID: PMC5917535.
2.
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DOI and Others

DOI: 10.7860/JCDR/2022/53093.16776

Date of Submission: Dec 24, 2021
Date of Peer Review: Jan 27, 2022
Date of Acceptance: Jun 14, 2022
Date of Publishing: Aug 01, 2022

AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was informed consent obtained from the subjects involved in the study? Yes
• For any images presented appropriate consent has been obtained from the subjects. Yes

PLAGIARISM CHECKING METHODS:
• Plagiarism X-checker: Dec, 29, 2021
• Manual Googling: Jun 11, 2022
• iThenticate Software: Jun 13, 2022 (2%)

ETYMOLOGY: Author Origin

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